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Patients With Seizure Disorders
Overview
The structure and function of the central nervous system (CNS) is altered by many neurologic disorders. Because the CNS controls affect, behavior, and cognition, neurologic disorders can lead to neuropsychiatric symptoms that resemble those found in primary psychiatric conditions. Therefore, the general hospital psychiatrist is frequently called on to assess patients who have classic psychiatric symptoms caused by an underlying neurologic condition (e.g., a seizure disorder).
In this chapter, we will review the management of patients with neurologic conditions that are commonly associated with neuropsychiatric phenomena. We will discuss seizure disorders and describe the diagnosis and management of non-epileptic seizures (formerly called pseudoseizures ).
Case 1
Ms. A, a 23-year-old woman, was admitted to the medical floor after she presented to the Emergency Department with a self-reported “big seizure” a few days earlier at home, and two weeks of recurrent brief spells of “panic” and out-of-body experience. A psychiatric consultation was requested given her extensive psychiatric history and suspected psychogenic non-epileptic seizure.
She reported having bipolar disorder, post-traumatic stress disorder (related to childhood sexual and physical abuse by a relative), and being a victim of physical assault as a teenager (involving a skull fracture and reported seizure). She endorsed smoking marijuana on a daily basis to control her anxiety symptoms, and a history of heavy drinking. She was currently unemployed and struggled with keeping her current living situation. She stopped her lamotrigine, which she was prescribed as a mood stabilizer, around a month ago. On exam she appeared anxious, but was euthymic. Other than a report of out of body (autoscopic) visual hallucinations along with the “panic spells” there were no other positive findings on the exam. She denied suicidal ideation or violent thoughts. The toxicology screen was positive for marijuana, and her alcohol and lamotrigine levels were undetectable. A head CT scan was reported as unremarkable.
The consultant confirmed the psychiatric history, provided input regarding management during the hospitalization, and expressed concern about the etiology of the spells; a neurology consultation was recommended as well as a video-EEG during the admission. An extended bedside EEG with video recording captured three identical events during which Ms. A remained conscious but appeared fearful. These were accompanied with slowing of the heart rate lasting for approximately 10 seconds, after which she reported the event to her nurse. Review of the EEG showed focal seizures arising from the right posterior temporal region.
The diagnosis of focal seizures with impairment of awareness from the right temporal lobe with presumed occasional secondary generalization and associated ictal bradycardia was made. The history of significant head trauma was considered the most likely etiology. Ms. A was re-started on lamotrigine, with levetiracetam as a second antiepileptic drug (AED) to protect her from generalized seizures while lamotrigine remained sub-therapeutic. As well as addressing co-morbid psychiatric diagnoses, the treatment team counseled Ms. A about medication adherence, contraception, avoidance of driving, and the risk of mood symptoms, aggression, or suicidal ideation with her new medication, levetiracetam. A neurology follow-up appointment was also made to address her new diagnosis, consider further work-up, and consider stopping the second AED.
The Management of Psychiatric Symptoms in Patients With Seizure Disorders
Approximately half of all patients with seizure disorders have co-morbid psychiatric syndromes; therefore, the general hospital psychiatrist should have a working knowledge of seizure disorders and the neuropsychiatric syndromes that are commonly associated with these disorders. Patients with seizures may have psychiatric symptoms that occur during a seizure ( ictal symptoms), immediately before or after a seizure ( peri-ictal symptoms), or between seizures ( inter-ictal symptoms). Some medical and surgical treatments for this condition are also associated with psychiatric symptoms.
