Sleep-related Epilepsy Research Articles

A Case of Sleep Masturbation Related to Dopamine Agonist Therapy

To the Editor: Dopamine agonists are well known for precipitating compulsive behaviors, including pathological gambling, compulsive eating, compulsive buying, and hypersexuality1,2 as well as compulsive or repetitive weighing of oneself, card/video game playing, locking/unlocking doors, and dressing and undressing.3 With regard to hypersexuality, compulsive masturbation has been previously described in the literature.4,5 However, we are not aware of any cases of sleep masturbation (ie, masturbating while fully asleep) during dopamine agonist therapy. In the following case report, we describe an elderly man, on treatment with pramipexole for Parkinson’s disease, whose wife reported his unusual behavior of masturbating while fully asleep, which was temporally related to dopamine agonist therapy. Case report. Mr A, a 75-year-old white, married man with a history of hypertension, coronary artery disease, benign prostatic hypertrophy, diabetes, gastroesophageal reflux, and mild dementia, was prescribed losartan 50 mg/d, clopidogrel 75 mg/d, atorvastatin 80 mg/d, omeprazole 20 mg/d, and donepezil 5 mg/d. In early 2010, the patient began to experience balance difficulties, stiffness, and shuffling gait. He was evaluated by his primary care physician in October 2010, diagnosed with Parkinson’s disease, and referred to a neurologist. The neurologist prescribed treatment with pramipexole, which was initiated in March 2011 at 0.375 mg/d and titrated to 1.5 mg/d over a 2-week period. When the patient was seen by his primary care physician in May 2011, the Parkinson’s symptoms had considerably improved. However, the patient reported new-onset daytime compulsive masturbation that temporally paralleled his exposure to pramipexole. The patient’s spouse of 10 years, who accompanied him to the appointment, reported that the patient masturbated during sleep as well. The patient was advised to discuss this possible adverse effect of pramipexole therapy with his neurologist. When seen again by his primary care physician in July 2011, the patient had discontinued pramipexole in response to his neurologist’s recommendation. With the cessation of pramipexole, the behavior of sleep masturbation promptly and totally abated. Hypersexuality related to dopamine agonist therapy appears to affect a minority of patients. According to Voon and colleagues,6 in a sample of 297 patients with Parkinson’s disease, 2.4% reported drug-related hypersexual behavior. Likewise, after initiating dopamine agonist therapy for Parkinson’s disease, Bostwick and colleagues7 reported the prevalence of either hypersexuality or new-onset gambling at 2.6%. Therefore, while dopamine agonist–induced hypersexuality is uncommon, it appears to affect a significant minority of patients. Importantly, masturbation during sleep has been reported in various medical or psychological conditions, which this patient did not exhibit. For example, Guilleminault and colleagues8 examined 11 individuals with sleep-related atypical sexual behavior, including masturbation, and found associations with psychological symptoms such as guilt, shame, and depression. Schenck and colleagues9 reported sleep masturbation among individuals with parasomnias and sleep-related epilepsy. Because hypersexuality, including sleep masturbation, is an embarrassing symptom that may not be spontaneously reported by patients on dopamine agonist therapy or their significant others/families, we suggest that all patients be queried about various compulsive behaviors after initiating therapy with dopamine agonists. These socially disabling behaviors typically abate with dose reduction or discontinuation of the dopamine agonist.1

Type II focal cortical dysplasia: Electroclinical phenotype and surgical outcome related to imaging

