Epidemiology of Traumatic Brain Injury

Consequences of Traumatic Brain Injury

Mechanisms Underlying Functional Recovery Following Traumatic Brain Injury

Effectiveness of Rehabilitation Interventions to Address Cognitive, Behavioral, and Emotional Consequences of Brain Injury

Models of Comprehensive Rehabilitation for Traumatic Brain Injury

Definitions of Traumatic Brain Injury

No single, concise, universally accepted definition of traumatic brain injury (TBI) exists. According to Lehmkuhl (1996), TBI is defined as "damage to living brain tissue caused by an external, mechanical force. It is ... characterized by a period of altered consciousness (amnesia or coma) that can be very brief (minutes) or very long (months/indefinitely). The specific disabling condition(s) may be orthopedic, visual, aural, neurologic, perceptive/cognitive, or mental/emotional in nature. The term does not include brain injuries that are caused by insufficient blood supply, toxic substances, malignancy, disease-producing organisms, congenital disorders, birth trauma, or degenerative processes." The Centers for Disease Control and Prevention (Thurman et al., 1995) defines TBI as either "an occurrence of injury to the head that is documented in a medical record with one or more of the following conditions attributed to head injury:

• observed or self-reported decreased level of consciousness
• amnesia
• skull fracture
• objective neurological or neuropsychological abnormality
• diagnosed intracranial lesion

or as an occurrence of death resulting from trauma, with head injury listed on the death certificate, autopsy report, or medical examiner’s report in the sequence of conditions that resulted in death."

The severity of TBI has been classified as mild, moderate, and severe. These levels are differentiated clinically. The classification must be made immediately after the injury (Alexander, 1995).

Mild Traumatic Brain Injury

Mild TBI is a very common injury, resulting in 290,000 hospital admissions each year (Whyte, in press). Many more people sustain mild TBIs that do not require hospitalization. About 80 percent of people admitted to a hospital with the diagnosis of TBI have mild TBI (Kraus et al., 1994). In a review article by Kraus and McArthur (1996), mild TBIs accounted for between 60 percent and 90 percent of the samples of selected epidemiological studies of TBI. The most common cause of mild TBI is a motor vehicle crash (Kraus et al., 1994).

According to Whyte (in press), the three symptom clusters characteristic of mild TBI are cognitive symptoms (e.g., attention and concentration difficulties, memory impairments); affective symptoms (e.g., irritability, depression, anxiety); and somatic symptoms (e.g., headache, dizziness, insomnia, fatigue, and sensory impairments). The literature suggests that mild TBI does not typically cause prolonged impairments and that recovery is expected to occur within 3 months of the injury (Kibby, Long, 1996). However, Kraus (1991) summarizes recent studies that suggest persistent unfavorable outcomes following mild TBI, including physical complaints, cognitive changes, and behavioral problems. These persistent symptoms are termed post-concussion syndrome (PCS). Similarly, Alexander (1995) notes that 15 percent of individuals who suffer mild TBI still have disabling symptoms after 1 year.

The definition of mild TBI has provoked a great deal of controversy in the clinical and research literature. This is because the lower limit of the injury (i.e., the most mild TBI) is difficult to detect and define.

Before 1991, mild TBI was defined as "an injury with an initial Glasgow Coma Scale score of 13 to 15, post-traumatic amnesia (PTA) of less than 24 hours, and a loss of consciousness (LOC) of less than 20 minutes" (Esselman, Uomoto, 1995). One disputed aspect of this definition was that it included only those persons whose injuries resulted in a LOC. This restriction is problematic because some mild TBIs can occur without LOC.

In 1991, the Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine (Kay et al., 1993) provided the following definition of mild TBI:

"A patient with mild traumatic brain injury is a person who has had a traumatically induced physiological disruption of brain function, as manifested by at least one of the following:

1. any period of LOC.
2. any loss of memory for events immediately before or after the accident.
3. any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused).
4. focal neurological deficit(s) that may or may not be transient, but where the severity of the injury does not exceed the following:

• posttraumatic amnesia not greater than 24 hours.
• after 30 minutes, an initial Glasgow Coma Scale of 13–15.
• LOC of approximately 30 minutes or less."

As compared with the previous definition, this definition of mild TBI includes a wider range of people, ranging from those who are only dazed to those who are hospitalized, require rehabilitation, and have permanent neurological deficits (Esselman, Uomoto, 1995). In addition, this new definition resulted in an increase in the number of persons diagnosed as having TBI because it adds those who do not have LOC. The problematic aspect of this definition, according to Kibby and Long (1996) and Kraus and colleagues (1994) is that it could include a person with normal performance on the Glasgow Coma Scale (GCS) (i.e., a score of 15) who had sustained a minor blow to the head with little or no evidence that the brain had been injured. They assert that nearly every child or adult at some point experiences an event which would be classifiable as mild TBI, as a result of a fall or sports injury, and therefore, there is a need to differentiate a superficial injury to the head from mild TBI. Kraus and colleagues (1994) questioned the use of the GCS in determining mild TBI, because "its use at the upper end of the scale lacks both validity and sensitivity in distinguishing among milder injuries."

One modification of the definition of mild TBI offered by Dicker (1989) is the additional criteria of symptoms (e.g., headache) or services (e.g., seeking medical care within 24 hours of the injury) that would more reliably and validly separate persons with mild TBI from those with superficial injuries to the head. Kibby and Long (1996) offer a different suggestion, namely requiring two or more of the four criteria in the American Congress of Rehabilitation definition of mild TBI instead of one. A study by Williams and colleagues (1990) demonstrated that persons with mild TBI and radiographic evidence of a focal brain lesion and/or depressed skull fracture had significantly worse outcomes than those who had mild TBI without complications. Hence, there may be a need to further differentiate the heterogeneous category of mild TBI.

Esselman and Uomoto (1995) offer a classification of concussions, which is a term often used interchangeably with mild TBI, based on Ommaya’s (1985) conceptualization:

• Grade I concussions result in confusion only.
• Grade II concussions result in amnesia, PTA, or retrograde (RGA) without LOC.
• Grade III concussions involve LOC for up to 6 hours. (Note that a Grade III concussion would exceed the definition of a mild TBI.)

The Quality Standards Subcommittee of the American Academy of Neurology (1997) published a grading system of concussions which differs from the Ommaya (1985) classification. In the American Academy of Neurology three-grade system, Grades 1 and 2 are defined by transient confusion but no LOC. In Grade 1 injuries, the concussion symptoms and mental status abnormalities are resolved in less than 15 minutes, whereas in Grade 2 injuries, the symptoms and abnormalities last longer than 15 minutes. Grade 3 concussions involve LOC for any period of time.

Moderate Traumatic Brain Injury

There is no clearly demarcated clinical transition from mild to moderate TBI (Alexander, 1995). According to Kibby and Long (1996), moderate TBI is defined as a GCS of 9–12 during the first 24 hours after the injury and post-traumatic amnesia lasting from 1 to 24 hours. In research conducted by Thurman and others (1996) in Utah, the definition of moderate TBI was expanded to include not only those with a GCS of 9–12 but also those with intracranial lesions or focal neurological deficits and a GCS of 9 or higher. However, there is no formal definition of moderate TBI as there is for mild TBI, and the demarcation between mild and moderate TBI is unclear.

In the Kraus and McArthur (1996) summary of epidemiological studies in the United States, between 10 and 30 percent of TBIs are classified as moderate TBIs. Unpublished data by Kraus suggest that 93 percent of those persons who suffer moderate TBI are discharged from the hospital alive. Recovery of cognitive functions following moderate TBI is expected in about 1 year, and 80 percent of adults are likely to have returned to work by that point (Kibby, Long, 1996). The cognitive impairments in persons with moderate TBI are more significant than in those with mild TBI (Williams et al., 1990). They have a longer duration of impaired consciousness, more impaired verbal memory shortly after the injury, and a lower likelihood of achieving a good recovery within 6 months (Williams et al., 1990).

Severe Traumatic Brain Injury

Severe TBI is defined as a GCS score of 8 or less (comatose) during the first 24 hours after the injury (Thurman et al., 1996). Jennett and colleagues (1977, 1979) defined severe TBI by loss of consciousness (a coma) for 6 hours or longer, either immediately after the injury or after an intervening period of lucidity. The incidence of severe TBI is lower than mild or moderate. Whyte (in press) reported that between 50,000 and 75,000 people suffer severe TBI each year in the United States; of these between one-third and one-half die. Kraus and McArthur (1996) noted that the incidence of severe TBI is between 5 and 25 percent of all cases with TBI. In an epidemiological study of TBIs that led to hospital admission or death in Utah over a 3-year period, 16 percent of the hospitalized cases were considered to have severe TBI and another 13 percent died before hospital admission (Thurman et al., 1996).

Individuals who suffer severe TBI are at risk for long-term disability. Their behavior can be disinhibited, egocentric, and, at times, disregarding of social conventions (Whyte, in press). As a result, they often have difficulty remaining employed, maintaining pre-injury relationships, and establishing new social contacts. Thomsen (1992) studied 31 individuals with severe TBI over a 20-year period. Fully 61 percent had no friends. Many followup studies report depression for years after the injury in the individual who sustains severe TBI (Whyte, in press).

Penetrating and Nonpenetrating Injuries

There are two types of TBI: penetrating and nonpenetrating. Penetrating TBIs, or open head injuries, occur when an object lacerates the scalp, fractures the skull, and enters the brain. The injury results from destruction of nerve cells in the path of the penetrating object. Sources of penetrating injuries include gunshot wounds, knife wounds, and accidents.

Nonpenetrating TBIs, also known as closed head injuries, involve the collision of the head with another surface. Brain damage results even though no object penetrates the brain. This is because the brain is hurled against the inside of the skull, resulting in focal damage (e.g., contusions, lacerations, hematomas, raised intracranial pressure) or diffuse lesions (e.g., ischemic brain injury, diffuse axonal injuries) that are the result of acceleration/deceleration effects (McIntosh et al., 1996). Focal injuries are more likely to be the consequence of a fall, whereas motor vehicle accidents are the most prominent cause of more diffuse acceleration/deceleration type injuries.

Reporting Mechanisms

Adequacy of Current Data

Until the recent emergence of State registries and surveillance systems, few population-based studies were available from which to draw conclusions about the absolute numbers of TBIs and the incidence of TBI in the United States. Most studies relied on hospital discharge data. These studies do not include TBI cases that are mild and do not require medical care, nor do they include persons with TBI who are treated in emergency departments or on an outpatient basis. Many studies exclude cases who die at the scene of the injury or in the emergency department. However, some studies based on hospital discharge information use death records to augment their cases with those who have died from TBI. Studies vary according to differences in the clinical definition used for diagnosis, in coding of hospital admissions, and in the external causes of injuries included in the study. Prior studies have often been confined to small geographic areas and have focused on short time intervals, precluding the assessment of time trends. These limitations make it difficult to get an accurate assessment of factors related to TBI on a national basis or to allow geographic comparisons.

Registries and Surveillance Systems

Surveillance systems are just beginning to document the incidence of TBI in the United States. These systems will also characterize the persons injured and the external causes of TBI. The Centers for Disease Control and Prevention (CDC) under Public Law 104-166 has been funding the collection of uniform data by States and has been designated as the lead Federal agency to coordinate and plan central nervous system (CNS) injury prevention programs. CDC has published guidelines for surveillance of CNS injury (CDC, 1995). This manual sets forth standards and recommendations for the uniform collection of data across the United States. As of 1993, 16 States had TBI surveillance systems in place or were in the process of developing a system. However, as of 1998, only a few of these States have published data from their systems. Important to the success of these systems is the enactment of reporting laws in each State legislature. Along with the reporting laws, it is also necessary for State legislatures to provide the resources for the staffing of these registries.

The Traumatic Brain Injury Model Systems of Care database is a multicenter project funded by the National Institute on Disability and Rehabilitation Research (NIDRR) of the U.S. Department of Education. This prospective, longitudinal, multicenter study examines the course of recovery and outcomes of persons with TBI. Although one goal of the project is to create a database for research, from an epidemiologic perspective it is limited in assessing the demographic characteristics of persons with TBI and the causes and severity of TBI. This limitation is the result of the marked selection bias of the population who participates in this program.

Epidemiology

Incidence and Absolute Numbers of TBI Cases in the United States

Using national data from available sources, Kraus estimated that in 1990 in the United States 75,000 deaths, 366,000 hospitalizations, and 1,975,000 medically attended cases of TBI of any severity occurred at a rate of 145 of 100,000 persons per year (Kraus, 1993). This rate was consistent with the U.S. rate of 136 of 100,000 estimated by Fife (1987) using data from the National Health Interview Survey (NHIS) (National Center for Health Statistics, 1985). Alternatively, Kraus (1993) used composite data from all U.S. studies published before 1990 to develop an overall estimate of incidence of 200 of 100,000 TBI cases per year, age-adjusted to the 1990 U.S. population. This rate of 200 of 100,000 per year eliminates studies with the highest and lowest rate of TBI and is the most widely accepted rate of TBI, corresponding to 500,000 cases per year. More recently, an analysis of the 1993 National Hospital Discharge Survey (NHDS) data estimated a rate of 102 TBI-related hospitalizations per 100,000 population (CDC, 1997a).

Incidence rates in TBI have been calculated in a number of defined geographic regions in the United States (Table 1). The rates reported vary from 98 of 100,000 in Oklahoma (CDC, 1997a) to 367 of 100,000 in the intercity Chicago area (Whitman et al., 1984). More recently, reported rates from State Surveillance Systems appear to be somewhat lower than those reported for the 1970s and early 1980s. This possible decline in the incidence of TBI is thought to reflect successful injury prevention efforts but may merely reflect changes in definitions and criteria for admitting individuals to hospitals (CDC, 1997a). The CDC estimates the number of serious brain injuries that occur each year in the United States to be 250,000 (CDC, 1997a).

Table 1. Brain injury incidence from selected reports from various geographical areas within the United States, 1980–1993*

* Updated from Kraus, 1993
** PAS - Professional Activities Study
*** DOA - Dead on Arrival

Mortality

Sosin (1995) estimates that on average, 52,000 U.S. residents die from TBI each year. The 1992 U.S. death rate due to TBI was 19.3 per 100,000 U.S. residents. This rate showed a 22 percent decline from 24.6 per 100,000 U.S. residents in 1979. Sosin (1995) attributed this decline to successful efforts to prevent TBI caused by motor vehicle crashes. Other estimates of fatality rates due to TBI range from 22 to 30 of 100,000 per year (Kraus, 1993). Surveillance studies in four U.S. States from 1990 to 1993 found that 23 percent of the 13,978 TBI cases reported in those States were fatal (CDC, 1997a).

Severity

An accurate U.S. distribution of TBI by severity is difficult to determine because studies vary by the clinical definitions to classify systems of severity. The proportion of brain injuries that were classified as severe varied from 5 to 27 percent in the studies that have reported severity (Table 2). It is likely that the methods of case ascertainment in the reported studies also have a strong effect on the distribution of TBI by severity level.

Characteristics of TBI Cases

Age. In most reports, the incidence of TBI is highest among young people, with a peak at age 15 to 24 (Kraus et al., 1990). Secondary peaks occur in the elderly at ages 65 or older and in children ages five and younger (Kraus et al., 1990; CDC, 1997a; Kraus 1993; Thurman et al. 1996; Jagger et al., 1984; Fife et al., 1986; LeMier et al., 1994). The data from the surveillance systems in Colorado, Missouri, Oklahoma, and Utah demonstrate this pattern (Table 3, CDC, 1997a). Mortality from TBI is highest among the elderly, followed by those who sustain an injury at age 15 to 24 (LeMier et al., 1994; Kraus et al., 1984; Sosin et al., 1989).

Table 2. Severity of traumatic brain injury in the United States—selected reports*

	Severity
Study Location	Mild	Moderate	Severe			Comments
Olmsted County, MN	63	29	7	Severity based on symptoms, diagnosis, and loss of consciousness.
San Diego County, CA	91		9	Severity distribution based on GCS** for a nonrandom sample of individuals admitted with head injury to 10 of 30 county hospitals.
North Central Virginia	49	26	25
San Diego County, CA	82	9	9	Severity based on GCS.**
Chicago, IL	86	9	5	Severity based on symptoms, diagnosis, and length of loss of consciousness.
Maryland	70	17	13	Severity based on ICD:*** AIS**** 1,2 = mild AIS 3 = moderate AIS 4.5 = severe
Utah†	33	35	27	Cases that led to hospital admission or death only. Severity based on GCS.** If no GCS** was available, severity was based on awake, obtunded, or comatose.
University of Virginia Hospital (Rimel et al.)	55	34	21	Based on 1,248 individuals with head injury admitted to U.V. Hospital. Severity measured by GCS.**

* Adapted from Kraus, 1993 in Cooper PR (ed.). Head Injury. 3rd edition.
** GCS - Glasgow Coma Scale
*** ICD - International Classification of Diseases
**** AIS - Abbreviated Injury Score
^†   3.5% had no classification.

Table 3. Rate* of traumatic brain injury^†, by age group and sex—Colorado, Missouri,
Oklahoma, and Utah, 1990–1993^‡

* Per 100,000 persons.
^† International Classification of Diseases, Ninth Revision, Clinical Modification, codes 800.0-801.9, 803.0-804.9, and 850.0-854.1.
^‡ Information was collected for 1991–1993 in Colorado, 1992–1993 in Missouri and Oklahoma, and 1990–1993 in Utah (CDC, 1997a).

Gender. In all studies, TBI is more common in males of all ages than females (Kraus, 1993; LeMier et al., 1994; CDC, 1997a) (Table 3). Overall, men have twice as many brain injuries as women, but the ratio varies by age. For children ages 5 and younger and the elderly ages 75 and older, the ratio of the rates is less than 2, with a higher absolute number of TBI cases among women 75 and older (Thurman et al., 1996). This reflects the larger number of older women than older men in our population. The mortality rate for males is higher at all ages (Kraus, 1993; Klauber et al., 1981).

Race. When information on race is available, black and other nonwhite races have higher rates of TBI (Sosin et al., 1996; Kraus et al., 1990; Jagger et al., 1984; Whitman et al., 1984). The age-adjusted incidence of TBI in the Bronx, New York, from March 1980 to February 1981 was 209 of 100,000 for white residents, 278 of 100,000 for black residents, and 261 of 100,000 for Hispanic residents (Cooper et al., 1983). TBI mortality rates followed a similar pattern, with 18.7 of 100,000 for white residents, 34.2 of 100,000 for black residents, and 28.7 of 100,000 for Hispanic residents. They speculated that these racial differences reflected underlying patterns of socioeconomic or environmental factors in the Bronx. Cooper noted that the excess TBI in the black and Hispanic populations was due to violence. In contrast, when Sosin and colleagues (1996) used a nationally representative household sample (1991 NHIS) to determine the incidence of self-reported medically attended mild and moderate TBI by race, they found that incidence varied little between white, black, and Hispanic respondents. MacKenzie and colleagues (1989) also found little difference in white TBI rates compared with nonwhite rates overall or by severity level. Kraus (1993) cautioned that most studies that addressed TBI incidence rates by race did not adjust for socioeconomic status or other potentially important community characteristics.

Urban/Rural. Gabella and colleagues (1997) compared the epidemiology of rural and nonrural TBI in Colorado, using the statewide population-based TBI surveillance system. They found that the overall ratio of the incidence of TBI in rural areas versus the metropolitan Denver-Boulder area was 1.8 to 1. This ratio was similar for males and females. The mortality rates were not different for women by urban/rural residence, but the mortality rates for males were more than doubled in the rural areas, particularly for suicide and causes other than motor vehicle crashes, falls, and assault/homicide.

Sosin and colleagues (1996) used the NHIS data base to assess the incidence rates of self-reported medically attended TBIs (mild to moderate) by urbanization. They did not find any differences in the incidence rates of city, suburban, or rural residence for these less severe injuries.

Le Mier and colleagues (1994) found that the five counties in Washington State with the highest TBI rates were counties that are considered predominately rural. The reason for this geographical distribution was not clear; however, it was speculated that these counties had proportionately higher numbers of high-risk populations, such as males 15 to 24 years of age, the elderly, and minorities.

Education/income. Sosin and colleagues (1996) reported on self-reported medically attended mild and moderate TBI by level of education and income using the 1991 NHIS. The incidence was 633 per 100,000 for the population with yearly household incomes less than $20,000, whereas the incidence was 395 per 100,000 for the population with yearly household incomes equal to or greater than $20,000. Although the differences in incidence rates were not as great by education, the TBI rate of the population with some college education, 416 per 100,000, was somewhat lower than that of the population with education less than high school, 476 per 100,000, or that of high school graduates, 536 per 100,000. Fife and colleagues (1986) examined the Rhode Island population for the incidence of TBI, excluding fatally injured persons and those who were never hospitalized, by income and population density. They reported that the incidence rates of TBI for the census tracts in the lowest decile of median income were twice those for the census tracts in the highest decile. In general, incidence rates in cities increased with increasing population density.

Seasonality. A number of studies have examined the distribution of TBI by month or season of occurrence (Klauber et al., 1981; Whitman et al., 1984; Cooper et al., 1983; Diamond, 1996; Kraus, 1980). Most of these studies found peak incidence during the late spring and summer months.

Work-related TBI. There is a dearth of information on work-related TBI. Annegers and colleagues (1980), using the Olmsted County, Minnesota, population, found that the rate of occupation-related TBI was 11 of 100,000. The events occurred most frequently among men, particularly those in the farming and construction occupations. Heyer and colleagues (1994) used the Washington State Workers’ Compensation System from 1988 through 1990 to estimate the incidence of TBI. They calculated an incidence rate of hospitalized occupation-related TBI of 9.4 of 100,000 per year. The highest relative risks of TBI were found among loggers, followed by roofers, garbage collectors, and road construction workers. He found a large proportion of injuries clustered in a few industries, offering opportunities for prevention.

Other Risk Factors

Alcohol. Alcohol intoxication is often a contributing factor in the occurrence of traumatic brain injury. It is well known that alcohol is frequently associated with motor vehicle crashes (CDC, 1997b; American Medical Association Council on Scientific Affairs, 1986). Studies that have specifically evaluated the relationship of alcohol use to TBI in the United States found 9 percent (Klauber et al., 1981), 49 percent (Gale et al., 1983), and 72 percent (Rimel, 1981) of TBI cases had alcohol as a contributing cause. Kraus (1990), in a study of persons with TBI in San Diego, found that among the 26 percent ages 15 to 19 years who were given blood tests, 51 percent had a measurable blood alcohol content. It is likely, however, that this was not a random sample of persons with TBI in this age group. Goodman and Englander (1992) reviewed the literature on TBI in the elderly. They noted chronic use of alcohol as an important factor in this age group for both motor vehicle and fall-related TBI. Braakman and colleagues (1980) found alcohol to be related to 30 percent of TBI cases in a study of elderly persons with a mean age of 74.8 at the time of the event. Hartshorne and colleagues (1997) analyzed 75 cases of fatal TBI that occurred as a result of ground-level falls and that were autopsied in King County, Washington, over a 48-month period. Postmortem toxicology reports or clinical records of alcohol analysis were available on 48 of the cases. Of those tested, ethyl alcohol was present in 48 percent. It is clear from the available studies that the testing for alcohol in persons with TBI has not been done in a consistent or unbiased manner.

TBI as a risk factor for TBI. Many persons who recover (or think they have recovered) from TBI return to the activities that may have led to the initial episode. Most of the research and reports on recurrent TBI have focused on sports-related injuries that involve repeated blows to the head, such as boxing and football (CDC, 1997c; Enzenauer et al., 1989; Sortland et al., 1989; Saunders et al., 1984). Of importance is that even mild TBI, if repeated within a short timespan, can result in high mortality and morbidity (Hilton, 1994). Annegers and colleagues (1980), in their Olmsted County, Minnesota, study estimated the risk of a second TBI among those with previous TBI to be threefold the risk among those without TBI. They attributed this high risk to "behavioral characteristics such as use of alcohol."

External Causes

In the majority of studies, transportation-related incidents account for approximately 50 percent of TBI (Kraus, 1993; CDC, 1997a). This proportion is highly weighted by the high rate of transportation-related injuries in the 15 to 24 year age group, the age group of highest TBI incidence (Table 4). Falls are the second leading cause of TBI, accounting for a little over 20 percent of the incidence of TBI. In contrast with transportation-related injuries, the age groups most affected by falls are children younger than age 5 and the elderly, ages 75 and older. Firearms and nonfirearm assaults account for close to 20 percent of the incidence, with the remainder accounted for by sports/recreation and other causes.

Prevention

Beyond the fetal and newborn period, TBI is the result of potentially preventable incidents and intentional injuries (Daemon, Leviton, 1997; Thurman et al., 1995; Sosin et al., 1995; Kraus, 1993). Unintentional injuries can be separated into those resulting from motor vehicle crashes, occupational mishaps, falls, organized and individual sports, and other recreation. Intentional injuries are the result of violence: child abuse, domestic violence, crime, street violence, and military actions or war. Alcohol and other consciousness-altering drugs also deserve special consideration in attempts to prevent TBI.

Table 4. Rate* of traumatic brain injury,^† by external cause of injury^‡ and age group—
Colorado, Missouri, Oklahoma, and Utah, 1990-1993.^¶

* Per 100,000 persons.
^† International Classification of Diseases, Ninth Revision, Clinical Modification, codes 800.0-801.9, 803.0-804.9, and 850.0-854.1.
^‡ Information obtained from all cases reported in Missouri and Oklahoma and random samples of cases reviewed in Colorado (13% sample) and Utah (10% sample). Estimated mean annual numbers of cases by cause were 6,597 transportation-related, 3,186 fall-related, 1,346 firearm-related, 1,191 nonfirearm assault-related, and 353 sports- and recreational-related. An estimated mean of 727 and 579 cases for each year was related to other and unknown causes, respectively.
^¶ Information was collected for 1991-1993 in Colorado, 1992-1993 in Missouri and Oklahoma, and 1990-1993 in Utah (CDC, 1997a).

Unintentional Injuries

Preventive strategies target both the prevention of events that can lead to injury and the prevention of TBI when these events do occur. Most strategies fall into one of three categories: improved technology development and dissemination, consumer education, and legislative actions and mandates. Motor vehicle injury prevention is a good example of the different strategies and targets. Seatbelts, shoulder harnesses, infant and child car seats, airbags, and their legislatively mandated use are all aimed primarily at the prevention of traumatic brain and spinal cord injury when motor vehicle crashes occur. Changes in speed limits, road design, and traffic control measures are aimed at the prevention of the crashes themselves (Jagger, 1987 and 1992; U.S. Department of Transportation, 1980).

Motorcycle and bicycle helmet laws are aimed at prevention of TBI, but do little if anything to affect the risk of spinal cord injury. Bicycle helmets have been shown to decrease both the occurrence and severity of TBI in cyclists (Thompson et al., 1989; Rodgers et al., 1994). Attempts to mandate helmet use, especially for adults, have met with opposition in many States. The rules governing driving of watercraft, snowmobiles, and all-terrain and three- and four-wheel off-road vehicles have received significantly less attention.

Attempts to reduce sports-related TBI include the modification and development of newer sports equipment such as better helmets for football, hockey, bicycling (Thompson et al., 1989), and horseback riding (Lantis, 1994; Nelson et al., 1992; American Academy of Pediatrics, 1992) and posterior neck pads or rolls for football players. Rule changes which prevent amateur athletes with even the mildest concussion from re-entering a game without physician approval have raised awareness of the risk of TBI in school and community sports and reduced the risk of exacerbation of existing injuries and immediate reinjury (American College of Sports Medicine, 1993; Cantu, 1987; Hugenholtz, Richard, 1982; Kelley et al., 1991). The success of these prevention activities has not been carefully studied (Torg, 1985). However, recent detailed research on the biomechanics of cervical spine and brain injuries offers hope for improved prevention strategies in the areas of better safety equipment, appropriate rules changes to enhance safety, and greater coach, player, and parent awareness (Winkelstein, Myers 1997).

Each new technology or legislative mandate is felt to warrant a careful evaluation. Although considered to be successful in overall injury prevention, some safety devices such as shoulder harnesses and airbags have had unanticipated adverse effects on children. Similarly, consumer education programs must be evaluated, even those that sound reasonable. The National Head and Spinal Cord Injury Prevention Program of the American Association of Neurological Surgeons and Congress of Neurological Surgeons is an educational intervention with teens regarding seatbelt and shoulder belt use. It has been shown to increase knowledge but not modify behavior (Neuwelt et al., 1989; Robertson, 1983).

Appropriate prevention strategies are also age dependent. For example, unintentional injuries in infants reflect their developmental stage and are often the result of falls from walkers, from strollers, down stairs or from shopping carts (Chadwick et al., 1991). Changes in the design of these devices and proper use by parents, including lap straps in shopping carts and gates for stairs, could prevent many of these injuries (Fisher, 1997). In primary school age children, injury prevention should focus on safety in recreational activities, such as bicycling and skate boarding, as well as vehicle passenger safety. In adolescents and young adults, injury concerns include driving and alcohol, sports, recreational activities, and violence.

Occupational injuries are the concern of the Occupational Safety and Health Administration (OSHA). Some of the required occupational injury prevention activities are obvious, such as wearing hardhats at construction sites. Other prevention strategies, such as rules regarding package stacking and storage, are less apparent to most Americans. Mortality and TBI surveillance for all job sites has helped to identify additional safety measures that may be helpful in TBI and spinal cord injury prevention.

Overall, the most effective unintentional injury prevention measures are reported to be legislative and regulatory controls in road, sport, and workplace settings. The ability of educational programs to modify behavior may be enhanced through the use of incentives (Munro et al., 1995; Halperin et al., 1983).

Intentional Injuries

Violence has been recognized as a pandemic (Beauchesne et al., 1997). In the United States, street violence, violent crimes, and child and domestic abuse are all associated with increased mortality and TBI in children and young adults. Since the Vietnam War, U.S. involvement in military actions has been limited to short periods of time or peace-keeping activities and has therefore accounted for a smaller portion of TBIs than in earlier decades.

Prevention of street violence, especially handgun violence, has not been very successful (Hausman et al., 1996; Nadel et al., 1996; Powell et al., 1996; Tolan, Guerra, 1996). Strategies have included both attempts to remove the tools of violence, such as handguns, and establishing programs to identify and modify the causes of violence, through interventions such as youth activity programs, control of illegal drugs, education and work programs, and changes in television network programming and viewing (Durkin et al., 1996; Grossman et al., 1997; Davidson et al., 1994; Finkelhor et al., 1995). Evaluation of most prevention activities has been scant (Powell et al., 1996).

Child abuse continues to be the etiology of thousands of childhood injuries and deaths each year (Committee on Child Abuse and Neglect, 1997; Billmire, Myers, 1985). Shaken baby syndrome results specifically in TBI and spinal cord injuries (Bruce, Zimmerman, 1989; Dykes, 1986; Hahn et al., 1983; Caffey, 1972; Cullen, 1975; Dickson, Leatherman, 1978; Gosnold, Sivaloganathan, 1980). Similarly, domestic violence affects children and adults of both genders. Prevention programs for child abuse and domestic violence are often secondary prevention efforts, attempting to prevent further abuse after a pattern of abusive behavior is recognized (Saltzman, Johnson, 1996). More recently, high schools, hospitals, and community centers have developed educational programs regarding conflict management and parenting, and pre- and postmarriage support groups (U.S. Advisory Board on Child Abuse and Neglect, 1991). Early education and support in high-risk families is often done either in the home of pregnant or new mothers or in community education, public health, or social services centers (Showers, 1992). In early assessment studies, such programs appear to have variable levels of efficacy in preventing abuse (Taal, Edalaar, 1997; Rispens et al., 1997). Legislators have proposed legislated "prevention" (Browne, 1994; Dresser, 1994). This would of course also include prevention of second injuries.

Most researchers agree that prevention of TBI due to violence will require major new programs and perhaps reevaluation of societal values and norms, changes in the judicial system, a reduction in poverty, and expanded educational and adequate employment opportunities for youth, especially inner-city youth and those of African American and Hispanic descent (Beauchesne et al., 1997; Committee on Child Abuse and Neglect, 1997; Taal, Edalaar, 1997; Rispens et al., 1997).

Alcohol and Drug Use

Alcohol and other drugs that alter cognitive abilities and judgement should receive special attention in the prevention of both unintentional and intentional injuries. Alcohol-impaired drivers kill and maim many Americans every day (Cunningham, 1996), and alcohol use is highly associated with physical and sexual abuse of children by parents and relatives (U.S. Advisory Board on Child Abuse and Neglect, 1991). Congress has recently debated strengthening laws that identify alcohol-impaired drivers. In many European countries, driving while drug or alcohol impaired results in immediate loss of license and/or vehicle. Whether it is the tougher laws or social norms, driving while intoxicated appears to result in fewer deaths and TBIs in countries with swift and definitive consequences of this offense (Dresser, 1995; Ross, 1995; Chafetz, 1995; O’Connor, Schottenfeld, 1998).

