Normal and Abnormal

Invented in the first half of the twentieth century by a psychiatrist (Hans Berger) and improved by computerization and correlation with patient videos, the EEG remains the most specific laboratory test for seizures. In addition, it still helps in the diagnosis of several other neurologic conditions. Neurologists liberally order an EEG as a painless, harmless, relatively inexpensive, and, when positive, helpful diagnostic test.

The routine EEG records cerebral electrical activity detected by “surface” or “scalp” electrodes (Fig. 10-1). Four frequency bands of cerebral activity, represented by Greek letters, emanate from the brain (Table 10-1).

FIGURE 10-1 In the standard array of scalp electrodes, most are named for the underlying cerebral region (e.g., frontal, temporal, central, parietal, and occipital). Odd-numbered ones are on the left, and even-numbered ones on the right. The P_g electrodes attach to nasopharyngeal leads and the A electrodes, the ears (aural leads).

TABLE 10-1 Common Electroencephalogram Rhythms

^*May be focal.

EEG readers first ascertain the patient’s age and level of consciousness. They also determine the display of the electrodes (the montage) and note the time scale, which is determined by vertical lines on the EEG paper or displayed as 1-second horizontal bars. Although approaches vary, most readers then determine the EEG’s background or dominant rhythm (see later), organization, and symmetry. EEG readers accord special attention to unusually pointed single discharges, called sharp waves or spikes, and abnormal patterns, especially if they occur in paroxysms. They judge all these features in relation to whether the patient is awake, asleep, unresponsive, or having observable seizure activity.

The normal background rhythm in an awake adult consists of waves of activity in the alpha range of 8–13 cycles per second (Hertz [Hz]) detectable mostly over the occipital region (Fig. 10-2). Neurologists refer to this pattern as the posterior dominant rhythm. It is prominent when individuals are relaxed with their eyes closed, but disappears if they open their eyes, concentrate, or are apprehensive. When people undergoing an EEG merely fix their gaze on a clock or add two single-digit numbers, faster rhythms replace alpha activity. Preoccupations, concerns, or anxiety eliminate alpha activity. Because alpha activity reflects an anxiety-free state, it represents an important parameter in “alpha training,” biofeedback, and other behavior modification techniques.

FIGURE 10-2 A, Alpha rhythm consists of regular 8–13-Hz activity overlying the occipital lobe. B, Beta rhythm consists of low-voltage, irregular >13-Hz activity overlying the frontal lobe. C, Theta rhythm consists of 4–7-Hz activity overlying the right frontal lobe. D, Delta activity consists of high-voltage <4-Hz activity present over the entire hemisphere.

Alpha activity also disappears when people fall asleep or take psychotropic medicines. In the elderly, the background rhythm typically slows but remains within or just below the alpha range. In the early stages of Alzheimer disease, the background activity is also slower than normal. In the more advanced stages of Alzheimer disease, as well as in many other neurologic illnesses, the background EEG activity not only slows well below the alpha range, but also loses its organization.

Beta activity consists of high (> 13 Hz)-frequency, low-voltage activity located maximally overlying the frontal region. It replaces alpha activity when people concentrate, become anxious, or take many hypnotics or sedatives, including benzodiazepines. Beta activity usually inserts itself into the background EEG activity of most adults.

Theta (4–7 Hz) and delta (< 4 Hz) activities occur normally in children and everyone during deep sleep, but are usually absent in healthy alert adults. When present over the entire brain, theta or delta activity in wakefulness often indicates a neurodegenerative illness, such as Alzheimer disease, or a metabolic derangement. Continuous focal slow activity with phase reversal in bipolar montages (Fig. 10-3) sometimes originates in an underlying cerebral lesion; however, the absence of theta or delta activity certainly does not exclude one.

FIGURE 10-3 This bipolar montage shows four channels from the right side (upper four) and four from the left (lower four). Each side progresses from the frontal to the occipital region. On at least five occasions (marked by dots), sharp waves and spikes, in phase reversal, appear to point toward each other. These sharp waves and spikes originate from the common electrode, F₃, situated over the left frontal lobe. Such isolated, phase-reversed sharp waves are associated with seizures, but, without additional clinical or EEG evidence, they are insufficient for a diagnosis of seizures.

Spikes, sharp waves, and slowing – nonspecific changes – occur in about 3–15% of the general, healthy population. When they are isolated and asymptomatic, these anomalies have no clinical significance and require no further investigation. However, when spikes and sharp waves are repetitive and phase-reversed, they are an indication of an irritative cerebral focus with potential to produce seizures. Moreover, paroxysms of them suggest the diagnosis.

Seizures

During a seizure (ictus), the EEG reveals paroxysmal activity usually consisting of bursts of spikes, slow waves, or complexes of spike-and-waves or polyspike-and-waves. Although ictal EEG abnormalities are distinct when captured, muscle or movement artifacts may obscure them. After the seizure, in the postictal period, EEGs commonly show only slow low-voltage activity, postictal depression, often followed by diffuse high-voltage slowing.

In most patients, EEGs obtained between seizures, in the interictal period, contain abnormalities that support – but do not prove – a diagnosis of epilepsy. On the other hand, because many epilepsy patients have no abnormalities on an interictal EEG, a normal interictal EEG cannot exclude a diagnosis.

EEG technicians employ certain maneuvers to provoke EEG abnormalities in patients suspected of having primary generalized epilepsy (see later). For example, the technicians ask patients to hyperventilate for 3 minutes or look toward a stroboscopic light during the test. If these strategies fail to yield diagnostic EEG patterns and a strong suspicion of seizures persists, neurologists might repeat an EEG following sleep deprivation. In about 30% of epileptic patients, a sleep-deprived EEG reveals abnormalities not apparent in routine studies.

In some epilepsy patients, specially placed electrodes reveal abnormalities undetectable by ordinary scalp electrodes. For example, anterior temporal scalp, nasopharyngeal, or sphenoidal electrodes can detect discharges from the temporal lobe’s inferior-medial (mesial or medial) surface (Fig. 10-4).

FIGURE 10-4 Nasopharyngeal electrodes, which are inserted through the nostrils, reach the posterior pharynx. There, separated by the thin sphenoid bone, they are adjacent to the temporal lobe’s medial surface, which is the focus (origin) of about 80% of complex partial seizures. (Figures in Chapter 20 show the relatively large distance between the temporal lobe’s medial surface and the scalp, and the closeness of the temporal lobe to the sphenoid bone.) Sphenoidal electrodes are inserted through the skin to reach the lateral surface of the sphenoid wing. Electrodes in this location are near the temporal lobe’s inferior surface. (Although nasopharyngeal and sphenoidal electrodes are valuable, specially placed scalp electrodes, new arrays, electronic filters, and critical reading of the EEG may be just as accurate and less invasive.) To pinpoint a seizure focus in anticipation of its surgical removal, neurosurgeons place a grid of electrodes in the subdural space.

Another diagnostic strategy, continuous EEG-video monitoring, consists of several days of video recordings of clinical activity and EEG usually undertaken in hospital epilepsy units. The monitoring system records any seizures, changes in behavior, and effects of sleep. At the same time, physicians might check serum AED concentrations and various physiologic data. Continuous EEG-video monitoring has become the gold standard for many epilepsy studies, including diagnosing, classifying, subclassifying, and determining the frequency of seizures, evaluating patients for epilepsy surgery, treating patients who seem to suffer from refractory seizures (frequent seizures that do not respond to AEDs), and identifying disorders that mimic epilepsy, particularly psychogenic nonepileptic seizures (PNES: see later). For example, continuous EEG-video monitoring would be the ideal test for a child who has developed discrete periods of abnormal repetitive behavior in whom the routine EEG has shown only a few spikes that did not occur in paroxysms and were not temporally associated with the questionable behavior. It would also be the ideal test for an adolescent who has developed a new pattern of seizures superimposed on the usual seizure pattern in whom routine EEGs never captured a seizure.

Finally, electrodes surgically implanted in the dura, subdural space, or cerebral cortex can localize an epileptic focus when conventional tests are inconclusive. Neurologists frequently use them to pinpoint a seizure focus prior to surgery (see later).

Quantitative EEG analysis or EEG brain mapping involves topographic displays and comparisons of a patient’s EEG to standard results. This technique, still essentially a research tool, remains too unreliable for clinical usefulness in neurologic conditions, including epilepsy, minor and moderate head injury, and postconcussive syndrome. Its uncertain status precludes its credibility in litigation.

With children, an evaluation could actually begin with parents making videos of suspected seizures or other episodic disturbances, including temper tantrums, breath-holding spells, night terrors, other parasomnias (see Chapter 17), dopamine-responsive dystonia, and other intermittent abnormal movements (see Chapter 18).

