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Until recently, nodding syndrome (NS) was considered as a mysterious disease of unknown etiology. A link between onchocerciasis and epilepsy was suspected for a long time. However, onchocerciasis was not considered as the cause of NS because NS was believed to occur only in onchocerciasis-endemic regions in Uganda, South Sudan, and Tanzania. In October 2015, with funding from the European Research Council, the NSETHIO group launched a trans-disciplinary, multi-country research project to identify the cause of NS and to study the link between onchocerciasis and epilepsy.
We reviewed NSETHIO activities as well as all published papers, and compared project findings with results of previous research on NS.
Findings from the NSETHIO project showed that NS is only one of the clinical manifestations in the wide spectrum of onchocerciasis-associated epilepsy (OAE) that could be prevented by strengthening onchocerciasis elimination programs. NSETHIO demonstrated that OAE is an important neglected public health problem in onchocerciasis-endemic areas with no or a sub-optimally functioning onchocerciasis control strategies.
Today there is overwhelming evidence that NS together with the Nakalanga syndrome is clinical presentations of OAE, a condition that could be prevented by strengthening onchocerciasis elimination programs. While research needs to continue to elucidate the pathophysiological mechanisms causing NS, new strategies to accelerate onchocerciasis elimination coupled with community-based surveillance and treatment programs for epilepsy are urgently needed in areas of high Onchocerca volvulus transmission.
Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system.
An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service.
The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be “evidence-based” and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future.
This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.
Rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RWA) have assumed much clinical importance with long-term data showing progression into neurodegenerative conditions among older adults. However, much less is known about RBD and RWA in younger populations. This study aims at comparing clinical and polysomnographic (PSG) characteristics of young patients presenting with RBD, young patients with other neurological conditions, and normal age-matched subjects.
A retrospective chart review was carried out for consecutive young patients (<25 years) presenting with clinical features of RBD; and data were compared to data from patients with epilepsy, attention deficit hyperactivity disorder (ADHD), and autism, as well as normal subjects who underwent PSG during a 2-year-period.
Twelve patients fulfilling RBD diagnostic criteria, 22 autism patients, 10 with ADHD, 30 with epilepsy, and 14 normal subjects were included. Eight patients with autism (30%), three with ADHD (30%), one with epilepsy (3.3%), and six patients who had presented with RBD like symptoms (50%) had abnormal movements and behaviors during REM sleep. Excessive transient muscle activity and/or sustained muscle activity during REM epochs was found in all patients who had presented with RBD, in 16/22 (72%) autistic patients, 6/10 (60%) ADHD patients compared to only 6/30 (20%) patients with epilepsy and in none of the normal subjects.
We observed that a large percentage of young patients with autism and ADHD and some with epilepsy demonstrate loss of REM-associated atonia and some RBD-like behaviors on polysomnography similar to young patients presenting with RBD.
The relationship between epilepsy and the presence of visceral larva migrans caused by Toxocara canis in Mexican children remains uncertain; however, this relationship needs to be elucidated because these parasite larvae can invade the human central nervous system. Accordingly, this study aimed to determine the frequency and specificity of anti-T. canis antibodies in the sera of children with epilepsy to determine the relationship between this parasite and epilepsy. The sera samples of 214 children were examined: 111 children diagnosed with epilepsy and 103 clinically healthy children without neurological disorders. In the sera of each group, the presence and specificity of anti-T. canis and anti-Ascaris lumbricoides antibodies, as well as the cross-reactivity between them, were assessed using enzyme-linked immunosorbent assay and Western blotting analysis. Among the children with epilepsy, 25.2% exhibited seropositivity to T. canis. Cross-reactivity against the A. lumbricoides antigen was present in 46.8% of the children with epilepsy, whereas 11.7% of the children with epilepsy and anti-T. canis antibodies did not exhibit cross-reactivity against this antigen. The Western blotting analysis of the sera from the children with epilepsy demonstrated the presence of T. canis proteins, with molecular weights of 24, 35, 55, 70, 120 and 210 kDa, and A lumbricoides proteins with molecular weights of 70, 80 and 110 kDa. Our results revealed the presence of anti-T. canis antibodies in the children with epilepsy; furthermore, cross-reactivity tests with A. lumbricoides showed the importance of the presence of anti-T. canis antibodies in revealing the relationship between this parasite and epilepsy in children.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Compound heterozygotes occur when different variants at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of variants at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 Genomes Project participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or infantile spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 Genomes Project data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 Genomes Project participants using minor allele frequency (MAF) cutoffs of 0.5 and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous variants in six genes, including three involved in neuronal growth and development – PRTG (p = 0.00086, 1% MAF, combined ancestries), TNC (p = 0.022, 1% MAF, combined ancestries) and MACF1 (p = 0.0245, 0.5% MAF, EU ancestry). Due to the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous variants should be considered in sporadic epilepsy.