Prevention of underage drinking may be especially important in the prevention of TBI, since it is the young impaired driver who is most likely to sustain or cause such injuries in passengers or victims (U.S. Department of Transportation, 1989). More strict drinking rules among student athletes and on college campuses have been instituted to curb underage drinking (Carr et al., 1996; Heyman, 1996; Tricker, 1996; Ungerleider, 1996).

Illegal drugs play a large role in street violence, and violent crime, both as mind-altering substances and as the reason for theft, violence, and injury. Attempts to control drug trafficking and the traffickers have met with limited success in the global market. Primary prevention of drug use in children and young adults has also met with limited success (Fawcett et al., 1997; Shope et al., 1996). Programs such as DARE have been used widely and studied little.

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Top

TBI may be classified as mild, moderate, or severe, but no matter the severity, consequences are rarely limited to one set of symptoms, clearly delineated impairments, or a disability that affects only part of a person’s life. Rather, consequences of TBI often affect human functions along a continuum: from altered physiologic functions of cells, through neurological and psychological impairments, to medical problems and disabilities that affect the individual with TBI, family, friends, and community, as well as society in general. Furthermore, the consequences of TBI may be insidious in that early manifestations of impairment with relatively mild symptoms may be overlooked or overshadowed by urgent medical problems related to trauma yet result in subtle impairments. This section reviews the neurological, functional, and medical consequences of TBI, as well as special issues related to TBI in children and the elderly. It also summarizes what is known about the social and economic consequences that TBI may have on the family, the community, and society.

Neurological Consequences

In general, neurological outcomes are directly influenced by the type of TBI and the severity of the neurophysical, neurocognitive, and neurobehavioral complications.

Neurophysical Sequelae

In this report, the term "neurophysical impairment" denotes the noncognitive and nonbehavioral neurological complications of TBI. These neurophysical impairments will have a direct impact on the overall neurological recovery of the individual. Neurophysical impairments that may be encountered after TBI are listed in Table 1.

Headaches represent the most common sequelae of TBI and may occur as a component of the postconcussion syndrome or as a consequence of any type of TBI. Posttraumatic headaches are typically caused by injury to the scalp, cervical spine, or intracranial structures and are more commonly associated with mild TBI than its more severe forms (Packard, Ham, 1994). Posttraumatic headaches may be accompanied by cognitive and somatic symptoms such as memory impairment, difficulty concentrating, dizziness, and fatigue. Although the pathophysiology of posttraumatic headache is poorly understood, most individuals will improve in 6 to 12 months (Packard, Ham, 1994), although persistent headaches may be anticipated in 15 to 20 percent (Speed, 1991).

Posttraumatic seizures are a relatively common complication of TBI and can be classified as early (within the first week) or late (after the first week). Risk factors for early seizures include posttraumatic amnesia lasting longer than 24 hours, depressed skull fracture, and acute intracranial hematoma (Jennett, Bond, 1975). Late seizures tend to be associated with a history of early seizures, depressed skull fracture, and acute intracranial hematoma (Jennett, Bond, 1975).

Motor and sensory impairments are relatively common consequences of moderate and severe TBI. Both have a profound effect on neurological and rehabilitation outcomes. Motor impairment can be present as weakness, ataxia, spasticity, or other forms of movement disorder. Hemiparesis can occur from focal lesions affecting the corticospinal tract in the cerebral hemispheres or brainstem. Spasticity usually emerges in the evolution of recovery from upper motor neuron weakness (Bachman, 1992). Ataxia after severe brain injury may occur secondary to damage to the cerebellum or cerebellocortical pathways (Haggard et al., 1995). Movement disorders encountered after TBI include tremor, dystonia, choreoathetosis, tics, and myoclonus (Goetz, Pappert, 1996).

Posttraumatic ventricular enlargement or hydrocephalus can occur as an acute or chronic complication of TBI. Symptoms of posttraumatic hydrocephalus usually occur within 1 year and include impaired consciousness, ataxia, failure to improve, behavioral changes, incontinence, and/or signs of increased intracranial pressure (Cardoso, Galbraith, 1985). Factors contributing to the development of posttraumatic hydrocephalus include meningitis, traumatic subarachnoid hemorrhage, posterior fossa mass, fibrosis related to craniotomy, and intracranial hematoma (Cardoso, Galbraith, 1985). Early diagnosis and ventricular shunting may improve neurological outcome and prevent further neurological deterioration (Scheffler et al., 1994).

Posttraumatic cerebrospinal fluid (CSF) leaks are associated with skull fractures and can be present as rhinorrhea or otorrhea. Individuals with CSF rhinorrhea usually have sustained a dural tear and a fracture of the ethmoid or sphenoid bone or the orbital plate of the frontal bone (Cooper, 1993).

Otorrhea typically occurs when there is a combination of a fracture of the petrous bone, a tear in the dura mater and arachnoid, and a rupture of the tympanic membrane (Cooper, 1993).

Compressive cranial neuropathies can occur with or without skull fractures. The most commonly injured cranial nerves in TBI include the olfactory, facial, and audio vestibular nerves, whereas the least involved cranial nerves are the trigeminal and lower cranial nerves (Kean, Baloh, 1996). Trauma to the ocular nerve and ocular motor nerves are intermediate in frequency (Keane, Baloh, 1996).

Neuroendocrine dysfunction secondary to posttraumatic hypopituitarism and hypothalamic damage is a relatively uncommon consequence of TBI. Hypothalamic or pituitary damage can occur after any type of head injury but tends to be associated with more severe brain injury. The clinical manifestations of hypopituitarism can be immediate or delayed and can include decreased growth hormone, decreased gonadotrophin, decreased thyrotropin, and/or increased prolactin production (Wyngaarden et al., 1992, p.1229). Other less frequently encountered neurological complications of TBI include arachnoid cysts, arteriovenous malformations, posttraumatic aneurysms, and posttraumatic subdural hygromas.

Neurocognitive Consequences

Several cognitive functions can be affected by TBI (Table 2). In TBI, memory, attention/concentration, executive functioning, and information-processing speed are the most commonly affected functions. Visual-spatial skills and language function are less commonly impaired unless associated with focal or penetrating brain injury. Intelligence, which is the sum of an individual’s knowledge and problem-solving skills (Capruso, Levin, 1996), may also be impaired following severe TBI (Levin et al., 1979b). Levin and colleagues (1979b) noted that

designed to assess cognitive function after TBI. These include the Galveston Orientation and Amnesia Test (GOAT) (Levin et al.,1979a), the Children’s Orientation and Amnesia Test (COAT) (Ewing-Cobbs et al., 1990), and the Levels of Cognitive Functioning Scale (Hagan et al., 1979).

TBI has profound effects on memory function. Memory deficits following TBI include anterograde (impaired memory for events after TBI) and retrograde (impaired memory for events before TBI) amnesia. The period of anterograde or posttraumatic amnesia (PTA) appears to be a reliable predictor of outcome following TBI (Ellenberg et al., 1996). In addition to the acute effects of TBI on memory function, more chronic memory problems such as dementia pugilistica and posttraumatic dementia may be encountered (Jordan, 1998). Dementia pugilistica, which is primarily exhibited by retired boxers, represents the chronic, long-term consequences of repetitive concussive blows to the head and is distinguished from posttraumatic dementia characterized by an individual experiencing long-term memory impairment after a single severe TBI, typically associated with prolonged coma (Jordan, 1998). In addition, TBI has been linked to the pathophysiology of Alzheimer’s disease (Van Duijn, 1996), especially in those harboring the apolipoprotein E allele (Mayeux et al., 1995; Katzman et al., 1996).

Neurobehavioral Sequelae

Problematic behavioral and emotional consequences of TBI are common and varied (Table 3) yet poorly understood. One or more forms of neurobehavioral sequelae are estimated to exist in up to 94 percent of victims. The major problems reported are restlessness, agitation, aggression, withdrawal, emotional outbursts including violence, and a variety of personality changes (Levin et al., 1987; Silver, Lux, 1994; Galski et al., 1994; Volavka, 1995). Individuals with severe TBI, compared with those with mild and moderate TBI, are at greatest risk for developing and sustaining these problems. Disruptive behaviors, for example, agitation, hostility, and verbal and physical aggression, are particularly common and troublesome; they appear early (1 to 3 weeks) and may persist more than 5 years after TBI (Wroblewski et al., 1997; Fugate et al., 1997; Olver et al., 1996; Fowler et al., 1995; Brooke et al., 1992; Dunlop et al., 1991; Levin et al., 1987). There is some suggestion that restlessness (i.e., continuous activity) may be distinguished from agitated behaviors, be time limited, and reflect early recovery (Brooke et al., 1992). An inverse relationship exists between agitation and cognitive function in the early rehabilitation period (Corrigan et al., 1989; 1992). Instruments commonly used to measure problem behaviors include (1) Overall and Gorhams’ Brief Psychiatric Rating Scale, (2) Neurobehavioral Rating Scale, (3) Overt Aggression Scale, and (4) Agitated Behavior Scale. Posttraumatic amnesia confounds agitated states (Sandel, Mysiw, 1996). Agitation often lessens as amnesia clears (Corrigan, 1989). In children with TBI, premorbid behaviors appear highly relevant for understanding posttrauma behavior patterns (Max et al., 1997a; 1997b, 1997c; Bijur et al., 1996). There is some indication that frontal lobe damage impairs inhibitory control over limbic activity leading to a prevailing pattern of agitation, disorganization, and disinhibition. Disinhibition in children has been associated with impulsivity, forgetfulness, and antisocial behavioral. In general, agitation, aggression, emotional lability, and disinhibition are inversely related to cognitive function. There is also a tendency for behaviors and emotions to deteriorate over time (Dunlop et al., 1991; Olver et al., 1996). Although this might be explained by nonadaptive neuroplastic changes, persistent PTA, increased cognitive demands, sensitization through a central fear system, or some combination of these, little definitive evidence exists to explain events or guide therapy.

Mood disorders and psychiatric manifestations are also prevalent after TBI. Following moderate or severe TBI, major and bipolar depression is estimated to occur in anywhere from 4 to 77 percent of individuals; personality changes and major anxiety disorders (panic attacks, phobias, and obsessive-compulsive disorders ) are estimated to occur in 50 to 60 percent of individuals (Rosenthal et al., 1998; Van Reekum et al., 1996; Emilien, Waltregny, 1996; Jorge et al., 1993a; 1994). Apathy is also a frequent symptom and may occur alone or in combination with depression (Kant et al., 1998). The onset of negative affective symptoms may occur early or late. A more extended longitudinal perspective is needed to determine the persistence of mood alterations in moderate- to severe-TBI groups. Jorge and colleagues (1993a) report that depression alone lasts an average of 1.5 months and is associated with left dorsolateral frontal or basal ganglia damage. These authors suggest that when depression is combined with anxiety disorder, the duration of symptoms is almost 8 months and the origin of injury is often the right hemisphere. Mild TBI is also associated with persistent mood disorders and emotional problems. These tend to take the forms of depression (in 26 to 37 percent of subjects studied), general anxiety, and posttraumatic stress disorders (in 50 percent), which may persist for months after injury in both adults and children (Parker, Rosenblum, 1996).

Psychiatric Disorders After Traumatic Brain Injury

Historically, the neurobehavioral psychosocial consequences of TBI have been measured by either neuropsychological (e.g., attentional, executive, or memory impairments), emotional (e.g., personality assessment profiles), or psychosocial (e.g., return to work or school, quantity and quality of interpersonal relationships) variables. Recent research has begun to document specific psychiatric morbidity following TBI. The findings of this research are reviewed below.

Jorge and colleagues (1993a, b) assessed depression and anxiety disorders in a group of 66 adults hospitalized for treatment of TBI. They conducted assessments during the acute hospitalization and at 3, 6, and 12 months postinjury. A total of 28 subjects met criteria for major depression, 17 during the acute stage and 11 (17 percent) during followup. The mean duration of depression was 4.7 months. Seven of the 17 subjects who were depressed during the acute stage also met diagnostic criteria for generalized anxiety disorder with a mean duration of 1.5 months.

Review of a controlled prospective study of mild TBI in children and adolescents (Asarnow et al., 1995), 30 studies involving mild TBI, and the data from the prospective study by Max and colleagues (1997a,b,c) described below suggests that the evidence in support of the pathogenesis of behavior problems as a direct effect of TBI resulting from an accident, or as a long-term secondary effect of the injury, is weak for the group of mild cases as a whole.

There are only three prospective studies available that use standardized psychiatric assessment methods to assess children with moderate or severe TBI. The first was conducted by Sir Michael Rutter’s group in England (Brown et al., 1981). This was a study of 28 children with severe TBI (PTA 1 week), 29 with mild TBI (PTA 1 hour to 1 week), and 28 control subjects, ages 5 to 14 years. Psychiatric assessments were done at 4 months, 1 year, and 2 to 14 years postinjury. Within the severe injury group, 12 psychiatric diagnoses "attributable to brain injury" were made.

Max and colleagues reported on psychiatric disorders in a group of 50 children and adolescents, ages 6 to14 years, at 3 months (Max et al., 1997a), 6 months (Max et al., 1997b) and 2 years (Max et al., 1997c) following TBI. At 3-month followup (n=37; mild = 46 percent; moderate = 24 percent; severe = 30 percent), a "novel" (i.e., post-TBI onset) psychiatric disorder occurred in 17 of 37 subjects (46 percent). The specific diagnoses were "organic personality syndrome" (10; 4 resolved), attention deficit hyperactivity disorder (ADHD) (6), anxiety disorder (6; 3 resolved), major depression (5; all resolved), mania (1), oppositional defiant disorder (ODD) (3), obsessive compulsive disorder (OCD) (1), mania (1), and adjustment disorder (1; resolved). Of note, in a post hoc forward stepwise logistic regression analysis, the variable most likely to predict novel psychiatric disorder was severity of injury (i.e., lowest postresuscitation Glasgow Coma Scale [GCS] score), which correctly predicted 76.7 percent of novel disorders.

At 6-month followup, 10 of 41 subjects had a novel psychiatric disorder (Max et al., 1997b). In seven of the subjects, novel disorders had persisted from the first 3 months of followup; in two subjects the initial novel disorder had been replaced by another; and in one subject the novel disorder had developed during the second 3 months of followup. The specific disorders were organic personality syndrome (5), ADHD (4), ODD (4), anxiety disorder (2), mania (1), hypomania (1), and OCD (1). The post hoc forward stepwise logistic regression analysis revealed that severity of injury (lowest postresuscitation GCS score) predicted 85 percent of the novel disorders.

At 2-year followup, 15 of 42 subjects had a novel psychiatric disorder (Max et al., 1997c). Novel disorders had persisted from the previous (unpublished) 12-month assessment in 11 subjects (3 had developed an additional novel disorder in the interim); the other 4 subjects developed their disorder during this 12-month period. The disorders included ODD (8; 2 resolved), ADHD (6; 1 resolved), organic personality syndrome (4; comorbid with novel ADHD in all cases), anxiety disorder (4; 1 resolved), mania (1), hypomania (1), adjustment disorder (1; resolved), and marijuana dependence (1; resolved). The post hoc forward stepwise logistic regression analysis revealed that global family function, the first variable, predicted 76 percent of novel disorders; severity of injury (lowest postresuscitation GCS score), the second variable, predicted 78.6 percent; and lifetime psychiatric diagnosis, the third variable, predicted 81 percent of the novel disorders.

Gerring and colleagues (1998) studied 99 children, ages 6 to14 years, with moderate (GCS score = 9 to 12) or severe (GCS score = 3 to 8) TBI. Psychopathology, specifically ADHD and OCD, were systematically assessed immediately after injury and at 1-year followup. Premorbid prevalence of ADHD was 20 percent, significantly higher than a reference population (4.5 percent). Fifteen of the remaining 80 children (19 percent) developed ADHD (except for the age-of-onset criterion) by the end of the first year postinjury. Eight of 72 subjects (11 percent) developed "new onset" OCD at the 1-year followup.

Taken together, these followup studies of children with TBI indicate that psychiatric disorders are rare following mild TBI and common following moderate or severe TBI. The most common psychiatric disorders that persist to 1 or 2 years postinjury are ADHD, personality changes, and OCD. Depression appears to resolve during the first year postinjury. Some anxiety disorders and oppositional behavior also persist, but it is difficult to know whether this is a direct consequence of brain injury or the psychosocial sequelae of the injury. Depression and anxiety are also common following TBI in adults. In general, the anxiety resolves over a few months, whereas the depression may persist in a minority of individuals.

Theoretically, neurological outcome measures after TBI document the associated neurological sequelae or impairments. The distinction between impairment and disability is important because neurological impairments do not always translate into functional disabilities. The majority of individuals who exhibit neurological impairments following TBI reach their maximal outcome within 6 months of injury and very few change after 1 year (Jennett et al., 1981).

Functional Consequences of TBI

Attentional processes are commonly affected following TBI and should be carefully assessed before attributing cognitive dysfunction to a specific domain. After TBI, detailed neuropsychological testing can reveal deficits in vigilance (sustained attention), freedom from distraction (focused attention), and the capacity for divided attention (Capruso, Levin, 1996). The inability to attend to incoming information can result in an information-processing deficit that can affect performance in other cognitive domains (Lovell, Franzen, 1994). Slowed information-processing speed is a sensitive and well-documented sequela of TBI (Capruso, Levin, 1996).

Executive dysfunction is a common sequela of TBI because the frontal lobes are particularly susceptible to vectors of TBI. Cognitive functions that are subserved by the frontal lobes that can be affected by TBI include abstraction, planning, mental flexibility, and mental control.

Dysfunction in visual-spatial skills is infrequently encountered following TBI unless associated with a right hemispheric focal lesion. The relative preservation of complex perception reflects the anterocaudal gradient of TBI that results in more involvement of the anterior cortices and less involvement of the posterior cortices (Capruso, Levin, 1996).

Language dysfunction is variably affected after TBI. Language deficits encountered after TBI can include mutism, anomia, impaired comprehension, decreased fluency, impaired repetition, paraphasia, circumlocution, disorganized and impoverished narrative, tangential or socially inappropriate conversation, disturbances in speech intonation, and the loss of speech spontaneity (Lovell and Franzen, 1994; Capruso and Levin, 1996).

Medical Complications of TBI

TBI (even mild TBI) may affect many organ systems of the body and result in both acute and long-term medical problems that hamper return to normal functioning and increase use of health care services. The potential medical complications can be divided between those occurring within the first days to months following injury and those occurring in the postacute phases.

Acute Complications

Severe TBI resulting in loss of consciousness for greater than 12 to 24 hours is often accompanied by a host of extra cerebral manifestations of the stress, polytrauma, hypermetabolic state, neurological insults, and deficits acutely associated with TBI (Cole et al., 1994; Bloomfield, 1989; Groswasser et al., 1990; Clifton et al., 1984; Balzola et al., 1980).

Pulmonary complications (Slack, Shucart, 1994) include neurogenic pulmonary edema (Dettbarn, Davidson, 1989), adult respiratory distress syndrome, pulmonary emboli from fat and blood clots (Sobus et al., 1994), aspiration pneumonia (Klingbeil, 1988; Citta-Pietrolungo et al., 1993; Splaingard et al., 1988), and the effects of unrecognized blunt trauma to the chest (Cole et al., 1994; Baigelman, O’Brien, 1981; Miyashi et al, 1994; Karaaslan et al., 1995).

Erosive gastritis is an almost universal complication of TBI in individuals not receiving prophylactic gastric acid inhibition (Becker et al., 1978; Arseni, Oprescu, 1975; Halloran et al., 1980). This condition may in turn cause bacteria overgrowth in the stomach, thus increasing the risk of aspiration pneumonia. Associated blunt trauma to the abdomen may lead to pancreatitis or small bowel edema and dysfunction. The frequently observed stress-induced hypermetabolic state and glucogenesis may lead to muscle wasting and starvation of other organ systems.

Fluid and electrolyte balance are hampered by the hypermetabolic state, the need to control intracranial pressure, and dysfunction of the pituitary axis hormones. As a result, both a condition known as "Syndrome of Inappropriate Secretion of Antidiuretic Hormone" (SIADH) (Webster, Bell, 1997) and hypothyroidism (Woolf et al., 1988) are often seen in TBI.

With polytrauma, the need for external airway and ventilation management and immune cellular dysfunction makes infection a likely complication in the majority of persons with severe TBI (Groswasser et al., 1990; Lanza et al., 1990; Quattrocci et al., 1991; Melossi et al., 1991). A hyperdynamic cardiovascular state may occur in more than 25 percent of persons with TBI. This condition can be aggravated by unrecognized blunt trauma to the chest and myocardium, which is common in individuals with severe TBI and polytrauma.

Coagulopathies, such as disseminated intravascular coagulation, frequently aggravate general management of the individuals with TBI and exacerbate CNS damage. Unrecognized extracerebral injuries, such as fractures (Sobus et al., 1993), peripheral nerve injuries (Stone, Keenan, 1988; Cosgrove et al., 1989), and secondary deep vein thrombosis (Stone, Keenan, 1992) may lead to unanticipated secondary disabilities from TBI (Stone et al., 1990).

The involvement of primary care providers in the acute phase of care for severe TBI is usually limited to the provision of information on any relevant medical history to the trauma team and perhaps to initial stabilization and transfer of the individual to a trauma center. However, primary care providers usually become responsible for providing and/or coordinating care for persons with TBI, once they return to the community. This is especially the case for persons with mild TBI, who do not require hospitalization. It is therefore important that primary care physicians recognize the many acute and long-term symptoms and complications common in even mild TBI (Browne, 1994). These include headaches, impaired memory, irritability, depression, anxiety, dizziness, hearing loss, insomnia, and fatigue (Jones et al., 1992; Englander et al., 1992; Rosenthal, 1993; Barrett et al., 1994).

Long-term Complications

People who survive a severe TBI face a variety of extra-cerebral medical complications that depend in part on their state of consciousness, ability to ambulate and care for themselves, and the kind of other injuries sustained (Grosswasser et al., 1990; Twyman, Bivins, 1986; Sazbon, Grosswasser, 1991).

Individuals who remain in a vegetative state following TBI may have medical problems associated with almost any organ system ranging from pressure sores of the skin to recurrent bladder infections, often ending with progressive multiple organ system failure (Fleischer et al., 1978; Bevilaqua, Fornaciari, 1975). Individuals who regain consciousness following TBI may have a variety of complications that are associated with the severity of the injury, the duration of impaired consciousness, and the duration of nutritional and ventilatory support received.

More than 50 percent of all people who regain consciousness after severe TBI report chronic pain (usually headaches) that requires some type of therapy (Beetar et al., 1996; Lahz, Bryant, 1996; Jensen et al., 1990; Uomoto, Esselman, 1993). Postural instability, both static and dynamic, may make ambulation, attention to visual tasks, and complex task integration of motor and cognitive functions difficult (Geurtz et al., 1996).

Chronic endocrine problems, usually thyroid or sexual hormone dysfunction, are common (Sandel et al., 1996; Fok et al., 1989; Kreutzer, Zasler, 1989). Sexual dysfunction is most often reported in male TBI survivors, with complaints of both lower sexual drive and erectile dysfunction associated with lowered testosterone levels (Kreutzer, Zasler, 1989; Su-Ching et al., 1994). Precocious puberty is a possible (although uncommon) consequence of TBI in children. However, when it occurs, it may alarm both parents and children (Sockalaski et al., 1987; Blendonohy, Philip, 1991). Fluid and electrolyte imbalance caused by SIADH may require lifelong monitoring in both children and adults following TBI (Anmuth et al., 1993; Webster, Bell, 1997; Fleischer et al., 1978), as may high blood pressure, because the incidence of chronic hypertension appears to be doubled in those surviving severe TBI (Labi, Horn, 1990).

Heterotopic ossification is more frequent in children with TBI than in the general population. It may affect up to 20 percent of all TBI survivors, even those without recognized fractures of long bones. The most common sites affected are the hip, shoulder, and elbow, resulting in pain, decreased mobility, and the potential for peripheral nerve dysfunction (Citta-Pietrolungo et al., 1992; Garland, 1988).

TBI survivors may experience gastroparesis once they progress to oral feeding. This is thought to be caused by vagal or other nerve dysfunction (Jackson, Davidoff, 1989; Altmayer et al., 1996; Haig et al., 1996). Chronic dysphagia is also common and may hamper rehabilitation efforts and the individual’s ability to maintain adequate calorie intake and ideal weight (Cherney, Halper, 1996).

Individuals with limited ambulatory ability are at increased risk of deep venous thrombosis and secondary pulmonary emboli (Baigelman, O’Brien, 1981). Prolonged and severe physical deconditioning may result in chronic dyspnea and tachycardia even with mild exercise (Becker et al., 1978).

Dysfunction of the immune system and impairment of the urinary and reproductive systems, such as neurogenic bowel and bladder problems, and decreased cough reflex can increase the risk for acute infections and sepsis.

Psychological complications after TBI are common, most often depression and posttraumatic stress disorder (Wroblewski et al., 1996; Jorge et al., 1993a). Alcohol and drug abuse are not uncommon after TBI. However, these problems are also common contributing factors to the initial injury, especially in young adult males (Corrigan, 1995; Kramer et al., 1993; Bombardier et al., 1997).

Chronic insomnia and sleep disturbances may last for years after TBI, aggravating the individual’s inability to cope with other medical, cognitive, and emotional problems (Cohen et al., 1992; Beetar et al., 1996).

Seizure disorders are not uncommon among TBI survivors (Segatore, Jacob, 1993). These manifestations may be difficult to recognize and distinguish from other movement disorders (Krauss et al., 1996). In addition, the seizures may also be hard to control, especially if they require medications that can exacerbate cognitive or other subclinical dysfunctions. The chronic subclinical, and often unrecognized, dysfunction of the endocrine and immune system (Melossi et al., 1991; Quattrocci et al., 1991) may exacerbate the medical problems and increase the need for special medical attention for TBI survivors. In addition, failure to achieve healthy lifestyle habits, such as regular physical exercise and appropriate diet, may further complicate the long-term health of persons with TBI with cognitive or ambulatory disabilities. Whatever their reasons for seeking care, TBI survivors may have difficulty accessing the health care system because of ambulatory, emotional, or cognitive dysfunctions.

The combination of multiple subclinical dysfunctions, unrecognized by either the physician or the individual, may hamper the attempt to provide good primary care services (Hillier et al., 1997; McAllister, 1997). Furthermore, a person’s decreased ability to control impulse behavior, mild to moderate agitation, or lack of ability to achieve comfortable social interaction may combine with chemical dependency problems or lifestyle choices related to high-risk behavior. These interactions may seriously jeopardize the success of patient-provider interaction and cooperation (Powell et al., 1996; Spatt et al., 1997).

Assessment of TBI

A plethora of measures has been used to assess functional outcomes from TBI. A number of concerns have been raised relating to their use, particularly as they apply to long-term outcome. This brief review discusses some of the measures that are available and have been successfully used, highlighting their various strengths and weaknesses. Because of the prominence in rehabilitation provided by the World Health Organization’s (WHO) original distinctions between impairment, disability, and handicap (World Health Organization, 1980) and its more recent characterization (World Health Organization, 1997), this review will be cast in WHO’s framework. This new version supplants the concepts of disability and handicap, respectively, with limitations of activities that result from impairment and the consequent restrictions to participate in society to the same degree as before the occurrence of the impairment (in this case, before the onset of TBI).

It is not particularly difficult to distinguish impairment measures (i.e., those that directly measure cognitive, neuropsychiatric, behavioral, and linguistic consequences of TBI) from those purported to address the impact of these impairments on interpersonal and societal functioning. However, the lines of demarcation between the latter are often far from clear, tending to blur in application. In this review, impairment measures followed by a selected number of more frequently used outcome measures that address participation in family, work, community, and so forth following TBI will be discussed. The measures reviewed here are largely, although not exclusively, guided by recommendations made by Hall and Johnston (1994) for the development of a nationwide data system to describe functional outcomes for TBI rehabilitation. This section ends with a short critical comment on assessment of functional outcomes following TBI.

Some measures are used to predict outcome; others, typically administered at the beginning and again at the end of rehabilitation, are used to document progress in treatment and more indirectly relate to functional outcomes. Descriptive measures, largely directed toward restrictions in activity and participation in society, become important during rehabilitation, when work and community reentry programs might be in place or when rehabilitation interventions in a formal sense have ceased. It is at this stage, too, when the chronic effects of TBI have surfaced, that rating scales and quality-of-life measurements can best be supplemented with hard demographic information enumerating such things as return to work or school, resumption of family life and social contact, and so forth and that issues of care-giver burden can be addressed.

Measures Used During Rehabilitation

Predictive Measures of General Impairment

Cifu and associates (1997) have investigated a number of measures administered during the acute stage of TBI that can collectively predict return to work. These measures are described below.

The Glasgow Coma Scale (GCS) (Teasdale, Jennett, 1974). This simple assessment technique is used to assess level of impaired consciousness and coma during the acute stage of TBI postinjury. The GCS has three main components, which address (1) the minimal stimulus necessary to elicit eye opening (4 = spontaneous, 1 = does not respond); (2) verbal responding (5 = can converse, is oriented; 1 = makes noise); and (3) best motor response (6 = follows simple commands, 1 = no motor response to pain). Scores can range from 3 to 15, with severe = GCS < 8; moderate = 9 to 12; mild >13. The GCS has wide general acceptance for determining severity of TBI. It is currently thought to be the best initial predictor of recovery (Bishara et al., 1992; Klonoff et al., 1986; Ponsford et al., 1995). However, Ponsford and colleagues also noted that when used alone, GCS scores appear to account for less that one-third of the variance in prediction of outcome. Zafonte and colleagues (1996) studied the considerable database of the Multicenter TBI Model Systems and concluded that when the GCS was used as the only variable, it had only a modest, but statistically significant, relationship with other measures of outcome and is thus of limited utility in prediction of outcome.

Level of Cognitive Functioning Scale (LCFS). Also known as the Rancho Scale (for the hospital in which it was developed), this 8-point scale was developed to measure levels of responsiveness during hospitalization or rehabilitation. The LCFS ranges from 1 = nonresponsive to 8 = purposeful and appropriate response. Although it has been widely adopted, it suffers a lack of systematic data on its reliability and validity. Mysiw and colleagues (1989) report that the scale discriminates between people who can return to competitive employment and those who might benefit from vocational training, but it is insensitive to lower levels.

Glasgow Outcome Scale (GOS) (Jennet, Bond, 1975). Although it has been widely criticized because of its difficulty in discriminating at the higher end of its 5-point scale, the GOS is mentioned here because of its pervasive use in rehabilitation. Outcomes are graded as 1 = death, 2 = persistent vegetative state, 3 = severe disability (conscious but disabled), 4 = moderate disability, and 5 = good recovery. Marshall (1987) notes: "A problem we have encountered with the GOS is the tendency to equate a good outcome with a return to normal behavior, when in fact any patient who has suffered a severe head injury will experience some deficits."

Measures of Cognitive Impairment

TBI has potential for disturbing a wide array of cognitive processes, including attention, speed and depth of information processing, language, memory, executive functioning, complex reasoning, and so forth. An even larger array of tests for assessing the variety of behaviors subsumed under these broad headings exists. For example, Lezak, in the latest edition of her comprehensive text of neuropsychological measures (1995), lists more than 100 neuropsychological measures for which some (possibly rudimentary) standardization exists and which could be of potential interest for individuals with TBI. Similarly, Frank and Barrineau (1996) surveyed speech language pathologists and reported that their respondents used 36 different (and largely standardized) measures for assessing language and communication. Finally, a number of comprehensive neuropsychological test batteries are also frequently used.

Most TBI treatment programs appear to have an institutionally selected protocol of such measures in place to permit routine assessment of cognitive impairment, but there is wide variation in the tests chosen for these protocols. Typically, detailed assessments are made early in the treatment both to guide treatment and to provide a basis for comparison at discharge, although this assessment process has recently been challenged (Ricker, in press). Changes on such measures at discharge are taken as indications reflective of the effectiveness of the treatment provided.

Concerns have been raised regarding the use of impairment measures to predict outcome. Such measures, taken relatively early in the course of recovery from TBI, may be contaminated by spontaneous recovery. More important is concern over the ability of such measures to reflect changes in behaviors that are important in daily living (i.e., they have poor ecological validity) (Crapeau, Scherzer, 1993; Rattok et al.,1992; Ricker, in press.)

In addition to the above-identified impairment-based measures, a number of rating scale approaches to predicting outcome are invoked on discharge from formal rehabilitation. Like the impairment measures described above, these measures typically have also been used early in the rehabilitative process. Included here are what appear to be some of the most widely used measures, again guided in part by the measures cited by Hall and Johnston (1994) and Cifu and colleagues (1997).