Toxic-Metabolic Encephalopathy

During the initial phase of toxic-metabolic encephalopathy (delirium), when patients have only subtle behavioral or cognitive disturbances, theta and delta activity replaces alpha activity. The organization of the EEG deteriorates as the patient’s sensorium disintegrates. The EEG in toxic-metabolic encephalopathy almost always shows generalized slowing and disorganization. Additional EEG changes point to specific diagnoses. Hepatic and uremic encephalopathies characteristically produce triphasic waves (Fig. 10-5). In fact, with hepatic failure, triphasic waves often appear before bilirubin levels rise. While metabolic derangements are the most common cause of triphasic waves, this EEG finding may also be seen with toxic levels of several medications, including lithium. Benzodiazepine use produces beta activity. Herpes simplex encephalitis produces spikes and periodic lateralizing epileptiform discharges over the temporal lobes.

FIGURE 10-5 This EEG obtained from a patient with hepatic encephalopathy reveals characteristic triphasic waves overlying the frontal lobes (the first and fifth channels in this montage). In addition to the presence of triphasic waves, the EEG lacks the normal, organized alpha activity over the occipital lobes (the fourth and eighth channels).

Just like a toxic-metabolic encephalopathy almost always produces EEG abnormalities, the converse holds equal weight. A normal EEG reliably precludes a toxic-metabolic encephalopathy.

Dementia

In early Alzheimer disease, the background activity usually slows to below 8 Hz. As previously mentioned, in late Alzheimer disease, the background is unequivocally slow and often disorganized.

Vascular dementia also induces EEG abnormalities. However, these changes cannot reliably differentiate vascular dementia from Alzheimer disease dementia (see Chapters 7 and 11).

In contrast, the EEG is almost definitive in diagnosing subacute sclerosing panencephalitis and common, sporadic Creutzfeldt–Jakob disease (see Chapter 7). In these conditions – characterized clinically by dementia and myoclonus – the EEG shows periodic sharp-wave complexes (Fig. 10-6). (Variant Creutzfeldt–Jakob disease [“mad cow disease”] fails to produce these EEG changes [see Chapter 7].)

FIGURE 10-6 Periodic sharp-wave complexes classically appear in all channels as fairly regular, 1–3-second bursts of electrical activity followed by minimal activity. Neurologists often describe this EEG pattern as “burst suppression.” Myoclonic jerks represent the clinical counterpart of the periodic complexes. Together myoclonic jerks and periodic complexes are cardinal features of two illnesses characterized by dementia: subacute sclerosing panencephalitis and Creutzfeldt–Jakob disease (see Chapter 7).

The EEG can also help distinguish between pseudodementia and dementia – to the extent that they constitute separate entities (see Chapter 7). In pseudodementia the EEG ideally would remain normal, but in dementia from almost any cause, it would show slowing. For the many patients with a mixture of depression and mild dementia, the EEG cannot measure each condition’s relative contribution to cognitive impairment.

Even though EEGs are relatively inexpensive and carry no risk, neurologists do not routinely order them in the evaluation of a patient with dementia except under certain circumstances: when dementia develops in less than 3–6 months, when myoclonus accompanies dementia (suggesting Creutzfeldt–Jakob disease or a related illness), when a patient’s level of consciousness fluctuates (indicating a toxic-metabolic encephalopathy), or if depression rather than dementia might explain poor cognitive performance.

Structural Lesions

The EEG does not reliably detect or exclude structural lesions, even those that frequently cause seizures, such as brain tumors and cysticercosis. In fact, the EEG is normal in many of these conditions and, when abnormal, does not distinguish among them. Computed tomography (CT) and especially magnetic resonance imaging (MRI) are standard and, despite their expense, cost-effective for detecting structural lesions (see Chapter 20). Although CT may suffice, MRI better detects small structural lesions. More important, MRI is especially effective in detecting mesial temporal sclerosis, which underlies many complex partial seizures (see later).

Altered States of Awareness

The EEG shows distinctive changes during normal progressively deeper stages of sleep and during dreaming. Coupled with monitors of ocular movement and muscle activity in the polysomnogram, the EEG is critical in diagnosing sleep disturbances (see Chapter 17), which can include sleep-related behavioral disturbances and involuntary movement disorders, as well as seizures.

The EEG is also useful in diagnosing the locked-in syndrome, a condition in which patients cannot speak or move their trunk or limbs. Although patients in the locked-in syndrome appear comatose or demented, they remain fully alert and in possession of their cognitive capacity (see Chapter 11). The locked-in syndrome most commonly results from either an infarction in the base of the lower brainstem or extensive cranial and peripheral nerve damage. With their cerebral hemispheres and upper brainstem intact, patients retain normal cerebral activity and normal EEG activity.

Physicians must identify the locked-in syndrome and differentiate it from the persistent vegetative state (PVS), which is also characterized by patients’ inability to speak. PVS typically follows cerebral cortex anoxia from cardiac arrest, drug overdose, or carbon monoxide poisoning. Most importantly, because patients in a PVS have sustained extensive cerebral cortex injury, they have profound cognitive impairment. Nevertheless, their vegetative functions, such as breathing and digesting food, continue. In addition, their eyes continue to open and close, but mostly randomly or in response to light. As would be predicted, the extensive cerebral cortical damage leads to slow and disorganized EEG activity.

Finally, absence of EEG activity (electrocerebral silence), in most circumstances, indicates “brain death.” Making that determination before the heart stops beating permits procurement of organs for transplantation. Exceptions – hypothermia or drug overdose – preclude a diagnosis of brain death based on the EEG. For example, people may fully recover from either barbiturate overdose or drowning in icy water that initially left them with no obvious signs of life and a “flat” EEG.

Psychiatric Disturbances and Psychotropics

Because the EEG does not show abnormalities consistently indicative of psychiatric illnesses, obtaining EEGs on a routine basis for psychiatric patients remains unwarranted. EEGs in uncomplicated psychiatric illness show either normal patterns or frequently only minor, nonspecific abnormalities, such as excessive beta or theta activity, a few sharp waves or spikes, or poor organization.

As a confounding factor, psychotropic medications induce EEG changes. Although these changes are usually minor and nonspecific, some are prominent and persist for up to 2 months after medications are withdrawn.

There are few guidelines for assessing psychotropics’ EEG effects. Most produce background slowing into theta but sometimes delta range. Benzodiazepines and barbiturates typically produce beta activity, which may be a telltale sign of surreptitious drug use. Phencyclidine (PCP) and other excitatory drugs cause generalized, paroxysmal discharges. Phenothiazines, even at therapeutic serum concentrations, also produce sharp waves. Lithium at toxic levels, clozapine, and tricyclic antidepressants (TCAs) cause spikes and sharp waves. As described previously, lithium toxicity may induce triphasic waves on EEG monitoring. Of the antipsychotics, clozapine, olanzapine, and trifluoperazine generally produce the most EEG changes, and quetiapine, loxapine, and haloperidol, the least.

Electroconvulsive therapy (ECT) also induces EEG changes. During and immediately after ECT, EEG changes resemble those of a generalized tonic-clonic seizure and its aftermath. Subsequently, EEG slow-wave activity develops over the frontal lobes or the entire cerebrum and persists for up to 3 months. When ECT is unilateral, EEG slowing is less pronounced and more restricted to the treated side. Although ECT-induced EEG slowing is associated with memory impairment, it is also associated with more effective treatment of depression.

EEG and Etiology

During elementary partial seizures, EEGs show spikes, sharp or slow waves, or spike-wave complexes overlying the seizure focus. For example, during seizures with motor symptoms, EEG abnormalities are usually detectable in channels overlying the frontal lobe (Fig. 10-8), and, during the interictal period, EEGs may still show occasional spikes in the same channels.

FIGURE 10-8 During a partial seizure with motor symptoms, this EEG contains a paroxysm of 4-Hz sharp-wave activity with phase reversals referable to the F₃ electrode. Because the F₃ electrode overlies the left frontal region, the seizure probably consists of right face or arm motor activity and, in some of the cases, a deviation of the head and eyes to the right.

In most cases, neurologists cannot determine the cause of partial seizures. Of those cases where neurologists can establish the cause, the patient’s age at the onset of the seizures is one of the most important factors. For example, when young children develop partial seizures, typical causes are congenital cerebral malformations, such as cortical dysgenesis, and neurocutaneous disorders (see Chapter 13). In young adults, common causes of elementary partial seizures are head trauma, arteriovenous malformations (AVMs), and previously asymptomatic congenital injuries. However, posttraumatic seizures are not associated with trivial head injuries, but with serious trauma, such as trauma causing more than 30 minutes of unconsciousness, depressed (not just linear) skull fractures, intracranial hematomas, and penetrating wounds.

Young adults with major psychiatric and neuropsychiatric disorders are prone to seizures. For example, about 30% of autistic individuals and 70–90% of those with Rett syndrome develop epilepsy by the time they are adults. Also, genetic abnormalities in sodium or calcium channels or the GABA_A-receptor subunit can cause both partial and generalized seizures. Such genetically determined varieties of epilepsy generally arise between infancy and adolescence. Also, in these varieties, myoclonus, mental retardation, and other stigmata of neurologic disease accompany the epilepsy.

