Andrew Bleasel

Semiological seizure classification

Summary: We propose an epileptic seizure classification based exclusively on ictal semiology. In this semiological seizure classification (SSC), seizures are classified as follows:

Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis.

To describe a distinctive seizure semiology that closely associates with voltage‐gated potassium channel (VGKC)‐complex/Lgi1 antibodies and commonly precedes the onset of limbic encephalitis (LE).

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1

Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.

Incidence and Mechanisms of Cardiorespiratory Arrests in Epilepsy Monitoring Units (MORTEMUS): A Retrospective Study.

BACKGROUND Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. FUNDING Commission of European Affairs of the International League Against Epilepsy.

Sodium-channel defects in benign familial neonatal-infantile seizures

Ion-channel gene defects are associated with a range of paroxysmal disorders, including several monogenic epilepsy syndromes. Two autosomal dominant disorders present in the first year of life: benign familial neonatal seizures, which is associated with potassium-channel gene defects; and benign familial infantile seizures, for which no genes have been identified. Here, we describe a clinically intermediate variant, benign familial neonatal-infantile seizures, with mutations in the sodium-channel subunit gene SCN2A. This clinico-molecular correlation defines a new benign familial epilepsy syndrome beginning in early infancy, an age at which seizure disorders frequently have a sombre prognosis.

Validation of a New Quality of Life Measure for Children with Epilepsy

Summary: Purpose: There is no adequate measure of health‐related quality of life (HRQOL) specifically for children with epilepsy. The aim of this study was to develop an epilepsy‐specific HRQOL questionnaire for children, covering five domains: physical function, emotional well‐being, cognitive function, social function, and behavior. Second, we aimed to demonstrate the instruments reliability and validity, and its sensitivity to differences in epilepsy severity.

Memory function in childhood epilepsy syndromes

Objective:  Children with epilepsy are at risk of specific cognitive deficits. We aimed to compare and characterize the memory function of children with childhood absence epilepsy (CAE), frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE).

The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability.

Summary:  Purpose: To determine whether refractory epilepsy affects the health‐related quality of life (HRQOL) of children with or without intellectual disability (ID), and if the presence of ID independently compromises HRQOL in children with refractory epilepsy.

The Neuropsychological and Language Profile of Children with Benign Rolandic Epilepsy

Summary:  Purpose: Benign rolandic epilepsy (BRE) has an excellent prognosis for seizures, but recent research has raised concerns using cognition as an outcome measure. Methodologic problems related to recruitment bias and assessment processes are evident in previous studies. With well‐defined criteria for inclusion and comprehensive assessment, the aim of this study was to define the cognitive profile of children with BRE and to assess the effect of interictal EEG activity.

Intelligence in childhood epilepsy syndromes

UNLABELLED Intellectual deficits play a significant role in the psychosocial comorbidity of children with epilepsy. Early educational intervention is critical. OBJECTIVE This study aims to determine the intellectual ability of children with common childhood epilepsy syndromes-generalised idiopathic epilepsy (GIE), generalised symptomatic epilepsy (GSE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), central epilepsy (CE) and non-localised partial epilepsy (PE). METHODS A prospective consecutive series of 169 children were recruited. Epilepsy syndrome was identified by clinical data, seizure semiology, interictal and ictal EEG in each child, using International League Against Epilepsy criteria. Each child had neuropsychology assessment using age-normed and validated instruments. After adjusting for important epilepsy variables, 95% confidence intervals were generated for mean full-scale intelligence quotient (FSIQ) using ANCOVA. RESULTS Significant differences between epilepsy syndrome groups were found for age of onset (P<0.001), duration of active epilepsy (P=0.027), seizure frequency (P=0.037) and polytherapy (P=0.024). Analysing FSIQ, children with GIE, CE and TLE performed best, and did not differ statistically. Children with GSE had a statistically lower FSIQ than other syndrome groups except PE. FLE functioned significantly better than GSE, but did not differ statistically from other groups. CONCLUSIONS In childhood epilepsy, delineation of the syndrome has important implications when considering intellectual potential. This information is invaluable in planning educational interventions and supporting the family.