Association of GABAA Receptor Gene with Epilepsy Syndromes

GABA has always been an inviting target in the etiology and treatment of epilepsy. The GABRA1, GABRG2, and GABRD genes provide instructions for making α1, ?2, and δ subunits of GABAA receptor protein respectively. GABAA is considered as one of the most important proteins and has found to play an important role in many neurological disorders. We explored the association of GABAA receptor gene mutation/SNPs in JME and LGS patients in Indian population. A total of 100 epilepsy syndrome patients (50 JME and 50 LGS) and 100 healthy control subjects were recruited and analyzed by AS-PCR and RFLP-PCR techniques. In our study, GABRA1 965 C?>?A mutation and 15 A?>?G polymorphism gene may play an important role in modulating the drug efficacy in LGS patients. The GABRA1 15 A?>?G polymorphism may also play an important role in the susceptibility of LGS and the inheritance of GG genotype of this polymorphism may provide an increased risk of development of LGS. The GABRG2 588 C?>?T polymorphism may decrease the duration of seizures in JME patients. The GABRD 659 G?>?A polymorphism may play an important role in the susceptibility of JME and LGS and this polymorphism may also increase the duration of postictal period in JME patients but may decrease the duration of seizure in LGS patients.     

Anleitung („instruction manual“) zur Anwendung der operationalen Klassifikation von Anfallsformen der ILAE 2017

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. The classification is illustrated by tables, a glossary of relevant terms, a table mapping old to new terms, recommended abbreviations and examples. Basic and extended versions of the classification are available depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categorization of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can be further optionally characterized with respect to whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it classified as a focal impaired awareness seizure. Focal seizures can be further optionally characterized by the first motor signs and symptoms as atonic, automatisms, clonic, epileptic spasms, hyperkinetic, myoclonic or tonic activity. Nonmotor onset seizures can be manifested as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which can then further progress to other signs and symptoms. Focal seizures can become bilateral tonic–clonic seizures. Generalized seizures include an early involvement of bilateral networks from the onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic–atonic, myoclonic–tonic–clonic, tonic or tonic–clonic manifestatíons. Nonmotor (absence) seizures are typical or atypical or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown origin may have features that can still be classified as motor, nonmotor, tonic–clonic, epileptic spasms or behavior arrest. This users’ manual for the ILAE 2017 seizure classification can assist the acceptance of the new system.     

Frontal subcutaneous lipoma associated with large interhemispheric lipoma and corpus callosum agenesis

Intracranial lipomas are extremely rare fat-containing lesions that comprise 0.1%-0.5% of all primary brain tumors. They are congenital lesions that arise due to persistence and maldifferentiation of the meninx primitive (subarachnoid space precursor). We report a case of a 30-year-old woman who presented with seizures due to an intracranial lipoma and no neurological deficits. CT (computerized tomography) imaging findings demonstrated a large interhemispheric partially calcified lipoma that communicated with a large scalp lipoma and was associated with agenesis of the corpus callosum. Compared to the prior CT imaging, the lipoma increased in size from 3.4 cm to 4.1 cm transversely. A recent CT angiogram done due to suspicion of an aneurysm showed the lipoma now measuring 6 cm by 4.7 cm. Most cases of intracranial lipoma have been reported in the pediatric age group. Here, we report a rare case of interhemispheric intracranial lipoma in the adult age group. This case also demonstrates the importance of imaging modalities for detecting intracranial lipoma without performing invasive brain biopsy.     

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open-label extension study

Objective

This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox–Gastaut syndrome (LGS).

Methods

Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months.

Results

As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2–4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was −28.6% over the entire OLE (n = 241) and −50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was −45.9% (n = 192, p = .0038). Generalized tonic–clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%–44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%–41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed.

Significance

Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.