560565 research-article2014
EEGXXX10.1177/1550059414560565Clinical EEG and NeurosciencePavlova et al
Original Article
Sleep in Psychogenic Nonepileptic Seizures and Related Disorders
Clinical EEG and Neuroscience 1–8 © EEG and Clinical Neuroscience Society (ECNS) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059414560565 eeg.sagepub.com
Milena K. Pavlova1, Rebecca M. Allen2, and Barbara A. Dworetzky, MD1
Abstract Psychogenic nonepileptic seizures (PNES), a form of functional neurological symptom disorder (FNSD), are very rarely seen in genuine, electroencephalography (EEG)-confirmed sleep. However, they are more commonly reported as a nocturnal occurrence, likely from a state that is misidentified as sleep (termed by some as “pseudosleep”). Sleep state can be helpful to distinguish FNSD from other neurological disorders. Pseudo-cataplexy, a form of “psychogenic” narcolepsy, “pseudoparasomnia” and PNES can have a similar presentation. PNES and posttraumatic stress disorder (PTSD) frequently share previously experienced psychological trauma, and therefore the sleep abnormalities found in PTSD may be similarly present in PNES. Future research should use EEG monitoring to evaluate the sleep physiology of patients with FNSD such as PNES, as insights into sleep abnormalities may enable further understanding of the etiology and manifestations of PNES. Keywords psychogenic nonepileptic seizures, PNES, seizures, epilepsy, parasomnia, narcolepsy, sleep Received August 1, 2014; accepted October 29, 2014.
Introduction FNSD is extremely common, representing about 16% of all disorders referred to neurologists.1 The term is used synonymously with “psychogenic” and “conversion disorder,” and encompasses experiencing one or more neurological symptoms affecting voluntary motor or sensory function, which are not intentionally produced, and for which there is incompatibility between the symptoms and the physiological dysfunction seen in the disorder it mimics.2 FNSD encompass psychogenic paralysis, functional movement disorders, psychogenic sleep disorders such as pseudo-narcolepsy and pseudo-parasomnias, and PNES. The most common subtype of FNSD seen in neurological practice is PNES, followed by functional sensory symptoms, such as numbness, and motor symptoms such as paralysis, weakness, or movement disorders.1 Although patients with PNES often report sleep disturbances, the relationship between sleep disturbances and FNSD is insufficiently studied. There is little reported systematic data specifically investigating the relationship between PNES and sleep, which is surprising, given the increasing interest in the overlap of epilepsy and sleep and the rising number of publications in this area. The lack of data for PNES and sleep may be due to the variety of specialists who treat sleep disturbances, many of whom are not neurologists and thus may not identify somatic symptoms as PNES; alternatively, those with a strong interest in functional neurological symptoms may not have expertise in the interpretation of sleep data. Despite these barriers, there is an
available literature on the relationship between sleep and other forms of FNSD. Because of the relationship between traumatic experiences and FNSD, sleep disturbances in PTSD are particularly relevant. In this article, we review the available literature on the connection between sleep and FNSD, including PNES. We also discuss some basics of sleep, sleep disturbances commonly seen in PNES and PNES look-alikes seen in sleep, and the relationship between PTSD (a common comorbid disturbance in PNES) and sleep disturbances.
Basics of Sleep Sleep has been colloquially called “the normal loss of consciousness,” to describe the process of disconnection between brain activity and the consciously planned, directed activity of wakefulness. Neurophysiologically, sleep is a dynamic process with the different stages defined by specific EEG patterns. Generally, non–rapid eye movement (NREM) sleep, 1
Department of Neurology, Brigham and Women’s Hospital, Faulkner Sleep Testing Center, Harvard Medical School, Boston, MA, USA 2 Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Corresponding Author: Milena K. Pavlova, Department of Neurology, Brigham and Women’s Hospital, Faulkner Sleep Testing Center, Harvard Medical School, Suite 4970, 1153 Center Street, Boston, MA 02130, USA. Email: [email protected]
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encompassing the majority of sleep, is characterized by EEG synchronization, with vertex waves in sleep stage 1 (N1), sleep spindles and K-complexes in sleep stage 2 (N2), and high-voltage slow-wave activity defining sleep stage 3 (N3). Behaviorally, regular respirations, a lower muscle tone, and lower central nervous system oxygen demand are seen in NREM sleep. There is some dreaming during NREM sleep, but the dreams are described as fragments or images, while complex story dreams occur in rapid eye movement (REM) sleep. In addition to vivid or elaborate dreams, REM sleep is characterized by desynchronized EEG activity (comparable to wakefulness or N1 sleep), rapid eye movements, and loss of muscle tone or atonia, which helps distinguish this stage from drowsiness. These stages alternate multiple times each night, repeating in cycles, which in most humans last for around 90 minutes. Each sleep stage may be associated with various abnormalities and sometimes predispose for a stage specific disorder. For example, epileptic seizures are more frequent in NREM sleep, while obstructive sleep apnea is usually worse in REM sleep.
Sleep Disorders In general, sleep disorders that are treated by sleep specialists include insomnia, hypersomnias, circadian rhythm disorders, obstructive sleep apnea and other sleep-related breathing disorders, narcolepsy with cataplexy, and parasomnias (Table 1). In the clinical evaluation of sleep disorders, patients are notoriously unreliable when reporting their own quantity of sleep.3 While the average patient will unintentionally exaggerate how little or how much sleep he or she is getting, at times this misperception strays into extremes. The term paradoxical insomnia refers to a patient reporting not sleeping when, in fact, sleep has occurred and is confirmed on EEG. The opposite of paradoxical insomnia is “pseudosleep,” a term coined in 1996 to refer to a state that has all the behavioral characteristics of normal sleep, that is, the patient is supine, motionless, and with closed eyes, but has EEG with evidence of wakefulness, including alpha rhythm, active muscle artifact with active eye blinking, and no slow rolling eye movements.4 Therefore, objective measures of sleep such as polysomnograms or EEG, are essential to its clinical evaluation. Two types of sleep disorders are of particular relevance here as they can mimic FNSD: narcolepsy and parasomnias. Narcolepsy with cataplexy needs to clinically be distinguished from both epileptic and nonepileptic events, and, interestingly, FNSD can mimic narcolepsy (“pseudo-narcolepsy”) just as PNES mimics epilepsy. Narcolepsy is a disorder of REM sleep regulation. The essential abnormality is invasion of components of REM sleep into different states of consciousness. The typical symptoms fall into 4 categories: hypersomnolence (sleep inappropriately occurring during the typical wakefulness period), sleep paralysis (atonia of REM sleep on awakening), hypnagogic hallucinations (imagery typical of REM sleep occurring in wakefulness), and cataplexy (atonia of REM sleep in clear wakefulness, often associated with laughing; International Classification of Sleep Disorders, third edition).
