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Background: Vanishing white matter syndrome is one of the leukoencephalopathies caused by recessive mutations in gene EIF2B1-5 . Adult-onset EIF2B-pathies (clinical onset after age 16 years) have been reported to be less common., Objective: Description of the clinical, imaging and genetic profile of adult-onset EIF2B-pathies and comparison of Indian cohort with Asian and European cohorts., Methods: Report of two cases of adult-onset EIF2B-pathies and a comprehensive review of genetically confirmed adult-onset EIF2B-pathies since 2001 from Indian, Asian and European cohorts., Results: Two patients were females, with median age at presentation of 25.5 years (24-27 years) and onset at 19 years (18-20 years). The median duration of symptoms was 6.5 years (6-7 years). Both had cerebellar ataxia, spasticity, cognitive impairment and bladder involvement. Brain magnetic resonance imaging (MRI) showed leukoencephalopathy with rarefaction in both patients and corpus callosum involvement in one patient. Genetics showed homozygous missense variant in the EIF2B3 gene in both patients. The Indian cohort of seven patients had similar clinical and radiological features and common variants in EIF2B3 ( n = 4). The Asian cohort had 24 cases, and the European cohort had 61 cases with similar clinical features, radiological features and common variants in EIF2B5 ., Conclusion: Adult-onset EIF2B-pathies have a distinct clinical profile of female predominance with cerebellar ataxia, spasticity and cognitive decline as the commonest triad of clinical manifestations and leukoencephalopathy with rarefaction on brain MRI. Variants in EIF2B5 were common in the Asian and European cohorts and EIF2B3 in the Indian cohort.

Congenital Muscular Dystrophies (CMD) are phenotypically and genotypically heterogenous disorders with a prevalence of 0.68 to 2.5/100,000, contributing to significant morbidity and mortality. We aimed to study the phenotype-genotype spectrum of genetically confirmed cases of CMD. This was retrospective & descriptive study done at a quaternary care referral centre in south India. Genetically confirmed cases of CMDs seen between 2010 to 2020 were recruited. Detailed clinical history, including pedigree, MRI brain/muscle, next generation sequencing results of 61 CMD cases were collected. Collagen VI-related dystrophy (COL6-RD) (36%) was the most common subtype with variants frequently seen in COL6A1 gene. Other CMDs identified were LAMA2-RD (26%), alpha-dystroglycan-RD (19%), LMNA-RD (8%), CHKB-RD (7%) and SEPN1-RD (3%). Similar to previous cohorts, overall, missense variants were common in COL-6 RD. Variants in triple helical domain (THD) of COL6-RD were seen in 11/22 patients, 5 of whom were ambulatory contrary to previous literature citing severe disease with these variants. However, our follow-up period was shorter. In the LAMA2-RD, 2/16 patients were ambulatory & all 16 carried truncating variants. Among dystroglycanopathies, FKRP-RD was the commonest. Milder phenotype of FKRP- RD was observed with variant c.1343C > T, which was also a recurrent variant in our cohort. p.Arg249Trp variant in LMNA-CMD associated with early loss of ambulation was also identified in 1/5 of our patients who expired at age 2.8 years. The current retrospective series provides detailed clinical features and mutation patterns of genetically confirmed cases of CMD from a single center in India., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Dizziness is a frequent complaint encountered in neurology clinics. Dizziness can be spontaneous or triggered, which includes orthostatic dizziness. Orthostatic dizziness can be acute (reflex/vasovagal syncope), chronic (orthostatic hypotension (OH), or postural orthostatic tachycardia syndrome (POTS). Since dizziness has numerous causes, these patients undergo extensive investigations before a diagnosis is made. Here, we describe five patients who presented with dizziness and were diagnosed to have POTS on evaluation., Materials and Methods: We conducted a retrospective study of patients who presented to the Department of Neurology from August 2020 to November 2021 with the complaint of dizziness and were diagnosed with POTS. The clinical history, neurological examination, treatment response, routine blood investigations, magnetic resonance imaging (MRI) brain, and autonomic function tests (AFTs) of the patients were reviewed from patients' clinical records. Patients with dizziness and with diagnosis other than POTS were excluded from the study., Results: Among the five patients, males were predominant with a male to female ratio of 3:2. All the patients were in their early fourth decade with a mean age of 35.4 years. The presenting symptom was dizziness, and the key associated symptoms were anxiety and headache. Due to the orthostatic nature of symptoms and absence of orthostatic fall in blood pressure (BP), a detailed AFT was carried out, leading to the diagnosis of POTS. Patients were assessed at 3-6 months after treatment and there was a moderate response in one and no response in the remaining four patients., Conclusion: POTS should be considered a possible etiology when patients present with orthostatic dizziness in the absence of orthostatic fall in BP. Anxiety and headache may be associated with this type of dizziness., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Competing Interests: There are no conflicts of interest.