Because drug and alcohol abuse carries multiple neurologic ramifications, neurologists often consider substance abuse in young adults presenting with seizures. Especially when seizures are accompanied by psychotic or otherwise abnormal behavior, physicians should suspect use of cocaine, PCP, and amphetamine intoxication. (Cocaine leads to seizures not only reducing the seizure threshold, but, by causing strokes, leading to noncompliance with AED regimens, and disrupting sleep.) However, although neonates may develop seizures during opiate withdrawal, adult drug addicts generally do not develop seizures during heroin use, withdrawal, or detoxification. Also, marijuana does not lead to seizures and actually has a slight antiepileptic effect.

Profound alcohol intoxication or alcohol-induced hypoglycemia can precipitate seizures. Also, 1–3 days of abstinence from chronic, excessive alcohol consumption produces seizures (see later). Although the clinical and EEG manifestations of these seizures resemble those of genetically determined seizures, the interictal EEG is normal. Withdrawal from daily use of benzodiazepines (especially alprazolam) is similar and these withdrawal seizures often evolve into status epilepticus. Most cases of benzodiazepine-withdrawal seizures are associated with prescription medicines rather than “street” drugs.

Although a seizure associated with drug or alcohol abuse may reveal dependency or addiction, it does not necessarily constitute epilepsy. Moreover, a neurologic complication of substance abuse, rather than withdrawal, may be the cause of the seizure. For example, cocaine routinely causes vasoconstriction or cerebral hemorrhages that in turn cause seizures. Similarly, although heroin may not directly produce seizures, its intravenous use can lead to bacterial endocarditis, episodes of cerebral anoxia, acquired immunodeficiency syndrome (AIDS), hepatitis, and vasculitis, which all can cause seizures.

Adults aged 40–60 years most often develop seizures because of a structural lesion, such as a primary or metastatic brain tumor. By contrast, older people are more likely to have a stroke rather than a tumor. In young adults with AIDS, the cause is most likely cerebral toxoplasmosis. The patient’s geography also suggests the cause. For example, in South and Central America, cerebral cysticercosis is the most common cause of seizures. In the Indian subcontinent, tuberculomas are one of the most common causes. By extension, those infections may very well underlie the development of epilepsy in recent immigrants to the United States.

Etiology

Mesial temporal sclerosis, probably the most common cause of epilepsy with complex partial seizures, is characterized by sclerosis of the hippocampus and atrophy of the temporal lobe. Although anoxia at birth, other perinatal insults, and prolonged febrile seizures – but not brief, occasional febrile seizures – lead to most cases of mesial temporal sclerosis, some studies suggest that temporal lobe infections with herpesvirus or prions cause this variety of epilepsy in many cases. Other possible causes are temporal lobe hamartomas, astrocytomas, and lesions underlying elementary partial seizures (see above).

Menses, intercurrent illness, or low AED serum concentration may precipitate complex partial as well as other varieties of seizures. For example, up to 80% of women with epilepsy report an increase in seizure frequency around the time of their menses. Lack of sleep and self-reported stress and anxiety often predate seizures.

Ictal Symptoms

Symptoms of complex partial seizures in 20–80% of patients include a characteristic premonitory sensation, called an aura (Greek, breeze or soft wind). Not merely a warning, the aura constitutes the first portion of the seizure.

During most of a complex partial seizure, patients usually display a blank stare and are inattentive and uncommunicative. They always – by definition – have impaired consciousness. In most cases, they also have partial or complete memory loss, amnesia, presumably because seizure discharges besiege the limbic system in the temporal lobe. The amnesia is so striking that it may appear to be a patient’s only symptom. (Thus, physicians should strongly consider complex partial seizures among the neurologic causes of the acute amnestic syndrome [see Box 7-1].)

Physical manifestations of complex partial seizures usually consist of only simple, repetitive, purposeless movements (automatisms) of the face and hands. Present in about 80% of complex partial seizures originating in the temporal lobe, common automatisms include repetitive swallowing, mouthing, kissing, lip smacking, and lip licking – oral automatisms – or fumbling with clothing, scratching, rubbing the abdomen, or fidgeting – manual automatisms (Fig. 10-9). Other physical manifestations are simple actions, such as standing, walking, pacing, or even driving; however, sometimes these actions are simply ingrained tasks that continue despite the seizure. In addition, more than 25% of patients utter brief phrases or unintelligible sounds.

FIGURE 10-9 During complex partial seizures, patients typically appear dazed. They perform only rudimentary, purposeless actions, such as pulling on their clothing, and pay little or no attention to their surroundings or examiners. Their hands and fingers move in clumsy and misdirected patterns. Repetitive, simple oral, limb, or body movements, automatisms, such as lip smacking, occur in approximately 80% of cases with a temporal lobe focus and the majority of those with absence seizures.

Many times the environment triggers actions and words. For example, a child may clutch and continually stroke a nearby stuffed animal while repeating an endearing phrase. Impaired consciousness, apparent self-absorption, and subsequent failure to recall the event would separate these activities from normal behavior.

Complex partial seizures occasionally cause elaborate visual or auditory hallucinations accompanied by emotions that are appropriate, inconsistent, or exaggerated. Although dramatic, such elaborate symptoms are rare.

Physicians should maintain skepticism regarding nonspecific “experiential phenomena” – déjà vu (French, previously seen or experienced), jamais vu (French, never seen or experienced), dream-like states, mind–body dissociations, and floating feelings. Having crept into the popular vocabulary, these terms have lost most of their diagnostic value. Moreover, reliable symptoms and signs and EEG findings rarely corroborate their relationship to seizures.

Another frequently encountered symptom with a dubious association with complex partial seizures is the rising epigastric sensation. This symptom consists of a sensation of swelling in the abdomen that, as if progressing upward within the chest, turns into tightness of the throat and then a sensation of suffocation. Although it could be an aura, a rising epigastric sensation may also represent a panic attack or globus hystericus, a commonly occurring psychogenic disturbance that causes a similar tightening of the throat and an inability to breathe. Likewise, when seizures originate in the amygdala, they are said to cause overwhelming fear as the primary or only symptom. However, the medical literature does not support the notion that pronounced fear, as an isolated sensation, is a seizure manifestation. More likely, it would represent a panic attack.

Many complex partial seizures, like simple partial seizures, intermittently undergo secondary generalization. In contrast, in partial status epilepticus, seizures with their same limited symptoms persist or recur in quick succession. In nonconvulsive status epilepticus, patients demonstrate hours of neuropsychological aberrations, such as thought disorder, language impairment, or change in sensorium. Patients’ behavior may be so bizarre that it merits the label ictal psychosis. It often mimics delirium, traumatic brain injury (TBI), and numerous other neurologic disorders as well as an acute psychotic episode. Neurologists usually encounter nonconvulsive status epilepticus most often in epilepsy patients, particularly in ones who have been noncompliant with their AEDs. They also see it in the critically ill patients who have sustained cerebral injury or anoxia. Neurologists diagnose it by obtaining an EEG as part of the evaluation they perform on stuporous patients. Intravenous administration of a benzodiazepine will usually abort status epilepticus and awaken the patient.

Sex, Violence, and Aggression

During seizures, patients sometimes fumble with buttons, tug at their clothing, or make rudimentary masturbatory movements. They may even seem to undress partially. However, these patients are not deliberately exposing themselves or attempting to engage in sex. Except for very rare instances, seizures are unaccompanied by erotic or interactive sexual behavior. In fact, most seizure-like symptoms that develop during sexual activity, such as lightheadedness, are simply manifestations of anxiety. (On the other hand, severe headaches that develop during sexual intercourse are ominous [see coital headache and subarachnoid hemorrhage, Chapter 9].)

Continuous EEG-video monitoring has demonstrated that ictal violence, allowing for rare exceptions, consists only of random shoving, pushing, kicking, or verbal abuse, such as screaming. This behavior is fragmented, unsustained, ineffectual, and, most importantly, unaccompanied by rage or anger. Moreover, violence, which occurs in less than 0.1% of cases, is virtually never the sole manifestation of a complex partial or any other type of seizure.

Belligerence or resistive violence, a different form of seizure-related violence, occurs when patients fight against restraints during their ictal or postictal period. Much more frequently occurring than ictal violence, resistive violence stems largely from patients’ fighting off health care workers or family members who attempt to restrain them or give them injections, as well as placing leather straps around their wrists or body.

Physicians must distinguish ictal violence, with its lack of aggression, from both criminal violence, which is characterized by aggression, and episodic dyscontrol syndrome (see later). For neurologists to consider it aggression, the behavior must be directed, have a conscious or unconscious rationale, and be accompanied by a consistent affect. Although aggression may consist only of threats or taking control, it often leads to deliberate personal and property damage.

