Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

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Abstract

Most cases with new onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic workup. The aim of this study was to analyze the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic, and outcome parameters were characterized. We performed post hoc screening for known or potentially novel ...

Abstract

Objective

Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments which might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional MRI (fMRI).

Methods

Sixty-five patients with JME (median age 27 years, IQR 23–34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to ...

Abstract

One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non-invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre-surgical planning, increasing ...

Abstract

Objective

A pathological excitatory action of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) has been observed in epilepsy. Blocking the Cl⁻ importer NKCC1 with bumetanide is expected to reduce the neuronal intracellular Cl⁻ concentration ([Cl⁻]_i) and thereby attenuate the excitatory GABA response. Accordingly, several clinical trials of bumetanide for epilepsy were conducted. Although NKCC1 is expressed in both neurons and glial cells, an involvement of glial NKCC1 in seizures has not yet been reported. Astrocytes maintain high [Cl⁻]_i with NKCC1, and ...

Abstract

Objective

In the absence of safety data in humans, the use of cannabidiol (CBD) is not recommended during pregnancy. Yet >50% of pregnancies in women with epilepsy are unintended, making fetal exposure to CBD possible. As a small-molecule, highly lipid-soluble drug, CBD is likely to distribute into the placenta and cross it. To estimate the placental distribution profile of CBD and its potential short-term placental effects, we conducted an ex vivo perfusion study in human placentas.

Methods

Placentas were obtained from healthy women ...

Abstract

Objective

Cognitive impairment often impacts quality of life in epilepsy even if seizures are controlled. Word-finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word-finding difficulty in patients, and if so, through which cognitive mechanism(s).

Methods

Twenty-three patients undergoing intracranial monitoring for drug-resistant epilepsy participated in multiple tasks involving word-production (auditory naming, short-term verbal free recall, repetition) to probe word-finding difficulty across different cognitive domains. We ...

Abstract

Missense variants of HCN ion channels cause variable phenotypes, ranging from mild generalized epilepsy to developmental and epileptic encephalopathy (DEE). While variants of HCN1 are an established cause of DEE, those of HCN2 have been reported in generalized epilepsies. Here, we describe the first case of DEE caused by the novel de novo heterozygous missense variant c.1379G>A (p.G460D) of HCN2. Functional characterization in transfected HEK293 cells and neonatal rat cortical neurons revealed that HCN2 p.G460D currents were strongly reduced compared ...

Abstract

Many patients suffering from epilepsy undergo exome or genome sequencing as part of a diagnostic work-up, however, many remain genetically unsolved. There are various factors that account for negative results in exome/genome sequencing for epilepsy patients; 1) the underlying cause is not genetic, 2) there is a complex polygenic explanation, 3) the illness is monogenic but the causative gene remains to be linked to a human disorder, 4) family segregation with reduced penetrance, 5) somatic mosaicism or the complexity of ...

Abstract

Objective

GABA_A receptor subunit gene mutations are major causes of various epilepsy syndromes, including severe kinds such as Dravet syndrome. Although the GABA_A receptor is a major target for antiseizure medications, treating GABA_A receptor mutations with the receptor channel modulators is ineffective. Here we determined the effect of a novel treatment with 4-phenylbutyrate (PBA) in the Gabrg2
^+/Q390X
knockin mice associated with Dravet syndrome.

Methods

We used biochemistry in conjunction with differential tagging of the wildtype and the mutant alleles, live brain ...