Copy Number Variation and Epilepsy: State of the Art in the Era of High-Throughput Sequencing-A Multicenter Cohort Study.

BACKGROUND: Genetic epilepsy diagnosis is increasing due to technological advancements. Although the use of molecular diagnosis is increasing, chromosomal microarray analysis (CMA) remains an important diagnostic tool for many patients. We aim to explore the role and indications of CMA in epilepsy, given the current genomic advances. METHODS: We obtained data from 378 epileptic described patients, who underwent CMA between 2015 and 2021. Different types of syndromic or nonsyndromic epilepsy were represented. RESULTS: After excluding patients who were undertreated or had missing data, we included 250 patients with treated epilepsy and relevant clinical information. These patients mostly had focal epilepsy or developmental and epileptic encephalopathy, with a median start age of 2 years. Ninety percent of the patients had intellectual disability, more than two thirds had normal head size, and 60% had an abnormal magnetic resonance imaging. We also included 10 patients with epilepsy without comorbidities. In our cohort, we identified 35 pathogenic copy number variations (CNVs) explaining epilepsy with nine recurrent CNVs enriched in patients with epilepsy, 12 CNVs related to neurodevelopmental disorder phenotype with possible epilepsy, five CNVs including a gene already known in epilepsy, and nine CNVs based on size combined with de novo occurrence. The diagnosis rate in our study reached 14% (35 of 250) with first-line CMA, as previously reported. Although targeted gene panel sequencing could potentially diagnose some of the reported epilepsy CNVs (34% [12 of 35]). CONCLUSIONS: CMA remains a viable option as the first-line genetic test in cases where other genetic tests are not available and as a second-line diagnostic technique if gene panel or exome sequencing yields negative results.

Genetic generalized epilepsy and generalized onset seizures with focal evolution (GOFE).

"Generalized Onset with Focal Evolution" (GOFE) is an underrecognized seizure type defined by an evolution from generalized onset to focal activity during the same ictal event. We aimed to discuss electroclinical aspects of GOFE and to emphasize its link with Genetic Generalized Epilepsy (GGE). Patients were identified retrospectively over 10 years, using the video-EEG data base from the Epilepsy Unit of Strasbourg University Hospital. GOFE was defined, as previously reported, from an EEG point of view with an evolution from generalized onset to focal activity during the same ictal event. Three male patients with GOFE were identified among 51 patients with recorded tonic-clonic seizures. Ages at onset of seizures were 13, 20 and 22 years. Focal clinical features (motor asymmetric phenomenology) could be identified. EEG showed generalized interictal discharges with focal evolution of various localization. Four seizures were recorded characterized by 2-3 s of generalized abnormalities followed by focal (parieto-occipital or frontal) discharges. There were initially uncontrolled seizures with lamotrigine, but all patients reported a good outcome with valproate monotherapy. We emphasize that GOFE presents many similarities with GGE. Recognition of the GOFE entity could bring a therapeutic interest avoiding misdiagnosis of focal epilepsy and consequently inappropriate use of narrow spectrum anti-seizure medicine.

A rise in cases of nitrous oxide abuse: neurological complications and biological findings.

BACKGROUND: The recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent. METHODS: We report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse. RESULTS: Our patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients. CONCLUSION: We report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made.

And if we had to do it all over again, would we send medical students to the emergency departments during a pandemic? Lessons learned from the COVID-19 outbreak.

The COVID-19 pandemic has led to increased staffing needs in emergency departments. The question quickly arose as to whether it was appropriate to offer medical students the opportunity to assist this staff. The dilemma stems in part from the potential impact on their psychological well-being as well as their academic and clinical performances. We sought to determine the level of anxiety of medical students during the COVID-19 outbreak, and whether it was higher among the students who chose to return to the clinical setting, especially in first-line units (i.e., emergency departments and resuscitation units). In May 2020, 1180/1502 (78.5%) undergraduate medical students at Strasbourg Medical School (France) completed a questionnaire assessing their anxiety and clinical experience. A 2018 cohort of undergraduate medical students served as the baseline. The 2020 COVID cohort had higher rates of anxiety than the 2018 cohort. This difference was specifically observed in the students who chose not to return to the clinical setting during the crisis (N = 684, 59%). At linear regression, the main factors associated with anxiety were gender (p < 0.005) and perceived clinical activity personal conditions (p < 0.001). Employment site, including COVID first-line units, was not correlated with anxiety. Working in the clinical setting during the COVID-19 outbreak is not a risk factor for anxiety in medical students. Instead, it is an active coping strategy, suggesting that there are no barriers to allowing students to return to clinical settings during a pandemic, including first-line units, in terms of their psychological well-being.