By way of definition, a clinical seizure is an abnormal paroxysmal discharge of cerebral neurons sufficient to cause clinically detectable events that are apparent to the patient or an observer. Patients with a chronic course of repeated, unprovoked seizures are said to have epilepsy. Seizures can be focal (starting in a particular area of the brain, i.e., the focus) or generalized (involving both hemispheres simultaneously). Focal seizures (formerly called “partial seizures”) may remain limited to their focus on the same brain hemisphere, or propagate throughout the rest of the cortex, often called secondary generalization . Consciousness is often fully or partially preserved as long as the seizure activity is restricted to only limited parts of the brain. Clinical symptomatology may be variable in this setting, correlating with the involved brain areas. Generalized seizures are associated with loss of consciousness, ranging from seconds of staring spells in absence seizures (formerly called petit mal ) to generalized tonic–clonic convulsions ( grand mal ). Generalized tonic-clonic (GTC) seizures can occur after an immediate or delayed spread of focal seizure activity to the rest of the brain, or so-called secondary generalization . A primary generalized seizure happens in the absence of a suspected focus and in the setting of a genetic/idiopathic epilepsy syndrome, or due to metabolic disarray (such as hypoglycemia, hyponatremia, toxic exposure). GTCs are characterized by a sudden loss of consciousness with a brief tonic phase marked by contraction of skeletal muscles and upward deviation of the eyes. A more prolonged clonic phase (characterized by rhythmic movements and jerking of the extremities) follows. These seizures are almost always followed by a post-ictal state with decreased responsiveness and a state similar to deep sleep that lasts minutes to hours. Absence seizures are characterized by brief (usually 5 to 10 seconds) lapses in consciousness and by motionless staring, without loss of muscle tone, and without any post-ictal change in consciousness. These seizures occur primarily in children and are rare after puberty. Myoclonic seizures are characterized by brief and sudden, often bilateral, muscle contractions that may occur singly or repeatedly; these are seen in a variety of epileptic syndromes in children but also occur in adults with advanced neurodegenerative diseases. Atonic seizures (“ drop attacks ”) are a type of generalized seizure characterized by sudden loss of muscle tone leading to falls, without clonic activities seen in tonic-clonic seizures.
The terminology for focal seizures has changed repeatedly over the last decade which has caused some confusion. Focal seizures are generally described based on how they affect consciousness. Focal seizures with impairment of consciousness or awareness (formerly complex partial seizures, also known as focal unaware seizures) deserve special mention, insofar as they are the most common type of seizure in adults and are commonly associated with neuropsychiatric phenomena. Particular types of focal seizures that also have a high prevalence of neuropsychiatric symptoms during and between seizures include temporal lobe epilepsy (TLE ) and psychomotor seizures . On the other hand, focal seizures without impairment of consciousness or awareness (formerly simple partial seizures, also known as focal aware seizures) have symptoms limited to the area of cortex that are stimulated, such as simple motor seizures with twitching of corresponding muscle groups, or simple visual seizures with occurrence of visual experiences in the visual field corresponding to seizing cortex.
Focal seizures may involve sensory, affective, perceptual, behavioral, or cognitive symptoms. They may include hallucinations of any sensory modality; they can be olfactory (e.g., a noxious odor, like burning rubber), gustatory (metallic or other tastes), auditory, visual, or tactile. The most common affective symptoms are fear and anxiety, although depression may also occur; rage is uncommon. Such affective symptoms usually have a sudden onset and offset.
Behavior during focal seizures with impairment of awareness may also be abnormal; automatisms are common and may include oral or buccal movements (e.g., lip smacking or chewing), picking behaviors, or prolonged staring. Cognitive symptoms associated with focal seizures include déjà vu (a feeling of familiarity), jamais vu (a feeling of unfamiliarity), macropsia, micropsia, and dissociative, or “out-of-body” experiences. Patients with neuro-psychiatric symptoms secondary to seizures may be mistakenly diagnosed with a primary psychiatric disorder because the symptoms are often similar to those of psychiatric disorders, and because the inter-ictal (and even ictal) scalp electroencephalograms (EEG) may appear normal due to deep localization of involved cortices. Therefore, the general hospital psychiatrist must be particularly astute in differentiating patients with focal seizures from those with primary psychiatric disorders.
In the following discussion, the phenomenology and treatment of neuropsychiatric symptoms among patients with seizure disorders is outlined. The ictal, peri-ictal, and inter-ictal neuropsychiatric symptoms will be discussed, as will ways to delineate how these symptoms differ from those seen in patients without seizure disorders.
Ictal Neuropsychiatric Phenomena
Ictal psychiatric symptoms are most commonly associated with focal seizures, although they can also occur with generalized seizures. Anxiety, fear, and psychosis are the most common psychiatric symptoms experienced during a seizure. Up to one-third of patients with focal seizures with impairment of awareness have anxiety or fear as part of their seizures; the anxiety is often intense and may last throughout the course of the seizure. It is important to keep in mind that subtle focal seizures, such as a stereotyped anxiety, might be described as an “aura” (a term no longer recommended for describing these seizures) by patients and some physicians. Such symptoms may resemble those of panic attacks with autonomic symptoms, nausea, intense anxiety, and depersonalization. Therefore, patients with epilepsy may have both ictal anxiety and inter-ictal panic attacks that are difficult to distinguish. The more circumscribed the symptoms are to associated seizure phenomena (e.g., automatisms or hallucinations during an episode, or confusion or severe lethargy after the event), the more likely it is that the anxiety is ictal.
