Convulsion No Epileptica Psicogenica

Psychogenic nonepileptic seizures Author Alan B Ettinger, MD Section Editor Timothy A Pedley, MD Deputy Editor Janet L Wilterdink, MD Last literature review version 17.1: January 2009 | This topic last updated: February 5, 2009 (More) INTRODUCTION — Clinicians are regularly challenged to identify the nature of episodic neurologic symptoms. Events associated with prominent motor activity or altered consciousness are often presumed to be epileptic seizures. However, the event may actually represent one of a wide array of nonepileptic paroxysmal events, such as syncope, parasomnias, and movement disorders. Another notable type of episodic behavior is a psychogenic nonepileptic seizure (PNES). Characterized by sudden and time-limited disturbances of motor, sensory, autonomic, cognitive, and/or emotional functions, PNES can mimic epileptic seizures. However, in contrast to epileptic seizures, PNES are not associated with physiological central nervous system dysfunction but are instead psychogenically determined [1-4] . Other terms, such as pseudoseizures or hysterical seizures, have been used to describe these episodes. The term "hysterical" seizures or "hysteroepilepsy" is now discouraged as both pejorative and oversimplified, failing to capture the broad range of underlying psychopathology. The term "pseudoseizures" is also discouraged, since the root "pseudo," or false, invalidates the genuine, even if psychogenic, disorder that a patient experiences. It is important that clinicians consider PNES when evaluating patients with episodic symptoms. Missing this diagnosis may result in inappropriate treatment with antiepileptic drugs that are associated with potential morbidity, especially if drug toxicity is incurred in the attempt to suppress episodes [5-7] . Prolonged episodes, "psychogenic status epilepticus" in particular, are often treated with toxic antiepileptic drug doses, intubation, and iatrogenically induced coma [6-14] . When PNES occur during pregnancy, these treatments pose additional risks to the fetus [2] . Recurrent visits to the emergency room and hospitalizations for uncontrolled, unrecognized PNES place a cost burden on the healthcare system [15] . Finally, failure to recognize psychiatric issues may promote the persistence of conversion symptoms and deny the patient needed psychiatric interventions. The diagnosis of PNES can be challenging. In some case series, delay to PNES diagnosis has been as long as 9 to 16 years [16,17] . This is due in part to the broad diversity of PNES presentations and the lack of one single unifying presenting symptom. Other sources of

misdiagnosis include an inadequate history, co-occurrence of PNES and epilepsy in the same patient, poor physician-patient rapport, reliance upon clinical observation of the event, discomfort in making a psychiatric diagnosis, and reluctance to obtain a psychiatric evaluation before the clinician feels confident about the diagnosis [18] . While advances in technology, especially the advent of video-electroencephalography, have greatly advanced our ability to recognize PNES, an accurate diagnosis is best achieved by assimilating a wide variety of clues including a detailed history from the patient and observers, the physical examination, selected testing, and a psychiatric evaluation. The epidemiology, clinical features, diagnosis, and treatment of PNES are discussed here. Other nonepileptic paroxysmal disorders are discussed separately. (See "Nonepileptic paroxysmal disorders in adolescents and adults"). EPIDEMIOLOGY — Incidence rates of PNES in the general population are not well established. One epidemiologic study in Iceland reported an incidence rate of 1.4 per 100,000 individuals over age 15 years; a study in Ohio documented a mean incidence of 3 per 100,000 between 1995 and 1998 [3,5,19] . The prevalence of PNES has been estimated to be between 2 to 33 per 100,000 [20] . Among patients referred to outpatient epilepsy centers, 5 to 25 percent of patients are felt to have PNES, while 25 to 40 percent of patients evaluated in inpatient epilepsy monitoring units for intractable seizures are diagnosed with PNES [3,21] . PNES most commonly presents in the third decade of life [17,22-25] . However, most age groups can be affected, including young children and the elderly [26-28] . One study suggests that the age of onset may be influenced by pre-existing features; patients with learning disabilities had a relatively younger age of onset compared to those with a history of physical or psychosocial trauma [29] . (See "Nonepileptic paroxysmal disorders in children" and see "Seizures and epilepsy in the elderly: Diagnosis and treatment"). PNES has a female predominance ranging from 66 to 99 percent in different series [5,22,23,25,28,30-34] . This is consistent with gender ratios described in conversion disorder, one of the salient psychiatric conditions underlying PNES [35,36] . (See "Psychosocial history" below). Race, marital status, and years of education do not appear to influence the prevalence of PNES [24] . CLINICAL FEATURES OF EVENTS — Recognizing PNES can be challenging even for experienced observers, in part because of the broad diversity of PNES presentations. Nonetheless, clues that arouse suspicion for this diagnosis are often apparent from the clinical history. It is important to remember that no single feature is either sensitive or specific for PNES. A history from patients with suspected PNES should elicit information relevant to any paroxysmal disorder including seizures: Detailed description of the event as perceived by the patient and as witnessed by others, including prodromal and postictal features Precipitants, circumstances in which episodes occur Episode frequency, duration Factors that reduce seizure frequency or attenuate an episode

Precipitants and setting — The setting in which an episode occurs can be helpful in distinguishing PNES and epilepsy. Most episodes of PNES occur in front of witnesses [37,38] . In one study, the occurrence of an episode in the doctor's waiting or examination room was estimated to have a 75 percent predictive value for PNES [37] . PNES tend not to occur during sleep. In contrast, epileptic seizures can occur during sleep, and in some forms of epilepsy, nocturnal episodes are most frequent. However, nocturnal seizures are frequently unwitnessed, and patients with PNES may report (erroneously) that seizures occur during sleep [39-41] . Patients with PNES may appear to be asleep just before seizure-onset, but the EEG in these cases demonstrates wakefulness [40] . (See "Video-EEG monitoring" below). While it is intuitive that PNES would be more likely to be associated with stressful situations, stress is commonly cited as a seizure precipitant in patients with epilepsy [42,43] . Increased seizure frequency during the perimenstrual time period suggests epileptic seizures. In one series, perimenstrual exacerbation was associated with 13 of 27 patients with epileptic seizures versus 1 of 38 patients with PNES [44] . PNES are often frequent. At the time of evaluation, most report at least daily episodes; less than one event a week is uncommon [5,17,23,25,34,38,45] . This observation may reflect a sampling bias. Ictal features — Unresponsive behavior with motor manifestations mimicking a generalized convulsion or a complex partial seizure is the most common manifestation of a PNES [22,23,28,32,38,45-47] . Less common are events that mimic atonic, absence, or simple partial seizures. A variety of clinical behaviors may occur during PNES, some of which are useful in distinguishing them from epileptic seizures (show table 1). However, no single semiologic feature is either sensitive or specific for PNES [5] . A variety of convulsive-like motor activity can occur in PNES. While motor manifestations of an epileptic seizure usually take the form of brief tonic posturing or a synchronized convulsion with a defined progression of motor activity; movements in PNES are more often asynchronous, variable, and wax and wane over the course of the ictus [21,22,48] . Specific movements such as writhing, thrashing, pelvic thrusts, opisthotonus (arched back), and jactitation (rolling from side to side) suggest a PNES, but these are not always present [22,38,46,48] . Moreover, some epileptic seizures, such as those of frontal lobe origin, can produce unusual-appearing motor activities similar to PNES [21,39,4954] . Stereotyped and consistent lateralization of motor features usually, but not always, suggests epilepsy [39,47] . (See "Localization-related epilepsy: Causes and clinical features", section on Frontal lobe epilepsy). Classic symptoms of epileptic seizures such as tongue biting, incontinence, and self-injury, are more common in epileptic seizures, but they can occur in a third or more of patients with PNES [16,17,22,23,34,45,55] . A tongue bitten on the side is more specific for epileptic seizure, than when bitten on the tip [56] . Incomplete loss of consciousness during the episode, suggested either by responsiveness to stimuli or by later recall of events during the ictus, suggests PNES [22,57] . Weeping, ictal stuttering, and vocalizations are relatively uncommon in epileptic seizures and suggest PNES [58-61] . When vocalization occurs in an epileptic seizure, it usually occurs at seizure onset, not during the convulsion. A seizure aura is frequently reported in PNES (25 to 60 percent) and may be a more common symptom than in epilepsy [32,34,38] . Autonomic manifestations during an ictus (eg, tachycardia, cyanosis) suggest epileptic seizure, and their absence, particularly during a major convulsion, suggests PNES [48,61,62] . Eyes are usually open during the ictus of a generalized convulsive seizure [56,63] . Forced eye closure in particular suggests PNES.