Background: Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking., Objectives: This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation., Methods: A retrospective chart review of genetically confirmed CMs was evaluated between January 2016 and December 2020 at the neuromuscular clinic. The clinical, genetic, and follow-up data were recorded in a pre-structured proforma as per the medical records, and the data was analyzed., Results: A total of 31(M: F = 14 : 17) unrelated patients were included. The median age at onset and duration of illness are 2.0(IQR:1-8) years and 6.0(IQR:3-10) years respectively. Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology was available in 38.7% of patients, and centronuclear myopathy was the most common histopathology finding. The pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%) genes. Novel mutations were observed in 30.3% of the cohort. Follow-up details were available in 77.4% of children, and the median duration of follow-up and age at last follow-up was 4.5 (Range 0.5-11) years and 13 (Range 3-35) years, respectively. The majority were ambulant with minimal assistance at the last follow-up. Mortality was noted in 8.3% due to respiratory failure in Centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON)., Conclusion: This study highlights the various phenotypes and patterns of genetic mutations in a cohort of pediatric patients with congenital myopathy from India. Centronuclear myopathy was the most common histological classification and the mutations in RYR1 followed by DNM2 gene were the common pathogenic variants identified. The majority were independent in their activities of daily living during the last follow-up, highlighting the fact that the disease has slow progression irrespective of the genotype.

Neurodevelopmental disorders (NDDs) are a spectrum of conditions with commonalities as well as differences in terms of phenome, symptomatome, neuropathology, risk factors and underlying mechanisms. Immune dysregulation has surfaced as a major pathway in NDDs. However, it is not known if neurodevelopmental disorders share a common immunopathogenetic mechanism. In this study, we explored the possibility of a shared immune etiology in three early-onset NDDs, namely Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Intellectual Disability Disorder (IDD). A panel of 48 immune pathway-related markers was assayed in 135 children with NDDs, represented by 45 children with ASD, ADHD and IDD in each group, along with 35 typically developing children. The plasma levels of 48 immune markers were analyzed on the Multiplex Suspension Assay platform using Pro Human cytokine 48-plex kits. Based on the cytokine/chemokine/growth factor levels, different immune profiles were computed. The primary characteristics of NDDs are depletion of the compensatory immune-regulatory system (CIRS) (z composite of IL-4, IL-10, sIL-1RA, and sIL-2R), increased interleukin (IL)-1 signaling associated with elevated IL-1α and decreased IL-1-receptor antagonist levels, increased neurogenesis, M1/M2 macrophage polarization and increased IL-4 as well as C-C Motif Chemokine Ligand 2 (CCL2) levels. With a cross-validated sensitivity of 81.8% and specificity of 94.4%, these aberrations seem specific for NDDs. Many immunological abnormalities are shared by ASD, ADHD and IDD, which are distinguished by minor differences in IL-9, IL-17 and CCL12. In contrast, machine learning reveals that NDD group consists of three immunologically distinct clusters, with enhanced neurogenesis, Th-1 polarization, or IL-1 signaling as the defining features. NDD is characterized by immune abnormalities that have functional implications for neurogenesis, neurotoxicity, and neurodevelopment. Using machine learning, NDD patients could be classified into subgroups with qualitatively distinct immune disorders that may serve as novel drug targets for the treatment of NDDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)