Peripheral blood mononuclear cell activation sustains seizure activity

Abstract

Objective

The influx of immune cells and serum proteins from the periphery into the brain due to a dysfunctional blood-brain barrier (BBB) has been proposed to contribute to the pathogenesis of seizures in various forms of epilepsy and encephalitis. We evaluated the pathophysiological impact of activated peripheral blood mononuclear cells (PBMCs) and serum albumin on neuronal excitability in an in vitro brain preparation.

Methods

A condition of mild endothelial activation induced by arterial perfusion of lipopolysaccharide (LPS) was induced in the whole brain ...

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In vivo hippocampal cornu ammonis 1–3 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes

Abstract

Objective

Previous positron emission tomography (PET) studies using [11C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes.

Methods

We obtained magnetic resonance imaging (MRI) and [11C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. ...

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The SANTÉ study at 10 years of follow‐up: Effectiveness, safety, and sudden unexpected death in epilepsy

Summary

Objective

We evaluated the efficacy and safety of deep brain anterior thalamus stimulation after 7 and 10 years, and report the incidence of sudden unexpected death in epilepsy (SUDEP) and overall mortality in adults in the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTÉ) study.

Methods

After the 3-month blinded and 9-month unblinded phases, subjects continued to be assessed during long-term follow-up (LTFU) and later a continued therapy access phase (CAP), to further characterize adverse events and the incidence of SUDEP. ...

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The long‐term efficacy of cannabidiol in the treatment of refractory epilepsy

Abstract

Objective

Cannabidiol (CBD) has been shown to reduce seizures among patients with refractory epilepsies of various etiologies in recent clinical trials and an expanded access program (EAP). Most studies report efficacy over short time periods (<1 year), with little published on longer term efficacy. Here, we investigate the efficacy of CBD for a treatment period of up to 60 months (median = 45.5 months).

Methods

We conducted a retrospective review of patient-reported seizure logs and medical records for 54 subjects with refractory epilepsy who enrolled in ...

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Epilepsy, antiepileptic drugs, and the risk of major cardiovascular events

Summary

Objective

This study was undertaken to determine whether epilepsy and antiepileptic drugs (including enzyme-inducing and non-enzyme-inducing drugs) are associated with major cardiovascular events using population-level, routinely collected data.

Methods

Using anonymized, routinely collected, health care data in Wales, UK, we performed a retrospective matched cohort study (2003–2017) of adults with epilepsy prescribed an antiepileptic drug. Controls were matched with replacement on age, gender, deprivation quintile, and year of entry into the study. Participants were followed to the end of the study for the ...

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CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity

Abstract

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were ...

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Systemic administration of ivabradine, a hyperpolarization‐activated cyclic nucleotide‐gated channel inhibitor, blocks spontaneous absence seizures

Abstract

Objective

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to be involved in the generation of absence seizures (ASs), and there is evidence that cortical and thalamic HCN channel dysfunctions may have a proabsence role. Many HCN channel blockers are available, but their role in ASs has been investigated only by localized brain injection or in in vitro model systems due to their limited brain availability. Here, we investigated the effect on ASs of orally administered ivabradine (an HCN channel blocker approved ...

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Patient‐detectable responsive neurostimulation as a seizure warning system

Abstract

Many people with epilepsy are not aware of their seizures or do not have reliable auras. The responsive neurostimulation system (RNS) delivers stimulation triggered by intracranial epileptiform activity. If an epileptiform pattern continues, the RNS repeats stimulation up to five times per event. The RNS can cause acute stimulation-related symptoms that can be avoided by reducing stimulation. Because each of the five therapies can be programmed independently, it may be possible to program the latter therapies to induce a seizure ...

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Missed, mistaken, stalled: Identifying components of delay to diagnosis in epilepsy

Abstract

A substantial proportion of individuals with newly diagnosed epilepsy report prior seizures, suggesting a missed opportunity for early epilepsy care and management. Consideration of the causes and outcomes of diagnostic delay is needed to address this issue. We aimed to review the literature pertaining to delay to diagnosis of epilepsy, describing the components, characteristics, and risk factors for delay. We undertook a systematic search of the literature for full-length original research papers with a focus on diagnostic delay or seizures ...

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Disparate treatment outcomes according to presence of pathogenic mutations in West syndrome

Abstract

Objective

It has been known that West syndrome (WS) patients with an unknown etiology have better clinical outcomes than patients with an identified etiology of any kind. However, after the exponential discovery of genes with mutations responsible for developmental and epileptic encephalopathy (DEE), a significant proportion of patients with a previously unknown etiology have been reclassified as having a genetic etiology, requiring reinvestigation of this concept. Therefore, this study investigated clinical outcomes of WS patients with genetic and unknown etiologies.

Methods

Patients diagnosed ...

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