Paroxysmal Arousals Research Articles

Nocturnal paroxysmal dystonia to sleep-related hypermotor epilepsy: A critical review.

Sleep-related paroxysmal motor episodes (SPMEs) have been described by various names, including nocturnal paroxysmal dystonia, nocturnal frontal lobe epilepsy (NFLE), and sleep-related hypermotor epilepsy. The underlying pathophysiology has been debated over the years, with these episodes assumed to be a form of paroxysmal dystonia or parasomnia versus a form of epilepsy. In most studies published on SPMEs and their variants (paroxysmal arousals, nocturnal paroxysmal dystonia, and episodic nocturnal wanderings) in the early 1990s, the authors speculated on the pathophysiology but did not commit to one idea. It was not until the mid-1990s that epilepsy became the leading prospect. We performed a narrative review of the major articles that have described this syndrome in a chronological fashion. We identified three eras, 1972-1993, 1994-1998, and 1999 to the present, each era marked by a landmark study. Our critical review of these early studies shows that the neurophysiological data supporting epilepsy as the sole basis for all SPME cases is very weak. In 1994-1995, a familial pattern of this syndrome was described and the term autosomal dominant NFLE was coined, with the authors claiming that all their patients had a form of frontal lobe epilepsy. With the exception of a few reference cases, the neurophysiological evidence that all patients had frontal lobe epilepsy was very weak. Compared to articles published on surgical series of frontal lobe epilepsy, the percentage of SPME cases with positive interictal/ictal electroencephalograms remained very low, seriously questioning the epileptic basis of the syndrome. Our critical review and analysis of the published literature shows that the evidence presented in favor of SPMEs being a homogenous focal epilepsy syndrome is very weak. Neurologists must recognize that SPMEs could be a form of movement disorder, parasomnia, or epilepsy. We recommend a pragmatic semiology-based classification of these episodes using the four-dimensional classification system.

Paroxysmal arousals in Sleep-related Hypermotor Epilepsy (SHE) and Simple arousal movements in Disorders of Arousal (DoA): semiological and clinical features make a difference

Paroxysmal arousals in Sleep-related Hypermotor Epilepsy (SHE) and Simple arousal movements in Disorders of Arousal (DoA): semiological and clinical features make a difference

Commonalities and Differences in NREM Parasomnias and Sleep-Related Epilepsy: Is There a Continuum Between the Two Conditions?

Introduction: Differential diagnosis between disorders of arousal (DoA) and sleep-related hypermotor epilepsy (SHE) often represents a clinical challenge. The two conditions may be indistinguishable from a semiological point of view and the scalp video-polysomnography is often uninformative. Both disorders are associated with variable hypermotor manifestations ranging from major events to fragments of a hierarchical continuum of increasing intensity, complexity, and duration. Given their semiological overlap we decided to explore the sleep texture of DoA and SHE seeking for similarities and differences.Methods: We analyzed sleep macrostructure and CAP (cyclic alternating pattern) parameters in a cohort of 35 adult DoA patients, 40 SHE patients and 24 healthy sleepers, all recorded and scored in the same sleep laboratory. Nocturnal behavioral manifestations included minor motor events, paroxysmal arousals and major attacks in SHE, and simple, rising, or complex arousal movements in DoA.Results: Compared to healthy controls, DoA and SHE showed similar amounts of sleep efficiency, light sleep, deep sleep, REM sleep, CAP subtypes. Both groups also showed slow wave sleep fragmentation and an increased representation of stage N3 in the second part of the night. The only discriminating elements between the two conditions regarded sleep length (more reduced in DoA) and sleep instability (more elevated in SHE). In DoA recordings, all motor episodes arose from NREM sleep: 37% during light NREM stages and 63% during stage N3 (simple arousal movements: 94%). In SHE recordings, 57% of major attacks occurred during stage N3.Conclusions: So far, emphasis has been placed on the differentiation of sleep-related epilepsy and NREM arousal disorders. However, the impressive analogies between DoA and SHE suggest the existence of an underestimated continuum across the conditions, linked by increased levels of sleep instability, higher amounts of slow wave sleep and NREM/REM sleep imbalance. Sleep texture is extremely similar in the two conditions, although CAP metrics disclose quantitative differences. In particular, SHE patients show a higher arousal instability compared to DoA subjects. Given their clinical and epidemiological overlap, a common genetic background is also hypothesized. In such a perspective, we suggest that the consolidated dichotomy DoA vs. SHE should be reappraised.