Ictal psychosis has also been seen in patients with focal seizures. Ictal psychotic symptoms are most often associated with temporal lobe foci, but nearly one-third of patients have non-temporal lobe foci. Hallucinations during a seizure are much more likely to be olfactory or gustatory; auditory hallucinations (common in primary psychotic disorders) are less common, but simple auditory symptoms, such as echoing, might happen in the setting of a simple focal seizure involving auditory perception cortices. Paranoia is uncommon and usually short-lived. In contrast to patients with primary psychosis, consciousness is usually impaired during ictal psychosis, and affected patients are usually amnestic for the episode.
Ictal depression is uncommon; it occurs as part of the aura in approximately 1% of patients with epilepsy. Such depressive symptoms, as with other ictal symptoms, appear abruptly, in a stereotypical manner, and without obvious psychosocial precipitants. Although depressive symptoms often disappear abruptly, some authors have noted that ictal depressed mood may extend beyond other ictal or post-ictal symptoms. Ictal crying (so-called dacrystic seizure ) has been described in seizures with involvement of limbic structures.
Ictal anger, agitation, and aggression have also been reported, but appear to be exceedingly rare (fewer than 0.5% of patients in one large series ). Furthermore, ictal aggression is poorly directed and does not involve significant interactive behavior. Stereotyped shouting and pushing are among the most common manifestations, while patients rarely perform intricate, directed acts of violence during a seizure.
Determining whether anxiety, depression, or other psychiatric symptoms are ictal events or part of primary psychiatric conditions can be difficult. Table 19-1 describes some distinguishing characteristics of ictal and non-ictal symptoms. In general, ictal symptoms are more often abrupt in onset and offset, occur in concert with other stereotyped manifestations of seizures, and are frequently short-lived, usually lasting less than 3 minutes. The most convincing evidence for the ictal nature of a symptom is a more or less stereotyped pattern; that is, a patient will not experience fear with one seizure and depressive symptoms with another—the pattern of symptoms will generally be the same.
TABLE 19-1
Clinical Characteristics That Help Distinguish Epileptic From Non-Epileptic Events
| EPILEPTIC SEIZURES | NON-EPILEPTIC SEIZURES/EVENTS | |
|---|---|---|
| Onset | Sudden onset and offset | Often gradual |
| Duration | Often <3 minutes | Variable |
| Perception | May experience olfactory, gustatory, visual hallucination; déjà vu; derealization | May experience auditory hallucinations; paranoia |
| Eyes during event | Open | Closed |
| Incontinence | Common | Rare |
| Awareness | Often impaired; can stay aware during some focal seizures | Variable; may be responsive during parts of the event |
| Recall of event | None or limited (e.g. aura) | Usually intact |
| Ictal EEG | Almost always abnormal | Unchanged from baseline |
| Inter-ictal EEG | Normal or abnormal | Often normal |
| Tongue bite | Lateral tongue | None or tip of tongue |
| Injury | May be present | Rarely present (suggestive of serious psychopathology) |
| Incontinence | May be present | Rare |
| Post-ictal state | Confusion or drowsiness is common | Rare |
| Prolactin | Elevated; or normal | Normal; rarely elevated from baseline |
Prolonged or frequent focal seizures, sometimes qualifying as status epilepticus , may result in prolonged ictal psychiatric symptoms that further complicate the diagnosis. Therefore, the EEG remains a key tool for establishing whether symptoms are ictal. Since most focal seizures have an identifiable focus such as an ischemic, neoplastic, or vascular lesion, brain imaging should be considered early if ictal symptoms are suspected. A patient's history, such as history of systemic malignancy, cerebrovascular risk factors, or suspicion for an inflammatory or infectious process in the brain, should decrease the threshold for imaging. Unfortunately, CT scans have low sensitivity and specificity for detecting many etiologies, despite their ready availability and lower cost; a magnetic resonance imaging (MRI) protocoled and reviewed by a radiologist for finding seizure foci, is strongly recommended.
Treatment of ictal psychiatric symptoms requires a careful evaluation. Primary psychiatric symptoms and ictal psychiatric symptoms are similar, frequently co-morbid, and have different treatments. Therefore, working with a neurologist for careful clinical evaluation, EEG monitoring, and when indicated, other diagnostic procedures should be followed to distinguish these phenomena. Once symptoms have been identified as ictal, treatment of the associated psychiatric symptoms requires treatment of the seizure with anticonvulsants. Treatment of ictal psychosis with antipsychotics or ictal anxiety with non-anticonvulsant anxiolytics is generally not indicated. Measures to reduce the risk of falls or other injury are crucial for patients whose seizure disorders remain active.
