Sleep related hyper motor epilepsy (SHE): a unique syndrome with heterogeneous genetic etiologies

Abstract Sleep-related hypermotor epilepsy (SHE), formerly known as Nocturnal Frontal Lobe Epilepsy is a focal epilepsy characterized by seizures with complex hyperkinetic automatisms and/or asymmetric tonic/dystonic posturing occurring mostly during sleep. SHE is a rare disease with an estimated minimum prevalence of 1.8/100,000 individuals and represent about 10% of drug-resistant surgical cases. This disorder, though uncommon, is of considerable interest to a broad spectrum of specialists, from child neurologists to neurosurgeons. Distinguishing this condition from non-epileptic paroxysmal behaviour occurring physiologically or pathologically during sleep is often difficult and sometimes impossible on clinical grounds alone, even for experienced epileptologists and sleep physicians. Recognized aetiologies of SHE are heterogeneous and include acquired injuries, genetic causes and structural anomalies such as focal cortical dysplasia. Multiple aetiologies (structural-genetic) are also possible. Non-specific clinical features distinguished different aetiologies even if SHE due to structural lesions usually manifests with early-onset drug-resistant seizures and showed a worse long-term prognosis. The causative genes for SHE are multiple and encode for proteins involved in different molecular pathways. The cholinergic system and the mTOR pathway are the most relevant. This review will provide an exhaustive overview of the genetic background of SHE

3D figure of epilepsy syndromes

We propose an instructive figure that summarized the classification of epilepsy syndromes according to the 2022 report of the ILAE Task Force on Nosology and Definitions. Our aim is to present, in one figure, different concepts such as the names of epilepsy syndromes, their extreme and classical ages of onset, their epilepsy types (generalized, focal or generalized and focal) but also their membership in groups of epilepsy syndromes as for self-limited or developmental and epileptic encephalopathy. With this figure, we provided an interactive tool, as supplementary data, helping to present this classification and link it to electro-clinical mandatory, alerts and exclusionary criteria of each syndrome, in accordance with the ILAE position papers on syndromes classification and nosology. This report may be used as an illustrative tool for teaching epilepsy syndromes and as a practical and comprehensive aid for the classification of epilepsy individuals' syndromes

IDIOPATHIC PARTIAL EPILEPSY WITH AUDITORY FEATURES (IPEAF): A CLINICAL AND GENETIC STUDY OF 53 SPORADIC CASES

The purpose of our study was to describe the clinical characteristics of sporadic (S) cases of partial epilepsy with auditory features (PEAF) and pinpoint clinical, prognostic and genetic differences with respect to previously reported familial (F) cases of autosomal dominant partial epilepsy with auditory features (ADPEAF). We analysed 53 patients (24 females and 29 males) with PEAF diagnosed according to the following criteria: partial epilepsy with auditory symptoms, negative family history for epilepsy and absence of cerebral lesions on NMR study. All patients underwent a full clinical, neuroradiological and neurophysiological examination. Forty patients were screened for mutations in LGI1/epitempin, which is involved in ADPEAF. Age at onset ranged from 6 to 39 years (average 19 years). Secondarily generalized seizures were the most common type of seizures at onset (79%). Auditory auras occurred either in isolation (53%) or associated with visual, psychic or aphasic symptoms. Low seizure frequency at onset and good drug responsiveness were common, with 51% of patients seizure-free. Seizures tended to recur after drug withdrawal. Clinically, no major differences were found between S and F patients with respect to age at onset, seizure frequency and response to therapy. Analysis of LGI1/epitempin exons failed to disclose mutations. Our data support the existence of a peculiar form of non-lesional temporal lobe epilepsy closely related to ADPEAF but without a positive family history. This syndrome, here named IPEAF, has a benign course in the majority of patients and could be diagnosed by the presence of auditory aura. Although LGI1 mutations have been excluded, genetic factors may play an aetiopathogenetic role in at least some of these S cases

Selection of antiseizure medications for first add-on use: A consensus paper.

Abstract Introduction When monotherapy used alone or sequentially fails to achieve seizure control, a trial of combination therapy may be considered. Objective To define optimal criteria to guide choice of an antiseizure medication (ASM) for use as first add-on. Methods A standardized Delphi procedure was applied to produce a list of consensus statements. First, an Expert Board consisting of 5 epileptologists agreed on a set of 46 statements relevant to the objective. The statements were then finalized through an iterative process by a Delphi Panel of 84 Italian pediatric and adult neurologists with expertise in the management of epilepsy. Panel members provided anonymous ratings of their level of agreement with each statement on a 9-point Likert scale. Results Consensus, defined as agreement by at least 80% of Panel members, was reached for 36 statements. Medication-related factors considered to be important for drug selection included efficacy, tolerability and safety, interaction potential, mechanism of action, and ease of use. The need to optimize adherence and to tailor drug selection to individual characteristics was emphasized. Conclusions Choice of an ASM for first add-on requires consideration of many factors, many of which also apply to choose initial treatment. Factors more specifically relevant to add-on use include drug interaction potential and the preference for an ASM with a different mechanism of action

MECP2 duplication syndrome: The electroclinical features of a case with long-term evolution

MECP2 duplication syndrome (MDS) is a rare and severe neurodevelopmental disorder frequently associated with epilepsy. Different seizure types and electroencephalographic (EEG) patterns were described in patients with MDS, although it lacks a specific phenotype. We report on an adult patient with long-term epilepsy showing an evolution of the EEG pattern that progressively changed into burst suppression (BS) during sleep. As BS has not been previously reported in MDS, this report expands the neurophysiological phenotype of MDS and further suggest the possible occurrence of a longitudinal spectrum of seizure types and EEG patterns in MDS