Cataplexy can more easily be distinguished from epileptic seizures as it is a motor phenomenon, and unlike an epileptic seizure, the cataplectic attack occurs in response to positive emotion (typically laughter or telling a joke) with full consciousness maintained throughout the event. The diagnosis of narcolepsy is established with a multiple sleep latency test (MSLT), which is considered supportive of narcolepsy if the patient falls asleep during nap opportunities (within 8 minutes on average) and if REM is seen within 15 minutes of falling asleep on at least 2 occasions, in the absence of confounding effect of sleep deprivation or medications. Other supportive evidence includes low hypocretin in the cerebrospinal fluid (in narcolepsy with cataplexy) or human leukocyte antigen (HLA) testing, in which presence of DQB1*0602 increases the likelihood of narcolepsy. Parasomnias are abnormal nocturnal behaviors that can mimic both epileptic seizures and PNES. Clinically, parasomnias are characterized by undesirable physical events that occur in transition to sleep, during sleep, or immediately after an arousal. Although sometimes provoked by stress, they are not psychogenic in nature. The EEG will show sleep during parasomnias (with confusional arousal as a notable exception). Like narcolepsy, with elements of sleep intruding into wakefulness, parasomnias are thought of as abnormal combinations of REM, NREM, and waking characteristics. There are 3 main neurophysiological processes hypothesized to lead to parasomnias: (a) incomplete sleep or incomplete wakefulness, or “state instability”; (b) persistence of the altered awareness into wakefulness, known as “sleep inertia”; and (c) abnormal stimulation of a central nervous system area generating a specific set of behaviors, or a “central locomotive pattern generator.” A large variety of behaviors can occur within the parasomnia spectrum. Some are mostly associated with REM sleep, such as REM behavior disorder, sleep-related hallucinations, and sleep paralysis, while others are mostly associated with NREM sleep, such as sleepwalking, sleep terrors, confusional arousals, and sleep eating. Unlike typical epileptic seizures, parasomnias may involve complex behaviors. The individual episodes are not stereotypic, last longer than epileptic seizures, and may have a waxing–waning course. Directed actions, such as locomotion (leaving the bed), sleep eating, and sleep-related sexual behaviors are fairly well described.12,13 Some parasomnias are commonly associated with comorbid psychiatric disturbances. For example, nightmare disorder, a parasomnia arising from REM sleep, is significantly more frequently reported by patients with generalized anxiety disorder, depression, PTSD, and other psychiatric disturbances (DSM5). Childhood trauma may significantly increase the frequency of nightmare experiences.14 Nocturnal panic attacks, panic attacks that arise during typical hours of sleep, have a similar spectrum of comorbidities. They usually occur either during or immediately after awaking from NREM sleep, most often within the first half of the sleep period (or within 4 hours of sleep onset). They often correlate with the frequency of nightmares and dysphonic dreams.
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Pavlova et al Table 1. Sleep and Functional Neurological Symptom Disorders. Sleep disorders Narcolepsy with cataplexy •• Invasion of components of rapid eye movement (REM) sleep into different states of consciousness •• Diagnosed with multiple sleep latency test •• Symptoms: •• Hypersomnolence: Sleep inappropriately occurring during the typical wakefulness period •• Sleep paralysis: Atonia of REM sleep on awakening •• Hypnagogic hallucinations: Imagery typical of REM sleep occurring in wakefulness •• Cataplexy: Occurs in response to positive emotion with full consciousness maintained throughout the event Parasomnias •• Undesirable physical events that occur in transition to sleep, during sleep, or immediately after an arousal •• Not psychogenic •• Abnormal combinations of REM, non-REM (NREM), and waking characteristics •• REM parasomnias: REM behavior disorder, sleep-related hallucinations, sleep paralysis, nightmare disorder •• NREM parasomnias: Sleepwalking, sleep terrors, confusional arousals, sleep eating •• Nocturnal panic attacks •• Occur during or immediately after awakening from NREM sleep •• Comorbid with multiple psychiatric disorders •• Tourette syndrome tics •• Among the few movement disorders that persist during sleep •• May be seen in REM sleep, despite normal REM atonia Other sleep disorders •• Insomnia •• Hypersomnia •• Circadian rhythm disorders •• Obstructive sleep apnea and other sleep-related breathing disorders •• Restless legs syndrome Functional neurological symptom disorders (FNSD) Psychogenic nonepileptic seizures (PNES) •• Mimics epilepsy •• Most common subtype of FNSD seen in neurological practice •• Strongly associated with trauma, especially childhood abuse •• PNES events very rarely arise from genuine sleep •• Nocturnal PNES events mostly arise from pseudosleep •• Small increase in percentage of REM sleep, similar to sleep architecture changes seen in depression •• Relationship to sleep abnormalities is largely unstudied, however, as a trauma-related disorder PNES may share many of the same sleep abnormalities found in posttraumatic stress disorder (PTSD) Psychogenic sleep disorders •• Pseudo-narcolepsy •• Mimics narcolepsy just as PNES mimics epilepsy •• Hicks and Shapiro (1999)5: 44-year-old woman with sleepiness, hypnagogic hallucinations, and spells with loss of tone •• Krahn (2005)6: 48-year-old woman with sleepiness and episodes of sudden-onset bilateral leg weakness •• Pizza et al (2013)7: 2 sisters, ages 17 and 12 years, with sleepiness and emotionally triggered sudden falls •• Pseudo-parasomnias •• Psychogenic symptoms mimicking parasomnias, usually diagnosed as nocturnal dissociation events •• Schenck et al (1989)8: 8 cases presenting with features suggestive of a parasomnia, but with EEG wakefulness •• Calamaro and Mason (2008)9: 6-year-old girl with bizarre episodes of dramatic regressive behavior around the time of sleep •• Paradoxical insomnia •• Patient reports not sleeping when, in fact, sleep has occurred and is confirmed on EEG •• Pseudosleep •• All the behavioral characteristics of normal sleep, that is, the patient is supine, motionless, and with closed eyes, but has EEG with evidence of wakefulness •• Functional movement disorders •• Includes tremor, dystonia, and weakness •• Comorbid with sleep disturbances •• Ahmed et al (2008)10: Case series of 5 children, aged 7-14 years, with abnormal movements that disappeared during sleep, aiding diagnosis of psychogenic movements •• Functional sensory symptoms •• Psychogenic paralysis •• Shahar et al (2012)11: Case series of 3 adolescents, aged 13-15 years, presenting with hemiparesis, but the supposedly paralyzed limbs were observed to move during sleep Downloaded from eeg.sagepub.com at UNIV OF MIAMI on December 31, 2014
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The ticks in patients with Tourette syndrome are among the few movement disorders that persist during sleep, and may even be seen in REM sleep (despite the normal atonia of REM sleep),15 consistent with impaired dopamine regulation pathways. Given the above associations, it would be natural to expect a high rate of parasomnias (both REM and NREM related) among patients with PNES. However, this issue has never been studied systematically. Factors that cause sleep state instability include stress (as it often leads to sleep loss) and thus may also precipitate parasomnia events. Many medications also contribute to parasomnias. Because of the complexity of the behaviors, the longer duration, and the waxing–waning course, parasomnias are more likely to be confused with PNES than with epileptic seizures. Parasomnias are, however, less frequent, and thus they are not commonly encountered during continuous video EEG monitoring for definitive diagnosis.16
Sleep and Functional Neurological Symptom Disorder Patients with functional motor symptoms, such as tremor, dystonia, and weakness report multiple other symptoms, including sleep disturbances.17 One small study compared sleep architecture in 8 women with PNES with 10 patients with epileptic seizures and no comorbid PNES. The authors reported a small, but statistically significant difference in the percentage of REM sleep (23% in the PNES patients versus 18% among the patients with epilepsy). They found no difference in total sleep time or the individual NREM stages. The authors also discussed that the increase in REM percentage is similar to the sleep architecture changes seen in depression, probably indicating similar mechanisms given the frequent association of PNES with mood disorders, as was the case in the PNES cohort of this study. Few studies have investigated the relationship between sleep and other types of FNSD. Most of the literature published on sleep and FNSD falls into 2 categories: case reports and clinical case series highlighting sleep as a method of distinguishing medical from psychogenic symptoms, and case reports and series focusing on functional symptoms mimicking sleep disorders, particularly narcolepsy.