Epilepsy and mental illness have a bidirectional association. Psychiatrists are likely to encounter epilepsy as comorbidity. Seizures may present as mental illness. Equally, the management of psychiatric conditions has the potential to destabilise epilepsy. There is a need for structured epilepsy awareness and training amongst psychiatrists. This paper outlines key considerations around diagnosis, treatment and risk while suggesting practical recommendations.
Neurocysticercosis (NCC) occurs following brain infection by larvae of the cestode Taenia solium. It is the leading cause of preventable epilepsy worldwide and therefore constitutes a critical health challenge with significant global relevance. Despite this, much is still unknown about many key pathogenic aspects of the disease, including how cerebral infection with T. solium results in the development of seizures. Over the past century, valuable mechanistic insights have been generated using both clinical studies and animal models. In this review, we critically assess model systems for investigating disease processes in NCC. We explore the respective strengths and weaknesses of each model and summarize how they have contributed to current knowledge of the disease. We call for the continued development of animal models of NCC, with a focus on novel strategies for understanding this debilitating but often neglected disorder.
Multiple genes/variants have been implicated in various epileptic conditions. However, there is little general guidance available on the circumstances in which genetic testing is indicated and test selection in order to guide optimal test appropriateness and benefit. This is an account of the development of guidelines for genetic testing in epilepsy, which have been developed in Ontario, Canada. The Genetic Testing Advisory Committee was established in Ontario to review the clinical utility and validity of genetic tests and the provision of genetic testing in Ontario. As part of their mandate, the committee also developed recommendations and guidelines for genetic testing in epilepsy. The recommendations include mandatory prerequisites for an epileptology/geneticist/clinical biochemical geneticist consultation, prerequisite diagnostic procedures, circumstances in which genetic testing is indicated and not indicated and guidance for selection of genetic tests, including their general limitations and considerations. These guidelines represent a step toward the development of evidence-based gene panels for epilepsy in Ontario, the repatriation of genetic testing for epilepsy into Ontario molecular genetic laboratories and public funding of genetic tests for epilepsy in Ontario.
The benefit of mandibular advancement devices in patients with sleep-disordered breathing and as a potential option for obstructive sleep apnoea syndrome is well recognised. Their use in the setting of epilepsy or other seizure disorders is typically contraindicated.
A 48-year-old patient with a history of poorly controlled epilepsy and obstructive sleep apnoea syndrome was referred for ENT review for possible tracheostomy. The patient was wheelchair-bound with 24-hour continuous positive airway pressure, but sleep studies demonstrated persistent, severe episodes of apnoea and notable sleep disturbance. Sleep nasendoscopy demonstrated marked improvement on capnography with the laryngeal mask airway in situ, and this was maintained with mandibular advancement using jaw thrust following removal of the laryngeal mask airway. A mandibular advancement device was subsequently trialled; this had no subjective benefit for the patient, but the seizures resolved and control of apnoea was achieved with the combination of a mandibular advancement device and continuous positive airway pressure.
This paper highlights a novel application of mandibular advancement devices, used in combination with continuous positive airway pressure, which resulted in complete resolution of sleep deprivation and apnoea-induced epileptic events.
Objectives: Naming assessment is a core component of neuropsychological evaluation, particularly in the surgical work up for patients with pharmacologically refractory epilepsy. Specifically, naming deficits are typically associated with left, but not right hemisphere epilepsy, thereby assisting with lateralization of seizure onset. We sought to determine whether bilingual (English as second language, ESL) and monolingual epilepsy patients with comparable education, intelligence, and objective vocabulary performance would perform similarly on standard naming measures, and whether ESL patients would demonstrate laterality effects in naming, similar to that observed in monolingual patients. Methods: Participants were 242 adults with epilepsy (186 native, 56 ESL) who underwent neuropsychological evaluation and obtained normal range or higher scores on the Wechsler Adult Intelligence Scale (R/III/IV) Vocabulary subtest (scaled score≥8). Groups were compared on demographic factors and language performances (i.e., Boston Naming Test, Auditory & Visual Naming Test, word reading, fluency). Results: Groups did not differ with respect to age, education, FSIQ, vocabulary, reading, or verbal fluency. However, ESL speakers earned poorer scores than native English speakers on all naming measures. Moreover, among ESL participants with unilateral epilepsy, a significant proportion of right hemisphere patients scored below cutoff for impairment. This contrasted with the more typical finding among native English speakers, whereby a significant proportion of left patients demonstrated naming impairment. Conclusions: These results underscore the complexity of verbal assessment in bilinguals, suggesting that naming performances by ESL individuals, even those considered proficient, with strong performances on other English verbal measures, cannot be interpreted by the same standards applied for native speakers. (JINS, 2018, 24, 1057–1063)