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Laino, Charlene

Special Report

Traumatic brain injury is common, resulting in about one million visits to the emergency room each year, according to the Centers for Disease Control and Prevention. About 280,000 people are hospitalized for more severe injuries, and 50,000 of them die. The highest rates are among persons 15 to 24 years and those over 65 years.

But the actual incidence is probably even higher, as some people may not seek care for their injury, said Mark P. Cilo, MD, Founder of the Brain Injury Treatment Program at Craig Hospital in Englewood, CO.

As with the neurological symptoms, the emotional consequences of traumatic brain injury (TBI) are important, experts believe. However, there have been few studies to ascertain the facts. It is thought that post-traumatic symptoms may include depression, aggression, agitation, learning difficulties, shallow self-awareness, altered sexual functioning, impulsivity, and social disinhibition. Mood disorders, personality changes, altered emotional control, and anxiety are also common.



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Children with TBI face their own set of emotional consequences. Interactions of physical, cognitive, and behavioral sequelae can interfere with learning. There may be a poor fit between the needs of affected children and the typical school educational programs. These youngsters also may have difficulties with peers due to cognitive processing, behavioral problems, or difficulty comprehending social cues.

In most cases of mild injury, emotional problems in patients of any age resolve on their own. For some, symptoms become fixed because of litigation and the promise of compensation. For many patients, the neurologist can play a critical role in ensuring emotional recovery, experts told Neurology Today.

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In addition to the primary insult, head trauma sets off secondary injury cascades: excitotoxicity, ischemia, secondary brain swelling, and axonal injury, according to Patrick Kochanek, MD, Vice Chairman of the Department of Critical Care Medicine and Director of the Safar Center at the University of Pittsburgh. “Superimposed on all of that is inflammation and regeneration.”

All of these acute changes contribute to the ultimate spectrum of problems, he said. Nevertheless, the development of emotional disorders after TBI is something of a mystery. “The causes of emotional disturbances down the road are poorly understood,” Dr. Kochanek said. “Only now are the appropriate tools being created.”

Some evidence suggests that chronic stress and depression not only interfere with rehabilitation in the obvious ways, but also may cause further cerebral damage or slow the recovery process, according to Mel B. Glenn, MD, Associate Professor in the Department of Physical Medicine and Rehabilitation at Harvard Medical School in Boston, MA.

Animal research, for example, shows that stress is a major factor for suppressing neurogenesis, while other studies have shown that recurrent depression and chronic stress induce neuronal atrophy and death and decrease neurogenesis after hippocampus damage, he reported in the Journal of Head Trauma Rehabilitation (2003;18:201–203).

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When discussing the emotional impact of traumatic brain injury, patients can be divided according to the severity of symptoms, because the consequences of mild trauma differ from those of more severe trauma, Dr. Cilo said.

Norman S. Namerow, MD, Clinical Professor of Neurology at the University of California-Los Angeles School of Medicine, agreed. “The emotional impact of traumatic brain injury depends on the severity of the trauma. If severe, the patient may have no insight into what is happening or even recognize any change. Mild injury brings on a whole spectrum of response, and that response may be out of proportion to the severity of the head injury itself,” he said.

About 90 to 95 percent of TBI fall into the mild category, Dr. Cilo said, characterized by no or brief loss of consciousness and some degree of memory impairment lasting minutes to hours. The patients are generally not hospitalized, although most make a visit to the emergency room. The Glasgow Coma Scale score is 13 to 15 points.

The emotional symptoms are those that can occur with any illness that affects quality of life: depression, anxiety, stress, and irritability. But here the similarity ends, he said. “Unlike a physical illness, the brain is affected by the injury and patients may not be aware of their symptoms. It's not like becoming depressed after breaking a leg. The patients may not understand why they are so frustrated and depressed. As a result, they might not seek help or get the proper medical care. Even the neurologist may not appreciate the significance of the injury in causing the symptoms,” Dr. Cilo said. Diagnosis becomes a challenge.

Dr. Cilo offered up a typical scenario: A person hits his head, goes to the emergency room, is evaluated, and is sent home. But the patient becomes irritable and cannot work. No one has explained that this is a normal reaction, so the patient becomes anxious and depressed. With proper diagnosis and intervention, this vicious cycle can usually be interrupted, Dr. Cilo said.

The role of the neurologist, he stressed, is not only to evaluate the neurological symptoms, but also to help the patient understand what is happening to reduce frustration and confusion. This in turn will help patients manage their lifestyle and recover, he said.