During seizures, patients cannot engage in sequential activities, premeditated actions, or meaningful interactions with other people – requirements of criminal activity. Patients also lack the cognitive ability to operate mechanical devices. These limitations preclude violent crimes either in the midst of a seizure or as a manifestation of a seizure. Overall, most neurologists accept violence, but neither aggression nor criminal acts, as a rare manifestation of seizures.

Immediate Postictal Symptoms

Immediately after a complex partial seizure, which has an average duration of 2–3 minutes, patients characteristically experience confusion, clouding of the sensorium, disorientation, flat affect, and sleepiness. However, seizures occasionally lead not to somnolence, inactivity, and withdrawal, but to agitation, i.e., postictal agitation. If seizures involve the brain’s language region and cause transient aphasia (see Chapter 8), postictal symptoms may be more pronounced. Similarly, if the seizure focus includes the cortical areas involved with motor function, patients may have a Todd’s hemiparesis. For 15–40 minutes after a seizure, many patients have measurable physiologic changes: Approximately 40% of them have an elevated serum prolactin concentration and focal EEG depression.

Astute physicians are unlikely to mistake complex partial seizures for psychotic episodes. Complex partial seizures usually last only a few minutes, consist of stereotyped symptoms, necessarily include impaired consciousness, and usually have debilitating postictal manifestations. After recovering from a seizure and its aftermath, patients gradually return to their interictal personality, which admittedly might be abnormal. In contrast, psychotic episodes, which are frequently triggered by factors in the environment, typically last at least several days. Also, the manifestations of the psychosis vary greatly from episode to episode and often include hypervigilance.

Frontal Lobe Seizures

Named for the region of the brain where they originate, frontal lobe seizures constitute a distinct, important variety of complex partial seizures. Their manifestations consist of abrupt, aura-less onset of vocalizations, and bilateral complex movements lasting for a relatively short time (less than 1 minute). They are followed by little or no postictal confusion. In addition, frontal lobe seizures tend to begin in the adult years, occur relatively frequently (several times a month), develop predominantly during sleep, and produce paroxysmal EEG discharges that are difficult to detect by conventional EEG studies.

Frontal lobe seizures, even compared to complex partial seizures of temporal lobe origin, are most apt to cause bizarre behavior and the few instances of aggressive violence. With their behavioral manifestations and EEG changes usually undetectable, frontal lobe seizures mimic PNES. In addition, when frontal lobe seizures arise exclusively during sleep, they mimic sleep disorders (see Chapter 17).

Testing During and Between Complex Partial Seizures

EEG

During a complex partial seizure, the EEG most often shows paroxysms of spikes, slow waves, or other abnormalities in channels overlying the temporal or frontotemporal region. Even though a seizure focus may be unilateral, bilateral EEG abnormalities appear because of additional foci, interhemispheric projections, or “reflections.” Nasopharyngeal and other specially placed leads may capture temporal lobe discharges that routine scalp electrodes fail to detect (Fig. 10-10).

FIGURE 10-10 An interictal EEG with nasopharyngeal electrodes (P_g1 and P_g2) shows phase-reversed spikes that routine scalp electrodes may not detect.

In the interictal period, the routine EEG contains spikes or spike-and-wave complexes over the temporal lobes in about 40% of cases. When accompanied by an appropriate history, these EEG abnormalities are specific enough to corroborate the diagnosis. Looking at the situation in reverse, about 90% of persons with anterior temporal spikes on the EEG will have complex partial seizures. Nevertheless, a diagnosis of seizures should not be based entirely on EEG spikes. Diagnosis of complex partial or other seizures requires correlation of EEG abnormalities with symptoms and signs.

If the diagnosis remains a problem, especially where episodic behavioral abnormalities are believed to result from seizures, physicians should arrange for continuous EEG-video monitoring. EEG corroboration of complex partial seizures might begin with a routine EEG, but it has only a 40% yield. Although EEGs performed during sleep and wakefulness or following sleep deprivation might offer a greater yield, EEG-video monitoring offers virtually a 100% yield when an event is captured.

Depression

Depression is more prevalent in epilepsy than in other chronic neurologic illnesses, including Alzheimer and Parkinson diseases. With its prevalence in epilepsy patients ranging between approximately 7.5% and, in intractable seizure patients, 55%, depression is epilepsy’s most common psychiatric comorbidity. Given those rates, many authors assert that physicians under-diagnose and under-treat depression in epilepsy patients.

Risk factors for comorbid depression include complex partial seizures, onset of epilepsy in late adult years, and, in most studies, frequent seizures. Ironically, several AEDs – levetiracetam, tiagabine, topiramate, and vigabatrin – carry a risk for depression and self-destructive behavior (see later). In contrast, a long history of epilepsy and the laterality of the seizure focus are weak risk factors. Some studies ironically associate depression with a failure of partial seizures to undergo secondary generalization – as though experiencing a generalized seizure ameliorates underlying depression.

Once depression complicates epilepsy, seizure frequency increases. For example, depression-associated behavior, such as sleep deprivation, noncompliance with an AED regimen, or substance abuse, precipitates seizures. Depressed patients may also consciously or unconsciously superimpose PNES on epileptic ones. Additionally, depressed epilepsy patients are more likely to require hospitalization than patients suffering from depression alone.

Whatever the cause, comorbid depression worsens epilepsy patients’ quality of life. It exerts a more powerful effect than the frequency of seizures, variety of seizures, use of AEDs, or toxicity of AEDs. It is also one of several risk factors for suicide (see later).

Physicians should direct initial therapy of comorbid depression not necessarily toward depression, but toward better seizure control. Seizure control will probably improve patients’ mood, reduce behavioral disturbances, and restore some cognitive function. Fortunately, several AEDs possess mood-stabilizing as well as anticonvulsant properties: carbamazepine (which bears a structural similarity to TCAs), lamotrigine, and valproate (valproic acid/divalproex). These AEDs raise serotonin levels.

Once patients and physicians achieve optimum seizure control, they may add antidepressants to their AED regimen; however, their use carries several caveats. While antidepressants improve patients’ mood, they will probably not further reduce the frequency of seizures. Because of their effect on cytochrome P450 enzymes, psychotropic drugs may render certain AEDs ineffective on one hand or toxic on the other (see later). In the situation of depression comorbid with epilepsy, for example, prescribing an enzyme-inhibiting antidepressant, such as fluoxetine, to an AED regimen of carbamazepine or phenytoin, may lead to toxic levels of the AED. Even some apparently benign, readily available substances may alter AED serum concentrations. For example, grapefruit juice can increase concentrations of carbamazepine and zonisamide, and St. John’s wort can decrease their concentrations. Not only do AEDs potentially cause adverse drug–drug interactions, AEDs alone or in combination with other medicines may induce mental status changes (see later).

Most importantly, psychotropics, perhaps more than any other class of medication, precipitate seizures in epilepsy patients. They even cause seizures in patients with no history of epilepsy. Risk factors for psychotropic-induced seizures generally include a history of epilepsy; other neurologic disorders, including Alzheimer disease and TBI; prior ECT; and drug or alcohol abuse.

Especially with an overdose, psychotropics induce seizures. TCAs lead to seizures in approximately 5–25% of overdose cases, and the incidence following overdose of amoxapine and maprotiline is even greater. Overdose-induced seizures most often appear within 3–6 hours, but almost never after 24 hours.

Psychotropic-induced seizures, in general, most often occur during the first week of treatment, following sudden large elevations in dose, or with regimens involving multiple medicines. With routine antidepressant treatment, the risk of seizures is typically dose-dependent. For example, the incidence of seizures with bupropion immediate-release formulations at up to 400 mg daily is less than 1%, but at higher doses, the incidence rises to unacceptable levels. In an exception, clomipramine led to seizures in 1.5% of patients taking 300 mg or less per day. This relatively high rate represents clomipramine’s most significant adverse reaction. Moreover, this risk does not diminish over time, as is the case with most other antidepressants.

In contrast to the relatively high rates of seizures associated with tricyclic and heterocyclic antidepressants, monamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and other serotonin-norepinephrine reuptake inhibitors produce seizures in less than 0.3% of cases. Overall, for practical purposes, most cases of antidepressant-induced seizures result from overdose.

As a supplement or an alternative to antidepressants, ECT can alleviate depression in epilepsy patients provided that their seizures are under control. It also helps depressed patients taking AEDs; however, physicians must sometimes reduce the AED regimen before ECT. The general rule is that psychiatrists can administer ECT to patients taking an AED.

Although prolonged seizures may unexpectedly follow ECT, that complication is rare and readily responds to AEDs. (On a historical note, ECT originated in the observation that depressed epileptic patients’ mood improved after a seizure. That benefit led to physicians inducing hypoglycemic seizures by injections of large amounts of insulin. Later attempts used electricity.)

Seizures have also complicated treatment with transcranial magnetic stimulation for medication-resistant depression.

