Treatment of neuropsychiatric sequelae
The neuropsychiatric sequelae of brain injury, both socially and in the workplace, are well appreciated. Verbalizations and behavior can be striking, especially when the patient has a reduced ability to self-monitor and is unconcerned.64,65 Neurologic abnormalities may not be as distressing to the patient and his or her family as personality changes and inappropriate behavior. Suitable treatment of neurobehavioral sequelae will often decrease patient and caregiver distress and markedly improve overall outcome.
Intellectual impairments increase as the duration of posttraumatic amnesia rises from less than 1 hour to longer than 7 days. Inappropriate behavior associated with frontal, temporal, and limbic connections (e.g., poor social judgment, increased irritability, and poor impulse control) is particularly common, even in patients in whom imaging studies show no focal pathology. Frontal-thalamic reticular circuit damage may also cause fatigue and frequent sleep disturbances.
Depression
Studies consistently show a 25% to 50% incidence of depression after TBI. In one study, of the 75% of TBI patients who were not depressed at the initial interview, 25% developed depression during the first year of follow-up; the mean duration of depression was 4 to 5 months for the total sample.67 Patients frequently complain of hopelessness, a loss of interest in usual activities, self-deprecation, a lack of energy, and a lack of self-confidence. Anxiety symptoms may be prominent, especially within 6 months after injury.
Many reports suggest that the depression associated with stroke and TBI has a neurologic basis. Acutely depressed patients with TBI frequently have left anterior lesions, whereas patients with mixed anxiety and depression are more likely to have right-hemisphere lesions, a longer duration of depression, and poorer psychosocial outcome.67 The incidence of depression, its duration, and its associated symptoms, such as anxiety, may therefore be related to the location and laterality of cerebral pathology.
Antidepressants are indicated in the treatment of depression and of mixed anxiety and depression in TBI [see 13:VIII Anxiety Disorders]. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine are favored because they are safe and easy to administer and do not cause unwanted anti-cholinergic side effects. Tricyclic antidepressants may also be used; desipramine and nortriptyline have the fewest anticholin-ergic and antihistaminic properties. The antidepressant ven-lafaxine is both serotoninergic and dopaminergic. Although stimulants such as methylphenidate and dextroamphetamine have primarily been used in TBI patients to treat attention difficulties, they can also be used to treat depression or to augment antidepressant treatment with SSRIs or tricyclic antidepressants. Bupropion should be given only with caution to patients with brain injury, because it can lower the seizure threshold.
Anxiety
Anxiety disorders, alone or in combination with depression, occur in patients with TBI and are treated with SSRIs, tricyclic antidepressants, benzodiazepines, or buspirone. As with antide-pressants, buspirone has a 2- to 3-week latency period until it reaches full therapeutic effect. Patients with phobic avoidance are best treated with a combination of cognitive-behavioral therapy and benzodiazepines. Symptoms of posttraumatic stress disorder (PTSD) may occur and are more common in patients with MTBI than in patients with more severe TBI. Longer periods of posttraumatic amnesia, in which an explicit memory of the upsetting events is not established, may protect against the development of nightmares and intrusive thoughts about the trauma.68 The development of PTSD symptoms probably entails implicit memory by a mechanism similar to negative conditioning and thus may not require explicit memory of the event.69
Irritability and Aggression
Irritability occurs in more than 50% of patients with moderate or severe traumatic head injury during the first 6 months after injury. Aggressive outbursts in brain-injured patients tend to be verbal and brief and are precipitated by seemingly trivial provocations. Patients may be remorseful and apologetic afterward but seem to be unable to curtail subsequent outbursts. Irritability and aggression may occur in patients without a history of such behavior; disinhibition caused by frontal system dysfunction and possible injury to limbic and hypothalamic structures is im-plicated.70 Impaired serotonin transmission may also be involved, because low levels of 5-hydroxyindoleacetic acid (5-HIAA) have been noted in the cerebrospinal fluid of impulsive, violent patients. Anticonvulsants, lithium, buspirone, beta block-ers, SSRIs, and stimulants have been variously reported to be of use in decreasing the amount of aggression.71
Attention Deficits
The stimulants dextroamphetamine and methylphenidate may improve attention and concentration and are often used in the clinic in selected patients. A randomized, controlled study of methylphenidate in adults with moderate TBI found a more rapid rate of recovery of attention and improved scores on motor and disability tests but no change in ultimate overall outcome through the use of methylphenidate.72 Findings of a recent controlled crossover study on the use of methylphenidate in children suggested that there is no difference in behavior, attention, memory, or processing speed between persons receiving medication and those given placebo.73 Clear guidelines on the use of stimulants to treat attention deficits in TBI await additional studies.