Seizures with paroxysmal arousals in sleep-related hypermotor epilepsy (SHE): Dissecting epilepsy from NREM parasomnias.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy characterized by seizures occurring mostly during sleep, ranging from brief seizures with paroxysmal arousals (SPAs) to hyperkinetic seizures and ambulatory behaviors. SPAs are brief and stereotypic seizures representing the beginning of a major seizure. Distinguishing SPAs from disorders of arousal (DOAs) and their briefest episodes called simple arousal movements (SAMs) is difficult. We performed a characterization of SPAs and SAMs to identify video-polysomnographic (VPSG) features that can contribute to the diagnosis of SHE or DOA. Fifteen SHE, 30 DOA adult patients, and 15 healthy subjects underwent full-night VPSG. Two neurologist experts in sleep disorders and epilepsy classified all the sleep-related movements and episodes recorded. For each SPAs and SAMs, sleep stage at onset, duration, limb involvement, progression, and semiology have been identified. A total of 121 SPAs were recorded, emerging mostly during stage 1-2 non-rapid eye movement (NREM) sleep (median duration: 5seconds). At the beginning, the SPAs motor pattern was hyperkinetic in 78 cases (64%), involving more than three non-contiguous or all body parts. The standard was a constant progression of movements during SPAs without any motor arrests. In DOA patients a total of 140 SAMs were recorded (median duration: 12seconds) mostly emerging during stage 3 NREM sleep. In SAMs, we did not observe any tonic/dystonic or hypermotor patterns or stereotypy; motor arrest was present over the course of about half of the episodes. In comparison with both DOA and healthy subjects, SHE patients showed a higher number of sleep-related movements per night and a reduction of sleep efficiency. SPAs and SAMs present different semiological and clinical features. Their recognition could be useful to drive the diagnosis when major episodes are not recorded during VPSG in patients with a clear clinical history of SHE or DOA.

History of frontal lobe seizures

Any historical review of seizures originating in the frontal lobes (FLS) is faced with several difficulties: the huge diversity of ictal manifestations, from the most simple myoclonic event originating in the elementary precentral motor cortex, to very bizarre and misleading phenomena, involving associative cortices and widely distributed networks, that were not rarely misinterpreted as psychogenic attacks (Tharp [1] ); the often unclear relationship between semiologic patterns and sublobar localization in spite of many attempts to characterize typical anatomical-clinical-electrical patterns that would be typical of a given sub region, like the orbito-frontal or medial frontal lobe areas [2] , [3] ; the different terminologies employed to characterize FLS, reflected in the evolving classifications of the International League Against Epilepsy (ILAE) between 1981 and 2017. FLS are often brief, sometimes a few seconds, due to the rapid propagation pathways which are offered inside and outside the frontal lobe to the epileptic discharge , making the observation and the analysis difficult, although seizures in a given patient with frontal lobe epilepsy are generally stereotyped, with a stable and reproducible electro-clinical pattern. And last but not least, FLS are often nocturnal, without obvious electroencephalographic (EEG) correlations, and have been often in the past misdiagnosed as parasomnia . The manifestations include: paroxysmal arousals, characterized by brief and sudden recurrent motor paroxysmal behavior; nocturnal paroxysmal dystonia, motor attacks with complex dystonic–dyskinetic features; and episodic nocturnal wanderings, stereotyped, agitated somnambulism. The recognition of their epileptic nature led to the terminology of Nocturnal Frontal Lobe Epilepsy, and a familial clustering permitted the discovery of several pathogenic gene variants [4] , [5] . In spite of this complexity, the study of frontal lobe seizures has largely contributed to our understanding of the pathophysiology of epileptic discharges: the first description of focal clonic seizures by J.F. Bravais in 1827, then Hughlings Jackson in 1867, who related clonic seizures to electric discharges in the contralateral precentral region and described a “march”, this stepwise invasion of neighboring areas of the motor cortex by the ictal discharge, with progressive somatotopic engagement of limb musculature. Other frontal lobe seizure types , however, showed that this march phenomenon cannot be considered as a universal model of emergence and spreading of the discharge. Supplementary motor area seizures producing speech arrest (a negative phenomenon), unilateral arm posturing, and head or eye deviation, later referred to as “fencing posture” by Penfield [6] , illustrate rapid modalities of subcortical propagation. Using stereoencephalography , Bancaud and Talairach [2] defined frontal lobe automatisms , and detailed descriptions of complex partial seizures of frontal lobe origin followed with P. Williamson et al. [7] . The term “hypermotor seizure” was also proposed. In the revised ILAE classification, FLS are classified as “focal seizures” with further descriptors such as “either aware or with impaired awareness”, or “with or without observable motor components” [8] . Frontal lobe seizures with secondary generalization are now described as focal evolving to bilateral tonic-clonic seizures .

