Traumatic Brain Injury

Traumatic brain injury (TBI) is a significant cause of disability in the United States, with an incidence of about 1.5 million cases per year (National Institutes of Health Consensus Development Panel, 1999). It is associated with both neurologic and psychiatric consequences. Although the neurologic problems usually stabilize with time, the psychiatric disorders often continue to remit and relapse. Factors associated with the development of psychiatric disorders include older age, arteriosclerosis, and chronic alcoholism, all of which interfere with the reparative process within the central nervous system. Other contributors to psychiatric disability include a pre-TBI history of psychiatric illness, illicit drug abuse, and lack of social support. Because post-TBI psychiatric disturbances interfere with rehabilitation and cause emotional and financial burden for patients and caregivers, early diagnosis and treatment are important. Post-TBI psychiatric disturbances are best classified according to their clinical presentation. These disturbances are discussed below and their pharmacologic and nonpharmacologic treatment strategies are recommended. The mood disturbances most commonly associated with TBI are major depression, mania, anxiety, and apathy. Major depression is seen in about 25% of people with TBI. Symptoms of major depression include persistent sadness; guilt; feelings of worthlessness; hopelessness; suicidal thoughts; anhedonia; and changes in patterns of sleep, appetite, and energy. Sometimes these symptoms may be associated with psychotic features such as delusions and hallucinations. It is important to remember that changes in sleep, appetite, or energy are not specific to the syndrome of major depression and may be due to the brain injury itself, or to the noise, stimulation, or deconditioning associated with hospitalization. If due to the latter conditions, gradual improvement occurs with time in most patients. Sadness in excess of the severity of injury and poor participation in rehabilitation are strong indicators of the presence of major depression. The presence of poor social functioning pre-TBI and left dorsolateral frontal and/or left basal ganglia lesion have been associated with an increased probability of developing major depression following brain injury ( Jorge et al., 1993a; Jorge et al., 2004). Major depression should be differentiated from demoralization, primary apathy syndrome, and pathologic crying.

Stroke

With an annual incidence of more than 600,000 cases, thromboembolic stroke is the third leading cause of death in the United States after heart disease and cancer (Kochanek et al., 2004). The number of stroke survivors has increased to 4.5 million adults nationally as the management of acute stroke continues to improve (AHA, 2002). Psychiatric syndromes are common complications of stroke and are associated with psychologic distress, increased impairment, poor rehabilitation outcomes, and excess morbidity. The purpose of this chapter is to describe clinically important poststroke psychiatric disorders and suggest appropriate treatment. Cognitive deficits are the most common psychiatric complication of stroke and affect nearly all stroke survivors. The type of cognitive disturbance depends on the location of the brain injury. Left hemisphere strokes frequently cause aphasia. Right hemisphere strokes cause substantial (but often underrecognized) cognitive impairments such as diminished insight, decreased attention, impaired spatial reasoning, and neglect syndromes. Furthermore, depending on the location of a stroke, other functions such as motivation, memory, judgment, and impulse control may also be affected. A large stroke or a series of small strokes affecting both hemispheres may lead to the global cognitive impairment of dementia. When a series of strokes is involved, the cognitive decline develops in a stepwise manner. This vascular dementia or multi-infarct dementia may be difficult to distinguish from Alzheimer’s disease. Autopsy studies of patients diagnosed with vascular dementia have often demonstrated the presence of Alzheimer’s disease pathology. As many as 25% of all dementia cases are attributable to a combined neuropathology of Alzheimer’s disease and multiple infarcts (Massoud et al., 1999). In addition to strategies such as speech and language therapy, physical and occupational therapy, and cognitive rehabilitation, pharmacologic treatment may improve cognitive deficits in some stroke patients. The parallels between vascular dementia and Alzheimer’s disease, as well as the evidence that reduced cholinergic function may play a role in both (Gottfries et al., 1994) have encouraged the use of acetylcholinesterase inhibitors (eg, donepezil) in vascular dementia. These drugs have shown modest benefits in such patients (Roman et al., 2005), and their use is described in Chapter 20.

