Consensus Statement On Immune Modulation in Multiple Sclerosis and Related Disorders During the COVID-19 Pandemic: Expert Group on Behalf of the Indian Academy of Neurology.

Knowledge related to SARS-CoV-2 or 2019 novel coronavirus (2019-nCoV) is still emerging and rapidly evolving. We know little about the effects of this novel coronavirus on various body systems and its behaviour among patients with underlying neurological conditions, especially those on immunomodulatory medications. The aim of the present consensus expert opinion document is to appraise the potential concerns when managing our patients with underlying CNS autoimmune demyelinating disorders during the current COVID-19 pandemic.

Multiple sclerosis in India: An overview.

Multiple sclerosis (MS) is being increasingly diagnosed in India mainly due to increase in the number of practicing neurologists and easy and affordable availability of magnetic resonance imaging (MRI). The clinical features and course are largely similar to those seen in the West. The term optico-spinal MS (Asian MS) was coined in the pre-MRI days. Many such patients turn out to be cases of neuromyelitis optica - a distinct disorder and not a variant of MS. Others have shown the classical features of MS on MRI scan. Several of the disease-modifying agents, not all, are now available in India. Their use, however, has been limited in view of the high cost.

Asian adaptation and validation of an English version of the multiple sclerosis international quality of life questionnaire (MusiQoL).

INTRODUCTION: The Multiple Sclerosis International Quality of Life questionnaire (MusiQoL) is a self-administered, multi-dimensional, patient-based health-related quality of life (HRQoL) instrument. With increasing prevalence of multiple sclerosis (MS) in Asian countries, a valid tool to assess HRQoL in those patients is needed. The aim of this study was to evaluate patient acceptability, content validity and psychometric properties of an Asian version of the English MusiQoL in Singapore, Malaysia and India. MATERIALS AND METHODS: English speaking patients older than 18 years of age with a defi nite diagnosis of MS were included. The self-administered survey material included the adapted HRQoL questionnaire, a validated generic HRQoL questionnaire: the short-form 36 (SF-36), as well as a checklist of 14 symptoms. We assessed the internal and external validity of the adapted MusiQoL. RESULTS: A total of 81 patients with MS were included in the study. The questionnaire was generally well accepted. In the samples from Malaysia and Singapore, all scales exhibited good internal consistency (Cronbach's alpha >0.70). Correlation to SF-36 was generally good, demonstrating high construct validity (P <0.001) in some aspects of the MusiQoL. CONCLUSION: The Asian adaptation of the English version of the MusiQoL in evaluating HRQoL seems to be a valid, reliable tool with adequate patient acceptability and internal consistency.

Genetic and clinical heterogeneity in eIF2B-related disorder.

Eukaryotic initiation factor 2B (eIF2B)-related disorders are heritable white matter disorders with a variable clinical phenotype (including vanishing white matter disease and ovarioleukodystrophy) and an equally heterogeneous genotype. We report 9 novel mutations in the EIF2B genes in our subject population, increasing the number of known mutations to more than 120. Using homology modeling, we have analyzed the impact of novel mutations on the 5 subunits of the eIF2B protein. Although recurrent mutations have been found at CpG dinucleotides in the EIF2B genes, the high incidence of private or low frequency mutations increases the challenge of providing rapid genetic confirmation of this disorder, and limits the application of EIF2B screening in cases of undiagnosed leukodystrophy.

Megalencephalic leukoencephalopathy with subcortical cysts.

Megalencephalic leukoencephalopathy with subcortical cysts is one of the newly described white-matter disorders for which recognition has been brought about by advances in imaging technology. The essential diagnostic features include megalencephaly noted in infancy, motor disability in the form of spasticity, ataxia, occasional seizures, mild cognitive decline, and slow progression. Magnetic resonance imaging (MRI) shows bilateral extensive white-matter changes with cysts in the temporal regions. Based on the clinical and MRI features, megalencephalic leukoencephalopathy with subcortical cysts can be distinguished from other conditions (ie, Alexander's disease, Canavan's disease, glutaricaciduria type I) that present in infancy with megalencephaly. Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal recessive disorder, and mutations in the MLC1 gene have now been shown to cause this condition. Several genotypic and phenotypic variations have been described. In India, megalencephalic leukoencephalopathy with subcortical cysts occurs predominantly in the Agarwal community. A common mutation in the MLC1 gene has been seen in 31 Agarwal patients, which suggests a founder effect.

Modulation of age at onset in Huntington's disease and spinocerebellar ataxia type 2 patients originated from eastern India.

To identify the genetic modifier(s) that might alter the age at onset in Huntington's disease (HD) we have analyzed variations in GluR6 kainate receptor (GluR6), CA150 gene, Delta2642 and polymorphic CCG repeat variation in huntingtin (htt) gene in 77 HD patients and normal individuals. In addition, variation in the RAI1 gene was analyzed in 30 spinocerebellar ataxia (SCA2) patients and normal individuals to show the possible influence on the age at onset. Multiple regression analysis indicated that variation in GluR6 and CCG repeat genotype might explain 6.2% and 3.1%, respectively, of the variability in the age at onset in HD. Similar analysis with SCA2 patients indicated that RAI1 might explain about 13% of the variability in the age at onset. Specific alleles in GluR6 and CA150 locus were only observed in HD patients.