Functional Neurological Symptom Disorder Mimicking Sleep Disorders Just as FNSD can mimic epilepsy, stroke, and movement disorders, functional neurological symptoms can also mimic sleep disorders, including parasomnias and narcolepsy. Multiple case reports have described this phenomenon. There are no available diagnostic criteria to positively distinguish between a parasomnia and FNSD. Nevertheless, specific cases have been described of FNSD mimicking parasomnias. Schenck et al8 published 8 cases with video and polysomnographic documentation of a dissociative disorder that presented with features suggestive of a parasomnia. One of the cases was a 19-year-old man with a 4-year history of twice
weekly nocturnal episodes in which he crawled around the house for 1 to 2 hours while growling and hissing, and he was amnestic for these behaviors, but did report dreaming that he was a large cat in a zoo. A sleep study showed that these episodes were arising from EEG wakefulness.8 Calamaro and Mason9 reported a case of a 6-year-old girl who initially presented with bizarre episodes of dramatic regressive behavior, around the time of sleep, consisting of sudden rolling back of the eyes, crawling on the ground, intermittent facial twitching, and infantile speech with guttural noises. In the sleep laboratory, she vocalized during these episodes and placed random objects, such as a remote, into her mouth. The differential diagnosis for these episodes include parasomnias such as agitated sleepwalking, confusional arousals, sleep terrors, REM behavior disorder, nightmares, as well as nocturnal seizures. These cases, however, were ultimately identified as nocturnal dissociation events, a psychiatric term encompassing these “pseudoparasomnias.” Nocturnal dissociation has been further considered in the differential diagnosis of de novo parasomnia seen in association with medical disorders, such as thyroid disease.18 In addition to FNSD mimicking parasomnias, cases of FNSD mimicking narcolepsy have also been described. In 1999, Hicks and Shapiro5 reported on a 44-year-old woman with a history of recurrent depression who presented with excessive daytime sleepiness, hypnagogic and hypnopompic hallucinations, and migraine headaches. She also had spells, in response to intense emotion such as fear and anxiety, consisting of sudden bilateral loss of motor tone in her face and arms, her head dropping forward with her eyes closed, and no response to her name for several minutes. These symptoms are not consistent with cataplexy, as in cataplexy the patient is usually awake. After disclosing that she was having an affair with her hypnotherapist, her symptoms completely resolved. The authors conclude that she likely had a “hysterical functional neurological disorder,” which they label as “pseudo-narcolepsy.”5 While the term pseudo-narcolepsy is not commonly used, additional case reports of FNSD mimicking narcolepsy have appeared in the literature. Krahn6 described the case of a 48-year-old woman with episodes of sleepiness followed by sudden-onset bilateral leg weakness with inability to walk for hours at a time, often dragging her legs in a dramatic fashion in public, but never falling or injuring herself. After her first sleep study and MSLT, she was diagnosed with narcolepsy with cataplexy, but she sought a second and then a third opinion, and was tested 2 more times, both in sleep disorder centers. Her electromyogram (EMG) tone was normal during spells when she reported inability to move, her HLA determination was negative for DQB1*0602, and during a spell her deep tendon reflexes were intact. She was then identified as suffering from FNSD, attributed to life stressors, including unemployment and marital discord.5 Pizza et al7 described the case of 2 sisters, aged 17 and 12 years, with daytime sleepiness and spontaneous and emotionally triggered sudden falls to the ground, both positive for the
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Pavlova et al HLA DQB1*0602 allele. The elder sister’s spells clinically appeared consistent with cataplexy: sudden falls to the ground, occurring both while standing or sitting, elicited by emotions, with immobility up to a few minutes. However, during these episodes she had normal EMG muscle tone and deep tendon reflexes, ruling out cataplectic attacks. Her younger sister presented with sudden episodes of vertigo followed by apparent brief loss of consciousness and falls to the ground with seconds to minutes of unresponsiveness, several times per day, in the context of restless legs symptoms, daytime sleepiness, attention deficit hyperactivity disorder symptoms, and sleep talking. Like her older sibling, she showed EEG wakefulness during the episodes, normal EMG muscle tone, and normal deep tendon reflexes during her spells. Both sisters were ultimately diagnosed with FNSD.7 Presumably, pseudo-narcolepsy has a similar etiology to PNES and a patient presenting with sudden leg weakness, falls to the ground, or brief periods of unresponsiveness could just as easily have been identified as having PNES rather than pseudo-cataplexy. The diagnosis may depend more on the expertise of the physician evaluating the patient than the characteristics of the presentation. However, it is notable that all of the patients with pseudo-narcolepsy had other symptoms of disordered sleep, such as daytime sleepiness, sleep-related hallucinations, and sleep talking, in addition to cataplexy-like events. In the case of narcolepsy, reliably distinguishing FNSD from other neuropsychiatric disorders is difficult by clinical interview alone and may involve polysomnography/MSLT, cerebrospinal fluid analysis, and physical examination during cataplectic spells. Similarly to PNES, while a negative diagnosis (ruling out narcolepsy) is a first diagnostic step, providing a positive diagnosis (which would be the same for PNES or “pseudo-narcolepsy”) becomes the most important next therapeutic move.
Functional Paralysis, Functional Movement Disorders, and Sleep While many movement disorders do improve or disappear during sleep, there are a number of case reports in the literature of sleep being used to distinguish neurological symptoms from an identified neurological disorder versus those from psychogenic origin. In 2008, Ahmed et al10 described 5 children, varying in age from 7 to 14 years, presenting with abnormal movements diagnosed as psychogenic. These movements included intermittent tremor of the left leg, repetitive rhythmic clonus-like abnormal movements of the left ankle and knee joint, side-to-side head shaking, and constant tic-like movements of the head and shoulders. Interestingly, the last patient, an 11-year-old boy with forward-and-backward twitching of his head with jerklike movements of his shoulders, also suffered from other sleep disturbances that included sleepwalking, tiredness, sleeptalking, excessive daytime sleep, and nightmares. In all cases, the abnormal movements disappeared during sleep, and this absence of symptoms during sleep aided in the diagnosis.10
Using sleep to identify psychogenic symptoms is not just limited to movement disorders. Stein et al19 reported the case of an adolescent with psychogenic cough in whom the cough disappeared during sleep. Shahar et al11 in 2012 reported a case series of 3 adolescents, a girl aged 13 years and 2 boys aged 14 and 15 years, who presented with hemiparesis and 1-sided sensory symptoms strongly suggestive of acute stroke or other focal lesion. In all 3 cases, suspicion of somatoform disorder arose in significant part because the supposedly paralyzed limbs were observed to move during sleep. Moreover, the Hoover sign was positive in these patients. These 3 patients also presented as comfortable, content, and emotionally detached from their grave condition, which in the authors’ experience was markedly different from the agitated effect of children who suffer vascular strokes.11 These cases suggest that the mechanism that leads to psychogenic paralysis is bypassed or altered in sleep, possibly explained by a change in the attention system, or thalamocortical gating; that is, sleep may prevent influence of the cortex from suppressing body movements. Observation during sleep of patients suspected to suffer from FNSD could be potentially helpful information, guiding accurate diagnosis in certain specific cases. In cases where symptoms are voluntarily fabricated, such as with malingering, the reason why the symptoms disappear during sleep is obvious: the higher level, intentional control of the body is naturally suppressed during sleep. In FNSD, which is an unconscious and nonintentional process, the issue of intentional control becomes controversial. Several models have been proposed to explain the association between trauma history and development of functional neurological symptoms.20 In psychoanalytic thought, FNSD emerges when the brain tries to suppress the conscious recall of negative memories associated with trauma exposure by converting the negative affect into somatic symptoms that were present at the time of trauma exposure, or are a symbolic representation of it. This model explains the often observed apparent lack of concern about the somatic symptoms (“la belle indifference”), as the defensive reaction succeeds in reducing the patient’s overall anxiety.20 A recent model,21,22 based on neuroimaging findings, is that patients with functional neurological symptoms have overly sensitive fear responses from the amygdala, potentially facilitated by prior traumatic experiences, resulting in abnormal self-directed attention and a misinterpretation of movements or perceptual experiences as involuntary symptoms of an underlying disease. This model explains why functional neurological symptoms tend to abate when the patient is distracted. One can hypothesize that if attention instability is part of the genesis of these symptoms, sleep-related absence of attention could lead to the return of “normal” movements during sleep.23 A similar mechanism may explain why PNES events are very rarely seen to arise from sleep.