Nonpharmacologic Interventions Other Than Psychotherapy

Several nonpharmacologic interventions are available to the physician for the management of psychiatric disturbances in patients with neurologic disease. These include education, providing day-to-day structure, and caregiver interventions. They are discussed individually in this chapter. Patient education is a critical aspect of management that can reassure patients, help them better understand what is happening to them, reduce distress, promote a stronger clinician– patient relationship, and enhance adherence to treatment.When treating psychiatric symptoms in a patient with neurologic disease, it is important to set aside time to provide such education. Several approaches to patient education might be incorporated. For the patient who has limited insight into his or her psychiatric symptoms, it is important to approach education delicately and nonjudgmentally, emphasizing treatment options without directly confronting the patient about the lack of insight. For example, a man might be told that his symptoms of anxiety, irritability, and trouble sleeping represent a ‘‘mood disorder’’ for which effective treatment is available to reduce his suffering. By focusing on doing something to help, the physician avoids conflict and preserves the clinician–patient relationship while asking the patient to keep an open mind about diagnosis and therapy. For the patient who has better insight, education involves more detailed explanation of the psychiatric diagnosis and the physician’s best judgment about its cause. For example, ‘‘you are seeing things that are very real to you but that others do not see. I have no doubt that these are real to you, and that they are troubling. Many patients with Parkinson’s disease develop such symptoms that we call hallucinations. They may be caused by some of the medication you take for your condition or by the brain damage caused by the Parkinson’s disease. I think we might be able to make them better.’’ Sometimes, and commonly in the context of dementia care, a patient’s condition precludes constructive discussion of diagnosis. The patient may be incapable of understanding or may not even recognize that anything is wrong with him. In some cases, the patient may become upset and agitated if a diagnosis is discussed.

Psychotherapy

To nonpsychiatric physicians the term psychotherapy often sounds vague and mysterious. Yet, the art of providing healing through the clinician–patient relationship is as old as medicine itself. Psychotherapy is a form of treatment that uses psychologic techniques within the context of this confiding clinician–patient relationship to treat mental symptoms and relieve emotional distress. Psychotherapy may be the main approach to treatment of identified symptoms, or it may be used as an adjunct to pharmacotherapy. The clinician–patient relationship at the core of psychotherapy can be distinguished from other confiding relationships a person may have with family members, friends, mentors, and advisors. In psychotherapy, there is a clearly identified provider of care and a recipient of that care. The provider is specially trained to deliver the care in a professional and coherent way, using specific psychologic techniques. Both the provider and the patient focus their attention on the patient’s specific problems and work together in partnership to address the elements of psychologic distress and improve the patient’s symptoms. The goal of psychotherapy may differ depending on the patient and his or her situation. Sometimes, the goal of psychotherapy is symptom reduction (eg, to decrease anxiety, improve mood, or reduce friction in an interpersonal relationship). It may be used to help an individual replace unhealthy, counterproductive ways of thinking or reacting with more adaptive ones. In other instances, the goal of psychotherapy may be educational or instructive and involve teaching techniques to expand an individual’s coping abilities or communication skills. All forms of psychotherapy develop an individual’s self-awareness and help bolster appropriate self-esteem. The therapeutic setting between patient and clinician establishes validation that the patient’s concerns are worth addressing and provides a sense of hopefulness that things can improve. As new options are explored and new techniques for dealing with distressing situations are discussed, patients develop an increased sense of mastery and feel less overwhelmed by life circumstances. Psychotherapy may take three main forms of: (1) individual, (2) couples or family, or (3) group. In individual psychotherapy, a single patient and therapist work together, focusing on the patient’s unique attitudes, perceived experiences, and behaviors that are associated with his or her current distress.