Peri-ictal Neuropsychiatric Phenomena
Despite the above-mentioned rarer ictal neuropsychiatric phenomena, the majority of neuropsychiatric disturbances happen in peri-ictal, and mostly post-ictal phases of seizures. They usually occur several hours after a seizure. Pre-ictal symptoms can occur and include psychosis, mood changes, or aggression in the hours or minutes before a seizure have been described and should not be confused with focal seizures that are sometimes called auras . These symptoms tend to increase until the onset of the clinical seizure and, depending on the time course and nature of the symptoms, may be conceptualized as prodromes separate from the ictus or as ictal events.
Post-ictal neuropsychiatric symptoms are relatively common. Approximately 8% to 10% of patients with seizures have post-ictal behavioral disturbances. These symptoms may occur in the context of a diffuse post-ictal suppression of the cortical activity that involves disinhibited, sub-cortical behavior (such as moaning, crying, laughing, cursing, sexual behavior, or rage). Autonomic instability may contribute to what is observed as a post-ictal behavior as well. Patients are often amnestic to these events, and difficult to control. Neuropsychiatric symptoms may also arise post-ictally, despite the presence of a clear consciousness. Patients may remember parts of events or even try to justify their behavior. By definition, post-ictal symptoms should remit spontaneously and are often short-lived, and persistence of symptoms beyond 72 hours should be considered as a possible inter-ictal symptom. However, such symptoms may persist for days or even weeks. Patients with well-defined, prolonged post-ictal neuropsychiatric syndromes may be more likely to develop persistent inter-ictal symptoms.
Psychosis is the most common post-ictal neuropsychiatric symptom, occurring in up to 7.8% of epilepsy patients, and often appears after a non-psychotic post-ictal period. It occurs most commonly in patients with focal-unaware seizures that become secondarily generalized, especially in those with temporal lobe or bilateral foci. Psychotic symptoms vary widely, and affective symptoms (depressive or manic) may also be present. Symptoms can include paranoid or grandiose delusions and hallucinations in a variety of sensory modalities; Schneiderian first-rank symptoms of schizophrenia are rare. Symptoms tend to resolve spontaneously but recur an average of two to three times per year. In a minority of patients, such symptoms become chronic, even in the absence of clear clinical seizures.
Post-ictal depression is also associated with focal-unaware seizures but is less common than post-ictal psychosis. Patients with post-ictal depression may have flattened affect and anhedonia more often than sadness, and post-ictal depression is commonly associated with delirium and other post-ictal cognitive disturbances. Kanner and Balabanov found that symptoms last an average of 24 hours, although symptoms may be more prolonged. In most cases, post-ictal depressive symptoms do not just represent a reactive response to the stress of having a seizure. Other post-ictal symptoms are less common. Acute post-ictal anxiety is relatively infrequent and is usually associated with post-ictal depression. Post-ictal mania and hypomania occur infrequently. Post-ictal aggression can also occur; however, it is generally associated with delirium, psychotic symptoms, or abnormal mood states.
The management of patients with post-ictal neuropsychiatric symptoms has a number of tenets. First, enhanced treatment of the seizure disorder is crucial; patients whose seizure disorders are poorly controlled appear to have a greater tendency toward post-ictal affective and psychotic symptoms. In addition to anticonvulsants for seizure prophylaxis, other psychotropic medications may be indicated, especially if symptoms are prolonged, present a risk to the patient or to others, or adversely affect the patient's ability to receive appropriate treatment. Such situations occur most commonly with psychosis, and low doses of antipsychotics can reduce agitation and diminish psychotic symptoms. If such symptoms are limited to the post-ictal period, these medications can be discontinued once symptoms resolve, because the best prophylaxis against recurrence of psychosis is treatment with anticonvulsants to prevent seizures. Antidepressants are uncommonly indicated for depressive symptoms limited to the post-ictal period.
In addition to medications, behavioral treatments can be instituted to facilitate coping and to maintain the patient's safety. Such interventions may include the use of restraints or observers, frequent re-orientation, or the presence of familiar family members. Finally, it is important to know the patient's post-ictal pattern of symptoms to prepare caregivers and family members for what lies ahead. Seizures and their neuropsychiatric sequelae are commonly stereotyped; that is, patients tend to have the same post-ictal symptomatology from seizure to seizure. If a patient is known to become psychotic or dangerous after a seizure, the treatment team can be prepared with antipsychotic treatments or other safety-enhancing measures.
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