Disability Level

Disability Rating Scale (DRS) (Rappaport et al., 1982). The DRS rates behavior in four categories: (1) arousability and responsivity, (2) cognitive ability for self-care, (3) dependence on others, and (4) psychosocial adaptability, with ratings being made for various behaviors in each category. Level of disability is indicated by the cumulative scores of each category, ranging from no disability (cumulative score of 0) to death (score = 30). The DRS is simple to administer and has well-documented validity and reliability (Grouvier et al., 1987). Ponsford and colleagues (1995) found that although a combination of variables correctly predicted work status at 2 years postinjury (and was cross-validated with a second group of individuals), the DRS "was by far the greatest contributor to the discriminant function (correlation = .86)."

Functional Independence Measure/Functional Assessment Measure (FIM/FAM) (State University of New York at Buffalo, 1993; Hall, 1992). These are possibly the most widely used measures addressing issues of functional outcomes of the rehabilitation process. Self-care, sphincter control, mobility, locomotion, communication, and social cognition are rated on a 7-point scale addressing relative independence. The FIM/FAM are a part of the data set gathered by the Traumatic Brain Injury Model Systems of Care Project. Preliminary Model Systems data indicate improvement in functional ability from a level of moderate assistance to modified independence at 1 and 2 years postinjury (Rosenthal, presentation to Panel, 1998). A general limitation of the FIM/FAM for measuring functional outcome is its relative lack of coverage of cognitive and communication issues, with resultant insensitivity to them. Substantial ceiling effects also have been noted, again limiting sensitivity for changes, particularly in community followup (Hall et al., 1996).

Living With the Consequences of TBI: Participating in Daily Activities, Functioning in Society

The mixture and complexity of psychosocial, behavioral, and interpersonal problems that can occur following the injury, as well as its effects on family, colleagues, and the workplace (or school), have received considerable attention. Community reentry has been a dominant theme of extensive research in TBI. Numerous outcome measures have been developed for the study of various long-term aspects of many chronic diseases and conditions. What follows is a sampling of some of the measures that have been relatively well used and appear to have potential for expanding knowledge in this area.

Craig Handicap Assessment and Reporting Technique (CHART) (Whiteneck et al., 1992). This 30-item measure samples 6 domains (assistance, mobility, transportation, activities, social relationships, finances) and was specifically designed to quantify handicap. It was initially validated for individuals with spinal cord injury but has recently been used effectively to measure the handicap associated with TBI as well (Boake, High, 1996; Corrigan et al., 1998).

Community Integration Questionnaire (CIQ) (Willer et al., 1993). This is a 15-item scale in the form of a structured interview requiring simple 1- or 2-word responses for rating home and social integration and integration into productive activities. It has been shown to have good test-retest reliability and internal consistency. The CIQ also discriminates between individuals with TBI and those with no apparent disabilities. Sander and colleagues (1996) recently used the CIQ to document the adverse impact of TBI on employment, although they reported that the measure did not clearly document the effect of brain injury on socialization and home activity patterns. Hall and colleagues (1996) recently noted ceiling effects for two of its three subscales. Dijkers’ (1997) review of 11 studies using the CIQ suggests that, although the measure is promising, it should still be considered as a research instrument with future modifications addressing its relationship to impairment and disability, further work with norming, and so forth.

Portland Adaptability Inventory (PAI) (Lezak, 1987). This inventory provides a systematic record of personal and social difficulties that have potential to interfere with resumption of normal family relationships and social activities. Three general categories are sampled: temperament and emotionality, activities and social behavior, and physical capabilities. The PAI has strong psychometric properties and has been shown by Malec and colleagues (1993) to predict rehabilitation outcome well. However, because of the lack of sensitivity found with the temperament and emotionality scale, Malec and Thompson (1994) adapted it (into the Portland-Mayo Adaptability Inventory) and reported on its successful use.

Katz Adjustment Scale-Relatives Form. (KAS-R) (Katz, Lyrely, 1963). This scale has been in use to study TBI for more than a decade. It was originally designed to assess personal, interpersonal, and social adjustment of psychiatric patients. The unique feature of this measure is that its data are collected from a relative’s perspective, on the basis that many persons with TBI cannot reliably rate their own behaviors. The KAS-R has five subscales, addressing social behavior, level of performance, expectations for performance of social activities, and two scales concerning how time is spent. A modification designed specifically for individuals with TBI has been developed by Jackson and colleagues (1992), and further work attesting to the appropriateness of a different revision has been provided by Goran and Fabiano (1993).

The American Speech-Language-Hearing Association Functional Assessment of Communication Skills for Adults (ASHA/FACS) (Frattali et al., 1995). This scale is mentioned here because it has been standardized on adults with TBI as well as those who suffered aphasia as a result of stroke. Its goal is to provide a special assessment of the communication behaviors that have an impact on daily living. ASHA/FACS has been carefully constructed, has excellent test-retest and interrater reliability, and has sound psychometric properties.

Quality of Life/Life Satisfaction

Although several studies have been conducted using some of the hundreds of available quality-of-life assessment instruments, no such instruments have been validated for specific use with the population of individuals with TBI. The larger issues of quality of life, independent of return to the community, school, or work, have been largely ignored in relation to TBI. One possible explanation is that quality-of-life measures to some large extent depend on subjective evaluations, and perhaps investigators have been reluctant to undertake such measures with individuals who are likely to have residual difficulties with self-awareness. An additional problem could be related to language difficulties encountered in some individuals with TBI. Nonetheless, at least these two following brief measures should be applicable, perhaps in modified form, such as using them as interviews.

The Dartmouth COOP Functional Assessment Charts (Nelson et al., 1987; Nelson et al., 1996). COOP charts focus on a different aspect of functional status: physical fitness, feelings, daily activities, change in health, overall health, social support, quality of life, and pain. Each response is scored on a 5-point ordinal scale, illustrated by a drawing depicting a level of well-being. The charts have good test-retest reliability and good convergent and discriminant construct validity. Their simple format is promising for use with the population of persons with TBI.

Medical Outcomes Study (MOS) 36-Item Short Form Health Status Survey (SF-36) (Ware, Sherbourne, 1992). This 36-item measure has the goal of providing a basis for describing population health in comprehensive terms and for comparing the relative burden of disease. Most items fit into eight scales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. This measure is widely available and very well documented. Ware and Sherbourne suggest using the SF-36 as a "generic core," supplementing it with other more specific measures.

Consequences of TBI for Children

The available literature does not suggest different mechanisms for recovery as a function of age of injury. That is to say that the primary mechanism whereby change is effected in children is learning. The well-recognized greater plasticity of younger over older brains suggests that recovery should be more easily effected in some areas in younger versus older children and in children compared with adults. There are some data to substantiate this notion, particularly for children who have experienced mild to moderate TBI (Tompkins et al., 1990; Ewing-Cobbs et al., 1997). However, there is also a body of information suggesting that severe TBI in infants and preschoolers produces a large array of persistent cognitive deficits (Ewing-Coggs et al., 1989). These deficits affect not only age-appropriate skills. For example, Chapman and colleagues (1998) point out that some children with apparent recovery of spoken language following TBI later have difficulty in organizing their discourse and their thinking and, ultimately, learning to read. These authors also question the notion that younger infants and toddlers, supposedly those with the most plastic of brains, have the least profound consequences of severe TBI. Berney and colleagues (1994) have noted that TBI is different in infants, toddlers, and older children, with different physiological consequences. For example, although TBI is considered to be less severe in infants, seizures were a much more frequent consequence in infants than in older children. Furthermore, some evidence suggests that bilateral prefrontal injury probably impairs young children more than it impairs adolescents and young adults. Finally, some researchers (Damasio, 1997) have suggested that dorsolateral and dorsomedial prefrontal brain damage results in persistent inefficient or ineffective ability to store information and to control impulsivity and lack of self-awareness and self-regulation.

Bates and colleagues (1992; in press) advance the argument that in a maturing organism, it is difficult to talk about recovery in an absolute sense, suggesting rather that the process is strongly influenced by stages of development; that is, children recovering from TBI go through the process again and again as more complex behavior is expected at subsequent stages of development. These investigators state that prefrontal TBI in childhood creates substantial vulnerability for behavioral and psychosocial disability in development. They argue that vulnerability is not inevitability, that it is important to be on the alert for the possibility of delayed consequences of prefrontal injury in children, and that there is no reason to be fatalistic about intervention.

Patterns of injury are different for children of different ages. Infants and toddlers have more skull fractures, more benign injuries, and fewer comas. They also more frequently have lateralized signs than older children have, and early seizures are much more frequent in infants than in older children. Older children (age > 15) have more comas but less subdural effusion or contrecoup. Children ages 9 to 15 have consequences more similar to those of older children than to those of infants and toddlers. Parents and schools are critical components of the learning mechanism for children with TBI. Much of pediatric rehabilitation is centered on orienting, training, and supporting parents and school staff, in addition to some direct interventions undertaken with children themselves.

Not surprisingly, outcomes for children with TBI are typically measured in different ways from outcomes for adults. The choice of measures used is highly age dependent. For infants and toddlers, outcomes are often related to the age at which developmental milestones, such as relevant features of age-appropriate language, are acquired subsequent to TBI. For older children, grade-schoolers, and even adolescents, measures of intellectual functioning, language functioning, and school performance are typically substituted for the more specifically outcome-oriented measures that characterize outcomes measurement in adults. Because of the persistence of language disorder and cognitive disorganization as manifested through discourse in what appears as a distinctive subgroup of TBI children, Chapman and colleagues (1998) suggest that analysis of discourse might be a powerful measurement of outcome.

Fletcher and coworkers (1996) studied behavioral outcomes and adaptive functioning in a large group of children following mild to severe TBI. They measured outcomes with an instrument specifically developed for children, the Children’s Orientation and Amnesia Test (COAT), a measure for assessment of cognition during early stages of recovery. This test, an adaptation of the adult Galveston Orientation and Amnesia Test (GOAT) (Levin et al., 1979a), is reported to be a better predictor of verbal and nonverbal memory performance than is the GCS at 6 and 12 months postinjury (Ewing-Cobbs et al., 1990).

Consequences of TBI for the Family

Most of the research studies and clinical investigations of the effect of TBI have focused on the individual with the injury, including his or her acute and long-term physical, cognitive, and behavioral symptoms, the extent to which and when he or she is able to resume previously held roles, and his or her continuing need for services and support. The impact for society, particularly the cost of TBI, has also received some attention.

In addition, there is a growing literature on the impact of TBI on the family of the person with TBI. Although this literature is limited by methodological problems, a clear pattern of findings has emerged. Most studies on the effect of TBI on the family have found that family caregivers experience considerable stress and strain and suffer long-range negative consequences as a result of their care-giving responsibilities for the family member who has TBI (see Kreutzer et al., 1992, for a review of the literature).

In general, studies show that family members manifest different patterns at various points after TBI. Initially, the most common reactions are relief that the relative has survived the injury and denial of the long-range consequences (Resnick, 1993). However, over the course of the first year postinjury, family members are at increasing risk for anxiety, depression, and social isolation (Kreutzer et al., 1992). In general, the physical sequelae of TBI are not as stressful for the family caregiver as the behavioral sequelae (Gray et al., 1994; Kreuzer et al., 1992). In addition, although the individual’s symptoms tend to stabilize during the first year after the injury, the family caregiver remains distressed over a much longer period of time (Gray et al., 1994). For example, Linn and colleagues (1994) found that on an average of 6 years after the injury, 73 percent of the spouses of persons with TBI had symptoms of depression and 55 percent had elevated levels of anxiety. Feelings of subjective burden have been found to remain high over the course of many years (Brooks et al., 1987).

There is some evidence of different impacts on the family depending on the type of kinship relationship between the family caregiver and the person with TBI. In general, spouses (mainly wives, given the sex of most persons with TBI) have been found to have more adverse reactions than parents (Kreutzer et al., 1992; Leathem et al., 1996; Liss, Willer, 1990). Reasons for the more adverse outcomes for wives include the following: (1) wives are alone in the role of primary caregiver when the husband is injured, whereas parents can share responsibility for care-giving for their injured child; (2) parents can revert to their prior role of taking care of their child, whereas a wife must assume a care-giving role for someone who previously was an equal partner; (3) wives experience more social isolation than parents because they do not have partners with whom to participate in social activities; and (4) there are greater negative financial impacts on wives because of the loss of the earnings of their injured husbands and the need to reduce their own work hours to provide care, whereas it is generally the case that at least one parent of a person with TBI can maintain employment (Hall et al., 1994). In addition, TBI has been shown to put the marital couple at risk of emotional and sexual dysfunction (Kreutzer et al., 1992) and divorce (Liss, Willer, 1990).

Comparatively less research has been conducted on family caregivers other than the parents or spouses of an adult suffering a TBI. Pediatric TBI has a unique set of impacts on the family (Crouchman, 1990). Parents of injured young children experience a range of stresses resulting from the shock of the injury and the anticipation of the need to provide often decades of care, which can impair their psychological and social well-being. For example, Rivara and colleagues (1992) reported that at 12-months postinjury more than half of the families in their sample (n = 94) had high levels of stress and problematic family relationships. Well-functioning families often are able to deal with the challenges of parenting a child with TBI, whereas parents who already were experiencing difficulties may not be as successful (Conoley, Sheridan, 1996; Wade et al., 1996).

As with other family caregivers, the initial reaction of parents to TBI in their child is the concern for the survival of their son or daughter. After the child has been stabilized, parents are often encouraged by the rapid recovery that children experience in the early months after injury. However, the rate of recovery generally slows down after 1 year. As has been reported for other family caregivers of persons with TBI, parents often find that the psychological, behavioral, and emotional changes in their child are more difficult to cope with than the physical changes (Conoley, Sheridan, 1996).

There are few studies of the effect of TBI on other kinship relationships. For example, Pessar and colleagues (1993) studied children whose parent had suffered TBI and reported that such children had an elevated level of psychological and social adjustment problems. Others have reported similar patterns (Lezak, 1988; Urbach, Culbert, 1991), although at least one study did not show differences in children of TBI parents, as compared with controls (Hansell, 1990). Well siblings of persons with TBI have received almost no research attention, although they, like all other family members, are at risk for altered family life and long-range care-giving responsibilities (Maurer, 1991).

Although these studies converge in portraying family members of persons with TBI as at risk for psychological and physical distress, the research is limited by a number of methodological problems. Among the limitations of these studies are small sample sizes, differential lengths of time between injury and assessment of family impacts, and often a lack of a control group. In addition, several researchers have noted that even before the injury, families of persons who had TBIs had higher than average rates of emotional difficulties (Kreutzer et al., 1992) that may increase the risk of the TBI. There is no research that has separated the effects of these preinjury emotional problems (e.g., alcoholism in the family) from postinjury deleterious effects or determined whether such effects are additive or interactive. Nevertheless, the impacts on the family are noteworthy. Although individual accounts of personal experiences highlight family strengths and coping as well as family and personal distress (Johnson, 1995; Williams, Kay, 1991), the losses experienced by the family and their long-range risk of stress and strain remain the hidden impacts of TBI.

Consequences of TBI for the Elderly

Increasingly older people are surviving TBI. The incidence of TBI rises dramatically after age 50, reaching approximately 200 per 100,000 by age 65. Falls are the predominant cause; subdural and epidural hematomas are the most common pathologies. Effects, trajectories, and outcomes of TBI in the elderly are not yet fully delineated. Many agree that TBI in individuals beyond age 50 results in increased mortality, greater late mortality, delayed neurosurgical complications, increased morbidity, more severe functional and cognitive disabilities, and lengthened institutional stays (Pentland, Miller, 1986; Adams et al., 1989; Katz, Alexander, 1994; Levin, 1993; van Aalst et al., 1991; Rakier et al., 1995). Yet, others maintain that good outcomes are achievable (Cifu et al., 1996; Reeder et al., 1996; Gershkoff et al., 1993; Saywell et al., 1989). Indeed, up to 85 percent of elderly persons with TBI are discharged to community settings (Cifu et al., 1996; van Aalst et al., 1991; Davis, Acton, 1988). Using retrospective data from the National TBI Model Systems Projects (TBIMS), Reeder and colleagues (1996) reported that age was not associated with, and did not predict, the amount of functional improvement (FIM and DRS) after inpatient rehabilitation; in fact, age accounted for only 1 to 2 percent of the variance. In contrast, a prospective analysis (Cifu et al., 1996) of subjects from the TBIMS revealed that older subjects (55 to 86 years) had greater levels of functional disability as measured by FIM and DRS; it is noteworthy that the older group took twice as long to achieve one unit of change in functional measures. Thus, the elderly do benefit from rehabilitation efforts but exhibit much slower rates of functional recovery than do the young. No length-of-stay differences were found for the elderly with TBI in acute care settings (Cifu et al., 1996) but they had significantly greater lengths of stay (almost double the time) in rehabilitation settings incurred at significantly greater cost (Cifu et al., 1996). Lehmkuhl and colleagues (1993) found no relationship between length of stay and designated payer for rehabilitation services. In contrast, High and colleagues (1996) report that age, severity of injury, and complications all predict rehabilitation length of stay as well as hospital costs; further, payer sources associated with age influenced length of stay.

In a prospective study of cognitive performance, elderly persons with mild or moderate TBI were significantly more impaired after approximately 6 months than age-matched controls; more than half the sample exhibited poor memory, difficulty with attention, language problems, irritability, and slowness (Goldstein et al., 1994). This study supports findings from Mazzucchi and colleagues (1992) that global cognitive performance is impaired in more than half of aged individuals with TBI. Yet, it appears unlikely that age alone predicts outcomes. Factors that reduce the likelihood of independent living, such as medical complications, frailty, poor cognitive status, comorbidities, and absence of family support, need to be factored into prediction models along with age (Reeder et al., 1996). Over time, cognitive deterioration is common (Mazzucchi et al., 1992) and may even extend age-related cognitive declines (Klein et al., 1996). There is growing evidence that older adults may be at greater risk for developing frontal lobe dementia or Alzheimer’s disease (AD) following severe TBI (Heyman et al., 1984; Gedye et al., 1989; Mazzucchi et al., 1992; Mayeux et al., 1993; Tang et al., 1996). Altered personality and behaviors such as social withdrawal, apathy, and disinhibition, common in elders after TBI, are consistent with frontal lobe dementia. Individuals with a history of TBI and genetic susceptibility for AD (i.e., apolipoprotein E epsilon 4 genotype) are at a 10-fold risk for developing the dementia (Tang et al., 1996) and may show symptoms at an earlier age (Gedye et al., 1989). On postmortem exam, beta amyloid deposits are present in a third of persons with TBI spanning 8 weeks to 85 years of age (Roberts et al., 1995). In adults, increased deposits of beta amyloid 4 (particularly in temporal cortex) are greater than projected by normal aging, in fact, 20 percent more than in controls at age 60 or older (Roberts et al., 1995). Whether morphological changes are initiated by injury, indicative of preexisting pathology, and/or consistent with a given genotype requires further substantiation. It is noteworthy that in elderly persons with abnormal amyloid deposits, falls are the predominate cause of TBI. Many authors indicate a further need to prospectively examine recovery trajectories within and across age groups, identify constellations of factors that best predict recovery, clarify goals of rehabilitation, and analyze cost factors.

Economic and Societal Consequences of TBI

The economics of TBI is a multidimensional concept because the cost of this condition may be realized by many different parties, and these costs may be incurred over different periods. The main types of costs that should be examined are (1) direct costs for acute care and rehabilitation, (2) costs incurred by society because of the decreased ability of some persons with TBI to fully contribute as gainfully employed members of the work force, (3) indirect social costs related to decreases in the ability of family members and other caretakers to contribute in the job market and increased costs to judicial or social services systems, and (4) intangible costs of TBI, which attempt to enumerate the value of the decrement in health caused by the pain and suffering that individuals and their families experience.

Direct Medical Care Costs

A recent study using the TBIMS national database that followed individuals for 1 year postinjury found that the average charge in 1995 dollars for hospitalization for acute care was $105,823 and for inpatient rehabilitation was $58,415. Charges will vary by severity of TBI, with combined acute care and inpatient rehabilitation charges ranging from $72,628 to $117,260 for GCS scores 13 to 15 and 3 to 5, respectively (Lehmkuhl et al., 1993).

Reports of direct medical and rehabilitation costs may be somewhat misleading in that they are approximated using charges for the individual’s care, and costs and charges in the U.S. health care system are often not of similar magnitude. A certain portion of these charges may well be paid indirectly by other social or economic groups as uncollectable bills or hidden cost-shifting in services to others.

Furthermore, the costs reported are based on average costs calculated for groups of individuals. These costs are diluted by the relatively low cost for persons who do not complete their rehabilitation program because of lack of or discontinuation of funding. Ashley and colleagues (1993) reported that 9 of 238 individuals in a case series discontinued postacute rehabilitation because of lack of funding. The same authors report an increase in the proportion of individuals with the poorer coverage provided by accident and health policies, a decrease in program length of 18 percent or 45.7 days, and a 13 percent decrease in mean individual cost when records from 1986 to 1989 were compared with data from 1990 to 1991. They did not find these differences to be statistically significant, which is not surprising, given that they used ANOVA for their analysis. The use of multivariate regression models that controlled for risk, or transformed cost and resource use variables to improve the distribution of the data, might have found these large, economically important differences to be statistically significant, even under the constraint of such a small sample.

Other direct costs that may continue to recur for the life of the person with TBI include items such as medical equipment (e.g., wheelchairs and orthotics); attendants, home health aides, and long-term institutionalization; intermittent and/or continuous therapeutic modalities (e.g., physical therapy, occupational therapy, and marital counseling); drugs and supplies; home furnishings and accessories; and routine and crisis-related medical care for events, such as depression or suicide attempts, which have been reported in up to 30 percent of people with TBI, a much higher rate than is observed in a general population (Leon-Carrion, 1997).

Few recent studies have evaluated the cumulative averages for these costs for the current population. However, older studies such as the one cited by Stonnington (1991) found the "long-range costs of head injuries can run to well over a million dollars" over a lifetime. Johnston and Hall (1994) cite literature that indicates the estimates for rehabilitation and nursing home costs associated with TBI at $4.49 billion.

Direct, Indirect, and Intangible Social Costs

Johnston and Hall (1994) cite literature that indicates the estimates for costs of TBI associated with lost work are $20.6 billion and disability are $12.7 billion annually in the United States. McIntosh and colleagues (1996) estimate the "social cost(s) of TBI" (reflecting the lost productivity resulting from injury or death) to be between $1 billion and $25 billion per year in the United States.

These figures may grossly underestimate the total economic burden of TBI. They do not take into account other indirect social costs that are quantitatively inestimable and might include such items as loss of social contributions by the person with TBI to his or her community, family, and/or friends; increased social costs related to substance abuse and/or increased conflict with law enforcement or the legal system; increased costs to social support systems like Social Security, State, and local social services; and lost work productivity by family members caring for the person with TBI. Furthermore, none of these financial data will capture the enormous intangible cost that TBI places on individuals, families, and communities in terms of pain and suffering.

Impact of Reimbursement Policies and Access to Care on Rehabilitation Outcomes

The Panel sought published evidence for the effects of changes in medical insurance coverage on access to rehabilitation and outcomes for persons with TBI but found no pertinent reports. Ashley and colleagues (1993) report decreased charges and length of stay and a higher proportion of individuals with less comprehensive coverage in 1990 to 1991 than in 1986 to 1989 but no effect on outcomes. However, their choice of analytical methods makes a Type II error (missing an effect that is truly there) quite likely, given that they also report that nine individuals discontinued their program because of financial problems and that individuals who discontinued had significantly lower occupational status measures at discharge.

Anecdotal evidence indicates that access to rehabilitation for persons with TBI with cognitive problems is affected by at least two major factors: insurance coverage and the extent of physical consequences. This supposition is supported by reports in the literature: (1) Both charges and length of stay for inpatient rehabilitation vary greatly by payer (Lehmkuhl et al., 1993); and (2) individuals with mild or moderate TBI, and those with mainly cognitive problems, are less likely to receive inpatient rehabilitation than individuals with obvious and multiple physical impairments and functional limitations (Aronow, 1987).

Access to cognitive rehabilitation may also be affected by geographic location of facilities, but the Panel was unable to find data describing geographic patterns in access to and cost of care for TBI.

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Introduction

This chapter addresses what is known about the mechanisms underlying functional recovery following TBI and the implications of this knowledge for purposes of TBI rehabilitation. To focus on the most important issues, it is necessary to make a number of refinements in the concepts under consideration.

Mechanisms of Rehabilitation

The first aspect of the question to be refined is the meaning of rehabilitation and the time of onset of rehabilitative services. After investigating the neurobiology and neuropsychology of TBI mechanisms and potential treatment strategies for TBI, it appears that from the standpoint of scientific inquiry, the onset of rehabilitation must be construed as the onset of the brain injury itself. Why is this so, given the standard medical models of rehabilitation services, in which rehabilitation takes second place to acute medical interventions during the time immediately after the injury? The likely explanation is that the current medical model was devised before the concept of neurorehabilitation incorporated the emerging notion that the earliest period after an injury represents the period of greatest opportunity for brain and behavioral plasticity. Because this appears to be the case, this early period must be viewed as both the time of critical medical management and the time for the onset of rehabilitative intervention.

The second aspect of the question that must be refined is the scope of rehabilitation itself. Because rehabilitation must be construed as beginning in the acute period, does that mean that all interventions during this period are rehabilitative in nature? This is certainly not the case, because there is a significant amount of neurological and intensive medical care that must be delivered during this period, including control of the injury itself and its cause (e.g., bleeding) and management of the sequelae of the injury (e.g., edema, hypoxia). On the other hand, introduction of drugs or other treatments aimed at improving synaptic growth or short-term memory processes during this period are distinctly rehabilitative.

Finally, a third refinement concerns which mechanisms are to be discussed and which are beyond the framework of this chapter. This chapter focuses on biological and psychological mechanisms of TBI recovery and interventions to affect the course of this recovery. It does not address the medical sequelae and complications of TBI (e.g., aspiration pneumonia), the systemic manifestations of the injured brain (e.g., spasticity), or the social issues faced by people with brain injuries. These topics are addressed in other chapters of this document.

Levels of Inquiry

There are a number of levels of organization and of scientific inquiry of the central nervous system (CNS), and each level focuses on particular types of scientific entities, incorporates its own set of theoretical constructions, and leads to specific types of treatment ideas. Each of these frameworks provides insights into the mechanisms of TBI and recovery and consequently to the applied issues of neurorehabilitation.

Within this hierarchy of scientific inquiry for neuroscience are three focal points for study: (1) the nerve cell (neuron) itself, its components, its development, and its functioning; (2) the neural network and its structure and function; and (3) the organism and its behavior. The mechanisms of TBI can best be understood neurobiologically with respect to these perspectives, as can the possible courses of intervention based on these mechanisms.

The neuron undergoes dramatic changes with TBI, many of which lead to some of the damaging sequelae of the injury. Cellular and molecular changes after TBI include ion concentrations, membrane function, and protein synthesis. Many neural networks manifest changes after TBI, such as neurotransmitter concentrations, pattern of connectivity, efficiency of communication, and other functions. These levels of inquiry and understanding affect the ways in which the mechanisms of TBI have been investigated and are reflected here.

This chapter is organized into three broad sections, focusing on (1) the biological mechanisms of TBI, (2) the cognitive and behavioral mechanisms of TBI, and (3) the mechanisms of effecting change in behavior and biology following TBI.

Basic Cellular and Molecular Mechanisms of TBI

The initial event in TBI is the transmission of mechanical forces through the calvarium and distortion and disruption of neural and vasculature structures. Following this primary mechanical insult, multiple cascades of delayed or secondary neuropathological processes are initiated that can potentially exert profound effects on neurological homeostasis, function, and recovery.

Axonal Injury

Axonal injury is a prominent feature of TBI and can occur as either an immediate or a delayed consequence. In TBI, primary mechanical disruption of axons usually does not cause instantaneous cell death, but it does lead to axonal disruption over a longer time period (Graham, 1996). Traumatic axonal injury and dysfunction are determined by the amount of axonal stretch and can be categorized into four distinct stages (Gennarelli, 1996), including (1) nodal membrane injury, (2) reversible cytoskeletal damage, (3) secondary axotomy, and (4) primary axotomy.

Ionic Fluxes

Alterations in ionic intracellular and extracellular concentrations represent an early pathologic consequence of TBI. Widespread neuronal depolarization may result from shifts in ionic gradients and excessive neurotransmitter release (Hayes et al., 1992). Calcium, magnesium, and potassium all have been implicated in the pathophysiology of TBI. The extent to which these transient ionic fluxes influence acute functional impairment remains to be determined.

Calcium

Finerman and colleagues (1993) observed a prolonged accumulation of intracellular calcium following a lateral fluid percussion (FP) brain injury in the rat. This accumulation, which occurred primarily in the ipsilateral cerebral cortex, dorsal hippocampus, striatum, amygdala, and lateral geniculate, was dependent on the severity of the injury. In animals that sustained no gross morphological damage, the calcium accumulation resolved within 4 days, whereas animals experiencing morphological changes after lateral FP injury exhibited a longer lasting accumulation of calcium. It has been suggested by Nilsson and colleagues (1993) that the massive calcium intracellular entry associated with compression contusion trauma is mediated by leaky membranes exposed to shear stress that results in acute functional impairment.

Potassium

An increase in extracellular potassium concentration of the rat hippocampus following FP concussive brain injury has been reported (Katayama et al., 1990). Nilsson and colleagues (1993) observed that contusion trauma produced a transient membrane depolarization associated with a pronounced cellular release of potassium. Takahashi and colleagues (1981) postulated that the potassium efflux in the cerebral cortex and brainstem during the acute stage of experimental TBI plays a role in the genesis of concussion. During impact, alterations in the neuronal membrane result in increased extracellular potassium that enhances neuronal excitability at modest levels and impedes neuronal activity at markedly elevated levels. In support of this hypothesis, Eidelberg and colleagues (1975) have suggested that axonal conduction block caused by increased extracellular potassium could interfere with long tract function immediately after spinal cord injury.

Magnesium

Declines in intracellular free magnesium may be associated with irreversible tissue injury after TBI (Vink et al., 1988a). Vink and colleagues performed phosphorus magnetic resonance spectroscopy (MRS) and found that FP brain injury in rats resulted in a profound and rapid decrease in intracellular free magnesium that correlated with the severity.

Neurotransmitters

Several neurotransmitters have been implicated in the cascade pathophysiological events following TBI. Excitatory neurotransmitters, such as glutamate and acetylcholine (ACh), have received the most attention, yet alterations in dopamine (DA), serotonin (5HT) and gamma-amino butyric acid (GABA) function can also be anticipated.

Glutamate

Brain trauma results in the release of glutamate and the activation of N-methyl D-aspartate (NMDA) receptor-mediated neurotoxicity. Faden and colleagues (1989) noted a marked increase in extracellular glutamate and aspartate adjacent to TBI induced by FP in rats. This elevation correlated with the severity of TBI and was associated with a reduction in intracellular free magnesium. Treatment with a noncompetitive NMDA antagonist dextrorphan limited the resultant neurological dysfunction and increased the intracellular free magnesium.

Similarly, Nilsson and colleagues (1990) and Palmer and colleagues (1993) reported increased extracellular glutamate and aspartate levels following TBI using a cortical impact model in the rat. Bullock and colleagues (1991) observed that severely ischemic cortex underlying an experimentally induced subdural hematoma glutamate and aspartate levels increased more than 750 percent over basal levels. The magnitude of glutamate release correlated with the extent of focal ischemia. In humans, elevated concentrations of glutamate in the cerebrospinal fluid (CSF) have also been reported (Baker et al., 1993).

Acetylcholine

ACh levels increase acutely as a result of widespread neuronal depolarization associated with TBI. Gorman and colleagues (1989) reported a transient increase in ACh within 5 to 10 minutes of experimental TBI. Saija and colleagues (1988) noted that concussive brain injury leads to a striking increase in ACh turnover in the dorsal pontine tegmentum at 12 minutes and 4 hours after injury. An increase in ACh turnover was noted in the thalamus at 4 hours. There were no significant changes in hippocampal ACh content or turnover following injury. A decrease in ACh turnover was noted in the amygdala 4 hours after injury.

It has also been observed that ACh is present in the CSF within a few hours of TBI and may last as long as 48 hours (Bornstein, 1946). In humans experiencing severe TBI, it has been observed that these individuals exhibit low cholinesterase activity and elevated ACh levels in the CSF (Tower, McEachern, 1948). These abnormalities were noted to resolve with recovery. It has been suggested that "free ACh" may be one of the physiological factors underlying the acute paralytic and excitatory phenomena of cerebral concussion and more severe craniocerebral injuries (Bornstein, 1946). In support of the notion that ACh may be involved with the acute effects of TBI, it has been speculated that concussive unconsciousness may be partially attributable to the activation of cholinergic dorsomedial pontine tegmentum (Hayes et al., 1984). Pretraumatic depletion of ACh, which blunts the ACh response to FP brain injury, significantly attenuates components of behavioral suppression observed after concussion in experimental animals (Robinson et al., 1990).

