Sulthiame use in children with pharmacoresistant epilepsies: A retrospective study.

OBJECTIVE: This retrospective study aimed to assess the efficacy and tolerability of sulthiame as an add-on treatment in children with pharmacoresistant epilepsies. METHODS: All patients with epilepsy who received sulthiame at Montreal Children's Hospital over an 11-year period were included. Medical charts were reviewed, and extracted data included patient age and sex, seizure types, epilepsy syndrome, electroencephalography (EEG) reports, brain imaging reports, antiseizure treatments trialed, starting and final dose of sulthiame, duration of sulthiame treatment, adverse events attributed to sulthiame, and seizure frequency before and after sulthiame treatment. EEG studies were also analyzed and spike-wave index (SWI) in the first 10 min of sleep was calculated. RESULTS: Sixteen patients were included, all of whom had pharmacoresistant epilepsies (mean of 9.9 trials of other antiseizure treatments). Six had genetic diagnoses, four had in utero/perinatal acquired brain injury, one had a suspected focal cortical dysplasia, and five were idiopathic. Ten patients had developmental and epileptic encephalopathy with spike-wave activation in sleep, three had Lennox-Gastaut syndrome, and one each had sleep-related hyperkinetic epilepsy, self-limited epilepsy with centrotemporal spikes, and mixed generalized and multifocal epilepsy. Of the 12 patients with uncontrolled seizures at the time of sulthiame initiation, 4 had improvement in seizure frequency, including 2 who became seizure free. Eight patients had EEG data available that allowed calculation of sleep SWI; from this group, SWI decreased from 81.1% +/- 17.6% to 45.1% +/- 36.5% (p = .007). The most common adverse events reported were somnolence/drowsiness, aggression, and increased seizure frequency. Of the patients with genetic etiologies, significant positive responses were seen in patients with pathogenic variants in NDUFS1 and SATB1. SIGNIFICANCE: These data demonstrate the therapeutic potential of sulthiame, even in patients with highly pharmacoresistant epilepsy. Improvements may be seen in both seizure frequency and sleep SWI.

Ataxia and Diplopia: A New SCN8A-Related Phenotype.

Objectives: The objective of this study was to describe the first patient with recurrent ataxia and diplopia in association with a pathogenic variant in SCN8A. Methods: We identified a girl with a heterozygous SCN8A pathogenic variant and performed thorough phenotyping. Results: A 10-year-old girl was previously well with normal intelligence. She had recurrent diplopia, dysmetria, and unsteady gait, which occurred only in the context of febrile illnesses. EEG during her initial acute episode showed multifocal epileptiform discharges, with similar findings seen on a follow-up study 3 months later when she was well. Brain MRI finding was normal. A gene panel identified a de novo SCN8A variant, p.Arg847Gln, classified as likely pathogenic. One year after her initial presentation, the girl is well and developmentally normal and has never had an event concerning for seizure. Discussion: This case presentation demonstrates that SCN8A pathogenic variants should be considered in children with transient ataxia, dysmetria, and diplopia in the context of viral febrile illnesses, even if there is no history of seizures. While there are clinical and molecular data suggesting that SCN8A dysfunction can cause temperature-sensitive phenotypes, further research is necessary to determine how the functional changes caused by our patient's SCN8A variant result in her unique phenotype.

Maternal risk factors and newborn infant vitamin D status: a scoping literature review.

Low vitamin D (VitD) status is common among newborn infants, more so in temperate latitudes with evidence that maternal VitD deficiency is a major risk factor given that the neonate relies solely on maternal-fetal transfer of VitD. This scoping review was conducted to provide an overview of the latest evidence from studies regarding the impact of maternal risk factors on infant 25-hydryoxyvitamin D [25(OH)D] concentrations with a focus on studies in Canada and the United States. Several maternal risk factors that contribute to low maternal-fetal 25(OH)D concentrations have been reported over many decades, but no clear pattern has been established for multiethnic populations. For example, darker skin pigmentation and ethnicity are common risk factors for low VitD status. Studies in predominantly white women showed that supplementation of VitD during pregnancy causes significant increases in maternal serum 25(OH)D which often improves cord serum 25(OH)D values. In addition, VitD recommendations by health care professionals and adherence to supplementation by pregnant women appear to positively influence maternal and infant 25(OH)D concentrations. Conversely, winter season, obesity, lower socioeconomic status including lifestyle factors (smoking), and use of medication pose risk for lower maternal-fetal transfer of VitD. However, there is still a dearth of pertinent data on the relationship between some of the maternal risk factors and newborn 25(OH)D concentrations, for instance, relationships between gestational diabetes and neonatal VitD status. Additional research is required to determine if the same target for 25(OH)D concentrations applies for pregnant women, neonates, and infants.