Type II focal cortical dysplasia (TTFCD), a highly epileptogenic lesion with severe epilepsy curable by surgery, is missed by magnetic resonance imaging (MRI) in about one third of cases. Little is known about the electroclinical presentation in these MRI-negative patients and a poor surgical outcome is frequently reported. We compared the clinical and neurophysiologic features in MRI-negative and MRI-positive cases in order to better identify candidates for surgery. Among 62 consecutive TTFCD patients (38 male, 24 female; 7-52 years old; 22 children) operated for intractable epilepsy, 25 (40%) presented negative MRI findings. We compared the history of epilepsy; the type, frequency, and distribution of seizures; neurologic examination cognitive and psychiatric impairment; interictal-ictal electroencephalography (EEG) and stereo-EEG (SEEG) data, fluorodeoxyglucose positron emission tomography (FDG-PET) data, neuropathologic findings; and surgical outcome in the MRI-negative and the MRI-positive groups. Severe partial epilepsy beginning in childhood, high seizure frequency including status epilepticus, stereotyped seizures suggestive of precise brain localization, extratemporal location and functional area involvement were characteristic and similarly found in both groups. On EEG, pseudorhythmic activity was found in about 40% of patients in each group. SEEG recordings demonstrated the typical pattern characterizing TTFCD in both groups. FDG-PET had a localization value in 84% of the MRI-negative cases and helped to delineate the dysplastic cortex in 65% of the MRI-positive cases. The combination of imaging and neurophysiologic data allowed us to perform safe and restricted resections, limited to a single gyrus in more than half of all cases. In addition, we were able to avoid invasive monitoring in most MRI-positive cases and even in some selected MRI-negative cases. The proportion of patients with a favorable surgical outcome was comparable in both groups (88% in MRI-negative and 94% in MRI-positive cases). The main difference between the groups was a significantly higher frequency of sleep-related epilepsy in the MRI-negative group (p = 0.028). This phenotypic characteristic provides a new argument for TTFCD in MRI-negative extratemporal epilepsy. These results lead us to consider that children or adult patients in whom electroclinical data suggest TTFCD, are highly suitable for surgery, especially for cryptogenic sleep-related epilepsy.

Sleep-related epilepsy in a Long-Evans hooded rat model of depression.

Neonatal treatment with clomipramine (CLI) has been shown to have reliable behavioral and biological changes that mimic major symptomatic and biochemical changes found in depression. This paper further explores a common feature of depression, the comorbidity of seizure activity and depressive behaviors in this mode. Rat pups were neonatally treated with 40mg/kg/day of CLI from postnatal day 8 through 21. In adulthood, they were instrumented with electroencephalographic (EEG) and electromyographic (EMG) electrodes for 24h of polysomnogram (PSG) recordings. PSG data were analyzed for: (1) sleep-wake cycle; (2) spectral power; and (3) epileptiform activity, including NREM-to-REM transition (NRT) bursts. Neonatal treatment with CLI reliably produces enhanced levels of REM (p < 0.01) and reduced sexual activity (p < 0.05). Theta power was enhanced during NREM sleep in the CLI group (p = 0.02). CLI-treated animals experienced increased frequency at the NRT (p < 0.01), as well as additional epileptiform activity of continuous (CTS; p < 0.05) and petite-continuous (P-CTS; p < 0.01) types, across the sleep-wake cycle. There is a strong temporal correlation with increased REM sleep duration, increased frequency of NRT bursts, and increased theta power during NREM sleep in CLI-treated animals. Neonatal CLI-treated animals experienced significantly more epileptiform activity as a whole, in addition to comorbid features of depression in adulthood. Neonatal exposure to CLI will not only produce depressive phenotype but may also enhance risk for epilepsy in some individuals. This warrants further investigation into currently acceptable medicinal use in humans.