Another effect of TBI on the cholinergic system is a reduction in central cholinergic transmission, which may be responsible for the memory impairment associated with TBI. Rats subjected to FP injury exhibit memory deficits that are similar to those that have received lesions to the septohippocampal system (Gorman et al., 1996). Gorman and colleagues (1996) noted decreases in choline acetyltransferase activity in areas related to memory (the dorsal hippocampus and the frontal and temporal cortices) 1 hour after TBI. In other animal studies, choline acetyltransferase immunoreactive cells in the basal forebrain were found to be reduced 10 days after FP injury (Leonard et al., 1994). Although loss of cholinergic neurons has been noted in the ventrobasal forebrain, corresponding loss of cholinergic neurons in the pontomesencephalic region has not been observed (Schmidt, Grady, 1995). Postmortem brain examination of persons with TBI noted a decrease in presynaptic cholinergic neurotransmission in the inferior temporal gyrus (Dewar, Graham, 1996). This reduction of choline acetyltransferase in persons with TBI was approximately 50 percent that of controls. In rodents, it has been postulated that TBI-induced loss of ventrobasal forebrain cholinergic neurons that project to hippocampus (i.e., medial septal nucleus, nucleus of the diagonal band of Broca, and the nucleus basalis of Meynert) is linked to the impairment of spatial learning (Schmidt, Grady, 1995).

In addition to the above-mentioned aspects, ACh may affect other pathophysiologic processes involved with TBI. ACh may potentiate the neurodegenerative actions of glutamate and lower the threshold for glutamate-induced neurotoxicity in cultured hippocampal neurons (Mattson, 1989). It also has been observed that the release of amyloid precursor protein stimulates the activation of muscarinic ACh receptors (Nitsch et al., 1992).

Dopamine

Changes in dopaminergic function have been observed in TBI. Hypothalamic levels of dopamine (DA) are increased following FP injury in the rat (McIntosh, Yu, 1989). Gennarelli and colleagues (1994) noted DA receptor changes following TBI in humans. These investigators reported increased uptake of DA in the striatum along with reductions in D1 receptors and increases in the D2 receptors. In the motor cortex, D2 receptors were increased. In the temporal lobe, there were D2 receptor elevation and marked reductions in D1 receptors. It was concluded by these investigators that DA transporter sites are unregulated in response to increased levels of DA release following severe TBI (Gennarelli et al., 1994).

Serotonin

The serotonergic system has been implicated in the pathophysiology of TBI. In experimental animals, 3 days after the cerebral cortex was lesioned, 5HT synthesis increased throughout the injured cortex and coincided with the time of greatest glucose hypometabolism (Tsuiki et al., 1995). Increased 5HT synthesis was also noted in the medial geniculate and the dorsal raphe. It was suggested that glucose hypometabolism in the cortex of the lesioned hemisphere is associated with increased 5HT synthesis mediated by the dorsal raphe (Tsuiki et al., 1995).

Gamma Amino Butyric Acid

Extracellular levels of GABA are markedly elevated following concussive brain injury in experimental animals (Nilsson et al., 1990). However, whether GABAergic inhibition plays a protective role in TBI remains to be delineated.

Endogenous Opioids

Evidence suggests that the endogenous opioid peptide dynorphin may be a mediator of secondary brain injury following experimental TBI. McIntosh and colleagues (1987b) measured alterations in regional concentrations of endogenous opioids following TBI in the cat and found that severe TBI caused a significant increase in dynorphin immunoreactivity in the striatum, frontal cortex, parietal cortex, pons, and medulla. Regional cerebral blood flow (McIntosh et al., 1987a) and neuropathological changes (McIntosh et al., 1987b) tended to be more pronounced in the regions exhibiting significant increases in dynorphin, therefore suggesting a role for dynorphin in the injury process. It has been suggested that dynorphin exerts its effect via a kappa opiate receptor because the administration of an opioid kappa-receptor antagonist improved neurological outcome following experimental TBI in the cat (McIntosh et al., 1987a).

In addition, it has been observed that dynorphin also causes increases in extracellular concentrations of glutamate and aspartate when stereotactically administered into the rat hippocampus (Faden, 1992). Accordingly, the pathophysiologic effects of dynorphin may involve both opioid and non-opioid mechanisms.

Inflammatory and Immunological Responses

TBI triggers a variety of inflammatory and immunological responses that are either protective and/or detrimental to CNS. Soares and colleagues (1995a) observed that TBI elicits an inflammatory leukocytic recruitment in areas where there is concomitant blood brain barrier (BBB) breakdown and neuronal degeneration. The breakdown of the BBB after TBI is also associated with pronounced abnormal permeability to endogenous immunoglobulins and extravascular accumulation in the brain parenchyma (Tanno et al., 1992).

Arachidonic Acid and Eicosanoids

Arachidonic acid released from cell membrane phospholipids and its metabolites (eicosanoids) represent physiologically active unsaturated fatty acids that are potent mediators and/or modulators of delayed or secondary brain injury in TBI. The eicosanoids include the primary prostaglandins, the cyclic endoperoxides, the prostanoids, the leukotrienes, and other acid lipids (Leslie, Watkins, 1985). Both the cyclooxygenase and lipoxygenase pathways have been implicated in the pathophysiology of TBI.

In rats, experimental FP injury results in dramatic increases in brain prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) (Dewitt et al., 1988). Transient elevation of brain prostaglandin levels (lasting less than 1 hour) may be associated with some neuropathologic processes following TBI (Ellis et al., 1981). Increased prostaglandin synthesis after concussive TBI in experimental animals generates oxygen free radicals that result in arteriolar damage (Wei et al., 1981). Shohami and colleagues (1987) suggest that increased synthesis of PGE2 and prostacyclin (PGI2) may be partially responsible for posttraumatic brain edema.

Leukotrienes formed by the breakdown of arachidonic acid via the lipoxygenase pathway may also be involved in the pathophysiology of TBI. Kiwak and colleagues (1985) found an increase in brain leukotriene immunoreactivity following concussive brain injury in the gerbil. Peak levels of immunoreactivity occurred within 15 to 30 minutes after the traumatic insult and returned to baseline within 24 hours. Dhillon and colleagues (1996), using a lateral FP injury paradigm in the rat, observed elevated levels of leukotriene C4 (LTC4) in the injured cortex and the ipsilateral hippocampus that persisted for 2 hours. These investigators speculated that LTC4 may play a role as a mediator in the BBB breakdown associated with FP injury in rats. Support of this hypothesis is provided by the observation that intraparenchymal injections of leukotrienes and arachidonic acid increased BBB permeability in the rat and that the response to arachidonic acid was prevented by pretreatment with a lipoxygenase inhibitor (Black, Hoff, 1985).

Cytokines

Both animal and human studies suggest that cytokines play a pathophysiological role in TBI. Increases in brain interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF) alpha have been observed after experimental TBI in the rat (Woodroofe et al., 1991; Yan et al., 1992; Taupin et al., 1993; Fan et al., 1995). In persons experiencing TBI, increased plasma and ventricular IL-6 (McClain et al., 1991) and plasma TNF (Goodman et al., 1990) have been reported. Sources of cytokine production include macrophages and neutrophils, which have infiltrated brain and microglia that reside in the brain (Woodroofe et al., 1991). It has been speculated that elevated cytokines play a major role in secondary tissue injury (Ott et al., 1994).

Oxygen Free Radical Formation

Oxygen free radicals may be important mediators of brain injury and brain edema (Ikeda, Long, 1990). Several pathways of oxygen free radical production have been identified and include arachidonic acid metabolism, catecholamine oxidation, mitochondrial reduction of oxygen, xanthine oxidase, activated neutrophils, and the accumulation of reduced metabolites (Ikeda, Long, 1990). Kontos and Wei (1986) demonstrated that experimental TBI results in the generation and appearance of superoxide in the extracellular fluid space that persists for at least 1 hour following TBI. This superoxide and/or radicals derived from it are responsible for sustained vasodilation and reduced responsiveness of cerebral arterioles to arterial hypocapnia following TBI.

Neurotrophic Factors

Neurotrophic factors (NTF) promote neuronal outgrowth in the developing nervous system and may potentiate neuronal survival and synaptic connectivity in response to TBI.

Nerve Growth Factor

Using the weight drop and controlled cortical contusion models of TBI, DeKosky and colleagues (1994) noted significant increases in nerve growth factor (NGF) protein in the cortex. In addition, NGF RNA increased fivefold by 1 day after the trauma. It was hypothesized that the elevation of NGF following TBI induces up-regulation of enzymes that suppress free radical formation and that NGF serves as a mediator of oxidative homeostasis (Goss et al., 1997). Furthermore it was suggested that elevated IL-1B following TBI initiates a cascade of events among which may be an up-regulation of NGF (DeKosky et al., 1994).

Leonard and colleagues (1994) observed a significant decrease in NGF receptor immunoreactivity 10 days after FP injury in the rat. It was speculated by these investigators that this reduction in NGF receptor neurons may reflect the down-regulation of protein synthesis rather than neuronal death.

Basic Fibroblast Growth Factor

Finkelstein and colleagues (1988) observed increased basic fibroblast growth factor (bFGF) immunoreactivity at the borders of focal brain wounds that localized to a dense accumulation of cells that resembled reactive astroglia. Regional increases in bFGF have also been reported in the hippocampus following entorhinal cortex (EC) lesioning of fimbria-fornix transection (Gomez-Pinilla et al., 1992). Fibroblast growth factor (FGF) has also been reported to raise the threshold for glutamate neurotoxicity and antagonize the dendritic outgrowth-inhibiting actions of glutamate, presumably by reducing glutamate-induced rises in intracellular calcium (Mattson et al., 1989). A delayed response of bFGF includes the stabilization of calcium homeostasis and induction of antioxidant enzymes (Mattson, 1996).

Amyloid Precursor Protein

Amyloid precursor protein (APP), a transmembrane glycoprotein that is the source of the beta amyloid peptide, may be an acute phase reactant to TBI (Graham et al., 1995) and may be a marker of axonal injury (Gentleman et al., 1993; Blumbergs et al., 1994; Sheriff et al., 1994). Deposits of beta amyloid protein have been observed in the brains of 30 percent of people with fatal TBI (Graham et al., 1995).

Apolipoprotein E (APOE) genotype may also play a role in amyloid deposition and neurological outcome following TBI. Nicoll and colleagues (1995) noted that frequency of amyloid deposition following TBI was higher in individuals who possessed an APOE e4 allele compared with those without the e4 allele. In addition, APOE genotype may influence outcome following acute (Teasdale et al., 1997; Seliger et al., 1997) and chronic TBI (Jordan et al., 1997), suggesting a genetic predisposition to the effects of TBI. Furthermore, individuals harboring an APOE e4 allele who experience TBI may also be at increased risk of Alzheimer’s disease (Mayeux et al., 1995; Katzman et al., 1996). Support of the hypothesis that APOE influences outcome from brain trauma is also suggested by animal studies. Chen and colleagues (1997) noted that APOE-deficient mice exhibited an impaired ability to recover from closed TBI.

Mechanisms for Effecting Neurobiological Change in TBI

These basic cellular and molecular mechanisms of TBI, discussed above, suggest approaches to intervention. As is usual in most fields of medicine, the major type of intervention under investigation is pharmacological. Given the neurobiological complexity of TBI as just described, the extent and diversity of proposed pharmacological strategies should come as no surprise. These strategies aim at limiting the extent of injury and/or recovering lost function. Of course, the first type of intervention must be started as soon after the injury as possible, whereas the latter, that is, recovery of lost function, fits into a number of different frameworks, some requiring intervention early, others not.

Neurotransmitter Systems

One type of intervention that has received considerable attention is repletion or augmentation of injured neurotransmitter systems. Monoaminergic transmission after TBI (Vecht et al., 1975) has received considerable attention, in part because of the effects of shear damage to axial brain structures on the significant concentrations of monoamines normally found there (Gualtieri, 1988).

Dopamine

Postulated decreased levels of central dopamine in TBI have led to attempts to use levodopa (with carbidopa) (Lal et al., 1988; Haig, Ruess, 1990), bromocriptine (Pulaski, Emmett, 1994), and amantadine (Gualtieri et al., 1989) in severe TBI. Although study designs have generally been inadequate, there have been purported benefits in decreased anxiety and agitation; increased alertness, responsiveness, and motor activity; and faster reaction times (Pulaski, Emmett, 1994; Gualtieri et al., 1989; Chandler et al., 1988; Gualtieri et al., 1989; Nickels et al., 1994). There does not seem to be a relationship between effectiveness and time postinjury.

Norepinephrine

The earliest treatment studies with catecholamines used amphetamines (Mailing, Acheson, 1946; Meyer et al., 1963) and were replicated later (Feeney, Hovda, 1983). Following a large number of studies over many years, this latter group of investigators has concluded that "short term enhancement of noradrenergic synaptic activity, combined with symptom relevant experience, promotes functional recovery of some symptoms of cortical damage in rat, cat, and human beings even when treatment is initiated from days to weeks after injury" (Feeney et al., 1993).

Nonselective Monoamines

Dextroamphetamine and methylphenidate act nonselectively to stimulate the release of biogenic amines from storage sites in the nerve terminal. There is a postulated increase in synaptic plasticity (Uranova et al., 1989) and "reversal of diaschisis" (Feeney, Sutton, 1987) resulting from noradrenergic stimulation. The data on dextroamphetamine therapy in TBI and stroke are very mixed, and the data remain unclear (Feeney, 1997; Crisostomo et al., 1988; McNeil et al., 1997; McNeil et al., 1995; Walker-Batson et al., 1995; Hornstein et al., 1996). Most trials have been poorly designed, have ignored the confound of depression (Jorge et al., 1993a), and are generally difficult to interpret (Small, 1994). Data on methylphenidate in TBI are also ambiguous (Gualtieri, Evans, 1988; Speech et al., 1993).

GABA

In the acute period, GABA may protect against excitotoxicity (Mattson, Scheff, 1994), leading to improved cognitive outcome (i.e., Morris water maze [MWM] performance).

Acetylcholine

ACh has the longest history of any attempted pharmacotherapy in brain injury (Chavany, 1928; Feeney, Sutton, 1987; Ward, Kennard, 1942). The rationale for cholinergic therapy in TBI (Levin et al., 1986) has concerned the role of these central cholinergic neurons in memory (Aigner, Mishkin, 1986; Drachman, Leavitt, 1974; Squire, Davis, 1981), including involvement of the cholinergic limbic system and cholinergic innervation of cerebral cortex by basal forebrain (Lewis, Shute, 1967). Studies aimed at increasing ACh levels have been mixed, with some investigators reporting improvement in cognitive functioning (MWM) (Pike, Hamm, 1995, 1997), and some not (Levin et al., 1986; Phillips et al., 1997). The results may depend on early, that is, within 24 hours, intervention and continued treatment (Pike, Hamm, 1995). In human subjects, the same mixed results have been found (McLean et al., 1987; Goldberg et al., 1982; Levin et al., 1986; Walton 1982; Cardenas et al., 1994). Note that ACh may potentiate excitotoxicity, thus providing a completely different rationale for acute intervention in this system (Mattson, Scheff, 1994).

Cellular Response to Injury

Excitotoxic and Oxidative Injury

The brain-cell response to injury involves an intertwined relationship among excitatory amino acid release, oxygen radical reactions, and nitric oxide production (Zink, 1996). The cascade starts with the injury, causing massive neuronal depolarization. This leads to release of excitatory amino acids and influx of calcium. Increased intracellular calcium leads to decreased protein phosphorylation, decreased protease function, and alterations in enzyme production and function. This causes formation of oxygen radicals, lipid peroxidation, and membrane dysfunction, edema, and cell lysis. Lipid peroxidation also causes activation of nitric oxide synthase and more oxygen radical formation. The membrane dysfunction causes more release of excitatory amino acids.

Excitatory Amino Acid Antagonism

Agents known to attenuate excitotoxicity (Mattson, Mark, 1996) include N-methyl-D-aspartate (NMDA), GABA+diazepam, basic FGF, nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), neurotrophin-3 (NT-3), insulin growth factors (IGFs), transforming growth factor-b (TGF-b), tumor necrosis factor (TNF), and secreted beta-amyloid precursor proteins (b-APPs). ACh and IL-1 are thought to potentiate excitotoxicity. Although there are significant data on the in vitro characteristics of these relationships, there is little in vivo information and even less that relates to actual clinical situations.

After TBI, the release of the excitatory amino acids glutamate and aspartate can lead to toxic overexcitation of neurons and cause cell death (Coyle, 1983; Coyle, Schwarcz, 1976; Nilsson et al., 1990). Of the two types of neuronal degeneration, apoptosis and necrosis (Wyllie, 1993), excitotoxic damage seems to take place via necrotic cell death, including swelling, vacuolation, and cell lysis (Mattson, Mark, 1996). Antagonists to the excitatory amino acids have been given immediately after TBI and continued for at least 4 days (Zauner, Bullock, 1995). Both NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) antagonists have demonstrated some promise, but it may be that AMPA antagonists have more future than NMDA antagonists (Novack et al., 1996). Other possibilities include adenosine and magnesium, both natural antagonists for glutamate (Novack et al., 1996).

Both before TBI (McIntosh, 1994; Hayes et al., 1988; McIntosh et al., 1989) and immediately after TBI (McIntosh et al., 1990; Smith et al., 1993), administration of an NMDA receptor antagonist has attenuated motor dysfunction in animal models. Although glutamate release after TBI may be limited to the first hour or 2 posttrauma (Palmer et al., 1993), it may nonetheless be possible to intervene as long as 18 hours posttrauma and still have a beneficial effect (Toulmond et al., 1993). TBI in infant rats has been found to be amenable to intervention with NMDA antagonists (Ikonomidou et al., 1996).

Antioxidants

Oxygen-derived free radicals are important mediators of tissue damage in traumatic injury to the CNS (Brown, Hall, 1992; Kontos, Wei, 1986; Muizelaar et al., 1993). A variety of endogenous antioxidants (e.g., vitamins E, C, A, coenzyme Q) have been found to be reduced after CNS trauma (Panter, Faden, 1992). Although the superoxide scavenger molecule, superoxide dismutase, has been shown to be of benefit in experimental ischemia, (Davis et al., 1988), it has shown ambiguous results on outcome (Muizelaar et al., 1993; Muizelaar, 1993). Another free radical scavenger, dimethylurea, has been evaluated in a model of ischemia and was thought to delay rather than ameliorate lesion extension (Kiyota et al., 1993).

Nitric Oxide

Nitric oxide has important functions in homeostasis and cell defense (Nathan, 1992) and in the CNS seems to mediate neuronal responses to excitatory amino acids (Bredt et al., 1990) and may thus play a role in mediating long-term potentiation (LTP) (Schuman, Madison, 1991) and depression (Shibuki, Okada, 1991). Nitric oxide synthase inhibitors prevent neurotoxicity by excitatory amino acids in cell culture (Dawson et al., 1991). In ischemic brain injury, it may reduce (Nowicki et al., 1991) or may not reduce (Yamamoto et al., 1992) the volume of damage.

Lipid Peroxidation

Oxygen radical mediated lipid peroxidation may play a role in posttraumatic neuronal degeneration (Hall, 1993). Corticosteroids (independent of their glucocorticoid effects) and other agents can inhibit this peroxidation (Sanada et al., 1993; Brown, Hall, 1992). Methylprednisolone has significant antioxidant effects at high doses and improves neurological recovery after spinal cord injury (SCI) (Bracken et al., 1990; Hall, 1993). Its value in TBI is less clear (Hall, 1992; Giannotta et al., 1984; Braakman et al., 1983; Cooper et al., 1979; Chesnut, 1997). So far, positive suggestive effects are noted when this drug is given within 6 to 8 hours postinjury (Bracken, Holford, 1993; Giannotta et al., 1984).

Ion Homeostasis

Calcium: Changes in calcium ion homeostasis are thought to play a role in neurodegeneration following TBI (Shapira et al., 1989; Nilsson et al., 1993), possibly via calcium entry through voltage-sensitive calcium channels (Farber, 1990). Nonetheless, calcium-antagonist therapy has not been shown to be effective either in SCI or TBI (Ford, Malm, 1985; Teasdale, 1991; European Study Group on Nimodopine in Severe Head Injury, 1994). Alternatively, calcium might mediate cellular dysfunction and death via activation of the calcium-dependent neutral protease calpain, with calpain inhibition showing some promise in animal models (Saatman et al., 1996).

Sodium: Influx of sodium occurs through voltage-dependent sodium channels, glutamate receptors, and specific ion-exchange mechanisms. Evidence suggests that blockade of voltage-dependent sodium channels has some benefit in TBI (Sun, Faden, 1995) (by contrast to the lack of success with the calcium channel blockers).

Magnesium: Decreases in free and total brain magnesium may occur after experimental TBI, with the largest change at the site of injury (Vink et al., 1987; Vink et al., 1988b). Magnesium ion also plays a role in excitotoxic TBI through its effects on the NMDA receptor (Foster, Fagg, 1987). Preinjury or very acute postinjury treatment with magnesium may have a protective effect in experimental TBI (Vink et al., 1988b; Smith et al., 1993).

Potassium: Potassium homeostasis seems to play a restricted role after TBI, involving primarily fluid balance and edema during the acute phase (McIntosh, 1994).

Other Neurochemical Factors

Additional types of neurochemical factors have been postulated to mediate TBI, although they have not led to clear therapeutic efforts (McIntosh, 1994).

Arachidonic breakdown products: Leukotrienes, thromboxanes, and free fatty acids may be associated with worsened outcome in persons with TBI. The complement cascade may also play a role in TBI outcome (Faden, 1996).

Ceramide: C2-ceramide protects hippocampal neurons against excitotoxic and oxidative insults in culture via activation of NFkB, a transcription factor activated by various signals associated with TBI (Goodman, Mattson, 1996).

Growth Promotion

Many ideas about stimulating cell growth and synapse formation derive from studies of the development of the CNS. During CNS development, there is a period of developmental cell death, possibly coordinated in part by the nature of signals from postsynaptic target cells to presynaptic neurons. NTs seem to play a role in this signaling (Purves et al., 1996), including bFGF, NGF, ciliary neurotrophic factor (CNTF), and IGFs, which promote neurite outgrowth during development. Neurotransmitters (especially glutamate) may play a role in developmental plasticity (Mattson, 1988).

Many potential neuroprotective factors (NPFs) are increased in response to TBI (Mattson, Scheff, 1994). Possible roles of NPFs include protection against glutamate toxicity, glucose deprivation injury, excitotoxicity, neuronal injury, anoxic injury, and iron-induced cell injury. Useful NPFs may all possess tyrosine kinase activity.

Neurotrophins

Nerve growth factor: Exogenous administration of NGF may attenuate the cholinergic deficits of TBI (Dixon et al., 1997; Sinson et al., 1997; Pike, Hamm, 1997). Intraventricular (Tuszynski et al., 1990; Kromer, 1987; Williams et al., 1986) and direct hippocampal (Hagg et al., 1990) infusions of NGF promote regeneration of damaged cholinergic neurons and modify fiber distribution. Sinson and colleagues (1995) found that NGF infusions beginning 24 hours after FP injury in rats and lasting up to 2 weeks significantly improved behavioral recovery measured by recall of spatial memory performance after 1 week; marked CA3 pyramidal cell loss was confirmed in these animals. This study suggests that the therapeutic window for NGF administration may extend beyond 24 hours. In a similar behavioral model, infusion of NGF was found to attenuate loss of cholinergic neurons in addition to improving cognitive performance (Sinson et al., 1997).

Insulin-like growth factor-1: IGF-1 can cross the BBB and seems to play a trophic role. In vitro, IGF-1 enhances neuronal survival and differentiation, has strong mitogenic effects on neurons and glia, promotes neurite outgrowth, and protects cultured neurons against several types of neurotoxicity (iron, hypoglycemic, hypoxic). In vivo, IGF-1 can enhance functional recovery, including improved motor activity (beam walking) as well as spatial learning in the MWM (Saatman et al., 1997). The precise mechanism of cell survival following IGF-1 administration has not been determined.

Basic fibroblast growth factor: In an animal model of TBI, bFGF may attenuate posttraumatic memory dysfunction, with unclear anatomical changes (McDermott et al., 1997).

Neurotrophin-3 and brain-derived neurotrophic factor: It appears that BDNF is a trophic factor for cortical neurons and works in conjunction with activation of voltage-sensitive calcium channels (Ghosh et al., 1994). BDNF gene expression may be enhanced during forebrain ischemia in both hippocampus and cortex and, at certain doses, may have a preventive effect on the delayed hippocampal neuronal death observed after transient forebrain ischemia (Tsukahara et al., 1994).

Scar production: There is some suggestion (Maxwell et al., 1990; Logan et al., 1994) that growth responses after TBI are attenuated by scar production that interferes with functional recovery. Using a penetrating TBI model in adult rats, Logan and colleagues (1994) found that TGF-B1 regulated scar production, which suggests a potential therapeutic role for TGF-B1 antagonists.

Gene therapy of neurotrophic factors: Although NTs seem to play a role in neuronal repair, the methods of exogenous delivery of such factors to responsive neurons require specific delivery to targets, minimal diffusion to nontargets, chronic well-tolerated delivery, and minimal invasiveness. Gene therapy may ultimately be a way to achieve this (Tuszynski et al., 1994).

Growth Promoting Agents

Gangliosides: Gangliosides, that is, cell membrane glycolipids, seem to exert "trophic-like" activity, both in vitro and in vivo (Cuello et al., 1989), and may promote neural outgrowth and improve behavioral recovery (Gorio et al., 1984). One ganglioside, GM1, also seems to potentiate beta-NGF activity in preventing retrograde degeneration of forebrain cholinergic neurons following unilateral decortication (Cuello et al., 1989). Gangliosides may have a "facilitatory" effect on both the early stages of CNS injury and on long-term CNS plasticity.

Peripheral injections of gangliosides seem to enhance learned alternation performance and time to recovery in animals with EC lesions (Ramirez et al., 1987a, 1987b, 1991; Karpiak, 1983; Karpiak, Mahadik, 1984; Karpiak et al., 1987). Although it has been hypothesized that the enhanced performance reflects crossed temporal-dentate sprouting, animals with bilateral lesions showed similar improvements that preclude this process; thus, neural events other than cross temporal-dentate sprouting are thought to play a role in the behavioral advantage created by ganglioside administration. It now appears that the benefits induced by gangliosides originate in the early acute period. Karpiak (1983; Karpiak, Mahadik, 1984; Karpiak et al., 1987) has demonstrated that exogenous gangliosides must be available during early phases of injury if optimal functional recovery is to be achieved and that early effects actually reduce damage (less edema and reductions in loss of membrane Na+K+-ATPase activity and intracellular K+) and prepare the brain for recovery.

Cytokines: The cytokines IL-1 and TNF-alpha are growth-promoting factors for astrocytes (Taupin et al., 1993). Cytokines seem to play a role in response to TBI, with animal models suggesting that the concentrations of some of these mediators (IL-1, IL-2, IL-6, TNF-alpha) increase substantially following experimental injury. These cytokines have different time courses of elevation but are generally maximal in ipsilateral cortex with lesser elevations present in contralateral cortex and bilateral hippocampus (Taupin et al., 1993).

Fetal Tissue Grafting

Preliminary work on fetal tissue grafting has been conducted in Parkinson’s disease (Wictorin, 1992) and cerebellar degeneration (Sotelo, Alvarado-Mallart, 1987a, 1987b) with some success. Neural transplantation in TBI is in an earlier stage, with one study successfully transplanting fetal cells into hippocampal regions CA3 in an animal model of lateral injury (focal temporoparietal contusion with cell death in CA3 pyramidal neurons) (Soares et al., 1995b). Another study demonstrated both anatomical and functional benefit with transplantation at the site of a cortical injury (Sinson et al., 1996b), which was even better with concomitant administration of NGF (Sinson et al., 1996b; Tuszynski, Gage, 1995a). The attenuation of motor dysfunction in this setting may relate to release of BDNF (Sinson et al., 1996a), which may interact with motor neurons (Ghosh et al., 1994). The window for transplantation, based on physiological receptivity to ingrowth of specific cell type, may not be restricted to the immediate acute period (Sotelo, Alvarado-Mallart, 1987b), such as 2 to 3 days postinjury (Sinson et al., 1996a).

Other Interventions

Pharmacotherapy of Cognition

Nootropes: These novel compounds, developed recently to enhance cognitive function, have been tested in animal models. One such compound, BMY-21502, a substituted pyrrolidinone, has been evaluated as an agent to improve cognitive ability in TBI. In the FP model of TBI and the MWM spatial learning paradigm, learning impairments were attenuated, but performance did not equal that of controls and effects were short term (Pierce et al., 1993). Thus, the ability of this pharmacological agent to enhance long-term potentiation (LTP) is uncertain; however, it may provide a viable therapeutic avenue.

Piracetam: Certain pharmacological agents used in adults and children with dementia, learning deficits, and attentional disorders have also been proposed for use in persons with TBI, but controlled trials and scientific evidence of efficacy (and in many cases even promise) are lacking (Gualtieri, Evans, 1988). One prominent example of such agents is piracetam (Dimond, Brouwers, 1976), which has not been useful in TBI (Gualtieri, Evans, 1988).

Kindling

Animals studies using the experimental "kindling" model of epilepsy (Hamm et al., 1995; Hernandez, Schallert, 1988) suggest that posttraumatic seizures may be beneficial to recovery by attenuating the neuronal depression seen after TBI; better learning in the MWM is reported in injured animals with pentylenetetrazol (PTZ)-induced seizures.

Vascular System: Platelet-Activating Factor Antagonists

Intrathecal administration of platelet-activating factor (PAF) causes dose-dependent paralysis associated with decreased spinal cord blood flow (Faden, 1996). Treatment with PAF antagonists has been found to prevent this damage (Faden, Halt, 1992) and improve outcome after TBI (Yue, Feuerstein, 1994).

Acute Interventions

Barbiturates: Although barbiturates are sometimes used for reducing intracranial hypertension in TBI, their use is controversial (Chesnut, 1997).

Hypothermia: One safe and effective way of managing intracranial hypertension and improving outcome from TBI in the acute period is the use of hypothermia (Marion et al., 1993).

Progesterone: It has been noted that cycling female rats have less cerebral edema than males after an impact injury to medial frontal cortex, and even less edema is present in female rats in a "pseudo-pregnant" state in which progesterone levels are very high. In a therapeutic study in an animal model, progesterone led to less edema, less neuronal degeneration in connected areas, and better outcome (Roof et al., 1994).

Opiates: Some data suggest that opiate antagonists can have a beneficial effect in traumatic CNS injury (SCI) (Arias, 1985; Haghighi, Chehrazi, 1987), perhaps through their effects on calcium homeostasis (Stokes et al., 1984) or on microcirculatory blood flow (McIntosh, 1994; Faden et al., 1981). This has not been supported in a number of studies on TBI (Wallace, Tator, 1986; Black et al., 1991; Hayes et al., 1990) or brain ischemia (Baskin et al., 1984; Cutler et al., 1983; Zabramski et al., 1984).

Thyroid releasing hormone: Thyroid releasing hormone (TRH) has excitatory effects in the spinal cord; these effects may be reduced in trauma and contribute to neurological impairment (Brown, Hall, 1992; Faden et al., 1986). TRH is also known to antagonize some effects of opiates. The use of TRH been explored in the treatment of TBI, with some success (Fukuda et al., 1979).

Mechanisms of Brain Plasticity after TBI

General Comments

Problems related to learning, memory, and inappropriate behaviors persist long after TBI. The medial temporal lobe memory system is implicated in learning difficulties and some portion of memory dysfunction, due in part to the extreme vulnerability of the CA1 as well as CA3 subfields of hippocampus. The hippocampal formation (HPC) is a highly plastic brain structure. Normally, learning and memory are initiated by physiological events and activation of the NMDA receptors leading to enduring morphological and physiological synaptic changes. FP models (for review, see Dixon et al., 1987) of TBI produce immediate physiological and long-term behavioral effects; damage to medial temporal structures including hippocampus and dentate gyrus (marked cell loss in CA1, CA2, and/or CA3 subfields), and temporal and EC is common.

The HPC is necessary for acquisition of spatial learning. Difficulties with spatial learning and memory, as measured by performance in the MWM, are common and prolonged in animals after TBI induced by mild or moderate FP injury (Saatman et al., 1997; Sinson et al., 1995; Smith et al., 1994; Hicks et al., 1993; Smith et al., 1991).