Sleep and Posttraumatic Stress Disorder While little has been published on the connection between sleep and FNSD, insights into potential sleep alterations in
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PNES and other FNSD may also be gained by examining PTSD-related sleep alterations. Similar to other FNSD, PNES have been found to be strongly associated with trauma, especially childhood abuse20,24 and PTSD.25 Although few studies have investigated the relationship specifically between sleep and FNSD, sleep has been extensively studied in PTSD. PTSD is a disorder that develops in certain vulnerable individuals following trauma, typically exposure to a life-threatening stressor. It consists of intrusive recollections of the incident such as flashbacks and nightmares, within 3 clusters of symptoms: reexperiencing, avoidance, and hyperarousal.2,26 A core feature of PTSD is the presence of nightmares (a reexperiencing symptom with signs of hyperarousal), which usually occur during REM sleep. In 1989, Ross et al27 hypothesized that PTSD may be fundamentally a disorder of dysfunctional REM sleep, leading to posttraumatic anxiety dreams and alterations in the startle response. Indeed, many sleep disturbances have been found to be associated with PTSD and have been hypothesized to be risk factors for development of the disorder. Sleep disturbance prior to trauma, and REM sleep fragmentation (multiple arousals or awakening during REM sleep) as well as nightmares soon after trauma, are associated with the eventual development of PTSD.28-30 PTSD is associated with a wide range of sleep complaints and disturbances: complaints of insomnia,29 diminished total sleep time,31 and decreased slow wave sleep.32 The most robust findings regarding sleep and PTSD have shown EEG alterations in REM sleep, including REM sleep fragmentation.29,30 A sleep neuroimaging study reported an increase in regional brain glucose metabolism in limbic and paralimbic regions, which was greater in adults with PTSD than in adults with depression.30 Moreover, hypervigilance has been found to be associated with alterations in REM; that is, the severity of the startle response in PTSD has been found to be negatively correlated with REM latency.32 One mechanism by which REM sleep dysregulation might contribute to the symptomatology in PTSD is through an alteration in sleep-dependent memory processing. Sleep processes memory in various ways, including memory stabilization and enhancement, selective consolidation of emotional and salient material, and finding insight, that is, recognizing patterns that were not noticed prior to sleeping.33 The dreams of REM sleep have long been identified as directly contributing to stress adaptation, mood regulation, and specifically lessening the emotional salience of memory.34 REM sleep does seem to decrease amygdala response to previously encountered emotional stimuli.35 The recurrent nightmares in PTSD have been hypothesized to occur as a result of the brain attempting, and repeatedly failing, to “decouple” the emotion from the traumatic memory.36 It has been hypothesized that because of this failure of sleep-dependent memory processing, individuals who suffer from PTSD reexperience trauma in vivid detail with intense emotion, even years after the event. The hypothesis, that sleep disturbance is a hallmark of PTSD and a direct contributor to its etiology, is further supported by data showing that treatment of sleep disturbances has a beneficial effect on
daytime PTSD symptoms. This has been demonstrated with both behavioral (imagery rehearsal therapy) and pharmacologic (prazosin, eszopiclone) interventions.30,31,37 In summary, PTSD is a condition resulting from exposure to trauma with considerable evidence that sleep is disturbed. As PNES and other FNSD are also significantly associated with trauma histories, it is reasonable to hypothesize that significant sleep alteration is also associated with or even characteristic of them. Similar to PTSD, sleep disruption may be a significant contributor to the etiology of PNES and requires future investigative efforts. Publications in PNES need to begin to characterize sleep as it may be an underinvestigated avenue for treatment of this otherwise difficult-to-treat disorder.
Psychogenic Nonepileptic Seizure Events Occurring in Association With Sleep Epileptic seizures are known to occur during sleep, so clinically events reported from sleep are presumed to be epileptic seizures rather than PNES. However, PNES patients sometimes do report events that occur while they are sleeping, and those who have had PNES for a shorter duration tend to report more such episodes.38 There is only 1 article documenting PNES events arising from EEG confirmed sleep. Of 118 events in a retrospective blinded review of video-EEG, only 8 PNES events from 5 unique subjects began during EEG-documented sleep, without intervening waking alpha rhythm (in 6 of the events) or within 7 seconds after the onset of an arousal.39 Mostly, nocturnal PNES events have been documented to arise from brief wakefulness during the main sleep period or from “pseudosleep,” that is, a state perceived as sleep, but documented by EEG to be wakefulness, and not from genuine sleep.16,40 In the initial study, which coined the term pseudosleep, preictal “pseudosleep” was seen in 10 of 18 patients with PNES and in none of 39 patients with epileptic seizures.16 Thus, the aberrant perception of state of consciousness is strongly correlated with the occurrence of PNES. In differentiating epileptic, nonepileptic, and parasomnia-related nocturnal events, video-EEG is the gold standard diagnostic test. Events occurring during “pseudosleep” are strongly suggestive of PNES.41 Thus, even though little is known about what sleep abnormalities are specifically seen in PNES and how these sleep alterations may relate to the etiology of the disorder, sleep is helpful in the evaluation of PNES.
Conclusion The relationship between PNES and sleep is sparse in the currently available literature. Epileptic seizures may arise from sleep, while PNES mostly arises either from wakefulness or from “pseudosleep.” Interestingly, there have been case reports and case series describing pseudo-cataplexy, a form of “psychogenic” narcolepsy, and many of these attacks are described as appearing similar to PNES events. One can hypothesize that the etiology and risk factors for PNES and pseudo-narcolepsy
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Pavlova et al might overlap, and whether a patient is diagnosed with one or the other may depend on the training background of a given provider. The relationship between FNSD in general and sleep has also not been extensively studied. However, as the mechanism of FNSD is hypothesized to be related in part to alterations in attention, and as attentional mechanisms are disrupted during sleep, sleep can provide valuable information to distinguish some psychogenic disorders such as psychogenic paralysis from organic neurological disorders, as the presenting symptoms disappear during sleep. Given the plethora of sleep abnormalities found in PTSD, and the common risk factor of trauma in both PTSD and PNES (or FNSD in general), similar sleep abnormalities may be present in PNES as well. Future research should use EEG monitoring to evaluate the sleep physiology of patients with functional neurological symptoms, such as PNES and pseudo-cataplexy. Insights into sleep abnormalities may enable further understanding of the etiology and manifestations of PNES. Declaration of Conflicting Interests The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
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somatoform unilateral weakness and sensory impairment mimicking vascular stroke. J Clin Neurosci. 2012;19:980-983. 12. Schenck CH, Arnulf I, Mahowald MW. Sleep and sex: what can go wrong? A review of the literature on sleep related disorders and abnormal sexual behaviors and experiences. Sleep. 2007;30:683-702. 13. Cramer Bornemann MA, Mahowald MW, Schenck CH. Parasomnia—clinical features and forensic implications. Chest. 2006;130:605-610. 14. Agargun MY, Kara H, Özer ÖA, Selvi YV, Kiran Ü, Kiran S. Nightmares and dissociative experiences: the key role of childhood traumatic events. Psychiatry Clin Neurosci. 2003;57:139-145. 15. Cohrs S, Rasch T, Altmeyer S, et al. Decreased sleep quality and increased sleep related movements in patients with Tourette’s syndrome. J Neurol Neurosurg Psychiatry. 2001;70:192-197. 16. Benbadis SR, O’Neill E, Tatum WO, Heriaud L. Outcome of prolonged video-EEG monitoring at a typical referral epilepsy center. Epilepsia. 2004;45:1150-1153. 17. Gelauff J, Stone J, Edwards M, Carson A. The prognosis of functional (psychogenic) motor symptoms: a systematic review. J Neurol Neurosurg Psychiatry. 2014;85:220-226. 18. Ajlouni K, Daradkeh TK, Ajlouni H, Mubaidin A, Jarrah N. De novo sleepwalking associated with hyperthyroidism. Sleep Hypn. 2001;3:112-116. 19. Stein M, Harper G, Chen J, Kohen D, Wells R. Persistent cough in an adolescent. Dev Behav Pediatr. 1999;20:434-438. 20. Roelofs K, Spinhoven P. Trauma and medically unexplained symptoms. Clin Psychol Rev. 2007;27:798-820. 21. Mehta AR, Rowe JB, Schrag AE. Imaging psychogenic movement disorders. Curr Neurol Neurosci Rep. 2012;13:402. 22. Carson AJ, Brown R, David AS, et al. Functional (conversion) neurological symptoms: research since the millennium. J Neurol Neurosurg Psychiatry. 2012;83:842-850. 23. Lauerma H. Nocturnal limb movements in conversion paralysis. J Nerv Ment Dis. 1993;181:707-708. 24. Sharpe D, Faye C. Non-epileptic seizures and child sexual abuse: a critical review of the literature. Clinical Psychol Rev. 2006;26:1020-1040. 25. Fiszman A, Alves-Leon SV, Nunes RG, D’Andrea I, Figueira I. Traumatic events and posttraumatic stress disorder in patients with psychogenic nonepileptic seizures: a critical review. Epilepsy Behav. 2004;5:818-825. 26. O’Donnell ML, Alkemade N, Nickerson A, et al. Impact of the diagnostic changes to post-traumatic stress disorder for DSM-5 and the proposed changes to ICD-11. Br J Psychiatry. 2014;205:230-235. 27. Ross RJ, Ball WA, Sullivan KA, Caroff SN. Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry. 1989;146:697-707. 28. Bryant RA, Creamer M, O’Donnell M, Silove D, McFarlane AC. Sleep disturbance immediately prior to trauma predicts subsequent psychiatric disorder. Sleep. 2010;33:69-74. 29. Kobayashi I, Cowdin N, Mellman TA. One’s sex, sleep, and posttraumatic stress disorder. Biol Sex Differ. 2012;3:29. 30. Germain A. Sleep disturbances as the hallmark of PTSD: where are we now? Am J Psychiatry. 2013;170:372-382. 31. Krystal AD. Psychiatric disorders and sleep. Sleep Disord. 2012;30:1389-1413. 32. Yetkin S, Aydin H, Özgen F. Polysomnography in patients with post-traumatic stress disorder: sleep in PTSD. Psychiatry Clin Neurosci. 2010;64:309-317.
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33. Stickgold R. Parsing the role of sleep in memory processing. Curr Opin Neurobiol. 2013;23:847-853. 34. Greenberg R, Pearlman C, Schwartz WR, Grossman HY. Memory, emotion, and REM sleep. J Abnorm Psychol. 1983;92:378-381. 35. van der Helm E, Yao J, Dutt S, Rao V, Saletin JM, Walker MP. REM sleep depotentiates amygdala activity to previous emotional experiences. Curr Biol. 2011;21:2029-2032. 36. Walker MP, van der Helm E. Overnight therapy? The role of sleep in emotional brain processing. Psychol Bull. 2009;135: 731-748. 37. Pollack MH, Hoge EA, Worthington JJ, et al. Eszopiclone for the treatment of posttraumatic stress disorder and associated insomnia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011;72:892-897.
38. Reuber M, Jamnadas-Khoda J, Broadhurst M, et al. Psychogenic nonepileptic seizure manifestations reported by patients and witnesses. Epilepsia. 2011;52:2028-2035. 39. Orbach D, Ritaccio A, Devinsky O. Psychogenic, nonepileptic seizures associated with video-EEG-verified sleep. Epilepsia. 2003;44:64-68. 40. 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: 1009-1012. 41. Avbersek A, Sisodiya S. Does the primary literature provide support for clinical signs used to distinguish psychogenic nonepileptic seizures from epileptic seizures? J Neurol Neurosurg Psychiatry. 2010;81:719-725.
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EEGXXX10.1177/1550059414560565Clinical EEG and NeurosciencePavlova et al
Original Article
Sleep in Psychogenic Nonepileptic Seizures and Related Disorders
Clinical EEG and Neuroscience 1–8 © EEG and Clinical Neuroscience Society (ECNS) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1550059414560565 eeg.sagepub.com
Milena K. Pavlova1, Rebecca M. Allen2, and Barbara A. Dworetzky, MD1
Abstract Psychogenic nonepileptic seizures (PNES), a form of functional neurological symptom disorder (FNSD), are very rarely seen in genuine, electroencephalography (EEG)-confirmed sleep. However, they are more commonly reported as a nocturnal occurrence, likely from a state that is misidentified as sleep (termed by some as “pseudosleep”). Sleep state can be helpful to distinguish FNSD from other neurological disorders. Pseudo-cataplexy, a form of “psychogenic” narcolepsy, “pseudoparasomnia” and PNES can have a similar presentation. PNES and posttraumatic stress disorder (PTSD) frequently share previously experienced psychological trauma, and therefore the sleep abnormalities found in PTSD may be similarly present in PNES. Future research should use EEG monitoring to evaluate the sleep physiology of patients with FNSD such as PNES, as insights into sleep abnormalities may enable further understanding of the etiology and manifestations of PNES. Keywords psychogenic nonepileptic seizures, PNES, seizures, epilepsy, parasomnia, narcolepsy, sleep Received August 1, 2014; accepted October 29, 2014.
Introduction FNSD is extremely common, representing about 16% of all disorders referred to neurologists.1 The term is used synonymously with “psychogenic” and “conversion disorder,” and encompasses experiencing one or more neurological symptoms affecting voluntary motor or sensory function, which are not intentionally produced, and for which there is incompatibility between the symptoms and the physiological dysfunction seen in the disorder it mimics.2 FNSD encompass psychogenic paralysis, functional movement disorders, psychogenic sleep disorders such as pseudo-narcolepsy and pseudo-parasomnias, and PNES. The most common subtype of FNSD seen in neurological practice is PNES, followed by functional sensory symptoms, such as numbness, and motor symptoms such as paralysis, weakness, or movement disorders.1 Although patients with PNES often report sleep disturbances, the relationship between sleep disturbances and FNSD is insufficiently studied. There is little reported systematic data specifically investigating the relationship between PNES and sleep, which is surprising, given the increasing interest in the overlap of epilepsy and sleep and the rising number of publications in this area. The lack of data for PNES and sleep may be due to the variety of specialists who treat sleep disturbances, many of whom are not neurologists and thus may not identify somatic symptoms as PNES; alternatively, those with a strong interest in functional neurological symptoms may not have expertise in the interpretation of sleep data. Despite these barriers, there is an
available literature on the relationship between sleep and other forms of FNSD. Because of the relationship between traumatic experiences and FNSD, sleep disturbances in PTSD are particularly relevant. In this article, we review the available literature on the connection between sleep and FNSD, including PNES. We also discuss some basics of sleep, sleep disturbances commonly seen in PNES and PNES look-alikes seen in sleep, and the relationship between PTSD (a common comorbid disturbance in PNES) and sleep disturbances.
Basics of Sleep Sleep has been colloquially called “the normal loss of consciousness,” to describe the process of disconnection between brain activity and the consciously planned, directed activity of wakefulness. Neurophysiologically, sleep is a dynamic process with the different stages defined by specific EEG patterns. Generally, non–rapid eye movement (NREM) sleep, 1
Department of Neurology, Brigham and Women’s Hospital, Faulkner Sleep Testing Center, Harvard Medical School, Boston, MA, USA 2 Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Corresponding Author: Milena K. Pavlova, Department of Neurology, Brigham and Women’s Hospital, Faulkner Sleep Testing Center, Harvard Medical School, Suite 4970, 1153 Center Street, Boston, MA 02130, USA. Email: [email protected]
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encompassing the majority of sleep, is characterized by EEG synchronization, with vertex waves in sleep stage 1 (N1), sleep spindles and K-complexes in sleep stage 2 (N2), and high-voltage slow-wave activity defining sleep stage 3 (N3). Behaviorally, regular respirations, a lower muscle tone, and lower central nervous system oxygen demand are seen in NREM sleep. There is some dreaming during NREM sleep, but the dreams are described as fragments or images, while complex story dreams occur in rapid eye movement (REM) sleep. In addition to vivid or elaborate dreams, REM sleep is characterized by desynchronized EEG activity (comparable to wakefulness or N1 sleep), rapid eye movements, and loss of muscle tone or atonia, which helps distinguish this stage from drowsiness. These stages alternate multiple times each night, repeating in cycles, which in most humans last for around 90 minutes. Each sleep stage may be associated with various abnormalities and sometimes predispose for a stage specific disorder. For example, epileptic seizures are more frequent in NREM sleep, while obstructive sleep apnea is usually worse in REM sleep.