Cholinesterase Inhibitors and Memantine

Several lines of evidence suggest that acetylcholine (ACh) neurotransmission is important to the normal functioning of memory, and loss of ACh-producing cells in the basal forebrain (nucleus basalis) is a consistent finding in patients with Alzheimer’s disease and other dementias. The most successful approach to increasing ACh in vivo has been to develop drugs that reduce its degradation by the synaptic enzyme acetylcholinesterase (AChE). Four cholinesterase inhibitors are available to treat memory and other cognitive symptoms in dementia patients. They may also stabilize or prevent the onset of milder non-cognitive neuropsychiatric or behavioral symptoms, although their use as exclusive agents for the more severe forms of the latter is not recommended. A recent Consensus Panel has articulated sound clinical principles regarding the use of these drugs in the context of the broader treatment of Alzheimer’s dementia (Lyketsos et al., 2006). Tacrine, donepezil, rivastigmine, and galantamine have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease. Tacrine should not ordinarily be used in light of the associated high risk of hepatotoxicity, its complex titration, and the availability of bettertolerated alternatives. The other three cholinesterase inhibitors seem similar in efficacy. All appear to modestly improve cognitive symptoms in 15% to 20% of patients, sometimes quite notably. In addition, they may either improve patient function and delay the emergence of behavioral symptoms or reduce the severity of the latter. The evidence does not support their use as single agents to treat more severe neuropsychiatric symptoms such as depression or delusions, although patients with apathy and visual hallucinations may respond. Any benefit of cholinesterase inhibitors to the long-term progression of dementia has not been shown conclusively. Some studies suggest that they may attenuate the long-term slope of cognitive or functional decline, but those studies have been flawed due to high levels of dropout and the use of historical untreated comparison groups. One brain imaging study, part of a clinical trial, has suggested that they may affect the size of the hippocampus or the integrity of hippocampal neurons. In the absence of replication or a better understanding of the imaging measures involved, these data are not conclusive.

Parkinson’s Disease

Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease (AD), causes a progressive neurologic syndrome characterized by bradykinesia, tremor, rigidity, and, in its later stages, postural instability. The motor signs of PD correspond to loss of dopaminergic neurons in the substantia nigra pars compacta within the ventral midbrain. Neuronal inclusions, called Lewy bodies, are also present in the same region, but they can also be present in limbic and cortical regions and, along with other neurotransmitter deficits, are associated with nonmotor aspects of the disease. PD is to be distinguished from parkinsonism, a general term that refers to clinical conditions with the same motor phenomena, but without reference to a specific etiology. Prevalence rates of PD vary. Epidemiologic studies show ageadjusted prevalence rates (per 100,000 individuals) range from 104.7 in Japan, 114.6 in the United States, 168.8 in Taiwan, and 258.8 in Sicily (Korell and Tanner, 2005). The disease affects about 1 million individuals in North America—approximately 0.5% to 1% of the population older than age 65 years of age. The average age of onset is about 60 years, but 5% to 10% of patients have young-onset PD, beginning before age 40 (Tanner and Ben-Shlomo, 1999). The disease affects all races, and there is a slightly higher prevalence of PD among men. The diagnosis of PD relies on the clinical history and motor examination, which usually distinguish it from other parkinsonian disorders. However, because there is no biological marker that verifies the diagnosis of PD, neuropathologic findings remain the gold standard for confirmation of the clinical diagnosis. Even at specialized movement disorder centers, autopsy studies reveal that 10% to 20% of patients with clinical diagnoses of PD have other neuropathologic diagnoses (Hughes, Daniel, and Lees, 2001). Two of the three cardinal motor signs (tremor, akinesia/bradykinesia, and rigidity) are required to establish the diagnosis of PD, but these motor features overlap with other parkinsonian disorders. However, in patients without an overt tremor, early signs of PD such as decreased arm swing, limb stiffness, and diminished facial expression can be subtle, and the diagnosis of PD maybe delayed for several years.