Release of excitatory amino acids, in particular glutamate, after TBI leads to toxicity within HPC and contributes to cell loss or death. Although considerable published work is available on neuroplasticity following ischemic lesions in the brain and in various models of brain development, exploration of mechanisms associated with neural plasticity after diffuse TBI is limited. "There is no information about how the brain might remodel its synaptic architecture following TBI involving both abnormal neuroexcitation and the secondary deafferentation resulting from axonal damage" (Phillips et al., 1997). "Continued efforts must be directed toward ascertaining if this neuroplastic change is anatomically adaptive or maladaptive, and similarly, if such structural change correlates with behavioral or functional recovery" (Povlishock et al., 1992).

Growth Factors

There is growing evidence that tissue environment influences recovery of function after TBI. In particular, nerve growth factors (NGFs) are thought to prevent neuronal degeneration and/or promote plasticity (for brief reviews, see Tuszynski, Gage, 1995b; Mattson, Scheff, 1994). Activity of various neurotrophic factors is induced following TBI; NGFs may initiate and control morphological activity, synaptic reorganization, and collateral sprouting. A number of growth factors may be involved in regulating the complex plastic responses (among them BDNF, NGF, IGF-1, FGF). In studies of humans, Patterson and colleagues (1993) report the appearance of NGF in CSF within 2 days after various types of CNS injury, including TBI. However, as late as 1994, McIntosh noted that "virtually nothing is known concerning the neurotrophic factor responses in models of experimental TBI." The highest titers of growth factors after TBI are seen in hippocampal and septal neurons (Whittemore et al., 1985). Astrocytes may be involved in the up-regulation of NGF that has been identified in hippocampal neurons after injury (Goss et al., 1998). Expression of BDNF and NT-3 is modulated by the hippocampus early (1 to 6 hours) after moderate FP injury (Hicks et al., 1997); increases of these chemicals are observed bilaterally in dentate and CA3 regions after unilateral damage.

It is well established that following transection of either fimbria/fornix that eliminates cholinergic afferents (Gage et al., 1984; Gibbs et al., 1991) or unilateral or bilateral destruction of EC that eliminates excitatory input to dentate and hippocampus proper (Kelly, Stewart, 1998; Nadler et al., 1997a, 1997b; Stanfield, Cowan, 1982; Cotman et al., 1973), surviving hippocampal neurons show growth and reorganization. It is not fully known to what extent these changes translate to functional improvements. As noted, following unilateral EC lesions or fimbria/fornix transection in rats, sprouting in dentate and HPC subfields is seen (Gomez-Pinilla et al., 1992); furthermore, within 2 to 7 days increases in the number of bFGF astrocytes and bFGF immunoreactivity occur in the outer molecular layer of ipsilateral dentate. Two weeks following FP brain damage in cats, spontaneous axonal sprouting and up-regulation of growth-associated proteins are also confirmed; however, exogenous supplementation with NGF did not enhance this spontaneous plastic capacity (Christman et al., 1997).

Long-term Potentiation

LTP, prominent in HPC, is an assumed physiological correlate of learning and memory. Examination of LTP is significant for the study of TBI-induced cognitive changes. CA1 pyramidal cells, which are necessary to encode memories, are highly vulnerable to insult. LTP as measured in CA1 of hippocampus is reduced within hours of TBI (Miyazaki et al., 1992). Persistence of learning and memory deficits suggests prolonged depression of LTP. Following FP brain injury, the introduction of stimulus pulses and electrophysiological recordings from CA1 or CA1 slices demonstrates that expression of LTP is disrupted (D’Ambrosio et al., 1998; Sick et al., 1998; Reeves et al., 1995). Reeves and colleagues (1995) report that LTP disruption is manifested by altered excitability, reduced mean population spike threshold, and lowered slope of the excitatory postsynaptic potential (EPSP), which persists over a 2-day period. The shift in EPSP slope continued over 2 weeks, suggesting impaired synaptic efficacy, whereas recovery of LTP components associated with neuroexcitation was noted within 1 or 2 weeks. If damage by fluid percussion is combined with EC lesions (Reeves et al., 1997), both LTP and NMDA receptor binding are compromised.

Widespread depolarization characterizes brain activity after TBI. Although not a correlate of LTP, widespread depolarization is confirmed in human subjects in whom prolonged central conduction time of evoked potentials is found (Keren et al., 1991); shortening of conduction times may reflect recovery. Restoration of normal physiological activity may be one mechanism to enhance cognitive function.

Issues

One of the major issues is that animal models of diffuse (vs. focal) injury, primarily FP brain injury or FP combined with entorhinal lesions, have not detailed morphology. Thus, it is not clear whether plasticity takes the form of collateral sprouting (numbers, size, shape), new synaptic contacts or vesicles, axonal regeneration, dendritic arborization (distribution, density, length), or some combination thereof. Furthermore, differences in morphological, physiological, and/or functional plasticity across mild, moderate, or severe TBI are yet to be determined. No aged model was found, and studies including female animals are insufficient. Other issues include variability in type of lesion (central vs. lateral; FP injury vs. combined) and the need to determine dose, timing, and duration of therapeutic interventions.

Types of Mechanisms of Recovery from TBI

Recovery from TBI has been shown to result from at least three different postulated sets of mechanisms (Luria, 1963; Whyte, 1990). First is the restoration of activity in temporarily inactivated brain tissue. Second is the wholesale transfer of a particular cognitive or behavioral function to a new, undamaged neural site. Third is the restructuring of a cognitive or behavioral function in order to achieve the same outcome by the integrated action of a set of neural elements that no longer includes the damaged areas. All three mechanisms proceed only in association with individual efforts to perform impaired function and thus are activity, use, or practice dependent. Such activity is rarely felt to be achieved in isolation, and social interaction has been noted to occupy a central role in recovery. Both "spontaneous" and treatment-related recovery depend on these same three sets of mechanisms, although treatment relies most heavily on the third set of mechanisms.

Types of Behavioral Recovery Mechanisms

The first set of mechanisms, that is, restoration of activity in temporarily inactivated tissue, results both from resolution of nonspecific injury-related sequelae such as edema and from restoration of activity in intact neurons deprived of the part of their innervation that had come from cells now destroyed by TBI. Activity may be increased by internal processes, such as receptor proliferation that amplifies remaining input, and by external application of pharmacologic agents.

The second set of mechanisms, the wholesale transfer of a particular cognitive or behavioral function, seems usually to occur in homologous areas in the uninjured hemisphere. A dramatic example of this mechanism of recovery is provided by the existence of apparently normal language (and other) functions in the right hemisphere of children who have had their left cerebral hemispheres removed surgically (e.g., Gott, 1973). In some instances, functions may be subserved after TBI by neural tissue with preexisting functional linkages that had been dormant before injury. For example, it has been demonstrated experimentally that neurons in the dorsal column of the spinal cord that normally respond only to stimulation of the foot will respond to stimulation of the abdomen when input from the foot is quieted by anesthesia (cited in Finger, Stein, 1982). Function may even be restored by local reinnervation by new cell types, as seen in rats with amelioration of behavioral deficits resulting from hippocampal destruction by ingrowth of noradrenergic fibers from the cervical ganglion. Sectioning of those fibers reinstitutes the deficit (Kesslak, Gage, 1986).

The third set of mechanisms, that is, the restructuring of a cognitive or behavioral function in order to achieve the same functional goals without dependence on the destroyed tissue, figures most centrally in treatment. Sometimes changes take place automatically and rapidly, such as when an individual ambulates with one leg and both arms after use of a leg is lost or transfers functions from the dominant to nondominant hand after use of the dominant hand is lost. Both examples are prototypical of this set of recovery mechanisms. The individual must first become aware of the specific disturbance that is the basis for the dysfunction, for example, know why he or she cannot walk in the same way as before. Next, the individual must select an adequate method for reorganization of the function, apply the method through conscious effort, and practice the method repeatedly. In some instances, the reorganization appears to proceed with less conscious awareness and effort, such as establishment of a new "functional macula" in the center of a constricted visual field after occipital lobe injury, but this is not usually the case, at least in the initial stages of reorganization of a disturbed function.

Historical Perspective on TBI Recovery Mechanisms

Application and development of these procedures for treatment of deficits in perceptual, gnostic, and speech and language function were done primarily by Russian physicians and psychologists treating soldiers injured in World War II (Luria, 1963). For example, individuals with lesions of the visual association cortex who were unable to recognize letters of the alphabet were shown that they could recognize the letters if they traced the outlines of the letters with their hands. After practice they were able to recognize letters by tracing the outlines with their eyes. Eventually recognition became rapid and automatic. Speech was retaught to individuals by helping them become aware of their lip and mouth movements during unaffected, automatic, nonspeech movements such as licking their lips, spitting out unpleasant food, smoking a cigarette, or blowing out a match. Building on such awareness, they were then able to learn to articulate speech sounds. For individuals with unaffected articulatory function but decreased flow and continuity and general poverty of speech, file cards with transition terms such as "then, afterwards, but, although, moreover" can provide external visual cues to extend and integrate discourse. Eventually these external cues become part of an internalized conversation, eliminating the need for the external cues. The potential for similar internal reorganization of memory and attentional processes, however, appears more limited. With conscious awareness of memory deficits, nevertheless, deliberate use can be made of external memory aids (e.g., notebooks).

Mechanisms of Effecting Cognitive Change after TBI

There are a number of mechanisms whereby individuals who have experienced TBI can improve. These mechanisms include, of course, spontaneous recovery, but this largely inevitable process is supplemented in early stages by pharmacological interventions and structured sensory stimulation applied in some cases before the return of consciousness. As individuals become increasingly responsive to their environments and after spontaneous recovery is thought to be well under way or even complete, an array of restorative and compensatory techniques that rely on learning principles is used. Finally, environmental modifications and aids are applied to lessen apparently intractable behavioral, neuropsychological, or communication problems. Each of these mechanisms is briefly discussed here, beginning with pharmacological intervention.

It should be noted at the outset that these comments apply largely to individuals who have incurred moderate or severe TBI. Although mild TBI is predominant, and people with mild TBI often have persisting psychological and behavioral consequences, little is apparently known about mechanisms for natural recovery from these sequelae or about effective interventions (Alexander, 1995).

Spontaneous Recovery

Spontaneous recovery is generally thought to follow a negatively accelerated course that appears to be the most rapid during the first 6 months following restitution of consciousness. The Glasgow Coma Scale (GCS), which grades the extent of coma, is possibly the current best predictor of recovery initially (Bishara et al., 1992; Klonoff et al., 1986; Ponsford et al., 1995), but there is considerable controversy over both when and how in the early period postinjury the GCS should be measured (Marion, Carlier, 1994). It should be noted that used alone, GCS scores appear to account for less than one-third of the variance in prediction of outcome (Ponsford, 1995). Like recovery from other forms of brain injury such as stroke, there is much individual variability in those recovering from TBI, incorporating in some cases stepwise (but still negatively accelerated) improvements and plateaus. Thus, both physiological and behavioral factors make it difficult to predict the time course and the full extent of spontaneous recovery in individual cases.

Because the brain acts to protect itself initially through a number of mechanisms, including changes in blood pressure and neurotransmitter functioning (Levin, 1992), part of the process of spontaneous recovery can be explained by the release of such protection (or suppression) at some unspecified time following injury. However, the mechanisms involved are still not well understood. One possible explanation is direct restoration of physiological function, which enables neural pathways to become active again (e.g., regeneration and collateral sprouting), as described in the previous sections.

Anatomical reorganization furnishes a second type of explanation. The brain’s remarkable capacity for adaptation, i.e., its plasticity, is well recognized, even in adulthood, and makes it possible to speculate that one part of the brain can take over the functions naturally ascribed to another. It should be noted that none of the various conceptualizations of plasticity (e.g., hemispheric equipotentiality, redundancy, hierarchical organization) has produced conclusive evidence concerning its role in recovery from TBI in humans.

Some researchers argue that functional adaptation, not physiological adaptation, is the mechanism whereby spontaneous recovery occurs. In other words, new solutions to problems are developed that avail themselves of still-intact areas and functions of brain. Alternative strategies are brought into play that compensate for the loss of function associated with particular brain lesions. Many examples from the animal studies support such notions, as well as studies on humans. As with other theories of spontaneous recovery, this explanation needs more empirical studies to support it.

Environmental Manipulation and Sensory Stimulation

Structured Sensory Stimulation

Particularly during the acute phase of rehabilitation, indeed sometimes even when the individual is still in coma (or more controversially, in vegetative state), environmental stimulation using personally relevant stimuli is thought by some (Ansell, 1993; Mitchell et al., 1990; Freeman, 1991) to contribute positively to subsequent improvement. Rationales for such stimulation include the observation that sensory deprivation is usually detrimental to recovery from other disorders. However, there is (at best) equivocal evidence for the effectiveness of structured sensory stimulation for persons in coma (Hall et al., 1992; Mitchell et al., 1990; Wilson et al., 1991; Pierce et al., 1990). Wood (1991) and Wood and colleagues (1993) even argue that sensory "regulation" (that is, limiting TV and noise levels) is an important alternative to consider.

Studies that have examined neurotransmitter levels, in addition to functional outcome, have reinforced the negative impressions from other studies (Johnson et al., 1993; Rader et al., 1989). Amount of treatment per day, frequency of family visits, premorbid education, age, time since injury, and neurological status do not seem to matter (Rader et al., 1989).

In a review of sensory stimulation, Ponsford (1995) suggests that in the light of conflicting evidence, it might be of theoretical interest to use structured sensory stimulation programs as a possible approach for determining the characteristics of that special and unexplained subgroup of persons with TBI, that is, those slow-to-recover individuals who do emerge from vegetative state.

Ecological Validity

The concept of "ecological validity" in science and clinical practice represents the view that tasks performed in research studies and therapeutic endeavors should be closely related to the types of tasks that people actually do in everyday circumstances. The role of ecological validity in studies of human behavior is becoming increasing recognized. The movements in speech, occupational, and physical therapy to employ "functional methods" constitute an applied aspect of this overall perspective. In rehabilitation of persons with TBI, a meal preparation program might be viewed as more valid than a block assembly task and in fact this might lead to better outcomes (Neistadt, 1994).

Systematic Environmental Manipulation

An attractive mechanism for stimulating plastic changes after TBI derives from systematic environmental manipulation. Environmental enrichment has been shown consistently to stimulate neural plasticity (in particular, increased dendritic branching) and, in turn, enhance learning and memory in models of the developing brain (healthy and injured) as well as after ischemic brain damage. Effects of environmental enrichment after TBI have not yet been delineated.

Kolb and Gibb (1991) manipulated environment to examine facilitation of functional recovery in rodents after unilateral and bilateral frontal lobe destruction; animals with complete absence of frontal cortex housed in enriched conditions for approximately 3 months showed marked behavioral recovery, with the exception of tongue extension and performance in the MWM. Minimal deficits were observed in the group with unilateral frontal lobe destruction. Animals housed in enriched settings had heavier brains and increased dendritic branching in visual cortex. However, lesions induced synaptogenesis in visual and parietal cortex under both isolated and enriched conditions.

Hamm and colleagues (1996) examined cognitive function after moderate TBI (FP) in male rats exposed to normal versus complex, multisensory environments for 15 days. Approximately 2 weeks after injury, rats exposed to enriched environments performed as well as controls on the MWM, and brain weights were similar. It appears that exposure to enriched environments may hold therapeutic value, but as yet few data exist on changes in synaptic architecture following diffuse injury and varied environmental conditions. Therapeutic management of environmental stimulation during rehabilitation may be necessary to optimal learning and recovery in humans; however, the type, dose, and timing of such intervention need to be determined (Neistadt, 1994).

Learning After Traumatic Brain Injury

Most procedures employed for treating the complex behavioral sequelae of TBI derive from the observation that injured brains are capable of new learning, or at least reestablishment of some functions that were compromised as the result of brain injury. Almost from their beginning, modern rehabilitative efforts have been interdisciplinary in nature (see reviews by Boake, 1991; Burke, 1995). Today, most efforts are programmatic and staffed by workers from a variety of disciplines, such as psychology, nursing, neuropsychology, speech-language pathology, social work, medicine, occupational and physical therapy, and often others. Along with family members, these individuals typically work as a team.

Many approaches to management of TBI rely on principles of operant conditioning, that is, reinforcement and punishment, shaping, errorless learning, etc. However, a number of alternative explanations exist for how people acquire information, habits, skills, and beliefs. In addition to operant models, other learning theories have been advanced as rationales for intervention in TBI, ever since the seminal work of Luria (1947, translation into English, 1970). The recent work of Damasio and colleagues (1991) has called into question the notion that operant procedures can be effective in relation to frontal lobe injuries so common in persons with TBI. Ylvisaker (1997) and Ylvisaker and colleagues (1998) have long advocated a conceptualization of learning that constitutes an alternative approach to management in persons with TBI. The conceptualization of frontal lobe functioning by Grafman (1995) and Grafman and colleagues (1993) represents still another relevant approach.

Most practitioners dichotomize clinical approaches into those that are aimed at restoring the behaviors that have been interrupted or changed as a result of TBI and those that emphasize development of alternative behaviors that support or compensate for behavioral impairments. Each is described briefly below.

Restorative Learning

Rationales for restorative learning techniques follow naturally from theories of spontaneous recovery that postulate restitution of function and anatomical reorganization. Intervention techniques and programs attempt to reestablish behaviors weakened or destroyed by TBI. Thus, the focus of restorative rehabilitation is on the attentional, memory, and executive control processes and associated problems (e.g., lack of self-awareness, disorganization, impulsivity, combativeness) that create altered and problematical interpersonal skills and pragmatic communication abilities.

Traditional retraining attempts start by defining an individual’s impairments through detailed neuropsychological and behavioral testing and then using highly structured, hierarchically arranged practice to overcome the deficits. Some such exercises use computers for presentation and responding. Some proponents of traditional restorative training believe it to be more efficient to focus on the "underlying causes" of behavioral difficulties than on their manifestations in everyday life (Sohlberg, Mateer, 1989; Sohlberg et al., 1993). Learning-based approaches to restoration invoke reinforcement, drill, shaping, provision and then fading of cues, and so forth.

A variety of specific restorative methods have been richly described in the literature of TBI; however, there is a notable lack of scientific data concerning the effectiveness of such interventions. On balance, the limited data available (Ben-Yishay et al., 1987; Gray et al., 1992; Malec, 1993; Ponsford, Kinsella, 1988) have also been equivocal with respect to the effectiveness of restorative approaches. There has been a particular difficulty in obtaining generalization to untrained tasks and, most critically, to daily life.

Compensatory Learning

Rather than directly targeting deficient behaviors, compensatory approaches focus on alternative strategies and supporting behaviors that can help individuals mitigate the effects of their impairments in daily life. Compensatory approaches emphasize methods for helping individuals understand their own deficits and increase their self-awareness (Crosson et al., 1989, Bergquist, Jacket, 1993), followed by training in compensation methods that are practiced in situations that, if not everyday routines, are likely to be simulations thereof. A critical feature is the training of strategic thinking, i.e., when and why particular compensation methods might be effective. Compensatory approaches also often include training of coworkers, family members, and peers to recognize the specific problems of individuals with TBI and help them cope more effectively with altered behaviors.

A special type of compensation involves environmental interventions and the use of external devices. Many problems experienced by individuals with TBI will remain intractable to behavioral intervention. For such problems, a variety of devices and environmental modifications have become the managements of choice. Diaries, timers, and electronic memory aids are all well described in the literature. A recent interesting example of an external device is a standard pager, adapted for providing reminders and cues for individuals with memory impairments (Hersh, Treadgold, 1994). Successful paper and pencil checklists and cueing systems have been devised by a number of investigators (Burke et al., 1991; Sohlberg et al., 1988). Most comprehensive rehabilitation programs advise and train both individuals and caregivers on procedures for simplifying the home environment and accommodating it to individuals’ particular limitations. The general belief is that the ability to profit from environmental manipulations and devices is directly related to the individuals’ understanding of their need, as well as their ability to learn to use the aids.

Compensatory approaches, like restorative ones, are also well described in the literature. Some approaches described by Ponsford (1995), Ylvisaker (1997), and Ylvisaker and Feeney (1998) have produced positive results from supported work programs. Although compensatory approaches have produced some generalization data (Cicerone, Wood, 1987; von Cramon et al., 1991), these also seem to lack sufficient research data. There is some indication that compensatory methods might be of limited utility to individuals with severe TBI (Lawson, Rice, 1989). Nevertheless, the rationales underlying compensatory approaches seem well founded in terms of working with behavioral systems thought to be only mildly impaired by TBI; for example, they rely heavily on procedural memory, which is generally thought to be relatively more intact following TBI than the other memory systems (Ewert et al., 1989).

This brief review has relied on the traditional dichotomy of restoration and compensation of function. However, it should be noted that the dichotomy is far from distinct, particularly in relationship to the executive functions that are often the focus of treatment in TBI. As noted above, if one trains a compensatory behavior in an individual with TBI, it is also necessary to help that person learn the value of the compensatory behavior itself and become aware of the circumstances in which the compensatory behavior might be useful. Without such "restoration," there is a strong possibility that the putative compensatory behavior would remain unused in daily life.

One feature of TBI that potentially interacts with the paucity of effectiveness data is the pathophysiology of TBI itself. Widespread diffuse axonal injury, as well as the typical involvement of frontal cortex and hippocampus, might limit the effectiveness of traditional teaching methods or limit the potential for restitution of function. For example, some researchers (Damasio et al., 1990; Grattan, Eslinger, 1991a, 1991b; Eslinger et al., 1997) have suggested that dorsolateral and dorsomedial prefrontal brain injury results in inefficient or ineffective ability to store information, control impulsivity, compensate for lack of self-awareness, and effect self-regulation. All these behaviors militate against the ability of a person with such injuries to understand and become skillful at applying newly relearned behaviors to everyday life. Similarly, damage to the hippocampus is thought to result in problems with declarative and explicit memory. Learning that depends on those systems for application to daily life could also be untenable.

Summary

In this section, the mechanisms underlying functional recovery following TBI have been discussed. These mechanisms fall into a number of broad categories, including cellular and molecular, neural network, and behavior. Within each mechanistic perspective, a number of events take place, and each such event suggests a variety of possible mechanisms of intervention. The goal of this section is to provide orientation to this broad array of changes and to the possible approaches to, and timing of, different interventions.

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Top

The question of the effectiveness of rehabilitation techniques designed to address the cognitive, behavioral, and emotional consequences of traumatic brain injury (TBI) is of major academic interest and clinical importance. This question of effectiveness also has been the subject of considerable scientific debate. Some of the controversy derives from perceived inadequacies in the degree of scientific rigor and number of formal investigations that have been conducted on the subject to date. Most of the reports on the topic of cognitive rehabilitation that are available in the medical (rehabilitation) literature are descriptions of specific rehabilitation programs, strategies, or interventions, including rather eloquent and detailed how-to portrayals of interventions, rather than studies of effectiveness. A review of these interventions and programs illustrates the diversity in their areas of emphasis, philosophical approaches, and specific practices. It is likely that it was the relatively extensive need for care presented by individuals disabled by TBI in the past, together with the perceived opportunities for professionals to provide that service and the availability of resources in what at the time was a growing specialty, that enabled the initial and continued use of these multiple disparate approaches, even with limited formal scientific evidence of effectiveness of any one intervention over another. Current social and scientific issues necessitate the application of considerably more scientific scrutiny of cognitive rehabilitation and its interventions than has been applied in the past, in order to justify their use and to advance the development of newer, more effective techniques.

Background

Historically, objective study of the effectiveness of cognitive rehabilitation also has been limited by a number of methodologic issues, consisting of a series of problems that have made it difficult to derive consistent, generalizable conclusions from the studies. Inconsistencies among the studies can be classified in many ways, including variations in subjects, interventions, and outcome measures. Individuals vary across studies in the severity, type, and distribution of their impairments; in the amount and severity of comorbidity; in their social support levels; in their premorbid functioning; and in a number of other ways that may have a potential influence on ultimate outcome. Variations among the available studies probably are greatest in the interventions that are tested. These differences may be in the specific type or nature of the intervention; in the onset, frequency, intensity, and duration of the intervention; in the degree to which the intervention is focused on a specific impairment or multifocused with many areas of emphasis; and, if focused, in the specific targeted cognitive function that is emphasized by the intervention. For example, more of the proposed interventions target memory than any other cognitive deficit, but some therapeutic programs are focused on attention, perception, or problem-solving ability. A major problem in much of the present literature on the topic is the apparent and relative lack of specificity with which the exact composition and nature of many of the existing programs have been described. Finally, outcome measures vary considerably; some studies have used global macro-level measures of outcome, such as return to work or community-level functioning, whereas others consider what might be called "intermediate" outcomes, such as the results of specific neuropsychological tests or ability to display specific focused cognitive skills, such as memory and attention.

Goals of cognitive rehabilitation are to enable individuals with brain damage to do those activities that they would like to do and need to do to be successful, but that they find difficult because of their cognitive disability. This includes processing information, performing everyday tasks, learning new information and skills, and adjusting to the disability (Ylvisaker, 1997).

Ylvisaker (1997) points out that cognitive rehabilitation efforts require a combination of stimulation and retraining, personal and environmental strategies and accommodation, and procedures to promote adjustment.

The cognitive functions that form the focus of the interventions are many, but a few specific areas are of particular importance; these are attention, concentration, orientation, information processing, memory (which can include short- and long-term memory, episodic and semantic memory, declarative and procedural memory, explicit and implicit memory, verbal and nonverbal memory, retrospective and prospective memory), new learning, problem-solving, abstract reasoning, insight, judgment, organization, other executive functions, motor planning, perceptual functioning, functional-integrative performance, and language (Ylvisaker, 1997). Behavioral problems that may result from TBI include impaired social skills, aggressiveness, impulsivity, apathy, and others. Affect and mood may be affected also; depression, anxiety, and altered self-esteem are particularly common. Difficulties in performing personal care tasks, mobility skills, vocational and other community-level activities, and social functions become significant consequences of these cognitive, behavioral, and emotional problems.

A Framework to Understand the Cognitive-Behavioral Interventions

There are a number of ways to classify the rehabilitation programs used to treat cognitive dysfunction. One of the important conceptual issues is to understand the difference between remediational or restorative cognitive rehabilitation and compensatory cognitive rehabilitation. Restorative training focuses on reducing the impairment or improving the specific cognitive function, whereas compensatory training teaches the individual to perform daily functions in a social environment despite continued cognitive deficit. It should be noted, however, that although this distinction is of conceptual importance, it is likely not of substantial practical significance because most interventions affect both the impairment and the disability. Ylvisaker (1997) calls this distinction a "false dichotomy." Another key issue in evaluating an intervention is whether the program uses a single strategy (such as computer training) or relies on an integrated or interdisciplinary approach. Likewise, many of the interventions are defined by the specific nature of their targeted areas of outcome; some are singularly focused on an isolated cognitive function, whereas other strategies are multifocused on several different but related outcomes. For those interventions that are focused in a specific target area, it is important to identify and distinguish the interventions on the basis of their various specific target cognitive functions. For example, those interventions that address attention (or perception, language, or others) are different from (but related to) those treatments that address memory. Finally, the therapeutic programs may be classified according to their definitions of outcome. Some define outcome according to global community levels of functioning, such as return to work or independent living at home. Other studies, usually those that are focused in their target approaches, define outcome according to the level of functioning in that specific area, such as memory, problem-solving ability, or insight.

Most of the approaches of brain injury rehabilitation are based on one of several theoretical models (Uzzell, 1997; Christensen et al., 1996), the foundations of which are grounded in specific theories of normal brain functioning and injury. The most commonly accepted theory is based on the principles developed by Luria (1963a, 1963b, 1980), who distinguished three hierarchical functional units of the brain: the arousal unit, the sensory input unit, and the organizational planning unit. Each unit is then organized hierarchically into primary areas that receive and send information, secondary areas that process information, and tertiary areas that integrate information from two or more areas. All units are essential to the functioning of tasks. According to this theory, the brain damage causes disinhibition, and recovery occurs when newly learned connections are established. These new connections can be made through cognitive retraining exercises targeted at the specific processes that were disrupted. In contrast, the model of Sohlberg and Mateer (1989), the process-specific approach, uses techniques that target specific cognitive processes repetitively in a systematic way according to the need for treatment. Tasks are arranged in graded levels of difficulty, and treatment is very specifically organized, systematic, and data-driven. Using a different treatment strategy, the stimulation model of treatment relies on the concept that any sensory stimulation can be used to improve cognitive functioning, rather than specific focused approaches. In contrast, the no-transfer-of-training model applies training of specific tasks in naturalistic settings.

A more detailed understanding of the breadth of cognitive rehabilitation programs requires some classification of the specific types of interventions. These approaches can be categorized as cognitive exercises or academic/educational drills, which may use a variety of cognitive strategies such as repetition, use of mnemonics, or mental imagery; use of computer aids; use of external aids, which may be manual (for example, memory books) or electronic; and training in compensatory strategies. Behavior modification approaches for both behavior management and social skills training, psychotherapy, and vocational rehabilitation can be included in this consideration, since they rely on similar strategies and emphasize similar outcomes. Interdisciplinary comprehensive models rely on many of these techniques, provided as a coherent, coordinated package, addressing the comprehensive needs of the individual. These different types of interventions, and a few others, will be discussed in this review. It will be seen that to some extent, the distinction between each of the approaches appears to be somewhat arbitrary and artificial and many of these strategies overlap with each other. For example, interdisciplinary approaches often use process-specific training, psychotherapy, and other techniques to focus on return-to-work outcomes. Therefore, categorizing the interventions is less important than understanding them and testing their effectiveness. Some of the newer techniques, such as surgical procedures, for example, neural transplants (Portavella, 1997) and gene therapy (Hayes, Yang, 1997), although fascinating and promising, are not discussed in this review.

Testing these general models and specific techniques is difficult (Uzzell, 1997) because of many of the methodologic reasons noted earlier. Subject selection bias, differences in treatments, and variations in outcome measures limit the extent to which rational evaluations of these models can be performed. Difficulties that are inherent in quantifying both the nature of the interventions and the achieved outcomes also limit comparisons between interventions significantly. Finally, the extent to which spontaneous natural recovery affects outcome must be considered in any test of treatment effectiveness. The conceptual principle to be applied in testing the effectiveness of these techniques is the determination of whether and to what extent the treatment results in changes in cognitive functioning that are above and beyond the effects of natural recovery alone. It is important to note, however, that the tasks that make up cognitive rehabilitation take place in a social context or setting. This means that even in studies that attempt to isolate the effect of a single type of intervention, other confounding environmental variables may exist, such as the potentially significant influence of the attention by a professional.

A review of the available literature on common interventions that are used to address cognitive, behavioral, and emotional consequences of TBI reveals both the diversity of strategies that have been employed in the past and the wide range in the level of evidence of efficacy for those clinical approaches.

Descriptions of Interventions and Studies of Their Effectiveness

Understanding the variety of existing therapeutic interventions is facilitated by an awareness of the various categories of interventions. A listing of these approaches includes cognitive-academic exercises, computer-assisted cognitive rehabilitation, compensatory skills training, use of external aids, communication skill training, psychotherapy, behavior modification/social skills training, vocational rehabilitation, art and music therapy, pharmacotherapy, aerobic training and other therapeutic exercise, nutritional interventions, spirituality, other alternative therapies, interdisciplinary models, and interventions for families. The literature describing and supporting some of these strategies, such as cognitive rehabilitation approaches, is stronger and more complete than the literature concerning some of the other techniques, such as nutritional interventions. The number of publications that provide descriptions of prevailing therapeutic interventions greatly exceeds the number of papers reporting on the results of scientific trials designed to determine effectiveness of these techniques. Both types of publications will be reviewed here.

Cognitive/Academic Exercises

Most attempts at remediation of neuropsychological deficits have emphasized the use of cognitive exercises as means of improving specific cognitive processes. Although measures that address many of the specific cognitive functions affected by TBI have been studied (or at least described), methods to improve memory and attention functions predominate in the presently published literature. Large proportions of the published studies have been single case design studies, although a few intergroup comparison trials have been performed.

Controlled Intergroup Comparisons

There are relatively few random assignment treatment vs. control group evaluations of cognitive exercises in the treatment of TBI. Those studies that do exist include only small samples, and most were published 3 to 10 years ago. No replication of results has been published. Four reports came from one laboratory (Ronald Ruff and associates). The first of these compared experimental and control groups (n = 10 in each), all of whom had medical and computed tomographic evidence of serious TBI (Ryan, Ruff, 1988). The experimental or treatment group participated in six 30-minute sessions of memory training per day, 4 days per week, for 6 weeks. Sessions included teaching external memory strategies, encoding strategies, and personalized emotional techniques; practicing rehearsal and computer-presented list and paired-associate learning tasks; and review. The control group spent a comparable amount of time playing video, board, and card games and participating in art projects and group discussions. Outcome was assessed with a battery of visual and auditory, verbal and nonverbal memory tests. Individuals were 1.5 to 7 years postinjury to eliminate effects of spontaneous recovery. No outcome differences were observed between groups. However, when only the five persons in each group with best baseline neuropsychological function were compared, the experimental group showed significantly greater gains on several tests. This is consistent with the results of another study comparing outcome in persons with severe and less severe TBI treated in an intensive, multidimensional rehabilitation program, although this study was somewhat confounded by use of length of stay in treatment as one measure of injury severity (Trexler, Zappala, 1988).

