Neuropsychiatric Effects of Traumatic Brain Injury
Neuropsychiatric Effects of Traumatic Brain Injury
From time to time every psychiatrist comes across patients whose problems are at least in part related to the neuropsychiatric consequences (behavioral, cognitive, and emotional) of traumatic brain injury (TBI). TBI affects approximately 2 of every 1000 persons per year. Those who are vulnerable to mental illness (eg, persons with alcohol abuse or antisocial personality disorder) are particularly at risk. Patients with TBI often have poor insight and may need hospitalization for their own safety. The neuropsychiatric and other sequelae are long-term; a head injury is for life.
A telling illustration from 1937 by Courville, a neuropathologist, nicely demonstrates why TBI is of interest to psychiatrists (see figure 1 in Fleminger 20091). The illustration is a composite of the location of contusions found in 50 patients who died of TBI. The sites of specific vulnerability to contusions are the medial orbital frontal lobe and the anterior temporal lobes (Figure 1). Areas where contusions rarely occur include the primary motor, somato-sensory, and visual cortex. Therefore, areas of the brain concerned with social function and decision making are particularly vulnerable.2 It is unsurprising that neuropsychiatric sequelae outstrip neurophysical sequelae as the major cause of disability after TBI.
Contusions are areas of cerebral bruising particularly involving gray matter, whereby blood leaks into the extravascular space. The contusion results in cell death and local loss of tissue. Diffuse axonal injury affects white matter anywhere throughout the cerebrum and brain stem. It may be followed by generalized atrophy with ventricular enlargement (Figure 2); this may take a few weeks or months to develop. Diffuse axonal injury in the brain stem is usually responsible for the slurred speech and severe ataxia that are seen in some severely disabled patients after TBI. Contusions and diffuse axonal injury may be complicated by anoxic brain injury that may occur soon after trauma because of poor cerebral perfusion secondary to raised intracranial pressure and focal strokes. In some patients, localized infarction occurs (Figure 3).
The neuropsychiatric assessment starts by evaluating the severity of brain injury. In this way, the likely outcomes attributable to direct effects of brain injury can be determined, and any mismatch between these and what is observed can be attributed to psychological reactions or independent events. So, for example, in somebody with a severe psychotic illness that develops 3 months after an injury with no loss of consciousness, one can be fairly confident that the illness is not a direct consequence of the effects of brain injury on delusion formation. It is possible that the psychological trauma of the injury has allowed an acute psychotic reaction, or even that the injury was irrelevant and that the person was on the path to becoming schizophrenic anyway. On the other hand, it is likely that the psychotic illness is a direct effect of the brain injury in somebody in whom a delusional misidentification syndrome develops 3 months after an injury that was followed by coma for a week and delirium for several weeks.
The severity of brain injury is measured by the following:
• Glasgow Coma Scale (used soon after injury)
• Duration of loss of consciousness
• Duration of posttraumatic amnesia (PTA), ie, the interval between the injury and the return of continuous day-to-day memories
The duration of PTA is particularly useful as a measure of the severity of the brain injury because it can be measured retrospectively, eg, in the clinic years after injury, and it is a good predictor of outcome.3 As a rule, if PTA lasts less than 1 week, a reasonably good outcome is expected. If PTA lasts longer than 1 month, significant disability is likely; a good proportion of those affected will not be able to return to work or to independent living. In general, younger individuals (those in their late teens or 20s) tend to do much better.
An MRI scan is essential in cases where the extent of damage is unclear because it may show unexpected brain injury. Gradient echo sequences are the most sensitive and should be undertaken, particularly in those with mild injury. A normal MRI scan does not rule out brain injury, but it does make significant disability as a direct effect of severe brain damage unlikely. Electroencephalography is usually not helpful, even as a predictor of posttraumatic epilepsy.
Neuropsychometric assessment can be useful in defining the severity of cognitive impairment and any areas of particular impairment. Such tests as the North American Adult Reading test are available and provide an estimate of the patient’s preinjury IQ. Such assessment is necessary for the accurate interpretation of a patient’s postinjury performance. Also, make sure that tests of executive function have been done. Note, though, that normal neuropsychometric test results do not rule out brain injury as the cause of problems with executive functions in everyday life.