Sleep‐related hypermotor epilepsy activated by rapid eye movement sleep

Most sleep-related seizures occur during non-rapid eye movement (NREM) sleep, particularly during stage changes. Sleep-related hypermotor epilepsy (SHE) is a rare epileptic syndrome characterized by paroxysmal motor seizures, mainly arising from NREM sleep. Here, we report a patient with SHE who had seven seizures captured on video-EEG-polysomnography during REM sleep. Ictal semiology of this patient ranged from brief paroxysmal arousals to hypermotor seizures. On EEG-polysomnography, the spontaneous arousals were more frequent during REM than NREM sleep, with a considerably higher arousal index in REM sleep (20/hour). While the reason for seizures during REM sleep in this patient is unclear, we speculate that the threshold and mechanisms of arousal during different sleep stages may be related to the occurrence of seizures. [Published with video sequences on www.epilepticdisorders.com].

Spontaneous epileptic seizures in transgenic rats harboring a human ADNFLE missense mutation in the β2-subunit of the nicotinic acetylcholine receptor

We generated a transgenic rat strain with a missense mutation in V286L (V286L-TG), in the gene encoding the neuronal nicotinic acetylcholine receptor β2 subunit (CHRNB2) found in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). To confirm that V286L-TG rats exhibit seizures similar to those observed in humans, gene expression patterns and behavioral phenotypes were analyzed. In situ hybridization using a V286L Chrnb2-selective probe indicated that the transgene was expressed at higher levels in the cortex, hippocampus, and cerebellum of V286L-TG than wild-type littermates (non-TG). Spontaneous epileptic seizures with ictal discharges in electroencephalograms were detected in 45% of V286L-TG rats and the frequency of seizures was 0.73 times a week. This seizure type is similar to “paroxysmal arousals” that are observed in human ADNFLE. V286L-TG rats displayed nicotine-induced abnormal motor activity including seizures in comparison to non-TGs. Response time following nicotine administration occurred faster in V286L-TG than in non-TG rats.V286L-TG rats demonstrated spontaneous epileptic seizures, which are similar to human ADNFLE, and also showed a higher sensitivity to nicotine administration. Thus, the V286L-TG rat model could be a valuable tool for developing novel mechanism-driven treatment strategies for epilepsy and provide a better understanding of ADNFLE.

Spotlight on the April 14 Issue

#### Notable in Neurology This issue features articles on nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function and on refining the phenotype variability and identifying factors that explain the clinical severity of the symptoms observed in Unverricht-Lundborg disease. Other featured articles focus on the recurrence of reversible cerebral vasoconstriction syndrome and on the long-term effects of fingolimod in multiple sclerosis. ### Memory fMRI predicts verbal memory decline after anterior temporal lobe resection![Graphic][1] The authors performed an fMRI word memory encoding paradigm and an out-of-scanner recognition assessment in 50 patients with … [1]: /embed/inline-graphic-1.gif

Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function.

