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Background Epileptic spasms are a devastating form of early infantile epileptic encephalopathy (EIEE) with various etiologies. Early diagnosis and a shorter lead time to treatment are crucial to stop the seizures and optimize the neurodevelopmental outcome. Genetic testing has become an integral part of epilepsy care that directly guides management and family planning and discovers new targeted treatments. Neuronal differentiation Factor 2 (NEUROD2) variants have recently been a cause of neurodevelopmental disorders (NDDs) and EIEEs with distinctive features. However, there is limited information about the clinical and electroencephalographic response of epileptic spasm treatment in NEUROD2-related NDD syndrome. Case presentation We report a female patient of Southeast Asian ethnicity with global developmental delay and epileptic spasms commencing in the first few months of life. A novel de novo heterozygous pathogenic NEUROD2 variant, p. E130Q, was subsequently identified by whole-exome sequencing. Electroencephalogram before treatment showed multifocal independent spikes predominantly in both posterior head regions and demonstrated marked improvement following combined vigabatrin and high-dose prednisolone treatment. However, multiple courses of relapse occurred after weaning off the antiseizure medication. Conclusions We propose that epileptic spasms related to de novo NEUROD2 pathogenic variant respond well to combined vigabatrin and high-dose prednisolone therapy. These findings may imply the benefit of using combination therapy to treat epileptic spasms in NEUROD2-related NDD syndrome.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterized by typical facial dysmorphism, generalized muscle stiffness, joint contracture, and skeletal abnormalities. This condition is caused by mutations in the heparan sulfate proteoglycan 2 ( HSPG2 ) gene, which encodes perlecan, a component of the basement membrane. The management of patients with SJS primarily aims to alleviate symptoms related to muscle stiffness. In this report, we describe a male patient with SJS type 1A. Trio whole-exome sequencing identified a pathogenic mutation (NM_001291860.1: c.10897C>T; p.Arg3633Ter) and variants of unknown significance (NM_001291860.2: c.413+10G>T). The patient experienced difficulty in opening his eyes and mouth, which significantly limited his daily activities. Botulinum toxin A injection was administered and demonstrated significant clinical improvement after the treatment.

ObjectiveTo elucidate the clinical characteristics and standard of care (SoC) of spinal muscular atrophy (SMA) patients in Thailand, focusing on primary endpoints: age at death and a composite of death or tracheostomy need.DesignRetrospective observational study.SettingSeven tertiary centres across Thailand.PatientsRecords of 110 patients with genetically confirmed SMA, spanning 2012–2021.InterventionsHistorical data review; no active interventions.Main outcome measuresAge at death and a composite measure of death or tracheostomy necessity.ResultsThe cohort included 1 SMA0, 50 SMA1, 40 SMA2 and 19 SMA3 cases. Median ages at the onset and diagnosis of SMA1 were 3 and 6.2 months. Of SMA1 patients, 63% required ventilators, and eight received dimethyltryptamines (DMTs) at a median of 15 months (range 6.4–24.5 months). The median time from onset to DMT was 11 months (range 4.2–20.5 months). Among SMA1 patients, 73% died by the study’s end. SMA2 and SMA3 patients' median onset ages were 11 and 24 months, respectively, with diagnosis at 24.8 and 68.7 months. Half of all types received physical therapy.ConclusionsSignificant delays in diagnosis and SoC access, including DMTs, were observed, underscoring urgent needs for improved diagnostic and care strategies to enhance SMA patient outcomes in Thailand.

ObjectiveTo correlate arterial umbilical cord gas (aUCG) and infant blood gas with severity of neurological injury.Study designRetrospective single-site study of infants evaluated for therapeutic hypothermia. Clinical neurological examination and a validated MRI scoring system were used to assess injury severity.ResultsSixty-eight infants were included. aUCG base deficit (BD) and lactate correlated with infant blood gas counterparts (r = 0.43 and r = 0.56, respectively). aUCG and infant pH did not correlate. Infant blood gas lactate (RADJ2 = 0.40), infant BD (RADJ2 = 0.26), infant pH (RADJ2 = 0.17), aUCG base deficit (RADJ2 = 0.08), and aUCG lactate (RADJ2 = 0.11) were associated with clinical neurological examination severity. aUCG and infant blood gas measures were not correlated with MRI score.ConclusionMetabolic measures from initial infant blood gases were most associated with the clinical neurological examination severity and can be used to evaluate hypoxic-ischemic cerebral injury risk.

