Genetic Diagnostic Yield in Autism Spectrum Disorder (ASD) and Epilepsy Phenotypes in Children with Genetically Defined ASD.

We compared the epilepsy phenotypes in children with genetically defined versus undefined autism spectrum disorder (ASD). A single-center retrospective study was conducted to investigate diagnostic yields of different genetic testing for children with ASD. Patients with at least one testing modality were included and classified as having genetically defined ASD or not based on updated genotype-phenotype correlation. Of the 523 patients included, 79 (15.1%) had results explaining their ASD diagnosis. WES (whole exome sequencing) outperformed CMA (chromosomal microarray) on diagnostic yield (23.0% versus 8.3%). Compared to those with non-diagnostic test(s), children with genetically defined ASD were associated with higher rates for microcephaly, hypotonia, dysmorphic features, and developmental delay/regression. The prevalence of epilepsy was significantly higher in children with genetically defined ASD than those without a genetic diagnosis (35.4% versus 16.4%, p < 0.001, power = 0.97). Furthermore, children with genetically defined ASD had a younger age of epilepsy onset (median 2.2 versus 5.0 years, p = 0.002, power = 0.90) and a higher rate of drug-resistant epilepsy although not reaching statistical significance (35.7% versus 21.9%, p = 0.20). Our study has provided further evidence to support WES as first-tier test for children with ASD and that an early genetic diagnosis has the potential to inform further surveillance and management for ASD comorbid conditions including epilepsy.

Clinical features and drug-resistance in pediatric epilepsy with co-occurring autism: A retrospective comparative cohort study.

OBJECTIVE: We conducted a retrospective comparative cohort study to determine the phenotypic and real-world management differences in children with epilepsy and co-occurring autism as compared to those without autism. METHODS: Clinical variables, EEG, brain MRI, genetic results, medical and non-medical treatment were compared between 156 children with both epilepsy and autism, 156 randomly selected and 156 demographically matched children with epilepsy only. Logistic regression analyses were conducted to determine predictors of drug-resistant epilepsy (DRE). RESULTS: As compared to the'matched' cohort, more patients with autism had generalized motor seizures although not statistically significant after Benjamini-Hochberg correction (54.5%, vs 42.3%, p = .0314); they had a lower rate of electroclinical syndromes (12.8%, vs 30.1%, p = .0002). There were more incidental MRI findings but less positive MRI findings to explain their epilepsy in children with autism (26.3%, vs 13.8% and 14.3%, vs 34.2%, respectively; p = .0003). In addition, LEV, LTG, and VPA were the most common ASMs prescribed to children with autism, as opposed to LEV, OXC, and LTG in children without autism. No difference in the major EEG abnormalities was observed. Although the rates of DRE were similar (24.8%, vs 26.6%, p = .7203), we identified two clinical and five electrographic correlates with DRE in children with both epilepsy and autism and a final prediction modeling of DRE that included EEG ictal findings, focal onset seizures, generalized motor seizures, abnormal EEG background, age of epilepsy onset, and history of SE, which were distinct from those in children without autism. SIGNIFICANCE: Our study indicates that detailed seizure history and EEG findings are the most important evaluation and prediction tools for the development of DRE in children with epilepsy and co-occurring autism. Further studies of epilepsy in specific autism subgroups based on their etiology and clinical severity are warranted.

Vitamin B6 decreases the risk of levetiracetam discontinuation in children with epilepsy: A retrospective study.

OBJECTIVES: Levetiracetam (LEV) is an anti-seizure medication (ASM) known to have significant behavioral side effects in children with epilepsy. These side effects may be improved by supplemental vitamin B6 (pyridoxine) use. Our research aimed to study risk factors for LEV side effects and the role of vitamin B6 in altering this risk. METHODS: We retrospectively analyzed the demographic and clinical profile of all pediatric patients on LEV treatment between July 2019 and December 2020. T-tests, Chi-square and Fisher exact tests were used to assess predictors of LEV discontinuation. A p-value of <0.05 was considered statistically significant. RESULTS: 150/240 (62%) children were on additional medications besides LEV for epilepsy management. Thirty-five percent children reported side effects, especially behavioral and mood concerns. Of the patients who reported side effects on LEV, 71% were taking vitamin B6 (n = 59). The rate of LEV discontinuation was significantly lower for children on vitamin B6 than children not taking B6, regardless of monotherapy or polypharmacy (49% v 88% respectively, p = 0.001). Over half of the patients who were able to remain on LEV reported improved behavior with B6 supplementation as compared to those who were unable to continue LEV (17/30, 57% versus 0/26, 0%; p < 0.001). CONCLUSIONS: Levetiracetam side effects significantly impact the tolerability of this ASM in children with epilepsy. Our results suggest that vitamin B6 supplementation can significantly reduce the odds of discontinuing LEV due to its behavioral side effects.