Sleep Disorders In general, sleep disorders that are treated by sleep specialists include insomnia, hypersomnias, circadian rhythm disorders, obstructive sleep apnea and other sleep-related breathing disorders, narcolepsy with cataplexy, and parasomnias (Table 1). In the clinical evaluation of sleep disorders, patients are notoriously unreliable when reporting their own quantity of sleep.3 While the average patient will unintentionally exaggerate how little or how much sleep he or she is getting, at times this misperception strays into extremes. The term paradoxical insomnia refers to a patient reporting not sleeping when, in fact, sleep has occurred and is confirmed on EEG. The opposite of paradoxical insomnia is “pseudosleep,” a term coined in 1996 to refer to a state that has all the behavioral characteristics of normal sleep, that is, the patient is supine, motionless, and with closed eyes, but has EEG with evidence of wakefulness, including alpha rhythm, active muscle artifact with active eye blinking, and no slow rolling eye movements.4 Therefore, objective measures of sleep such as polysomnograms or EEG, are essential to its clinical evaluation. Two types of sleep disorders are of particular relevance here as they can mimic FNSD: narcolepsy and parasomnias. Narcolepsy with cataplexy needs to clinically be distinguished from both epileptic and nonepileptic events, and, interestingly, FNSD can mimic narcolepsy (“pseudo-narcolepsy”) just as PNES mimics epilepsy. Narcolepsy is a disorder of REM sleep regulation. The essential abnormality is invasion of components of REM sleep into different states of consciousness. The typical symptoms fall into 4 categories: hypersomnolence (sleep inappropriately occurring during the typical wakefulness period), sleep paralysis (atonia of REM sleep on awakening), hypnagogic hallucinations (imagery typical of REM sleep occurring in wakefulness), and cataplexy (atonia of REM sleep in clear wakefulness, often associated with laughing; International Classification of Sleep Disorders, third edition).
Cataplexy can more easily be distinguished from epileptic seizures as it is a motor phenomenon, and unlike an epileptic seizure, the cataplectic attack occurs in response to positive emotion (typically laughter or telling a joke) with full consciousness maintained throughout the event. The diagnosis of narcolepsy is established with a multiple sleep latency test (MSLT), which is considered supportive of narcolepsy if the patient falls asleep during nap opportunities (within 8 minutes on average) and if REM is seen within 15 minutes of falling asleep on at least 2 occasions, in the absence of confounding effect of sleep deprivation or medications. Other supportive evidence includes low hypocretin in the cerebrospinal fluid (in narcolepsy with cataplexy) or human leukocyte antigen (HLA) testing, in which presence of DQB1*0602 increases the likelihood of narcolepsy. Parasomnias are abnormal nocturnal behaviors that can mimic both epileptic seizures and PNES. Clinically, parasomnias are characterized by undesirable physical events that occur in transition to sleep, during sleep, or immediately after an arousal. Although sometimes provoked by stress, they are not psychogenic in nature. The EEG will show sleep during parasomnias (with confusional arousal as a notable exception). Like narcolepsy, with elements of sleep intruding into wakefulness, parasomnias are thought of as abnormal combinations of REM, NREM, and waking characteristics. There are 3 main neurophysiological processes hypothesized to lead to parasomnias: (a) incomplete sleep or incomplete wakefulness, or “state instability”; (b) persistence of the altered awareness into wakefulness, known as “sleep inertia”; and (c) abnormal stimulation of a central nervous system area generating a specific set of behaviors, or a “central locomotive pattern generator.” A large variety of behaviors can occur within the parasomnia spectrum. Some are mostly associated with REM sleep, such as REM behavior disorder, sleep-related hallucinations, and sleep paralysis, while others are mostly associated with NREM sleep, such as sleepwalking, sleep terrors, confusional arousals, and sleep eating. Unlike typical epileptic seizures, parasomnias may involve complex behaviors. The individual episodes are not stereotypic, last longer than epileptic seizures, and may have a waxing–waning course. Directed actions, such as locomotion (leaving the bed), sleep eating, and sleep-related sexual behaviors are fairly well described.12,13 Some parasomnias are commonly associated with comorbid psychiatric disturbances. For example, nightmare disorder, a parasomnia arising from REM sleep, is significantly more frequently reported by patients with generalized anxiety disorder, depression, PTSD, and other psychiatric disturbances (DSM5). Childhood trauma may significantly increase the frequency of nightmare experiences.14 Nocturnal panic attacks, panic attacks that arise during typical hours of sleep, have a similar spectrum of comorbidities. They usually occur either during or immediately after awaking from NREM sleep, most often within the first half of the sleep period (or within 4 hours of sleep onset). They often correlate with the frequency of nightmares and dysphonic dreams.
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Pavlova et al Table 1. Sleep and Functional Neurological Symptom Disorders. Sleep disorders Narcolepsy with cataplexy •• Invasion of components of rapid eye movement (REM) sleep into different states of consciousness •• Diagnosed with multiple sleep latency test •• Symptoms: •• Hypersomnolence: Sleep inappropriately occurring during the typical wakefulness period •• Sleep paralysis: Atonia of REM sleep on awakening •• Hypnagogic hallucinations: Imagery typical of REM sleep occurring in wakefulness •• Cataplexy: Occurs in response to positive emotion with full consciousness maintained throughout the event Parasomnias •• Undesirable physical events that occur in transition to sleep, during sleep, or immediately after an arousal •• Not psychogenic •• Abnormal combinations of REM, non-REM (NREM), and waking characteristics •• REM parasomnias: REM behavior disorder, sleep-related hallucinations, sleep paralysis, nightmare disorder •• NREM parasomnias: Sleepwalking, sleep terrors, confusional arousals, sleep eating •• Nocturnal panic attacks •• Occur during or immediately after awakening from NREM sleep •• Comorbid with multiple psychiatric disorders •• Tourette syndrome tics •• Among the few movement disorders that persist during sleep •• May be seen in REM sleep, despite normal REM atonia Other sleep disorders •• Insomnia •• Hypersomnia •• Circadian rhythm disorders •• Obstructive sleep apnea and other sleep-related breathing disorders •• Restless legs syndrome Functional neurological symptom disorders (FNSD) Psychogenic nonepileptic seizures (PNES) •• Mimics epilepsy •• Most common subtype of FNSD seen in neurological practice •• Strongly associated with trauma, especially childhood abuse •• PNES events very rarely arise from genuine sleep •• Nocturnal PNES events mostly arise from pseudosleep •• Small increase in percentage of REM sleep, similar to sleep architecture changes seen in depression •• Relationship to sleep abnormalities is largely unstudied, however, as a trauma-related disorder PNES may share many of the same sleep abnormalities found in posttraumatic stress disorder (PTSD) Psychogenic sleep disorders •• Pseudo-narcolepsy •• Mimics narcolepsy just as PNES mimics epilepsy •• Hicks and Shapiro (1999)5: 44-year-old woman with sleepiness, hypnagogic hallucinations, and spells with loss of tone •• Krahn (2005)6: 48-year-old woman with sleepiness and episodes of sudden-onset bilateral leg weakness •• Pizza et al (2013)7: 2 sisters, ages 17 and 12 years, with sleepiness and emotionally triggered sudden falls •• Pseudo-parasomnias •• Psychogenic symptoms mimicking parasomnias, usually diagnosed as nocturnal dissociation events •• Schenck et al (1989)8: 8 cases presenting with features suggestive of a parasomnia, but with EEG wakefulness •• Calamaro and Mason (2008)9: 6-year-old girl with bizarre episodes of dramatic regressive behavior around the time of sleep •• Paradoxical insomnia •• Patient reports not sleeping when, in fact, sleep has occurred and is confirmed on EEG •• Pseudosleep •• All the behavioral characteristics of normal sleep, that is, the patient is supine, motionless, and with closed eyes, but has EEG with evidence of wakefulness •• Functional movement disorders •• Includes tremor, dystonia, and weakness •• Comorbid with sleep disturbances •• Ahmed et al (2008)10: Case series of 5 children, aged 7-14 years, with abnormal movements that disappeared during sleep, aiding diagnosis of psychogenic movements •• Functional sensory symptoms •• Psychogenic paralysis •• Shahar et al (2012)11: Case series of 3 adolescents, aged 13-15 years, presenting with hemiparesis, but the supposedly paralyzed limbs were observed to move during sleep Downloaded from eeg.sagepub.com at UNIV OF MIAMI on December 31, 2014
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The ticks in patients with Tourette syndrome are among the few movement disorders that persist during sleep, and may even be seen in REM sleep (despite the normal atonia of REM sleep),15 consistent with impaired dopamine regulation pathways. Given the above associations, it would be natural to expect a high rate of parasomnias (both REM and NREM related) among patients with PNES. However, this issue has never been studied systematically. Factors that cause sleep state instability include stress (as it often leads to sleep loss) and thus may also precipitate parasomnia events. Many medications also contribute to parasomnias. Because of the complexity of the behaviors, the longer duration, and the waxing–waning course, parasomnias are more likely to be confused with PNES than with epileptic seizures. Parasomnias are, however, less frequent, and thus they are not commonly encountered during continuous video EEG monitoring for definitive diagnosis.16
Sleep and Functional Neurological Symptom Disorder Patients with functional motor symptoms, such as tremor, dystonia, and weakness report multiple other symptoms, including sleep disturbances.17 One small study compared sleep architecture in 8 women with PNES with 10 patients with epileptic seizures and no comorbid PNES. The authors reported a small, but statistically significant difference in the percentage of REM sleep (23% in the PNES patients versus 18% among the patients with epilepsy). They found no difference in total sleep time or the individual NREM stages. The authors also discussed that the increase in REM percentage is similar to the sleep architecture changes seen in depression, probably indicating similar mechanisms given the frequent association of PNES with mood disorders, as was the case in the PNES cohort of this study. Few studies have investigated the relationship between sleep and other types of FNSD. Most of the literature published on sleep and FNSD falls into 2 categories: case reports and clinical case series highlighting sleep as a method of distinguishing medical from psychogenic symptoms, and case reports and series focusing on functional symptoms mimicking sleep disorders, particularly narcolepsy.