Dr. Cilo has observed that about 5 percent of patients with mild brain injury never recover and develop post-concussion syndrome, marked by chronic headaches, memory problems, dizziness, depression, anxiety, and sleep disturbances that can drastically affect their life. “But with proper education and early treatment, we can prevent or at least delay the risk of post-concussion syndrome,” he said.

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With severely injured patients, whose Glasgow Coma Scale score ranges from 3 to 9 points, the emotional complications are determined by the extent and severity of brain damage. “The brain injury interacts with the premorbid personality,” Dr. Cilo said. Many patients fall into one of two categories: those with injury to the frontal lobe and those with trauma to the temporal lobes, he said.

“In frontal lobe patients, the emotional symptoms are dominated by the frontal lobe injury. One pattern can lead to the patient becoming disinhibited, aggressive, and socially inappropriate, while another pattern is associated with a lack of emotional output and lack of affect. This patient is very stilted, with minimal emotional expression, and in some cases can become aggressive, even dangerous.”

Temporal lobe injury, on the other hand, is associated with difficulties with memory, he said. There can also be severe problems with motor function, cognition, and speech. As a consequence of severe cognitive, motor, and physical limitations, these patients may develop depression and other emotional problems, Dr. Cilo said. In some cases, however, the injuries are intermixed, he said, leading to unusual patterns of presentation.

Moderate brain injury is a more amorphous category, Dr. Cilo said. “On one end, the patient can look like the mild brain injury patient and on the other end, like the severely injured patient.” The bottom line: The neurologist has to offer individual care, Dr. Cilo said.

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Regardless of the severity of the trauma, depression is probably the most common emotional manifestation, Dr. Glenn said, affecting as many as 70 percent of patients over time. Paradoxically, with a mild head injury, depression may result from a lack of understanding of what is happening, Dr. Cilo said, while with severe trauma, it may be a result of a growing awareness of the extent of disability.

Dr. Namerow agreed, adding that depression often intensifies as the patient recognizes that full recovery has not been achieved and may never be achieved. Worsening the situation can be personality and cognitive changes that are significant enough to estrange the patient from family and friends, or an unsuccessful attempt to return to work, he said. “Any of these failures may intensify or deepen the patient's frustration, anxiety, and depression.”

While few studies have evaluated the prevalence of emotional symptoms after TBI, one Finnish study followed 60 patients an average of 30 years after the injury; nearly half had emotional disorders that began after the TBI and 62 percent had disorders during their lifetimes (Am J Psychiatry 2002;159:1315–1321).

The most common novel disorders were major depression in 27 percent of patients, alcohol abuse or dependence in 12 percent, panic disorder in 8 percent, and psychotic disorders in 7 percent of patients, the researchers reported. Also, 23 percent of patients had at least one avoidant, paranoid, or schizoid personality disorder. Without a control group, however, it is not known how many had personality disorders that led to head injury.

“These findings suggest that TBI not only temporarily disturbs brain function but may cause decades long or even permanent vulnerability to psychiatric disorders in some individuals,” wrote the authors, led by Salla Koponen, MD, of the Department of Psychiatry at Turku University Central Hospital in Turku, Finland.

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Overlapping symptoms can confound the recognition of the emotional syndrome, according to Dr. Glenn. For example, apathy, hypersomnolence, difficulty concentrating, forgetfulness, sleep disturbance, irritability, and aggression may be primary to the injury, or secondary to the depression, he said. Similarly, anxiety can lead to problems with concentration, sleep, irritability, and aggression.

Also, sleep disturbances can be primary problems following traumatic brain injury or may be secondary to anxiety and mood disorders, he said.

“Post-traumatic stress disorder may also be seen,” he said, “particularly after mild traumatic brain injury, and problems with impaired concentration, forgetfulness, and irritability overlap with those caused by brain injury. When depression and anxiety, as well as pain and insomnia, develop in the context of mild traumatic brain injury, it can be difficult or impossible to determine the contributions of each to persistent symptoms.” Other common emotional manifestations of TBI include phobic disorders and obsessive-compulsive disorder and, in rare cases, bipolar disorder, Dr. Glenn said.

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The neurologist may not ever see the patient who recovers from a mild brain injury, Dr. Cilo pointed out. “Usually it's about six months down the road, so the post-concussion syndrome is already developing.”

