Dataset Information

Evidence for long memory in focal seizure duration.

ABSTRACT:

Objective

A major source of disability for people with epilepsy involves uncertainty surrounding seizure timing and severity. Although patients often report that long seizure-free intervals are followed by more severe seizures, there is little experimental evidence supporting this observation. Optimal characterization of seizure severity is debated; however, seizure duration is associated with seizure type and can be quantified in electrographic recordings as a limited proxy of clinical seizure severity. Here, using chronic intracranial electroencephalography (cEEG), we investigate the relationship between interseizure interval (ISI) and duration of the subsequent seizure.

Methods

We performed a retrospective analysis of 14 subjects implanted with a responsive neurostimulation device (RNS System) that provides cEEG, including timestamps of electrographic seizures. We determined seizure durations for isolated seizures and for representative seizures from clusters determined through unsupervised methods. For each subject, the median ISI preceding long-duration seizures, defined as the top quintile of seizure durations, was compared with the median ISI preceding seizures with durations in the residual quintiles. In a group analysis, the mean seizure duration and the proportion of long-duration seizures were compared across ISI categories representing different lengths.

Results

For 5 out of 14 subjects (36%), the median ISI preceding long-duration seizures was significantly greater than the median ISI preceding shorter-duration seizures. In the group analysis, when ISI was categorized by length, the proportion of long-duration seizures within the high ISI category was significantly higher than that of the low ISI category (P < 0.001).

Significance

By leveraging cEEG and accounting for seizure clusters, we found that the likelihood of long-duration seizures positively correlates with ISI length, in a subset of individuals. These findings corroborate anecdotal clinical observations and support the existence of capacitor-like long memory processes governing the dynamics of focal seizures.

SUBMITTER: Fan JM

PROVIDER: S-EPMC7918332 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Evidence for long memory in focal seizure duration.

Fan Joline M JM Chiang Sharon S Rao Vikram R VR

Epilepsia open 20210107 1

<h4>Objective</h4>A major source of disability for people with epilepsy involves uncertainty surrounding seizure timing and severity. Although patients often report that long seizure-free intervals are followed by more severe seizures, there is little experimental evidence supporting this observation. Optimal characterization of seizure severity is debated; however, seizure duration is associated with seizure type and can be quantified in electrographic recordings as a limited proxy of clinical ...[more]

PMID: 33681657

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Project description:Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9-CAMK2A-EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9-CAMK2A-EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9-CAMK2A-EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability.

Dataset Information

Evidence for long memory in focal seizure duration.

Objective

Methods

Results

Significance

Publications

Evidence for long memory in focal seizure duration.

Similar Datasets

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