Unclassified Epilepsy Research Articles

Can seizures cause glycemic disorder in children with epilepsy? a cross-sectional study

Background: Aim of this study is to investigate the serum glucose level in children with epilepsy.Methods: A cross-sectional study was conducted at Pediatric Centre of Hue Central Hospital between June 2017 and June 2019. A serum glucose level test was performed after the seizure.Results: In total, 144 patients were included in the study. Of these, the most age group was 0 - <5 years (accounted for 59.7%), followed by group 5-10 years (24.3%) and 11-15 years (16%). Female was more likely than male (52.8% vs 47.2%). The most common type was generalized epilepsy (accounted for 72.2%), and the least was un-classified epilepsy (6.3%). The blood test investigated 19 (13.2%) of patients with hyperglycemia and 1 (1.4%) with hypoglycemia.Conclusions: The present study highlights that seizure can cause glycemic disorder in children with epilepsy.

What has been the impact of new drug treatments on epilepsy?

Nearly two dozen antiseizure medications (ASMs) with different mechanisms of action have been introduced over the past three decades with the aim of providing better efficacy or safety profile than the previous drugs. Several new ASMs with improvement on a classic drug family or have novel mechanisms of action have been recently approved for epilepsy. The present review explored recent studies or guidelines on new agents and discussed the potential impact of these novel treatments on epilepsy management and future directions of research. Long-term cohort studies showed that, collectively, the second-generation did not improve the overall prognosis of epilepsy. Individual monotherapy studies showed similar efficacy of second-generation (levetiracetam and zonisamide) and third-generation (eslicarbazepine acetate and lacosamide) ASMs compared to controlled-release carbamazepine for the treatment of focal epilepsy. However, there appears to be no evidence to support any second-generation or third-generation ASMs to be as efficacious as valproate monotherapy for generalized and unclassified epilepsies. Cannabidiol adjunctive treatments were found to be efficacious for Dravet syndrome and Lennox-Gastaut syndrome. Although most newer generation ASMs are less prone to drug-drug interactions, stiripentol and cannabidiol can elevate the plasma concentration of N-desmethylclobazam, the active metabolite of clobazam. Generally speaking, the second-generation ASMs have lower teratogenic risk than the older drugs but there is scant study on neurodevelopmental effect of third-generation ASMs. Although the newer generation ASMs may not have improved the overall seizure control they have advantages in terms of drug-drug interactions and teratogenicity, and thus offer valuable individualized options in the treatment of epilepsy.

Parental report of quality of life in children with epilepsy: A Spanish/French comparison

BackgroundEpilepsy is a chronic neurological condition that affects the quality of life (QoL) of patients and their families. In this study, we compare two sets of reports on QoL that were completed by two samples of parents whose children have epilepsy. MethodParents of children with various types of epilepsy from Spain (N = 196) and France (N = 219) completed the same QoL questionnaire. Medical variables were recorded from the referred specialist doctor for each patient. ResultsThe factors associated with parental reports on QoL were similar in both countries. Parents of children with nonidiopathic generalized or unclassified epilepsy reported poorer QoL and the highest proportion of learning and behavioral problems. However, the intensity of difficulties varied between the two samples. ConclusionsThis questionnaire made it possible to detect comorbidities and daily life difficulties in children with epilepsy and their families. The type of epilepsy had the same influence on Spanish and French families' ratings of QoL. Families shared the same comorbidities in terms of hyperactivity/attention/sociability problems. Nevertheless, the intensity of reported difficulties varied in both countries, possibly because of differences in cultural and educational environments. This aspect should be further explored in future research.

Pregnancy and Epilepsy: a Korean Tertiary Epilepsy Center Review.