Treatment of posttraumatic epilepsy
The risk of epilepsy in patients with closed-head injury is relatively small: 2% to 5% in all patients and about 10% to 20% in patients with severe closed-head injury.74 Some studies have shown a higher incidence of seizures in patients with depressed skull fractures (15%), hematomas (31%), and penetrating brain wounds (50%).75,76 In all cases, the risk decreases markedly with time. Although the relative risk of developing epilepsy 10 to 15 years after penetrating head injury is still 25 times higher than in the normal age-matched population, 95% of patients with penetrating head injury will remain seizure-free if they have no seizures during the first 3 years after injury.77
Because most patients who develop posttraumatic epilepsy in the first week after injury will have recurrent seizures for some time, anticonvulsant therapy is indicated in documented cases.78 Controlled, randomized studies have shown that the use of phenytoin, phenobarbital, carbamazepine, or valproate does not prevent the development of posttraumatic epilepsy beyond the first week after injury. It is now recommended as a standard of care that these medications not be used to prevent posttraumatic epilepsy in patients who have not had a seizure.79 In light of the sensitivity of the acutely traumatized brain to the secondary insult of a grand mal seizure, I recommend routine short-term use (for 1 to 2 weeks after injury) of phenytoin or carbamazepine in high-risk patients with acute TBI. Carbamazepine may be preferable because it helps control agitation in some patients.
Evidence suggests that iron-catalyzed lipid peroxidation may partly mediate the development of posttraumatic epilepsy; inhibitors of lipid peroxidation, such as methylprednisolone and a-tocopherol, can prevent iron-induced epilepsy in animals, but no well-controlled clinical trials have explored this avenue.80
Long-term Outcome
The young-adult brain has a remarkable capacity to compensate for many aspects of injury naturally. Although disabilities such as hemiparesis, seizures, and certain language disorders may initially appear more dramatic, the most devastating long-term impairments are the cognitive defects, attention deficits, and, in particular, behavioral changes that often persist after TBI.
Prognosis for full recovery must be more guarded in the elderly, who have been reported to have about twice the mortality of younger TBI patients. Likewise, seemingly less severe injuries often result in worse functional outcomes in older patients.
Measurement of outcome from TBI remains a challenge. Functional measurement instruments include the Glasgow Outcome Score, the Disability Rating Scale, the Rancho Los Amigos Score, the Functional Independence Measure, and various neu-ropsychological, behavioral, and quality-of-life measures. However, return to gainful employment is probably the best overall measure of long-term outcome.83 About 50% of patients who survive severe TBI eventually return to work. In recent studies, return to work was also the single best correlate of perceived quality of life.
Accurate predictors of outcome are also important to patients, their families, and caregivers in understanding recovery and planning for care. Early predictors of good outcome include a higher preinjury intelligence, youth, and a lower severity of in-jury.49 Certain genotypes, such as the ApoE4 allele, may affect recovery and outcome.86,87 In a large multidisciplinary study of survivors of penetrating head injury, the presence of seven factors were significantly predictive of unemployment: hemiparesis, epilepsy, visual field loss, verbal memory loss, visual memory loss, psychological problems, and violent behavior. These factors represent different domains of brain function and were relatively equipotent in the model (i.e., it was the number of impaired domains, not impairment in any one particular domain, that was predictive of unemployment). The brain may thus compensate for injury by utilizing whichever functional domains are still available to it.
Traumatic Brain Injury Rehabilitation
In the 1990s, the field of TBI rehabilitation blossomed. A profusion of therapies, including coma stimulation, cognitive rehabilitation, speech therapy, occupational therapy, and recreational therapy, are now available. Their use is largely empirical, and these sometimes expensive interventions have not been subjected to a high level of scientific scrutiny for efficacy and cost-effectiveness. Nevertheless, a growing body of animal and clinical literature supports the beneficial effects of training on the brain and on performance after injury.
The goals of therapy should be recovery of the patient’s independence and his or her reintegration into the community. The prevention of maladaptive behaviors is an important secondary goal. However, patients with scarce economic resources can find those resources depleted in the early phases of recovery by the evaluation of and therapy for specific neurologic or cognitive deficits that may resolve even without therapy or may ultimately be of marginal importance to the patient’s achieving the goal of independence. Interventions that may be more cost-effective, such as training in decision-making or other community reinte-gration skills and certain forms of behavioral management, may ultimately be omitted for lack of resources.
Although there is consensus about the benefits of some forms of rehabilitation for patients with TBI, the type, intensity, and duration of rehabilitation that are best for a given patient remain hotly debated.89,90 For example, a recent large prospective, randomized, controlled trial compared an intensive in-hospital program of cognitive rehabilitation with a limited (and much less expensive) home rehabilitation program in soldiers recovering from moderate to severe TBI.91 At 1 year after injury, there was no difference between the two groups with regard to return to work, fitness for military duty, or behavioral, neuropsychological, or quality-of-life measures. However, in a subset analysis of patients who were unconscious for longer than 1 hour after suffering TBI, there was a higher return-to-work rate for the patients who underwent hospital rehabilitation than for those who underwent home rehabilitation, suggesting the differential value of these approaches for selected patients. Thus, a fundamental challenge for rehabilitation is to distinguish the effect of the brain’s natural processes of recovery from the effects of treatment in patients with varying prognostic risk factors for long-term function. Clear resolution of these issues will require further properly designed, prospective, controlled, randomized trials.
