Nonepileptic Events
Nicholas J. Beimer
Linda M. Selwa
INTRODUCTION
Nonepileptic events are transient episodes, symptoms, or experiences that mimic epileptic seizures but are not the result of abnormal hypersynchronous neuronal activity. There are two main categories of nonepileptic events: behavioral and physiologic. Behavioral nonepileptic events include diagnoses such as psychogenic nonepileptic seizures (PNES), attentional staring spells, malingering, factitious disorder, panic disorder, and posttraumatic stress disorder (PTSD). Physiologic nonepileptic events are due to abnormal physiologic changes that impair normal cortical function and can be due to either neurologic or nonneurologic diagnoses. Examples of physiologic nonepileptic events include syncope, elevated intracranial pressure (ICP), abnormal-appearing behaviors or events in critical illness, delirium, metabolic derangements, intoxication, migraine, hyperkinetic movement disorders, sleeprelated nonepileptic events, sleep-disordered breathing, and breath-holding spells.
BEHAVIORAL NONEPILEPTIC EVENTS
Psychogenic Nonepileptic Seizures
PNES are episodes of abnormal movements, sensations, or experiences that mimic epileptic seizures, due to underlying psychological conflict that is often associated with traumatic life experiences and other diagnoses such as anxiety, depression, and personality disorders.1 PNES fall under the category of functional neurologic symptom (conversion) disorders in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.2 In contrast to epileptic seizures, PNES are not caused by abnormal hypersynchronous neuronal activity, and there is no abnormal EEG correlate during these events.3
The semiology of PNES is just as variable as that of epileptic seizures. Some patients describe being completely conscious, while others appear unconscious and do not show any signs of awareness during the event, even with external stimulation. Memory may persist variably around the time of the event, sometimes with amnesia just for the event itself while others can recall details before, during, and afterward. Some have partial control of bodily actions during the events, while others feel they have no control whatsoever.4 Despite significant variability, there are clinical signs that favor events being PNES, including long duration, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movements during convulsive events, eye closure, ictal crying, and memory recall. Frontal lobe seizures are also possible for events with asynchronous movements, pelvic thrusting, or bizarre behavior that would seem to suggest a psychogenic origin. Signs that favor epileptic seizures include onset of the event from EEG-confirmed sleep, postictal confusion, and abnormal breathing associated with convulsions. There is insufficient evidence for the utility of other signs such as gradual onset, nonstereotyped events, flailing/thrashing, opisthotonus, tongue biting, or urinary incontinence as favoring either PNES or epileptic seizures.5
A misconception about PNES is that patients consciously “fake” their events. In fact, PNES are generally not under volitional control. This feature distinguishes PNES from diagnoses such as malingering or factitious disorders, in which an individual has a conscious motivation for and control during the event (see below).6 This misconception may arise from the outdated term “pseudoseizure,” which is misleading due to the prefix pseudo-, meaning false. This is an important distinction, as the approach is very different when the patient produces symptoms intentionally for secondary gain. Health care professionals who inappropriately treat PNES patients as if they are faking symptoms will destroy rapport and erode patient confidence in their physician and the health care system.7 Ultimately, individuals suffering from
PNES have the best outcomes when approached with compassion. Fortunately, effective treatment approaches for PNES are in development.
PNES have the best outcomes when approached with compassion. Fortunately, effective treatment approaches for PNES are in development.
Current treatments under investigation for PNES include cognitive behavioral therapy (CBT)-based psychotherapy,8 mindfulness-based interventions,9 prolonged exposure therapy,10 and group-based therapy.11 There are also ongoing randomized clinical trials examining outcomes including seizure frequency and severity, psychological distress, psychosocial functioning, quality of life, use of health services, and cost-effectiveness of treatment.12 From these studies, readily available tools now exist for use by practitioners from diverse training backgrounds (Case 23.1).13
The gold standard for diagnosis of PNES involves capturing an event during inpatient long-term video-EEG monitoring after tapering off all antiseizure medications, with evidence of a normal EEG background before, during, and after a typical event.5 Weaning off antiseizure medications is important as this may unmask interictal epileptiform activity (IEA), which should raise suspicion for epilepsy but does not exclude a diagnosis of PNES. IEA may not appear until months later, so in cases where there is a high suspicion for epilepsy, repeating an EEG to look for IEA may also be helpful.14 An important caveat is that a normal EEG is not sufficient for the diagnosis of PNES, since focal seizures may not have an associated ictal EEG pattern, as with focal aware or frontal lobe seizures. If the semiology appears atypical for PNES or suggests a seizure type with no ictal EEG correlate, video-EEG data alone may not exclude a diagnosis of epilepsy. Other clinical data, including the clinical context, risk factors for epilepsy or PNES, and results of other testing may be required to make the diagnosis.