BackgroundPregnancy in women with epilepsy (WWE) is known to have a higher risk for fetal development complications, which may include congenital malformations. Unfortunately, information pertaining to pregnancy in WWE is difficult to obtain because there are considerable ethical issues preventing these studies from being conducted on pregnant women. Therefore, this study investigated the pregnancies of Korean WWE in a tertiary epilepsy center to observe data resulting from the outcome of the pregnancies.MethodsThis was a retrospective study of 48 pregnant WWE who were treated at the regional tertiary epilepsy center. All records of hospital visits before and after the period of pregnancy were analyzed to obtain information about the seizures as well as pregnancy-related outcomes, including the status of the newborns' conditions.ResultsThe subject group consisted of 31 (63.3%) with partial epilepsy, 6 (12.5%) with generalized epilepsy, and 11 (22.9%) with unclassified epilepsy. There were 27 subjects who took one antiepileptic drug (AED), and 12 who took two AEDs. The most commonly used drug was lamotrigine (29.8%). Of the 48 WWE involved in the study, 31 underwent caesarian sections and 17 opted for natural birth. Thirty-nine (81.3%) delivered at full-term, but 9 (18.7%) delivered at preterm. Compared to full-term infants, pre-mature infants showed lower birth weight, smaller head circumference, shorter height, and lower 1-minute Apgar scores, but seizure frequencies of the mothers did not differ.ConclusionIn WWE, epilepsy classification, number of AEDs taken, and frequency of seizures are not significantly correlated with delivery and fetal condition. This data could be used as a clinical reference for physicians to provide useful information to WWE if they are concerned about their pregnancies.

Genotypes and phenotypes of patients with Lafora disease living in Germany

BackgroundLafora progressive myoclonus epilepsy (Lafora disease) is a rare, usually childhood-onset, fatal neurodegenerative disease caused by biallelic mutations in EPM2A (Laforin) or EPM2B (NHLRC1; Malin). The epidemiology of Lafora disease in Germany is largely unknown. The objective of this retrospective case series is to characterize the genotypes and phenotypes of patients with Lafora disease living in Germany.MethodsThe patients described in this case series initially had the suspected clinical diagnosis of Lafora disease, or unclassified progressive myoclonus epilepsy. Molecular genetic diagnostics including next generation sequencing-based diagnostic panel analysis or whole exome sequencing was performed.ResultsThe parents of four out of the 11 patients are nonconsanguineous and of German origin while the other patients had consanguineous parents. Various variants were found in EPM2A (six patients) and in EPM2B (five patients). Eight variants have not been reported in the literature so far. The patients bearing novel variants had typical disease onset during adolescence and show classical disease courses.ConclusionsThis is the first larger case series of Lafora patients in Germany. Our data enable an approximation of the prevalence of manifest Lafora disease in Germany to 1,69 per 10 million people. Broader application of gene panel or whole-exome diagnostics helps clarifying unclassified progressive myoclonus epilepsy and establish an early diagnosis, which will be even more important as causal therapy approaches have been developed and are soon to be tested in a phase I study.

Genetic and clinical features of SCN8A developmental and epileptic encephalopathy

ObjectiveWe aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. MethodsNine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations. ResultsThe onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers. ConclusionSCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein.

ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology

The International League Against Epilepsy (ILAE) classification of the epilepsies has been updated to reflect the gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for the clinical diagnosis of patients but it is also critical for epilepsy research, development of antiepileptic treatment and communication around the world. The new classification is based on a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It consists of three levels starting with seizure type, where it is assumed that the epileptic seizures of the patient are defined by the new 2017 ILAE seizure classification. After diagnosis of the seizure type, the next step is the diagnosis of the epilepsy type, which includes focal epilepsy, generalized epilepsy, combined generalized and focal epilepsy and also an unclassified epilepsy group. At the third level the disease is assigned to a specific epilepsy syndrome. The new classification incorporates etiology at each stage, emphasizing the need to consider etiology at each step of the diagnosis, as it often carries significant treatment implications. The various etiologies can be assigned to six subgroups, defined with respect to the potential therapeutic consequences. New terminology is introduced, such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limiting and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the twenty-first century.

Topiramate versus carbamazepine monotherapy for epilepsy: an individual participant data review.

Topiramate versus carbamazepine monotherapy for epilepsy: an individual participant data review.

Brivaracetam in adults with drug-resistant epilepsy and psychiatric comorbidities

This is a case series of 25 patients with drug-resistant epilepsy and psychiatric comorbidities who started on brivaracetam (BRV) at St George's University Hospitals and Frimley Health in London. Median BRV dose was 150 mg for a median follow-up period of 8 months. Twenty had focal epilepsy, four had generalized epilepsies, and one had unclassified epilepsy; 76% had mood disorders (either depression or bipolar disorder), 12% intellectual disabilities with autism spectrum disorder and challenging behavior, and 12% psychoses. Forty percent of patients presented at least 50% seizure reduction, but none of them became seizure-free. A total of 44% of patients discontinued BRV, 20% because of adverse events, 20% because of inefficacy, and 4% because of both. Depression was reported by 8%, aggressive behavior by 8%, while 4% reported both. A total of 91.6% had received levetiracetam (LEV) before, in whom LEV was discontinued because of psychiatric adverse events (PAEs) in half. Seventy-seven percent of patients who developed PAEs with LEV did not do so on BRV suggesting that BRV is better tolerated than LEV in complex patients with psychiatric comorbidities and that the synaptic vesicle glycoprotein 2A (SV2A) protein modulation is unlikely to be implicated in LEV-related PAEs.

