Epilepsy,seizures, physical exercise,and sports: A report from the ILAE Task Force on Sports and Epilepsy

People with epilepsy (PWEs) are often advised against participating in sports and exercise, mostly because of fear, overprotection, and ignorance about the specific benefits and risks associated with such activities. Available evidence suggests that physical exercise and active participation in sports may favorably affect seizure control, in addition to producing broader health and psychosocial benefits. This consensus paper prepared by the International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy offers general guidance concerning participation of PWEs in sport activities, and provides suggestions on the issuance of medical fitness certificates related to involvement in different sports. Sports are divided into three categories based on potential risk of injury or death should a seizure occur: group 1, sports with no significant additional risk; group 2, sports with moderate risk to PWEs, but no risk to bystanders; and group 3, sports with major risk. Factors to be considered when advising whether a PWE can participate in specific activities include the type of sport, the probability of a seizure occurring, the type and severity of the seizures, seizure precipitating factors, the usual timing of seizure occurrence, and the person's attitude in accepting some level of risk. The Task Force on Sports and Epilepsy considers this document as a work in progress to be updated as additional data become available.     

Altered expression of GABA-A receptor subunits in the hippocampus of PTZ-kindled rats

Background

Changes in the expression of the GABA-A receptor subunits involved in phasic and tonic inhibition have been studied in a wide spectrum of animal models of epilepsy. However, there is no exhaustive data regarding the pentylenetetrazole (PTZ) kindling model of epilepsy.

Further delineation of the phenotype caused by loss of function mutations in PRMT7

PRMT7 encodes for an arginine methyltransferase that methylates arginine residues on various protein substrates and has been shown to play a role in various developmental processes. Mutations in PRMT7 have been recently shown to be implicated in a phenotype with intellectual disability, short stature and brachydactyly, and considered to be a phenocopy of pseudohypoparathyroidism. We report a patient with short stature, psychomotor delay, hearing loss and brachydactyly, for whom whole exome sequencing detected two mutations in PRMT7 and parental segregation studies detected biallelic mutation inheritance. Few patients with biallelic PRMT7 mutations have been reported so far in the literature. We report a new patient and review all reported cases to date to delineate the clinical manifestations that may help in diagnosis this disorder, known as Short Stature, Brachydactyly, Intellectual Developmental Disability, and Seizures syndrome, allowing appropriate management and genetic counselling.     

A novel EXT2 mutation in a consanguineous family with severe developmental delay,microcephaly, seizures,feeding difficulties,and osteopenia extends the phenotypic spectrum of autosomal recessive EXT2-related syndrome (AREXT2)

We report a consanguineous family where 2 boys presented with developmental delay, hypotonia, microcephaly, seizures, gastro-intestinal abnormalities, osteopenia, and neurological regression. Whole exome sequencing performed in one of the boys revealed the presence of a novel homozygous missense variant in the EXT2 gene: c.11C?>?T (p.Ser4Leu). Segregation analysis by Sanger sequencing confirmed homozygous by descent autosomal recessive transmission of this mutation. Another family was previously reported with homozygous mutations in this gene in four siblings affected with a nearly similar clinical condition (Farhan et al., 2015). We discuss the similarities and differences between the two syndromes and propose AREXT2 as a new acronym for EXT2-related diseases.     

Innovation Focus: the Patient with Arrhythmia

Great strides have been made over the last two decades in the management of patients with rhythm disorders. Despite this, however, the remaining critical problems of stroke related to atrial fibrillation or as a result of radiofrequency ablation require innovative solutions to fully realize the potential of these recent advances. Similarly, implanted cardiac devices have revolutionized the care of patients with bradyrhythmias and tachyarrhythmias. Dyssynchronus ventricular pacing associated with present devices; however, results in heart failure, tricuspid regurgitation, and inappropriate device therapy once again create a demand for creative solutions. While not technically an arrhythmia, epilepsy management today is riddled with many of the problems that plagued cardiac arrhythmia management previously, and thus an appreciation of the similarities in requirement for investigative solutions may yield groundbreaking solutions. In this paper, we describe some novel methods to reduce complications associated with rhythm disorders and their treatment and apply the lessons learned from cardiovascular arrhythmia management to the brain. These include: a method to reduce coagulum formation and thus subsequent thromboembolism with indwelling catheters specifically during radiofrequency ablation procedures; a technique to ligate the left atrial appendage through percutaneous subxiphoid pericardial access; development and testing of a novel intramyocardial pace-sense lead, particularly used in a unique anatomic location (the atrioventricular septum) to allow pacing the ventricles in a relatively synchronous manner without crossing the tricuspid valve or entering the coronary sinus; finally, novel modifications of the cardiovascular mapping and ablation techniques used for the management of the central nervous system disorders primarily via the venous drainage of the brain. Innovative and potential solutions to treat the patient with arrhythmia are presented.

Purine Seizure Disorders

Developing antiepileptic agents that are specifically tailored to a patient's individual biochemistry has long been a goal of neurology. Three patients who had hyperuricosuria combined with a seizure disorder that failed to respond to traditional anticonvulsants are described. The patients had the best control of their seizure disorder when a specific metabolic drug, allopurinol, was used as an anticonvulsant. All three patients had onset of the seizure disorder at 22 months of age, a finding possibly related to maturation of purine enzymes. Because elevated uric acid levels in the immediate postictal period may occur in seizure patients, the presence of an elevated uric acid clearance in seizure-free periods is needed to consider the diagnosis of an allopurinol-responsive seizure problem in any individual patient. In the two patients past the onset of puberty, lowering (one case) and cessation (other case) of the dose of allopurinol has been possible.     

Effect of kynurenine and quinolinic acid on the action of convulsants in mice

Intraventricular injection of DL-kynurenine and L-kynurenine sulfate (40 μg) into conscious mice potentiated convulsions and lethality produced by strychnine (1 mg/kg) and not by thiosemicarbazide nor pentylenetetrazol. Another metabolite of tryptophan with convulsive effect, quinolinic acid, was ineffective. Intraperitoneal injection of DL-kynurenine sulfate and quinolinic acid (25–100 mg/kg) was associated with prolongation of the latency of strychnine and thiosemicarbazide (only the former drug) seizures. Nicotinic, picolinic, and anthranilic acids (100 and 250 mg/kg) did not modify the action of convulsants. Data and suggestions about probable involvement of brain glycine and gamma-aminobutyric acid receptors in the convulsive action of kynurenines is discussed.     

Prevalence of Epilepsy and Seizure Disorders in an Urban Minority Population: A Feasibility Study

Information on the frequency of epilepsy/seizure disorders and factors associated with development of epilepsy in an underprivileged urban ghetto population is urgently needed. A feasibility study was undertaken, and a questionnaire to collect information on seizure activity and behavior in the community was administered to a series of households with known seizure disorders, a series of households with chronic diseases, and a series of households chosen at random. Sensitivity and specificity of the seizure questions were estimated to be 0.93 and 0.89 respectively. The community was receptive to a survey of this type, and the overall refusal/nonresponse rate was 7.2%. Factors that would contribute to the success of an urban minority community survey are considered.     

Effects of phenylalanine and 5-hydroxytryptophan on seizure severity in mice

The degree of audiogenic seizure was measured in DBA/2J (phenylalanine hydroxylase deficient) mice as a function of dietary phenylalanine (Phe) and injected 5-hydroxytryptophan (5-HTP), the precursor of serotonin (5-HT). Phe was shown to exacerbate seizures significantly, and seizure severity was found to be directly related to dietary concentration when animals were not treated with exogenous 5-HTP. 5-HTP was observed to significantly ameliorate seizures. The seizure-intensifying effect of Phe was reversible by 5-HTP injection and protection against seizures was directly related to 5-HTP concentration for animals on a high Phe diet. The results of this study indicate that Phe and 5-HTP are mutually antagonistic in modulating audiogenic seizure susceptibility.     

Comparison of anticonvulsive properties of eboracin and phenytoin in mice

The in vivo effects of phenytoin (diphenylhydantoin, Dilantin) and the experimental anticonvulsant, eboracin, a substituted indenopyrrole, were compared in mice. Pretreatment with varying dosages of either agent followed by challenge with the chemoconvulsant pentylenetetrazol (Metrazol) indicated that eboracin provided slightly less protection against seizures than phenytoin and was much less toxic. Intermediate doses of either agent led to a form of clonic status epilepticus which persisted for an average of 18 min in phenytoin-treated and 58 min in eboracin-treated mice. Pretreatment with higher or lower doses did not lead to these manifestations. Animals in which this syndrome had been induced should be of value in studies of the chemistry and physiology of the clonic state.