Taylor’s focal cortical dysplasia increases the risk of sleep‐related epilepsy

To analyze the topography of the epileptogenic zone (EZ) and the etiologic substrate as risk factors for sleep-related focal epilepsy. Three hundred three patients (172 males and 131 females, mean age at surgery 25.6 +/- 13.1 years), who were seizure-free after resective surgery for drug-resistant focal epilepsy, were retrospectively reviewed. Statistical analysis was conducted to evaluate the risk of presenting sleep-related epilepsy (SRE) against topography of resection (assumed to correspond or to include the EZ) and results of histology. Thirty-nine patients (12.8%) presented with an SRE. At bivariate analysis, a higher frequency of SRE was associated with a frontal lobe EZ (p = 1.94 x 10(-9)) and Taylor's FCD (TFCD, p = 2.20 x 10(-16)), whereas architectural FCD (p = 0.00977), ganglioglioma (p = 0.02508), and mesial temporal sclerosis (p = 2.47 x 10(-5)) were correlated with a reduced frequency of SRE. Multivariate analysis demonstrated that the only variable significantly associated with SRE was the presence of a TFCD, which increased 14-fold the risk of SRE [p = 1.66 x 10(-10); risk ratio (RR) = 14.44]. In this study, we have demonstrated a significant and strong association between SRE and TFCD in a select population of patients with drug-resistant focal epilepsy submitted to surgical resection of the EZ. Although our results cannot be applied to the entire spectrum of SRE, the presence of TFCD as the underlying etiology should be considered when evaluating patients with SRE, because surgery can provide excellent results on seizures in these cases.

Pleiotropic functional effects of the first epilepsy-associated mutation in the human CHRNA2 gene

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) can be caused by mutations in the neuronal nicotinic acetylcholine receptor (nAChR) subunit genes CHRNA4 and CHRNB2. Recently, a point mutation (α2-I279N) associated with sleep-related epilepsy has been described in a third nAChR gene, CHRNA2. We demonstrate here that α2-I279N can be co-expressed with the major structural subunit CHRNB2. α2-I279N causes a marked gain-of-function effect and displays a distinct biopharmacological profile, including markedly reduced inhibition by carbamazepine and increased nicotine sensitivity.

Aspects of parasomnias in childhood and adolescence

The many parasomnias now officially described often occur in young patients. They are at risk of being confused with each other if their characteristic features are not well known and...

Atypical presentation of NREM arousal parasomnia with repetitive episodes

The case report describes a distinct variant of non-REM (Rapid Eye Movement) arousal parasomnia, sleepwalking type, featuring repetitive abrupt arousals, mostly from slow-wave sleep, and various automatisms and semi-purposeful behaviours. The frequency of events and distribution throughout the night presented as a continuous status of parasomnia ('status parasomnicus'). The patient responded well to treatment typically administered for adult NREM parasomnias, and after careful review of the clinical presentation, objective findings and treatment outcome, sleep-related epilepsy was ruled out in favour of parasomnia.

The role of the nicotinic acetylcholine receptors in sleep-related epilepsy

The role of neuronal acetylcholine receptors (nAChRs) in epilepsy has been clearly established by the finding of mutations in a subset of genes coding for subunits of the nAChRs in a form of sleep-related epilepsy with familial occurrence in about 30% of probands and dominant inheritance, named autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sporadic and familial forms have similar clinical and EEG features. Seizures begin in middle childhood as clusters of sleep-related attacks with prominent motor activity, and sustained dystonic posturing. In addition to nocturnal seizures, psychosis or schizophrenia, behavioral disorders, memory deficits and mental retardation were described in some individuals. Although over hundred families are on record, only a minority of them have been linked to mutations in the genes coding for the α4, α2 and β2 ( CHRNA4, CHRNA2, and CHRNB2) subunits of the nAChRs, indicating that ADNFLE is genetically heterogeneous despite a relatively homogeneous clinical picture. Functional characterization of some mutations suggests that gain of the receptor function might be the basis for epileptogenesis. In vitro and in vivo studies have shown high density of nAChRs in the thalamus, over activated brainstem ascending cholinergic pathway and enhanced GABAergic function, reinforcing the hypothesis that cortico-subcortical networks, regulating arousal from sleep, play a central role in seizure precipitation in ADNFLE.