But whenever the patient is seen, the neurologist should become familiar with the medical, social, and psychiatric history of the patient, Dr. Glenn said, being sure to look for signs and symptoms of pre-existing psychological problems.

Diagnosis usually begins with a conventional MRI scan, although a traumatic injury is best seen using an MRI with gradient ECHO imaging, said James P. Kelly, MD, formerly an Associate Professor of Neurology at Northwestern University in Chicago, IL, who has just relocated to Denver, CO.

“Without a gradient ECHO, you can miss shearing injuries,” he said. Also indicated are a vestibular workup and EEG, Dr. Cilo said. A functional MRI may also be useful for determining the extent and severity of the illness, Dr. Namerow added.

The neurologist should be aware that up to 20 percent of patients with TBI have other structural injuries that, left undiagnosed, can lead to depression, anxiety, and other emotional problems, he added.

“You must take this into account in diagnosis,” he said. “Suppose you have a patient who becomes increasingly agitated and restless as his thoughts become more organized, and you don't know why. You must make sure no injury has been overlooked. Even a fractured finger can be painful enough to cause agitation.”

Also, the emotional impact of comorbidities needs to be ruled out, Dr. Glenn pointed out. “The residual effect of a severe infection such as pneumonia on a person with a severe brain injury can be seen for days or weeks after the infection has apparently resolved,” he said. “In the acute period following traumatic brain injury, malnutrition, dehydration, and electrolyte imbalance have similar effects, whether related to difficulties with oral intake, increased metabolic needs, syndrome of inappropriate secretion of antidiuretic hormone, or diabetes insipidus. At their worst, many of these medical disorders can result in a confusional or delirious state or aggressive behavior.”

Additionally, the patient should undergo an evaluation by a psychologist trained in evaluating head injury patients, Dr. Namerow said.

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It is crucial that the patient be evaluated, Dr. Glenn said. “This may seem obvious but with the cognitively impaired patient, this step is often bypassed. “Although it won't be a classic psychiatric exam, valuable information can be gained,” he said. “Talk about feelings and see how the patients react,” he advised. “Do they think life is worth living? Even if you have to use gestures, rather than words, valuable insights can be gleaned.”

Even more important, interview the staff, Dr. Glenn said. “Often the [physical] therapist who works with the patient knows more about how they really feel than anyone else, even the family. You'd be surprised how often patients tell their therapists that their life is not worth living when they would never tell a family member that.”

Also, family members may interpret statements inappropriately, Dr. Glenn added. For example, they may think a patient is being lazy or apathetic when in fact their symptoms have a neurological cause.



But Dr. Kelly said he prefers to interview the patient's family members. “They know what the patients were like before the injury so you can ask them about any changes in personality,” he explained.

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Treatment depends both on the severity of the illness and its emotional manifestations, but always requires a significant degree of education, the experts said.

With moderate and severe injuries, “the neurologist needs to help their patients and their families understand why the patients are behaving the way they are,” Dr. Cilo said. “A certain portion of therapy involves education on the brain injury and its physical, cognitive, and emotional consequences. It is not that different from treatment for dementia except the patient gets better instead of worse.”

The optimal treatment for the patient with mild head trauma is still unclear, he said, but probably involves a combination of medication and psychotherapy as well as physical therapy for symptoms such as dizziness, vertigo, and unsteady gait, he said.

While the use of antipsychotics for the treatment of patients with emotional disturbances after TBI is controversial, Dr. Glenn said there is a role for certain agents as long as they are prescribed with a caution.

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There have been few studies of antidepressant medication for TBI-related depression, Dr. Glenn said, but they can be helpful even if the depression is a reaction to the disability. In one of the studies in the literature, Dr. Wroblewski and colleagues showed that desipramine (Norpramin) can help relieve long-standing depression in patients with severe TBI, Dr. Glenn said.

In the study, 10 patients with depression were randomly assigned to start blindly on either desipramine treatment or placebo (J Clin Psychiatry 1996;57:582–587). Patients starting with desipramine stayed on the drug, while patients on placebo were blindly crossed over to desipramine after one month if there was no significant improvement in symptoms.

Of the seven evaluable patients, six (86 percent) demonstrated resolution of depression and depressed mood during desipramine treatment. Two patients, both on desipramine, dropped out because of adverse effects, including seizure and mania.

There may also be a role for serotonin or norepinephrine selective reuptake inhibitors, Dr. Glenn said. In studies of adult rodents, chronic administration of these medications resulted in upregulation of neurogenesis in the hippocampus and reversed the effects of stress on hippocampal neurons, he said.

