Objective
Eyelid myoclonia with absences (EMA) is a syndrome characterized by eyelid myoclonia with or without absences, eye closure‐induced generalized electroencephalographic (EEG) paroxysms and ...photosensitivity. Few data are available about the prognostic factors of this syndrome. The main objectives of our study were to describe the clinical and EEG features of a group of patients with EMA and to evaluate the presence of prognostic factors.
Methods
We retrospectively selected a cohort of patients with diagnosis of EMA evaluated in the epilepsy service of the Neurological Clinic of Catania, in the Neurology and Clinical Neurophysiopathology Unit of Oasi Research Institute, Troina and in the Regional Epilepsy Centre of Bianchi‐Melacrino‐Morelli Hospital of Reggio Calabria. We considered the features of the patients during the first year of disease, and at the last follow‐up visit. We stratified the patients into two groups: “seizure‐free”, defined as the absence of seizures for at least 2 years, and “not seizure‐free” and we evaluated the evolution of their characteristics and the presence of factors associated with outcome.
Results
We enrolled 51 patients (40 women (78%); mean age: 30.8 years ± 15.5 range 10‐79). The mean follow‐up time was 8.7 ± 5.8 years. Eleven patients (21.6%) achieved the condition of seizure‐free. Family history of epilepsy was associated with the condition of seizure‐free (P = 0.05). At the last follow‐up visit, EEG photosensitivity and eye closure sensitivity were significantly associated with the condition of “not seizure‐free”.
Significance
The results of our study revealed that a positive family history of epilepsy might be associated with a better outcome in EMA. Furthermore, the persistence of photosensitivity and eye closure sensitivity might indicate persistence of seizures, offering an aid in therapeutic management.
Summary
Objective
Seizures may occur in close temporal association with a stroke or after a variable interval. Moreover, epilepsy is often encountered in patients with leukoaraiosis. Although early ...post‐stroke seizures have been studied extensively, less attention has been paid to post‐stroke epilepsy (PSE) and to epilepsy associated with leukoaraiosis (EAL). The aim of this paper is to review data concerning pathophysiology, prognosis, and treatment of PSE and EAL.
Methods
We performed an extensive literature search to identify experimental and clinical articles on PSE and EAL. We also conducted a systematic review of risk factors for PSE and EAL among eligible studies.
Results
PSE is caused by enhanced neuronal excitability within and near the scar. The role played by white matter changes in EAL remains to be elucidated. Meta‐analysis showed that cortical involvement (odds ratio OR 3.71, 95% confidence interval CI 2.34–5.90, p < 0.001), cerebral hemorrhage (OR 2.41, 95% CI 1.57–3.70, p < 0.001), and early seizures (OR 4.43, 95% CI 2.36–8.32, p < 0.001) are associated with an increased risk of PSE. As regards EAL, no prospective, population‐based studies evaluated the role of different variables on seizure risk. Studies about the management of PSE are limited. PSE is generally well controlled by drugs. Data about risk factors, prognosis, and treatment of EAL are lacking.
Significance
Pathophysiology and risk factors are well defined for PSE but need to be elucidated for EAL. Management of PSE and EAL relies on the clinician's judgment and should be tailored on an individual basis.
A novel technique of quantitative EEG for differentiating patients with early-stage Creutzfeldt-Jakob disease (CJD) from other forms of rapidly progressive dementia (RPD) is proposed. The ...discrimination is based on the extraction of suitable features from the time-frequency representation of the EEG signals through continuous wavelet transform (CWT). An average measure of complexity of the EEG signal obtained by permutation entropy (PE) is also included. The dimensionality of the feature space is reduced through a multilayer processing system based on the recently emerged deep learning (DL) concept. The DL processor includes a stacked auto-encoder, trained by unsupervised learning techniques, and a classifier whose parameters are determined in a supervised way by associating the known category labels to the reduced vector of high-level features generated by the previous processing blocks. The supervised learning step is carried out by using either support vector machines (SVM) or multilayer neural networks (MLP-NN). A subset of EEG from patients suffering from Alzheimer's Disease (AD) and healthy controls (HC) is considered for differentiating CJD patients. When fine-tuning the parameters of the global processing system by a supervised learning procedure, the proposed system is able to achieve an average accuracy of 89%, an average sensitivity of 92%, and an average specificity of 89% in differentiating CJD from RPD. Similar results are obtained for CJD versus AD and CJD versus HC.
Objective
Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure‐induced seizures with ...electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM.
Methods
We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM− (isolated EEM) and EEM+ (EEM accompanied by intellectual disability ID or any other neurodevelopmental/psychiatric disorder).
Results
We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM− subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM− an established association. Burden analysis did not identify any single burdened gene or gene set.
Significance
Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene–disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM− and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM− remains to be elucidated.
According to the hygiene hypothesis, parasites could have a protective role in the development of Multiple Sclerosis (MS). Our aim was to assess the association between presence of anti-Toxoplasma ...gondii antibodies and MS. MS patients were randomly selected from a population-based incident cohort of MS patients in the city of Catania. Age and sex-matched controls were randomly selected from the general population. Clinical and sociodemographic variables were recorded with a structured questionnaire and a blood sample was taken for serological analysis. Specific T. gondii IgG have been detected with a commercial kit. Adjusted Odds Ratios (ORs) were estimated using unconditional logistic regression. 129 MS subjects (66.7% women with a mean age 44.7 ± 11.0 years) and 287 controls (67.3% women with a mean age 48.1 ± 15.6 years) have been enrolled in the study. Anti-T. gondii antibodies were found in 38 cases (29.5%) and 130 controls (45.4%) giving an adjusted OR of 0.56 (95%CI 0.34-0.93). History of mononucleosis and high educational level were significantly associated with MS (adjOR 2.22 and 1.70 respectively) while an inverse association was found between high educational level and T. gondii seropositivity (adjOR 0.42). Our results further support the protective role of parasitic infections in MS.
Although a striking female preponderance has been consistently reported in epilepsy with eyelid myoclonia (EEM), no study has specifically explored the variability of clinical presentation according ...to sex in this syndrome. Here, we aimed to investigate sex‐specific electroclinical differences and prognostic determinants in EEM. Data from 267 EEM patients were retrospectively analyzed by the EEM Study Group, and a dedicated multivariable logistic regression analysis was developed separately for each sex. We found that females with EEM showed a significantly higher rate of persistence of photosensitivity and eye closure sensitivity at the last visit, along with a higher prevalence of migraine with/without aura, whereas males with EEM presented a higher rate of borderline intellectual functioning/intellectual disability. In female patients, multivariable logistic regression analysis revealed age at epilepsy onset, eyelid myoclonia status epilepticus, psychiatric comorbidities, and catamenial seizures as significant predictors of drug resistance. In male patients, a history of febrile seizures was the only predictor of drug resistance. Hence, our study reveals sex‐specific differences in terms of both electroclinical features and prognostic factors. Our findings support the importance of a sex‐based personalized approach in epilepsy care and research, especially in genetic generalized epilepsies.
Objective
Epilepsy with eyelid myoclonia (EEM) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission ...and to a less favorable neuropsychiatric outcome. However, much work is still needed to better delineate this epilepsy syndrome.
Methods
In this multicenter retrospective cohort study, we included 267 EEM patients from nine countries. Data on electroclinical and demographic features, intellectual functioning, migraine with or without aura, family history of epilepsy, and epilepsy syndromes in relatives were collected in each patient. The impact of age at epilepsy onset (AEO) on EEM clinical features was investigated, along with the distinctive clinical characteristics of patients showing sporadic myoclonia involving body regions other than eyelids (body‐MYO).
Results
Kernel density estimation revealed a trimodal distribution of AEO, and Fisher–Jenks optimization disclosed three EEM subgroups: early onset (EO‐EEM), intermediate onset (IO‐EEM), and late onset (LO‐EEM). EO‐EEM was associated with the highest rate of intellectual disability, antiseizure medication refractoriness, and psychiatric comorbidities and with the lowest rate of family history of epilepsy. LO‐EEM was associated with the highest proportion of body‐MYO and generalized tonic–clonic seizures (GTCS), whereas IO‐EEM had the lowest observed rate of additional findings. A family history of EEM was significantly more frequent in IO‐EEM and LO‐EEM compared with EO‐EEM. In the subset of patients with body‐MYO (58/267), we observed a significantly higher rate of migraine and GTCS but no relevant differences in other electroclinical features and seizure outcome.
Significance
Based on AEO, we identified consistent EEM subtypes characterized by distinct electroclinical and familial features. Our observations shed new light on the spectrum of clinical features of this generalized epilepsy syndrome and may help clinicians toward a more accurate classification and prognostic profiling of EEM patients.
The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of ...Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.
•Forty-nine patients with progressive myoclonus epilepsy took perampanel in add-on.•Perampanel reduced myoclonus severity as assessed by minimal myoclonus scale.•Action myoclonus improved greatly as ...measured by the unified myoclonus rating scale.•Convulsive seizures were reduced by >50%.•Side effects occurred in 44.8% patients, the most common being irritability.
Perampanel (PER) is a novel anti-seizure medication useful in different types of epilepsy. We intended to assess the effectiveness of PER on cortical myoclonus and seizure frequency in patients with progressive myoclonus epilepsy (PME), using quantitative validated scales.
Forty-nine patients aged 36.6 ± 15.6 years with PME of various aetiology (18 EPM1, 12 EPM2, five with sialidosis, one with Kufs disease, one with EPM7, and 12 undetermined) were enrolled between January 2017 and June 2018. PER at the dose of 2–12 mg (5.3 ± 2.5) was added to existing therapy. Myoclonus severity was assessed using a minimal myoclonus scale (MMS) in all the patients before and after 4–6 months of steady PER dose, and by means of the Unified Myoclonus Rating Scale (UMRS) in 20 patients. Logistic regression analysis was used to identify the factors potentially predicting treatment efficacy.
Four patients dropped out in the first two months due to psychiatric side effects. In the remaining patients, PER reduced myoclonus severity as assessed using MMS (Wilcoxon test: p < 0.001) and UMRS (p < 0.001), with the ‘Action myoclonus’ section of the UMRS showing the greatest improvement. The patients with EPM1 or EPM1-like phenotype were more likely to improve with PER (p = 0.011). Convulsive seizures which have recurred at least monthly in 17 patients were reduced by >50%. Side effects occurred in 22/49 (44.8%) patients, the most common being irritability followed by drowsiness.
PER is effective in treating myoclonus and seizures in PME patients. The frequency of psychiatric side effects suggests the need for careful patient monitoring.
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