The Man Who Fought in Sleep

A 60-year-old Caucasian man presents to a sleep disorders clinic with a chief complaint of abnormal body movements and talking during sleep. He is accompanied by his wife, who reports that the patient frequently shouts, punches, and kicks during sleep. The episodes began 4 to 5 years ago. Initially, they were sporadic but have been occurring once or twice a week lately, usually in the later part of the night. Three nights ago, the patient punched his wife violently in sleep and then pushed her away while yelling loudly. When she woke him up, he said that he was dreaming that he was in a jungle, fighting a bear. She is now afraid to sleep with him and sleeps in a different bed. The patient feels embarrassed and says that he has frequently experienced dreams in which he fights an animal or a monster. He denies any daytime complaints. The patient has a history of hypertension and hypercholesterolemia. His medications include metoprolol 50 mg twice a day and simvastatin 20 mg once a day. He smoked 1 pack of cigarette a day for 35 years until he quit 8 years ago. He drinks 1 to 2 beers on the weekend but denies alcohol abuse. On examination, the patient is an overweight male. The remainder of the findings on physical examination are normal. The patient undergoes overnight polysomnography. The accompanying figure shows an epoch from the polysomnogram. The sleep technician notes that the patient was kicking and shouting in sleep during this episode. Figure 1 An epoch from the patient's polysomnogram. EOG refers to electrooculogram; EMG, electromyogram; EKG, electrocardiogram. Which of the following is true about this disorder? The dreams are usually associated with abrupt awakenings and a feeling of panic, with full alertness occurring immediately upon awakening. The patient has a higher likelihood of developing multiple system atrophy. The patient has a higher likelihood of having iron-deficiency anemia. Secondary enuresis and tongue-biting are common features. Answer: B Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a loss of the normal skeletal muscle atonia during REM phase of sleep. The disorder frequently manifests as enactment of dreams, resulting in shouting, flailing of arms, and moving and kicking during sleep, and may result in injury to self and to others.1 It is common for people affected by this disorder to report a history of vivid, intense, and violent dreams. RBD is predominantly a disease of older men (older than 50 years of age), with the mean age at presentation in 1 series being approximately 64 years.2 The polysomnogram frequently reveals augmented phasic or tonic muscular activity during REM sleep. The accompanying epoch demonstrates increased activity in chin -electromyogram and leg-electromyogram leads during REM stage, along with technician's notation, “talking in sleep.” RBD may be idiopathic in approximately 60% of cases, other cases being associated with neurologic disorders such as ischemic cerebrovascular disease, subarachnoid hemorrhage, Parkinson disease, multiple system atrophy, progressive supranuclear palsy, Shy-Drager syndrome, olivopontocerebellar degeneration, and multiple sclerosis. Many patients with “idiopathic” RBD will develop neurodegenerative disorders many years after the onset of parasomnia (choice B).3 Clonazepam is an effective therapy for most persons with RBD.1 This disorder should be differentiated from nightmares, which can occur at any age and are usually followed by abrupt awakenings accompanied by a sensation of fear or panic (choice A). Iron-deficiency anemia (choice C) is associated with restless leg syndrome and not RBD. Secondary enuresis and tongue biting (choice D) are features of epilepsy as opposed to RBD. Although sleep-related epilepsy would be a consideration in persons with focal limb movements during sleep, the history in this case is typical of RBD.

Clinical Identification of the Simple Sleep-Related Movement Disorders

Simple sleep-related movement disorders must be distinguished from daytime movement disorders that persist during sleep, sleep-related epilepsy, and parasomnias, which are generally characterized by activity that appears to be simultaneously complex, goal-directed, and purposeful but is outside the conscious awareness of the patient and, therefore, inappropriate. Once it is determined that the patient has a simple sleep-related movement disorder, the part of the body affected by the movement and the age of the patient give clues as to which sleep-related movement disorder is present. In some cases, all-night polysomnography with accompanying video may be necessary to make the diagnosis. Hypnic jerks (ie, sleep starts), bruxism, rhythmic movement disorder (ie, head banging/body rocking), and nocturnal leg cramps are discussed in addition to less well-appreciated disorders such as benign sleep myoclonus of infancy, excessive fragmentary myoclonus, and hypnagogic foot tremor/alternating leg muscle activation.