In a second study, including many of the same individuals and procedures, Ruff and colleagues (1989) compared 20 control individuals with TBI with 20 individuals receiving successive 2-week training blocks of attention, spatial integration, memory, and problem-solving. Training was done in four 50-minute sessions daily. Controls spent a similar amount of time playing computer and video games, participating in art classes, and receiving instruction in coping skills, health behavior, and independent living. Outcome was assessed with a large, multidimensional neuropsychological battery. All individuals were 1 to 7 years postinjury, and medical documentation suggested serious TBI in all. Data analyses showed improvement in both groups (p<.001) but no significant main effect or interactions with group. Analyses of individual tests showed greater improvement in the treatment group in the Selective Reminding Test (10 percent improvement vs. some deterioration in controls), the Rey Complex Figure reproduction, the 2 and 7 test of selective attention (30 percent improvement in treated persons vs. 0 percent in controls, p=.06) and verbal IQ (3.6 point increase vs. no change, p=.02).

In a third study, Niemann and colleagues (1990) compared the effects of attention training (group 1 = 13 individuals) and memory training (group 2 = 13 individuals) in individuals 12 to 72 months after moderate to severe TBI. Attention or memory exercises were given for approximately 1 hour twice a week for 7 weeks. Attention and memory function was assessed with one test battery weekly for 3 weeks before treatment, weekly during treatment, and twice after treatment. A second battery of similar tests was given once before and once after treatment. The group that received attention training showed greater improvement than the group that received memory training on one of the four attention tests in the first battery but not on a similar test in the second battery. There were no differences between the groups on any of the other outcome measures.

In their most recent published study, Ruff and colleagues (1994) compared two groups (n = 7 and n = 8) of persons with severe TBI (average coma duration 51 days, range 4 hours to 154 days), all at least 6 months post-TBI, in a multiple baseline A/B B/A design. Individuals received successive 20-hour blocks of memory and attention training, each consisting of 2-hour sessions over 10 days. One group received the memory block first, whereas the other received the attention block first. Training was provided by a multimedia computer system that allowed task parameters to be adjusted individually to maintain accuracy at 80 percent or better. Outcome was assessed before, between, and after blocks with computer tasks similar to the training tasks, with formal neuropsychological tests of attention and verbal and nonverbal memory, and with self-ratings and family ratings of attention and memory competence. Both groups showed gains in the computer and neuropsychological tests of attention and memory at both time points, indicating nonspecific effects of the training tasks. However, the neuropsychological tests also provided evidence of specific improvements in both verbal and nonverbal memory following the memory blocks.

A fourth controlled study evaluated the effect of adding 1 hour per day of computer-based attention training to the inpatient general rehabilitation program for 10 persons with TBI for 20 days (Wood, Fussey, 1987). Ten other comparable individuals in the same inpatient program served as controls. The average time since injury for all individuals was 32 months. The training task required detection of a moving target, the speed of which was varied to maintain the hit ratio between 40 and 80 percent. Outcome was assessed with six other tests of reaction time and sustained attention, as well as with staff ratings of individual attention to tasks in other parts of the rehabilitation program. There were no treatment effects evident on any objective measures, although staff reported that treated individuals paid better attention during the general rehabilitation program. The investigators stated that staff were blind with regard to group assignment, but one must question whether such a blind could be adequately maintained.

In the fifth controlled study, six subjects with TBI enrolled in a 6-month rehabilitation program had their treatment enriched with eight 2-hour group sessions during which they were instructed in techniques to enhance recall of paragraphs read to them (Freeman et al., 1992). These subjects showed improvement in the ability to recall paragraphs they heard, whereas a control group of individuals (n = 6) in the same general program showed no improvement.

In a recent report, Chen and colleagues, researchers who were active in developing computer-mediated cognitive treatment for TBI for more than 15 years, conducted a retrospective comparison of cognitive outcome in 20 persons with TBI who had received hierarchically based computer-assisted cognitive rehabilitation (CACR) with 20 closely matched persons with TBI who had received various other therapies, including speech therapy and occupational therapy (Chen et al., 1997). Significant improvement was noted on 15 outcome measures in the CACR group, but only on seven measures in the control group. However, none of the differences between groups in outcome measures was significant. The authors concluded that the extent and nature of gains related to CACR still need to be demonstrated in controlled, prospective group studies.

Two other studies compared groups of subjects with TBI receiving two different forms of cognitive exercises added to their general rehabilitation program. In one study, individuals (more than 85 days after TBI) received similar cognitive exercises (20 hours over 4 to 6 weeks) either via computer or from occupational therapists. Both groups showed comparable and significant improvement on a battery of neuropsychological tests (Batchelor et al., 1988). In the other study, individuals who were more than 3 years post-TBI received computer exercises (4 hours per week for 8 weeks) for either attention and memory or reasoning and logical thinking (Middleton et al., 1991). Both groups showed significant improvement on measures of attention, memory, and reasoning.

Further evidence of the ability of people with TBI to benefit from practice or instruction is provided by two additional studies. Neistadt (1992) compared the effects of having individuals practice a block assembly task (n = 22) with having individuals practice food preparation (n = 22). Interventions were provided in three 30-minute sessions per week for 6 weeks. Individuals were at least 6 months post-TBI or anoxic brain injury and were also enrolled in more general long-term treatment programs. Outcome was assessed with the same block design task that one group had practiced with a food preparation task and with a different block design task. Improvement on the block design task used in training was significantly greater in the group that had practiced that task, but the groups improved to a comparable degree on the other two outcome measures. Twum and Parente (1994) showed that both instructions to use verbal labeling and instructions to use visual imagery, given immediately before visual and verbal paired associate learning tasks, increased performance in people who were more than 6 months after severe TBI. These studies and several others described above, however, provided interventions that were limited in intensity and duration, and used narrowly limited outcome measures.

Finally, Kerner and Acker (1985) found that 12 subjects with TBI and memory impairments who underwent formal structured CACR improved their memory skills and recall more than did subjects with unstructured computer training and subjects with no computer training.

In summary, only a few controlled studies of cognitive remediation in persons with TBI are available. Only two of these studies have been published during the last 5 years. There appears to be some evidence of specific treatment-related improvements in memory and attention, but most studies have failed to find such effects. One study suggests that treatment effects may be greater in less impaired clients, yet all studies included only individuals with histories of serious TBI, often associated with extended coma. As the investigators suggest, it is possible that the treatment exercises were too difficult for the more impaired individuals and thus served only as another source of frustration. Only one study focused on individuals within the first year post-TBI (Batchelor et al., 1988), and most subjects in most studies were at least 2 years post-TBI. Treatment might be more effective if provided closer to the time of injury. However, one study using multiple pretreatment baselines found no benefit of attention training within the first year following severe TBI (Ponsford, Kinsella, 1988), and another found that a group of 22 persons less than 1 year after severe TBI showed improvement on only 5 of 16 computer perceptual and attentional training tasks despite two 2-hour practice sessions per week for 6 months (Ethier et al., 1989). Some optimism is provided by nonspecific improvement in cognitive function noted in subjects who are long enough postinjury to rule out continued spontaneous recovery, but the durability and basis of these improvements are not clear.

Case Studies

There have been two reports of successful application of targeted neurocognitive training tasks using multiple baselines to establish pretreatment stability of neuropsychological function and evaluating multiple subjects with TBI. Sohlberg and Mateer (1987) treated four individuals with seven to nine sessions per week of attention, memory, and visual processing training tasks, each in 4- to 6-week treatment blocks. All four showed improved attention function (on nontraining tasks) during the attention training block, and this improvement was maintained in subsequent blocks. All four individuals also showed increased spatial functioning during the spatial block, and in two subjects this improvement was maintained in subsequent blocks. Memory outcome was not reported. Gray and Robertson (1989) found improved function in three subjects in outcome measures thought to be related to cognitive training tasks, but not in unrelated outcome measures. However, the basis for considering some outcome measures related to the training tasks and not others was more obscure than in other studies. Case studies have also demonstrated improvement in specific, chronic, problematic behaviors or functions in individuals with structured feedback and instruction (Giles et al., 1988; Lawson, Rice, 1989).

There have also been single case studies reporting positive outcomes of cognitive exercises often accompanied by instructions (e.g., Luria, 1963a; Wood, 1986). Although the investigators have not employed a formal multiple baseline design, the density and duration (years) of the post-TBI deficits and the temporal association between treatment and improvement (often substantial) add confidence in these observations.

A few other studies should be noted. Gianutsos and Gianutsos (1979) showed modest improvement with repetitive practice in a single case design series. A successful trial of perceptual retraining was conducted by Weinberg and colleagues (1977), who demonstrated improved capacity to read. A number of useful reviews exist on available research into the value of specific cognitive remediation modules. In one of these reviews, Prigatano and colleagues (1986) pointed out that no therapy could "make a poor memory good," but that several studies have experimented with the use of mnemonics. He suggested that cognitive retraining was likely to be more successful in the area of compensation and substitution than in the area of remediation or direct retraining. Other studies describing rehabilitation for disorders of attention (Gray, Robertson, 1989; Sohlberg, Mateer, 1987; Ponsford, Kinsella, 1988; Novack et al., 1996), memory (Stern, Stern, 1989; Sohlberg et al., 1992; Malec, Questad, 1983; Lawson, Rice, 1989; Crovitz, 1979; Godfrey, Knight, 1988; Freeman et al., 1992), executive function (Burke et al., 1991), perceptual deficits (Lincoln et al., 1985; Gouvier, Cubic, 1991; Ben-Yishay, Diller, 1981), and combinations of problems (Pollack et al., 1984; Mateer et al., 1996; Harrington, Levandowski, 1987; Heilbronner et al., 1989) have been described.

Computer Assisted Training

Many of the efficacy trials of cognitive rehabilitation interventions rely on the use of computers as tools to facilitate the training. Whereas some of the papers have reported studies that compare outcomes of CACR with other forms of cognitive training, some of the published papers have described the design and uses of computers in cognitive remediation (Glisky et al., 1986; Hoepfer, 1996; Johnson, 1990; Kurlychek, Levin, 1987; Middleton et al., 1991; Robertson et al., 1990; Thomas-Stonell et al., 1994). Principal among the authors of these papers is Cole and Dehdashti (1990a, 1990b, 1992, 1998) and Cole and colleagues (1994).

Compensatory Technique Training

Rather than directly targeting deficient behaviors, compensatory learning approaches focus on alternative strategies and supporting behaviors that can help individuals to mitigate the effects of their impairments in daily life. Compensatory approaches emphasize methods for helping individuals to understand their own deficits, increase their self-awareness (Crosson et al., 1989; Bergquist, Jacket, 1993) and then go on to train compensations that are practiced in situations which, if not everyday routines, are likely to be simulations of them. A critical feature is the retraining of strategic thinking, that is, when and why particular compensations might be effective. Compensatory approaches also often include training of coworkers, family members, and peers to recognize the specific problems of individuals with TBI and to cope more effectively with their altered behaviors. Compensatory strategies may be classified as anticipatory compensation, recognition compensation, situational compensation, and external compensation (Crosson et al., 1989), and a number of factors enter into the decision as to which strategy to employ for a specific situation.

A special type of compensation involves environmental interventions and the use of external devices. These are described below.

Compensatory approaches, like restorative ones, are also richly described in the literature (Ponsford, 1995; Ylvisaker, 1997; Ylvisaker, Feeney, 1998). Wehman and colleagues (1989a, 1989b, 1990, 1991, 1993) in particular have produced highly positive results from supported work programs. Although compensatory approaches have produced some generalization data (Wehman et al., 1989a, 1989b, 1990, 1991, 1993; Cicerone, Wood, 1987; von Craemon et al., 1991, 1994), these studies suffer from modest availability of research data. On the negative side, there is some indication that the methods might be of limited utility to individuals with more severe TBI (Lawson, Rice, 1989). Nevertheless, the rationales underling these approaches seem well founded in terms of working with behavioral systems thought to be only mildly impaired in persons with TBI. For example, they rely heavily on procedural memory, which is generally thought to be relatively more intact following TBI than are the other memory systems (Ewart et al., 1989).

It is important to note that this brief review has relied on the traditional dichotomy between restorative and compensatory approaches. However, as noted earlier, this dichotomy is far from distinct, particularly in relationship to the executive functions that are often the focus of treatment in persons with TBI. If one trains a compensatory behavior in an individual who incurred TBI, it is also necessary to help that person to learn the value of the compensatory behavior itself and to become aware of the circumstances in which the compensatory behavior might be useful. Without such "restoration," there is a strong possibility that the putative compensatory behavior would remain unused in daily life.

Methodological problems explain, in part, why the effectiveness of training programs has been difficult to document scientifically. There are a number of reasons, many concerning the variability inherent in the group of persons with TBI themselves. For example, although TBI is predominantly a disorder of the young, it occurs across the lifespan and, as such, presents different challenges at different ages of onset. The complex and sometimes unpredictable patterns of impairments and residual abilities also contribute to variability. The idiosyncratic profiles of processing and executive functioning difficulties experienced by individuals with TBI also collude to make it almost impossible to provide uniform treatment across individuals.

Use of External Aids

Background

The use of external aids either to improve or to compensate for various cognitive deficits following TBI has been described with some frequency. Some of these articles describe programs in which external aids are used to improve cognitive function, others are case studies that describe the use of external aids, and still others can be categorized as research. A specific significant cognitive deficit for which there are concrete and objective interventions is memory.

Program Descriptions

Diller and Gordon (1981) reported on the renewed interest in the use of mnemonic devices to treat cognitive disorders (as originally described by Cermak, 1975; Crovitz, 1979; Lewinsohn et al., 1977; and Patten, 1972). A case study by Luria resulted in an increase in the use of mnemonic devices to retrain memory. However, most investigators appear to prefer technical aids to mnemonics to improve memory. Diller and Gordon (1981) described the difficulties in establishing and evaluating cognitive remedial programs, including identifying the specific problem being treated and the assessment of the problem, determining norms or a specific task, determining which factors of responses are indicators of impaired or improved performance, specifying the training procedure, defining positive results, and resolving the clinical issues. Harris and Sunderland (1981) conducted a survey to determine the methods used to manage memory disorders in persons with TBI. Twenty-two of the 49 questionnaires were returned. There did not seem to be any standardization of techniques or tests among the respondents. The reported aids and direct techniques to help included (1) external memory aids such as note pads, check lists, diaries, and electronic prompters, (2) internal memory aids such as imagery mnemonics, method of loci, and peg method, and (3) structured environment.

Newcombe (1982) lists four approaches to improving memory: internal strategies, physical treatments, external devices, and external aids. Mnemonics, such as verbal coding, rhyme, and letter cues, have been shown to improve memory, and imagery has been found to be a significant aid to recall, especially verbatim recall. The external aids suggested include lists and diaries to record and retrieve information. Some of the devices in use are cooking buzzers, alarm watches, electronic diaries, and alarm clock/calendars. The needs, age, and ability of the user determine the choice of a device. No objective evidence of effectiveness was presented in Newcombe’s paper. Namerow (1987) describes compensatory techniques/strategies to improve memory utilizing notebooks to keep track of appointments and daily routines, to provide ready access to dates and day of week, and to record telephone numbers and other pertinent information. Functional and behavioral outcomes were demonstrated, but not specific cognitive abilities. Cognitive rehabilitation can result in improved cognitive ability and, as part of a comprehensive TBI treatment program, can result in significant improvement in functional outcome.

Howard (1988) describes compensatory assistive devices for memory and learning. These include notebooks, logbooks, wallcharts, wristbands, notecards, microcomputers, and tape recorders. Training is needed to maximize utilization. Labels, wall charts, door, hall or corridor signs, and tape recorders can provide orientation information. Bottcher (1989) describes a nursing approach to cognitive rehabilitation, defining three phases: (1) stimulation phase (visual, auditory, olfactory, gustatory, cutaneous, and kinesthetic); (2) structure-oriented phase (agitation, structure environment, attentional deficits, memory); and (3) reintegration phase (provides reality testing and feedback.) Individuals keep their own memory aids (lists, calendars, appointment and address books) and a daily log of events to improve recovery of memory functions. Activities are grouped as relating to self, home responsibilities, and community responsibilities.

Parente and Anderson-Parente (1989) describe memory and memory training theory. They identify six memory retraining techniques: (1) domain specific training, (2) sensory memory training, (3) attention/concentration, (4) memory strategy, (5) academic therapy, and (6) stimulation therapy. These authors advocate the use of prosthetic memory aids, which are often electronic devices that cue the person with TBI to some future activity or store information for retrieval. They are effective in compensating for memory deficits. Among the devices listed are (1) checklists (after Kreutzer et al., 1990); (2) electronic signaling devices to find keys, car, wallet (e.g., clapping and whistle-sounding devices); (3) electronic cueing devices to store personal information and telephone numbers and to signal important appointments (e.g., wristwatches); (4) microcassette recorders for recording messages, notes, or instructions; (5) spelling and thesaurus machines and small calculators; and (6) computer programs that check spelling, punctuation, and grammar.

Mills and colleagues (1992) described a 6-week postacute rehabilitation program in which 42 persons with TBI participated. External aids were used to address individual goals at home, at leisure, in the community, and prevocationally. At home, a time planner was used as a memory aid for daily living; at leisure, an activity list was introduced, as well as the use of a carryall to organize belongings. Improved functioning and independence derived from treatment aimed at practical real-life goals (not at specific cognitive deficits) accompanied by psychological support. Late recovery depends more on behavioral substitution and learning new procedures and less on neurophysiological recovery. Malec and colleagues (1993) describe an outpatient nonresidential postacute brain injury rehabilitation program that uses external aids to improve memory for 29 enrollees. Results indicated that those living with no supervision increased from 59 to 93 percent, unemployment decreased from 76 to 31 percent, and, after 1 year, 21 had generally maintained their postprogram status. In this population, reading ability was the only predictor of successful outcome. The use of computers as external aids to improve cognitive function has been covered in another section of this document.

Case Studies

Godfrey and Knight (1988) used a single case study to present the effects of memory training and behavioral rehabilitation of an adult with severe TBI. The treatment consisted of daily group training sessions for 8 weeks. Emphasis was placed on attending to and utilizing memory cues, visual imagery, and rehearsing information effectively. Six activities were used: associate-learning tasks (the individual practiced learning and recalling verbal and pictorial information); orientation training (personal information and dates, routes around the facility); new learning (learning to locate geographic features on a map); picture recognition memory; concentration (matching pairs of cards); and memory for recent events. Results indicate that psychosocial factors, not cognitive factors, were critical for this person and that the treatment activities aimed at improving memory had no impact on memory ability. Although the memory impairment was resistant to cognitive rehabilitation efforts, it did not interfere with successful community placement.

Sohlberg and Mateer (1989) described the traditional approaches to memory rehabilitation, restoration, and compensation as often ineffective in the real world. They present a case study that demonstrates the effective use of a memory book system for daily living and employment. The components of a functional memory notebook system and the three-stage behavioral training procedure are described. The effective use of a memory book requires that the person using the book consistently and correctly record and refer to information in the book and that there be structured, sequenced training and repetition. Suggested notebook sections include the following items: orientation, memory log (diary of daily information), calendar, things to do, transportation, feelings log, names, and today at work. Three training phases are presented: acquisition phase, in which the person learns names, purpose, and use of each notebook section; application phase, in which the person learns appropriate methods of recording in the notebook; and adaptation phase, in which the person demonstrates appropriate notebook use in naturalistic settings via community training. It is suggested that the notebook be personalized in terms of size, style, and so forth to the individual who will be using it. The successful use of the memory notebook requires that the person has constant access to the book, that all staff and family receive training on the use of it, and that the clinician is responsible for ensuring that information in capabilities supported by the book is functionally based.

Lawson and Rice (1989) used a case study to describe executive strategy training aimed at improving the ability to identify a memory problem. The strategy involved task analysis, strategy selection and initiation, and monitoring of the strategy used. The person had used a diary and mnemonics as well. The purpose of using executive strategies was to present a means for self-initiation of the strategies. Recall performance improved up to 6 months after training was completed.

Burke and colleagues (1991) presented Lezak’s definition of executive function as "the ability to engage in independent, purposeful, self-directive and self-serving behavior." The major elements of executive function are self-initiation, problem-solving, and self-monitoring or regulation of behavior. Burke and colleagues used three case studies to demonstrate improved executive functioning in problem-solving, self-initiation, and self-regulation. A checklist (task analysis) was used to assist persons with TBI to complete vocational tasks resulting in the ability to perform the task and to continue to perform even when the checklist was removed. The self-initiation checklist reduced the amount of prompting and increased the number of tasks completed correctly. The conclusions of this study indicate that similar checklists for routine vocational tasks decrease the levels of external assistance and, therefore, increase independence in living and working. Checklists were withdrawn without deterioration of performance, suggesting that the task became routine and internalized.

Zencius and colleagues (1991) presented four case studies to demonstrate that memory notebook training improved performance of homework assignments and keeping appointments. In an earlier paper (Zencius et al., 1990), these authors demonstrated that compensatory strategies were more effective than mnemonic training. The more recent study capitalized on compensatory techniques to improve prospective as well as retrospective memory.

A case report was used to describe prospective memory training in a 51-year-old male with TBI. The person participated in a community reintegration day treatment program, 7 hours per day, 5 days per week. Training consisted of repetitive administration of prospective memory tasks specific to future times. The length of time was systematically increased between task administration and execution. Although entirely descriptive in nature, the results suggest that prospective memory did improve over time. No specific external aids were used.

Research

Three research studies utilizing external aids are included in this document. Ruff and colleagues (1989) used a single-blind randomized experimental design to compare the efficacy of neuropsychological treatment with a nonstructured treatment in a series of 40 persons with TBI. The participants were randomly assigned to one of two treatment protocols, each of which involved daily sessions over 8 weeks for a total of 160 hours. Neuropsychological functioning was assessed before and after treatment. The neuropsychological treatment addressed deficits in attention, spatial integration, memory, and problem-solving using computer-assisted training modules. The use of computers for cognitive rehabilitation is discussed earlier in this chapter. However, these authors report the use of external aids, specifically notebooks, calendars, schedules, timers, and other devices, to cue recall. The results of their study suggest that improvement in memory skills was the most important treatment effect.

Freeman and colleagues (1992) conducted a controlled treatment outcome study to compare a memory remediation treatment program with no treatment in a group of persons with TBI. Twelve subjects, six in the intervention group and six in the control group, participated. Memory remediation included compensation and executive training skills. The memory module consisted of 2½ weeks, 2 hours per day, three times per week and the third week, two times per week. The treatment was the repeated presentation of paragraphs. For the treatment group, the techniques to enhance paragraph retention included note-taking in a memory notebook, self-monitoring skills, prompting, restatement of presented material, use of imagery, encouragement and reinforcement, additional monitoring skills, and feedback. The intervention group showed significantly improved memory scores over those of the control group.

Bergquest and Jacket (1993) studied 21 persons with TBI in a postacute outpatient program in an attempt to improve goal setting and ultimately function following TBI. The program consisted of 28 weeks, 4½ hours per day, 5 days each week. The basic premise of the program was that individual self-awareness is essential to the success of compensation techniques. Four classes of compensation are identified: (1) anticipatory compensation, in which the person anticipates that a problem will occur if he/she does not compensate for it; (2) recognition compensation, in which the person recognizes that a problem is occurring and is able to implement a solution to correct it; (3) situational compensation, triggered by a specific type of circumstance, in which a deficit is likely to affect performance; and (4) external compensation, which is triggered by an agent other than the person, that is, by a modification to the environment or consistent use of cues from an employer or family member. In the population studied in the project, independent living increased from 59 to 93 percent.

External Aids as Compensatory Strategies

Many problems experienced by individuals with TBI will remain intractable to behavioral intervention. For these problems, a variety of devices and environmental modifications become the intervention of choice. These devices may be manual or electronic.

Many products categorized as external aids have been developed and marketed. Indeed, entire catalogues contain numerous devices to improve cognitive functioning in persons with TBI. These catalogues are produced for professionals such as physicians, occupational therapists, physical therapists, nurses, and speech-language pathologists, as well as for consumers, that is, individuals with TBI and their families. There are items available to assess and treat language skills, cognitive skills, and communication skills. They include exercises and devices to improve memory, social skills, reasoning, verbal skills, spatial orientation, immediate and short-term visual memory, sequential organization, problem-solving, and abstract reasoning. Stickers, worksheets, electronic reminders, and board games are but a few of the systems and devices to improve cognitive functioning following TBI.

Diaries, electronic memory aids, and so forth are described in some detail in the literature. Successful paper and pencil checklists and cueing systems have been devised by a number of investigators (Burke et al., 1991; Sohlberg et al., 1988). Most comprehensive rehabilitation programs advise and train both individuals and caregivers on procedures for simplifying the home environment and accommodating it to a person’s particular limitations. The general belief is that the ability to profit from environmental manipulations and devises is directly related to the individual’s understanding of his or her need and his or her ability to learn to use the item. A number of authors have advocated the use of these notebooks and other similar devices (Schmitter-Edgecombe et al., 1995; Goldstein et al., 1998; Zencius et al., 1991; Sohlberg, Mateer, 1989; Franzen, Harris, 1993; Johnson, 1990).

A recent interesting example of a commercially available electronic system, the NeuroPage (Hersh, Treadgold, 1994) is a simple portable paging system with a screen attached to a belt and microcomputers linked to a conventional computer memory and a paging system through the telephone. This pager is adapted for providing reminders and cues for individuals with memory impairments. In one report, this device was demonstrated to result in significant improvements between baseline and treatment in a single subject design study of 15 individuals with TBI and impairments in memory, planning, or mental organization (Wilson et al., 1997).

Communication Skill Training

Following TBI, only a small subset of individuals appear to display classical aphasic syndromes, and of those few, the most predominant pattern is that of anomic aphasia (Sarno et al., 1986). Such individuals, who share common ground with persons with left hemisphere stroke, are likely to be treated with the intervention techniques that are typically employed for aphasic individuals. No systematic data have demonstrated the efficacy of treatment for persons with TBI using these methods, although it is assumed that such individuals would profit from traditional aphasia treatment.

The far more common communication disorders following TBI have been characterized as pragmatic disorders, in which the complex interaction of disturbed information processing and difficulty in executive functioning is realized in spoken and written language. Features that distinguish language disorder in persons with TBI include disorganized discourse, inappropriate use of social language, disinhibition, lack of initiation, and others.

Communication problems such as these are different both in origin and in treatment from those that result from stroke. In stroke, damage that produces aphasia results from focal left hemisphere insult, that is, to the areas of the brain that are thought to be committed to language processing. In persons with TBI, diffuse frontal lobe damage, together with hippocampal damage, indirectly affects communication through interfering with the memory and executive functioning that play a role in the appropriate use of language in the transaction of human affairs.

Thus, restoration of appropriate communication skills following TBI seldom involves direct work on language divorced from its social and cognitive contexts. Coelho and colleagues (1996) in fact have summarized work on the cognitive and communicative impairments following TBI in terms of attention, memory, executive function, and social skills, rather than language per se. They concluded that there are a group of small "n" and single subject studies in these areas that support efficacy of treatment. These include 8 studies involving 81 individuals in attention treatment studies, 13 studies also involving 81 individuals receiving training to improve memory deficits, 7 studies involving 22 individuals enrolled in studies of executive functioning training, and 10 studies of 37 persons involved with social skills training. Like many other authors, Coelho and colleagues stress the need for more research including persons with severe TBI and emphasizing the importance of identifying subgroups of individuals with specific needs and broader outcome studies.

In general, however, speech-language pathologists largely function as members of rehabilitation teams, seeking to establish appropriate language use in conjunction with other rehabilitative activities in group settings, in vocational settings, and in interventions in which attempts are made to reestablish frontal lobe or memory functions through language-based activities.

A number of such programmatic approaches have been described in the literature, mostly texts that outline comprehensive rehabilitation programs. Three recent examples of authors who have made attempts to interweave communication and social skills training into the fabric of TBI rehabilitation are Sohlberg and Mateer (1989), Ylvisaker and Feeney (1998), and Ponsford (1995). The texts of all three of these sets of authors have as their goals the reintegration of the person with TBI into society and everyday life. Although the approaches are distinctive, they each rely heavily on the literature to establish clear rationales for their respective comprehensive approaches. Where data exist for justifying particular aspects of each approach, it has been taken into account. However, in common with most interventions in TBI rehabilitation, they have not been comprehensively evaluated in terms of their effectiveness.

Psychotherapy

The exact role of psychotherapy in the management of cognitive problems in persons with TBI has not been fully elucidated. The affective consequences of TBI are many and frequent, with incidence figures varying between 10 and 77 percent (Rosenthal et al., 1998), and it has been estimated that up to 30 percent of persons with TBI have had suicidal ideation or attempts (Leon-Carrion 1997). The emotional reactions to TBI are variable, and although less has been studied formally about these emotional disturbances than about the cognitive effects of TBI, the affective impairments are more often the focus of concern of individuals’ family members and relatives than are the cognitive deficits. Depression, anxiety, and loss of self-esteem are the most common consequences of TBI. Etiologies of depression vary. There is considerable evidence to suggest that depression and anxiety may be direct results of the brain injury itself, but it also is clear that situational depression, the effects of family dysfunction, and the emotional reactions to the onset or persistence of the disability may play significant roles in their genesis. There also is evidence to indicate that post-TBI depression is associated with poor social functioning and reduced ability to perform activities of daily living (Jorge et al., 1993; Jorge et al., 1994).

It is important to understand that emotion and motivation are tightly interconnected with arousal, perception, and self-awareness, which may confuse the picture somewhat (Prigatano, 1986). The emotional disorders may directly and adversely affect recovery from other functional deficits, participation in a therapeutic program, and many aspects of quality of life. These points are important as one considers treatment methods. Although psychotherapy by itself has been used in isolation, it is a generally accepted practice that psychotherapy is provided in the context of a comprehensive program in order to allow simultaneous treatment of the cognitive and emotional deficit problems, because treatment of one set of conditions facilitates treatment of the other problems.

According to Leon-Carrion (1997), treatment of emotional disorders should be directed toward supporting the individual by (1) offering hope; (2) offering explicit evidence of affection, especially by relatives; (3) promoting self-esteem; (4) dealing with issues that are emotionally relevant; (5) providing opportunities for group therapy participation; (6) providing weekly individual psychotherapy sessions; (7) carrying out therapy to assist with adjustment to reality; (8) involving the family in treatment; (9) focusing on the individual’s strong emotional and cognitive areas; and (10) developing socially adequate expression of emotion.

Prigatano and colleagues (1986) identify similar goals of psychotherapy: (1) to help the person understand the effects of the injury; (2) to help the individual deal with the meaning and implications of the brain injury; (3) to help the individual achieve a sense of self-acceptance and forgiveness; (4) to help the person make realistic plans to return to work, family, and the community; (5) to teach the person with TBI appropriate social competencies; (6) to provide compensatory neuropsychological strategies; and (7) to provide a realistic sense of hope.

Elements of the psychotherapeutic interventions include simple explanations, repetition of coping strategies, use of group "pressure" to influence behavior, use of individual insight and behavioral strategies to enhance coping skills, and involvement by families to understand the individual’s progress and to ensure followthrough.

Prigatano and colleagues (1986) provide an extensive and detailed set of specific suggestions for methods to conduct psychotherapy for individuals with TBI, but as with other types of interventions, minimal formal intergroup comparison testing has been conducted to determine the effectiveness of any of these techniques.

However, despite the eloquent descriptions of the goals and content of these psychotherapeutic interventions, little objective scientific evidence of the effectiveness of these approaches has been offered. To date, there exist no double-blind randomized controlled clinical trials of psychotherapy (or any other type of intervention for post-TBI depression, for that matter). However, uncontrolled case reports and single case design studies are available.

Forssmann-Falck and associates (1989a, 1989b) and others have recommended the use of outpatient group psychotherapy treatment in small closed groups in weekly 1-hour sessions for 1 year to provide a "social microcosm" for the individual with TBI, enabling members of the group to make behavioral changes through cognitive insight and emotional experience. Unfortunately, only descriptions of the programs, but no data to scientifically support their use, are provided.

Pharmacological treatment can be used to treat depression and anxiety, using a variety of commonly employed antidepressant medications. None of these has been shown scientifically to have a particular advantage in persons with TBI. It is important to note, however, that some of these medications may delay, slow, or impair recovery of cognitive functions (Prigatano et al., 1986; Rosenthal et al., 1998).

