Objective: Familial mesial temporal lobe epilepsy (FMTLE) is an important focal epilepsy syndrome; its molecular genetic basis is unknown. Clinical descriptions of FMTLE vary between a mild syndrome with prominent déjà vu to a more severe phenotype with febrile seizures and hippocampal sclerosis. We aimed to refine the phenotype of FMTLE by analyzing a large cohort of patients and asked whether common risk variants for focal epilepsy and/or febrile seizures, measured by polygenic risk scores (PRS), are enriched in individuals with FMTLE.
View Article and Find Full Text PDFThe diagnosis of antineutrophil cytoplasmic autoantibody-associated vasculitis in first-episode strokes is particularly challenging, especially in patients lacking features of systemic vasculitis. We present the case of a 71-year-old woman with positive myeloperoxidase antineutrophil cytoplasmic antibodies and negative proteinase 3 autoantibodies. The patient presented with 1 week history of pyramidal weakness in both upper and lower limbs, hyperreflexia, and clonus.
View Article and Find Full Text PDFThere are a number of familial focal epilepsy syndromes, each with distinct clinical characteristics. Here, we review the epilepsy phenotypes and the genetic architecture of these syndromes. Using an illustrative clinical case, we describe the important steps in making a diagnosis and ordering appropriate genetic tests.
View Article and Find Full Text PDFBackground And Purpose: Although a target of 80% medication adherence is commonly cited, it is unclear whether greater adherence improves survival after stroke or transient ischemic attack (TIA). We investigated associations between medication adherence during the first year postdischarge, and mortality up to 3 years, to provide evidence-based targets for medication adherence.
Methods: Retrospective cohort study of 1-year survivors of first-ever stroke or TIA, aged ≥18 years, from the Australian Stroke Clinical Registry (July 2010–June 2014) linked with nationwide prescription refill and mortality data (until August 2017).
Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1.
View Article and Find Full Text PDFBackground and Purpose- Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU.
View Article and Find Full Text PDFPeople with epilepsy are at heightened risk of sudden death compared to the general population. The leading cause of epilepsy-related premature mortality is sudden unexpected death in epilepsy (SUDEP). Postmortem investigation of people with SUDEP, including histological and toxicological analysis, does not reveal a cause of death, and the mechanisms of SUDEP remain largely unresolved.
View Article and Find Full Text PDFObjective: The cause of mesial temporal lobe epilepsy (MTLE) is often unknown. We ascertained to what extent newly diagnosed nonlesional MTLE actually represents familial MTLE (FMTLE).
Methods: We identified all consecutive patients presenting to the Austin Health First Seizure Clinic with MTLE and normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis over a 10-year period.
Background And Purpose: Interhospital transfer is a critical component in the treatment of acute anterior circulation large vessel occlusive stroke transferred for mechanical thrombectomy. Real-world data for benchmarking and theoretical modeling are limited. We sought to characterize transfer workflow from primary stroke center (PSC) to comprehensive stroke center after the publication of positive thrombectomy trials.
View Article and Find Full Text PDFWe measured the mortality rate and the rate of Sudden Unexpected Death in Epilepsy (SUDEP) in Dravet Syndrome (DS). We studied a cohort of 100 consecutively recruited, unrelated patients with DS; 87 had SCN1A mutations. Living cases had a median follow-up of 17 years.
View Article and Find Full Text PDFFamilial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder characterized by adult onset, involuntary muscle jerks, cortical myoclonus and occasional seizures. FAME is genetically heterogeneous with more than 70 families reported worldwide and five potential disease loci. The efforts to identify potential causal variants have been unsuccessful in all but three families.
View Article and Find Full Text PDFObjective: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms.
Methods: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants.
Results: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms.
Objective: The leading cause of epilepsy-related premature mortality is sudden unexpected death in epilepsy (SUDEP). The cause of SUDEP remains unknown. To search for genetic risk factors in SUDEP cases, we performed an exome-based analysis of rare variants.
View Article and Find Full Text PDFFor some time, paediatric neurologists have recognised glucose transporter type 1 (GluT1) deficiency syndrome as a cause of intractable infantile seizures, microcephaly, developmental delay and hypoglycorrhachia in the presence of a normal plasma glucose. It is caused by mutations in the SLC2A1 gene, coding for GluT1, leading to a reduction in the available glucose transporter sites; it responds to the ketogenic diet. Recently, a wider spectrum of seizure syndromes have been associated with functional impairment of glucose transport caused by SLC2A1 mutations.
View Article and Find Full Text PDFObjective: To determine the contribution of sequence variations in PHOX2B to sudden unexpected death in epilepsy (SUDEP).
Methods: Patients who died of SUDEP were identified in 2 major Australian cohorts, the Epilepsy Genetics research program in Melbourne and postmortem cases at the Department of Forensic Medicine in Sydney. Coding exons of the PHOX2B gene were sequenced and a fluorescent sizing assay was used to measure the PHOX2B polyalanine repeat sequence.
We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5-associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual).
View Article and Find Full Text PDFThe majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized.
View Article and Find Full Text PDFGlucose transporter 1 (GLUT1) deficiency caused by mutations of SLC2A1 is an increasingly recognized cause of genetic generalized epilepsy. We previously reported that >10% (4 of 34) of a cohort with early onset absence epilepsy (EOAE) had GLUT1 deficiency. This study uses a new cohort of 55 patients with EOAE to confirm that finding.
View Article and Find Full Text PDFBackground: Familial adult myoclonic epilepsy (FAME) is an autosomal dominant syndrome characterized by a core triad of cortical tremor, multifocal myoclonus, and generalized tonic-clonic seizures.
Objectives: To expand the phenotypic spectrum of FAME, to highlight diagnostic pointers to this underrecognized disorder, and to refine the FAME2 genetic locus.
Design: Observational family study.
Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging.
View Article and Find Full Text PDFParoxysmal losses of consciousness and other episodic neurological symptoms have many causes. Distinguishing epileptic from non-epileptic disorders is fundamental to diagnosis, but even this basic dichotomy is often challenging and is certainly not new. In 1907, the British neurologist William Richard Gowers published his book The Border-land of Epilepsy in which he discussed paroxysmal conditions "in the border-land of epilepsy-near it, but not of it" and their clinical differentiation from epilepsy itself.
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