We assessed the mutation frequency in nicotinic acetylcholine receptor (nAChR) subunits CHRNA4, CHRNB2, and CHRNA2 in a cohort including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and sporadic nocturnal frontal lobe epilepsy (NFLE). Upon finding a novel mutation in CHRNA2 in a large family, we tested in vitro its functional effects. We sequenced all the coding exons and their flanking intronic regions in 150 probands (73 NFLE, 77 ADNFLE), in most of whom diagnosis had been validated by EEG recording of seizures. Upon finding a missense mutation in CHRNA2, we measured whole-cell currents in human embryonic kidney cells in both wild-type and mutant α2β4 and α2β2 nAChR subtypes stimulated with nicotine. We found a c.889A>T (p.Ile297Phe) mutation in the proband (≈0.6% of the whole cohort) of a large ADNFLE family (1.2% of familial cases) and confirmed its segregation in all 6 living affected individuals. Video-EEG studies demonstrated sleep-related paroxysmal epileptic arousals in all mutation carriers. Oxcarbazepine treatment was effective in all. Whole-cell current density was reduced to about 40% in heterozygosity and to 0% in homozygosity, with minor effects on channel permeability and sensitivity to nicotine. ADNFLE had previously been associated with CHRNA2 dysfunction in one family, in which a gain of function mutation was demonstrated. We confirm the causative role of CHRNA2 mutations in ADNFLE and demonstrate that also loss of function of α2 nAChRs may have pathogenic effects. CHRNA2 mutations are a rare cause of ADNFLE but this gene should be included in mutation screening.

Nocturnal Paroxysmal Dystonia (NPD), two cases report

Nocturnal Paroxysmal Dystonia (NPD) is a rare condition characterized by recurrent attacks during NREM sleep of variable duration (seconds to minutes), with a complex clinical expression: repetitive stereotyped dystonic, ballistic or choreoathetoid movements involving single or all extremities and neck. It is associated with other conditions such as paroxysmal arousals, episodic nocturnal wanderings, dyskinetic or semipurposeful movements and vocalizations, often no ictal epileptic in surface EEG activity, and normal brain neuroimaging. Nowadays, it is clear that most of patients who fit the diagnosis of NPD have a form of sleep-activated focal epilepsy (nocturnal frontal lobe epilepsy). Our aim is to present two patients diagnosed with NPD. It is a descriptive study, enrolling two patients with NPD diagnosis. We report two cases. The first one, a 13 years old boy without relevant personal and family medical history, who debuted at 5 years old with dystonic and dyskinetic attacks during sleep that occurred many times per night. The second case is a 39 years old man, without relevant personal and family medical history. Since aged 31 years, he complained attacks of motor agitation with stereotypical movements every night and often several times per night. Both patients remained without neurological abnormalities in physical examination and brain neuroimaging. The EEGs during wakefulness and sleep were normal. Initially they were diagnosed as NREM parasomnia and followed many years without evidence of developing any neurocognitive disorder or neurological impairment, despite no treatment. The attacks of Nocturnal Paroxysmal Dystonia are a form of nocturnal frontal lobe epilepsy. The application of deep brain electrodes has led to the recognition that ”hypermotor seizures” may also be found in seizures originated from the temporal lobe and the insula. Functional brain imaging in frontal lobe seizures confirms that the peculiar motor patterns involve mesial and especially cingulate, motor areas. It is necessary to keep into consideration this rare and not well-known entity in the differential diagnosis of atypical parasomnias. Although the latest advances in Neurosciences, the polysomnography and the clinical history continue being pillars in the diagnosis of nocturnal frontal lobe epilepsy so the neurophysiological studies must always be considered when the diagnostic of a parasomnia is not well established. Dres. Quintana, Sáez y Paradinas.