Even though most psychotropic medicines in epileptic patients are generally safe, some words of warning are required. Despite all precautions, adding any psychotropic may increase seizure frequency. Physicians can reduce the risk by slowly introducing psychotropics, attempting to use low doses of a single medicine, checking for paradoxical effects and drug–drug interactions, and monitoring serum concentrations of medicines.

On the other hand, if a patient taking a psychotropic were to develop a seizure, physicians must guard against reflexively assigning the blame to it. For example, a brain tumor might be the cause of both the seizure and symptoms of depression. Similarly, a seizure in depressed patients may result from a deliberate medicine overdose or failure to take prescribed AEDs.

Not only is depression a comorbidity of epilepsy, it is a consideration in various epilepsy-related situations. For example, seizure-like episodes are occasionally a manifestation of depression or other psychiatric conditions (see later, psychogenic nonepileptic seizures). Also, chronic depression is a risk factor for a suboptimal outcome from epilepsy surgery.

Bipolar Disorder

Bipolar symptoms in epilepsy patients are uncommon, but occur more frequently than in either the general population or individuals with other medical disorders. When mania develops in epilepsy patients, they frequently display childish behavior, fluctuating moods, and rapid cycling. In addition to epilepsy patients who have comorbid bipolar disorder, epilepsy patients postoperative from temporal lobectomy, particularly right-sided procedures, and those with preoperative bilateral EEG abnormalities may develop mania. The positive response of bipolar disorder, with or without comorbid epilepsy, to AEDs should give a clue to its origin.

Anxiety

Various studies suggest that anxiety is comorbid with epilepsy in 20% to more than 60% of cases. Variable patients’ reports and physicians’ interpretations of the symptom may help explain the wide range in frequency. For example, in the face of an impending seizure, many patients are reasonably fearful and may panic. Additionally, a seizure’s aura may have anxiety-like components. In other cases, anxiety may be a manifestation of a generalized anxiety or panic disorder. Physicians may freely treat anxiety comorbid with epilepsy with benzodiazepines, as well as with antidepressants, because benzodiazepines have antiepileptic effects. However, abrupt withdrawal from benzodiazepines may precipitate seizures that lead to status epilepticus.

Psychosis

Besides being susceptible to postictal confusion, patients may develop a frank postictal psychosis. This thought disorder characteristically emerges after several hours to several days of clear sensorium and minimal symptoms (a “lucid interval”) following one or usually more seizures. It consists of hours to 2 weeks of hallucinations, delusions, agitation, and occasionally violence. Depending on its severity, patients usually require administration of benzodiazepines or antipsychotics.

The greatest risk factor for postictal psychosis is a preceding flurry of seizures – tonic-clonic, complex partial seizures, or both – in patients with chronic epilepsy. Up to 7% of complex partial seizures refractory to AEDs lead to postictal psychosis. Other risk factors include low intelligence, bilateral seizure foci, and a family history of psychiatric illness. Episodes of postictal psychosis, in turn, represent a risk factor for cognitive decline and interictal psychosis (see later).

Unlike postictal psychosis, interictal psychosis, loosely called “schizophreniform psychosis” or “schizophrenia-like psychosis of epilepsy” by neurologists, is a chronic condition. It generally arises when patients are 30–40 years old and their epilepsy began in childhood, especially between 5 and 10 years of age. In other words, interictal psychosis develops decades after the onset of their epilepsy. Its symptoms include persistent hallucinations, paranoia, and social isolation. Unlike typical schizophrenia patients, epilepsy patients with this interictal psychosis retain a relatively normal affect, do not deteriorate, and do not have an increased incidence of schizophrenia in their families.

Risk factors for interictal psychosis are childhood onset of epilepsy, physical neurological abnormalities, low intelligence, frequent seizures, multiple seizure types, seizures that require multiple AEDs, and episodes of postictal psychosis.

Patients with interictal psychosis also have neuropathological as well as clinical signs of brain damage. Their brains have large cerebral ventricles, periventricular gliosis, and focal damage. In an interesting comparison, multiple sclerosis (MS) patients, despite having equally extensive cerebral damage, rarely have these symptoms.

A related condition, which neurologists originally called forced normalization, followed a change in a patient’s AEDs regimen that completely suppressed abnormal EEG activity and eliminated long-standing seizures. Patients, then suddenly seizure-free, occasionally developed either psychosis or depression. Some researchers propose that the seizures, while troublesome, had suppressed a thought or mood disorder, perhaps through an ECT-like mechanism. Although the mechanisms surrounding forced normalization remain unclear, physicians should monitor patients who rapidly achieve complete seizure control. This caveat applies to epilepsy patients whose seizures suddenly come under control following epilepsy surgery or changes in their AED regimen.

In the opposite scenario, withdrawal-emergent psychopathology, after physicians or patients suddenly discontinue AEDs psychiatric disorders – particularly anxiety or depression – appear. (Although withdrawal-emergent psychopathology is a risk of suddenly stopping AEDs, status epilepticus is a much more frequent and life-threatening risk of abruptly stopping them.) Neurologists have postulated that, in patients with withdrawal-emergent psychopathology, the AEDs had suppressed a latent psychiatric disorder along with the epilepsy. Withdrawal-emergent psychopathology may also appear after epilepsy surgery – in this case because it allows patients to curtail, if not eliminate, their AED regimen.

In the preliminary version of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, (DSM-5), psychoses that occur during, immediately afterwards, or interictally would all fall into the category of Psychotic Disorder Associated with Another Medical Condition (epilepsy).

Many of the same rules apply to treating psychosis complicating epilepsy as to treating depression complicating epilepsy. Foremost, AEDs should remain the mainstay of treatment, but, if they alone are unsuccessful, neurologists or psychiatrists should add an antipsychotic. Another rule is that an overdose of an antipsychotic, just like an overdose of antidepressant, can lead to seizures. Among antipsychotics, an overdose of chlorpromazine is more likely than one of haloperidol, thioridazine, fluphenazine, or the newer atypical agents to cause seizures.

In therapeutic doses, antipsychotic-induced seizures are usually dose-dependent, occur with large increases in the dose, and develop more frequently in patients with epilepsy or underlying brain damage. In the therapeutic as well as the overdose range, chlorpromazine again remains most apt to provoke seizures. Except for clozapine, which leads to seizures in 4% of patients taking more than 600 mg daily, atypical antipsychotics carry a seizure risk of less than 1%.

Physicians forced to restart an antipsychotic following a medication-induced seizure should, while excluding other causes of psychosis and seizures, prescribe a different antipsychotic or slowly reintroduce the original one. If the patient requires clozapine or other seizure-inducing antipsychotic, physicians may offer some protection by simultaneously adding an AED.

Cognitive Impairment

Of individuals with either a congenital intellectual disability (which the preliminary version of the DSM-5 calls Intellectual Developmental Disorder, but neurologists persist in calling “mental retardation”) or cerebral palsy, 10–20% have comorbid epilepsy (see Chapter 13). In them, epilepsy usually appears before age 5 years and its incidence increases in proportion to their physical and intellectual impairments. Of individuals institutionalized because of these disorders, 40% have epilepsy. Also, children with autism and, more so, Rett syndrome are susceptible to seizures (see before).

When brain damage underlying seizures is progressive – as in tuberous sclerosis, storage diseases, mitochondrial encephalopathies, and some neurodegenerative illnesses – seizure control, cognitive capacity, and motor function all decline. Similarly, progressive cognitive decline or increasingly refractory seizures suggests a progressive rather than a congenital, static neurologic disorder. As with interictal psychosis, many risk factors for cognitive decline in epilepsy reflect underlying brain damage.

Many patients beset with complex partial seizures suffer increasingly severe cognitive impairment. Risk factors include longer duration of epilepsy, older age, and premorbid intellectual impairment. If epilepsy surgery or adjustment of AEDs controls their seizures, the cognitive decline may stop and partly reverse. However, if surgery does not arrest their seizures, their cognitive decline may accelerate. Moreover, unsuccessful surgery may lead to depression and other psychiatric disorders.

According to one explanation for the progressive cognitive impairment associated with complex partial seizures, underlying mesial temporal sclerosis leads to damage of the surrounding limbic system. Moreover, brief interictal EEG discharges in the temporal lobes probably disrupt memory and other cognitive processes.

Another, important explanation, which pertains to all seizure types and to children as well as adults, is that AEDs impair cognitive function (see later).

Destructive Behavior

Crime and Interictal Violence

The consensus among neurologists is that criminal violence cannot be a manifestation of a seizure. Instead, epilepsy-related factors – intellectual deficits, poor impulse control, and lower socioeconomic status – steer people toward crime but not violence. Studies have found that, although the incidence of epilepsy is at least four times greater among men in prison than in the general population, crimes of prisoners with epilepsy are no more violent than those with PNES. Similarly, the prevalence of epilepsy is the same in nonviolent criminals as violent ones. Also, EEG abnormalities do not correlate with violent offenses.