Functional Neurological Symptom Disorder Mimicking Sleep Disorders Just as FNSD can mimic epilepsy, stroke, and movement disorders, functional neurological symptoms can also mimic sleep disorders, including parasomnias and narcolepsy. Multiple case reports have described this phenomenon. There are no available diagnostic criteria to positively distinguish between a parasomnia and FNSD. Nevertheless, specific cases have been described of FNSD mimicking parasomnias. Schenck et al8 published 8 cases with video and polysomnographic documentation of a dissociative disorder that presented with features suggestive of a parasomnia. One of the cases was a 19-year-old man with a 4-year history of twice
weekly nocturnal episodes in which he crawled around the house for 1 to 2 hours while growling and hissing, and he was amnestic for these behaviors, but did report dreaming that he was a large cat in a zoo. A sleep study showed that these episodes were arising from EEG wakefulness.8 Calamaro and Mason9 reported a case of a 6-year-old girl who initially presented with bizarre episodes of dramatic regressive behavior, around the time of sleep, consisting of sudden rolling back of the eyes, crawling on the ground, intermittent facial twitching, and infantile speech with guttural noises. In the sleep laboratory, she vocalized during these episodes and placed random objects, such as a remote, into her mouth. The differential diagnosis for these episodes include parasomnias such as agitated sleepwalking, confusional arousals, sleep terrors, REM behavior disorder, nightmares, as well as nocturnal seizures. These cases, however, were ultimately identified as nocturnal dissociation events, a psychiatric term encompassing these “pseudoparasomnias.” Nocturnal dissociation has been further considered in the differential diagnosis of de novo parasomnia seen in association with medical disorders, such as thyroid disease.18 In addition to FNSD mimicking parasomnias, cases of FNSD mimicking narcolepsy have also been described. In 1999, Hicks and Shapiro5 reported on a 44-year-old woman with a history of recurrent depression who presented with excessive daytime sleepiness, hypnagogic and hypnopompic hallucinations, and migraine headaches. She also had spells, in response to intense emotion such as fear and anxiety, consisting of sudden bilateral loss of motor tone in her face and arms, her head dropping forward with her eyes closed, and no response to her name for several minutes. These symptoms are not consistent with cataplexy, as in cataplexy the patient is usually awake. After disclosing that she was having an affair with her hypnotherapist, her symptoms completely resolved. The authors conclude that she likely had a “hysterical functional neurological disorder,” which they label as “pseudo-narcolepsy.”5 While the term pseudo-narcolepsy is not commonly used, additional case reports of FNSD mimicking narcolepsy have appeared in the literature. Krahn6 described the case of a 48-year-old woman with episodes of sleepiness followed by sudden-onset bilateral leg weakness with inability to walk for hours at a time, often dragging her legs in a dramatic fashion in public, but never falling or injuring herself. After her first sleep study and MSLT, she was diagnosed with narcolepsy with cataplexy, but she sought a second and then a third opinion, and was tested 2 more times, both in sleep disorder centers. Her electromyogram (EMG) tone was normal during spells when she reported inability to move, her HLA determination was negative for DQB1*0602, and during a spell her deep tendon reflexes were intact. She was then identified as suffering from FNSD, attributed to life stressors, including unemployment and marital discord.5 Pizza et al7 described the case of 2 sisters, aged 17 and 12 years, with daytime sleepiness and spontaneous and emotionally triggered sudden falls to the ground, both positive for the
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Pavlova et al HLA DQB1*0602 allele. The elder sister’s spells clinically appeared consistent with cataplexy: sudden falls to the ground, occurring both while standing or sitting, elicited by emotions, with immobility up to a few minutes. However, during these episodes she had normal EMG muscle tone and deep tendon reflexes, ruling out cataplectic attacks. Her younger sister presented with sudden episodes of vertigo followed by apparent brief loss of consciousness and falls to the ground with seconds to minutes of unresponsiveness, several times per day, in the context of restless legs symptoms, daytime sleepiness, attention deficit hyperactivity disorder symptoms, and sleep talking. Like her older sibling, she showed EEG wakefulness during the episodes, normal EMG muscle tone, and normal deep tendon reflexes during her spells. Both sisters were ultimately diagnosed with FNSD.7 Presumably, pseudo-narcolepsy has a similar etiology to PNES and a patient presenting with sudden leg weakness, falls to the ground, or brief periods of unresponsiveness could just as easily have been identified as having PNES rather than pseudo-cataplexy. The diagnosis may depend more on the expertise of the physician evaluating the patient than the characteristics of the presentation. However, it is notable that all of the patients with pseudo-narcolepsy had other symptoms of disordered sleep, such as daytime sleepiness, sleep-related hallucinations, and sleep talking, in addition to cataplexy-like events. In the case of narcolepsy, reliably distinguishing FNSD from other neuropsychiatric disorders is difficult by clinical interview alone and may involve polysomnography/MSLT, cerebrospinal fluid analysis, and physical examination during cataplectic spells. Similarly to PNES, while a negative diagnosis (ruling out narcolepsy) is a first diagnostic step, providing a positive diagnosis (which would be the same for PNES or “pseudo-narcolepsy”) becomes the most important next therapeutic move.