Complete Agenesis of Corpus Callosum in KCNQ2-Related Neonatal Epileptic Encephalopathy

KCNQ2-associated brain abnormalities include thinning of the corpus callosum but complete ACC has never been reported

FDG-PET findings and alcohol-responsive myoclonus in a patient with Unverricht-Lundborg disease

The aim of this report is to describe clinical, EEG, and neuroimaging findings in a patient with UnverrichtLundborg disease (ULD), the most common form of progressive myoclonus epilepsy (PME). A 23-year-old male with genetically confirmed ULD had a phenotype consisting of myoclonus, generalized seizures, intellectual disability, ataxia, and dysarthria. Myoclonus and gait disturbance were strongly ameliorated by alcohol consumption. EEG revealed a posterior dominant rhythm with alpha variant, mild bilateral slowing, and anterior-predominant epileptiform abnormalities. Brain MRI showed mild cerebellar atrophy. FDG-PET revealed hypometabolism more prominent in the posterior brainstem, thalami, frontal and parietal lobes. This report confirms that alcohol may ameliorate myoclonus in a subset of patients with PME, including genetically confirmed ULD. In addition, the presence of FDG-PET hypometabolism predominant in the frontoparietal region and thalami has not been previously described in ULD, yet is consistent with previous brain morphometry studies showing motor cortex and thalamic atrophy in ULD, and brings into question the possibility of a shared metabolic pattern with other PMEs, notably Lafora disease. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Clinical features and pathophysiology of disorders of arousal in adults: A window into the sleeping brain

Introduction: Disorders of Arousal (DoA) are NREM parasomnias that have been typically regarded as self-limited childhood manifestations. It is now clear that DoA can persist in adults, often presenting with distinctive characteristics. So far, few studies have described the clinical course and characteristics of DoA in adulthood, therefore a large part of their semiology is ignored. The aim of this study is to describe the clinical manifestations of DoA in an adult population and to provide a pathophysiological interpretation of their features. Methods: We screened our database for all 1,600 adult ( 6515 years) patients with sleep-related motor behaviors between 1995 and 2016. We identified 45 patients with typical DoA episodes, of whom a complete history, neurological examination and diagnostic video-polysomnography (VPSG) were available. All patients provided a detailed description of their episodes (with particular regards to semiology, frequency, and association with stressful life events) in different life periods. VPSG recordings were reviewed and DoA episodes were identified and assigned to three different categories according to their complexity. Results: Our population was composed of 45 adult patients ranging between 15 and 76 years. Sleepwalking was reported by 86% of patients, possibly associated with complex interactions with the environment and violent behaviors in 53% of cases; distressing mental contents were reported by 64%. Recall of the episodes was reported in 77% of patients. Non-restorative sleep was reported in 46% of patients. Stress was a potential episode trigger in 80% of patients. VPSG recordings documented 334 DoA episodes. According to our classification of motor patterns, 282 episodes (84%) were Simple Arousal Movements (SAMs), 34 (10%) Rapid Arousal Movements (RAMs) and 18 (5%) Complex Arousal Movements (CAMs). Discussion: Our study confirms that DoA in adulthood present with distinctive characteristics, such as non-restorative sleep, violence and complex, or bizarre behaviors. Alternative classifications of DoA based on motor patterns could be useful to characterize DoA episodes in adults, as different motor patterns often coexist in the same individual and minor episodes are more common but generally underreported by patients. Prospective studies are needed for a definitive characterization of DoA in adulthood throughout the life course

Epilepsy With Auditory Features: From Etiology to Treatment

Epilepsy with auditory features (EAF) is a focal epilepsy belonging to the focal epileptic syndromes with onset at variable age according to the new ILAE Classification. It is characterized by seizures with auditory aura or receptive aphasia suggesting a lateral temporal lobe involvement of the epileptic discharge. Etiological factors underlying EAF are largely unknown. In the familial cases with an autosomal dominant pattern of inheritance several genes have been involved, among which the first discovered, LGI1, was thought to be predominant. However, increasing evidence now points to a multifactorial etiology, as familial and sporadic EAF share a virtually identical electro-clinical characterization and only a few have a documented genetic etiology. Patients with EAF usually have an unremarkable neurological examination and a good response to antiseizure medications. However, it must be underscored that total remission might be lower than expected and that treatment withdrawal might lead to relapses. Thus, a proper understanding of this condition is in order for better patient treatment and counseling. Further studies are still required to further characterize the many facets of EAF

If seizures left speechless: CA-P-S C-A-R-E, a proposal of a new ictal language evaluation protocol

Introduction: We aimed to create standardized protocol for language examination in patients who underwent video-EEG recording and assessed its efficacy in the characterization of ictal language impairment, its ability to differentiate this from impaired awareness, and interobserver reliability in clinical practice. Methods: From our database of video-EEG recordings, we selected a representative sample of 63 focal seizures with presumed language impairment. A multidisciplinary team of epileptologists, EEG technicians, and speech therapists analyzed the selected videos to highlight the critical issues of ordinary ictal language evaluation. We subsequently followed a multi-step process to develop the protocol and assess its interobserver reliability. Results: A protocol based on seven tests in hierarchical succession was created, summed up in the acronym CA-P-S C-A-R-E (Closed Answers, Pro-speak question, Simple orders, Common object denomination, Audio repetition, Reading, Evoke). Following its preliminary administration for 5 months, we assessed the inter-observer reliability of 16 healthcare professionals in distinguishing between language impairment and impaired awareness among a sample of 10 seizures, finding a substantial agreement (kappa 0.61). Conclusion: The proposed protocol, made of simple and easy to memorize tests, is an effective tool that evaluates multiple domains beyond language. Its use could help to recognize ictal aphasia effectively and differentiate it from impaired awareness, minimizing inter-examiner variability