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N.A. (Letter)

Epilepsy with Auditory Features (EAF) is a focal epilepsy syndrome mainly of unknown aetiology. LGI1 and RELN have been identified as the main cause of Autosomal Dominant EAF and anecdotally reported in non-familial cases. Pathogenic variants in SCN1A and DEPDC5 have also been described in a few EAF probands belonging to families with heterogeneous phenotypes and incomplete penetrance. We aimed to estimate the contribution of these genes to the disorder by evaluating the largest cohort of EAF. We included 112 unrelated EAF cases (male/female: 52/60) who underwent genetic analysis by next-generation sequencing (NGS) techniques. Thirty-three (29.5%) were familial cases. We identified a genetic diagnosis for 8% of our cohort, including pathogenic/likely pathogenic variants (4/8 novel) in LGI1 (2.7%, CI: 0.6-7.6); RELN (1.8%; CI: 0.2-6.3); SCN1A (2.7%; CI: 0.6-7.6) and DEPDC5 (0.9%; CI 0-4.9).This study shows that the contribution of each of the known genes to the overall disorder is limited and that the genetic background of EAF is still largely unknown. Our data emphasize the genetic heterogeneity of EAF and will inform the diagnosis and management of individuals with this disorder.

Objectives: We explored the impact of the coronavirus disease-19 (COVID-19) emergency on the health of people with epilepsy (PwE). We also investigated their attitude toward telemedicine.Methods: The PubMed database up to September 10, 2020 was searched for questionnaire-based studies conducted in PwE during the COVID-19 emergency, and the literature retrieved was reviewed. In addition, all patients who had a telephone consultation with our center between May 7 and July 31, 2020 were invited to fill in a 57-item online questionnaire focusing on epilepsy and comorbidities, any changes in lifestyle or clinical conditions and any emergency-related problems arising during the COVID-19 emergency, and their views on telemedicine. Associations between variables were detected through X2 test and Fisher's exact test. Univariate and multivariate logistic regression models were used to evaluate the effects of different factors on clinical conditions.Results: Twelve studies met the literature search criteria. They showed that the rate of seizure worsening during the emergency ranged from 4 to 35% and was mainly correlated with epilepsy severity, sleep disturbances and COVID-19-related issues. Our questionnaire was filled in by 222 PwE or caregivers. One hundred (76.6%) reported unchanged clinical conditions, 25 (11.3%) an improvement, and 27 (12%) a deterioration. Reported clinical worsening was associated with a psychiatric condition and/or medication (OR = 12.59, p < 0.001), sleep disorders (OR = 8.41, p = 0.001), limited access to healthcare (OR = 4.71, p = 0.016), and experiencing seizures during the emergency (OR = 4.51, p = 0.007). Telemedicine was considered acceptable by 116 subjects (52.3%).Conclusions: Most PwE did not experience a significant change in their clinical conditions during the COVID-19 emergency. However, severity of epilepsy, concomitant disability, comorbid psychiatric conditions, sleep disorders and limited access to healthcare may affect their health.

Veronica Menghi,1 Francesca Bisulli,2 Paolo Tinuper,2 Lino Nobili3,4 1Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 3“Claudio Munari” Center for Epilepsy Surgery, Niguarda Hospital, Milan, Italy; 4Department of Neuroscience (DINOGMI), IRCCS, Giannina Gaslini Institute, University of Genoa, Genoa, Italy Abstract: Sleep-related hypermotor epilepsy (SHE), previously called nocturnal frontal lobe epilepsy (NFLE), is a focal epilepsy characterized by asymmetric tonic/dystonic posturing and/or complex hyperkinetic seizures occurring mostly during sleep. SHE fulfills the definition of rare disease with an estimated minimum prevalence of 1.8/100,000 individuals, and it represents about 10% of drug-resistant surgical cases. Although SHE and autosomal-dominant SHE (ADSHE) have been considered benign epileptic conditions for a long time, emerging data have shed light on the severity of this disorder and some peculiar features can impact negatively on the quality of life of SHE patients. In fact, seizure frequency can be very high, resulting in nocturnal sleep fragmentation with possible diurnal consequences such as excessive sleepiness and fatigue. Moreover, recent studies, adopting a systematic neuropsychological assessment, have shown deficits in memory, executive functions and visuo-spatial abilities in almost half of SHE patients. Intellectual disabilities and psychiatric disorders have also been reported in some genetic forms. SHE may also exert a negative effect on health-related quality of life, especially in domains pertaining to a patient’s role in the family, social context and patient’s illness experience. Despite a good response to pharmacological treatment, especially with carbamazepine, 30% of SHE patients suffer from drug-resistant seizures. Finally, recent studies suggest a poor prognosis in a high percentage of SHE patients with a 20.4% cumulative probability of achieving terminal remission at 10 years from onset. For selected drug-resistant SHE patients, epilepsy surgery is the only treatment offering high probability of recovery, both for seizures and for epilepsy-related sleep alterations. Keywords: epilepsy, parasomnias, sleep-related hypermotor epilepsy, nocturnal frontal lobe epilepsy, epidemiology

