BACKGROUND:Myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a distinct immune-mediated neurological disorder requiring specific therapies. The study aims to evaluate relapse patterns, predictors, and compare relapse rates and disability outcomes of common immunotherapies in Indian MOGAD patients. METHODOLOGY:We conducted an observational cohort study of 155 pediatric and adult MOGAD patients, classifying phenotypes into optic neuritis (ON), myelitis (MYE), acute disseminated encephalomyelitis (ADEM), opticomyelitis (OM), brainstem (BS) and others. Annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) scores were calculated pre- and on-treatment for azathioprine (Imuran), mycophenolate mofetil (CellCept) and rituximab. Kaplan-Meier survival analysis and Cox proportional hazards regression identified predictors of relapse. RESULTS:ON (39.4 %) was the most common phenotype though pediatric patients had significantly more ADEM cases (p < 0.001). Over half experienced relapses, more in pediatric (p = 0.011), and ADEM patients (p < 0.001). More frequent relapses correlated with higher EDSS scores at last follow-up (rho=0.442, p < 0.001). MYE patients had the longest relapse-free survival (median 132 months, p < 0.001). Mean(SD) ARR reduced from 1.12(2.00) to 0.26(0.49) with azathioprine (Imuran), from 1.08(2.43) to 0.11(0.54) with MMF (p = 0.006) and from 1.23(2.30) to 0.71(2.01) with rituximab (p = 0.007). EDSS scores significantly improved with all therapies (p < 0.001-0.007). Higher baseline ARR predicted relapse after treatment initiation (HR 1.23[95 % CI,1.05-1.43], p = 0.009), while myelitis at onset was protective (HR 0.22[95 % CI,0.05-0.95], p = 0.042). CONCLUSION:Over half of MOGAD patients relapse, and increased relapses correlate with greater long-term disability. Myelitis at onset is associated with lower relapse risk. Conventional first-line immunotherapies are effective across medications, phenotypes and age groups.

There is a dearth of studies on neuroimaging correlates of Bipolar Disorder (BD) in Multiple Sclerosis (MS). We describe the clinical profile and neuroimaging findings of four cases of MS with BD. Among them, two patients had multiple mood episodes preceding the neurological symptoms, one had concurrent manic and neurological symptoms, and one had multiple depressive episodes and an isolated steroid-induced manic episode. Frontal and temporal lobes, and Periventricular White Matter were involved in all four cases, and hence may be considered biological substrates of BD in MS. Larger studies are needed to validate the utility of these findings.

Galactosaemia is a group of autosomal recessive metabolic disorders characterised by increased blood levels of galactose. It is characterised by cataracts, organomegaly, sepsis and developmental delay. We are reporting a case of galactosaemia presenting as a neurodegenerative disease with a leukodystrophy-like presentation. An 11-month-old boy born to a second-degree consanguineously married couple presented with developmental delay, vomiting, lethargy and refusal of feeds. Examination showed normocephaly, cataract, hepatomegaly and spasticity in all limbs with exaggerated deep tendon reflexes. Magnetic resonance imaging (MRI) of the brain was suggestive of diffuse hyperintensities in periventricular, subcortical and deep white matter on T2WI. Plasma galactose levels were high (3784.0 u M/L) and the RBC Galactose 1-Phosphate uridylyltransferase (GALT) enzyme was low (<0.04). Genetic testing showed homozygous missense mutation c.428C>T (p.Ser143Leu) in exon 5 of the GALT gene. For any child who presents with cataracts, hepatomegaly, developmental delay and leukodystrophy picture on an MRI of the brain, a treatable cause of galactosaemia should be considered.

Ethylmalonic encephalopathy is a rare neurometabolic disorder with central nervous system involvement and vasculopathy. It is presented in infancy with developmental delay, acrocyanosis, petechiae, chronic diarrhea, and early death. This was a retrospective study of confirmed cases of ethylmalonic aciduria from a tertiary care hospital over a period of 5 years from January 2015 to December 2020. Case details including analysis of clinical history, investigations, and outcomes are presented. Of six cases, male-to-female ratio was 4:2. Mean age of presentation was 35.5 months (range: 14-83 months). Consanguinity, global developmental delay, failure to thrive, skin rashes, microcephaly, hypotonia, and exaggerated deep tendon reflexes were observed in all cases. Chronic diarrhea was presented in five cases. The serum levels of C4 carnitine and urinary levels of ethylmalonic acid were increased in all cases. Magnetic resonance imaging (MRI) of the brain showed heterogenous bilateral symmetrical changes in the basal ganglia in five cases, and in one case, MRI could not be done. Genetic testing in two cases showed a homozygous variant in ETHE1 gene. Four children died, while the other two cases showed a decreased in recurrent encephalopathies and diarrhea after starting metronidazole. All children had global developmental delay, failure to thrive, skin rashes, central hypotonia, increased C4 carnitine levels in the serum, and increased ethylmalonic acid in the urine. Chronic diarrhea, acrocyanosis, and basal ganglia change in the MRI of the brain also give important clues for diagnosis. Metronidazole is useful in preventing recurrent episodes of encephalopathy.