CASE 23.1
A 30-year-old woman with a history of fibromyalgia, migraines, and events of tingling and discomfort in the hands and feet, followed by unresponsiveness, rigidity, and shaking movements, presents for diagnostic long-term EEG monitoring. She is currently being treated with antiseizure medications for these events, including clonazepam, lamotrigine, and oxcarbazepine. Two typical events occurred on the 2nd day of admission. Figure 23.1 shows the EEG during selected periods of the event, which began with eye fluttering and decreased responsiveness, followed by eye closure, body stiffening, and rotation to the left, then irregular tremulousness involving the hands and a “no no” motion of the head, along with back arching and extensor posturing of the arms and wrists. Throughout the event, the patient had chewing movements of the mouth, which were not typical of automatisms. The event ended with the described movements stopping and the patient becoming responsive to questions. Electrographically, parts of the EEG recording appeared rhythmic, but were consistent with movement artifact on video. When the movement artifact was not present, there was a normal awake EEG background.
If a patient reports numerous daily episodes, a short-term (1-6 hours) or routine 30-minute EEG may be an effective way to capture the events in question.15 However, inpatient long-term video-EEG monitoring is the gold standard, and preferred when epilepsy appears likely, there are multiple nonstereotyped semiologies, or events are nocturnal.16 Ambulatory EEG recordings are not as effective for diagnosis of PNES for several reasons: a cognitive assessment is not possible during the clinical event, technical artifact may limit the quality and interpretation of the EEG, antiseizure medications cannot be discontinued, and there may not be a satisfactory video recording of the clinical event.
In the absence of other pathology, the EEG before, during, and after a PNES should be normal as in Figure 23.1. The posterior dominant rhythm (PDR) is often seen during PNES because eye closure is a common feature (Fig. 23.1, panels A and B).4 There may be significant myogenic and rhythmic movement artifact during convulsivelike activity, which can make the interpretation challenging. Setting the high-frequency filter to 15-30 Hz may help remove some of the highfrequency myogenic artifact and allow better visualization of the underlying cerebral rhythm. At times, filtered rhythmic artifact may resemble ictal discharges, so careful attention to the presence or absence of evolution and to the brief periods of background between the movements is necessary to make the diagnosis. If a rhythmic-appearing pattern develops with filtering, recall that this may be due to an aliasing effect and may not represent an underlying cerebral rhythm.17 Periods of rhythmic activity on EEG should correlate with any physical movements noted on video, such as thrashing or head shaking (see movement artifact in Fig. 23.1, panel C). The physical movements during PNES can cause time-locked rhythmic activity on EEG that can mimic abnormal findings, such as rhythmic delta activity. Because the convulsivelike movements in PNES can occur in an irregular stop-start fashion, it is important to examine the underlying rhythm during the interval between movements, which may be the only time the EEG is interpretable.
The same provocative measures used for induction of epileptic seizures, such as hyperventilation and photic stimulation, can serve as a psychological suggestion to elicit and capture PNES.18 Other techniques for provoking PNES have included application of alcohol pads to an area of skin or placebo injections of saline, with the suggestion that these are activating substances that will induce seizures. However, these techniques may trigger atypical events19 and may impair the therapeutic relationship, despite subsequent explanation to the patient. In addition, intentional deception carries significant risk of psychological harm.20
PNES only occur during wakefulness, but can occur shortly after arousal from sleep. When suspected PNES occur at night from apparent sleep, it is important to
distinguish whether there is an arousal before the event.21 Events that occur directly from sleep on EEG should make one think of other causes. For example, frontal lobe onset seizures can occur from sleep and lack a significant scalp EEG correlate.22
distinguish whether there is an arousal before the event.21 Events that occur directly from sleep on EEG should make one think of other causes. For example, frontal lobe onset seizures can occur from sleep and lack a significant scalp EEG correlate.22
Testing responsiveness and memory during an event is important. To test memory, ask the patient to remember a unique phrase, such as a color and object combination. If the phrase occurs when the patient appears unconscious, but the EEG background shows normal wakefulness, the inability to recall the memory cue afterwards is consistent with PNES. However, not all patients are amnestic during PNES, and PNES patients are much more likely to recall a memory cue compared to those with focal impaired awareness seizures.23
Interpretation of the single-lead electrocardiogram (EKG) included in standard EEG recording during suspected PNES is important when the differential
diagnosis could include either epileptic seizures or syncope. Like the EEG, the EKG should show a normal physiologic rhythm before, during, and after the event. Ictal tachycardia during unresponsiveness is characteristic of epileptic seizures but can also occur in PNES.24 Bradyarrhythmias or asystole during the clinical event without an associated ictal pattern on EEG suggests a cardiogenic cause.
diagnosis could include either epileptic seizures or syncope. Like the EEG, the EKG should show a normal physiologic rhythm before, during, and after the event. Ictal tachycardia during unresponsiveness is characteristic of epileptic seizures but can also occur in PNES.24 Bradyarrhythmias or asystole during the clinical event without an associated ictal pattern on EEG suggests a cardiogenic cause.
Patients with PNES often describe nonstereotyped events. This creates a challenge in taking the history because we usually try to group events or sets of symptoms into different seizure types or semiologies, for example motor, nonmotor, etc. The challenge is to capture and characterize all event types during video-EEG recording, which reassures both patient and clinician that testing has been thorough and that diagnostic uncertainty is minimal. Practically, this may require additional EEG monitoring if the initial recording did not capture all semiology types. When there is doubt, repeated monitoring can be helpful, as in Case 23.2 below, which led to a mixed diagnosis of both PNES and epilepsy.
The video-EEG recording is useful not only for determining the diagnosis of PNES but also for presenting the diagnosis to the patient. Showing the recorded event to the patient while discussing the diagnosis allows the patient to witness a spell, possibly for the first time. Reviewing the video with witnesses can confirm capture of the target event and that no other spell types remain undocumented. Viewing the EEG and video together begins the process of educating the patient and family about the difference between epileptic and PNES.25 The transparency of showing the actual test results to the patient may help validate the experience, build rapport, and improve acceptance of the diagnosis.
CASE 23.2
A 53-year-old woman presents with 1 year of episodes of muscle spasms in the left leg, which spread to the back and neck and then develop into arching and slow movements of the left leg. During this time, she remains conscious but is verbally unresponsive and unable to control her actions for 10-15 seconds. The patient underwent resection of a right frontal meningioma about 3 months prior to the onset of symptoms. She had a significant early childhood history of abuse. Short-term EEG monitoring captured a typical event, during which there was no abnormal EEG correlate (Fig. 23.2). The only interictal EEG abnormality was a breach rhythm over the right centroparietal region. Levetiracetam was discontinued due to a suspected diagnosis of PNES. About a week later, she developed a new event type, which began with left leg jerking that slowly ascended the body over 20-30 minutes, eventually ending with loss of consciousness, eyes rolling back, and foaming of the mouth. This event recurred 2-3 times over several hours. Long-term EEG monitoring subsequently captured the event in question, which was in fact an epileptic seizure that lasted for 30 minutes, consistent with status epilepticus (see Fig. 23.3). The interictal EEG was also different from the short-term EEG recording when the patient was taking levetiracetam, as there were new right centroparietal (C4 and P4) sharp waves.
REVIEW
23.1: A 24-year-old woman presents with a history of seizures in elementary school and new-onset weekly diffuse shaking spells that are different from her old episodes. She takes levetiracetam but continues to have events. She prefers the least troublesome evaluation but the most accurate diagnosis. The best diagnostic test for her would involve:
a. 24-hour home EEG with video
b. Short-term monitoring in the EEG lab with alcohol pad application
c. Long-term EEG monitoring with medications tapered off
d. Long-term EEG monitoring during the day with medications continued
View Answer
23.1: c. The events are too infrequent to be captured with a 24-hour ambulatory EEG, and an induced event in the EEG lab triggered by suggestion may not be her habitual event. Tapering off medications is the best way to increase the likelihood of recording both epileptic and nonepileptic events.