Epilepsy

As many as 50% of patients with epilepsy have psychiatric syndromes, with mood, anxiety, and psychotic disturbances being the most common. Recognition and treatment of neuropsychiatric disturbances in individuals with epilepsy is influenced by the complexity of the epilepsies, which are a heterogeneous group of chronic conditions. Epileptic syndromes are classified according to seizure type and differ in their respective diagnostic criteria, epidemiology, etiologies, medical and surgical treatments, and associated psychiatric conditions. This chapter focuses on interictal psychiatric disturbances. Periictal and ictal psychiatric phenomena are addressed in the discussions of the differential diagnosis for the various interictal phenomena and in other reviews (Trimble, 1991; Schwartz and Marsh, 2000; Marsh and Rao, 2002). The prevalence of epilepsy ranges from 0.4% to 1%, with variation attributed to actual differences in the frequency of epilepsy among population subgroups as well as varying definitions of seizures and of epilepsy (Hauser and Rocca, 1996). The idiopathic generalized epilepsies comprise nearly one-third of all epilepsies and are primarily genetic in origin ( Jallon and Latour, 2005). Partial seizures are the most common seizure type and localization-related or focal epilepsy, especially of temporal lobe origin, is the most common epilepsy syndrome (Keranen, Sillanpaa, and Riekkinen, 1988). The incidence of epilepsy in industrialized countries is highest in the first year of life; it then remains stable until it peaks again after the age of 60 years, when epilepsy is associated with vascular and neurodegenerative conditions. In older adults, however, seizure presentations can be subtle and the diagnosis of epilepsy is frequently missed. Epilepsy is more common in men than women. Multiple factors contribute to higher rates of psychiatric illness in patients with epilepsy. Whether epilepsy itself increases the risk of psychiatric disturbance is unclear; it is important to understand the type and severity of the patient’s epilepsy syndrome, the ictal and peri-ictal features of the seizure, and the relationship of these to the occurrence of the psychiatric phenomena. It is also important to identify whether the patient has any of the special vulnerabilities that influence the risk of psychiatric dysfunction such as the presence of brain injury (eg, from head injury, a congenital neurodevelopmental disorder); use of medications to treat seizures or other conditions that have the potential for adverse psychoactive effects (eg, phenobarbital, benzodiazepines); untoward environmental and psychosocial circumstances; global versus selective cognitive impairments; and temperamental (ie, personality) traits that limit adaptability (Reynolds, 1981).

Multiple Sclerosis

Multiple sclerosis (MS) is characterized by demyelination, axonal injury, inflammation, and gliosis (scarring) and can involve the brain, spinal cord, and optic nerves. The course of MS is characterized either by episodes of exacerbation separated by periods of relative quiescence (relapsing-remitting) or by relentless progression, but it typically involves insults that are multiphasic and multifocal (ie, disseminated in time and location throughout the neuraxis). By conservative estimates, at least 350,000 individuals in the United States have MS (Anderson et al., 1992). MS is usually diagnosed between the ages of 20 and 40 years and is twice as common in women as men. In Western societies, MS is second in frequency only to trauma as a cause of neurologic disability in early to middle adulthood. MS can vary from a benign illness with minimal impairment to a rapidly evolving and incapacitating disease requiring profound lifestyle adjustments. The disability is manifest both as physical=sensory impairments and as neuropsychiatric disorders. Although the functional impairment and disability that can occur in MS is a source of distress as it would be in any physically impairing illness, the unpredictable course makes it particularly difficult for many patients to cope. It is more difficult to adapt to acute rather than gradual changes, and MS exacerbations usually start without warning and evolve over days to weeks. Moreover, its unpredictable and variable course can make MS a challenging illness to diagnose, so patients often undergo a frustrating course of multiple evaluations before finally receiving the correct diagnosis. Sometimes an individual’s capacity to adapt is overwhelmed by the stresses with which he is confronted, and he becomes discouraged, bewildered, and overwhelmed. This is a state called demoralization. Demoralization has been defined (Frank and Frank, 1991) as a state of helplessness, hopelessness, confusion, subjective incompetence, isolation, and diminished self-esteem. The subjective experience of demoralization involves feeling incapable of meeting both internal and external expectations, feelings of being trapped and powerless to change or escape, and feelings of being unique and therefore not understood. The combined effect usually leads to frustration, bewilderment, and isolation.