Sleep-Related Epilepsy in the A/J Mouse

Evident seizures during sleep are common in clinical practice but are uncommonly considered in animal models of epilepsy. A previous observation of spontaneous spike-and-wave activity during sleep in several A/J mice (A/J JAX) from Jackson Laboratory (Bar Harbor, ME) prompted this description of the inheritance of epileptic activity. Mice from A/J, C57BI/6J (B6), and chromosomal substitutions strains were instrumented to record EEG and EMG activity over time without and with anti-epileptic drugs. Intercrosses were performed using linkage analysis to localize sub-chromosomal regions. Spike-discharge patterns (n = 12 mice) were of average duration of 1.9 seconds at a rate per hour of 17, with an intrinsic frequency of 6.41 Hz and an amplitude of 634.8 microV. Clonic movements were observed in < 10% of the episodes. Episodes were expressed (> 75%) either in slow-wave sleep or in transitions to and from slow-wave sleep. Events were rare in paradoxical sleep. Compared with vehicle, intraperitoneal administration of ethosuximide (150 mg/kg) or diazepam (5 mg/kg) inhibited or eliminated seizure activity, respectively. In contrast, spontaneous spike-and-wave activity was not observed in A/J mice from Harlan National Laboratories (Indianapolis, Ind) or in B6 mice from Jackson Laboratory. In an intercross between A/J JAX and B6 mice, the trait was not present in the first generation. The trait was observed in 2 chromosome-substitution strains, B6.A4 and B6.A7. In the intercross second generation of these chromosome-substitution strains (n = 113), significant linkage was observed to loci on chromosome 4. This is a sleep-related epilepsy phenotype that exhibits an oligogenic pattern of allelic inheritance.

L0036 The role of continuous positive airways pressure therapy on the pathogenesis of sleep-related frontal lobe epilepsy in a child with obstructive sleep apnea syndrome

L0036 The role of continuous positive airways pressure therapy on the pathogenesis of sleep-related frontal lobe epilepsy in a child with obstructive sleep apnea syndrome

Schlaf und Bewegungsstörungen

The three different states of being (wakefulness, NREM and REM sleep) are associated with profound neurophysiological and neurochemical changes in the brain. These changes explain the existence of movement disorders appearing only or preferentially during sleep, and the effects of sleep on movement disorders. Sleep-related movement disorders are of clinical relevance for multiple reasons: 1) high frequency (e.g. restless legs syndrome (RLS)); 2) diagnostic relevance (e.g. REM sleep behavior disorder (RBD) as first manifestation of Parkinson disorder); 3) diagnostic uncertainty (e.g. parasomnias vs nocturnal epilepsy); 4) association with injuries (e.g. RBD, sleepwalking), sleep disruption/daytime sleepiness (e.g. RLS), and psycho-social burden (e.g. enuresis); 5) requirement of specific treatments (e.g. nocturnal epilepsy, stridor, RBD). This article gives an overview on clinical manifestations, pathophysiology, work-up and treatment of sleep-related movement disorders (e.g. RLS, bruxism), parasomnias (e.g. sleepwalking, RBD), sleep-related epilepsies, and on sleep-associated manifestations of movement disorders (e.g. Parkinson disease, multiple system atrophy).

Insulinoma with Early-Morning Abnormal Behavior

We report a 65-year-old man with insulinoma who initially developed stereotypical behaviors and then progressed to more complex behaviors occurring early in the morning. He could not remember the events during the episodes. Insulinoma was diagnosed based on fasting blood glucose level of 15 mg/dl, high fasting immunoreactive insulin/blood glucose ratio (more than 0.3), and a tumor in the pancreas head by abdominal CT. Hypoglycemia caused by insulinoma should be considered as one of the mechanisms underlying abnormal nocturnal behaviors since the symptoms are very similar to those of sleep-related epilepsy, parasomnia, and night delirium.

