Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder: Experience of >100 patients

Summary

Objective

Pathogenic variants involving the CDKL5 gene result in a severe epileptic encephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its ...

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Inherent vulnerabilities in monoaminergic pathways predict the emergence of depressive impairments in an animal model of chronic epilepsy

Summary

The objective was to determine whether the depression comorbid with epilepsy could be predicted based on inherent premorbid patterns of monoaminergic transmission. In male Wistar rats, despair-like and anhedonia-like behaviors were examined using forced swimming and taste preference tests, respectively. Serotonergic raphe nucleus (RN)–prefrontal cortex (PFC) and dopaminergic ventral tegmental area (VTA)–nucleus accumbens (NAcc) pathways were interrogated by fast scan cyclic voltammetry (FSCV). The assays were performed before and 2 months after pilocarpine status epilepticus. In a ...

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Prediction of specific depressive symptom clusters in youth with epilepsy: The NDDI-E-Y versus Neuro-QOL SF

Summary

Objective

Proper assessment and early identification of depressive symptoms are essential to initiate treatment and minimize the risk for poor outcomes in youth with epilepsy (YWE). The current study examined the predictive utility of the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y) and the Neuro-QOL Depression Short Form (Neuro-QOL SF) in explaining variance in overall depressive symptoms and specific symptom clusters on the gold standard Children’s Depression Inventory-2 (CDI-2).

Methods

Cross-sectional study examining 99 YWE (female 68, mean age ...

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Prediction of specific depressive symptom clusters in youth with epilepsy: The NDDI-E-Y versus Neuro-QOL SF

Summary

Objective

Proper assessment and early identification of depressive symptoms are essential to initiate treatment and minimize the risk for poor outcomes in youth with epilepsy (YWE). The current study examined the predictive utility of the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y) and the Neuro-QOL Depression Short Form (Neuro-QOL SF) in explaining variance in overall depressive symptoms and specific symptom clusters on the gold standard Children’s Depression Inventory-2 (CDI-2).

Methods

Cross-sectional study examining 99 YWE (female 68, mean age ...

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The prevalence of anxiety and associated factors in persons with epilepsy

Summary

The objectives of this study were to estimate the prevalence of, and factors associated with, anxiety in epilepsy. We conducted a cross-sectional analysis using data from the Neurological Disease and Depression Study. The prevalence of anxiety and associated factors were assessed using descriptive statistics and logistic regression. Of the total sample (n = 250 patients), nearly 40.0% of participants had anxiety according to the Hospital Anxiety and Depression Scale. The most prevalent symptom of anxiety was “worrying ...

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Acute and long-term effects of brivaracetam and brivaracetam–diazepam combinations in an experimental model of status epilepticus

Summary

Objective

To evaluate acute and long-term effects of intravenous brivaracetam (BRV) and BRV + diazepam (DZP) combination treatment in a rat model of self-sustaining status epilepticus (SSSE).

Methods

Rats were treated with BRV (10 mg/kg) 10 min after initiation of perforant path stimulation (PPS) as early treatment; or BRV (10–300 mg/kg), DZP (1 mg/kg), or BRV (0.3–10 mg/kg) + DZP (1 mg/kg) 10 min after the end of PPS (established SSSE). Seizure activity was recorded electrographically for 24 h ...

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Acute and long-term effects of brivaracetam and brivaracetam–diazepam combinations in an experimental model of status epilepticus

Summary

Objective

To evaluate acute and long-term effects of intravenous brivaracetam (BRV) and BRV + diazepam (DZP) combination treatment in a rat model of self-sustaining status epilepticus (SSSE).

Methods

Rats were treated with BRV (10 mg/kg) 10 min after initiation of perforant path stimulation (PPS) as early treatment; or BRV (10–300 mg/kg), DZP (1 mg/kg), or BRV (0.3–10 mg/kg) + DZP (1 mg/kg) 10 min after the end of PPS (established SSSE). Seizure activity was recorded electrographically for 24 h ...

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An economic evaluation of a multicomponent self-management intervention for adults with epilepsy (ZMILE study)

Summary

Objective

The objective of this (trial-based) economic evaluation was, from a societal perspective, to compare the cost-effectiveness of a multicomponent self-management intervention (MCI) with care as usual (CAU) in adult patients with epilepsy over a 12-month period.

Methods

In a randomized-controlled trial, participants were randomized into intervention or CAU group. Adherence, self-efficacy (Epilepsy Self-Efficacy Scale [ESES]), quality-adjusted life years (QALYs), healthcare costs, production losses, and patient and family costs were assessed at baseline and during the 12-month study period. ...

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Overexpressing wild-type γ2 subunits rescued the seizure phenotype in Gabrg2+/Q390X Dravet syndrome mice

Summary

Objective

The mutant γ-aminobutyric acid type A (GABAA) receptor γ2(Q390X) subunit (Q351X in the mature peptide) has been associated with the epileptic encephalopathy, Dravet syndrome, and the epilepsy syndrome genetic epilepsy with febrile seizures plus (GEFS+). The mutation generates a premature stop codon that results in translation of a stable truncated and misfolded γ2 subunit that accumulates in neurons, forms intracellular aggregates, disrupts incorporation of γ2 subunits into GABAA receptors, and affects trafficking of partnering α and β ...

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Abnormal γ-aminobutyric acid neurotransmission in a Kcnq2 model of early onset epilepsy

Summary

Objective

Mutations of the KCNQ2 gene, which encodes the Kv7.2 subunit of voltage-gated M-type potassium channels, have been associated with epilepsy in the neonatal period. This developmental stage is unique in that the neurotransmitter gamma aminobutyric acid (GABA), which is inhibitory in adults, triggers excitatory action due to a reversed chloride gradient.

Methods

To examine whether KCNQ2-related neuronal hyperexcitability involves neonatally excitatory GABA, we examined 1-week-old knockin mice expressing the Kv7.2 variant p.Tyr284Cys (Y284C).

Results

Brain slice electrophysiology revealed elevated ...

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