Objective The study evaluated the effectiveness of combination therapy with vigabatrin and prednisolone versus vigabatrin alone for treating infantile epileptic spasms syndrome (IESS). Methods This single‐center, single‐blind, randomized trial enrolled infants aged 2–14 months with new‐onset IESS, randomly assigned them (1:1) to receive either combination therapy with vigabatrin (100–150 mg/kg/day) and prednisolone (40–60 mg/day) or vigabatrin alone. The primary outcome was sustained spasm remission between days 14 and 42. The trial (ClinicalTrials.gov identifier) was terminated early due to an interim analysis revealing a significant difference between treatment groups. Results In all, 17 infants were assigned to combination therapy and 24 to vigabatrin alone. The median lead time to treatment for combination therapy was 30 days, compared to 60 days for the vigabatrin group (p = 0.442). Sustained spasm remission between days 14 and 42 occurred in 13 (77%) of 17 infants on combination therapy and in 8 (33%) of 24 infants on vigabatrin alone (OR 6.5, 95% CI 1.7, 29.6, p = 0.009). Combination therapy was more effective in achieving an electroclinical response by day 14 (OR 9.3, 95% CI 2.0, 54.3, p = 0.006) but not by day 42 (OR 1.9, 95% CI 0.5, 7.1, p = 0.351). Hospitalization occurred in six (35%) infants in the combination therapy group and two (8%) in the vigabatrin alone group (p = 0.05). One death was reported in the vigabatrin group. Interpretation Despite early termination, this study showed that combination therapy is significantly more effective in achieving clinical remission of spasms and an electroclinical response by day 14. Trial Registration NCT04302116

Background Sandhoff disease (SD) is an autosomal recessive lysosomal storage disorder, resulting in accumulation of GM2 ganglioside, particular in neuronal cells. The disorder is caused by deficiency of β-hexosaminidase B (HEX-B), due to pathogenic variant of human HEXB gene. Method This study describes clinical features, biochemical, and genetic defects among Thai patients with infantile SD during 2008–2019. Results Five unrelated Thai patients presenting with developmental regression, axial hypotonia, seizures, exaggerated startle response to noise, and macular cherry red spot were confirmed to have infantile SD based on deficient HEX enzyme activities and biallelic variants of the HEXB gene. In addition, an uncommon presenting feature, cardiac defect, was observed in one patient. All the patients died in their early childhood. Plasma total HEX and HEX-B activities were severely deficient. Sequencing analysis of HEXB gene identified two variants including c.1652G>A (p.Cys551Tyr) and a novel variant of c.761T>C (p.Leu254Ser), in 90 and 10% of the mutant alleles found, respectively. The results from in silico analysis using multiple bioinformatics tools were in agreement that the p.Cys551Tyr and the p.Leu254Ser are likely pathogenic variants. Molecular modelling suggested that the Cys551Tyr disrupt disulfide bond, leading to protein destabilization while the Leu254Ser resulted in change of secondary structure from helix to coil and disturbing conformation of the active site of the enzyme. Genome-wide SNP array analysis showed no significant relatedness between the five affected individuals. These two variants were not present in control individuals. The prevalence of infantile SD in Thai population is estimated 1 in 1,458,521 and carrier frequency at 1 in 604. Conclusion The study suggests that SD likely represents the most common subtype of rare infantile GM2 gangliosidosis identified among Thai patients. We firstly described a potential common variant in HEXB in Thai patients with infantile onset SD. The data can aid a rapid molecular confirmation of infantile SD starting with the hotspot variant and the use of expanded carrier testing.