Sensitivity and specificity of eye closure as a sign for PNES varies according to how it is defined [48] . One study that calculated duration of time for eye closure (rather than absolute presence or absence) found only moderate sensitivity, but high specificity for PNES [64] . In this report, patient and observer reports of ictal eye closure were not reliable. Ictal atonia is not a common PNES manifestation, however, when prolonged, this almost always represents PNES, not epileptic seizure [46] . While the ictus of an epileptic seizure is typically very brief, often less than one minute, PNES are rarely less than one minute and are usually much longer [22-24,39,47,53,65,66] . Prolonged episodes (ie, psychogenic status epilepticus) are not rare. In one series, 78 percent of patients with PNES reported at least one event longer the 30 minutes, and half of these patients had recurrent episodes of psychogenic status epilepticus [14] . Postictal symptoms: Rapid alerting and reorientation is common after PNES but uncommon with epileptic seizures, except for certain seizure types, such as absence or frontal lobe seizures [38,39,49] . However, in some case series, half or more of patients with PNES exhibited postictal confusion or drowsiness [32,38] . Postictal headache occurs in up to half of patients with epileptic seizures, but is rare in PNES [43] . The postictal period after a generalized tonic-clonic seizure was found in one cohort to be characterized by a breathing pattern of deep and prolonged inspiratory and expiratory phases, compared with shallow, rapid respirations in patients after a PNES [63] . Epileptic seizures arising from the frontal lobe, however, were associated with a postictal breathing pattern similar to PNES. Another case series described a stertorous postictal breathing pattern after 6 of 27 epileptic seizures but in none of the 15 observed PNES [48] . Postictal nose-wiping or coughing is a rare but somewhat specific feature of mesial temporal lobe seizures [67] . Response to treatment — Most patients with PNES have seizures for many years prior to diagnosis, and most are treated unsuccessfully with antiepileptic drugs [5,16,23,28,32,38,46] . A failure to make even small improvements in seizure frequency despite vigorous antiepileptic drug trials suggests the diagnosis of PNES. Similarly, patients who present with prolonged PNES are often treated with drug protocols for status epilepticus and fail to respond [7,10,13] . ASSOCIATED FEATURES AND CONDITIONS Psychosocial history — While patients with PNES have a higher burden of psychiatric disease and symptoms than control groups with epilepsy, these conditions are also common in patients with epilepsy and are not specific for PNES [17,22,24,25,34,65,68-70] . It is also true that the presence of these conditions is often not known at the time of presentation with PNES and may instead be revealed later as part of the evaluation when sufficient rapport has been established. Psychiatric conditions associated with PNES include [32,34,45,69-75] : Depression Anxiety Somatoform disorder Post-traumatic stress disorder Dissociative disorder Personality disorders, especially borderline personality disorder, but also obsessive-compulsive, narcissistic, histrionic, and antisocial personalities A history of sexual or physical abuse is also prevalent in patients with PNES; in various cohorts, this is reported in one-third to one-half of

patients [17,29,32-34,68,76] . Patients with PNES who report a history of sexual abuse may be more likely to have events that are clinically more severe and more likely to resemble epileptic seizures [77] . In another series they were also more likely to exhibit self-harming behaviors and other medically unexplained symptoms in addition to PNES [29] . Dysfunctional family relationships (poor communication or support, interpersonal conflict, trauma) are also reported by many PNES patients and/or family members [32,78-80] . In contrast, depression with major psychosis and schizophrenia are relatively uncommon in patients with PNES [28] . Some authors distinguish between comorbid and etiologic psychiatric conditions, but this implies a detailed understanding of the pathophysiology of these symptoms, which is lacking. These disorders overlap, and it is common for patients to have more than one of these conditions [69] . As an example, dissociation is often associated with post-traumatic stress disorder and/or a history of physical or sexual abuse. Dissociative disorders and somatoform/conversion disorders are felt to underlie most PNES, but this remains unproven [81] . In these conditions, physical symptoms occur in response to psychosocial stress, and are not intentionally produced [34,74] . This contrasts with factitious disorder or malingering, in which symptoms are, at least to some extent, voluntary and consciously produced. Factitious disorders and malingering are rarely responsible for PNES. While the clinician should seek evidence for potential primary gain (affording relief from emotional conflict or tension) and secondary gain (deriving advantages such as attention, relief from responsibilities, or attaining disability benefits), it should never be assumed that patients with PNES are "faking" their symptoms. Psychosocial stressors that may precipitate the emergence of PNES in vulnerable patients include bereavement; unwanted pregnancy; ongoing physical, verbal, or sexual abuse; lawsuits; job pressure; financial difficulties; impending divorce; domestic conflicts; and assault [2,17,32,34,71] . In children, separation anxiety, school avoidance, and parental discord or divorce may also play a role [26,82] . Sometimes the recent event seems relatively minor, but may serve as the "last straw" in a series of events or may serve as a reminder of more significant remote events [83] . Concurrent or past epilepsy — Estimates of the prevalence of concurrent epilepsy among patients with PNES vary from 5 to 56 percent, in part because of differing diagnostic criteria used to determine the coexistence of epilepsy [28,29,32,34,84-88] . In one case series with video-EEG documentation of both PNES and epileptic seizures in the same patient, there was notably different clinical semiology for PNES compared to epileptic seizures in 18 of 20 patients [89] . However, another series found that patients with PNES and probable temporal lobe epilepsy had symptoms that appeared to be more characteristic of temporal lobe seizures, possibly because of learned behaviors from their own seizures [90] . A few patients (2 to 9 percent) with epilepsy develop PNES after epilepsy surgery [91-93] . These typically emerge within the first several months, at a time when other psychiatric complications are also most incident. These patients often manifest other symptoms of

psychiatric distress (eg, anxiety, psychosis). The symptoms may approximate presurgical epileptic events but are often very different. This phenomenon may be due in part to a paradoxical dependence on seizures and all of its psychosocial ramifications. Seizure model — Patients with PNES have often witnessed epileptic events that may serve as a clinical model. A seizure history in a friend or relative, or an occupation as a healthcare worker is not uncommon [32] . In one study, patients with PNES were significantly more likely to have witnessed an epileptic seizure prior to their event than were patients with epilepsy (66 versus 11 percent) [94] . Alternatively, a patient's own history of epilepsy may be the model for their PNES. Comorbid neurologic and medical disease — While underlying neurologic disease is more prevalent among patients with epilepsy than PNES, a history of neurologic insults, particularly minor head trauma, is common (30 to 44 percent) in PNES patients [28,34,68,88,95-97] . It is not clear why such an association should exist. The head injury may be associated with psychological as well as physical trauma, which may serve as a precipitant for PNES. In some series, a patient's disability status or litigation for damages appeared to provide a source of secondary gain for PNES [68] . Recall bias may also contribute to this apparent association. PNES is also well-described in patients with neurologic developmental disabilities [28,98,99] . In this population, distinguishing these events from epileptic seizures and other repetitive, stereotyped behaviors is a particular challenge. In one study, individuals with PNES and learning disabilities were more likely to have circumstantial triggering of events and more prolonged events than individuals without learning disabilities [29] . A history of recurrent medical evaluations for other unexplained somatic complaints should be examined [69] . As examples, a history of chronic pain or fibromyalgia is common among patients with PNES [37,43,97] . In one series, 30 percent of PNES patients had a sufficient burden of gastrointestinal complaints, pain, fatigue, and other complaints to meet criteria for an undifferentiated somatoform disorder. (See "Somatization", section on Definitions). Examination findings — Physical examination of patients with PNES may be completely normal, demonstrate neurologic abnormalities associated with unrelated neurologic disorders, or exhibit classic signs of conversion disorder. In the latter circumstance, the clinician may find a variety of abnormalities that do not make physiologic sense [36] . A classic sign of conversion disorder is an apparent lack of concern for serious clinical symptoms (so-called "belle indifference"). However, some believe this finding is overemphasized in PNES patients and may be absent [100] . DIFFERENTIAL DIAGNOSIS — The primary consideration in the differential diagnosis of PNES are epileptic seizures [85] . Seizures arising from the frontal lobe in particular are often mistaken for PNES because of their unusual semiology. (See "Ictal features" above). Clinical features that suggest frontal lobe seizures rather than PNES are a brief duration (less than one minute), stereotyped manifestations, eyes-open during the ictus, and their occurrence during physiologic sleep [39,53,63] . In one video-EEG study, tonic contraction of the upper extremities in abduction was a feature of 90 percent of 63 supplementary motor

seizures and occurred in none of 111 PNES [39] . (See "Localization-related epilepsy: Causes and clinical features", section on Frontal lobe epilepsy). Other nonepileptic paroxysmal disorders may be mistaken for either epileptic seizures or for PNES [85] . These include sleep disorders, movement disorders, and syncope. These are discussed in detail separately. (See "Nonepileptic paroxysmal disorders in adolescents and adults"). DIAGNOSIS — While not without limitations, video-electroencephalography (EEG) is the gold standard test for the diagnosis of PNES [24] . However, patients with PNES are likely to undergo other diagnostic testing during the course of their evaluation. Some tests can provide support for the diagnosis, others may provide misleading information. Other testing, while not helpful in diagnosis of PNES, is potentially useful in evaluating comorbidities and choosing subsequent treatment. Electroencephalography Routine EEG — Routine EEG is often inadequate for distinguishing epileptic seizures from PNES. One reason is that a routine EEG records activity for only 20 to 30 minutes and is therefore unlikely to capture an ictus. A normal interictal EEG does not exclude the possibility of epilepsy or confirm the diagnosis of PNES [101] . At the same time, interictal epileptiform abnormalities do not rule out PNES. While more prevalent among patients with epilepsy, these are also seen in patients with PNES [16,89,102] . In patients felt to have PNES alone (no comorbid epilepsy), the prevalence of interictal EEG abnormalities ranges from 10 to 18 percent [16,23,87,88,96,102] . An abnormal interictal EEG is more common if there is a past or concurrent history of epilepsy or other underlying neurologic injury or disease. Video-EEG monitoring — Video-EEG monitoring combines extended EEG monitoring with time-locked video acquisition that allows for analysis of clinical and electrographic features during a captured event. The yield of monitoring is high; 73 to 96 percent of patients will have typical PNES within first 48 hours [24,103] . Caution is required for interpretation. While the majority of generalized tonic-clonic seizures reveal an ictal EEG correlate, the tracing may be obscured by muscle artifact. On the other hand, only 15 to 33 percent of simple partial seizures or seizure auras, which involve a limited brain area and are of deep origin, are associated with surface EEG abnormalities [104] . As a result, failure to see an electrographic seizure does not exclude epilepsy. (See "Video and ambulatory EEG monitoring in the diagnosis of seizures and epilepsy"). Accurate interpretation of video-EEG monitoring requires careful analysis of the clinical events with any changes in the EEG occurring before, during, and after the seizure. As one example, a finding of "preictal pseudosleep", the appearance of clinical sleep while the EEG tracing demonstrates wakefulness is a very specific, although insensitive, indicator of PNES [40] . Patients with diverse episode types may have both epileptic seizures and PNES. It is important to determine from both patients and family members that the event captured on video-EEG is typical of the events that are being evaluated. It can be helpful to show the video of the event

to family members who can indicate how closely it resembles prior events they have witnessed. Spell induction — Video-EEG monitoring may be supplemented with the administration of a placebo designed to induce a PNES. This may be helpful if the patient fails to have a spontaneous event during prolonged video-EEG monitoring. This maneuver is typically performed by administering intravenous saline or rubbing alcohol on the skin of the patient and telling the patient that this may induce an episode. Between 67 to 90 percent of patients with PNES will have a typical event in this setting [2,5,38,105-107] . While much less common, epileptic events have also been reported to occur in this setting [85,87,103,108-110] . Because of this, induction should be performed during video-EEG. It is also essential to confirm that the elicited episode is representative of the spells under investigation. A patient with epilepsy may have a PNES under these circumstances, but the features are usually atypical of their usual events [111] . Use of this technique is controversial. While facilitating diagnosis, the inherent deceit in this approach may jeopardize the physician-patient relationship and impede future treatment efforts. However, many experts believe that these considerations are outweighed by the benefits of making an accurate diagnosis and avoiding future morbidity associated with inappropriate treatments [5,112] . Alternative techniques that employ photic stimulation and/or hyperventilation with suggestion may obviate the deceitful aspects, as these are routinely used to precipitate epileptic seizures. As a result, these may be more acceptable to patients and physicians, although special care is required as an epileptic seizure is more likely to be precipitated with these techniques, than with placebo [38,105] . Some physicians report successful use of induction techniques when they inform the patient that they are being used to elicit a possible psychogenic as well as epileptic seizure [113] . Other monitoring techniques — Sometimes, in spite of prolonged video-EEG and use of induction techniques, no episode is recorded. In such cases, outpatient ambulatory EEG, ideally with concomitant video may be helpful. Advising family members to have a video camera ready to record on stand-by can be helpful as well. While the absence of concomitant EEG is a significant limitation, direct observation of the clinical event can provide the physician with valuable information that aids in the diagnosis [48] . (See "Ictal features" above). Serum testing — Certain laboratory studies can help differentiate PNES from epileptic seizure. Prolactin levels are often elevated after an epileptic seizure, depending on the seizure type [50,51] . Pooled sensitivity from several studies report prolactin level elevations (twice the baseline level) in 60 percent of generalized tonic clonic seizures and 46 percent of complex partial seizures [114] . The sensitivity is lower for simple partial seizures. Prolactin levels are less likely to rise after seizures that do not involve mesial temporal areas, making this a less sensitive test for epileptic seizures arising from the frontal lobe [115] . The timing of measuring prolactin is crucial. In typical cases, prolactin levels peak 15 to 20 minutes after the seizure and return to baseline levels within an hour [114] . A baseline prolactin level should be determined from a blood sample drawn six hours after the event.

Prolactin elevations have not been well characterized in the setting of repeated seizures or status epilepticus, and have unclear utility in this setting. Prolactin levels are unlikely to rise after a PNES, but elevations can occur after syncope [114,116] . Dopamine antagonists (eg, neuroleptic agents) can elevate prolactin levels and confound the results. Thus, an elevated prolactin level can be helpful in identifying a physiologic episode (epileptic seizure or syncope), however, a nonelevated prolactin level does not imply PNES. Other serum markers have been used to help distinguish PNES from epileptic seizures and other physiologic events. These include: creatine phosphokinase (CPK), cortisol, white blood cell count, lactate dehydrogenase, pCO2, and neuron specific enolase [117-119] . CPK levels in particular are often elevated after generalized tonic-clonic seizures, but not after partial seizures. The later rise and prolonged elevation, up to 24 hours postictally, makes this test somewhat more useful in the outpatient setting. However, a defined threshold level for abnormality, sensitivity, and specificity remain to be determined for CPK, as for other serum markers [120] . Neuroimaging — When a structural abnormality is seen on brain MRI, it suggests a neuroanatomic substrate for epilepsy, and provides support for a diagnosis of epilepsy. However, many series report abnormal brain MRI in 10 to 38 percent of patients with PNES [16,23,32,96,121] . At the same time, many patients with epileptic seizures have normal brain MRI. Abnormalities identified in PNES patients include arachnoid cyst, post-traumatic or gliotic change, hippocampal sclerosis, and venous angioma [96] . Abnormalities on interictal single photon emission computed tomography (SPECT) are also reported in PNES as well as epilepsy cases. However, a change in focal perfusion from in an ictal or postictal SPECT compared to an interictal SPECT can help distinguish epileptic seizures from PNES [121-124] . This technique may be particularly useful when movement-related muscle artifact obscures EEG interpretation. However, this test is not widely available, and the sensitivity and specificity are uncertain. Neuropsychological testing — Neuropsychological testing typically assesses both cognitive functioning as well as some psychological domains. The common occurrence of cognitive deficits, particularly in attention and memory, in both PNES and epilepsy patients limits the utility of neuropsychological testing for distinguishing between them [28,96,125,126] . Some of these deficits may be related to antiepileptic drugs and other medications. Neuropsychological testing may be suspicious for PNES when a pattern of failure to recognize words presented repeatedly is exhibited in the face of only rarely making false positive errors (termed a "negative response bias") [127] . Personality profile testing such as the Minnesota Multiphasic Personality Inventory (MMPI), a common component of neuropsychological testing, can be helpful in supplementing formal psychiatric evaluations and highlighting comorbid psychiatric disturbances [128] . Patients with PNES typically have high scores on hypochondriasis and hysteria subscales [24,32,102,128-130] . While a helpful adjunct in the evaluation of patients, studies give varying estimates of its ability to correctly categorize PNES versus epilepsy patients ranging from 70 to 90 percent.

Psychiatric evaluation — While essential in the evaluation of patients with suspected PNES, the role of psychiatric evaluation is not to establish or refute a PNES diagnosis, but rather to identify comorbid or underlying psychiatric conditions that will hopefully direct treatment [23,65] . An experienced clinician in a detailed psychiatric interview will elicit clinical features that may establish a diagnosis of depression, anxiety, somatoform, dissociative, and other disorders. Sufficient rapport may also be established in this setting, that allows for a previously unreported history of sexual abuse or other trauma to be revealed. (See "Psychosocial history" above). Findings on neuropsychological testing may supplement the interview in arriving at one or more psychiatric disorders. (See "Neuropsychological testing" above). PRESENTING THE DIAGNOSIS — Presenting the diagnosis of PNES to patients is a challenge. Most agree that this should not take place until the clinician feels very definite about the diagnosis [131,132] . Care providers who take on this role should be well-trained in delivering this information. Clinicians may prefer to reveal the diagnosis in a separate outpatient meeting rather than in the video-EEG monitoring unit. This conversation is crucially important for the patient's prognosis. Because most serious morbidity associated with PNES is from inappropriate aggressive treatment of presumed epileptic seizures, it is important for the patient and family to accept the diagnosis of PNES in order to avoid emergency room visits, as well as to obtain appropriate psychiatric treatment [15,132] . A useful method for communicating the diagnosis of PNES to patients emphasizes the presentation in a nonjudgmental fashion that strives to maintain patient dignity [133] . Techniques and talking points that we and others have found useful in this conversation include some of the following [74,133] : We state that we do not consider the episodes to be caused by epileptic discharges, but rather represent "the mind playing tricks on the body." We emphasize that this problem is as serious as one caused by epilepsy and deserves the attention and treatment that is accorded any illness. We discuss how stress afflicts each of us to variable degrees and in different ways. We note that "the body needs to blow off steam" in some fashion; some people release this stress with the development of headaches, others with tremors, and some with nonepileptic seizures. We emphasize that the episodes are experienced as real and disabling, and that although they relate to emotional or psychological causes, we do not dismiss the problem, and we do not consider the patient to be "crazy." We state that their disorder warrants different treatments than those administered for epilepsy. We tell our patients that we expect that they may react in many ways to this diagnosis. Many patients become angry in response to receiving the diagnosis. Some may acknowledge these feelings, while others may not. An angry reaction may forebode a poor prognosis [17,97] . In my experience, it is useful to anticipate these feelings at the time of revealing the diagnosis. We and others have also found that patients may exhibit exacerbations of their episodes after the diagnosis is revealed and we often warn the patients not to be surprised if this were to occur [17] .

NEUROLOGIC FOLLOW-UP — A frequent error on the part of neurologists is the immediate discharge of patients with PNES, with the rationale that the diagnosis is psychiatric and not neurologic. In fact, some experts advise instead that PNES patients should not be discharged from the neurologist's care until patients and families accept the fact that they do not have epilepsy, have transitioned to psychiatric care, and have agreed on the time to discontinue neurologic care [132,134] . Premature discharge can exacerbate episodes and increase resistance to accepting the diagnosis. Patients often report a poor understanding of the diagnosis and may complain in a follow-up that they did not receive a clarification of diagnosis even if a thorough discussion was rendered [17] . Ideally, a close dialogue should also be developed and maintained between neurologic, psychiatric, and primary care providers, who often disagree about the diagnosis and the accuracy of video-EEG monitoring [17,75,132,135] . This communication may limit mixed and conflicting messages from different doctors that can contribute to the overall poor prognosis [17] . Cautious discontinuation of antiepileptic drug (AED) therapy should be coordinated where possible. It is not infrequent for episodes to increase during this time period. In some cases, epileptic seizures as well as PNES emerge during this interval [136] . Repeat video-EEG monitoring may be needed if there is doubt that these episodes are different in nature than those documented to be PNES. Some AEDs have mood stabilizing properties and their discontinuation may exacerbate an underlying affective or panic disorder. TREATMENT — While some patients relinquish episodes soon after the diagnosis is revealed, most will continue to have episodes and will require long-term psychiatric interventions [22,28,73,131,137,138] . Treatment recommendations in PNES are based upon anecdotal experience or small case series [139-141] . There are no published, large, randomized, double-blind treatment trials for PNES, although a few such trials are underway. One problem in designing treatments and trials to assess their efficacy relates to the heterogeneous combinations of psychiatric disorders that underlie PNES [131] . Additionally, patients with PNES often do not adhere to treatment recommendations or return for follow-up, and may be particularly disinclined to enroll in treatment trials. Psychiatric interventions are the hallmark of treatment for PNES. These are individualized according to the underlying psychiatric diagnosis. One common psychiatric intervention is traditional psychotherapy. Reports on the success of this intervention are mixed [137,142] . Group therapy sessions also employ traditional psychodynamic techniques and have had mixed results in open-label studies of PNES [141,143,144] . The high prevalence of family problems in patients with PNES offer promise that family-related education and interventions may be useful, but these have not been systematically studied [78] .

Cognitive behavioral therapy (CBT)is an approach based upon a fear avoidance model and may be especially successful for patients who have PNES as a dissociative response in stressful circumstances. CBT employs progressive exposure to feared situations, and emphasizes problem solving techniques. In one study, 16 of 20 patients with "dissociative seizures" entered an open-label trial of 12-session CBT. Six months later, there was a reduction in episodes and some improvement in psychosocial functioning [145] . Antidepressants and anxiolytics may be prescribed. These may better address psychiatric comorbidities of depression and anxiety rather than an underlying causative psychiatric disorder. These medications have had mixed results in open-label studies of PNES [140,141] . Barriers to effective treatment of PNES patients include poor compliance and financial and insurance-related limitations for ongoing treatment. Another challenge is the difficulty finding psychiatric providers who are well-acquainted and comfortable dealing with PNES. PROGNOSIS — Most studies that have assessed the prognosis in patients after PNES diagnosis suggest that only a minority (25 to 33 percent) of patients achieve seizure freedom [4,17,23,32,73] . Children have a better prognosis than adults, with 70 to 80 percent achieving seizure remission [146] . While outcome is often reported as a percent of those with seizure remission, this narrow measure does not necessarily reflect the overall clinical outcome with respect to psychiatric and psychosocial status [4,23,145,151] . As an example, in one study, 56 percent of patients overall continued to depend on state-supported financial benefits at four years after PNES diagnosis [4,23] . The percentage was lower, but still substantial, 43 percent, among those in episode remission. Other studies have also found that occupational status, while more likely to improve if PNES cease, often does not even when episodes do remit [45,147] . In another study, psychosocial issues, not persistent PNES, were the primary cause of disability [145] . Both attempted and successful suicides have been reported in some series with follow-up [45,145,148] . In one of these cohorts, suicide attempts were equally frequent (11 of 56 patients overall) in those with or without seizure remission [45] . Some patients may develop new somatic complaints after their PNES remit. A structured interview of 56 patients, six or more months following PNES diagnosis, revealed moderate to severe pain syndromes, especially headaches, in 77 percent [43] . Twenty-six of 27 patients who stopped experiencing PNES still experienced moderate pain. While the etiologies or other details about these pain symptoms were not studied, it is possible that pain developed de novo or became more serious after the PNES diagnosis. Another study, however, suggested that the development of new somatic complaints was rare, at least within the first six months after PNES diagnosis [73] . Some of the risk factors inconsistently associated with a worse prognosis include [5,22,23,43,45,73,74,108,134,142,149,150]: Longer duration of symptoms Older age at onset Lower educational level, lower IQ More isolation, more limited family support Dependent lifestyle Male gender No formal treatment plan Unrelieved stressors (eg, ongoing abuse, family

conflict) Anger, rejection of PNES diagnosis More severe underlying psychiatric disorder, especially severe or generalized somatization or dissociative symptoms Some studies have associated clinical semiology with prognosis [23,134,150] . Patients with more dramatic motor features, self-injury, and prolonged episodes have a lower likelihood of remission than those with more passive or catatonic-like behaviors. However, the reason behind this association is unclear, and this finding is not universal [22] . SUMMARY AND RECOMMENDATIONS — Psychogenic nonepileptic seizures (PNES) are events that clinically mimic epileptic seizures, but are not associated with physiological central nervous system dysfunction and are instead psychogenically determined. PNES include a variety of clinical manifestations, some of which are suggestive, although not diagnostic, in distinguishing PNES from epileptic seizures. (See "Clinical features of events" above). The diagnosis of PNES is generally established by video-EEG monitoring, in which captured clinical events are examined in conjunction with electroencephalographic activity. Most patients with PNES will have an event within a few days of monitoring. The use of techniques to induce events is somewhat controversial, but can be helpful diagnostically, when patients do not have an event on monitoring. Other tests (interictal EEG, neuroimaging, neuropsychological tests, and laboratory studies) can be helpful in the evaluation of patients, but are generally not diagnostic of PNES. (See "Diagnosis" above). Frontal lobe seizures can have atypical clinical features and a normal ictal EEG and can be confused with PNES. Features that suggest that the events are frontal lobe seizures include short duration, stereotyped features, and occurrence during physiologic sleep. (See "Differential diagnosis" above). The diagnosis of PNES, once established, should be presented to patients and their families in a supportive, nonjudgmental fashion. (See "Presenting the diagnosis" above). We believe that neurologic follow-up should be maintained after PNES diagnosis to monitor the safe withdrawal of antiepileptic drugs, answer patient questions, and communicate with other treating physicians until such time as the patient has been fully transitioned to psychiatric care. (See "Neurologic follow-up" above). Psychiatric interventions are individualized according to the underlying psychiatric diagnosis and are coordinated by the treating psychiatrist. (See "Treatment" above). The prognosis for patients with PNES is guarded. Many patients will continue to have seizure-like events. Patients with and without PNES remission may have substantial psychiatric morbidity and functional limitations on follow-up. Further studies are needed to identify effective psychiatric interventions for these patients. (See "Prognosis" above).

REFERENCES Ozkara, C, Dreifuss, FE. Differential diagnosis in pseudoepileptic seizures. Epilepsia 1993; 34:294. DeToledo, JC, Lowe, MR, Puig, A. Nonepileptic seizures in pregnancy. Neurology 2000; 55:120. Szaflarski, JP, Ficker, DM, Cahill, WT, Privitera, MD. Four-year incidence of psychogenic nonepileptic seizures in adults in hamilton county, OH. Neurology 2000; 55:1561. Reuber, M, Mitchell, AJ, Howlett, S, Elger, CE. Measuring outcome in psychogenic nonepileptic seizures: how relevant is seizure remission?. Epilepsia 2005; 46:1788. Reuber, M, Elger, CE. Psychogenic

nonepileptic seizures: review and update. Epilepsy Behav 2003; 4:205. Smith, PE, Saunders, J, Dawson, A, Kerr, MP. Intractable seizures in pregnancy. Lancet 1999; 354:1522. Gunatilake, SB, De Silva, HJ, Ranasinghe, G. Twenty-seven venous cutdowns to treat pseudostatus epilepticus. Seizure 1997; 6:71. Peters, G, Leach, JP, Larner, AJ. Pseudostatus epilepticus in pregnancy. Int J Gynaecol Obstet 2007; 97:47. Tuxhorn, IE, Fischbach, HS. Pseudostatus epilepticus in childhood. Pediatr Neurol 2002; 27:407. Wilner, AN, Bream, PR. Status epilepticus and pseudostatus epilepticus. Seizure 1993; 2:257. Bateman, DE. Pseudostatus epilepticus. Lancet 1989; 2:1278. Howell, SJ, Owen, L, Chadwick, DW. Pseudostatus epilepticus. Q J Med 1989; 71:507. Reuber, M, Baker, GA, Gill, R, et al. Failure to recognize psychogenic nonepileptic seizures may cause death. Neurology 2004; 62:834. Reuber, M, Pukrop, R, Mitchell, AJ, et al. Clinical significance of recurrent psychogenic nonepileptic seizure status. J Neurol 2003; 250:1355. Martin, RC, Gilliam, FG, Kilgore, M, et al. Improved health care resource utilization following video-EEG-confirmed diagnosis of nonepileptic psychogenic seizures. Seizure 1998; 7:385. de Timary, P, Fouchet, P, Sylin, M, et al. Non-epileptic seizures: delayed diagnosis in patients presenting with electroencephalographic (EEG) or clinical signs of epileptic seizures. Seizure 2002; 11:193. Carton, S, Thompson, PJ, Duncan, JS. Non-epileptic seizures: patients' understanding and reaction to the diagnosis and impact on outcome. Seizure 2003; 12:287. Bhatia, MS. Pseudoseizures. Indian Pediatr 2004; 41:673. Sigurdardottir, KR, Olafsson, E. Incidence of psychogenic seizures in adults: a population-based study in Iceland. Epilepsia 1998; 39:749. Benbadis, SR, Allen Hauser, W. An estimate of the prevalence of psychogenic non-epileptic seizures. Seizure 2000; 9:280. Gates, JR, Ramani, V, Whalen, S, Loewenson, R. Ictal characteristics of pseudoseizures. Arch Neurol 1985; 42:1183. Meierkord, H, Will, B, Fish, D, Shorvon, S. The clinical features and prognosis of pseudoseizures diagnosed using video-EEG telemetry. Neurology 1991; 41:1643. Reuber, M, Pukrop, R, Bauer, J, et al. Outcome in psychogenic nonepileptic seizures: 1 to 10-year follow-up in 164 patients. Ann Neurol 2003; 53:305. Cragar, DE, Berry, DT, Fakhoury, TA, et al. A review of diagnostic techniques in the differential diagnosis of epileptic and nonepileptic seizures. Neuropsychol Rev 2002; 12:31. Szaflarski, JP, Hughes, C, Szaflarski, M, et al. Quality of life in psychogenic nonepileptic seizures. Epilepsia 2003; 44:236. Wyllie, E, Glazer, JP, Benbadis, S, et al. Psychiatric features of children and adolescents with pseudoseizures. Arch Pediatr Adolesc Med 1999; 153:244. McBride, AE, Shih, TT, Hirsch, LJ. Video-EEG monitoring in the elderly: a review of 94 patients. Epilepsia 2002; 43:165. Krumholz, A, Niedermeyer, E. Psychogenic seizures: a clinical study with followup data. Neurology 1983; 33:498. Duncan, R, Oto, M. Predictors of antecedent factors in psychogenic nonepileptic attacks: multivariate analysis. Neurology 2008; 71:1000. Metrick, ME, Ritter, FJ, Gates, JR, et al. Nonepileptic events in childhood. Epilepsia 1991; 32:322. Holmes, GL, Sackellares, JC, McKiernan, J, et al. Evaluation of childhood pseudoseizures using EEG telemetry and video tape monitoring. J Pediatr 1980; 97:554. Lancman, ME, Brotherton, TA, Asconape, JJ, Penry, JK. Psychogenic seizures in adults: a longitudinal analysis. Seizure 1993; 2:281. Alper, K, Devinsky, O, Perrine, K, et al. Nonepileptic seizures and childhood sexual and physical abuse. Neurology 1993; 43:1950. Scheepers, B, Budd, S, Curry, S, et al. Nonepileptic attack disorder: a clinical audit. Seizure 1994; 3:129. Couprie, W, Wijdicks, EF, Rooijmans, HG, van Gijn, J. Outcome in conversion disorder: a follow up study. J Neurol Neurosurg Psychiatry 1995; 58:750. Grattan-Smith, P, Fairley, M, Procopis, P. Clinical features of conversion disorder. Arch Dis Child 1988; 63:408. Benbadis, SR. A spell in the epilepsy clinic and a history of "chronic pain" or "fibromyalgia" independently predict a diagnosis of

psychogenic seizures. Epilepsy Behav 2005; 6:264. Luther, JS, McNamara, JO, Carwile, S, et al. Pseudoepileptic seizures: methods and video analysis to aid diagnosis. Ann Neurol 1982; 12:458. Kanner, AM, Morris, HH, Luders, H, et al. Supplementary motor seizures mimicking pseudoseizures: some clinical differences. Neurology 1990; 40:1404. Benbadis, SR, Lancman, ME, King, LM, Swanson, SJ. Preictal pseudosleep: a new finding in psychogenic seizures. Neurology 1996; 47:63. Duncan, R, Oto, M, Russell, AJ, Conway, P. Pseudosleep events in patients with psychogenic non-epileptic seizures: prevalence and associations. J Neurol Neurosurg Psychiatry 2004; 75:1009. Luciano, D, Devinsky, O, Perrine, K, et al. Psychic stress as a seizure precipitant- relationship to seizure type and region of ictal onset. Epilepsia 1996; 32:(abs)29. Ettinger, AB, Devinsky, O, Weisbrot, DM, et al. Headaches and other pain symptoms among patients with psychogenic non-epileptic seizures. Seizure 1999; 8:424. Ettinger, AB, Weisbrot, DM, Devinsky, O. Patient reporting of seizure exacerbation near the time of menses helps distinguish epileptic from nonepileptic seizures. J Epilepsy 1998; 11:332. Ettinger, AB, Devinsky, O, Weisbrot, DM, et al. A comprehensive profile of clinical, psychiatric, and psychosocial characteristics of patients with psychogenic nonepileptic seizures. Epilepsia 1999; 40:1292. Leis, AA, Ross, MA, Summers, AK. Psychogenic seizures: ictal characteristics and diagnostic pitfalls. Neurology 1992; 42:95. Gulick, TA, Spinks, IP, King, DW. Pseudoseizures: ictal phenomena. Neurology 1982; 32:24. Chen, DK, Graber, KD, Anderson, CT, Fisher, RS. Sensitivity and specificity of video alone versus electroencephalography alone for the diagnosis of partial seizures. Epilepsy Behav 2008; 13:115. Williamson, PD, Jobst, BC. Frontal lobe epilepsy. Adv Neurol 2000; 84:215. Wroe, SJ, Henley, R, John, R, Richens, A. The clinical value of serum prolactin measurement in the differential diagnosis of complex partial seizures. Epilepsy Res 1989; 3:248. Wyllie, E, Luders, H, MacMillan, JP, Gupta, M. Serum prolactin levels after epileptic seizures. Neurology 1984; 34:1601. Geyer, JD, Payne, TA, Drury, I. The value of pelvic thrusting in the diagnosis of seizures and pseudoseizures. Neurology 2000; 54:227. Saygi, S, Katz, A, Marks, DA, Spencer, SS. Frontal lobe partial seizures and psychogenic seizures: comparison of clinical and ictal characteristics. Neurology 1992; 42:1274. Jobst BC, Williamson PD. Frontal lobe seizures. Psychiatr Clin North Am 2005; 28:635. Oliva, M, Pattison, C, Carino, J, et al. The diagnostic value of oral lacerations and incontinence during convulsive "seizures". Epilepsia 2008; 49:962. DeToledo, JC, Ramsay, RE. Patterns of involvement of facial muscles during epileptic and nonepileptic events: review of 654 events. Neurology 1996; 47:621. Bell, WL, Park, YD, Thompson, EA, Radtke, RA. Ictal cognitive assessment of partial seizures and pseudoseizures. Arch Neurol 1998; 55:1456. Bergen, D, Ristanovic, R. Weeping as a common element of pseudoseizures. Arch Neurol 1993; 50:1059. Singh, RB, Niaz, MA, Ghosh, S, et al. Epidemiological study of magnesium status and risk of coronary artery disease in elderly rural and urban populations of north India. Magnes Res 1996; 9:165. Vossler, DG, Haltiner, AM, Schepp, SK, et al. Ictal stuttering: a sign suggestive of psychogenic nonepileptic seizures. Neurology 2004; 63:516. James, MR, Marshall, H, Carew-McColl, M. Pulse oximetry during apparent tonic-clonic seizures. Lancet 1991; 337:394. Opherk, C, Hirsch, LJ. Ictal heart rate differentiates epileptic from non-epileptic seizures. Neurology 2002; 58:636. Azar, NJ, Tayah, TF, Wang, L, et al. Postictal breathing pattern distinguishes epileptic from nonepileptic convulsive seizures. Epilepsia 2008; 49:132. Syed, TU, Arozullah, AM, Suciu, GP, et al. Do observer and self-reports of ictal eye closure predict psychogenic nonepileptic seizures?. Epilepsia 2008; 49:898. Berkhoff, M, Briellmann, RS, Radanov, BP, et al. Developmental background and outcome in patients with nonepileptic versus epileptic seizures: a controlled

study. Epilepsia 1998; 39:463. Gumnit, RJ, Gates, JR. Psychogenic seizures. Epilepsia 1986; 27 Suppl 2:S124. Wennberg, R. Postictal coughing and noserubbing coexist in temporal lobe epilepsy. Neurology 2001; 56:133. van Merode, T, Twellaar, M, Kotsopoulos, IA, et al. Psychological characteristics of patients with newly developed psychogenic seizures. J Neurol Neurosurg Psychiatry 2004; 75:1175. Westbrook, LE, Devinsky, O, Geocadin, R. Nonepileptic seizures after head injury. Epilepsia 1998; 39:978. Galimberti, CA, Ratti, MT, Murelli, R, et al. Patients with psychogenic nonepileptic seizures, alone or epilepsy-associated, share a psychological profile distinct from that of epilepsy patients. J Neurol 2003; 250:338. Bowman, ES. Etiology and clinical course of pseudoseizures. Relationship to trauma, depression, and dissociation. Psychosomatics 1993; 34:333. Reuber, M, Pukrop, R, Bauer, J, et al. Multidimensional assessment of personality in patients with psychogenic non-epileptic seizures. J Neurol Neurosurg Psychiatry 2004; 75:743. Kanner, AM, Parra, J, Frey, M, et al. Psychiatric and neurologic predictors of psychogenic pseudoseizure outcome. Neurology 1999; 53:933. Bowman, ES. Nonepileptic seizures: psychiatric framework, treatment, and outcome. Neurology 1999; 53:S84. Lacey, C, Cook, M, Salzberg, M. The neurologist, psychogenic nonepileptic seizures, and borderline personality disorder. Epilepsy Behav 2007; 11:492. Rosenberg, HJ, Rosenberg, SD, Williamson, PD, Wolford GL, 2nd. A comparative study of trauma and posttraumatic stress disorder prevalence in epilepsy patients and psychogenic nonepileptic seizure patients. Epilepsia 2000; 41:447. Selkirk, M, Duncan, R, Oto, M, Pelosi, A. Clinical differences between patients with nonepileptic seizures who report antecedent sexual abuse and those who do not. Epilepsia 2008; :. Krawetz, P, Fleisher, W, Pillay, N, et al. Family functioning in subjects with pseudoseizures and epilepsy. J Nerv Ment Dis 2001; 189:38. Moore, PM, Baker, GA, McDade, G, et al. Epilepsy, pseudoseizures and perceived family characteristics: a controlled study. Epilepsy Res 1994; 18:75. Wood, BL, McDaniel, S, Burchfiel, K, Erba, G. Factors distinguishing families of patients with psychogenic seizures from families of patients with epilepsy. Epilepsia 1998; 39:432. Lawton, G, Baker, GA, Brown, RJ. Comparison of two types of dissociation in epileptic and nonepileptic seizures. Epilepsy Behav 2008; 13:333. Patel, H, Scott, E, Dunn, D, Garg, B. Nonepileptic seizures in children. Epilepsia 2007; 48:2086. Bowman, ES, Markand, ON. The contribution of life events to pseudoseizure occurrence in adults. Bull Menninger Clin 1999; 63:70. Benbadis, SR, Agrawal, V, Tatum WO, 4th. How many patients with psychogenic nonepileptic seizures also have epilepsy?. Neurology 2001; 57:915. Parra, J, Iriarte, J, Kanner, AM. Are we overusing the diagnosis of psychogenic non-epileptic events?. Seizure 1999; 8:223. Martin, R, Burneo, JG, Prasad, A, et al. Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG. Neurology 2003; 61:1791. Lesser, RP, Lueders, H, Dinner, DS. Evidence for epilepsy is rare in patients with psychogenic seizures. Neurology 1983; 33:502. Reuber, M, Fernandez, G, Bauer, J, et al. Interictal EEG abnormalities in patients with psychogenic nonepileptic seizures. Epilepsia 2002; 43:1013. Devinsky, O, Sanchez-Villasenor, F, Vazquez, B, et al. Clinical profile of patients with epileptic and nonepileptic seizures. Neurology 1996; 46:1530. Henry, TR, Drury, I. Ictal behaviors during nonepileptic seizures differ in patients with temporal lobe interictal epileptiform EEG activity and patients without interictal epileptiform EEG abnormalities. Epilepsia 1998; 39:175. Ney, GC, Barr, WB, Napolitano, C, et al. New-onset psychogenic seizures after surgery for epilepsy. Arch Neurol 1998; 55:726. Glosser, G, Roberts, D, Glosser, DS. Nonepileptic seizures after resective epilepsy surgery. Epilepsia 1999; 40:1750. Parra, J, Iriarte, J, Kanner, AM, Bergen, DC. De novo psychogenic nonepileptic seizures after epilepsy surgery. Epilepsia 1998; 39:474.

Bautista, RE, Gonzales-Salazar, W, Ochoa, JG. Expanding the theory of symptom modeling in patents with psychogenic nonepileptic seizures. Epilepsy Behav 2008; 13:407. Barry, E, Krumholz, A, Bergey, GK, et al. Nonepileptic posttraumatic seizures. Epilepsia 1998; 39:427. Reuber, M, Fernandez, G, Helmstaedter, C, et al. Evidence of brain abnormality in patients with psychogenic nonepileptic seizures. Epilepsy Behav 2002; 3:249. Mokleby, K, Blomhoff, S, Malt, UF, et al. Psychiatric comorbidity and hostility in patients with psychogenic nonepileptic seizures compared with somatoform disorders and healthy controls. Epilepsia 2002; 43:193. DeToledo, JC, Lowe, MR, Haddad, H. Behaviors mimicking seizures in institutionalized individuals with multiple disabilities and epilepsy: a video-EEG study. Epilepsy Behav 2002; 3:242. Paolicchi, JM. The spectrum of nonepileptic events in children. Epilepsia 2002; 43 Suppl 3:60. Stone, J, Smyth, R, Carson, A, et al. La belle indifference in conversion symptoms and hysteria: systematic review. Br J Psychiatry 2006; 188:204. Ramani, V. Intensive monitoring of psychogenic seizures, aggression, and dyscontrol syndromes. In: Advances in Neurology, Gumnit RJ (Ed), Raven Press, New York 1986. p.203. Storzbach, D, Binder, LM, Salinsky, MC, et al. Improved prediction of nonepileptic seizures with combined MMPI and EEG measures. Epilepsia 2000; 41:332. Parra, J, Kanner, AM, Iriarte, J, Gil-Nagel, A. When should induction protocols be used in the diagnostic evaluation of patients with paroxysmal events?. Epilepsia 1998; 39:863. Devinsky, O, Kelley, K, Porter, RJ, Theodore, WH. Clinical and electroencephalographic features of simple partial seizures. Neurology 1988; 38:1347. Benbadis, SR, Johnson, K, Anthony, K, et al. Induction of psychogenic nonepileptic seizures without placebo. Neurology 2000; 55:1904. McGonigal, A, Oto, M, Russell, AJ, et al. Outpatient video EEG recording in the diagnosis of non-epileptic seizures: a randomised controlled trial of simple suggestion techniques. J Neurol Neurosurg Psychiatry 2002; 72:549. Slater, JD, Brown, MC, Jacobs, W, Ramsay, RE. Induction of pseudoseizures with intravenous saline placebo. Epilepsia 1995; 36:580. Lesser, RP. Psychogenic seizures. Neurology 1996; 46:1499. Walczak, TS, Williams, DT, Berten, W. Utility and reliability of placebo infusion in the evaluation of patients with seizures. Neurology 1994; 44:394. Lancman, ME, Asconape, JJ, Craven, WJ, et al. Predictive value of induction of psychogenic seizures by suggestion. Ann Neurol 1994; 35:359. Bazil, CW, Kothari, M, Luciano, D, et al. Provocation of nonepileptic seizures by suggestion in a general seizure population. Epilepsia 1994; 35:768. Gates, JR. Provocative testing should not be used for nonepileptic seizures. Arch Neurol 2001; 58:2065. Devinsky, O, Fisher, R. Ethical use of placebos and provocative testing in diagnosing nonepileptic seizures. Neurology 1996; 47:866. Chen, DK, So, YT, Fisher, RS. Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005; 65:668. Sperling, MR, Pritchard PB, 3rd, Engel, J Jr, et al. Prolactin in partial epilepsy: an indicator of limbic seizures. Ann Neurol 1986; 20:716. Oribe, E, Amini, R, Nissenbaum, E, Boal, B. Serum prolactin concentrations are elevated after syncope. Neurology 1996; 47:60. Willert, C, Spitzer, C, Kusserow, S, Runge, U. Serum neuron-specific enolase, prolactin, and creatine kinase after epileptic and psychogenic non-epileptic seizures. Acta Neurol Scand 2004; 109:318. Pritchard PB, 3rd, Wannamaker, BB, Sagel, J, Daniel, CM. Serum prolactin and cortisol levels in evaluation of pseudoepileptic seizures. Ann Neurol 1985; 18:87. Shah, AK, Shein, N, Fuerst, D, et al. Peripheral WBC count and serum prolactin level in various seizure types and nonepileptic events. Epilepsia 2001; 42:1472. Wyllie, E, Lueders, H, Pippenger, C, VanLente, F. Postictal serum creatine kinase in the diagnosis of seizure disorders. Arch Neurol 1985; 42:123. Ettinger, AB, Jandorf, L, Cabahug, CJ, et al. Post-ictal SPECT in