Interictal violence rather than ictal violence, which was discussed previously, usually consists of only verbal and minor physical acts. It occurs predominantly in epilepsy patients who are antisocial, schizophrenic, or mentally retarded. Epilepsy patients with interictal violence, compared to ones without it, show no differences in the variety or frequency of seizures, EEG abnormalities, or AED treatment.

In general, behavioral changes tend to develop in individuals with a history of epilepsy that had an early onset, seizures that undergo secondary generalization, and EEGs showing bilateral changes. Epilepsy patients with comorbid psychosis or mood disorders are particularly prone to show behavioral abnormalities.

Antiepileptic Drugs

Neurologists routinely prescribe AEDs as the primary treatment for epilepsy (Table 10-2). They generally prefer AED monotherapy to polytherapy (polypharmacy) because it minimizes side effects, noncompliance, and cost. However, when epilepsy remains refractory to monotherapy, neurologists usually add a second AED. Also, neurologists, occasionally thinking that small doses of two AEDs may be better than large doses of one AED, prescribe two AEDs. Nevertheless, only a minority of patients benefit from the addition of a second AED, and less than 5% benefit from the addition of a third one.

TABLE 10-2 Commonly Used Antiepileptic Drugs (AEDs)

N.B.: These AEDs have mostly replaced phenobarbital and its closely related AED, primidone (Mysoline), which both cause sedation, cognitive impairment, and depression. Also, barbiturates, particularly when used in children and adults with brain damage, may produce a “paradoxical reaction” of excitement and hyperactivity rather than sedation. On the other hand, most children with epilepsy and comorbid hyperactivity may safely use stimulants.

^*Recommended concentrations vary and should be altered depending on the clinical situation. Often a “subtherapeutic level” is sufficient, and increasing the dose will create side effects without improving seizure control.

^†To reach a steady state, five “half-lives” are required (e.g., carbamazepine 4–6 days; phenytoin 5–10 days; and valproate 3–6 days).

Neurologists refrain from instituting AED therapy following a first idiopathic seizure, which itself does not constitute epilepsy. Except for status epilepticus or other emergency situation, neurologists slowly initiate AED therapy.

AEDs can also paradoxically cause seizures. For example, carbamazepine and oxcarbazepine may induce hyponatremia severe enough to cause seizures. Also, toxic AED levels may cause seizures.

Vagus Nerve Stimulation

Vagus nerve stimulation (VNS), a technique for reducing refractory seizures, consists of an implanted pacemaker-like device that stimulates the cervical portion of the vagus nerve (cranial nerve X). VNS sends impulses upward along the vagus nerve’s afferent fibers to synapse in the medulla’s nucleus solitary nucleus, which projects to upper brainstem, hypothalamus, limbic system, and cortex (see Chapters 4 and 16). The vagus nerve seems the most appropriate conduit to the brain because it is readily accessible in its cervical portion, contains almost entirely afferent fibers but few pain-conveying ones, and carries, on the left side, few efferent cardiac fibers.

The VNS device regularly generates electric impulses, such as for 30 seconds every 5 minutes, which suppress seizures. In addition, when sensing an aura, the patient can activate the device and interrupt the seizure.

To a certain extent, VNS suppresses generalized and partial seizures in children and adults. Over 5 years, it reduces the mean seizure frequency by about 30%. In addition, VNS decreases AED requirements, but it does not eliminate them. For seizures with bilateral foci, VNS has almost completely replaced commissurotomy (see later). Neurologists suggest the procedure if multiple AED trials have failed in a patient for whom surgery would be inappropriate. Although VNS remains a credible therapy, patients must continue at least one AED and surgical resection remains more effective than VNS for seizures emanating from a single focus. VNS also reduces depression and anxiety comorbid with epilepsy.

Despite its benefits, VNS causes expectable side effects. In its most prominent one, the electrical stimulation briefly impairs the vagus nerve’s function. Thus, during activation, VNS often causes hoarseness and dyspnea.

Surgery

Under the appropriate circumstances, surgical removal of a cortical seizure focus with or without a surrounding portion of the brain has risen to the level of standard treatment. Although most patients who undergo surgery must continue taking an AED, approximately two-thirds of them enjoy a significant reduction in their seizures, if not their complete cessation. The surgical success rate is greatest for seizures emanating from mesial temporal sclerosis.

Neurologists have warned that the goal of epilepsy surgery is not to prevent the brain from generating seizures, but to allow AEDs to suppress seizures. If only by reducing the need for multiple or high doses of AEDs, surgery also often improves cognitive function and reduces comorbid depression and anxiety experience. When surgery controls epilepsy, patients enjoy great neuropsychologic benefits. Overall, surgery improves most patients’ quality of life.

With proper preoperative planning, surgeons can remove large areas of the temporal cortex and underlying hippocampus and amygdala without producing either language or memory impairment. Even with extensive resections, the surgical morbidity and mortality remain very low.

If epilepsy patients undergo three trials of appropriate AEDs at therapeutic doses that fail to suppress seizures, neurologists consider their epilepsy to be refractory. Children, adolescents, and adults who suffer from refractory epilepsy become candidates for surgery. For many refractory epilepsy patients with complex partial seizures, surgery offers unequivocal advantages over prolonged AED therapy even if it suppresses seizures.

Another surgical requirement for patients with refractory seizures is a single frontal or temporal lobe lesion clearly identifiable on clinical, EEG, and radiographic testing. In addition, if the lesion is located in their dominant hemisphere, patients often must also undergo a Wada test, functional MRI, or similar testing to determine if surgery might entail removal of a portion of the cerebral cortex that would lead to aphasia, amnesia, or other neuropsychologic problems (see Chapter 8). If both temporal lobes were injured from birth or during surgery, patients undergoing even a unilateral temporal lobectomy may suffer permanent amnesia or the Klüver–Bucy syndrome (see Chapters 12 and 16).

Despite the substantial benefits that epilepsy surgery offers, patients risk several postoperative complications. During the first 2 postoperative months, many patients experience depression, mania, and personality changes. The depression persists well beyond the postoperative period in about 10% of patients. It occasionally complicates surgery that completely eliminates seizures as well as less successful surgery. The depression’s origin remains speculative. Some investigators attribute it to the discontinuation of AEDs that had been suppressing psychiatric symptoms, as well as seizures, or the sudden complete seizure control causing a forced normalization. Also, loss of ECT-like effect of seizures may play a role. Psychologically oriented investigators note that the “cure” of patients’ chronic illness deprives them of their family’s attention and ability or “excuse” to avoid various obligations.

A different and more invasive procedure may rarely be indicated in individuals with intractable bilateral frontal seizures or infants with atonic seizures (“drop attacks”) who have no readily resectable seizure focus. In a commissurotomy or corpus callosotomy, a neurosurgeon longitudinally severs the anterior two-thirds or entire corpus callosum, interrupting the spread of discharges between cerebral hemispheres. Because it “splits” apart the cerebral hemispheres, this procedure may cause the split-brain syndrome (see Fig. 8-9).

Rolandic Epilepsy

Rolandic epilepsy (childhood epilepsy with centrotemporal spikes), the most common form of partial epilepsy in childhood, almost always begins between ages 5 and 9 years, occurs mostly in boys, and remits by puberty. The seizures consist of unilateral paresthesias, movements of the face, and speech arrest. They tend to undergo secondary generalization during sleep. Interictal EEG changes consist of high-voltage spikes in the central temporal region (Rolandic spikes) during sleep. AEDs usually suppress the seizures, though many neurologists favor nonaggressive pharmacologic therapy for this self-limited epilepsy syndrome.

Unlike other partial epilepsies, Rolandic seizures are restricted to childhood, not associated with an underlying structural lesion, and inherited (in an autosomal dominant pattern). In contrast to children with absences (see later), those with Rolandic epilepsy are not at risk of eventually developing other varieties of epilepsy.

Absences

Absences usually begin between ages 4 and 10 years and disappear in early adulthood. The seizures, which may occur many times daily, consist of 2–10-second lapses in attention, often accompanied by automatisms, subtle clonic limb movements, or blinking (Fig. 10-11). The blinking sometimes occurs rhythmically at 3 Hz, which is the frequency of the associated EEG abnormality. During the seizure, children maintain muscle tone and bladder control; however, they cannot carry on mental and physical activities. If they suffer from frequent seizures, children may appear inattentive, dull, or even mentally retarded. After a seizure, as though it had never occurred, children have no retrograde amnesia, confusion, agitation, or sleepiness.

FIGURE 10-11 Seen in the midst of an absence, this 8-year-old boy has staring that has suddenly and unexpectedly interrupted his playing with a friend. He has become glassy-eyed and mute, his eyes have rolled upward, and he blinks at 3 Hz. Although he has lost consciousness, he maintains bodily tone and does not become incontinent. At the end of his seizure, which will last for only 2–10 seconds, he will resume playing and be unaware of the pause.