Irritability and aggression are probably the most common behavioral consequences of TBI. However, it can be difficult to know the extent to which brain injury is a factor in aggressive behavior. Many patients who have sustained a TBI were prone to antisocial behavior before the injury. It is sometimes argued that because a behavior is sensitive to psychological cues, it is not the result of a brain injury; however, this is not correct. For example, just because extreme aggression is seen only in the context of the family and never at work does not necessarily mean that the aggressive behavior is unrelated to a brain injury.
Teasing out the role of brain injury can be difficult and usually relies on a good objective history of the behavior before and after the injury, along with an assessment of the likelihood of significant brain injury, which depends in part on the location of the injury. Cold, goal-directed aggression is seen in patients with psychopathic personality disorder, whereas the aggression of the brain-injured patient is usually impulsive and quite out of proportion to the trigger. The latter, when severe, may be described as episodic dyscontrol syndrome. But in practice, it is not easy to discern the origins of aggression (constitutional vs brain injury) from its phenomenology.
In patients with severe brain injury, a typical clinical picture consists of significant cognitive impairment, particularly in the domains of attention and concentration, psychomotor speed, memory, and executive function, as well as fatigue and problems with motivation. The patient is likely to be self-centered, thoughtless, and crude in social relationships. He or she may show disinhibited behavior that is often sexual. Agitation and repetitive purposeless behaviors may also be present. Lability of mood is common; patients are often described as childish or moody.
Mild traumatic brain injury
Chronic symptoms of a rather nonspecific nature are quite common after mild TBI (Glasgow Coma Scale score of more than 12; loss of consciousness, less than 30 minutes; PTA, less than 24 hours). Approximately one-half, one-quarter, and one-eighth of patients still have significant symptoms at 3, 6, and 12 months, respectively.4 Typical symptoms include headaches, fatigue, dizziness, depression, and difficulties with concentration and memory, which are often complicated by anxiety symptoms related to travel and posttraumatic stress disorder. Alteration of cerebral blood flow during working memory tasks 1 month after injury and long-standing changes in fractional anisotropy—an MRI measure of white matter integrity—have been shown.5
These postconcussional symptoms are nonspecific and are seen almost equally often in patients with musculoskeletal injuries but no head injury and in patients with chronic pain or chronic fatigue syndrome. In some patients with long-standing postconcussional symptoms, the extent and severity of the symptoms suggest that the illness is a form of somatization disorder. Perhaps the best model is that symptoms soon after injury are secondary to the direct effects of trauma to the head and brain, but that over time psychological factors intervene to prevent a healthy recovery.6
Management of patients with TBI
Agitation in the early postinjury period (eg, days or weeks after a severe injury) is common and usually self-limited. It is often associated with disinhibited behavior, particularly sexual disinhibition. There may be evidence of delirium and the patient is likely to show poor orientation and poor insight.
The development of agitation is a warning that something may not be right physically. For example, the patient may have thrown off some fat emboli from a fractured femur or be in urinary retention. Agitation may also be the first sign of infection entering through a cerebrospinal fluid leak. The first stage of management is a review of the patient’s medical and surgical recovery. Intoxication from medication may be to blame, and in some, agitation is a manifestation of craving because of substance abuse at the time of the injury.
Management rests on principles similar to those used in patients with delirium. Family and caregivers may be a helpful resource if they can spend time with the patient. The main task is to ensure the safety of the patient and others, monitor the patient’s physical recovery and prescriptions, and wait for improvement.
In the longer term (months and years after injury) aggression can be a major disability. It can cause severe family/caregiver burden and can interfere with a return to work. A good rehabilitation program can help by improving engagement in activities and self-confidence. Specific anger management techniques should be tried, but they do not always work.
Drug treatment should not be started at the first sign of agitation and aggression. Wait before starting drug therapy and, if possible, get repeated baseline measures of severity to see whether the problem persists. Symptoms wax and wane, often for no identifiable reason, and improvements can be attributed to the medication when in fact they were merely the result of the passage of time.
It is not possible to provide good evidence-based guidance on which drug to choose to manage agitation and aggression. Antidepressants, mood stabilizers, antipsychotics, and b-blockers may all have a role. Which to choose may be determined by comorbid symptoms (eg, depression, seizure disorder, or anxiety disorder). When treating agitation or aggression with medication, beware of making things worse by increasing confusion; adding akathisia to the problem list; disinhibiting the patient; or, by using rapid-acting anxiolytics, unwittingly reinforcing the behavior. A good resource when deciding which drug to use is provided by the Neurobehavioral Guidelines Working Group.7
Long-term functional deterioration
After a severe injury, most recovery occurs during the first 1 to 2 years. The patient then reaches a plateau and may be left with significant disability. Generally, the disability that remains at about 2 years postinjury is relatively fixed. However, some long-term follow-up studies have shown that a proportion of patients continue to change, for better or for worse, for many years after injury.8,9 Three clinical scenarios for deterioration of symptoms are possible.