Malingering and Factitious Disorders
Malingering and factitious disorders may underlie intentionally feigned nonepileptic events associated with conscious motivation.2 However, these disorders are quite uncommon causes of PNES. Malingering is simulating symptoms for secondary gain. An expert survey of neuropsychologists found that the prevalence of malingering in medical or psychiatric referrals not involving litigation or compensation was about 8%.26 Factitious disorder, in which the patient feigns symptoms to assume the patient role without secondary gain, is even more uncommon. A review of 1288 patients referred to a psychiatric consultation-liaison service found factitious disorder as the diagnosis in only 0.8% of cases.27 In contrast, PNES are common, diagnosed in up to a third of all epilepsy monitoring unit (EMU) admissions.28
For malingering, the motivation for this behavior is an external reward, such as acquiring sedative or hypnotic substances (eg, benzodiazepines) or escape from responsibility (eg, work, mandatory court appearance, examinations, jail time, etc.). In factitious disorders, there is no obvious external reward for the behavior other than assuming the sick role. A diagnosis of malingering requires identifying the reward for the behavior, which may be obvious from the clinical history. Videos of typical events may also provide clues to the diagnosis. As with PNES, the EEG in malingering and factitious disorders is normal before, during, and after the clinical event. Consultation with a psychiatrist and/or psychologist may be helpful when malingering or factitious disorders are likely diagnoses (Case 23.3).
Nonepileptic Staring
Nonepileptic staring, or “staring spells,” occurs frequently in pediatric populations but can also happen in adults. It can be due to inattention or daydreaming but may mimic absence seizures or focal unaware seizures. Nonepileptic staring does not present with oral automatisms, myoclonus, or eyelid blinking, unlike epileptic seizures.29 There is usually normal posture during the event, and a blank, motionless facial expression is characteristic. Nonepileptic staring may occur more often during boredom or inactivity and rarely occur during physical activity. The length is variable, lasting from seconds to minutes, and spells usually stop with tactile or vocal stimulation, which can distinguish nonepileptic staring from absence seizures.30 Waving a hand in
front of a person with nonepileptic staring is an unreliable means of interrupting the event. The EEG should show a normal awake background during nonepileptic staring, rather than the 3-Hz spike-and-wave pattern associated with absence seizures or the ictal EEG changes that occur with focal unaware seizures.
front of a person with nonepileptic staring is an unreliable means of interrupting the event. The EEG should show a normal awake background during nonepileptic staring, rather than the 3-Hz spike-and-wave pattern associated with absence seizures or the ictal EEG changes that occur with focal unaware seizures.
CASE 23.3
A 20-year-old man with a history of attention deficit hyperactivity disorder, mood disorder, and brain injury was admitted through the emergency department for seizurelike episodes. Spells continued despite antiseizure medications started after a prior outside hospital admission. He described the events as a feeling of his heart being heavy prior to the episodes, and witnesses described stiffness in the lower extremities and shaking of upper extremities with clenched fists. Spells could last 2-10 minutes. He had been admitted to psychiatry for 10 days about 2 months prior for an undetermined reason. Social history was significant for recent fighting with his girlfriend.
Long-term video-EEG monitoring captured multiple typical events. Just prior to onset, the patient would look out into the hallway for nearby staff, and upon seeing someone, he would spit and cough into an emesis basin, making it appear as if he had vomited. When staff entered the room, he would tilt his head back, close his eyes, and then develop diffuse, arrhythmic, asynchronous shaking of all four limbs that would suddenly stop, and he would immediately regain consciousness without postictal confusion. The EEG before, during, and after the events showed a normal awake background with overriding myogenic and movement artifact. The behavior on video suggested a diagnosis of malingering. The patient subsequently requested a letter from the attending physician to excuse him from a court appearance scheduled within the next few days, confirming suspected secondary gain.