Childhood absence epilepsy and electroencephalographic focal abnormalities with or without clinical manifestations

SummaryPurposeWe studied the electroclinical features and evolution in patients with childhood absence epilepsy (CAE) associated with electroencephalographic findings similar to those of benign focal epilepsies (BFE) with or without clinical manifestations compatible with these focal idiopathic syndromes.MethodsBetween June 1994 and June 2002, we found 203 (3.6%) patients with typical electroclinical features of CAE among 8285 children with epilepsy. From this population of 203, we found 30 cases (14.7%) that also showed focal abnormalities of BFE on the EEG. Seven of these 30 cases also had clinical manifestations of BFE that preceded the onset of the absences.ResultsThere were 20 (66.5%) boys and 10 (33.5%) girls. Age at onset of absences ranged from 2 to 10.5 years, with a mean age of 5.5 years. Of 30, 7 had focal clinical seizures as well. Three of seven had seizures characteristic of Panayiotopoulos syndrome (PS), and the other four had seizures compatible with childhood occipital epilepsy (COE) of Gastaut. The focal seizures started between 3 and 7 years of age. In all patients seizures were under control within 2–24 months (mean: 11 months) after onset. The focal discharges disappeared in 26 patients at a mean age of 8 years (range 4–13 years), 1 year after the typical absences had disappeared. In four patients the focal paroxysms are still present.ConclusionThe association of two different idiopathic focal and generalized epilepsies in the same patient may be merely coincidental, but a close genetic relationship between both epileptic syndromes might be another hypothesis. Another explanation could be that our series of patients represent a subgroup of CAE

Infantile spams without hypsarrhythmia: A study of 16 cases

AbstractIn this study, we present the electroclinical features and evolution of patients with epileptic spasms (ES) in clusters without hypsarrhythmia and with or without focal or generalized paroxysmal discharges on the interictal EEG. We also discuss how to nosologically define these cases.MethodsBetween February 1, 1990, and December, 2009, sixteen patients met the electroclinical diagnostic criteria of ES in clusters without hypsarrhythmia.ResultsES were cryptogenic in thirteen patients and symptomatic in three. Age at onset of ES was between 4 months and 30 months, with a mean age of 9 months and a median age of 7 months. Seven patients had seizures before the onset of ES. Focal spikes were observed in seven patients, bilateral spikes and spikes and waves in five, multifocal spikes in two, and two patients had a normal EEG. The ictal EEG recording showed diffuse high-amplitude slow waves in ten patients, diffuse slow waves followed by voltage attenuation in four patients, and diffuse fast rhythms in two. ES were cured in five patients. Mean follow-up was 6 years. Neuropsychological development has been normal in the five latter patients. Eleven patients continue with seizures refractory to antiepileptic drugs after a mean follow-up of 10 years. Of these eleven patients, five have severe mental retardation, three have moderate mental retardation, and two have mild mental retardation. All of them show behavioral disturbances.ConclusionThe patients in this series may be considered to have a variant of West syndrome rather than an electroclinically distinct epileptic syndrome

Arthroscopic treatment for chronic lateral epicondylitis

AbstractObjectiveTo report the clinical and functional results from arthroscopic release of the short radial extensor of the carpus (SREC) in patients with chronic lateral epicondylitis that was refractory to conservative treatment.MethodsOver the period from January 2012 to November 2013, 15 patients underwent arthroscopic treatment. The surgical technique used was the one described by Romeo and Cohen, based on anatomical studies on cadavers. The inclusion criteria were that the patients needed to present lateral epicondylitis and that conservative treatment (analgesics, anti-inflammatory agents, corticoid infiltration or physiotherapy) had failed over a period of more than six months. The patients were evaluated based on the elbow functional score of the Mayo Clinic, Nirschl's staging system and a visual analog scale (VAS) for pain.ResultsA total of 15 patients (9 men and 6 women) were included. The mean Mayo elbow functional score after the operation was 95 (ranging from 90 to 100). The pain VAS improved from a mean of 9.2 before the operation to 0.64 after the operation. On Nirschl's scale, the patients presented an improvement from a mean of 6.5 before the operation to approximately one. There were significant differences from before to after the surgery for the three functional scores used (p<0.01). No correlations were observed using the Spearman test between the results and age, gender, length of time with symptoms before the operation or injury mechanism (p>0.05).ConclusionArthroscopic treatment for lateral epicondylitis was shown to be a safe and effective therapeutic option when appropriately indicated and performed, in refractory cases of chronic lateral epicondylitis. It also allowed excellent viewing of the joint space for diagnosing and treating associated pathological conditions, with a minimally invasive procedure