• The patient “gives up.” After initial gains in the months or years after a severe injury, the patient becomes noncompliant with therapy and withdraws socially; rehabilitation gains are lost. This is possibly a consequence of the patient’s greater awareness of his very disabled state. The optimism of the early phases of recovery begins to be replaced by the realization that the rate of improvement has slowed and full recovery is unlikely. In my experience, it is not easy to help such patients.
• Psychosocial factors affect the patient’s recovery. Compared with patients who do well, patients who deteriorate—up to 10 years postinjury—tend to be more anxious and depressed. They have more problems with alcohol (both before and after the injury), have lower self-esteem, and are more likely to have been injured in an assault.10
• Dementia may ensue. Patients who have sustained a TBI may be at increased risk for Alzheimer disease or other dementias, or for a lesser degree of decline in cognitive function.11,12
Secondary complications of TBI need to be considered in any patient with functional deterioration (Table 1). Which medication to choose to reverse the deterioration may be a matter of trial and error. Antidepressants are a reasonable first-line therapy, particularly if there is evidence of depressive symptoms. If fatigue is prominent, modafinil may help; methylphenidate may help with concentration13; cholinergic agents may be worth trying in those with deteriorating cognition.14
The diagnosis of depression after TBI is not straightforward. The brain injury may have direct effects on the control of facial expression so that the patient looks depressed, regardless of how he is feeling. Brain injury can have direct effects on pathways involved in appetite, sleep, pleasure, and reward, resulting in biological symptoms of depression even though the patient may not be depressed. Symptoms of distress and sadness can be understood as a reasonable reaction to a desperate predicament. Other changes in mood control may be seen—most commonly lability of mood, but also alexithymia.
The assessment depends on understanding the severity of the distress and the degree to which it is intractable and enduring. Feelings of worthlessness, hopelessness, or guilt suggest that clinical depression may be present. Suicidal ideation is not uncommon, and rates of suicide after TBI are increased 2- to 3-fold.
Once the patient emerges from coma after a severe brain injury, there may be days or weeks of delirium. As with any delirium, hallucinations and delusions are common. When the patient emerges from the delirium, more discrete psychotic symptoms may become apparent. Confabulation, delusional disorientation, and delusional misidentification are characteristic of these early psychotic symptoms.
Confabulations are often banal. For example, a patient may describe visits from friends or family when in fact there have been none. However, confabulations may be more bizarre, (eg, a patient recalls a helicopter evacuation from the ward next door at the same time that a gun battle took place on the hospital roof). Delusional disorientation is common and might typically involve descriptions of the ward as being the patient’s place of work. Or the patient may believe that he is on a ship at sea.
Delusional disorientation may overlap with reduplicative paramnesia, so the patient may believe that he is in an annex of the hospital but in another part of the country. Other delusional misidentifications may be seen, particularly the Fregoli syndrome: the patient is convinced, for example, that the old lady in the bed opposite him is his aunt. Another delusion, also based on attributing familiarity when in fact there is none, is the patient’s belief that he has seen you, the treating doctor, before, whereas in fact you have never met.
Remember that confabulatory delusional states are part of a resolving organic mental state. Symptoms are likely to improve. Antipsychotic drugs may have little effect and, particularly if there are no concerns about patient safety because of delusions, are probably not needed.
Psychotic states that develop in the longer term may still be directly attributable to the brain injury. For example, depersonalization may result in nihilistic delusion, or poor memory may result in delusions of persecution. Morbid jealousy may be seen and is particularly dangerous in somebody who has suffered a brain injury, given the risk of violence and poor impulse control. Whether TBI can produce a schizophrenia-like psychotic disorder is uncertain.15 A study from Sweden suggests that TBI results in a slight increase of risk for nonaffective psychotic illness, not schizophrenia.16
Make sure that the patient is not taking any unnecessary psychotropic medication or other agent that may affect cognition. For example, many patients are given phenytoin in the acute postinjury period, and months or years later are still taking the drug despite never having had a seizure. There is good evidence that prophylactic anticonvulsants do not work and that phenytoin has adverse effects on cognition.
