Late-onset fabry disease due to the p.Phe113Leu variant: the first italian cluster of five families.

BACKGROUND: The GLA c.337T > C (p.Phe113Leu) is a known pathogenic variant associated to late-onset Fabry disease phenotype with predominant cardiac manifestations. A founder effect was demonstrated in a large cohort in the Portuguese region of Guimarães. Herein we report an in-depth phenotype description of a cluster of five Southern Italy families. METHODS: Family pedigrees of five index males with the p.Phe113Leu variant were obtained and all at-risk relatives underwent biochemical and genetical screening test. Carriers of GLA p.Phe113Leu variant underwent subsequent multidisciplinary clinical and instrumental evaluation. RESULTS: Thirty-one (16 M, 15 F) individuals with p.Phe113Leu pathogenic variant were identified. Sixteen out of 31 patients (51.6%) had cardiac manifestations. Notably, myocardial fibrosis was found in 7/8 patients, of whom 2 were under 40 years. Stroke occurred in 4 patients. White matter lesions were detected in 12/19 patients and occurred in 2/10 of subjects under 40 years. Seven females complained of acroparesthesias. Renal involvement occurred in 10 patients. Angiokeratomas were evident in 9 subjects. Eyes, ear, gastrointestinal and pulmonary involvement occurred in the minority of subjects. CONCLUSION: This study demonstrates that a cluster of subjects with p.Phe113Leu pathogenic variant is also present in Southern Italy. Disease manifestations are frequent in both sexes and may occur early in life. Cardiac involvement represents the core manifestation, but neurological and renal involvement is also frequent, suggesting that extra-cardiac complications deserve clinical attention.

Epilepsy in Cerebrovascular Diseases: A Narrative Review.

BACKGROUND: Epilepsy is a common comorbidity of cerebrovascular disease and an increasing socioeconomic burden. OBJECTIVE: We aimed to provide an updated comprehensive review on the state of the art about seizures and epilepsy in stroke, cerebral haemorrhage, and leukoaraiosis. METHODS: We selected English-written articles on epilepsy, stroke, and small vessel disease up until December 2021. We reported the most recent data about epidemiology, pathophysiology, prognosis, and management for each disease. RESULTS: The main predictors for both ES and PSE are the severity and extent of stroke, the presence of cortical involvement and hemorrhagic transformation, while PSE is also predicted by younger age at stroke onset. Few data exist on physiopathology and seizure semiology, and no randomized controlled trial has been performed to standardize the therapeutic approach to post-stroke epilepsy. CONCLUSION: Some aspects of ES and PSE have been well explored, particularly epidemiology and risk factors. On the contrary, few data exist on physiopathology, and existing evidence is mainly based on studies on animal models. Little is also known about seizure semiology, which may also be difficult to interpret by non-epileptologists. Moreover, the therapeutic approach needs standardization as regards indications and the choice of specific ASMs. Future research may help to better elucidate these aspects.

Convolutional Neural Network Classification of Rest EEG Signals among People with Epilepsy, Psychogenic Non Epileptic Seizures and Control Subjects.

Identifying subjects with epileptic seizures or psychogenic non-epileptic seizures from healthy subjects via interictal EEG analysis can be a very challenging issue. Indeed, at visual inspection, EEG can be normal in both cases. This paper proposes an automatic diagnosis approach based on deep learning to differentiate three classes: subjects with epileptic seizures (ES), subjects with non-epileptic psychogenic seizures (PNES) and control subjects (CS), analyzed by non-invasive low-density interictal scalp EEG recordings. The EEGs of 42 patients with new-onset ES, 42 patients with PNES video recorded and 19 patients with CS all with normal interictal EEG on visual inspection, were analyzed in the study; none of them was taking psychotropic drugs before registration. The processing pipeline applies empirical mode decomposition (EMD) to 5s EEG segments of 19 channels in order to extract enhanced features learned automatically from the customized convolutional neural network (CNN). The resulting CNN has been shown to perform well during classification, with an accuracy of 85.7%; these results encourage the use of deep processing systems to assist clinicians in difficult clinical settings.

Late epileptic seizures following cerebral venous thrombosis: a systematic review and meta-analysis.

BACKGROUND: Identifying late epileptic seizures (LS) following cerebral venous thrombosis (CVT) can be useful for prognosis and management. We systematically reviewed the literature to identify risk factors for LS due to CVT. METHODS: We systematically searched PubMed, Scholar, and Scopus databases (May 2021) to identify studies reporting data on prevalence and risk factors for CVT-LS. The methodological quality was assessed with the Ottawa-Newcastle Scale. The risk of developing CVT-LS was summarized in meta-analyses and expressed as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using random-effects models. RESULTS: Out of the 332 records retrieved, four studies were eventually included with a total of 1309 patients with CVT and 142 (11%) with CVT-LS. The most relevant predictors of CVT-LS were symptomatic seizures (OR 5.66, 95% CI 3.83-8.35), stupor/coma (OR 6.81, 95% CI 1.18-39.20), focal neurologic signs (OR 6.81, 95% CI 1.18-39.2), hemorrhagic component (OR 3.52, 95% CI 2.45-5.06), and superior sagittal sinus involvement (OR 1.52, 95% CI 1.04-2.21). CONCLUSION: There are several risk factors for CVT-LS that should be considered in clinical practice. Further high-quality studies are warranted to develop predictive models for individualized risk stratification and prediction of CVT-LS.

Psychiatric and Behavioural Side Effects Associated With Perampanel in Patients With Temporal Lobe Epilepsy. A Real-World Experience.

Psychiatric and behavioural side effects are common, undesirable effects associated with antiseizure medication use. Temporal lobe epilepsy is the most common focal epilepsy in adults and it is frequently associated with drug resistance. Patients with intractable epilepsy are more likely to have psychiatric and behavioural side effects when taking antiseizure medications and seem to be at higher risk for psychiatric comorbidities. Perampanel is a novel anti-seizure medication approved for focal and generalised epilepsies as add-on therapy. This is a 12-week short-term observational prospective study on people with focal epilepsy consecutively recruited from an Italian tertiary epilepsy centre, aimed to compare incidence and severity of psychiatric and behavioural side effects associated with perampanel use in patients with temporal lobe epilepsy as compared to other focal epilepsies. All patients received add-on perampanel according to indication and clinical judgement. Incidence and severity of psychiatric and behavioural side effects were rated by Neuropsychiatric Inventory Questionnaire. All patients enrolled answered the questionnaire before starting perampanel and after 12 weeks of treatment. We found no significant difference in terms of incidence and severity of psychiatric and behavioural side effects associated with perampanel in patients with temporal lobe epilepsy as compared to other focal epilepsies. In line with the literature, the most common adverse effects were "irritability" for both groups and "aggression" for patients with other focal epilepsies.

Predictive factors of Status Epilepticus and its recurrence in patients with adult-onset seizures: A multicenter, long follow-up cohort study.

PURPOSE: Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures. METHODS: We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model. RESULTS: Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p<0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p<0.001). CONCLUSIONS: In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.

Diagnostic and therapeutic approach to drug-resistant juvenile myoclonic epilepsy.

INTRODUCTION: Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of generalized epilepsy of presumed genetic origin representing up to 10% of all epilepsy cases. Despite adequate anti-seizure medication (ASM) treatment, seizures persist in one-third of JME patients. AREAS COVERED: A literature search was conducted using Pubmed search on the topics of drug-resistant JME. EXPERT OPINION: About 30% of JME patients are drug-resistant. Valproate (VPA) is considered the first-choice drug. In women of childbearing potential, levetiracetam (LEV) should represent the first-choice treatment. Alternative monotherapy or add-on therapy should be considered in subjects with resistant seizures after the exclusion of pseudo-drug resistance. The choice of the add-on ASM depends on the predominant seizure type. In subjects with persistent bilateral tonic-clonic seizures, LEV or lamotrigine should be firstly considered. In patients with difficult-to-treat myoclonic seizures, clonazepam or LEV are recommended. In case of persistent absences, ethosuximide should be considered. With appropriate selection and safeguards in place, VPA should remain available as an option in women of childbearing potential whose seizures are resistant to other treatments.

Evaluation of relational reasoning by a transitive inference task in attention-deficit/hyperactivity disorder.

OBJECTIVE: Here we explored whether children with ADHD have a deficit in relational reasoning, a skill subtending the acquisition of many cognitive abilities and social rules. METHOD: We analyzed the performance of a group of children with ADHD during a transitive inference task, a task requiring first to learn the reciprocal relationship between adjacent items of a rank ordered series (e.g., A>B; B>C; C>D; D>E; E>F), and second, to deduct the relationship between novel pairs of items never matched during the learning (e.g., B>D; C>E). RESULTS: As a main result, we observed that children with ADHD were impaired in performing inferential reasoning problems. The deficit in relational reasoning was found to be related to the difficulty in managing a unified representation of ordered items. CONCLUSION: The present finding documented a novel deficit in ADHD, contributing to improving the understanding of the disorder. (PsycINFO Database Record