Migrating focal seizures and myoclonic status in ARV1-related encephalopathy

Objective: To report longitudinal clinical, EEG, and MRI findings in 2 sisters carrying compound heterozygous ARV1 mutations and exhibiting a peculiar form of developmental and epileptic encephalopathy (DEE). Neuropathologic features are also described in one of the sisters. Methods: Clinical course description, video-EEG polygraphic recordings, brain MRI, skin and muscle biopsies, whole-exome sequencing (WES), and brain neuropathology. Results: Since their first months of life, both girls exhibited severe axial hypotonia, visual inattention, dyskinetic movements, severe developmental delay, and slow background EEG activity. Intractable nonmotor seizures started in both at the eighth month of life, exhibiting the electroclinical characteristics of epilepsy of infancy with migrating focal seizures (EIMFS). In the second year of life, continuous epileptiform EEG activity of extremely high amplitude appeared in association with myoclonic status, leading to severely impaired alertness and responsiveness. Repeated brain MRI revealed progressive atrophic changes and severe hypomyelination. WES identified a compound heterozygous in the ARV1 gene [(p.Ser122Glnfs*7) and (p.Trp163*)] in one patient and was subsequently confirmed in the other. Both sisters died prematurely during respiratory infections. Postmortem neuropathologic examination of the brain, performed in one, revealed atrophic brain changes, mainly involving the cerebellum. Conclusions: This report confirms that biallelic ARV1 mutations cause a severe form of DEE and adds epilepsy with migrating focal seizures and myoclonic status to the spectrum of epilepsy phenotypes. Considering the potential role of human ARV1 in glycosylphosphatidylinositol (GPI) anchor biosynthesis, this severe syndrome can be assigned to the group of inherited GPI deficiency disorders, with which it shares remarkably similar clinical and neuroimaging features. ARV1 should be considered in the genetic screening of individuals with EIMFS

CDKL5 deficiency disorder: progressive brain atrophy may be part of the syndrome

The clinical phenotype of Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) has been delineated but neuroimaging features have not been systematically analyzed. We studied brain magnetic resonance imaging (MRI) scans in a cohort of CDD patients and reviewed age at seizure onset, seizure semiology, head circumference. Thirty-five brain MRI from 22 unrelated patients were included. The median age at study entry was 13.4 years. In 14/22 patients (85.7%), MRI in the first year of life was unremarkable in all but two. In 11/22, we performed MRI after 24 months of age (range 2.5-23 years). In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain (-17.7%, P-value = 0.014), including both white matter (-25.7%, P-value = 0.005) and cortical gray matter (-9.1%, P-value = 0.098), with a reduction of surface area (-18.0%, P-value = 0.032), mainly involving the temporal regions, correlated with the head circumference (&amp; rho; = 0.79, P-value = 0.109). Both the qualitative structural assessment and the quantitative analysis detected brain volume reduction involving the gray and white matter. These neuroimaging findings may be related to either progressive changes due to CDD pathogenesis, or to the extreme severity of epilepsy, or both. Larger prospective studies are needed to clarify the bases for the structural changes we observed

Bloqueio atrioventricular total congênito

Objetivos: Descrever as características de pacientes menores de 18 anos com bloqueio atrioventricular total congênito submetidos a implante ou troca de marcapasso definitivo. Métodos: Foram analisados retrospectivamente 34 pacientes que foram submetidos a implante ou troca de marcapasso entre janeiro de 2011 e maio de 2017 em um único centro. Os pacientes foram divididos em 2 grupos (grupo I: implante e grupo II: troca) e avaliados de acordo com o sexo, idade, cardiopatia congênita, indicação do implante, técnica utilizada, complicações e mortalidade. Resultados: 47,1% eram do sexo feminino. A mediana para idade no momento do implante foi de 2 anos e 6 meses e para peso foi de 17,5Kg. Cardiopatia congênita teve prevalência de 52,9% nos pacientes. As indicações para implante de marcapasso definitivo foram: frequência cardíaca menor que 70 bpm com cardiopatia ou disfunção (44,1%), frequência cardíaca menor que 55 bpm sem cardiopatia (26,5%), sinais e sintomas de baixo débito cardíaco (20,6%) e disfunção ventricular (8,8%). A técnica epicárdica foi realizada em 73,5% e a endocárdica em 26,5% dos pacientes. Foi implantado marcapasso bicameral em 53% e monocameral em 47% deles. Complicações foram observadas em 23,5% e a mortalidade foi de 8,8%. Conclusões: A criteriosa avaliação desses pacientes permite uma adequada escolha do sistema e da técnica de implante. Pouco mais da metade dos pacientes tinham cardiopatia congênita, a técnica epicárdica foi a mais realizada, a maioria recebeu marcapasso bicameral, e as complicações e a mortalidade foram semelhantes as encontradas na da literatura.

A registry for Dravet syndrome: The Italian experience

Objectives: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. / Methods: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. / Results: At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0–9) while at last follow-up was 11 years (IQR 5–18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). / Significance: The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes

Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues