Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy

Summary

Objective

Variants in neuronal voltage-gated sodium channel α-subunits genes SCN1A, SCN2A, and SCN8A are common in early onset epileptic encephalopathies and other autosomal dominant childhood epilepsy syndromes. However, in clinical practice, missense variants are often classified as variants of uncertain significance when missense variants are identified but heritability cannot be determined. Genetic testing reports often include results of computational tests to estimate pathogenicity and the frequency of that variant in population-based databases. The objective of this work was ...

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BGG492 as an adjunctive treatment in patients with partial-onset seizures: A 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study with an open-label extension

Summary

Objectives

To evaluate dose–response relationship of BGG492 as add-on therapy to 1–3 antiepileptic drugs in patients with partial-onset seizures and to investigate safety and tolerability of BGG492.

Methods

This was a 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study (core study) with a 30-week, flexible-dose, open-label extension. In the core study, patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1, and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d. On ...

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BGG492 as an adjunctive treatment in patients with partial-onset seizures: A 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study with an open-label extension

Summary

Objectives

To evaluate dose–response relationship of BGG492 as add-on therapy to 1–3 antiepileptic drugs in patients with partial-onset seizures and to investigate safety and tolerability of BGG492.

Methods

This was a 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study (core study) with a 30-week, flexible-dose, open-label extension. In the core study, patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1, and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d. On ...

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Child- and parent-reported quality of life trajectories in children with epilepsy: A prospective cohort study

Summary

Objective

To describe the developmental trajectories of quality of life (QoL) in a large cohort of children with epilepsy, and to assess the relative contribution of clinical, psychosocial, and sociodemographic variables on QoL trajectories.

Methods

Five assessments during a 28-month prospective cohort study were used to model trajectories of QoL. Participants were recruited with their parents from six Canadian tertiary centers. A convenience sample of 506 children aged 8–14 years with epilepsy and without intellectual disability or autism spectrum ...

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Child- and parent-reported quality of life trajectories in children with epilepsy: A prospective cohort study

Summary

Objective

To describe the developmental trajectories of quality of life (QoL) in a large cohort of children with epilepsy, and to assess the relative contribution of clinical, psychosocial, and sociodemographic variables on QoL trajectories.

Methods

Five assessments during a 28-month prospective cohort study were used to model trajectories of QoL. Participants were recruited with their parents from six Canadian tertiary centers. A convenience sample of 506 children aged 8–14 years with epilepsy and without intellectual disability or autism spectrum ...

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Enriched environment attenuates behavioral seizures and depression in chronic temporal lobe epilepsy

Summary

Objective

Temporal lobe epilepsy (TLE) is commonly associated with depression, anxiety, and cognitive impairment. Despite significant progress in our understanding of the pathophysiology of TLE, it remains the most common form of refractory epilepsy. Enriched environment (EE) has a beneficial effect in many neuropsychiatric disorders. However, the effect of EE on cognitive changes in chronic TLE has not been evaluated. Accordingly, the present study evaluated the effects of EE on chronic epilepsy–induced alterations in cognitive functions, electrophysiology, and ...

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Enriched environment attenuates behavioral seizures and depression in chronic temporal lobe epilepsy

Summary

Objective

Temporal lobe epilepsy (TLE) is commonly associated with depression, anxiety, and cognitive impairment. Despite significant progress in our understanding of the pathophysiology of TLE, it remains the most common form of refractory epilepsy. Enriched environment (EE) has a beneficial effect in many neuropsychiatric disorders. However, the effect of EE on cognitive changes in chronic TLE has not been evaluated. Accordingly, the present study evaluated the effects of EE on chronic epilepsy–induced alterations in cognitive functions, electrophysiology, and ...

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Weather as a risk factor for epileptic seizures: A case-crossover study

Summary

Objective

Most epileptic seizures occur unexpectedly and independently of known risk factors. We aimed to evaluate the clinical significance of patients’ perception that weather is a risk factor for epileptic seizures.

Methods

Using a hospital-based, bidirectional case-crossover study, 604 adult patients admitted to a large university hospital in Central Germany for an unprovoked epileptic seizure between 2003 and 2010 were recruited. The effect of atmospheric pressure, relative air humidity, and ambient temperature on the onset of epileptic seizures under ...

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Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany

Summary

Objective

To evaluate factors predicting efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice.

Methods

A multicenter, retrospective cohort study recruiting all patients who started BRV between February and November 2016 with observation time between 3 and 12 months.

Results

Of a total of 262 patients (mean age 40, range 5–81 years, 129 male) treated with BRV, 227 (87%) were diagnosed to have focal, 19 (7%) idiopathic generalized and 8 (3%) symptomatic generalized epilepsy, whereas 8 (3%) were ...

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Reduced steroidogenesis in patients with PCDH19-female limited epilepsy

Summary

Patients affected by protocadherin 19 (PCDH19)–female limited epilepsy (PCDH19-FE) present a remarkable reduction in allopregnanolone blood levels. However, no information is available on other neuroactive steroids and the steroidogenic response to hormonal stimulation. For this reason, we evaluated allopregnanolone, pregnanolone, and pregnenolone sulfate by liquid chromatographic procedures coupled with electrospray tandem mass spectrometry in 12 unrelated patients and 15 age-matched controls. We also tested cortisol, estradiol, progesterone, and 17OH-progesterone using standard immunoassays. Apart from estradiol and progesterone, ...

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