Functional Paralysis, Functional Movement Disorders, and Sleep While many movement disorders do improve or disappear during sleep, there are a number of case reports in the literature of sleep being used to distinguish neurological symptoms from an identified neurological disorder versus those from psychogenic origin. In 2008, Ahmed et al10 described 5 children, varying in age from 7 to 14 years, presenting with abnormal movements diagnosed as psychogenic. These movements included intermittent tremor of the left leg, repetitive rhythmic clonus-like abnormal movements of the left ankle and knee joint, side-to-side head shaking, and constant tic-like movements of the head and shoulders. Interestingly, the last patient, an 11-year-old boy with forward-and-backward twitching of his head with jerklike movements of his shoulders, also suffered from other sleep disturbances that included sleepwalking, tiredness, sleeptalking, excessive daytime sleep, and nightmares. In all cases, the abnormal movements disappeared during sleep, and this absence of symptoms during sleep aided in the diagnosis.10
Using sleep to identify psychogenic symptoms is not just limited to movement disorders. Stein et al19 reported the case of an adolescent with psychogenic cough in whom the cough disappeared during sleep. Shahar et al11 in 2012 reported a case series of 3 adolescents, a girl aged 13 years and 2 boys aged 14 and 15 years, who presented with hemiparesis and 1-sided sensory symptoms strongly suggestive of acute stroke or other focal lesion. In all 3 cases, suspicion of somatoform disorder arose in significant part because the supposedly paralyzed limbs were observed to move during sleep. Moreover, the Hoover sign was positive in these patients. These 3 patients also presented as comfortable, content, and emotionally detached from their grave condition, which in the authors’ experience was markedly different from the agitated effect of children who suffer vascular strokes.11 These cases suggest that the mechanism that leads to psychogenic paralysis is bypassed or altered in sleep, possibly explained by a change in the attention system, or thalamocortical gating; that is, sleep may prevent influence of the cortex from suppressing body movements. Observation during sleep of patients suspected to suffer from FNSD could be potentially helpful information, guiding accurate diagnosis in certain specific cases. In cases where symptoms are voluntarily fabricated, such as with malingering, the reason why the symptoms disappear during sleep is obvious: the higher level, intentional control of the body is naturally suppressed during sleep. In FNSD, which is an unconscious and nonintentional process, the issue of intentional control becomes controversial. Several models have been proposed to explain the association between trauma history and development of functional neurological symptoms.20 In psychoanalytic thought, FNSD emerges when the brain tries to suppress the conscious recall of negative memories associated with trauma exposure by converting the negative affect into somatic symptoms that were present at the time of trauma exposure, or are a symbolic representation of it. This model explains the often observed apparent lack of concern about the somatic symptoms (“la belle indifference”), as the defensive reaction succeeds in reducing the patient’s overall anxiety.20 A recent model,21,22 based on neuroimaging findings, is that patients with functional neurological symptoms have overly sensitive fear responses from the amygdala, potentially facilitated by prior traumatic experiences, resulting in abnormal self-directed attention and a misinterpretation of movements or perceptual experiences as involuntary symptoms of an underlying disease. This model explains why functional neurological symptoms tend to abate when the patient is distracted. One can hypothesize that if attention instability is part of the genesis of these symptoms, sleep-related absence of attention could lead to the return of “normal” movements during sleep.23 A similar mechanism may explain why PNES events are very rarely seen to arise from sleep.
Sleep and Posttraumatic Stress Disorder While little has been published on the connection between sleep and FNSD, insights into potential sleep alterations in
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PNES and other FNSD may also be gained by examining PTSD-related sleep alterations. Similar to other FNSD, PNES have been found to be strongly associated with trauma, especially childhood abuse20,24 and PTSD.25 Although few studies have investigated the relationship specifically between sleep and FNSD, sleep has been extensively studied in PTSD. PTSD is a disorder that develops in certain vulnerable individuals following trauma, typically exposure to a life-threatening stressor. It consists of intrusive recollections of the incident such as flashbacks and nightmares, within 3 clusters of symptoms: reexperiencing, avoidance, and hyperarousal.2,26 A core feature of PTSD is the presence of nightmares (a reexperiencing symptom with signs of hyperarousal), which usually occur during REM sleep. In 1989, Ross et al27 hypothesized that PTSD may be fundamentally a disorder of dysfunctional REM sleep, leading to posttraumatic anxiety dreams and alterations in the startle response. Indeed, many sleep disturbances have been found to be associated with PTSD and have been hypothesized to be risk factors for development of the disorder. Sleep disturbance prior to trauma, and REM sleep fragmentation (multiple arousals or awakening during REM sleep) as well as nightmares soon after trauma, are associated with the eventual development of PTSD.28-30 PTSD is associated with a wide range of sleep complaints and disturbances: complaints of insomnia,29 diminished total sleep time,31 and decreased slow wave sleep.32 The most robust findings regarding sleep and PTSD have shown EEG alterations in REM sleep, including REM sleep fragmentation.29,30 A sleep neuroimaging study reported an increase in regional brain glucose metabolism in limbic and paralimbic regions, which was greater in adults with PTSD than in adults with depression.30 Moreover, hypervigilance has been found to be associated with alterations in REM; that is, the severity of the startle response in PTSD has been found to be negatively correlated with REM latency.32 One mechanism by which REM sleep dysregulation might contribute to the symptomatology in PTSD is through an alteration in sleep-dependent memory processing. Sleep processes memory in various ways, including memory stabilization and enhancement, selective consolidation of emotional and salient material, and finding insight, that is, recognizing patterns that were not noticed prior to sleeping.33 The dreams of REM sleep have long been identified as directly contributing to stress adaptation, mood regulation, and specifically lessening the emotional salience of memory.34 REM sleep does seem to decrease amygdala response to previously encountered emotional stimuli.35 The recurrent nightmares in PTSD have been hypothesized to occur as a result of the brain attempting, and repeatedly failing, to “decouple” the emotion from the traumatic memory.36 It has been hypothesized that because of this failure of sleep-dependent memory processing, individuals who suffer from PTSD reexperience trauma in vivid detail with intense emotion, even years after the event. The hypothesis, that sleep disturbance is a hallmark of PTSD and a direct contributor to its etiology, is further supported by data showing that treatment of sleep disturbances has a beneficial effect on
daytime PTSD symptoms. This has been demonstrated with both behavioral (imagery rehearsal therapy) and pharmacologic (prazosin, eszopiclone) interventions.30,31,37 In summary, PTSD is a condition resulting from exposure to trauma with considerable evidence that sleep is disturbed. As PNES and other FNSD are also significantly associated with trauma histories, it is reasonable to hypothesize that significant sleep alteration is also associated with or even characteristic of them. Similar to PTSD, sleep disruption may be a significant contributor to the etiology of PNES and requires future investigative efforts. Publications in PNES need to begin to characterize sleep as it may be an underinvestigated avenue for treatment of this otherwise difficult-to-treat disorder.
Psychogenic Nonepileptic Seizure Events Occurring in Association With Sleep Epileptic seizures are known to occur during sleep, so clinically events reported from sleep are presumed to be epileptic seizures rather than PNES. However, PNES patients sometimes do report events that occur while they are sleeping, and those who have had PNES for a shorter duration tend to report more such episodes.38 There is only 1 article documenting PNES events arising from EEG confirmed sleep. Of 118 events in a retrospective blinded review of video-EEG, only 8 PNES events from 5 unique subjects began during EEG-documented sleep, without intervening waking alpha rhythm (in 6 of the events) or within 7 seconds after the onset of an arousal.39 Mostly, nocturnal PNES events have been documented to arise from brief wakefulness during the main sleep period or from “pseudosleep,” that is, a state perceived as sleep, but documented by EEG to be wakefulness, and not from genuine sleep.16,40 In the initial study, which coined the term pseudosleep, preictal “pseudosleep” was seen in 10 of 18 patients with PNES and in none of 39 patients with epileptic seizures.16 Thus, the aberrant perception of state of consciousness is strongly correlated with the occurrence of PNES. In differentiating epileptic, nonepileptic, and parasomnia-related nocturnal events, video-EEG is the gold standard diagnostic test. Events occurring during “pseudosleep” are strongly suggestive of PNES.41 Thus, even though little is known about what sleep abnormalities are specifically seen in PNES and how these sleep alterations may relate to the etiology of the disorder, sleep is helpful in the evaluation of PNES.
Conclusion The relationship between PNES and sleep is sparse in the currently available literature. Epileptic seizures may arise from sleep, while PNES mostly arises either from wakefulness or from “pseudosleep.” Interestingly, there have been case reports and case series describing pseudo-cataplexy, a form of “psychogenic” narcolepsy, and many of these attacks are described as appearing similar to PNES events. One can hypothesize that the etiology and risk factors for PNES and pseudo-narcolepsy
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Pavlova et al might overlap, and whether a patient is diagnosed with one or the other may depend on the training background of a given provider. The relationship between FNSD in general and sleep has also not been extensively studied. However, as the mechanism of FNSD is hypothesized to be related in part to alterations in attention, and as attentional mechanisms are disrupted during sleep, sleep can provide valuable information to distinguish some psychogenic disorders such as psychogenic paralysis from organic neurological disorders, as the presenting symptoms disappear during sleep. Given the plethora of sleep abnormalities found in PTSD, and the common risk factor of trauma in both PTSD and PNES (or FNSD in general), similar sleep abnormalities may be present in PNES as well. Future research should use EEG monitoring to evaluate the sleep physiology of patients with functional neurological symptoms, such as PNES and pseudo-cataplexy. Insights into sleep abnormalities may enable further understanding of the etiology and manifestations of PNES. Declaration of Conflicting Interests The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
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