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BackgroundRecent clinical observations have reported the potential benefit of vagus nerve stimulation (VNS) as an adjunctive therapy for pediatric epilepsy. Preliminary evidence suggests that VNS treatment is effective for seizure reduction and mental development in young participants between 3 and 6 years of age who suffer from intractable epilepsy. However, robust clinical evidence for quantifying the difference of the efficacy and safety of VNS treatment in this specific patient population has yet to be reported.Methods/designA two-armed, multicenter, randomized, double-blind, prospective trial will be carried out to evaluate whether VNS is beneficial and safe for pediatric epilepsy. Pediatric participants aged between 3 to 6 years old with intractable epilepsy will be recruited and randomly assigned to experimental and control groups with a 1:1 allocation using a computer-generating randomization schedule. Before enrollment, informed consent will be signed by the parents of the participants and the study researchers. Participants in the experimental group will receive electrical stimulation over 24 weeks under standard stimulation parameters. Participants in the control group will not receive any stimulation during the 12 weeks of the double-blind period. The guardians of the participants are required to keep a detailed diary to record seizure activity. Outcome assessments including seizure frequency, Gesell Mental Developmental Scale scores, use of antiepileptic drugs and dosages, and adverse events will be collected at baseline, 6, 12, 18 and/or 24 weeks after electrical stimulation is initiated. The effects of treatment will be analyzed with time and treatment group comparisons.DiscussionThis trial will evaluate quantitative differences in efficacy and safety with/without VNS treatment for pediatric participants aged between 3 to 6 years with intractable epilepsy and will explore whether the current age range of VNS therapy can be expanded.Trial registrationClinicalTrials.gov, ID: NCT03062514, Registered on 23 February 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3087-4) contains supplementary material, which is available to authorized users.

BackgroundIsolated sulfite oxidase deficiency (ISOD) is an autosomal recessive disorder caused by a deficiency of sulfite oxidase, which is encoded by the sulfite oxidase gene (SUOX). Clinically, the disorder is classified as one of two forms: the late-onset mild form or the classic early-onset form. The latter is life-threatening and always leads to death during early childhood. Mild ISOD cases are rare and may benefit from dietary therapy. To date, no cases of ISOD have been reported to recover spontaneously. Here, we present three mild ISOD cases in one family, each with a stable clinical course and spontaneous recovery.Case presentationAll three siblings had two novel compound heterozygous mutations in the SUOX gene (NM_000456; c.1096C > T [p.R366C] and c.1376G > A [p.R459Q]). The siblings included two males and one female with late ages of onset (12–16 months) and presented with specific neuroimaging abnormalities limited to the bilateral globus pallidus and substantia nigra. The three patients had decreased plasma homocysteine levels. They exhibited a monophasic clinical course continuing up to 8.5 years even without dietary therapy.ConclusionThis is the first report of mild ISOD cases with a stable clinical course and spontaneous recovery without dietary therapy. Our study provides an expansion for the clinical spectrum of ISOD. Furthermore, we highlight the importance of including ISOD in the differential diagnosis for patients presenting with late-onset symptoms, bilaterally symmetric regions of abnormal intensities in the basal ganglia, and decreased plasma homocysteine levels.

Background: The study aimed to explore cortical morphology in benign childhood epilepsy with centrotemporal spikes (BECTS) and the relationship between cortical characteristics and age of onset and intelligence quotient (IQ). Methods: Cortical morphometry with surface-based morphometry (SBM) was used to compare changes in cortical thickness, gyrification, sulcal depth, and fractal dimension of the cerebral cortex between 25 BECTS patients and 20 healthy controls (HCs) with two-sample t-tests [P<0.05, family-wise error (FWE) corrected].Relationships between abnormal cortical morphological changes and age of onset and IQ, which included verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full-scale intelligence quotient (FIQ) were investigated with Spearman correlation analysis (P<0.05, uncorrected). Results:The BECTS patients showed extensive cortical thinning predominantly in bilateral frontal, temporal regions, and limbic system. Cortical gyrification increased in the left hemisphere and partial right hemisphere, and the decreased cortical gyrification was only in the left hemisphere. The increased sulcal depth was the left fusiform gyrus. There are no statistically significant differences in the fractal dimension.Correlation analysis revealed the negative correlation between age of onset and cortical thickness in the right precentral gyrus. It also revealed the negative correlation between the age of onset and cortical gyrification in the left inferior parietal gyrus. Also, there was negative correlation between VIQ and cortical gyrification in the left supramarginal gyrus of BECTS patients.Conclusions: This study reveals aberrant cortical thickness, cortical gyrification, and sulcal depth of BECTS in areas related to cognitive functions including language, attention and memory, and the correlation between some brain regions and VIQ and age of onset, providing a potential marker of early neurodevelopmental disturbance and cognitive dysfunction in BECTS.