Automatic video analysis and classification of sleep-related hypermotor seizures and disorders of arousal.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy with seizures occurring mostly during sleep. SHE seizures present different motor characteristics ranging from dystonic posturing to hyperkinetic motor patterns, sometimes associated with affective symptoms and complex behaviors. Disorders of arousal (DOA) are sleep disorders with paroxysmal episodes that may present analogies with SHE seizures. Accurate interpretation of the different SHE patterns and their differentiation from DOA manifestations can be difficult and expensive, and can require highly skilled personnel not always available. Furthermore, it is operator dependent. METHODS: Common techniques for human motion analysis, such as wearable sensors (e.g., accelerometers) and motion capture systems, have been considered to overcome these problems. Unfortunately, these systems are cumbersome and they require trained personnel for marker and sensor positioning, limiting their use in the epilepsy domain. To overcome these problems, recently significant effort has been spent in studying automatic methods based on video analysis for the characterization of human motion. Systems based on computer vision and deep learning have been exploited in many fields, but epilepsy has received limited attention. RESULTS: In this paper, we present a pipeline composed of a set of three-dimensional convolutional neural networks that, starting from video recordings, reached an overall accuracy of 80% in the classification of different SHE semiology patterns and DOA. SIGNIFICANCE: The preliminary results obtained in this study highlight that our deep learning pipeline could be used by physicians as a tool to support them in the differential diagnosis of the different patterns of SHE and DOA, and encourage further investigation.

Spindles insufficiency in sleepwalkers' deep sleep.

OBJECTIVES: Sleepwalkers have consistently shown N3 sleep discontinuity, especially after sleep deprivation. In healthy subjects, sleep spindles activity has been positively correlated to sleep stability. We aimed to compare spindles density during N3 sleep between sleepwalkers and healthy controls. METHODS: Two cohorts of 10 and 21 adult sleepwalkers respectively controlled with 10 and 18 healthy volunteers underwent one baseline and one recovery sleep recording after 38h (cohort 1) and 25h (cohort 2) of sleep deprivation. For the two recordings, we performed an automatic detection of spindles (11-16Hz) from EEG signal during N3 sleep, restricted to the first sleep cycle and repeated for all cycles. For better interpretation of results, we extended the analysis to N2 sleep and we also measured the density of slow waves oscillation (SWO) (0.5-4Hz) during the same periods. RESULTS: Compared to controls, sleepwalkers showed significantly lower spindle densities during N3 sleep considering the first sleep cycle (both cohorts) or all cycles (cohort 1). SWO densities did not differ (cohort 1) or were lower (cohort 2) for sleepwalkers. The effect of sleep deprivation did not interact with the effect of group on spindles and SWO densities. CONCLUSION: This work suggests that the instability of N3 sleep inherent to sleepwalkers may be underpinned by a specific alteration of spindles activity.

Successful Treatment of Somnambulism With OROS-Methylphenidate.

None: Somnambulism is a non-rapid eye movement sleep parasomnia with potential for significant injury as well as functional nighttime and daytime impairment. Clonazepam is frequently used as first line pharmacotherapy. However, the optimal treatment of somnambulism has not been established. In this article, we present the cases of two patients with severe somnambulism who showed a significant therapeutic response to osmotic release oral system methylphenidate (OROS-MPH). In addition to its practical therapeutic implications, this first report of the successful treatment of somnambulism with OROS-MPH may provide additional insight into the neurobiological underpinnings of this medical condition.

Interictal epileptiform discharges in sleep and the role of the thalamus in Encephalopathy related to Status Epilepticus during slow Sleep.

EEG activation of interictal epileptiform discharges (IEDs) during NREM sleep is a well-described phenomenon that occurs in the majority of epileptic syndromes. In drug-resistant focal epilepsy, IED activation seems to be related to slow wave activity (SWA), especially during arousal fluctuations, namely phase A of the cyclic alternating pattern (CAP). Conversely, in childhood focal epileptic syndromes, including Encephalopathy related to Status Epilepticus during slow Sleep (ESES), IED activation seems primarily modulated by sleep-inducing and maintaining mechanisms as reflected by the dynamics of spindle frequency activity (SFA) rather than SWA. In this article, we will review the effect of sleep on IEDs with a particular attention on the activation and modulation of IEDs in ESES. Finally, we will discuss the role of the thalamus and cortico-thalamic circuitry in this syndrome.

Clinical features of sleep-related hypermotor epilepsy in relation to the seizure-onset zone: A review of 135 surgically treated cases.

OBJECTIVES: Sleep-related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep-related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset-zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. METHODS: We retrospectively analyzed the clinical features of patients with drug-resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. RESULTS: Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure-frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1-4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3-4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. SIGNIFICANCE: Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.