A case of nocturnal frontal lobe epilepsy in a patient with spinocerebellar ataxia type 17

Nocturnal frontal lobe epilepsy (NFLE) comprises a complex spectrum of distinct paroxysmal sleep-related attacks of variable intensity, including paroxysmal arousals, nocturnal paroxysmal dystonias and epileptic nocturnal wanderings. Scalp EEG and brain MRI are unable to reveal abnormalities in a considerable amount of patients. In those cases the epileptic nature of NFLE is supported by the stereotypical clinical presentation of the episodes and the often dramatic response to antiepileptic drugs (AEDs) like Carbamazepine, Clonazepam or Topiramate. Spinocerebellar ataxia type 17 (SCA 17) is a neurodegenerative disease caused by the expansion above 44 units of a CAG/CAA repeat in the coding region of the TATA box binding protein (TBP) gene. It is one of the rarer forms amongst autosomal dominant cerebellar ataxias, with extreme variable age at onset and clinical phenotype. Epilepsy is quite commonly observed among SCA 17 patients, however it is exclusively described in terms of generalized tonic–clonic seizures. We report a case of NFLE occurring in a SCA 17 patient and brilliantly responsive to Topiramate after failure of the first line therapy with Carbamazepine.

Distinctive polysomnographic traits in nocturnal frontal lobe epilepsy

To describe the polysomnographic features and distribution of epileptic motor events, in relation to conventional sleep measures and cyclic alternating pattern (CAP) parameters, in 40 untreated patients with nocturnal frontal lobe epilepsy (NFLE). We analyzed the basal polysomnographic recordings of 40 patients (20 male and 20 female; mean age: 31 ± 10 years) with a diagnosis of nocturnal frontal lobe epilepsy. Conventional sleep measures and CAP parameters were assessed. Polysomnographic recordings were subdivided in sleep cycles. The distribution of the epileptic motor events (including minor motor events, paroxysmal arousals, tonic-dystonic, or hyperkinetic seizures and epileptic nocturnal wandering) was analyzed throughout: total sleep time, non-rapid eye movement (NREM) and REM sleep, light sleep (S1 + S2), slow wave sleep (SWS), each sleep cycle, CAP or non-CAP sleep, phase A and phase B of CAP. Only clear epileptic motor events supported by video-polysomnographic evidence were taken into consideration. Polysomnographic findings of patients with NFLE were compared with those of 24 age- and gender-balanced healthy subjects without sleep complaints. Compared to controls, patients with NFLE showed a significant increase in wake after sleep onset, SWS duration, and REM latency, whereas REM sleep duration was significantly lower in NFLE patients. The patients with NFLE showed a significant increase of CAP time, CAP rate (72% vs. 32% in control group), CAP cycles, and mean duration of a CAP sequence. These findings were associated with a significant enhancement of all subtypes of the A phases of CAP (mainly subtype A1). A total of 139 epileptic motor events supported by video-polysomnographic evidence were counted: 98% of all seizures occurred in NREM sleep and 72% of NREM seizures emerged from SWS, the latter being particularly collected in the first sleep cycles and decreasing in frequency together with the progressive decline of deep sleep. Ninety percent of total NREM seizures occurred during a CAP sequence, and CAP-related seizures occurred in association with a phase A. Significant polysomnographic alterations seem to emerge in patients with NFLE (increased REM latency, epileptic fragmentation of SWS, and increase of CAP rate). The analysis of seizure distribution showed that most epileptic events occurred in SWS, with predominance in the first sleep cycle and decreasing in frequency together with the homeostatic decline of SWS across the night. Within the NREM sleep, CAP is a manifestation of unstable sleep and represents a powerful predisposing condition for the occurrence of nocturnal motor seizures, which arise in concomitance with a phase A.