Absence status epilepticus typically leads to a several-hour episode of apathy, psychomotor retardation, and confusion. Such an attack usually develops in children or young adults with a history of absences or other seizures who suddenly stopped taking their AEDs. Absence status epilepticus in any age group mimics acute psychosis. If an EEG confirms a clinical diagnosis of absence status epilepticus, intravenous benzodiazepine will abort it.

EEG, Etiology, and Treatment

During an absence, the EEG shows synchronous 3-Hz spike-and-wave complexes in all channels (Fig. 10-12). Even in the interictal period, an EEG reveals occasional asymptomatic bursts of 3-Hz spike-and-wave complexes lasting 1–1.5 seconds. This discharge reflects an underlying abnormality in the reciprocal circuits between the thalamus and the cerebral cortex.

FIGURE 10-12 Absences are often so brief and liable to be confused with either inattention or complex partial seizures that neurologists often attempt to precipitate them for diagnostic purposes in an EEG laboratory. One common practice consists of asking a child suspected of having absences to count numbers slowly while hyperventilating. An absence would be evident when the counting pauses and the EEG shows regular, symmetric, and synchronous 3-Hz spike-and-wave complexes arising from and returning to a normal EEG background – as in this reproduction.

In patients with absences, either hyperventilation or photic stimulation can precipitate the characteristic clinical and EEG abnormalities. Just as the EEG abnormality reflects generalized cerebral dysfunction, PET scans performed during absences show increased metabolism in the thalamus and the entire cortex.

Patients’ relatives often also have absences or 3-Hz spike-and-wave complexes that can be precipitated by hyperventilation. This finding supports the hypothesis that patients inherit a predisposition in an autosomal dominant pattern. In contrast to tonic-clonic seizures, absences are not associated with drug withdrawal, metabolic aberrations, or structural lesions. Therefore, as a general rule, CTs and MRIs are not indicated in evaluating children with absences.

Neurologists usually prescribe ethosuximide for absences in children. About two-thirds of them enjoy a permanent remission during adolescence. In the others, tonic-clonic seizures frequently replace absences.

Although absences bear a superficial resemblance to complex partial seizures, physicians should distinguish the two conditions by their different manifestations, EEG abnormalities, prognoses, and treatments (Table 10-3).

TABLE 10-3 Comparison of Partial Complex and Absence Seizures

Feature	Partial Complex	Absence
Aura	Often	Never
Consciousness	Impaired	Lost at onset
Movements	Usually simple, repetitive, but may include complex activity	Blinking and facial and finger automatisms
Postictal behavior	Amnesia, confusion, and tendency to sleep	No abnormality, except amnesia for ictus
Frequency	1–2 per week	Several daily
Duration	2–3 minutes	1–10 seconds
Precipitants		Hyperventilation, photic stimulation
Electroencephalogram	Spikes and polyspike and waves, usually over one or both temporal regions	Generalized 3-Hz spike-and-wave complexes
Antiepileptic drugs	Carbamazepine, phenytoin	Ethosuximide, valproate

Tonic-Clonic Seizures

Even though they are both varieties of generalized seizures and share, at their onset, the characteristic loss of consciousness and generalized EEG abnormalities, tonic-clonic and absence seizures have completely different clinical manifestations, treatment, and prognosis. Tonic-clonic seizures begin at any age after infancy, persist through adult life, and cause massive motor activity and profound postictal residua. Although patients may have a prodrome of malaise or a depressed mood, tonic-clonic seizures usually arise as an unheralded explosion. In the initial tonic phase, patients lose consciousness, roll their eyes upward, and, as if to form a back-bending arch, extend their neck, trunk, and limbs. Immediately afterwards, in a dramatic clonic phase, patients violently and symmetrically jerk their limbs, neck, and trunk (Fig. 10-13).

FIGURE 10-13 A, This man in the tonic phase of a tonic-clonic seizure arches his torso and extends his arms and legs. He assumes this position because of the relatively greater strength of the extensor muscles compared to the flexor muscles. Simultaneous diaphragm, chest wall, and laryngeal muscle contractions force air through his tightened larynx to produce the shrill “epileptic cry.” During this phase, he may also bite his tongue and lose control of his urine. B, In the clonic phase, his head, neck, and legs contract symmetrically and forcefully for about 10–20 seconds. Saliva, aerated and often blood-tinged from tongue lacerations, froths from his mouth. His pupils dilate and he sweats profusely. Finally, his muscular contractions lose strength. The seizure usually ends with stertorous breathing. In the immediate postictal period, he remains unresponsive. Before regaining consciousness, he often passes through a state of confusion and agitation, loosely termed “postictal psychosis.”

A potential diagnostic problem is that, during this terrible episode of tonic-clonic movement, a primary generalized seizure resembles a partial seizure that has undergone secondary generalization. Often only a detailed history, a trained observer, or an intraictal EEG can distinguish between them.

If electronic filters could eliminate the superimposed muscle electric artifact during the tonic phase, the EEG would show repetitive, increasingly higher-amplitude spikes occurring with increasing frequency in all channels. Then, in the clonic phase, slow waves would interrupt the spikes, which usually decrease in frequency (Fig. 10-14).

FIGURE 10-14 During a tonic-clonic seizure, the EEG ideally shows paroxysms of spikes, polyspikes, and occasional slow waves in all channels; however, muscle artifact can obscure this pattern. Even during interictal periods, the EEG contains multiple bursts of generalized spikes in the background. In contrast to occasional temporal lobe spikes, this pattern confirms a diagnosis of epilepsy in patients with seizures.

After the clonic phase, the EEG shows postictal depression. The postictal EEG is often the only one available, but it can support the diagnosis. Similarly, after ECT, EEG activity slows. After most tonic-clonic or ECT-induced seizures, as well as after approximately 40% of complex partial seizures, the serum prolactin concentration rises for 10–20 minutes. The postictal change also carries diagnostic value – and in both directions. In particular, a lack of prolactin elevation after an apparent tonic-clonic seizure casts doubt on its having been an epileptic seizure.

About 50% of patients with tonic-clonic seizures have interictal asymptomatic, brief bursts of spikes, polyspikes, or slow waves on the EEG. Photic stimulation or hyperventilation may precipitate seizures and accompanying EEG abnormalities.

Febrile Seizures

Febrile seizures, occurring at least once in 2–4% of all children, are the most common variety of childhood seizure. These seizures usually last less than 30 seconds and lack focal findings. Older literature suggested that febrile seizures often cause mesial temporal sclerosis, which in turn would lead to complex partial epilepsy. Recent studies demonstrate that children experiencing brief febrile seizures have little or no increased risk of complex partial seizures, but that febrile status epilepticus may be a risk factor for epilepsy.

Pediatricians and neurologists, in the past, would routinely prescribe prophylactic phenobarbital or valproic acid for febrile seizures. However, those and other AEDs not only provided little protection, they impaired cognitive function and produced hyperactivity. Today, pediatricians and neurologists sometimes recommend oral or rectal diazepam only when fevers develop to prevent febrile seizures.

Nonepileptic Psychogenic Seizures

The epilepsy community, with some dissenters, has changed the term psychogenic seizures or attacks to psychogenic nonepileptic seizures (PNES). Using “attack” instead of “seizure” in this setting, the dissenters suggest, would more accurately describe the event and not endow it with a medical aspect. Moreover, PNES lacks the punch of the original. All this being said, this book conforms to current nomenclature, PNES.

Using the preliminary version of DSM-5, psychiatrists will probably diagnose most patients with PNES as having a Conversion Disorder (Functional Neurologic Symptom Disorder), but sometimes a pseudoneurologic symptom of a Somatic Symptom Disorder or simply a Factitious Disorder.

PNES occur 5–10% as frequently as epileptic ones, and usually develop in females aged 19–35 years, relatives of patients with epilepsy, and individuals reporting a history of abuse. On several occasions, a group of individuals – particularly families, classmates, or friends, especially female adolescents – has simultaneously or in succession succumbed to seizure-like episodes. The neurologic literature terms small epidemics of seizure-like episodes or similar disturbances “mass hysteria.”

As with epileptic seizures, PNES tend to be stereotyped for the individual. The most important difference is that, despite the apparently generalized nature of PNES, patients retain consciousness throughout them. Also, patients with PNES often demonstrate slow development of limb movements without a preceding tonic period. Once the nonepileptic seizure starts, patients frequently rock their head from side to side and move their pelvis with suggestive thrusts. They forcefully close their eyes and, if medical personnel place them on their side, as if to prevent aspiration, they look downward. They will even look downward if rocked from side to side. When patients speak, they often stutter or stammer.

Sometimes, as in epileptic seizures, PNES patients bite their lip or tip of their tongue, urinate on themselves, or bang their head or limb. As fatigue ensues, the movements decline in intensity and regularity, but often resume after rest. The duration of PNES – typically 2–5 minutes – exceeds that of the average epileptic seizure. Studies have shown that patients bringing along a stuffed animal, particularly a teddy bear, to their continuous EEG-video monitoring, is a positive predictive indicator for PNES.