Kamath, Sneha Dayanand; Bhat, Maya Dattatraya1; Santhosh, Vani2; Arunachal, Gautham3; AR, Prabhuraj; Kulanthaivelu, Karthik1; Ahmed, Sabha1; Asranna, Ajay; Kenchaiah, Raghavendra Author Information

The clinical symptoms of ADAR gene mutation are heterogenous. Mutation in ADAR gene is associated with Aicardi-Goutières syndrome type 6 (ASG6) which is an autosomal recessive severe infantile encephalopathy with intracranial calcifications, dyschromatosis symmetrica hereditaria (DSH), nonsyndromic bilateral striatal necrosis [ [1] Samanta D. Ramakrishnaiah R. Recurrent encephalopathy with spinal cord involvement: an atypical manifestation of aicardi-goutières syndrome. Ann. Indian Acad. Neurol. 2019 Jan-Mar; 22: 111-115 Crossref PubMed Scopus (9) Google Scholar ]. Hereby, we present a child who developed generalized dystonia with regression of milestones and skin lesion suggestive of pigmentary mosaicism type IV. Genetic analysis showed novel variants in ADAR gene.

Background:To study the efcacy and safety of DMF (Dimethyl fumarate) and factors related to drug response, switching and adherence of DMF in the Indian population. We aimed to evaluate the efcacy, safety and tolerability of DMF in multiple sclerosis (MS). A chart review Methods: was performed for patients treated with DMF in MS from the MS registry maintained at the hospital. We performed analyses to assess relationships between baseline parameters and DMF efcacy, outcome and Expanded Disability Status Scale (EDSS) progression status. The study Results: included 37 patients (median follow-up = 27.5 months). The majority had previously been treated with other Disease modifying therapies -DMTs (59.5%). The average EDSS before DMF was 3.5± 1.8 and average EDSS after minimum 6 months of DMF was 3.01±1.9. During the follow-up period, 10 (27%) patients switched treatment; eight were due to clinical or radiological relapse. None of them had tolerability issues. Conclusions: We conrm that DMF shows a good efcacy in both drug-naïve patients and patients switching from other rst-line DMTs with denite improvement in EDSS.

Background and Objectives X-linked adrenoleukodystrophy (X-ALD) occurs due to the mutation in the ABCD1-gene. Our study was to correlate the clinical, radiological, and biochemical features in a cohort of X-ALD patients. Methods We retrospectively analyzed 48 (M: F: 47:1) biochemically confirmed cases of X-ALD, classified them as cerebral ALD (childhood, adolescent, and adult), adrenomyeloneuropathy, Addisonian only. The Magnetic Resonance Imaging (MRI) of the radiological patterns was classified based on Loes classification. Results The various clinical phenotypes were childhood cerebral X-ALD (58.3%), adolescent cerebral X-ALD (14.6%), adult-cerebral X-ALD (20.8%), Addisonian variant (4.2%), and adrenomyeloneuropathy (AMN) (2.1%). The imaging features were posterior white matter (Pattern-1) observed in 33 (68.75%) patients, cerebellar white matter (Pattern-4) noted in 5 subjects, anterior white matter (Pattern-2) observed in 3 patients, combined parieto-occipital and frontal white matter (Pattern-5) observed in 3 patients, isolated projection fiber (Pattern-3) observed in 1 patient. Rare features of the involvement of optic tract, anterior and lateral columns of cervicodorsal cord, bilateral central tegmental tracts, basal ganglia, and tigroid appearance were observed. Interpretation This is a comprehensive clinical, biochemical, and imaging analysis with follow-up information of one of the largest series of X-ALD patients. The knowledge regarding the clinical features, typical and atypical imaging patterns is of vital importance for early diagnosis and treatment.

Abstract Cribriform appearance of the brain in Canavan disease is a rare finding. The two presented cases broaden the magnetic resonance imaging (MRI) phenotype wherein numerous oval, cystic structures, a few resembling dilated Virchow-Robin (VR) spaces, were noted in the centrum semiovale, periventricular, and lobar white matter producing a cribriform pattern. Besides, discrete round to oval cysts were present at the gray–white matter junctions in the second case, which were larger and appeared morphologically distinct from the VR spaces. These cysts did not elongate in any plane on imaging and were more representative of giant intramyelinic vacuoles. Genetic analysis revealed novel mutations in the aspartoacylase or ASPA gene that possibly accounts for the severe form of Canavan disease, which probably explains the imaging findings. The multicystic appearance of the white matter in Canavan disease is unusual and possibly represents two different histopathological substrates.