Physiologic Pseudoseizures

The misdiagnosis of epilepsy may occur from the misinterpretation of a routine scalp EEG. Typically, interictal epileptiform discharges are misidentified on EEGs because of the overinterpretation of normal variants or variations in normal electrocerebral activity. Most reports of misinterpretation have arisen from patients diagnosed with psychogenic nonepileptic attacks using in-patient video-EEG monitoring. However, because seizures are rarely captured in the routine performance of EEG in the outpatient setting, ictal overinterpretation is much less likely to occur. However, some physiologic conditions may also occur with paroxysmal hypersynchronous patterns on EEG and lead to a misdiagnosis of epilepsy. We report an adult woman with untreated obstructive sleep apnea and major depressive disorder that was self-referred for the evaluation of seizures. Brief episodes of delayed responsiveness associated with prolonged reading demonstrated the "generalized paroxysmal pattern" that was misinterpreted as a seizure during routine EEG at an outside institution. Subsequently, in-patient video-EEG monitoring reproduced multiple nonepileptic physiologic paroxysmal hypersynchronous arousals after prolonged reading. Treatment of the underlying sleep apnea, psychologic support, and limited prolonged reading lead to remission of her nonepileptic "spells" and successful discontinuation of antiepileptic drugs.

Paroxysmal arousals and myoclonic movements associated with interictal epileptiform discharges in NREM and REM sleep

Department of Neurology, Michael O’Callaghan Federal Hospital, 4700 N. Las Vegas Blvd, Nellis AFB, NV 89191, United States Division of Pediatric and Developmental Neurology, Campus Box 8111, Room 12E25, St. Louis Children’s Hospital, One Children’s Place, Saint Louis, MO 63110, United States Campus Box 8111, Department of Neurology, Washington University Medical Center, 660 South Euclid Avenue, Saint Louis, MO 63110, United States

Familial frontal lobe epilepsy and its relationship with other nocturnal paroxysmal events

Familial frontal lobe epilepsy and its relationship with other nocturnal paroxysmal events

Rats Harboring S284LChrna4Mutation Show Attenuation of Synaptic and Extrasynaptic GABAergic Transmission and Exhibit the Nocturnal Frontal Lobe Epilepsy Phenotype

Mutations of genes encoding alpha4, beta2, or alpha2 subunits (CHRNA4, CHRNB2, or CHRNA2, respectively) of nAChR [neuronal nicotinic ACh (acetylcholine) receptor] cause nocturnal frontal lobe epilepsy (NFLE) in human. NFLE-related seizures are seen exclusively during sleep and are characterized by three distinct seizure phenotypes: "paroxysmal arousals," "paroxysmal dystonia," and "episodic wandering." We generated transgenic rat strains that harbor a missense mutation S284L, which had been identified in CHRNA4 in NFLE. The transgenic rats were free of biological abnormalities, such as dysmorphology in the CNS, and behavioral abnormalities. The mRNA level of the transgene (mutant Chrna4) was similar to the wild type, and no distorted expression was detected in the brain. However, the transgenic rats showed epileptic seizure phenotypes during slow-wave sleep (SWS) similar to those in NFLE exhibiting three characteristic seizure phenotypes and thus fulfilled the diagnostic criteria of human NFLE. The therapeutic response of these rats to conventional antiepileptic drugs also resembled that of NFLE patients with the S284L mutation. The rats exhibited two major abnormalities in neurotransmission: (1) attenuation of synaptic and extrasynaptic GABAergic transmission and (2) abnormal glutamate release during SWS. The currently available genetically engineered animal models of epilepsy are limited to mice; thus, our transgenic rats offer another dimension to the epilepsy research field.

Response

I very much appreciate the comments of Romigi et al. regarding their recent experience with the use of oxcarbazepine in nocturnal frontal-lobe epilepsy. As they mentioned, carbamazepine is generally considered the first-choice treatment in nocturnal frontal-lobe epilepsy, with a proposed mechanism of action through the inhibitory effects of hyperfunctional, mutated neuronal acetylcholine receptors. With a similar chemical structure, oxcarbazepine likely shares such a mechanism of action in nocturnal frontal-lobe epilepsy, and topiramate might share also this mechanism of action. I agree that the observations of better efficacy with these antiepileptic drugs in nocturnal frontal-lobe epilepsy, compared with other antiepileptic drugs, are of significance, and such observations will likely help guide the design of studies to elucidate the pathophysiology of nocturnal frontal-lobe epilepsy. Oxcarbazepine in Nocturnal Frontal-Lobe Epilepsy: A Further Interesting ReportPediatric NeurologyVol. 39Issue 4PreviewWe read with great interest the article by Raju et al. [1] concerning the efficacy of oxcarbazepine in children with nocturnal frontal-lobe epilepsy. This study solicited a further interesting report. We recently observed a 13-year-old boy affected by untreated nocturnal frontal-lobe epilepsy, manifesting nocturnal paroxysmal arousals with dystonic and dyskinetic movements of the upper and lower limbs (2-3 episodes per night) since age 11 years. The patient experienced 3 generalized tonic-clonic seizures triggered by sleep deprivation in the 2 months before our evaluation. Full-Text PDF