The principles of drug treatment in somebody with a brain injury are outlined in Table 2. Treatment trials of psychotropics in brain-injured patients are lacking. Therefore the best advice when treating mental symptoms in a patient with a brain injury is to be symptom-specific and to use the same drug you would for someone without a brain injury. However, the medications tend to be less effective and symptoms are more difficult to treat in brain-injured persons.17,18 Patients who have had a TBI are more vulnerable to adverse effects of medication and are less likely to show evidence of benefit. Symptoms will often improve spontaneously. Furthermore, there may not be an indication for the symptom that the drug is being used for. It is prudent to continue drug treatment of behavioral, cognitive, and psychiatric symptoms after TBI only if there is good evidence that the patient is benefiting.
References1. Fleminger S. The neuropsychiatry of head injury. In: Gelder MG, Andreasen NC, Lopez-Ibor JJ Jr, Geddes JR, eds. New Oxford Textbook of Psychiatry. 2nd ed. Oxford, UK: Oxford University Press; 2009:387-399.
2. Cicerone KD, Tanenbaum LN. Disturbance of social cognition after traumatic orbitofrontal brain injury. Arch Clin Neuropsychol. 1997;12:173-188.
3. McMillan TM, Jongen EL, Greenwood RJ, et al. Assessment of post-traumatic amnesia after severe closed head injury: retrospective or prospective? J Neurol Neurosurg Psychiatry. 1996;60:422-427.
4. Iverson GL. Outcome from mild traumatic brain injury. Curr Opin Psychiatry. 2005;18:301-317.
5. McAllister TW, Saykin AJ, Flashman LA, et al. Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study. Neurology. 1999;53:1300-1308.
6. Lishman WA. Physiogenesis and psychogenesis in the “post-concussional syndrome.” Br J Psychiatry. 1988;153:460-469.
7. Neurobehavioral Guidelines Working Group, Warden DL, Gordon B, McAllister TW, et al. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006;23:1468-1501.
8. Millar K, Nicoll JA, Thornhill S, et al. Long term neuropsychological outcome after head injury: relation to APOE genotype. J Neurol Neurosurg Psychiatry. 2003;74:1047-1052.
9. Hammond FM, Grattan KD, Sasser H, et al. Five years after traumatic brain injury: a study of individual outcomes and predictors of change in function. NeuroRehabilitation. 2004;19:25-35.
10. Whitnall L, McMillan LM, Murray GD, Teasdale GM. Disability in young people and adults after head injury: 5-7 year follow up of a prospective cohort study. J Neurol Neurosurg Psychiatry. 2006;77:640-645.
11. Corkin S, Rosen TJ, Sullivan EV, Clegg RA. Penetrating head injury in young adulthood exacerbates cognitive decline in later years. J Neurosci. 1989;9:3876-3883.
12. Fleminger S, Oliver DL, Lovestone S, et al. Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry. 2003;74:857-862.
13. Whyte J, Hart T, Vaccaro M, et al. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil. 2004;83:401-420.
14. Zhang L, Plotkin RC, Wang G, et al. Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil. 2004;85:1050-1055.
15. David AS, Prince M. Psychosis following head injury: a critical review. J Neurol Neurosurg Psychiatry. 2005;76(suppl 1):i53-i60.
16. Harrison G, Whitley E, Rasmussen F, et al. Risk of schizophrenia and other non-affective psychosis among individuals exposed to head injury: case control study. Schizophr Res. 2006;88:119-126.
17. Ashman TA, Cantor JB, Gordon WA, et al. A randomized controlled trial of sertraline for the treatment of depression in persons with traumatic brain injury. Arch Phys Med Rehabil. 2009;90:733-740.
18. Dinan TG, Mobayed M. Treatment resistance of depression after head injury: a preliminary study of amitriptyline response. Acta Psychiatr Scand. 1992;85:292-294.
Further ReadingFleminger S. Head injury. In: David AS, Fleminger S, Kopelman MD, et al, eds. Lishman’s Organic Psychiatry: A Textbook of Neuropsychiatry. 4th ed. Chichester, UK: Wiley-Blackwell; 2009:167-280.
Silver JM, McAllister TW, Yudofsky SC, eds. Textbook of Traumatic Brain Injury. Washington, DC: American Psychiatric Publishing, Inc; 2005.