Seizure duration and latency of hypermotor manifestations distinguish frontal from extrafrontal onset in sleep-related hypermotor epilepsy.

Sleep-related hypermotor epilepsy (SHE) is an epilepsy syndrome that is characterized by the occurrence of sleep-related hypermotor seizures of variable complexity and duration. Seizures usually arise in the frontal lobe, but extrafrontal seizure onset zones are well described. To identify clinically relevant ictal features of SHE that could distinguish a frontal from an extrafrontal onset zone, we conducted a retrospective analysis of seizure characteristics in 58 patients with drug-resistant SHE (43 frontal and 15 extrafrontal) who underwent video-stereo-electroencephalographic recordings and became seizure-free after epilepsy surgery. We found that the mean duration of electrographic seizures and clinically observable ictal manifestations were significantly shorter in frontal SHE compared to extrafrontal SHE. The mean latency between electrographic seizure onset and the onset of hypermotor manifestations was also shorter in frontal SHE. Accordingly, a latency > 5 seconds between the first video-detectable movement (eg, eye opening or a minor motor event) and the onset of hypermotor manifestations yielded a sensitivity of 75% and a specificity of 90% for an extrafrontal onset, thereby indicating that specific ictal features in SHE can provide clinically useful clues to increase diagnostic accuracy in this syndrome.

Proton MR Spectroscopy in Patients with Nonlesional Insular Cortex Epilepsy Confirmed by Invasive EEG Recordings.

BACKGROUND AND PURPOSE: Recent studies suggest that a nonnegligible proportion of drug-resistant epilepsy surgery candidates have an epileptogenic zone that involves the insula. We aimed to examine the value of proton magnetic resonance spectroscopy (1 H-MRS) in identifying patients with insular cortex epilepsy. METHODS: Patients with possible nonlesional drug-refractory insular epilepsy underwent a voxel-based 1 H-MRS study prior to an intracranial electroencephalographic (EEG) study. Patients were then divided into two groups based on invasive EEG findings: the insular group with evidence of insular seizures and the noninsular group with no evidence of insular seizures. Sixteen age-matched healthy controls were also scanned for normative data. RESULTS: Twenty-two epileptic patients were recruited, 12 with insular seizures and 10 with extra-insular seizures. Ipsilateral and contralateral insular N-acetyl-aspartate concentrations ([NAA]) and NAA/Cr ratios were found to be similar in both patient groups. No significant differences in [NAA] or NAA/Cr ratios were found between the insular group, noninsular group, and healthy controls. [NAA] and NAA/Cr asymmetry indices correctly lateralized the seizure focus in only 16.7% and 0% of patients, respectively. CONCLUSIONS: Our preliminary findings suggest that 1 H-MRS fares poorly in identifying patients with nonlesional insular epilepsy.

Global and local complexity of intracranial EEG decreases during NREM sleep.

Key to understanding the neuronal basis of consciousness is the characterization of the neural signatures of changes in level of consciousness during sleep. Here we analysed three measures of dynamical complexity on spontaneous depth electrode recordings from 10 epilepsy patients during wakeful rest (WR) and different stages of sleep: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability over time of the set of channels active above a threshold; (iii) synchrony coalition entropy, which measures the variability over time of the set of synchronous channels. When computed across sets of channels that are broadly distributed across multiple brain regions, all three measures decreased substantially in all participants during early-night non-rapid eye movement (NREM) sleep. This decrease was partially reversed during late-night NREM sleep, while the measures scored similar to WR during rapid eye movement (REM) sleep. This global pattern was in almost all cases mirrored at the local level by groups of channels located in a single region. In testing for differences between regions, we found elevated signal complexity in the frontal lobe. These differences could not be attributed solely to changes in spectral power between conditions. Our results provide further evidence that the level of consciousness correlates with neural dynamical complexity.

Sleep-related epileptic behaviors and non-REM-related parasomnias: Insights from stereo-EEG.

During the last decade, many clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviors have been clarified. Advances have been achieved in part through the use of intracerebral recording methods such as stereo-electroencephalography (S-EEG), which has allowed a unique "in vivo" neurophysiological insight into focal epilepsy. Using S-EEG, the local features of physiological and pathological EEG activity in different cortical and subcortical structures have been better defined during the entire sleep-wake spectrum. For example, S-EEG has contributed to clarify the semiology of sleep-related seizures as well as highlight the specific epileptogenic networks involved during ictal activity. Moreover, intracerebral EEG recordings derived from patients with epilepsy have been valuable to study sleep physiology and specific sleep disorders. The occasional co-occurrence of NREM-related parasomnias in epileptic patients undergoing S-EEG investigation has permitted the recordings of such events, highlighting the presence of local electrophysiological dissociated states and clarifying the underlying pathophysiological substrate of such NREM sleep disorders. Based on these recent advances, the authors review and summarize the current and relevant S-EEG literature on sleep-related hypermotor epilepsies and NREM-related parasomnias. Finally, novel data and future research hypothesis will be discussed.