Unless they deliberately mimic an epileptic seizure, PNES patients recover their attentiveness and motor function immediately after the movements. Most patients have no lingering confusion, headache, retrograde amnesia, or hemiparesis. In short, postictal symptoms do not follow most PNES.

During a PNES, EEGs would ideally be normal, but muscle movement artifacts obscure the recording. An EEG after the episode, which is more feasible, would lack the usual postictal depression. Also, unlike following an epileptic seizure, the serum prolactin concentration remains normal.

If routine testing fails to provide a diagnosis, continuous EEG-video monitoring would probably differentiate psychogenic nonepileptic from epileptic seizures. The portion of the monitoring obtained during sleep is especially important because epileptic seizures – not nonepileptic ones – often arise from genuine sleep.

The extremes – often a burlesque – are readily identifiable. Nevertheless, several subtle diagnostic pitfalls remain. PNES can be quite convincing. They can include urination, tongue biting, and, in as many as 20% of cases, deliberate or inadvertent self-injury. Applying only clinical criteria, the distinction between psychogenic nonepileptic and epileptic seizures in most studies is no more than 80–90% accurate.

Another pitfall remains as to whether patients with PNES also have epileptic ones. Although only 5–10% of adult patients with PNES have comorbid epileptic seizures, 25–40% of children with PNES have comorbid epileptic seizures. In cases when these seizures are comorbid, epilepsy patients’ psychogenic seizures so closely mimic their epileptic seizures that physicians must perform continuous EEG-video monitoring to distinguish them. The combination of psychogenic nonepileptic and epileptic seizures may occasionally explain “refractory epilepsy.” Still another pitfall is that some frontal lobe and complex partial seizures produce such bizarre behavior that neurologists might summarily decide that the patient has a psychiatric condition.

Compared to patients with epileptic seizures, those with PNES, whether or not they also have epileptic ones, fare poorly. Although psychiatric intervention often helps patients with many different psychogenic neurologic symptoms, such as psychogenic hemiparesis, it provides little benefit to those with psychogenic seizures. PNES are usually refractory to psychotherapy, psychotropics, and AEDs. Potentially helpful approaches include cognitive-behavioral therapy and treatment directed at psychiatric comorbidities, such as depression, rather than the seizures themselves. In general, psychogenic nonepileptic seizure patients remain at least partially dependent on caregivers and their quality-of-life ratings are especially low. They remain as disabled as if they had epilepsy. Risk factors for persistent PNES have been anxiety, depression, receiving Social Security payments, and female gender.

Episodic Dyscontrol Syndrome/Intermittent Explosive Disorder

The episodic dyscontrol syndrome – roughly equivalent to Intermittent Explosive Disorder in the preliminary version of DSM-5 – usually consists of violently aggressive, primitive outbursts, including screaming, punching, wrestling, and throwing objects that injure people or destroy property. Minor stimuli, such as verbal threats, anger, or frustration, especially after consuming even small amounts of alcohol, often trigger episodes; however, if alcohol “fully accounts” for the episodes, the preliminary version of DSM-5 would not include them as an Intermittent Explosive Disorder. A highly charged affect often precedes and accompanies the outburst. After it, patients typically claim justification, repentance, or amnesia for the event.

In contrast to violent complex partial seizures (see above), which are rare, episodic dyscontrol episodes are nonstereotyped, at least momentarily purposeful, and highly emotional. Furthermore, the episodes have a clear directed and aggressive intent. They occur predominantly in young men who have congenital malformations or TBI, borderline intelligence, and minor physical neurologic abnormalities. Many have interictal EEG abnormalities. Although the neurologic community does not equate episodes of episodic dyscontrol syndrome or Intermittent Explosive Disorder with seizures, neurologists generally agree with the use of AEDs as mood stabilizers.

Driving

The motor vehicle accident rate of epilepsy patients compared to the general population is sevenfold greater. Not only might they have seizures while driving, the AEDs can make them sleepy enough to cause traffic accidents. Epilepsy patients also have increased rates of traffic violations, including driving under the influence of alcohol or drugs. As in the general population, automobile accidents are most closely associated with male drivers younger than 25 years.

Almost all states require a waiting period for a driving license or renewal after having a seizure, but modifications are sometimes allowed for seizures arising from an isolated medical illness, such as hypoglycemia, and for those with a prolonged aura. Most states set a waiting period of 3–12 months, but several, including New York and California, allow some flexibility for noncommercial driving. They also require applicants to reveal any history of seizures or loss of consciousness (for any reason). In addition, several states require physicians to report drivers with seizures (“mandatory physician reporting”).

Although many patients with epilepsy die suddenly and unexpectedly, certain activities represent known hazards. Drowning is probably the most common cause of accidental death. In addition, during their seizures, patients sometimes sustain nonlethal injuries, such as head trauma, limb dislocations, lacerations, and ocular injuries.

Alcohol

Drinking alcoholic beverages in moderation should not give rise to seizures in epileptic patients. On the other hand, AEDs will not prevent seizures that arise from alcohol abuse or withdrawal, mostly because, when people drink, they usually neglect to take their medicines. Even if they do, AEDs will not prevent such seizures. Thus, neurologists do not prescribe long-term AEDs to alcoholics prone to alcohol-withdrawal seizures. If one were to occur, benzodiazepines, probably because of their similarity to alcohol, act as an effective AED.

Cerebrovascular Disturbances

TIAs resemble partial seizures because both may cause momentarily impaired consciousness and physical deficits (see Chapter 11). In general, however, TIAs have slower onset and rarely cause loss of consciousness.

Of the various cerebrovascular disturbances, transient global amnesia (TGA) most closely resembles complex partial seizures (see Chapter 11). During a TGA episode, a frequent cause of transient amnesia (see Box 7-1), patients cannot remember new information, such as the date, location, and examining physicians; however, they retain basic memories, such as their name, address, and telephone number. This discrepancy separates TGA from psychogenic amnesia, in which basic as well as new information is lost.

During TGA, EEGs may show spikes, but not paroxysmal bursts, typically emanating from a temporal lobe. MRIs may show bilateral temporal lobe abnormalities indicative of ischemia. Because physicians rarely see a patient during the amnestic episode and reliable diagnostic laboratory data do not exist, they must diagnose TGA, although with some uncertainty, by its clinical features.

Migraines, which also partly result from vascular disturbance, may induce episodes of confusion and personality change followed by a tendency to sleep (see Chapter 9). Migraines particularly mimic seizures when they lead to transient hemiparesis and abnormal EEGs. In fact, migraine patients have a greater than usual incidence of seizures, making migraines a risk factor for epilepsy. The diagnosis of migraines relies almost entirely on the patient’s history.

Sleep Disorders

Bizarre behavior during the night might represent a sleep disorder (see Chapter 17) rather than a nocturnal seizure. Some sleep disorders so closely mimic seizures that only polysomnography or continuous EEG-video monitoring can distinguish them. For example, children might have a night terror or another parasomnia, and older adults are liable to develop REM behavior disorder. In patients who experience repeated bouts of unresponsiveness, the narcolepsy-cataplexy syndrome, which includes several seizure-like symptoms, such as momentary loss of body tone (cataplexy) and dream-like hallucinations, represents a diagnostic alternative to seizure disorder. Unlike seizures, the narcolepsy-cataplexy syndrome has no aura, motor activity, incontinence, or subsequent symptoms. Moreover, during attacks of narcolepsy, an EEG or polysomnography shows REM activity.

Metabolic Aberrations

Of the various metabolic aberrations that can mimic seizures, reactions to medicines are probably the most common. Many medicines, including some administered as eyedrops, produce transient mental and physical alterations; however, they almost never induce stereotyped movements or thoughts.

Hyperventilation commonly induces giddiness, confusion, and other psychologic symptoms that can be confused with seizures (see Chapter 3). When prolonged and deep, hyperventilation may precipitate seizures, but probably only in epileptic individuals.

Hypoglycemia, which can result from excessive insulin, alcohol intoxication, skipping meals, and prediabetic states, can induce anxiety and seizure-like symptoms. Similar disturbances occur with excessive coffee intake. Although the severity and frequency of these symptoms are probably overestimated, small, frequent meals and reduction of caffeine consumption should remedy most cases.

Sudden Unexplained Death in Epilepsy (SUDEP)

Neurologists define SUDEP as “sudden, unexpected, witnessed or unwitnessed, nontraumatic, and nondrowning death in epilepsy, with or without evidence for a seizure and excluding documented status epilepticus, in which postmortem examination does not show a toxicological or anatomical cause for death.” Although SUDEP represents a significant mortality cause – up to 17% in one study – in this population, neurologists have a poor understanding of its mechanism. Studies have shown that frequent generalized tonic-clonic seizures are a risk factor for SUDEP and they suggest that autonomic abnormalities during seizures and respiratory difficulties from seizures clustering in sleep may be responsible for the fatalities.