The influence of genetics on epilepsy syndromes in infancy and childhood

Genetics is rapidly evolving and is actively playing a role in how we diagnose and manage epilepsy.The definition of an epilepsy syndrome has changed throughout the years.The International League Against Epilepsy(ILAE)has developed a classification of the epilepsies and has recently described specific epilepsy syndromes taking into account emerging genetic information which is rapidly evolving as well as etiology-specific syndromes.Understanding genetics can help clarify the syndrome and its treatment.This review provides a history of the definition of a syndrome,and the evolving contribution of genetic information that is part of the syndromic classification.We provide few examples of several phenotypes/genotypes of epilepsy syndromes in infancy and childhood and treatment issues that may arise from the available genetic information.Epilepsy syndromes and their genetics have been rapidly changing as new gene technologies are being developed.Understanding genetics can help clarify the syndrome,its treatment,and will help change the field of epilepsy to improve patients qualify of life by creating new means of preventing,controlling,and curing epilepsy.

Preliminary analysis of the effect of vagus nerve stimulation in the treatment of children with intractable epilepsy

BACKGROUND Implant vagus nerve stimulation is an adjunctive treatment for intractable epilepsy when patients are not suitable for resective surgery.AIM To identify the safety and efficacy of vagus nerve stimulation in children with intractable epilepsy and analyze the effects on different epilepsy syndromes.METHODS Eligible children with intractable epilepsy were admitted to the study.We collected data from preoperative assessments as the baseline.During the followup time,we recorded the process of seizures(frequency,duration,and seizure type),the changes of drugs or parameters,the complications,etc.The mean reduction rate of seizures,response rate,and McHugh scale were chosen as the outcomes.RESULTS A total of 213 patients were implanted with Tsinghua Pins vagus nerve stimulators,and the average age was 6.6 years.In the follow-up time of postoperative 3 mo,6 mo,12 mo,18 mo,and 24 mo,the average reduction rate was 30.2%,49.5%,56.3%,59.4%,and 63.2%,while the response rate was 21.8%,62.5%,57.1%,69.2%,and 70.7%.In addition,implanted vagus nerve stimulation had different effects on epilepsy syndromes.The reduction rate of West syndrome increased from 36.4%(postoperative 6 m)to 74.3%(postoperative 24 m).The reduction rate of Lennox-Gastaut syndrome improved from 25.4%to 73.1%in 24 mo.The chi-square test of the five efficacy grades showed P<0.05.The comparison between the 3-mo follow-up and the 6-mo follow-up showed P<0.05,and the comparison between the 6-mo follow-up and the 24-mo follow-up showed P>0.05.CONCLUSION Vagus nerve stimulation is safe and effective in children with intractable epilepsy,and the seizure reduction occurred in a time-dependent manner.Moreover,patients with West syndrome may get the most benefits.

Genetic variant reanalysis reveals a case of Sandhoff disease with onset of infantile epileptic spasm syndrome

Background Sandhoff disease(SD)i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy,psychomotor retardation and developmental delay.However,infantile SD with onset of infantile epilepsy spasm syndrome(IESS)is extremely rare.Case presentation The case presented here was a 22-month-old boy,who presented with IESS and psychomotor retardation/regression at 6 months of age.The patient showed progressive aggravation of seizures and excessive startle responses.The whole exome sequencing data,which initially revealed negative results,were reanalyzed and indicated a homozygous mutation at the c.1613+4del splice site of the HEXB gene.The activities ofβ-hexosaminidase A and total hexosaminidase were significantly decreased.The fundus examination showed cherry red spots at the macula.Conclusions IESS can be an epileptic phenotype of infantile SD.Clinical phenotypes should be adequately collected in genetic testing.In the case of negative sequencing results,gene variant reanalysis can be performed when the patients show clinically suspicious indications.

The ketogenic diet for paediatric patients with super-refractory status epilepticus in febrile infection-related epilepsy syndrome

Objective:To investigate the effect and safety of ketogenic diet(KD)for the treatment of paediatric patients with super-refractory status epilepticus(SRSE)in febrile infection-related epilepsy syndrome(FIRES).Method:From January 1,2015 to October 31,2017,ten critically ill paediatric patients with SRSE in FIRES were included in this study and treated with KD.The treatment effects of KD were evaluated by using continuous encephalography(CEEG)and amplitude-integrated electro-encephalography(aEEG).Results:All 10 patients fulfilled the diagnostic criteria of SRSE in FIRES and achieved ketosis within 24–72 h following the administration of KD.CEEG and aEEG were monitored for several weeks to assess the efficacy of KD on status epilepticus(SE).SE was contained in 8 patients within 2 to 19 days after initiation of KD,and KD was discontinued in the other 2 patients.One of the 10 patients demonstrated severe adverse effects.Conclusion:KD may be an alternative and safe treatment option in critical paediatric patients with SRSE in FIRES.

A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged Red Fibers Syndrome in a Chinese Patient

Background： Myoclonic epilepsy with ragged red fibers （MERRF） syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers （RRFs） in the muscle. T-to-C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid （tRNA^Gla） gene has previously been associated with maternally inherited diabetes and deathess. However, the association between MERRF and mitochondrial T14709C mutation （m.TI4709C） has never been reported before. Methods： Clinical information of a 17-year-old patient was collected; muscle biopsy and next-generation sequencing （NGS） of whole mitochondrial and neuromuscular disease panel were then conducted. Finally, sanger sequencing was carried out to confirm the mutations. Results： The patient presented a typical MERRF phenotype with muscle weakness, epileptic seizure, clonic episodes, cerebellar ataxia, and spinal scoliosis. Muscle biopsy showed RRFs which indicated abnormal mitochondrial functions. NGS of whole mitochondrial gene revealed m.TI4709C mutation, confirmed by Sanger sequencing. Conclusion： We present a sporadic patient with typical MERRF presentation carrying the mutation ofm.T14709C, which expanded the spectrum of re.T14709C.

Brief potentially ictal rhythmic discharges on intraoperative electrocorticography predict a good outcome of focal cortical dysplasia after surgical resection: a case report

Background Focal cortical dysplasia(FCD)is a common cause of drug-resistant epilepsy.Electroencephalography(EEG)biomarkers that predict good postoperative outcomes are essential for identifying patients with focal epilepsies.Case presentation We report the case of a 21-year-old female with seizure onset at the age of 9,characterized by left-hand dystonic posturing and impaired awareness,which evolved to bilateral tonic-clonic seizures,evaluated in a neurological referral center in Lima,Peru.During 6-h video-EEG,interictal EEG revealing focal brief potentially ictal rhythmic discharges(BIRDs)over the right frontal central region,lasting less than 10 s.The ictal features were characterized by low-voltage fast activity over the same area.Brain magnetic resonance imaging(MRI)demonstrated a focal lesion of focal cortical dysplasia type II in the right frontal lobe.The patient underwent a lesionectomy guided by electrocorticography,which showed continuous polyspikes.BIRDs showing a brief burst of spikes lasting longer than 0.5 s,were also identified on intraoperative electrocorticography(ECoG)and helped define the extent of resection.The patient obtained an Engel Outcome Class IA at 6 years of follow-up.Conclusions The atypical BIRDs on ECoG can be used as a prognostic biomarker for prolonged seizure-freedom outcome in patients with epilepsy.Additional reports are needed in developing countries with and without brain MRI lesions to advance outpatient presurgical evaluations despite limited resources.