Behavior Modification

Behavioral disorders that result from TBI include aggressiveness, impulsiveness, disinhibition, social inappropriateness, apathy, dependence, and others. Often these personality and behavior changes are the most troubling problems caused by TBI, and they are typically more problematic for family members than for the individuals themselves. Managing the behavior in order to enhance the person’s cooperation with the therapeutic program, improve functional skill performance, and reduce social inappropriateness are important goals of the rehabilitation program. The application of classical behavior modification techniques to the behavioral disorders of individuals with TBI has been considered and studied because many of the problems with which persons with TBI present are similar to the problems for which behavior modification has been practiced in the past. This approach also might be useful to train the person in the proper performance of social skills (Brotherton et al., 1988), defined as competencies that enable the individual to interact with others in a socially acceptable manner that accomplishes desired goals at minimal cost, without manipulative behavior. These behaviors create positive first impressions and enhance communication.

Eames and Wood (1985a) reported on their behavior modification treatment approach for persons with TBI conducted in a dedicated behavior modification unit, the Kemsley Unit at St. Andrew’s Hospital in Northampton, United Kingdom. This treatment is based on the use of "positive reinforcement" of desirable adaptive behavior (using "tokens," "treats," privileges, and, in particular, increased attention and praise), and strict avoidance of reinforcement (using "timeout") of inappropriate, maladaptive, or socially unacceptable behaviors. Consistency, repetition, and rewards are used in a structured and supportive environment. Other authors, including several based at the Kemsley Unit itself (Goodman-Smith, Turnbull, 1983; Giles, Clark-Wilson, 1988; Eames, Wood, 1985b; Giles et al., 1988; Alderman, 1991) and some at other programs (Machuca et al., 1997; Hollon, 1973; Goodkin, 1966; Slifer et al., 1993; Brotherton et al., 1988; Gajar et al., 1984; Horton, Barrett, 1988; Horton, Howe, 1981; Yuen, Benzing, 1996; Peters et al., 1992; Turkat, Behner, 1989; Tate, 1987; Howard, 1988; Lloyd, Cuvo, 1994; Hogan, 1988; Wood, Cope, 1989), have commented favorably on the success of the approach, but most have relied on descriptions, anecdotes, and case reports. Only Eames and Wood (1985a) published the results of a trial of the behavior modification approach, although this study lacked a formal experimental design. In this trial, 24 persons with severe disability, including behavior disorders, resulting from TBI sustained at least 1½ years earlier underwent treatment in the Kemsley Unit, an environment in which the principles of behavior modification were strictly enforced. At followup, the persons with TBI demonstrated improved placements and socially acceptable behaviors, as judged by family members.

Comprehensive Interdisciplinary ("Milieu") Models

Arguably the most commonly used model of practice in rehabilitation for persons with TBI is interdisciplinary treatment provided by a team of experienced professionals from different backgrounds in a therapeutic environment that promotes learning, coping, and adaptation to the new disability. Several types of models are used; comprehensive interdisciplinary rehabilitation may be provided in an inpatient hospital setting, an outpatient therapy setting, or a residential environment. Some of the programs attempt to address all of the problems that are experienced by the individual with TBI, including physical and sensory-motor deficits; these are commonly conducted in inpatient hospital settings, although outpatient treatment may address these as well. Other comprehensive programs, perhaps more commonly described for persons with TBI, focus more heavily on the emotional, cognitive, and behavioral issues, and especially on their impact on vocational and community activities. These are typically conducted in an outpatient environment, where the program may be known as "day rehabilitation."

Attempts are made in these programs to resocialize persons with TBI, to reintegrate them into society, to focus on activities that will foster their return to work and community-level activities. A particular emphasis is on training for deficits in cognitive skills. This involves direct retraining of the cognitive function to minimize the impairment, as well as substitution training and compensation training.

An important feature of the interdisciplinary model is that it emphasizes more than cognitive retraining alone. The physical skills required for successful community reintegration are taught, social skills training is provided, and often psychotherapy is offered to address the emotional needs of the individual. In the "milieu" environment, interaction among individuals with TBI provides another opportunity for a therapeutic intervention.

Rehabilitation professionals who are involved include physical therapists, occupational therapists, speech-language pathologists, neuropsychologists, vocational rehabilitation specialists, and, to varying extents, social workers, therapeutic recreational specialists, rehabilitation nurses, rehabilitation physicians, and others. Although each professional provides a slightly different area of expertise to benefit the individual with TBI, the specialty of the professional is considered less important than the nature of the therapeutic interaction. Whereas the specific programs may vary, there are some common features of the interdisciplinary rehabilitation care model. Many of the interventions are genuinely interdisciplinary, involving more than one type of specialist. The therapy program is coordinated to minimize unnecessary duplication and to maximize individual progress. There is synergy among the various professionals so that the "gestalt" of the program is felt to be greater than the sum of the individual specialists’ interventions.

The most commonly cited interdisciplinary models to address the cognitive, emotional, behavioral, social, and vocational issues of brain-injured individuals are those by Prigatano and colleagues (1984, 1986) and Ben-Yishay and colleagues (1981, 1985, 1987). Other authors of anecdotal or observational reports of programs include Malec and colleagues (1993), Mills and associates (1992), Mackay and associates (1992), Cope and colleagues (1991), Johnston and Lewis (1991), Sahgal and Heinemann (1989), Burke and colleagues (1988), Scherzer (1986), Stern and associates (1985), Rosenbaum and colleagues (1978), Najenson and colleagues (1974), and Rusk and associates (1969).

Studies evaluating scientifically the effectiveness of these approaches have been few in number, but an efficacy literature is now emerging. In his own program, Prigatano and colleagues (1984, 1986) reported that modest improvements in neuropsychological test performance were seen in the individuals who received the very intense milieu form of treatment and that substantial improvements also were seen in affective functioning. However, only 50 percent of the persons with TBI maintained full employment at the time of followup, but this was favorable when compared with the 36 percent rate among controls. These investigators suggested that the milieu form of treatment may have helped individuals feel better about themselves and improve in their neuropsychological performance but that this treatment only slightly improved the likelihood of return to work.

In a very recently published quasi-experimental study (Semlyen et al., 1998), functional and health status outcomes of persons with severe TBI who underwent coordinated multidisciplinary rehabilitation in a hospital-based rehabilitation unit were compared with those of persons who received a single-discipline approach to therapy provided by local hospitals. The group of individuals who received the coordinated multidisciplinary rehabilitation program demonstrated significant gains in several functional independence measures during the 2-year study period and after the treatment ended, in contrast with the comparison group, who did not demonstrate functional gains or posttreatment effects.

Vocational Rehabilitation

Background

Return to work may be considered the last frontier in the rehabilitation of persons with TBI. It has been described as the most significant outcome characteristic of successful rehabilitation and community integration (Thomas, Menz, 1997). In the last 10 years, numerous articles, books, and book chapters have appeared that describe the broad spectrum of approaches to return to employment following TBI. However, most of this literature focuses on describing evaluation techniques and program design. Very few papers present objective data supporting the efficacy of the techniques used to return persons with TBI to competitive employment. In fact, most of the literature can be categorized as follows: (1) articles that focus on identifying variables that predict work outcomes, (2) articles that describe how vocational assessment and rehabilitation services should be conducted, and (3) articles that address efficacy and needs for various employment approaches (Thomas, Menz, 1997). Rarely have authors of these papers described methods to assess job-seeking skills, structure job searches, or identify behaviors critical to sustaining employment in a competitive market (Thomas, Menz, 1997).

Of the 206 articles reviewed for this chapter, 22 were selected for analysis and presentation. They are categorized as follows: (1) problems/barriers to return to work (Ryan et al., 1992; Crisp, 1992); (2) program descriptions (Lyons, Morse, 1988; Johnston, Lewis, 1991; Johnston, 1991; Hogan, 1988; Cope et al., 1991; Milton, 1988; Kreutzer et al., 1988; Wehman et al., 1989a, 1989b, 1990, 1993; Ben-Yishsay et al., 1987; Buffington, Malec, 1997; Jacobs, 1997; Bogner et al., 1997; Jacobs, DeMello, 1996); (3) interventions (Stapleton et al., 1989; Wehman et al., 1989a, 1989b); (4) problems and interventions (Sander et al., 1997); and 5) relevant general information, including numerous references to categorize this vast body of vocational rehabilitation literature (Zasler, 1997; Thomas, Menz, 1997).

Barriers to Return to Work

In general, most authors agree about the major problems or barriers to return to work. Even the most successful prevocational programs and vocational rehabilitation programs have identified universal barriers to return to work after TBI. Ryan and colleagues (1992) studied 80 individuals in order to identify whether traditional neuropsychological measures would predict successful vocational training in a severely neurologically impaired population. The persons studied were evaluated before prevocational training, which consisted of cognitive remediation and psychosocial interventions. They found that the most significant neuropsychological predictors of vocational outcome were reading comprehension, immediate and delayed verbal memory, level of depression, and dysphasic symptomatology. Crisp (1992) reviewed 29 studies to identify variables related to vocational reentry after TBI. According to Crisp, most of the literature is dominated by medical and clinical neuropsychological studies. Factors that have been associated with vocational outcome include severity of injury, cognitive deficits, personality change, psychosocial adaptation, physical impairment, age, preinjury work/education history, and access to intensive rehabilitation. Reference was also made to employer attitudes as a barrier to achieving vocational goals following TBI. The most important, according to this author, are cognitive deficiencies, personality change, psychosocial adaptation, and access to rehabilitation services.

Sander and colleagues (1997) conducted a quasi-experimental fixed effects factorial design study on an outpatient population of persons with TBI. The purpose of their study was to determine differences between employed and unemployed persons with TBI with regard to their substance abuse and neurobehavioral problems. Descriptive and correlational analyses were employed to determine factors related to successful employment. The main outcome measures included the Neurobehavioral Functioning Inventory (NFI), the Quantity Frequency Variability Index (QFVI), and the General Health and History Questionnaire (GHHQ). Results indicated that (1) the unemployed reported greater frequency of difficulty on the NFI depression, attention/memory, aggression, communication, and motor scales; (2) more unemployed received mental health services; (3) a higher proportion of employed were classified as moderate to heavy drinkers; and (4) there was a low rate of drug abuse and no difference in drug abuse in the employed versus the unemployed. Three major areas of difficulty were identified: physical, cognitive, and personality and mood. According to Sander and associates (1997), the 10 most frequently reported neurobehavioral problems for the employed included impatience, fatigue, headaches, slow reading ability, decision-making problems, reduced physical strength, drops things, easily distracted, complains, and learns slowly. The most frequently reported neurobehavioral problems for the unemployed included boredom, slow movement, frustration, impatience, slow reading ability, fatigue, easily distracted, restless, learns slowly, and loses train of thought. The intervention phases were (1) pre-placement, in which skills, knowledge, and attitudes are enhanced to prepare the client; (2) job-matching and development, in which the person is helped to find work that fits his/her interests and abilities and to find accommodating employers; and 3) post-placement intervention, in which the person is helped to learn and maintain the job. This last phase included job site advocacy, reorganizing the work environment, and developing compensatory strategies. Proponents of this approach advocated the use of memory notebooks, calendars, checklists, alarms, mnemonics, and imagery training for pre-placement intervention of cognitive difficulties.

Description of Vocation Rehabilitation Programs and Interventions

Fifteen papers described programs specifically developed to facilitate return to work of the individual with TBI. Lyons and Morse (1988) described an eight-phase therapeutic work program designed to assess and develop pre-vocational skills in adults with TBI. The phases were described as follows: Phase 1. Individualized assessment and treatment employing an interdisciplinary approach; Phase 2. Group treatment with emphasis on interaction and interpersonal skills; Phase 3. Vocational focus through therapeutic work groups (determining potential, supervised work, school or training, homemaking, supervised functional mobility, manageable social behavior, 30 minutes or more of attention span, ability to follow two-step written, verbal, and demonstrated directions, ability to establish goals with guidance); Phase 4. Structured therapeutic work groups (5 days/week, 3 hours/day; individualized treatment goals and work tasks; occupational therapy collaboration with vocational counselors); Phase 5. Supervised work placement within the hospital; Phase 6. Supervised work outside the hospital in which the worker role replaces the individual role; Phase 7. Placement in competitive or noncompetitive employment following individualized vocational counseling, work site evaluations, vocational evaluations, and meetings with former and potential employers; Phase 8. Followup. Mean length of time at the therapeutic work program was 6.2 months. Of the 29 respondents to the followup questionnaire, 79 percent (23) of the original population who participated in the program were engaged in occupational activities, 17 competitively, 2 as students, 4 as primary homemakers. Some of the problems identified were poor work satisfaction, subjective work difficulty, and poor self-evaluation of job performance. This program’s strengths included the continuation of individualized occupational therapy during group treatment, strong intra- and interdisciplinary communication, grading of responsibility and task difficulty, strong vocational rehabilitation intervention, and followup by the rehabilitation team.

Johnston and Lewis (1991) used the Rehabilitation Outcome Questionnaire to measure the effect of a community reentry program on independent living and productive activities. They evaluated 82 persons with TBI from 9 national for-profit postacute facilities. These were listed as "transitional living," "education," and "employment programs." All treatment teams were multidisciplinary. At 1 year after discharge, there was evidence that participation in their program resulted in enduring improvements in independent living and productive activities. Total supervision requirements decreased substantially and paid employment increased. They concluded that community reentry programs produce enduring improvement in independent living and in a range of productive activities (paid or unpaid). The average program costs were $106,000 per person (Johnston, 1991). Unfortunately, the specifics of the interventions were not described.

Hogan (1988) described a behavior management program for community reentry and indicated that behavior disorders were the most significant deficit in the workplace. Although this paper consisted of a description of a program, it identified succinctly the significant vocational issues that should be addressed in an effective program. These include (1) setting vocational goals early, (2) emphasizing work readiness behaviors, (3) setting up situational vocational assessments, (4) identifying strengths and weaknesses, (5) counseling to promote work adjustment in realistic work settings, and (6) interventions for stamina and conditioning since physical exercise is especially important for behavioral disorders.

Cope and colleagues (1991) used a single-blind interview methodology to study residential status, level of productive activity, and hours per day of attendant care or supervision. One hundred forty-five persons with TBI were followed in a program that consisted of a coordinated system of postacute rehabilitation including a continuum of neurobehavioral, residential, day treatment, and community and home programs. This included medical and rehabilitation care; behavior management; activities of daily living (ADL); self-management; substance abuse; social, academic, and vocational skills training; and counseling and family education. Results indicated that the program was successful in increasing competitive employment and academic activity (6.1 percent compared with 22.9 percent at followup), increasing noncompetitive activities (3 percent compared with 20 percent), increasing volunteer activities (0 to 8.6 percent), and increasing recreation activities (0 to 2.9 percent). Methodological limitations included no matched controls, no random treatment versus no treatment, no data on coma and neuropathology findings, and dependence on self-report for some of the data.

Milton (1988) described the subtle cognitive communication deficits evident after TBI. Communication problems following TBI may reflect cognitive impairments of attention, inhibition, memory, integration and organization of information, and speed of processing. The vocational rehabilitation program presented was both home and community based. It included job analyses process and outcome, work strategies, and memo writing. Specific skills and compensatory strategies were identified to increase cognitive communication. It offered opportunities for structured behavior observation, performance feedback, strategy reinforcement, and monitoring of overall effectiveness of plan. Basic considerations and guidelines of the process included (1) focus on functional communication competency, (2) consideration of range of factors that may influence communication behaviors, (3) maintenance of an ecologic-systematic perspective, (4) awareness that a positive relationship between neurological predictors of rehabilitation outcome and actual improvement of communication skills may not be present, (5) flexible evaluation of communication skills and structured and unstructured observation, and (6) use of compensatory techniques.

Supported employment methodologies were reported in four of the papers reviewed. Supported employment is defined as paid work in a variety of settings, particularly regular work sites especially designed for persons with disability for whom competitive employment has not traditionally occurred and who, because of disability, need intensive ongoing support to perform in the work setting (Kreutzer et al., 1988). Its primary purpose is to provide service at the employment site. Supported employment blends behavioral rehabilitation techniques with recent advances in medical and neuropsychological rehabilitation. Four phases of supported employment have been presented by Kreutzer and associates (1998): (1) job placement, in which job needs are matched to the client’s abilities, communication is facilitated, travel requirements are identified, and the job environment and possible obstacles are analyzed; (2) job site training and advocacy; (3) ongoing assessment; and (4) job retention and follow-along. Cognitive rehabilitation and compensatory strategies include the computer, which is used to develop compensatory materials. This allows for rapid preparation and revision of checklists and schedules. Two case studies were presented in Kreutzer and associates’ report to demonstrate the successful outcomes of this approach.

Wehman and colleagues (1989a) described the cognitive impairment and remediational implications for employment. They discussed task analysis and visual cues as useful compensatory strategies for employed persons with TBI in supported employment programs. They emphasized compensatory strategies rather than skill-building approaches so that individuals are encouraged to use techniques that have direct and immediate application to daily work. Family support, education, substance abuse, self-awareness, interpersonal behavior, effects of emotional adjustment, and recreational pursuits are elements of ideal programs.

In another paper, Wehman and associates (1989b) described the effect of supported employment on vocational outcomes in five males with TBI. These men were placed in competitive employment using the individual placement model of supported employment. A multiple baseline design across persons was used to evaluate the results (wages earned and hours worked). The employment specialist’s intervention averaged 339 hours per case. Job placement was based on individual interest, job compatibility, job availability, available transportation, and family support. Supported employment uses a job coach who provides daily on-site training, support, and advocacy until the individual has demonstrated independence (20 percent staff time on site). The major problems encountered included insubordinate and disruptive behavior and inappropriate social behaviors. The outcomes for the five men studied are as follows: their average wages were $4.25 to $5 per hour; hours worked ranged from 15 to 40 hours per week; employment specialist intervention hours ranged from 210 to 451 (mean = 339); mean cost per person was $8,641. One subject dropped out of the program. For the remaining subjects, the mean amount of intervention time to stabilization (until staff time on the participants was reduced to 20 percent or less of work hours) was 256 hours. Therefore, the average cost for the initial job site training was $6,400 or $50 per week.

In their 1990 paper, Wehman and colleagues described their model of supported employment for persons with TBI. Their model included (1) individual placement into competitive positions paying at least minimum wage and (2) provision of job site training and support services by trained rehabilitation professionals (job coach or employment specialist). The program components included job placement that is made after extensive ecological analysis of potential work environment and consumer abilities, limitations, and interests; job site training and advocacy individualized for each placement; and monitoring by an employment specialist of performance and social adjustment after the client has achieved competence. In this study, 41 persons with TBI were placed in competitive employment during 30 months. Of this population, 71 percent continued. The mean hours worked were 31.2 hours per week; the mean hourly wage was $4.61. Most of the jobs were in warehouses or clerical and service-related positions.

In 1993, Wehman and colleagues reported on the supported employment outcomes of 80 persons with TBI after 5 years of competitive employment. The monthly employment ratio (MER) was used to calculate the results. This is derived from dividing the number of months employed during an employment phase (pre- or post-TBI) by the total possible months the individual would have the opportunity to be employed. The results indicate that the MER increased from 13 percent for individuals with TBI but no supported employment compared with 76 percent for those with supported employment services. The majority of the jobs were warehouse work and clerical and service-related occupations. Two hundred fifty staff intervention hours were required to train and provide followup services to participants. The limitations of the study were lack of a control group, validity of the self-report regarding employment history and prior services received, and the fact that no one is excluded from initially participating in the program (open door policy, including substance abusers). A total of 38 separations occurred, 75 percent of which were for multiple reasons: layoff, employment setting issues, interpersonal relationship issues, mental health/substance abuse/criminal activity, attendance, transportation, and involvement in litigation. These authors stressed that supported employment does not promote job readiness training; rather, it emphasized using a person’s current abilities and strengths.

As a complement to supported employment, Stapleton and colleagues (1989) described job coaching and the factors affecting its success. Job coaching is defined as teaching persons with TBI an actual job to be performed in the workplace. Its primary goal is to transfer work skills from the training site to the job site. Job coaches break down jobs into achievable and learnable components that reduce decision-making demands on the client. These authors describe five main categories of problems in the work site: (1) poor judgment, planning, insight, and social skills, which limit the person’s ability to work around people; (2) participants may not be able to perceive new information correctly or to retain it over time; (3) personality problems may limit the person’s ability to perform on the job or work in conjunction with others; (4) physical limitations and mobility problems may limit the person’s ability to get to and from work; and (5) academic deficits limit ability to perform job function. A seven-point survey instrument was used to identify problems in the work site (0 = not an issue, 7 = typically a problem). Six major problems were identified: slow accession of job skills, verbal memory, judgment, visual memory, inflexible thinking, and anxiety. Twelve moderate problems, including inability to complete work in a timely fashion, obsessive/compulsive behaviors, inability to detect/correct errors, and inability to work independently, were also identified. Problems considered minor included depression, communication problems, and punctuality. The results indicate that although job coaching did not obviate the person’s problems, it did minimize them, indicating that job coaching is a promising employment model.

Ben-Yishay and associates (1987) summarized the reported rates of return to work after TBI. The results indicate that in the 37 works cited, the rates of return to work varied greatly from author to author. This variability is derived from the TBI severity differentials, lack of uniform criteria for defining what return to work means, absence of adequate and consistent verification of work performance and status, and poor followup over time. The most frequently cited reasons for failure to return to work after rehabilitation for TBI are cognitive impairment (attention, persistence, memory, and executive skills), problems associated with disinhibition, impaired interpersonal skills, lack of awareness of the implications of the injury, and unrealistic expectations concerning the types of employment for which they are suited. Additionally, these investigators designed a study to determine the percentage of participants in their program who were able to attain competitive employment and the stability of the long-term vocational adjustment. Ninety-four persons with TBI had participated in a comprehensive outpatient day program ("therapeutic community"), which they attended 5 hours each day, 4 days per week, for a total of 20 hours per week. Before enrollment in the study, each person received a baseline comprehensive neuropsychological, functional behavioral, and interpersonal assessment. The three phases of the study were (1) comprehensive and systematic "holistic" remedial individualized interventions; (2) individualized guided occupational trials culminating in actual vocational placement and establishment of appropriate liaison, maintenance, and followup procedures; and (3) actual followup (assist individuals in finding work, familiarize them with the new job, and assist them in adjustment). The employment rating scale was described as 1 = unproductive; 2 to 4 = productive but not competitive (subsidized) work; and 5 to 10 = full- or part-time competitive (gainful) employment. Results indicated that at the conclusion of the program, 84 percent had attained the ability to engage in productive endeavors, 63 percent were at the competitive level, 21 percent were in a subsidized capacity, and 16 percent were unemployable. At 6 months, there was relatively little change in these rates. Followup data were obtained on 36 persons 3 years after participation in the program: 28 percent were unemployable, 22 percent were productive/noncompetitive, 25 percent were competitive/unskilled, 19 percent were competitive at a higher level, and 6 percent were competitive/gainful. The principle causes for lack of work stability during followup were social isolation, forgetting to consistently apply acquired rehabilitation strategies and use compensatory mnemonic aids, and financial disincentives.

Buffington and Malec (1997) described a vocational rehabilitation continuum for persons with TBI. They used a prospective case series of 80 adults in both inpatient and outpatient rehabilitation programs. Outcome measures included the vocational outcome scale, individual satisfaction survey, level of independent living, job type and setting, rate of pay, and number of hours worked each week. The intervention included emphasizing early vocational approaches, integration of the early vocational intervention with medical rehabilitation treatment, and providing a smooth transition from medical to community services. Hospital-based services included integrating vocational goals into rehabilitation goals, assessment of vocational readiness, a team approach with a transition from hospital to community, and programs to improve function (cognitive, psychosocial, and emotional; job trials, comprehensive return to work plans; and adjustment to disability). Community-based services focus on improving interagency linkages. The team approach—local agencies including State rehabilitation, work rehabilitation, centers for independent living, county social services, and State human services—addresses the needs of persons with TBI and works through community reintegration problems. Social support—family and significant others—must be actively involved. Evaluations include vocational assessment measures, on-the-job evaluations, and support from a job coach. Long-term followup is considered essential.

Jacobs (1997) described the clubhouse model, a member-directed, community-based program of supports to help persons with TBI return to work and sustain employment. All work is related to member goals and program operation. The costs range from $30 to $60 per day. Skill development encompasses practical goals, that is, large global skills broken down into daily steps. Events in the clubhouse provide support and cues to advocate experiential learning. Members look to one another as well as to staff. The long-term focus encourages the assimilation of skills. People learn skills in situations where the skills are customarily used. Social supports to behavioral and vocational ability include abilities over disabilities, member-directed participation, long-term supports, and community basis. Results of this model indicate that 17 to 35 percent of clubhouse members participated in compensated work (Jacobs, DeMello, 1996).

Bogner and colleagues (1997) described a retrospective study designed to demonstrate the effect of integrating substance abuse treatment with vocational rehabilitation after TBI. Additionally, this study was designed to assess the effectiveness of the TBI network model for treating substance abuse. The TBI network model of treatment is community-based and interdisciplinary. Early intervention, family involvement, and working closely with acute and postacute health care providers are also essential. Seventy-two subjects were enrolled consecutively in this treatment program. The QFVI, the GHHQ, the Addition Severity Index, and the Employability Rating Scale measured substance abuse and productivity. The results indicate improved productivity and abstinence. The factors that resulted in success were aggressive identification of substance abuse problems, belief that change can be promoted collaboratively, and establishment of ad hoc community teams to facilitate a coordinated approach.

Zasler (1997) has described the role of the physiatrist in vocational rehabilitation. Although this article is a clinical opinion and not the result of a research effort, the information is relevant to this subject. A physiatrist is rarely involved in the postacute vocational rehabilitation of persons with TBI. The physiatrist often provides the individual, family or significant other, and rehabilitation team with information regarding whether the person with TBI has achieved his/her maximal medical improvement and has the potential (medically, psychologically, and neurobehaviorally) to return to work. The physiatrist shares an understanding of the medical and cognitive sequelae of TBI with other members of the rehabilitation team and thus can contribute to the appropriate direction of vocational rehabilitation.

Thomas and Menz (1997) described the validation of the Vocational Assessment Protocol (VAP). One hundred forty-nine persons with TBI completed the VAP, and 116 participated in the followup assessment. The VAP addresses functional skills and vocationally related behaviors. Components include a structured interview to obtain demographic information; physical, social-emotional, and neuropsychological clinical profiles; and the vocational profiles of job search skills, interviewing skills, critical work behavior, and social adaptive behavior. An employment data questionnaire at 6 months is also used. The results indicate that the VAP is reliable and valid for assessing the basic vocational skills and functional behaviors related to employment for persons with TBI. Additionally, this article presents an extensive historical review of the literature on the topic of vocational rehabilitation for persons with TBI.

Pharmacotherapy

There are potentially at least two broad conceptual areas in which pharmacologic agents may be used for persons with TBI; medications may help to enhance cognitive recovery, and they may be used to treat cognitive, emotional, or behavioral disorders. At present, however, their usefulness appears to be primarily theoretical; no formal controlled trials have yet demonstrated the efficacy of medications for these purposes in TBI.

Pharmacotherapy for Recovery After TBI

There are currently no drugs available that are of demonstrated benefit in promoting cognitive and motor recovery from TBI, although the literature from animal model systems and human studies suggests the benefit of a number of different agents or classes of agents. At present, none of this research has been of sufficient impact to change the standard practice in TBI rehabilitation, which remains focused on behavioral and social interventions to aid recovery and additional interventions (some of which include pharmacologic interventions) to help manage the medical sequelae of TBI. Interventions to impact the neuroanatomy or neuropharmacology of recovery (involving the mechanisms described in the previous chapter) have gained common acceptance.

Animal model studies after TBI have suggested alterations in concentrations of catecholamines (Brown et al., 1974; Cohen et al., 1975; Robinson et al., 1980; Robinson et al., 1975; Vecht et al., 1975; Gualtieri, 1988) and glucose utilization (Feeney, Hovda, 1985). Efforts to replete catecholamines have focused on dextro-amphetamine (Mailing, Acheson, 1946; Meyer et al., 1963) and its progenitors such as methylphenidate (Gualtieri, Evans, 1988; Speech et al., 1993), with unclear results in both groups of animals (Feeney et al., 1982; Goldstein et al., 1988; Feeney, Hovda, 1985; Feeney, Hovda, 1983) and humans (Crisostomo et al., 1988; Walker-Batson et al., 1995; Hornstein et al., 1996). Although some of these studies showed a beneficial effect, they are difficult to interpret because of problems with study design, including individual selection; inclusion/exclusion criteria, such as depression (Jorge et al., 1993); and control groups (Small, 1994).

These catecholaminergic agents are sometimes used empirically in the rehabilitation setting, albeit infrequently and with only theoretical or anecdotal rationales. The cholinergic agents comprise another class of agents that also is used occasionally in the clinical treatment of TBI. Acetylcholine has an historical basis for use in TBI (Chavany, 1928; Ward, Kennard, 1942; Feeney, Sutton, 1987), with a rationale (Levin et al., 1986) concerning the role of central cholinergic neurons in memory (Aigner, Mishkin, 1986; Drachman, Leavitt, 1974; Squire, Davis, 1981), which is impaired in some persons with TBI (Dikman et al., 1987). Different animal models (Phillips et al., 1997) and human studies (Goldberg et al., 1982; Levin et al., 1986; Walton, 1982; Cardenas et al., 1994; Eames, Sutton, 1995) have also shown mixed results. With new cholinergic agents on the market (e.g., tacrine and donepezil) for degenerative memory disorders, empirical treatment with cholinergic agents currently plays an informal role in TBI rehabilitation.

Other agents are the subjects of ongoing investigations and are discussed in more detail in the previous chapter that describes the biological mechanisms of TBI. Some such agents include those that affect the neurotransmitter GABA (Mattson, Scheff, 1994; O’Dell, Hamm, 1995), various corticosteroids and nonglucocorticoid antioxidant steroids (Bracken, Holford, 1993; Hall, 1992; Giannotta et al., 1984; Brown, Hall, 1992; Hall, 1993), ACTH (Witter et al., 1975; van Rijzingen et al., 1996), progesterones (Roof et al., 1994), opiates (Wallace, Tator, 1986; Black et al., 1991), and opiate antagonists (Hayes et al., 1983; Hayes et al., 1990), TRH (Fukuda et al., 1979; McIntosh, 1994); barbiturates (Chesnut, 1997); "memory enhancing" agents (Pierce et al., 1993; Gualtieri, Evans, 1988), and neurotrophic factors.

One of the most promising lines of research, summarized in the previous chapter, is the use of neurotrophic factors to stimulate the development of new synaptic connections in the brain after injury. Examples of such agents include nerve growth factor (Sinson et al., 1995; Sinson et al., 1997), insulin-like growth factor-1 (Saatman et al., 1997), fibroblast growth factor (McDermott et al., 1997), neurotrophin 3, and brain-derived neurotrophin factor (Cheng, Mattson 1994; Ghosh et al., 1994). This line of research is exciting, but currently remains a "work in progress." Additional studies may yield favorable therapeutic outcomes.

Medications for Behavioral, Emotional, and Psychiatric Conditions

A substantial body of scientific literature documents the safety and efficacy of various psychotropic medications for the treatment of depression, anxiety, ADHD, OCD, psychosis, and agitation in individuals who do not have TBI. Although many of these problems are common sequelae of TBI, there is no significant body of literature documenting the safety and efficacy of these medications in individuals with TBI.

A decade ago, Gualtieri (1988) reviewed the pharmacotherapy of TBI. This comprehensive review, which included 185 references, did not include a single placebo-controlled drug trial. During the past decade, there was one double-blind placebo-controlled study of methylphenidate, a stimulant medication, in the treatment of adults with TBI (Speech et al., 1993). Outcome measures assessed attention, learning, cognitive processing speed, and social/personality functioning. There was no difference between the active medication and placebo groups on any of the outcome measures. The results of this study suggest that response to psychotropic medications may differ between individuals with and without TBI.

More recently, there has been an emerging recognition that some of the cognitive and behavioral sequelae of TBI may be alleviated through the use of a number of neuropharmacologic and psychopharmacologic agents (Zasler, 1992; Stein et al., 1994; Perino, Rago, 1997; Elovic, Antoinette, 1997; Raghupathi, McIntosh, 1997; Harmon, Boyeson, 1997; Novack et al., 1996). Although many drugs have been used, agents that have gained the broadest acceptance recently have been amantadine (Nickels et al., 1994; Gualtieri et al., 1989), bromocriptine (Muller, Cramon, 1994), and the levodopa/carbidopa combination ("Sinemet") (Lal et al., 1988; Haig, Ruess, 1990; Wolf, Gleckman, 1995). Methods to best integrate pharmacologic interventions with other rehabilitation interventions have been considered by some authors (Cope, 1994; Pulaski, Emmett, 1994). Despite this growing literature, no controlled efficacy studies exist regarding any of these medications.