Objective: To assess the long-term outcome of epilepsy with auditory features (EAF) and to identify the clinical predictors for prognosis. Methods: The study involved consecutive EAF patients with a follow-up of ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimate to calculate the cumulative time-dependent probability of conversion to TR. Log-rank test and multivariate Cox regression analyses were performed to study the association between time to TR and prognostic determinants. Results: We included 123 EAF patients (male/female = 58/65) with a median follow-up of 11 years (1626.9 person-years). Most were sporadic cases (68.3%), whereas 31.7% reported a family history of epilepsy. At last assessment, 42 patients had achieved TR (34.1%). Of the remaining 81 cases with no TR (65.9%), 37% had been in remission for 1-4 years and 62.9% still had seizures within the past year. The cumulative rates of TR were 26.6%, 35.7%, and 51.6% at 10, 20, and 30 years from inclusion. On multivariate analysis, age at onset > 10 years (hazard ratio [HR] = 3.2, P = .028), auditory aura characterized by distortions only versus simple/complex hallucinations (HR = 2.9, P = .041), and unremarkable scalp electroencephalogram (EEG) versus EEG with focal epileptiform activity (HR = 3.5, P = .041) were associated with TR. Significance: Our data show a wide prognostic spectrum of EAF, ranging from mild forms with spontaneous remission, to severely refractory epilepsy addressed to surgery. The outcome, less favorable than expected from previous studies, appears to be primarily a function of 3 prognostic negative risk factors: age at onset < 10 years, auditory aura characterized by complex auditory hallucinations, and focal epileptiform abnormalities on scalp EEG. These predictors, easy to collect even at the first visit, may inform both clinicians and patients about the long-term prognosis and aid patient management.

ObjectiveThe differential diagnosis between sleep-related hypermotor epilepsy (SHE) and disorders of arousal (DOA) may be challenging. We analyzed the stage and the relative time of occurrence of parasomnic and epileptic events to test their potential diagnostic accuracy as criteria to discriminate SHE from DOA.MethodsVideo-polysomnography recordings of 89 patients with a definite diagnosis of DOA (59) or SHE (30) were reviewed to define major or minor events and to analyze their stage and relative time of occurrence. The “event distribution index” was defined on the basis of the occurrence of events during the first versus the second part of sleep period time. A group analysis was performed between DOA and SHE patients to identify candidate predictors and to quantify their discriminative performance.ResultsThe total number of motor events (i.e. major and minor) was significantly lower in DOA (3.2 ± 2.4) than in SHE patients (6.9 ± 8.3; p = 0.03). Episodes occurred mostly during N3 and N2 in DOA and SHE patients, respectively. The occurrence of at least one major event outside N3 was highly suggestive for SHE (p = 2*e-13; accuracy = 0.898, sensitivity = 0.793, specificity = 0.949). The occurrence of at least one minor event during N3 was highly suggestive for DOA (p = 4*e-5; accuracy = 0.73, sensitivity = 0.733, specificity = 0.723). The “event distribution index” was statistically higher in DOA for total (p = 0.012) and major events (p = 0.0026).ConclusionThe stage and the relative time of occurrence of minor and major motor manifestations represent useful criteria to discriminate DOA from SHE episodes.

Objective: The aim of this study was to characterize the neuropsychological features of a representative sample of Sleep-related Hypermotor Epilepsy (SHE) patients and to highlight clinical associations. Methods: This cross-sectional study included 60 consecutive patients with video/video-electroencephalography–documented SHE. All were assessed by measures of intelligence. Individuals with normal scores underwent a standardized battery of tests. The Fisher exact test and Wilcoxon rank-sum test for statistical analysis. Results: Mean total IQ was 96.96 ± 21.50, with significant differences between verbal and performance scores (p < 0.0001). Nine patients (15%) had intellectual disability (ID)/cognitive deterioration. Of the 49 assessed by the extensive battery, 23 (46.9%) showed deficits in at least one test evaluating phonemic fluency (24.5%), memory (24.5%), inhibitory control (22.4%), or working memory (10.2%). Patients with mutations in SHE genes had lower IQ than patients without mutations, irrespective of the specific gene (p = 0.0176). Similarly, pathological neurological examination (NE) and “any underlying brain disorder” (at least one among pathological NE, abnormal brain magnetic resonance imaging findings, perinatal insult) were associated with ID (p = 0.029, p = 0.036). A higher seizure frequency at last assessment and poor prognosis correlated with worse scores in visuo-spatial memory (p = 0.038, p = 0.040) and visuo-spatial abilities (p = 0.016). Status epilepticus (p = 0.035), poor response to antiepileptic drugs (p = 0.033), and poor prognosis (p = 0.020) correlated with lower shifting abilities, whereas bilateral convulsive seizures correlated with worse working memory (p = 0.049). Conclusion: In all, 53.3% of SHE patients had neuropsychological deficits. The profile of impairment showed worse verbal IQ, as well as deficits in extrafrontal and selective frontal functions. Our data support the contribution of genetics in ID by different biological mechanisms. Variables of clinical severity affect memory and executive functioning.