Increased Sensitivity of the Neuronal Nicotinic Receptor α2 Subunit Causes Familial Epilepsy with Nocturnal Wandering and Ictal Fear

Sleep has traditionally been recognized as a precipitating factor for some forms of epilepsy, although differential diagnosis between some seizure types and parasomnias may be difficult. Autosomal dominant frontal lobe epilepsy is characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements and has been associated with mutations of the alpha 4 and beta 2 subunits of the neuronal nicotinic acetylcholine receptor. We performed a clinical and molecular genetic study of a large pedigree segregating sleep-related epilepsy in which seizures are associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. We identified a new genetic locus for familial sleep-related focal epilepsy on chromosome 8p12.3-8q12.3. By sequencing the positional candidate neuronal cholinergic receptor alpha 2 subunit gene (CHRNA2), we detected a heterozygous missense mutation, I279N, in the first transmembrane domain that is crucial for receptor function. Whole-cell recordings of transiently transfected HEK293 cells expressing either the mutant or the wild-type receptor showed that the new CHRNA2 mutation markedly increases the receptor sensitivity to acetylcholine, therefore indicating that the nicotinic alpha 2 subunit alteration is the underlying cause. CHRNA2 is the third neuronal cholinergic receptor gene to be associated with familial sleep-related epilepsies. Compared with the CHRNA4 and CHRNB2 mutations reported elsewhere, CHRNA2 mutations cause a more complex and finalized ictal behavior.

New Manual Aids Diagnosis Of Sleep Disorders

New Manual Aids Diagnosis Of Sleep Disorders

Study on clinical features and misdiagnosis reasons of sleep related epilepsy

目的 探讨睡眠相关性癫痫的临床特点与误诊原因.方法对22例睡眠相关性癫痫患者进行回顾性分析.结果夜间睡眠癫痫发作主要表现为嗜睡和睡眠障碍以及常规EEG检查无痫样放电,为本组病例的主要误诊原因.结论对于睡眠障碍的患者,应常规行24 h脑电和多导睡眠图监测,以便尽早诊断和鉴别诊断。

To Sleep, Perchance to Seize: the Odd Marriage of Sleep and Epilepsy

ABSTRACT.This article reviews the complex and increasingly scrutinized relationship between sleep and epilepsy, emphasizing the differential activation of interictal epileptiform discharges and seizures during different sleep stages, the sleep-related epilepsies (those with preferential occurrence during sleep or following arousal), and sleep disorders that may exacerbate or mimic epilepsy. Recognition and treatment of nocturnal seizures and primary sleep disorders in patients with epilepsy may lead to improvements in seizure burden and quality of life.

Sleep-related epilepsy.

Sleep is important for the general health of all, but is particularly essential for individuals with epilepsy. In these patients, a complex relationship exists between seizures and sleep, and both must be considered for optimal care. In this review, recent advances in the field of epilepsy and sleep are considered. These include sleep disorders with a specific relationship to epilepsy, the influences of sleep and sleep deprivation on interictal epileptiform discharges, detrimental effects of seizures on sleep, and the effects (good and bad) of epilepsy treatments on sleep.

The indications for polysomnography and related procedures.

This paper is a review of the literature on the use of polysomnography in the diagnosis of sleep disorders in the adult. It is based on a search of MEDLINE from January 1966 through April 1996. It has been reviewed and approved by the Board of Directors of the American Sleep Disorders Association and provides the background for the accompanying ASDA Standards of Practice Committee's Parameters for the Practice of Sleep Medicine in North America. The diagnostic categories reviewed are: sleep-related breathing disorders; other respiratory disorders; narcolepsy; parasomnias and sleep-related epilepsy; restless legs syndrome and periodic limb movement disorders: insomnia; and circadian rhythm sleep disorders. Where appropriate, previously published practice parameters papers are cited and discussed. The relevant published peer-reviewed literature used as the basis for critical decisions was compiled into accompanying evidence tables and is analyzed in the text. In the section on the assessment of sleep apnea syndrome, options for estimating pretest probability to select high risk patients are also reviewed. Sleep-testing procedures other than standard polysomnography are also addressed (daytime polysomnography, split-night studies, oximetry, limited full respiratory recordings, and less-than-full respiratory recording) and treatment-related follow-up studies are discussed.