Sleep Related Hypermotor Seizures with a Right Parietal Onset.

Nocturnal frontal lobe epilepsy (NFLE) is a syndrome characterized by the occurrence of sleep related seizures of variable complexity and duration. Hypermotor seizures (HMS) represent a classic manifestation of this syndrome, associated with a perturbation of the ventromesial frontal cortex and anterior cingulate gyrus regions. Nevertheless, in recent years, reports have showed that the seizure onset zone (SOZ) need not be of frontal origin to generate HMS. Here we report an unusual case of a patient presenting with a seven-year history of drug-resistant sleep related HMS arising from the mesial parietal region. The presence of an infrequent feeling of levitation before the HMS was key to suspecting a subtle focal cortical dysplasia in the right precuneus region. A stereo-EEG investigation confirmed the extra-frontal seizure onset of the HMS and highlighted the interrelationship between unstable sleep and seizure precipitation.

The utility of magnetoencephalography in the presurgical evaluation of refractory insular epilepsy.

PURPOSE: To study the utility of magnetoencephalography (MEG) in patients with refractory insular epilepsy. Covered by highly functional temporal, frontal, and parietal opercula, insular-onset seizures can manifest a variety of ictal symptoms falsely leading to a diagnosis of temporal, frontal, or parietal lobe seizures. Lack of recognition of insular seizures may be responsible for some epilepsy surgery failures. METHODS: We retrospectively reviewed and analyzed MEG data in 14 patients with refractory insular seizures defined through intracranial electroencephalography (EEG) or by the presence of an epileptogenic lesion in the insula with compatible seizure semiology. MEG was performed as part of the noninvasive presurgical evaluation, using a 275-channel whole head MEG system. MEG data were analyzed using a single equivalent current dipole model. MEG localization was compared to interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) results and to the resection margin. KEY FINDINGS: Three patterns of MEG spike sources were observed. Seven patients showed an anterior operculoinsular clusters and two patients had a posterior operculoinsular cluster. No spikes were detected in one patient, and the remaining four patients showed a diffuse perisylvian distribution. Spike sources showed uniform orientation perpendicular to the sylvian fissure. Nine patients proceeded to insular epilepsy surgery with favorable surgical outcome. Among patients with anterior operculoinsular cluster who proceeded to have surgery, MEG provided superior information to ictal SPECT in four of six patients and to interictal PET in five of six patients. SIGNIFICANCE: MEG is useful in identifying patients who are likely to benefit from epilepsy surgery targeting the insula, particularly if a tight dipole cluster is identified even if other noninvasive modalities fail to produce localizing results.

Hippocampal atrophy and abnormal brain development following a prolonged hyperthermic seizure in the immature rat with a focal neocortical lesion.

In rats subjected to a focal cortical lesion soon after birth, hyperthermia at P10 induces a prolonged epileptic seizure, often followed by temporal lobe epilepsy in the adult. To determine whether brain damage and notably hippocampal atrophy occur early on in this model, whole brain as well as hemispheric, cortical, subcortical and hippocampal volumes was measured in non-lesioned and lesioned rat pups, 2 days (P12) and 12 days (P22) after the hyperthermic seizure. All pups with a cortical lesion showed reductions in whole brain and in ipsilateral hemispheric, cortical and hippocampal volumes at P12, which persisted at P22 in pups having also sustained a prolonged hyperthermic seizure at P10. Limiting the duration of the seizure with Diazepam prevented the hippocampal atrophy. Thus, a prolonged hyperthermic seizure in immature brain with a subtle neocortical lesion impairs normal brain development, and the duration of the seizure appears to be a key factor in generating hippocampal atrophy.

Febrile seizures in the predisposed brain: a new model of temporal lobe epilepsy.

The atypical febrile seizure has important clinical implications because of its association with the mesial temporal lobe epilepsy syndrome, which is the most common of the intractable epilepsies. However, whether a causal relation exists between these conditions is currently unknown. We have previously shown that a focal cortical lesion induced in the neonatal rat predisposes to the development of atypical hyperthermic seizures. We show here that 86% of the lesion plus hyperthermia group experience development of spontaneous recurrent seizures recorded from the amygdala ipsilateral to the lesion. Control rats did not have spontaneous recurrent behavioral or electrographic seizures. Lesioned rats with hyperthermic seizures also showed an impaired performance on the Morris water maze when compared with naive control rats, suggesting mild deficits in learning and memory. These findings support a link between the atypical febrile seizure and mesial temporal lobe epilepsy, and at the same time establish a new model for this condition through which new preventative and therapeutic strategies can be tested.