Oxcarbazepine in Nocturnal Frontal-Lobe Epilepsy: A Further Interesting Report

We read with great interest the article by Raju et al. [1] concerning the efficacy of oxcarbazepine in children with nocturnal frontal-lobe epilepsy. This study solicited a further interesting report. We recently observed a 13-year-old boy affected by untreated nocturnal frontal-lobe epilepsy, manifesting nocturnal paroxysmal arousals with dystonic and dyskinetic movements of the upper and lower limbs (2-3 episodes per night) since age 11 years. The patient experienced 3 generalized tonic-clonic seizures triggered by sleep deprivation in the 2 months before our evaluation.

Nocturnal epileptic seizures versus the arousal parasomnias

We review here the clinical features of Nocturnal Frontal Lobe Epilepsy (NFLE) and the arousal parasomnias, to define possible differential diagnostic criteria and their inter-observer reliability, and to determine whether both conditions share a common disturbance of arousal mechanisms. Polysomnographic recordings defined several types of seizures in NFLE: Paroxysmal Arousals (PA), Nocturnal Paroxysmal Dystonia (NPD), Epileptic Nocturnal Wanderings (ENW). There are however several difficulties with the diagnosis of NFLE, not the least being that EEG discharges during the seizures are not universally found. These diagnostic difficulties are highlighted, as well as the fact that studies of the inter-observer reliability of the video polysomnographic features of NFLE were found unsatisfactory, especially for the PA. When NFLE patients and their relatives were matched to control subjects and analysed in regard to personal and family history for the parasomnias, the arousal parasomnias were reported significantly higher by patients with NFLE and their relatives. This higher recurrence of a personal and family history for the parasomnias in NFLE patients suggests that the two conditions share a common underlying mechanism. Based on evidence from Autosomal Dominant NFLE, a genetic disorder with mutations in nicotinic acetylcholine receptors(nAchR), we hypothesise that arousal parasomnias and NFLE both, have abnormal arousal mechanisms in the dorsal cholinergic arousal branch triggering peculiar motor patterns in the medial frontal lobe regions.

Oxcarbazepine in Children With Nocturnal Frontal-Lobe Epilepsy

Nocturnal frontal-lobe epilepsy is characterized by paroxysmal arousals, motor seizures with dystonic or hyperkinetic features, and episodic nocturnal wanderings. Carbamazepine is effective for seizure control in some of these patients, but seizures may be refractory to multiple antiepileptic drugs. We report on eight children between ages 4-16 years with nocturnal frontal-lobe epilepsy who had a dramatic response to oxcarbazepine at standard recommended doses, some of whom were refractory to previous antiepileptic medications. Brain magnetic resonance imaging, routine electroencephalogram, and prolonged, continuous video-electroencephalogram telemetry were performed in all children. Nocturnal frontal-lobe epilepsy was diagnosed by demonstrating ictal electroencephalogram changes originating from the frontal lobes. The children were followed for response of seizures to oxcarbazepine, side effects, and routine blood tests, including serum 10-monohydroxide derivative levels. The mean oxcarbazepine dose was 30.4 mg/kg/day +/- 11.7 (mean +/- SD); the mean 10-monohydroxide level was 23.1 microg/mL +/- 8.6 (mean +/- SD). Seizures improved within 4 days of oxcarbazepine initiation in six children, whereas two children required higher doses. Their follow-up has ranged from 12 to 24 months, without seizure recurrence or serious side effects. Our patients demonstrate the efficacy of oxcarbazepine for nocturnal hyperkinetic seizures in children with nocturnal frontal-lobe epilepsy.