In an eight-week single-blind trial of sertraline (Zoloft) for individuals with mild TBI, both depression and cognitive functioning improved (Psychosomatics 2001;42:48–54), Dr. Glenn said.

As for TBI-related anxiety, “the problem is that the best medications are the benzodiazepines, which can cause memory problems even in people without brain injury,” Dr. Glenn said. Buspirone (Buspar) may be a better choice, as it causes less cognitive impairment, he said.

Treatments for epilepsy can sometimes be useful for controlling impulsivity and irritability, Dr. Kelly said. “I have the best luck with carbamazepine [Tegretol] and there is some evidence that divalproex [Depakote] might be useful,” Dr. Kelly said. “Also, there is growing interest in topiramate.”

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As for sleep disturbances, 50 to 100 mg of trazodone (Desyrel) at bedtime can help patients sleep through the night, Dr. Kelly said. “And make sure to give it at the exact same time every night so you get the patient into a routine sleep-and-wake cycle.”

If the patient has trouble falling asleep, on the other hand, 500 to 1000 mg of chloral hydrate at bedtime may help, he said.

“While sleep is not an emotional problem per se, patients who sleep better can focus better during the day, easing the return to a normal routine,” Dr. Kelly said. The drugs should be given for a period of weeks to months and then tapered off, he added.

While there is very little literature available on risperidone and brain injury, a single case report showed that a patient who suffered from sleep disturbances, psychosis, and paranoid jealously who failed other medications improved on 2 mg per day (J Head Trauma Rehabil 2003;18:177–195). Side effects can be substantial however, the researchers noted.

In addition to pharmacological therapy, psychotherapy can help the patient to better understand his injury and deal with the consequences as they relate to loss of self-concept and self-esteem, Dr. Namerow added. “The patient often loses confidence and withdraws from daily life activities. Awareness of deficits can be improved in a supportive setting, both through confrontation and by example of others. Presentations of information on brain function and injury, with opportunity for discussion, can be a useful adjunct.”

Dr. Cilo noted that psychotherapy is of little help for patients with severe trauma, although behavioral modification techniques are very useful.

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One of the biggest mistakes in treating severely injured patients, according to Dr. Namerow, is overstimulation. “You need a controlled environment with no more stimulation than the patient can handle. You want minimal sensory input, not a lot of noise. You don't want to agitate him.”

The paradigm for treating emotional disorders in head injury patients is a team approach, Dr. Cilo said. “This is not something a neurologist should take on himself. You need a neurologist, a rehabilitation physician, a neuropsychologist, a physical therapist, an occupational therapist, and a speech therapist. These are very complex injuries and they affect every aspect of the patient's and their family's life.” Which is why, experts told Neurology Today, there needs to be more extensive controlled studies of this important issue.

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  • ✓ There have been few studies to ascertain actual prevalence, but specialists in treating traumatic brain injury say the emotional consequences of traumatic brain injury may include depression, aggression, agitation, learning difficulties, shallow self-awareness, altered sexual functioning, mood disorders, anxiety, impulsivity, and social disinhibition.
  • ✓ The emotional impact of traumatic brain injury depends on the severity of the trauma.
  • ✓ Experts advocate that neurologists assume a team approach to treatment, involving neuropsychologists, physical therapists, occupational therapists, and speech therapists.
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• Elovic EP, Lansang R, Li Y, Ricker JH. The use of atypical antipsychotics in traumatic brain injury. J Head Trauma Rehabil 2003;18(2):177–195.
    • Fann JR, Uomoto JM, Katon WJ. Cognitive improvement with treatment of depression following mild traumatic brain injury. Psychosomatics 2001;42(1):48–54.
      • Koponen S, Taiminen T, Portin R, Himanen L, Isoniemi H, Heinonen H, Hinkka S, Tenovuo O. Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study. Am J Psychiatry 2002;159(8):1315–1321.
        • Perna RB, Rouselle A, Brennan P. Traumatic brain injury: depression, neurogenesis, and medication management. J Head Trauma Rehabil 2003;8(2):201–203.
          • Wroblewski BA, Joseph AB, Cornblatt RR. Antidepressant pharmacotherapy and the treatment of depression in patients with severe traumatic brain injury: a controlled, prospective study. J Clin Psychiatry 1996;57(12):582–587.
            ©2003 American Academy of Neurology