Patient-Focused Drug Development Methods for Benefit-Risk Assessments: A Case Study Using a Discrete Choice Experiment for Antiepileptic Drugs.

Regulatory decisions may be enhanced by incorporating patient preferences for drug benefit and harms. This study demonstrates a method of weighting clinical evidence by patients’ benefit–risk preferences. Preference weights, derived from discrete choice experiments, were applied to clinical trial data to estimate the expected utility of alternative drugs. In a case study, the rank ordering of antiepileptic drugs (AEDs), as indicated from clinical studies, was compared with ordering based on weighting clinical evidence by patients’ preferences. A statistically significant change in rank ordering of AEDs was observed for women of childbearing potential who were prescribed monotherapy for generalized or unclassified epilepsy. Rank ordering inferred from trial data, valproate > topiramate > lamotrigine, was reversed. Modeling the expected utility of drugs might address the need to use more systematic, methodologically sound approaches to collect patient input that can further inform regulatory decision making.

Diaper changing-induced reflex seizures in CDKL5-related epilepsy.

Mutations in the CDKL5 (cyclin-dependent kinase-like-5) gene are known to determine early-onset drug resistant epilepsies and severe cognitive impairment with absent language, hand stereotypies, and deceleration of head growth. Reflex seizures are epileptic events triggered by specific stimuli and diaper changing is a very rare triggering event, previously described in individual cases of both focal and unclassified epilepsy, as well as in Dravet syndrome. Our aim was to describe diaper changing-induced reflex seizures as one of the presenting features in a case of CDKL5-related epilepsy, providing video-EEG documentation and focusing discussion on hyperexcitability determined by the disease. [Published with video sequence on www.epilepticdisorders.com].

Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy.

We aimed to determine the frequency of probable obstructive sleep apnea (pOSA) in refractory epilepsy monitoring unit inpatients and clinical features associated with pOSA, including risk for sudden unexpected death in epilepsy (SUDEP). We prospectively recruited 49 consecutive adult patients admitted to the Mayo Clinic Epilepsy Monitoring Unit with focal, generalized, or unclassified epilepsy syndromes. pOSA was identified using oximetric oxyhemoglobin desaturation index (ODI) and the Sleep Apnea-Sleep Disorders Questionnaire (SA-SDQ) and STOP-BAG screening tools. Revised SUDEP Risk Inventory (rSUDEP-7) scores were calculated, and epilepsy patients with and without pOSA were compared with Wilcoxon signed-rank tests. Correlation and regression analyses were utilized to determine relationships between pOSA and rSUDEP-7 scores. Thirty-five percent of patients had pOSA, with a mean ODI of 11.3±5.1/h (range = 5.1-22.8). Patients with pOSA were older and heavier, and more frequently had a focal epilepsy syndrome and longer epilepsy duration, with higher SA-SDQ and STOP-BAG scores (all P<0.05). Median rSUDEP-7 score was 3±1.4 (range = 0-6). Higher rSUDEP-7 scores were positively correlated with higher ODI (P=0.036). rSUDEP-7 score ≥ 5 was associated with pOSA by ODI, SA-SDQ, and STOP-BAG questionnaire criteria (P<0.05). Our pilot study identified a high frequency of pOSA in refractory epilepsy monitoring patients, finding that pOSA patients were older and heavier, with higher screening symptoms for sleep apnea and more frequent focal seizures with a longer epilepsy duration. We also found a possible association between OSA and SUDEP risk. Identification and treatment of OSA in patients with epilepsy could conceivably provide a novel approach toward preventing the risk of SUDEP. Future studies with polysomnography are needed to confirm predictive features for OSA in epilepsy populations, and to determine whether OSA is associated with SUDEP risk.