Pelizaeus-Merzbacher-like disease 1 (PMLD1) is a slowly progressive leukodystrophy that typically presents during the neonatal or early infantile period with nystagmus, commonly associated with hypotonia, delayed acquisition of motor milestones, speech delay and dysarthria. We present a 7-year-old female born to a nonconsanguineous marriage with developmental delay. On examination, she had 22 teeth, and nystagmus with pseudophakia. Neurological examination showed spasticity with increased deep tendon reflexes. On investigation, MRI of the brain done at 3 years showed hypomyelination. Targeted exome sequencing revealed a homozygous non-synonymous variation c.138C>G in exon 2 of the GJC2 gene. Sanger sequencing was done which showed the presence of a variant in the heterozygous state in both parents. PMLD1 should be suspected in any child presenting with diffuse hypomyelination with abnormal eye movements, especially in a girl child with PelizaeusMerzbacher disease phenotype with hypomyelination in the pons.

A bstract Background: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder due to the deficiency of arylsulfatase A enzyme. Materials and Methods: This is a retrospective analysis of all clinically suspected MLD cases and confirmed by genetics, enzyme assay, and/or nerve biopsy between June 2015 and May 2020 at a tertiary care center. The clinical profile, enzyme levels, nerve conduction studies, MRI of the brain, and variants of ARSA gene causing MLD were analyzed. Results: Out of the 19 cases of MLD, four were juvenile, and the rest were late infantile variants. Eleven were male. The mean age of presentation in the late infantile variant was 28.4 months, and that of the juvenile variant was 44.5 months. The clinical features of the late infantile variant were developmental delay (30.75%), neuroregression (100%), spasticity (66.6%), dystonia (66.6%), small head (60%), whereas the juvenile variant presented with gait difficulties and neuroregression in all (100%), and seizures in 3 (75%). MRI of the brain showed bilateral symmetrical confluent white matter T2 hyperintensities with sparing of subcortical-U-fibers in all cases. The tigroid pattern was seen in two cases. Normal enzyme level was seen in one, but this child had a pathogenic variant PSAP gene resulting in saposin B deficiency. The targeted next-generation sequencing was done in 11/19 cases and showed ARSA gene variant in 10 and PSAP gene in one child. Nerve conduction studies were done in 12 children, and all showed features suggestive of demyelinating motor polyneuropathy. Nerve biopsy showed metachromatic granules in four children. Conclusion: MLD can present with a developmental delay with or without regression, with or without seizures, with normal or small head. MRI and nerve conduction studies are helpful in diagnosis. Normal enzymes do not rule out MLD. Nerve biopsy may be useful in non-affordable families.

Gangliosidoses are progressive neurodegenerative disorders caused by the deficiency of enzymes involved in the breakdown of glycosphingolipids. There are not much data about gangliosidosis in India; hence, this study was planned. The aim is to study the clinical, biochemical, and molecular profile of gangliosidosis. A retrospective chart review, in the pediatric neurology department from January 2015 to March 2020, was performed. Children diagnosed with Gangliosidosis were included. The disorder was confirmed by reduced activity of enzymes and/or pathogenic or likely pathogenic variants in associated genes. We assessed age at presentation, gender, parental consanguinity, clinical manifestations, neuroimaging findings, enzyme level, and pathogenic or likely pathogenic variants. Clinical data for 32 children with gangliosidosis were analyzed, which included 12 (37.5%) with GM1 gangliosidosis, 8 (25%) with Tay-Sachs disease (TSD), 11 (34.37%) with Sandhoff disease (SD), and 1 AB variant of GM2 gangliosidosis that occurs due to GM2 ganglioside activator protein deficiency. Twenty-four (75%) children were the offspring of consanguineous parents. Thirty-one (97%) had developmental delay. The median age at presentation was 15.5 months. Nine (28.12%) had seizures. Five children (41.6%) with GM1 gangliosidosis and two with SD had extensive Mongolian spots. Ten children with GM1 gangliosidosis (83.3%) had coarse facial features. Cherry red spot was found in 24 out of 32 children (75%). All children with GM1 gangliosidosis and none with TSD had hepato-splenomegaly. Two children (2/8; 25%) with TSD and seven (7/11; 63%) with SD had microcephaly. One child with SD had coarse facies and three did not have hepato-splenomegaly. Neuroimaging findings revealed bilateral thalamic involvement in 20 (62.5%) patients and periventricular hypomyelination in all cases. One child had a rare AB variant of GM2 gangliosidosis. GM2 Gangliosidoses are more common compared with GM1 variety. All of them had infantile onset except one child with TSD. Microcephaly can be present while usually megalencephaly is reported in the literature. The absence of hepato-splenomegaly does not rule out SD. Extensive Mongolian spots can be seen in GM2 gangliosidosis. AB variant of GM2 gangliosidosis should be considered when the enzyme is normal in the presence of strong clinical suspicion.