Physical Exercise/Physical Therapy/Aerobic Training

Training in physical and functional skills forms the centerpiece of most comprehensive rehabilitation programs for persons with a variety of disabling conditions. For individuals with TBI, therapeutic exercises designed to reduce sensory-motor deficits and improve ability to perform daily living activities are frequently used in a variety of settings. In addition, aerobic conditioning training exercises may be used to enhance the fitness levels and endurance of persons with TBI. The exact effects of therapeutic exercise, in the form of strength, functional, and/or aerobic fitness training, on cognitive and behavioral functioning have not yet been fully examined. Improved self-esteem might be an expected favorable result from the enhanced physical functioning, improved independence levels, and increased aerobic capacity that might derive from therapeutic physical exercise, but similar to the effects on cognitive and behavioral functions, the full effects of physical exercise on emotional functioning after TBI are not known. Many authors have written on the importance of considering cognitive issues in developing a therapeutic exercise regimen for persons with TBI (Giles, 1989; Malkmus, 1983; Umphred, 1983; Mercer, Boch, 1983; Nelson, 1983; Pietrapiana et al., 1997), but few have scientifically studied the impact of these exercises on cognition. Jankowski and Sullivan (1990) reported that a circuit aerobic fitness training program of moderate intensity resulted in increased oxygen capacity, but also reduced fatigability and improved vocational outcome, in a group of 14 persons with TBI.

Art and Music Therapy

Prigatano and colleagues (1986) and others have commented favorably on the value of art as a means of providing opportunities for the use of "symbolism" for therapeutic purposes and for allowing the individual with TBI to have an outlet for portraying thoughts and feelings. Art has been used as adjunctive therapy in comprehensive models or, less commonly, on an individual or isolated basis. Art therapy can use many types of expression, but predominantly drawing. However, there is primarily anecdotal evidence of the usefulness of art therapy for individuals with TBI.

Music therapy has been used to address deficits in attention following TBI. A recent review summarizes the literature to date on the value of music in rehabilitation of brain-injured persons (Knox, Jutai, 1996).

Nutrition

Although a small but growing body of literature describes the importance of the role of nutritional assessment and intervention as components of the comprehensive management of persons with TBI, the specific impact on cognitive, emotional, or behavioral outcomes of improving nutritional intake has not been determined. Most available literature to date consists of descriptions of nutritional problems in individuals with TBI and reports of experiences in managing such problems (Clifton et al., 1986; Twyman et al., 1986; Middaugh, 1989; Ott et al., 1989; Varella, 1989; Young et al., 1992). Scientific rigor apparently has not yet been applied to testing the value of these nutritional support methods. This may be important since TBI causes massive systemic and metabolic insult, resulting in hypermetabolism, increased sympathetic activity, and increased catecholamine levels. Later, other changes occur that may require individualized nutritional assessment and management. The effects of nutritional problems and effective treatment of these on cognitive and behavioral functioning remain unclear.

Spirituality

There are numerous anecdotal accounts of the value of other nontraditional "interventions" or activities to improve cognitive, emotional, or behavioral functions after TBI. One specific personal narrative (Linge, 1990) derives from a clinical psychologist who sustained TBI himself. He comments on the role of "faith, hope, and love" as "nontraditional therapy" during his experience of recovery of function. There are no controlled studies available on the role of spirituality in enhancing cognitive, emotional, or behavioral outcome after TBI.

Other "Alternative" or Nontraditional Therapies

There is little scientific data to demonstrate whether specific "alternative" or unconventional therapy techniques are safe or effective, or what outcomes might be attained from their use. The Office of Alternative Medicine at the National Institutes of Health was initiated by Congressional mandate in October 1991 and began operation in October 1992. The goal of this Office is to evaluate alternative medical treatments. A few small grants awarded for exploratory studies specific to TBI rehabilitation have included music therapy and homeopathy. Other projects being supported by the Office of Alternative Medicine that are not specific to TBI rehabilitation have focused on the value of dance therapy, movement therapy, art therapy, exercises, massage, aquatic and touch therapies, acupuncture, macrobiotic diets, biofeedback, tai chi, and yoga.

Many rehabilitation centers and other practitioners include alternative therapies in TBI rehabilitation programs. Many consumers and their families pay "out of pocket" for alternative therapies. Alternative therapies are often used together with traditional therapies for persons with TBI. There is to date no scientific evidence of the effectiveness of these "alternative" therapies alone or in combination with other therapy approaches.

Interventions for Families and Relatives

Interventions for the family members of individuals with TBI are considered very valuable. Interactions between clinical rehabilitation professionals and family members usually involve more than the provision of psychological and social support, although these are important. Family members are felt to benefit from skills training, individual psychotherapy, support groups, family therapy, networking, and other intervention methods. Although the value of early and frequent involvement of family members in the rehabilitation program has been supported through considerable clinical experience and intuition, no scientific studies are available on the effectiveness of interventions to support the family or to secure family involvement. Authors who have commented on the importance of interventions with family members, and who have provided instruction on how to work with families, include Brooks (1984), Lezak (1978), Fujii and associates (1996), Quine and colleagues (1988), Freeman and colleagues (1992), Kreutzer and associates (1990), Forssmann-Falck and associates (1989a, 1989b), and Rosenthal and Muir (1983), but their reports do not contain empiric studies evaluating effectiveness of interventions.

Common Conceptual Themes

Review of the various types of rehabilitation interventions for persons with TBI reveals the presence of several common recurring themes. Generally, the interventions appear to be structured in their format and use consistent systematic approaches to treatment. Treatment is goal directed and usually focused on real-life situations and problems, except that some of the process-specific treatments emphasize "intermediate" outcomes. The individual with TBI is provided with a series of tasks and challenges, in an effort to enhance skill performance. Professional caregivers provide education, support, encouragement, supervision, and feedback. An ideal rehabilitation setting may be described as similar to an educational environment. For this reason, rehabilitation professionals/interventionists must rely on principles of learning theory, using graded levels of task difficulty, demonstration, and provision of feedback on performance.

A major feature of the rehabilitation activity, and one that frequently is overlooked in formal program descriptions, is that personal interactions between professionals and persons with TBI characterize much of what occurs in the rehabilitation program. Once again, no formal objective research has been conducted to demonstrate the effectiveness or relative value of any of these individual factors, although some rationale for their usefulness exists. It is important to note that some studies evaluated and found an impact of an intervention on ability to perform daily living activities; the use of external devices as compensatory aids generally were found to be more effective as an intervention than remediational efforts. Improvements in some specific cognitive functions, especially attention and memory, were demonstrated in some trials and case reports. It is unclear whether and to what extent there might be generalization or a "transfer of training" effect to either everyday living situations or other cognitive functions from the improvements that might be realized during focused structured cognitive-behavioral rehabilitation efforts.

Discussion

A recent discussion in the literature (Berrol, 1990; Volpe, McDowell, 1990; Levin, 1990; Hachinski, 1990) debated the controversy as to whether cognitive rehabilitation was efficacious for persons with traumatic brain injury. After reviewing similar data, the discussants reached a somewhat different conclusion. It ultimately was concluded that additional evaluation of cognitive rehabilitation is warranted.

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Howard A. Rusk is generally credited with being the pioneer of comprehensive, general rehabilitation in the United States; he was an early advocate for multidisciplinary, rehabilitative care. However, specialized models of brain injury rehabilitation were not initiated until the 1970s with the advent of the Glasgow Coma Scale (Teasdale, Jennett, 1974) and the Glasgow Outcome Scale (Jennett, Bond, 1975). Indeed, Rosenthal (1996) has described the period from 1975 to 1979 as the "era of enlightenment" for the field of rehabilitation following traumatic brain injury (TBI). During this period, improvements occurred in emergency medical services and acute care, and individuals began to be transferred to comprehensive TBI rehabilitation programs rather than to facilities for purely custodial care. According to Rosenthal (1996), the years from 1980 to 1984 can be described as the "era of proliferation" for TBI programs. In just a few years, the number of TBI rehabilitation programs swelled to approximately 500 (Rosenthal, 1996), and the continuum of care expanded substantially (Cope, 1985). Rosenthal (1996) has described the years from 1985 to 1989 as the "era of refinement." During these years, skepticism about the efficacy of TBI rehabilitation arose, and the scientific literature began to expand rapidly. New professional journals dedicated to TBI emerged, training programs for TBI professionals expanded, and major governmental funding became available. Rosenthal (1996) has described the years from 1990 to 1994 as the "era of accountability." During those years, allegations of provider abuse and fraud were published (Kerr, 1992), and a congressional subcommittee was charged to investigate consumer complaints. As a result, ethical guidelines and rehabilitation standards were assimilated by TBI professionals. Finally, Rosenthal (1996) has noted that the field of TBI rehabilitation has now entered the "era of consolidation;" this era mirrors the nationwide changes that are occurring in the health care industry. Specifically, there is an increasing shift toward outpatient care, reduction of costs, and earlier discharge from inpatient rehabilitation programs. After nearly 25 years of rapid evolution, the field of TBI rehabilitation is in need of an in-depth, scientific review.

A review of the TBI rehabilitation literature presents many difficulties, as has been noted by several authors. First, studies vary widely with regard to the definition of TBI, which complicates comparisons across studies. Second, most rehabilitation programs are heterogeneous in terms of treatments; that is, many rehabilitation strategies are used simultaneously so there is difficulty ascertaining which of the multiple components are actually effective. Third, studies vary widely in terms of the adequacy of outcome measures; the consistent use of standardized and ecologically valid measures is needed. Fourth, definitive outcome research requires a no-treatment control group, but a deliberate decision not to provide rehabilitative care for persons with TBI may be considered unethical. Therefore, randomized no-treatment studies generally have not been considered as an option. Fifth, many studies have relied on convenience samples rather than representative, national cohorts. For these reasons, the existing literature on TBI rehabilitation must be viewed with caution and with a recognition that definitive conclusions are difficult to draw.

A Conceptual Model of TBI Rehabilitation

The articulation of a model of TBI rehabilitation is challenging in its own right. The literature is replete with imprecise terms and labels that have been used by different authors in different ways. For example, terms such as "acute," "postacute," and "subacute" have been applied inconsistently. However, Malec and Basford (1996) have presented a conceptual framework that serves as a good starting point for a discussion of a comprehensive model of TBI rehabilitation (see figure 1). In Malec and Basford’s model, the acute phase of care following TBI includes emergency medical treatment, emergency room care, intensive care unit/acute hospital care, acute rehabilitation, and subacute rehabilitation (e.g., coma management). Accordingly, everything that follows acute-phase treatment is described as postacute care. In Malec and Basford’s model, the postacute phase includes interdisciplinary rehabilitation assessment, outpatient community reentry programs, comprehensive day treatment programs, residential community reintegration programs, neurobehavioral programs, and community-based services. Although not specifically mentioned in the Malec and Basford model, postacute programs also include home-based rehabilitation, independent living programs, and, more recently, "clubhouse" programs. Jacobs (1997) described the concept of a clubhouse as a member-directed residential/rehabilitation setting designed to facilitate community reentry and return to employment. To establish a firm basis for the consistent use of terminology, the Malec and Basford model has been adopted here as a framework for organizing this literature review, figure 1.

Overview of the Literature

A literature review by Cope (1995) examined the efficacy of key components of a comprehensive model of TBI rehabilitation. Cope reviewed the literature from the standpoint of several rehabilitation settings as follows: (1) ICU/acute neurosurgical care, (2) acute inpatient hospital rehabilitation, (3) outpatient/day treatment rehabilitation, (4) residential postacute rehabilitation, and (5) neurobehavioral programs. Cope selected studies with quasi-experimental designs that included significant elements of experimental methodology, validity, and functional and/or economic outcome measures. This review updates (and expands) the Cope review; the studies selected for discussion include observational reports and uncontrolled trials that were viewed by the Consensus Panel as "representative" studies in the TBI rehabilitation literature. However, this review is by no means all inclusive. Studies of TBI rehabilitation vary on many important parameters such as nature of injury, severity of impairment, sampling methodology, treatment setting, and experimental design, among many others. A full description of these relevant parameters is beyond the scope of this review. However, the evidence tables from the Evidence Report on Rehabilitation of Persons With Traumatic Brain Injury (Chesnut et al., 1998) contain this relevant information in a concise, well-organized format.

ICU/Acute Neurosurgical Care

In the Cope (1995) review, two studies of the ICU/acute neurosurgical care setting were described. ICU/acute neurosurgical care refers to the practice of including physiatrists and other rehabilitation specialists at the earliest possible point following TBI. Morgan and colleagues (1988) found that persons with TBI given early rehabilitation had significantly shortened lengths of stays and better functional outcomes at discharge. Mackey and colleagues (1992) found that persons with TBI who received early rehabilitation had shorter coma lengths and shorter rehabilitation stays in comparison with a matched control group who did not receive acute rehabilitation. However, a cautionary note about the Mackey study is that the shorter coma length for the rehabilitation group may be construed as a potential methodological shortcoming.

Acute Inpatient Hospital Rehabilitation

Cope (1995) reviewed several studies on TBI in the category of acute inpatient hospital rehabilitation, which refers to the use of an interdisciplinary approach to in-hospital rehabilitative care; this typically includes medical stabilization, physical rehabilitation, and cognitive/behavioral rehabilitation. Heinemann and colleagues (1990) conducted a descriptive study of persons with TBI discharged from an inpatient rehabilitation program and found demonstrative improvements in functional status and ADL capacity at 3 months after discharge. Blackerby (1990) found that increasing the intensity of rehabilitation activities led to reduced length of stay. Cope and Hall (1982) found that individuals referred for "early" comprehensive rehabilitation had a greater than 50 percent reduction in hospital treatment days compared with individuals who were referred for "late" rehabilitation. However, the groups in the Cope and Hall study did not differ in terms of functional recovery or functional status at 2 years postinjury. Spivack and colleagues (1992) found that both length of stay and intensity of treatment were associated with improved outcomes as measured by both physical and cognitive skills. Aronow (1987) found that individuals who received inpatient TBI rehabilitation had better outcomes than those who received only acute neurotrauma care on such measures as living arrangements, functional status, daily care requirements, and vocational status.

In addition to the studies reviewed by Cope in 1995, Davis and Acton (1988) examined the outcomes following acute inpatient rehabilitation for a group of persons with TBI who were elderly and found that 85 percent eventually returned to a home setting; more than half the sample achieved independence in activities of daily living. Keyser and colleagues (1995) examined persons with TBI immediately following acute inpatient rehabilitation and found generally low mean factor scores on the Neurobehavioral Rating Scale. Whitlock and Hamilton (1995) examined functional outcome following acute inpatient rehabilitation and found that even the most severely disabled persons with TBI can show a large degree of measurable functional improvement following acute inpatient rehabilitation. Heinemann and colleagues (1995) studied a cohort of persons with TBI following acute inpatient rehabilitation and found that the intensity of the rehabilitative therapies was not related to functional status gains. Tobis and colleagues (1992) examined outcomes following acute inpatient rehabilitation and found improvements in self-care and ambulation but limited benefits in terms of social and vocational functioning.

Outpatient/Day Treatment Rehabilitation

The Cope (1995) review included nine studies in the category of outpatient/day treatment rehabilitation, which refers to postacute rehabilitative strategies that deliver integrated, interdisciplinary rehabilitation services on an outpatient basis. Ben-Yishay and associates (1987) treated individuals in an outpatient cognitive rehabilitation program and found statistically significant improvement in employment at discharge and at 3-year followup. Prigatano and colleagues (1984) examined a postacute rehabilitation group, compared with a matched control group, on measures of neuropsychological functioning, emotional distress, and productivity; the treated group showed little improvement on neuropsychological measures but demonstrated improved productivity and decreased emotional distress. Ruff and Niemann (1990) compared outpatient day treatment with formal cognitive rehabilitation and found essentially equal outcomes on measures of depression. Scherzer (1986) followed a cohort of individuals who participated in a multidisciplinary day treatment program; he found improvements in neuropsychological status. Malec and associates (1993) found improvements in independent living and work outcome in two subgroups of persons with TBI (i.e., those treated within 1 year and those treated later than 1 year following injury). Fryer and Haffey (1987) found that a group of individuals with TBI who received an outpatient cognitive retraining program showed better outcomes on ratings of disability and psychosocial status in comparison with a matched control group. Haffey and Abrams (1991) found that persons with TBI who participated in a work reentry program, as contrasted with comparison groups, showed an improved employment rate. Wehman and colleagues (1990) used a vocational rehabilitation program (i.e., supported employment model) as an intervention and found increased employment rates at followup. Mills and colleagues (1992) reported on the treatment of persons with TBI in an outpatient rehabilitation program and found improvement in five-point level but not on cognitive measures.

In addition to the studies reviewed by Cope (1995), Lyons and Morse (1998) evaluated a community-based therapeutic work program and found that 79 percent of the participants returned to meaningful occupational activities. Buffington and Malec (1997) demonstrated that early vocational intervention (closely integrated with medical rehabilitative treatment) resulted in the placement of 40 percent of program participants within a 3-month period. Namerow (1987) followed a group of persons with TBI before and after an outpatient rehabilitation program and found modest improvements on both neuropsychological measures and functional scores. Switzer and Hinebaugh (1991) reported functional, vocational, or academic improvements in approximately 78 percent of participants with TBI in an intensive day treatment program. Rattok and associates (1992) studied three types of rehabilitation programs: (1) a balanced program emphasizing cognitive remediation and interpersonal therapies, (2) a program emphasizing primarily cognitive remediation, and (3) a program emphasizing primarily interpersonal therapies. All three rehabilitation programs were equally effective with regard to capacity to return to work and level of vocational achievement. Stern and associates (1985) studied a cohort of individuals with TBI who completed a daily treatment rehabilitation program and found cognitive improvements in 37 percent of the sample and improvement in family life/occupational status in approximately one-third of the sample. Prigatano and colleagues (1994) found that persons with TBI who underwent a neuropsychological rehabilitation program were more productive (as students or workers) than a matched historical group who did not participate in the rehabilitation program.

Residential Postacute Rehabilitation

Cope (1995) identified two studies in the category of residential postacute rehabilitation, which refers to residential rehabilitative programs that provide integrated cognitive, behavioral, physical, and vocational rehabilitation services to persons who are unable to participate in outpatient programs. Johnston and Lewis (1991) reported results from nine postacute rehabilitation programs and found a decreased need for supervision and/or care following the intervention. Cope and colleagues (1991) reported that comprehensive postacute rehabilitation resulted in improvements on measures of residential status, productivity, and dependency.

In addition to the studies reviewed by Cope (1995), Jones and Evans (1992) conducted a followup of persons with TBI who received services in a residential postacute rehabilitation program; they found that there was a significant increase in the percentage of clients living at home and a subsequent reduction in the need for inpatient care. Harrick and colleagues (1994) found improvements in productive activity, place of residence, and level of supervision for persons with TBI who participated in a transitional living program. McLaughlin and Peters (1993) reported that individuals with TBI participating in an innovative transitional living program were more independent in activities of daily living than those who engaged in only inpatient rehabilitation.

Neurobehavioral Programs

In the Cope (1995) review, three studies were identified within the category of neurobehavioral rehabilitation programs, which refers to residential programs that provide intensive behavioral treatments for persons with TBI who manifest severe behavioral disturbances. Eames and Wood (1985) reported that an intensive inpatient neurobehavioral intervention for persons with severe TBI (late-stage postinjury) resulted in improvements in residential options after treatment and better scores on behavioral and daily living scales. Ashley and associates (1990) found that individuals assessed at admission and discharge from an inpatient postacute rehabilitation program showed improvements on ratings of disability and living status. Sundance and colleagues (1992) found that individuals treated in a residential neurobehavioral program showed improvements in Rancho Los Amigos levels and disability ratings; 84 percent of the sample of persons with brain injuries were discharged home.

In addition to the outcomes reviewed by Cope in 1995, Eames and associates (1995) found that an intensive rehabilitation program for persons with TBI resulted in improvements in functional skills and social behavior. Ashley and colleagues (1997) found a pattern of positive long-term outcome stability following postacute TBI rehabilitation, except that vocational status decreased over the followup interval. Burke and colleagues (1988) followed the outcomes for persons with TBI discharged from a rehabilitation center and reported that nearly 70 percent of adults were placed in a less restrictive setting; approximately two-thirds were successfully placed in employment situations.

Outcomes Following Unspecified Rehabilitation or No Treatment

An evaluation of the TBI rehabilitation literature requires an examination of outcomes following unspecified rehabilitation or no treatment at all. Studies in this category examine outcomes for persons with TBI following unspecified rehabilitation, minimal rehabilitative programming, or no apparent rehabilitation. Kraft and associates (1993) surveyed occupational and educational achievements of Vietnam veterans with TBI 15 years postinjury and found that 56 percent were gainfully employed and that the occupational distribution was little different from uninjured controls. Dombovy and Olek (1996) conducted a telephone followup of persons with TBI (most of whom were discharged without rehabilitation) and found that physical disability was minimal but that approximately one-third remained cognitively impaired at 6 months; approximately two-thirds of persons with TBI remained unemployed. Brooks and colleagues (1987) conducted a followup of persons with TBI for the first 7 years after severe head injury and found that the employment rate had dropped from a preinjury level of 86 percent to a postinjury level of 29 percent. Stambrook and colleagues (1990) conducted a followup on a group of individuals with severe impairments following TBI; whereas all had been employed full-time before their injury, only 55 percent were employed full-time following their injury. Schalen and colleagues (1994) described a nonspecific management protocol for persons with TBI; the authors found that the number of individuals who returned to work was significantly higher after the introduction of the management protocol. Ruff and associates (1993) conducted a followup of a cohort of persons with severe TBI; after 6 months, only 18 percent of former workers had returned to gainful employment and only 62 percent of former students had returned to school. Dikmen and colleagues (1993) found that many persons who were moderately to severely impaired following TBI were unable to support themselves and work independently at 2 years postinjury.

Home-Based Rehabilitation, Independent Living Programs, and Clubhouse Programs

Recently, the postacute phase of TBI rehabilitation has been extended into home-based situations, independent living programs, and clubhouse programs. However, outcome data on the effectiveness of these new postacute rehabilitation approaches are mostly nonexistent. Lockhart and colleagues (1994) described a home-based rehabilitation approach for persons with TBI, although outcome data were not provided. In the home-based approach, visiting providers from home health agencies deliver rehabilitation services in the client’s home environment. In addition, rehabilitation services are increasingly available in the context of independent living programs and clubhouse programs. In general, there is an increasing emphasis on rehabilitation services in the "natural" setting (Carnevale, 1996); this emphasis typically includes training caregivers to implement and sustain behavioral management programs or other appropriate rehabilitation strategies (Fujii et al., 1996; Ragnarsson et al., 1993). These new postacute TBI rehabilitation programs appear to have promise, but there are limited data to support their efficacy at this time.

TBI Model Systems

The National Institute on Disability and Rehabilitation Research (NIDRR) funded the Traumatic Brain Injury Model Systems of Care. Until 1998, the TBI Model Systems encompassed five sites: (1) Rehabilitation Institute of Michigan/Wayne State University, (2) Santa Clara Valley Medical Center in San Jose, California, (3) Institute for Rehabilitation and Research in Houston, (4) Ohio State University, and (5) Moss Rehabilitation Research Institute in Philadelphia, but recently other such centers have been funded. These original five centers were involved in a prospective, longitudinal study examining the recovery and outcomes of a coordinated system of acute neurotrauma and rehabilitation. This multisite trial incorporates measures of impairment, disability, and handicap, according to the definitions of the World Health Organization. The TBI Model Systems are of particular interest because the continuum of care includes the following: (1) emergency medical services, (2) acute neurosurgical care, (3) comprehensive rehabilitation services, and (4) long-term interdisciplinary followup and rehabilitation services (Ragnarsson et al., 1993); this prospective, multisite trial has already generated valuable epidemiologic information regarding the causes and course of TBI. However, there appear to be distinct limitations to the Model Systems trial. First, there is no control group (or even a comparison group) to permit an examination of the effectiveness of the Model Systems approach in comparison with a no-treatment group. Second, there is an inevitable selection bias in a sample restricted to only five sites. Third, the treatments provided at the various Model Systems sites are not uniform, which complicates outcome analyses. Fourth, attrition during the first year has been found to be high (39 percent). Last, there are methodological limitations in the ability to track postacute service utilization. In spite of these limitations, data collection by the TBI Model Systems trial may provide considerable information on demographics, course, and outcome following comprehensive, multidisciplinary rehabilitation in the future.

Institute of Medicine Rehabilitation Model

In 1997, an important report titled Enabling America: Assessing the Role of Rehabilitation Science and Engineering was published by the Institute of Medicine (IOM), National Academy of Sciences (Brandt, Pope, 1997). The IOM report is particularly instructive because conventional models of rehabilitation are strongly challenged. Traditionally, rehabilitation has been conceptualized as the process of restoring a person’s functionality to permit him or her to live optimally in the environment. In short, the focus of rehabilitation has typically been on the "individual" and the restoration of his or her "functional capacity." The IOM model (see figure 2) depicts the "disabling" process as the situation in which a person’s needs are "large" in relation to the existing environment.

In contrast with "traditional rehabilitation," the IOM model depicts the "enabling" process as containing two strategic possibilities. First, a program of functional "restoration" (i.e., rehabilitation) might be pursued to permit a person to regain the capacity to function within the existing environment. Or second, a systematic effort could be made to "enlarge" the existing environment to make everyday functioning easier for a person with TBI. In this latter approach, the focus is more on changing the environment than on changing the individual. From this new IOM perspective, the manifestation of a disability occurs at the interaction of the person with his or her environment. As depicted in figure 3, a person brings to his or her environment a certain potential for pathology, impairment, or functional limitation. In turn, environments vary dramatically in terms of the physical and social factors that make them either more or less supportive. Therefore, for a given individual, disability becomes a function of the interaction between himself or herself and a specific environment. If the environment is sufficiently supportive for a given person, disability is minimized (or possibly nonexistent). If the environment is not sufficiently supportive for that person, then "potential" disability becomes manifest. The IOM model is highly instructive because it shifts the focus away from "rehabilitation" in the traditional sense to "enablement" in the broader sense of permitting a person to function within his or her environment. In the field of TBI, there will be a need to explore the utility of the new IOM model for its ability to generate new approaches to the minimization of disability.

Perspective of Persons With Brain Injuries and Their Families

In 1994, the Office of Special Education and Rehabilitation Services sponsored a national TBI conference titled Life After Brain Injury: Finding Answers I Can Live With. The advocacy statement of the conference attendees was that services for persons with TBI must be consumer driven and focused on consumer preferences to be effective. In short, consumer involvement and choice throughout the entire TBI rehabilitation and enablement process are the clear expectation of the majority of persons with TBI and their families. However, the literature on TBI models is surprisingly lacking in the area of consumer involvement. Therefore, the entire literature on comprehensive, multidisciplinary rehabilitation models for TBI can be questioned from the standpoint of its applicability to the real-life needs of persons with TBI. Clearly, future research on TBI rehabilitation and enablement will need to be much more attentive to the expressed needs of consumers.

One development viewed as positive from a consumer standpoint is the requirement of projects funded by the National Institute on Disability and Rehabilitation Research that participatory action research (PAR) (Whyte, 1991) be incorporated into the study methodology. With the PAR approach, consumers are included as participants in the research process at all levels. Specifically, consumers help define relevant research questions, conceptualize clinically meaningful methodologies, and participate in the interpretation of findings. In the PAR process, there is a commitment to a partnership between experts who possess scientific skills and consumers who can enhance clinical relevance. To date, the field of TBI outcomes research appears to be lacking in studies describing the area of appropriate consumer involvement.

Evidence Report on Rehabilitation of Persons With Traumatic Injury

An evidence report on rehabilitation of persons with TBI was prepared by the Evidence-Based Practice Center at Oregon Health Sciences University and submitted to the Agency for Health Care Policy and Research (Chesnut, 1998). The methodology in the evidence report was rigorous, beginning with a comprehensive search of key databases (e.g., MEDLINE, HealthSTAR, CINAHL, and PsychINFO). Identified articles were reviewed independently by two members of the research team and judged as to their appropriateness for inclusion on the basis of specified eligibility criteria. Articles that met the eligibility criteria were abstracted from the standpoint of individual characteristics, co-interventions, outcomes, study methods, relevance to specified questions, and results. Studies were characterized into three categories: (1) Class I = randomized, controlled trials; (2) Class II = well-done, prospective, quasi-experimental, or longitudinal studies; or (3) observational studies, case reports, or expert opinion. Evidence tables were constructed to address five questions:

1. Should interdisciplinary rehabilitation begin during the acute hospitalization for TBI?
2. Does the intensity of inpatient interdisciplinary rehabilitation affect long-term outcomes?
3. Does the application of compensatory, cognitive rehabilitation enhance outcomes for persons who sustain TBI?
4. Does the application of supported employment enhance outcomes for persons with TBI?
5. Does the provision of long-term care coordination enhance the general functional status of persons with TBI?

Evidence tables were constructed, and the conclusions were as follows:

1. There was weak evidence supporting an association between acute inpatient rehabilitation and decreased length of stay.
2. There was no evidence that the intensity of acute inpatient TBI rehabilitation is related to outcome.
3. There was Class II and Class III evidence that electronic aids and computer-assisted cognitive rehabilitation strategies can be useful for improving performance on neuropsychological tasks.
4. There was Class II evidence that the vocational outcomes of TBI survivors could be improved through the use of supported employment programs.
5. There was mixed evidence for the effectiveness of case management approaches to the rehabilitation of persons with TBI; firm conclusions could not be drawn.

Summary of Findings

The literature pertaining to comprehensive, multidisciplinary models of TBI rehabilitation can be summarized as follows:

1. There has been a rapid evolution in the field of TBI rehabilitation over the past 25 years. The field of TBI rehabilitation has emerged as a viable rehabilitation specialty, has grown dramatically, and has reached the point at which a thorough scientific review of the literature is possible.
2. In the field of TBI rehabilitation, there is great discrepancy in definitions of terms. The work of Malec and Basford (1996) provides a usable overview of the components of a comprehensive, multidisciplinary rehabilitation model.
3. A promising development in the field of TBI rehabilitation is the sponsorship by NIDRR of the TBI Models Systems of Care. Although the TBI Model Systems research strategy has apparent methodological limitations, the comprehensiveness of the data set may help answer certain research questions in the future.
4. The publication of the IOM "enablement" model has considerable implications for the field of TBI rehabilitation. The new IOM model suggests that researchers, clinicians, and consumers may need to think more in terms of enablement than rehabilitation per se. The IOM model also suggests the importance of focusing on the expansion of environmental opportunities and the removal of barriers for persons with potentially disabling conditions such as TBI.
5. Few scientific studies are available that describe consumer involvement in TBI rehabilitation. PAR strategies may offer a valuable framework for effectively including consumers in the research process on TBI rehabilitation.
6. The literature on TBI rehabilitation outcomes is significant in terms of the numbers of published studies. However, the inability to include a no-treatment control group in most if not all studies has precluded the execution of "true" randomized, controlled, scientific experiments. Therefore, conclusions from the TBI rehabilitation literature must be drawn with great caution. When assessing the TBI rehabilitation research literature, there is value in the AHCPR evidence report on rehabilitation of persons with TBI. Based on a review of well-done observational, longitudinal studies, the report concludes that there is weak evidence suggesting that acute-stage TBI rehabilitation programs are effective for reducing length of stay. Based on a limited number of quasi-experimental studies, the report concludes that there is moderate evidence for the effectiveness of computer aids for memory improvement and for the use for supported employment under well-coordinated conditions. The report futher concludes that the remainder of the TBI research literature either shows mixed results or ambiguous findings or is otherwise inadequate from a methodological standpoint to permit more generic conclusions.

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Figure 2. Conceptual overview of the enabling-disabling process. The environment, depicted as a square, represents both physical space and social structures (family, community, society). A person who does not manifest a disability (a) is fully integrated into society and "fits within the square." A person with potentially disabling conditions has increased needs (expressed by the size of the individual) and is dislocated from his or her prior integration into the environment (b) that is, "doesn't fit in the square." The enabling (or rehabilitative) process attempts to rectify this displacement, either by restoring function in the individual (c) or by expanding access to the environment (d) (e.g., building ramps).

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Source: "Enabling America: Assessing the Role of Rehabilitation Science and Engineering," Copyright 1997, by the National Academy of Sciences. Courtesy of the National Academy Press, Washington, D.C.

Figure 3. The person-environment interaction. The enabling-disabling process is depicted as being an active part of the individual person. The physical and social environments are depicted as a three-dimensional mat, with social factors on one side and physical factors on the other. The interaction of the person and the "environmental mat" is depicted as a selection in the mat.

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Source: "Enabling America: Assessing the Role of Rehabilitation Science and Engineering," Copyright 1997, by the National Academy of Sciences. Courtesy of the National Academy Press, Washington, D.C.