epileptic vs. non-epileptic seizures. J Epilepsy 1998; 11:67. Spanaki, MV, Spencer, SS, Corsi, M, et al. The role of quantitative ictal SPECT analysis in the evaluation of nonepileptic seizures. J Neuroimaging 1999; 9:210. Biraben, A, Taussig, D, Bernard, AM, et al. Video-EEG and ictal SPECT in three patients with both epileptic and non-epileptic seizures. Epileptic Disord 1999; 1:51. Varma, AR, Moriarty, J, Costa, DC, et al. HMPAO SPECT in non-epileptic seizures: preliminary results. Acta Neurol Scand 1996; 94:88. Almgren, PE, Nordgren, L, Skantze, H. A retrospective study of operationally defined hysterics. Br J Psychiatry 1978; 132:67. Bendefeldt, F, Miller, LL, Ludwig, AM. Cognitive performance in conversion hysteria. Arch Gen Psychiatry 1976; 33:1250. Bortz, JJ, Prigatano, GP, Blum, D, Fisher, RS. Differential response characteristics in nonepileptic and epileptic seizure patients on a test of verbal learning and memory. Neurology 1995; 45:2029. Dikmen, S, Hermann, BP, Wilensky, AJ, Rainwater, G. Validity of the Minnesota Multiphasic Personality Inventory (MMPI) to psychopathology in patients with epilepsy. J Nerv Ment Dis 1983; 171:114. Derry, PA, McLachlan, RS. The MMPI-2 as an adjunct to the diagnosis of pseudoseizures. Seizure 1996; 5:35. Schramke, CJ, Valeri, A, Valeriano, JP, Kelly, KM. Using the Minnesota Multiphasic Inventory 2, EEGs, and clinical data to predict nonepileptic events. Epilepsy Behav 2007; 11:343. Lesser, RP. Treatment and Outcome of Psychogenic Nonepileptic Seizures. Epilepsy Curr 2003; 3:198. Kanner, AM. More controversies on the treatment of psychogenic pseudoseizures: an addendum. Epilepsy Behav 2003; 4:360. Shen, W, Bowman, ES, Markand, ON. Presenting the diagnosis of pseudoseizure. Neurology 1990; 40:756. Selwa, LM, Geyer, J, Nikakhtar, N, et al. Nonepileptic seizure outcome varies by type of spell and duration of illness. Epilepsia 2000; 41:1330. Harden, CL, Burgut, FT, Kanner, AM. The diagnostic significance of video-EEG monitoring findings on pseudoseizure patients differs between neurologists and psychiatrists. Epilepsia 2003; 44:453. Oto, M, Espie, C, Pelosi, A, et al. The safety of antiepileptic drug withdrawal in patients with non-epileptic seizures. J Neurol Neurosurg Psychiatry 2005; 76:1682. Aboukasm, A, Mahr, G, Gahry, BR, et al. Retrospective analysis of the effects of psychotherapeutic interventions on outcomes of psychogenic nonepileptic seizures. Epilepsia 1998; 39:470. Farias, ST, Thieman, C, Alsaadi, TM. Psychogenic nonepileptic seizures: acute change in event frequency after presentation of the diagnosis. Epilepsy Behav 2003; 4:424. Silver, FW. Management of conversion disorder. Am J Phys Med Rehabil 1996; 75:134. LaFrance, WC Jr, Devinsky, O. The treatment of nonepileptic seizures: historical perspectives and future directions. Epilepsia 2004; 45 Suppl 2:15. LaFrance, WC Jr, Barry, JJ. Update on treatments of psychological nonepileptic seizures. Epilepsy Behav 2005; 7:364. Ettinger, AB, Dhoon, A, Weisbrot, DM, Devinsky, O. Predictive factors for outcome of nonepileptic seizures after diagnosis. J Neuropsychiatry Clin Neurosci 1999; 11:458. Zaroff, CM, Myers, L, Barr, WB, et al. Group psychoeducation as treatment for psychological nonepileptic seizures. Epilepsy Behav 2004; 5:587. Barry, JJ, Wittenberg, D, Bullock, KD, et al. Group therapy for patients with psychogenic nonepileptic seizures: a pilot study. Epilepsy Behav 2008; 13:624. Goldstein, LH, Deale, AC, Mitchell-O'Malley, SJ, et al. An evaluation of cognitive behavioral therapy as a treatment for dissociative seizures: a pilot study. Cogn Behav Neurol 2004; 17:41. Wyllie, E, Friedman, D, Luders, H, et al. Outcome of psychogenic seizures in children and adolescents compared with adults. Neurology 1991; 41:742. Walczak, TS, Papacostas, S, Williams, DT, et al. Outcome after diagnosis of psychogenic nonepileptic seizures. Epilepsia 1995; 36:1131. Savard, G, Andermann, F, Teitelbaum, J, Lehmann, H. Epileptic Munchausen's syndrome: a form of pseudoseizures distinct from hysteria and malingering. Neurology 1988; 38:1628. Lempert, T, Schmidt, D. Natural history and outcome of

psychogenic seizures: a clinical study in 50 patients. J Neurol 1990; 237:35. Arain, AM, Hamadani, AM, Islam, S, Abou-Khalil, BW. Predictors of early seizure remission after diagnosis of psychogenic nonepileptic seizures. Epilepsy Behav 2007; 11:409. Lawton, G. Epilepsy Behav 2009; 14:167. More common features distinguishing epileptic seizures and psychogenic nonepileptic seizures* Sign Epileptic PNES Duration Usually brief, less than 1-2 minutes Usually longer than 2 minutes Eyes Eyes usually open during event Eyes often closed Forced eye closure suggests PNES Motor activity Stereotyped Synchronized Build, progress Variable Forward pelvic thrusting, rolling side to side, opisthotonus Wax and wane Vocalization Uncommon, especially during convulsion May occur Prolonged ictal atonia Very rare May occur Incontinence Common in convulsive seizures Less common Autonomic signs Cyanosis, tachycardia common with major convulsion Uncommon Postictal symptoms Usually confused, drowsy Headache common May rapidly awaken and reorient Headache rare * No single feature is sensitive or specific for epileptic versus psychogenic nonepileptic seizures.