Overview of Psychiatric Symptoms and Syndromes

This chapter provides an overview of psychiatric symptoms and syndromes that can be seen with neurologic diseases. Our goal is not to discuss every psychiatric disorder that might occur but to focus on those that are the most common. Important characteristics of this condition include: • Intermittently sad mood • Identifiable precipitant • Absence of major depression Just as grief is a normal response to loss, demoralization is a normal response to adversity. When bad things happen, our spirits fall. Because adversity is common with neurologic diseases, so is demoralization. Thus, patients may become demoralized when they learn they have a neurologic disease (eg, amyotrophic lateral sclerosis, Alzheimer’s disease, Huntington’s disease), when they experience the symptoms of such a disease (eg, blindness, aphasia, pain), or when they develop the side effects of treatment for the disease (eg, weight gain from prednisone, dyskinesias from levodopa). Demoralization is not linked to any particular group of neurologic diseases, but it tends to be more common in those that are chronic, progressive, painful, debilitating, or disfiguring. Demoralized patients are almost always sad, but they may also be frustrated, irritable, pessimistic, or anxious. These unpleasant emotions are directly related to the patient’s situation and diminish as that situation improves. Someone who is demoralized by pain cheers up when the pain is relieved. Even when patients are demoralized by circumstances that cannot be reversed, their mood often improves when they discover that they are not powerless in the face of adversity. In this way, patients who become demoralized when they are told that they have a terminal illness may feel better as they start to focus on what they can do with the time left to them, and patients who become demoralized by the onset of a paraplegia may brighten as they begin to make progress in rehabilitation. This direct relationship between the patient’s mood and his or her situation helps distinguish the sadness of demoralization from that of major depression, because in the latter condition the patient’s mood remains low despite improving circumstances. Other features of a demoralized state also help differentiate demoralization from major depression.

Neuroleptics

The ‘‘neuroleptic’’ antipsychotic group of pharmacologic agents was so named because the original agents, now called ‘‘conventional’’ antipsychotics, produced significant neurologic side effects in the form of extrapyramidal symptoms (EPS). However, neuroleptics were the first drugs to be effective in treating psychosis and remain the cornerstone of pharmacologic management of psychotic symptoms, whether such symptoms are primary or arise in the context of neurologic disorders. Although the only U.S. Food and Drug Administration (FDA)–approved use of antipsychotic agents is for the treatment of schizophrenia, mania, and ‘‘psychosis,’’ there is strong agreement among dementia experts that both the conventional antipsychotics and the newer ‘‘atypical’’ agents have a place in the management of several behavioral symptoms in persons with dementia (Small et al., 1997). Concerns have been raised regarding increased risk of stroke and increased mortality in the elderly, and a recent meta-analysis found the use of both conventional and atypical antipsychotics in dementia to be associated with a small increased risk for death compared with placebo (Schneider, Dagerman, and Insel, 2005). When choosing an antipsychotic medication, these and other risks should be considered within the context of an individual patient’s medical need for the drug, medical comorbidity, and the efficacy and safety of alternatives. In psychiatric disorders complicating neurologic diseases, antipsychotic drugs are used to treat specific syndromes (mania, delusional depression, schizophrenia) and target symptoms (hallucinations, delusions, tics in Tourette’s syndrome, chorea in Huntington’s disease). They are also used to ameliorate severe agitation or other behavioral problems that threaten the safety of the patient or others and have not responded to alternative interventions. These indications for antipsychotic drug use are further detailed in the chapters on specific neurologic diseases. Antipsychotic medications should not be used for milder behavioral disturbances, such as the wandering, disinhibited social intrusiveness, or frustration-induced emotional lability seen in some patients with cognitive impairment. In these instances, nonpharmacologic methods such as environmental manipulation should be tried first. For example, gentle redirection of the patient, assistance with activities of daily living, a night light in the bedroom, structured schedules of activities, and caregiver education about such strategies may alleviate some problem behaviors.