Latest Findings

Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic encephalopathy

May 4, 2017

A cohort of 31 patients with severe infantile epileptic encephalopathy with seizure onset prior to 24 month was investigated in this paper. Next-generation sequencing was used for 430 epilepsy-associated genes to identify pathogenic variants in this cohort. One patient reported an SCN8A mutation (p.Arg1617Gln) with moderate intellectual disability and developmental regression.

Read more

Phenytoin as a last‐resort treatment in SCN8A encephalopathy

May 16, 2017

A case report of a 5-year old boy with an SCN8A mutation (p.Val233Ile) is presented here. Initial treatment of the boy consisted of valproic acid and phenobarbital which granted seizure freedom for 1 year. After this status epilepticus events occurred once every 2-3 months so phenobarbital was switched out and other drugs were used as part of the child's drug therapy. Ketogenic diet, levetiracetam, zonisamide, and topiramate therapy all led to rapid deterioration. Phenytoin was found to be a reasonable rescue medication, but as a maintenance drug was found to cause severe side effects.

Read more

Common terms for rare epilepsies: Synonyms, associated terms, and links to structured vocabularies.

January 29, 2018

Due to missing codes in the International Classification of Diseases (ICD) system identification of rare epilepsy syndromes can be difficult. This group surveyed parent advocates, providers, and caregivers and found that emerging rare epilepsies, like SCN8A, were underrepresented. This illustrates the need for medical vocabularies to fill the gaps in representation of these rare epilepsies.

Read more

Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence

March 18, 2018

A systematic literature review was conducted in October 2017 looking at evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. This included 6 randomized controlled trials (RCT) and 30 observational studies. Data suggests that cannabinoids may be an effective adjuvant treatment for reducing seizure frequency.

Read more

Transition from oxcarbazepine to eslicarbazepine acetate: A single center study

December 2, 2016

Patients 18 years of age or older were enrolled in this study to report the transitioning of patients with focal epilepsy from oxcarbazepine (OXC) to eslicarbazepine acetate (ESL). It was shown that patients who suffered from OXC-related adverse events had an improvement in tolerability after switching to ESL, and maintained seizure control.

Read more

Vitamin D supplementation for bone health in adults with epilepsy: A systematic review

February 4, 2018

This paper is a review of nine published literature on the efficacy of vitamin D intervention on bone health in adults with epilepsy. While there did appear to be positive changes in bone turnover markers, the varying methodologies used in each study made the impact of vitamin D on bone mineralization inconclusive.

Read more

Transient upregulation of Nav1.6 expression in the genu of corpus callosum following middle cerebral artery occlusion in the rats

April 20, 2017

The expression and distribution of Nav1.6 in rats in a stroke-like model was examined in this paper. The expression of Nav1.6 mRNA levels was decreased in these rats during the acute phase after reperfusion. Interestingly, the number of Nav1.6 positive cells was dramatically increased at 6 hours, and then decreased at 12 and 24 hours.

Read more

Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing

February 1, 2018

Using next generation sequencing, 74 patients with early-onset epilepsy were assessed with a panel that included 172 genes. The panel identified 28 patients with genetic abnormalities, one of them being an SCN8A mutation (p.Cys261Phe).

Read more

A Novel Inherited Mutation of SCN8A in a Korean Family with Benign Familial Infantile Epilepsy Using Diagnostic Exome Sequencing

November-December 2017

Diagnostic exome sequencing identified a novel inherited mutation (p.Gly1476Asp) in the SCN8A gene. The paper reports the case of an infant and father with this mutation who had early onset benign familial infantile epilepsy but no cognitive impairment.

Read more

Chemical–genetic attenuation of focal neocortical seizures

May 27, 2014

One of the commonly known pharmacoresistant epilepsy types is focal epilepsy, and many patients have no effective treatment options. In this paper, a chemical-genetic approach was taken to achieve localized suppression of neuronal excitability using viral expression in rats.

Read more

Loss-of-function variants of SCN8A in intellectual disability without seizure

August 2017

Two SCN8A missense mutations (p.Gly964Arg and p.Glu1218Lys) were examined in this paper that present with intellectual disability and developmental delay but no seizures. Both these mutations completely prevented the generation of sodium currents within transfected cell lines. These observations extend the established phenotypic spectrum of SCN8A.

Read more

De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy

October 2nd, 2017

Exome sequence data from 54 epilepsy patients and their unaffected parents to help identify the molecular diagnoses that were not initially provided. In the 54 trios, two de novo missense variants in SCN8A in the alternative exon 5A. This helps expand the range of SCN8A variants in epileptic encephalopathy.

Read more

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies

November 2nd, 2017

The cause of developmental and epileptic encephalopathies is unknown in a majority of cases. The authors performed whole-genome sequencing in 197 individuals and performed meta-analysis to document de novo mutations in certain candidate genes.

Read more

Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection

February 9th, 2017

This paper summarizes current literature on the cannabinoid effects in animal models of seizures.

Read more

Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels

October 30th, 2017

It has been shown that cannabidiol (CBD) can alleviate certain epilepsies, however its pharmacological profile is unknown. The authors tested whether the anticonvulsant effects of CBD would be prevented by cannabinoid and vanilloid receptor blockers to help determine its pharmacological profile.

Read more

Early-onset epileptic encephalopathy with de novo SCN8A mutation

October 28th, 2017

In this case study, a de novo mutation was reported in an EOEE patient who died from SUDEP. The data found help strengthen the association between SCN8A and EOEE and urge the screening for this mutation for early prevention of SUDEP.

Read more

Impaired bone and muscle development in young people treated with antiepileptic drugs

September 7th, 2017

A case-controlled study of patients ranging from 5-18 years old was completed to investigate the effects of antiepileptic drugs on bone development in young people. Researchers found that that those taking antiepileptic drugs had an increased prevalence of fractures, with the distal radius being the most common fracture site in this study.

Read more

The impact of genetic and experimental studies on classification and therapy of the epilepsies

August 16th, 2017

This review article discusses the advances made in the realm of genetic epilepsies and how these advances helped to demonstrate that gene-related mechanisms do in fact play a role in epileptogenesis.

Read more

Aberrant sodium channel currents and hyperexcitability of medial entorhinal cortex neurons in a mouse model of SCN8A encephalopathy

July 4th, 2017

Effects of the N1768D mutation on the neurons within the medial entorhinal cortex (mEC) were studied in this paper. mEC neurons are known to provide excitatory input to the dentate gyrus and hippocampus and are known to elevate the circuit excitability in animal models with temporal lobe epilepsy. It was found that unlike hippocampal or neocortical neurons, the mEC neurons are hyperexcitable and this increase in excitability precedes the onset of seizures by more than one month.

Read more

Non-ketogenic combination of nutritional strategies provides robust protection against seizures

July 1st, 2017

The ketogenic diet has shown to be successful in reducing seizures in pharmaco-resistant epilepsy patients, however it is highly unpalatable and difficult to follow. A new diet which combines medium-chain fatty acids, polyunsaturated fatty acid, low glycemic index carbohydrates, and a high BCAA/AAA ratio has shown to reduce excitatory drive and produce results similar to the ketogenic diet.

Read more

Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy

July 1st, 2017

While it is unknown whether SCN8A mutations can lead to skeletal complications, there have been reports of children with SCN8A mutations who also suffer from skeletal fractures. Researchers analyzed skeletal phenotypes of 2-week-old SCN8A-null mice and revealed there was reduced bone mass as compared to control littermates.

Read more

CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience

April 27th, 2017

A retrospective study was conducted in five Israeli pediatric clinics examining the effect of cannabidiol (CBD) on children with intractable epilepsy. The results showed that CBD had a positive effect on seizure load and also was associated with improvements in behavior, language, communication, motor skills, and sleep. Some adverse events were also reported which included drowsiness, fatigue, gastrointestinal disturbances and irritability. Further clinical trials using CBD are warranted to validate these findings.

Read more

Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

April 7th, 2017

Carbamazapine and oxcarbazepine are some of the common choices for the treatment of focal epilepsy. One of the common side-effects from using these drugs is hyponatremia (low sodium levels in the blood). This study collected sodium blood levels of adults taking these drugs and looked at the prevalence for hyponatremia within this cohort.

Read more

Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment

February 15th, 2017

This article outlines recent findings in a variety of genetic mutations related to epilepsy, including SCN8A. It summarizes how precision medicine and gene discovery are facilitating rapid progress in the classification of epilepsy, as well as development of medications targeted toward patients with these specific genetic mutations.

Read more

Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy

February 13th, 2017

Recent experimentation through mouse models suggests that a N1768D mutation in SCN8A results in hyperexcitability and an elevated persistent sodium current in hippocampal neurons. This data suggests that SCN8A plays a role in neural excitability, which could explain the mechanism through which early infantile epileptic encephalopathy (EIEE) causes severe seizures and cognitive impairment.

Read more

Cardiac Arrhythmia in a Mouse Model of Sodium Channel SCN8A Epileptic Encephalopathy

October 23rd, 2016

De novo mutations in the SCN8A gene are at an increased risk for sudden unexpected death in epilepsy (SUDEP). In this study, the cardiac phenotype of a mouse model expressing the p.Asn1768Asp mutation in Scn8a was investigated for alterations in cardiac excitability. The authors observed prolongation of the early stages of action potential repolarization in mutated myocytes.

Read more

Detection of Fetal Seizures Guides Approach to Diagnosis and Treatment

October 10th, 2016

This paper describes the first reported case of a SCN8A mutation (p.Ile240Val) with clinical prenatal-onset seizures. Ultrasonography was found to be useful for identifying fetal seizures which may be treatable in utero. Finally the authors report that the clinical approach to fetal seizures should involve a multidisciplinary team.

Read more

SCN8A-Related Epilepsy with Encephalopathy

August 25th, 2016

A summary of the clinical characteristics of SCN8A-related epilepsy. This complete review covers everything from available testing and diagnostic procedures available for SCN8A-related epilepsy, to the management of symptoms, in order to serve as a point-of-care resource for clinicians.

Read more

The SCN8A Mutation p.ll1327Val Displays Elevated Sensibility to the Anticonvulsant Phenytoin

July 4th, 2016

In a recent study it was shown that high doses of phenytoin were effective in four patients with SCN8A encephalopathy. Researchers have created a cell line with a SCN8A mutation (p.Ile1327Val) to study the cell's response to phenytoin.

Read more

How Antiepileptic Drugs (AEDs) May Relate to Fracture Risk

June 21st, 2016

IFracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of these channels in osteoblasts raises the question of whether altered bone signaling increases bone fragility. This study aimed to confirm the expression of voltage-gated sodium (NaV) channels in mouse osteoblasts, and to investigate the action of carbamazepine and phenytoin on NaV channels.

Read more

SCN8A mutation in a child presenting with seizures and developmental delays

November 1st, 2016

Researchers identified a de novo missense SCN8A mutation (p.Leu267Ser, c.800T>C) in a 4 year old female. This case report provides information on the child's clinical presentation,family history, and genetic analysis.

Read more

Benign Infantile Seizures and Dyskinesia - An Unexpected Twist

December 22nd, 2015

SCN1A was initially discovered in GEFS+, an autosomal dominant familial epilepsy syndrome. SCN2A was first identified in Benign Familial Neonatal-Infantile Seizures (BFNIS), also representing an autosomal dominant familial epilepsy syndrome. SCN8A, the third epilepsy-related sodium channel gene, has only...

Read more

2015 - This is What You Need to Know About SCN8A

August 31st, 2015

In 2015, SCN8A has emerged as an important gene in epileptic encephalopathy. SCN8A encodes the voltage-gated sodium channel alpha subunit Nav1.6, and was first implicated in epileptic encephalopathy in 2012. Since then, approximately 100 cases of early-infantile...

Read more

SCN8A Encephalopathy - How it differs from Dravet Syndrome

January 13th, 2015

For some reason, SCN8A always met some resistance. In contrast to other epilepsy genes, it took a while for the community to embrace this gene as a genuine cause of epileptic encephalopathies. A recent publication in Neurology now investigates the phenotypic spectrum of SCN8A encephalopathy – and points out important features that distinguish this condition from Dravet Syndrome.

Read more

Genome Sequencing Finds Unknown Cause Epilepsy

February 23rd, 2012

Only 10 years ago, deciphering the genetic information from one individual in a matter of weeks to find a certain disease-causing genetic mutation would have been written off as science fiction.

It was the time of the Human Genome Project, and it had taken armies of sequencing robots working around the clock for almost a decade to unravel the complete sequence of the human genetic code – referred to as the genome

Read more

Neurotransmitters and Sodium Channelopathies; Possible Link?

November 2017

This brief reviews a published paper that reported findings on neurotransmitter deficiencies in two patients with mutation in voltage-gated sodium genes (SCN2A and SCN8A).

Read more

Beyond seizures — the importance of comorbidities in epilepsy

August 17th, 2017

The exact prevalence of comorbidities in pediatric patients is somewhat unknown at this time as comorbidities can be under-diagnosed. This News & Views article provides insight on the importance of early identification and treatment of comorbidities with children with epilepsy.

Read more

Regulation of Thalamic and Cortical Network Synchrony by SCN8A

February 23rd, 2017

This article outlines the mechanisms through which a mutation in SCN8A results in seizures. Through experimentation in mouse models, researchers have found that decreased SCN8A function in the cortex can lead to convulsive seizure resistance, while decreased SCN8A function in the thalamus can generate absence seizures. The results of this study could motivate future research on the role of SCN8A in other thalamic processes including sleep, attention, and consciousness.

Read more

Progress in Epilepsy: Latest Waves of Discovery

February 22th, 2017

This article summarizes advancements in biotechnology and recent discoveries in epilepsy, which will prospectively be translated into distinct therapy options for the individual patient. These discoveries include the role of inflammatory cell types in the development of epilepsy, the use of intracranial neurostimulation in interrupting seizures, as well as a discussion of the role of bioinformatics in gene identification.

Read more

This page was last modified on: 4/18/2018 9:59:40 AM