Dataset Information

MTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update.

ABSTRACT: Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression is sufficient to induce epilepsy in experimental models, while rescuing autophagy prevents epileptogenesis, improves behavioral alterations, and provides neuroprotection in seizure-induced neuronal damage. The implication of autophagy in epileptogenesis and maturation phenomena related to seizure activity is supported by evidence indicating that autophagy is involved in the molecular mechanisms which are implicated in epilepsy. In general, mTOR-dependent autophagy regulates the proliferation and migration of inter-/neuronal cortical progenitors, synapse development, vesicular release, synaptic plasticity, and importantly, synaptic clustering of GABAA receptors and subsequent excitatory/inhibitory balance in the brain. Similar to autophagy, the ubiquitin-proteasome system is regulated downstream of mTOR, and it is implicated in epileptogenesis. Thus, mTOR-dependent cell-clearing systems are now taking center stage in the field of epilepsy. In the present review, we discuss such evidence in a variety of seizure-related disorders and models. This is expected to provide a deeper insight into the molecular mechanisms underlying seizure activity.

SUBMITTER: Limanaqi F

PROVIDER: S-EPMC7084443 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update.

Limanaqi Fiona F Biagioni Francesca F Busceti Carla Letizia CL Fabrizi Cinzia C Frati Alessandro A Fornai Francesco F

International journal of molecular sciences 20200228 5

Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression is sufficient to induce epilepsy in experimental models, while rescuing autophagy prevents epileptogenesis, improves behavioral alterations, and provides neuroprotection in seizure ...[more]

PMID: 32121250

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Project description:ObjectiveEarly and accurate diagnosis of patients with psychogenic nonepileptic seizures (PNES) leads to appropriate treatment and improves long-term seizure prognosis. However, this is complicated by the need to record seizures to make a definitive diagnosis. Suspicion for PNES can be raised through knowledge that patients with PNES have increased somatic sensitivity and report more positive complaints on review-of-systems questionnaires (RoSQs) than patients with epileptic seizures. If the responses on the RoSQ can differentiate PNES from other seizure types, then these forms could be an early screening tool.MethodsOur dataset included all patients admitted from January 2006 to June 2016 for video-electroencephalography at UCLA. RoSQs prior to May 2015 were acquired through retrospective chart review (n=405), whereas RoSQs from subsequent patients were acquired prospectively (n=190). Controlling for sex and number of comorbidities, we used binomial regression to compare the total number of symptoms and the frequency of specific symptoms between five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of RoSQs to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and the number of medical comorbidities.ResultsOn average, patients with PNES or mixed PNES and ES reported more than twice as many symptoms than patients with isolated ES or PSLE (p<0.001). The prospective accuracy to differentiate PNES from ES was not significantly higher than naïve assumption that all patients had ES (76% vs 70%, p>0.1).DiscussionThis analysis of RoSQs confirms that patients with PNES with and without comorbid ES report more symptoms on a population level than patients with epilepsy or PSLE. While these differences help describe the population of patients with PNES, the consistency of RoSQ responses was neither accurate nor specific enough to be used solely as an early screening tool for PNES. Our results suggest that the RoSQ may help differentiate PNES from ES only when, based on other information, the pre-test probability of PNES is at least 50%.

Dataset Information

MTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update.

Publications

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update.

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