Novel and de novo mutations in pediatric refractory epilepsy

Pediatric refractory epilepsy is a broad phenotypic spectrum with great genetic heterogeneity. Next-generation sequencing (NGS) combined with Sanger sequencing could help to understand the genetic diversity and underlying disease mechanisms in pediatric epilepsy. Here, we report sequencing results from a cohort of 172 refractory epilepsy patients aged 0–14 years. The pathogenicity of identified variants was evaluated in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria. We identified 43 pathogenic or likely pathogenic variants in 40 patients (23.3%). Among these variants, 74.4% mutations (32/43) were de novo and 60.5% mutations (26/43) were novel. Patients with onset age of seizures ≤12 months had higher yields of deleterious variants compared to those with onset age of seizures > 12 months (P = 0.006). Variants in ion channel genes accounted for the greatest functional gene category (55.8%), with SCN1A coming first (16/43). 81.25% (13/16) of SCN1A mutations were de novo and 68.8% (11/16) were novel in Dravet syndrome. Pathogenic or likely pathogenic variants were found in the KCNQ2, STXBP1, SCN2A genes in Ohtahara syndrome. Novel deleterious variants were also found in West syndrome, Doose syndrome and glucose transporter type 1 deficiency syndrome patients. One de novoMECP2 mutation were found in a Rett syndrome patient. TSC1/TSC2 variants were found in 60% patients with tuberous sclerosis complex patients. Other novel mutations detected in unclassified epilepsy patients involve the SCN8A, CACNA1A, GABRB3, GABRA1, IQSEC2, TSC1, VRK2, ATP1A2, PCDH19, SLC9A6 and CHD2 genes. Our study provides novel insights into the genetic origins of pediatric epilepsy and represents a starting-point for further investigations into the molecular pathophysiology of pediatric epilepsy that could eventually lead to better treatments.

Pattern of executive functioning in adolescents with epilepsy: A multimethod measurement approach

Youth with epilepsy demonstrate deficits in executive functioning (EF), the skills necessary for goal-directed behavior (e.g., problem-solving, initiating, monitoring, organization, planning, and working memory). Despite 30–50% of youth with epilepsy demonstrating EF deficits, no extant studies have utilized both performance and questionnaire-based measures to examine the pattern of EF deficits in adolescents with epilepsy. Study aims were to 1) identify the pattern of EF deficits in adolescents with epilepsy and 2) identify which assessment tools are most sensitive to EF deficits in this population (adolescents, ages 13–17, with epilepsy). An exploratory aim was to examine group differences on measures of EF by epilepsy type. Standard performance-based neuropsychological measures (Wechsler Intelligence Scale for Children – Version V or Wechsler Adult Intelligence Scale Working Memory Index-Version IV, Delis Kaplan Executive Functioning System, NIH Toolbox, Test of Everyday Attention for Children) and the Behavior Rating Inventory of Executive Functioning (BRIEF) comprised the multimethod assessment battery. Depending on the measure, 30% of adolescents with epilepsy had deficits in working memory, 17% in cognitive flexibility/problem solving, 6% in inhibition, and 18% in planning/organization. Attention was a significant problem for 15% of adolescents with epilepsy. Correlations among the various EF measures were quite poor.Across various EF domains, results indicated that adolescents with localization-related epilepsy demonstrated better EF skills compared to adolescents with unclassified epilepsy. Overall, our findings suggest that executive functioning deficits are selective and different from those observed in other neurological populations (e.g., attention deficit hyperactivity disorder (ADHD), traumatic brain injury) where problems with self-regulation (i.e., inhibition, planning/organization) are more pronounced. These findings support utilizing multiple measures, including both performance-based neuropsychological tests and parent- and self-reports, to assess executive functioning difficulties in adolescents with epilepsy as they are uniquely sensitive to executive functioning domains. Adolescents with unclassified epilepsy also appear to be at higher risk for EF deficits and thus represent an important group to target for intervention.

Effective clinical classification of chronic epilepsy into focal and generalized: A cross sectional study

PurposeInvestigations such as EEG and brain imaging are often difficult to obtain in primary care settings of resource-limited regions impacting millions of epilepsy patients. We wanted to test the hypothesis that classification of chronic epilepsy into focal and generalized based on clinical history and examination alone would be comparable to making such a classification with additional inputs from EEG and brain imaging. MethodsTwo investigators independently classified consecutive chronic epilepsy patients into focal, generalized and unclassified epilepsy. Investigator 1 made this determination using clinical history and examination alone whereas Investigator II additionally used EEG and brain imaging too. We calculated inter observer agreement between the two investigators and also looked at the predictors of focal and generalized epilepsy. ResultsFive hundred and twelve patients were recruited. Inter observer agreement between the two investigators in making the focal versus generalized classification was 96.8%, kappa 0.91 (p<0.0001). When EEG and neuroimaging findings were added to clinical information, there was a change in classification in 3.2% patients. Several predictors of focal and generalized epilepsy were identified. ConclusionsClassification of chronic epilepsy into focal and generalized can be done reliably in most patients using clinical information alone. Investigating chronic epilepsy patients with EEG and brain imaging may not be necessary in every patient. The results of our study are especially significant for epilepsy patients living in resource-limited regions where such investigations may not always be available.

Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy.

To examine baseline psychological functioning and antiepileptic drug (AED) behavioral side effects in new onset epilepsy and determine, by age, whether baseline psychological functioning predicts AED behavioral side effects 1month following AED initiation. A retrospective chart review was conducted between July 2011 and December 2014 that included youths with new onset epilepsy. As part of routine interdisciplinary care, caregivers completed the Behavior Assessment System for Children, 2nd Edition: Parent Rating Scale to report on baseline psychological functioning at the diagnostic visit and the Pediatric Epilepsy Side Effects Questionnaire to identify AED behavioral side effects at the 1-month follow-up clinic visit following AED initiation. Children (age = 2-11years) and adolescents (age = 12-18years) were examined separately. A total of 380 youths with new onset epilepsy (Mage =8.9±4.3years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1% generalized epilepsy, 23.7% unclassified epilepsy) were included. Seventy percent of youths had at-risk or clinically elevated baseline psychological symptoms. Children had significantly greater AED behavioral side effects (M=25.08±26.36) compared to adolescents (M=12.36±17.73), regardless of AED. Valproic acid demonstrated significantly greater behavioral side effects compared to all other AEDs, with the exception of levetiracetam. Higher hyperactivity/impulsivity at baseline significantly predicted higher AED behavioral side effects 1month after AED initiation in both age groups. Younger children seem to be more prone to experience behavioral side effects, and these are likely to be higher if youths with epilepsy have baseline hyperactivity/impulsivity. Baseline psychological screening, specifically hyperactivity, can be used as a precision medicine tool for AED selection.

Valproate in the treatment of epilepsy and status epilepticus

According to Hungarian guidelines, valproate - with the exception of infants and small children as well as fertile women - is the first drug of choice in generalized and unclassified epilepsies because it is effective in most seizure types and epilepsy syndromes. It is highly effective in juvenile myoclonic epilepsy. Even though it is not the first-line drug in focal epilepsies, if the first-line therapy is ineffective, it is a plausible alternative as second choice therapy, owing to its different mechanism of action. If the type of epilepsy can't be surely established, valproate is the drug of choice, as it possesses the broadest-spectrum among antiepileptic drugs. After administration of benzodiazepines, intravenously applied valproate can be a first choice therapy in all types of status epilepticus, owing to its broad-spectrum and efficacy. Valproate is the first-choice therapy in patients with glioblastoma - independently of the seizure type -, as it is likely to improve the survival rate with 2-10 months and the effectivity of chemo- and radiotherapy. Valproate is generally not suggested for fertile women, but - as it is the most effective therapy in some epilepsy syndromes -, the patient has the right to choose valproate therapy, thus undertaking the elevated risk of developmental abnormalities, for higher safety regarding seizures. If only valproate therapy owns the ability to obtain seizure freedom, then stopping its administration is not suggested, but a low dosage has to be aimed (500-600 mg/day, but not more than 1000 mg/day): according to some studies, most idiopathic generalized epilepsies can be controlled by low valproate dosage. Stopping valproate therapy in case of an ongoing pregnancy is not suggested.

Topiramate versus carbamazepine monotherapy for epilepsy: an individual participant data review.

Topiramate versus carbamazepine monotherapy for epilepsy: an individual participant data review.

Progressive myoclonus epilepsy associated with SACS gene mutations.

Pathogenic variants in the SACS gene (OMIM #604490) cause autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). ARSACS is a neurodegenerative early-onset progressive disorder, originally described in French Canadians, but later observed elsewhere.(1) Whole-exome sequencing of a large group of patients with unclassified progressive myoclonus epilepsies (PMEs) identified 2 patients bearing SACS gene mutations.(2) We detail the PME clinical features associated with SACS mutations and suggest the inclusion of the SACS gene in diagnostic screening of PMEs.

TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.

Objective:To evaluate the phenotypic spectrum associated with mutations in TBC1D24.Methods:We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24).Results:Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function.Conclusions:TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes.