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Background : While the clinical and immunocytochemical features of sarcoglycanopathies have been reported from India, genetic aspects have not been studied. There is large variation in the sarcoglycan mutations among the studied populations. Aim : To study the spectrum of mutations in sarcoglycan genes (SG). Materials and Methods : Patients fulfilling Bushby's criteria for limb girdle muscular dystrophy were prospectively analyzed. Patients gave their medical history and underwent a clinical examination, serum creatine kinase estimation, electrophysiology, muscle biopsy with immunostaining for alpha, beta, gamma, and delta subunits and mutational analysis using denaturing high pressure liquid chromatography and direct sequencing. Results : Mutations in SG accounted for 26.4% of the cohort of limb girdle muscular dystrophy. The mean age of these 18 patients was 22.5 years. Generally, proximal weakness affected the flexor and adductor compartments of the lower and upper limbs. The clinical profile of various mutations was indistinguishable from each other. Gamma SG mutations were most common, seen in 8 patients, followed by delta SG mutation in 5 patients and alpha mutation in 4 patients, while only 1 patient had mutation in the beta sarcoglycan gene. The most prevalent mutation in the gamma SG gene was 525del T. This is of interest as the mutation has been known to exist only in specific populations. Conclusion : This study, the first mutational analysis of Indian patients with sarcoglycanopathies suggests gamma SG mutations were the most common and the most prevalent mutation in the gamma SG gene was 525del T. [ABSTRACT FROM AUTHOR]

Background: Becker muscular dystrophy (BMD) is caused by mutations in the dystrophin gene with variable phenotypes. Becker muscular dystrophy patients have low levels of nearly full-length dystrophin and carry in-frame mutations, which allow partial functioning of the protein.Aim: To study the deletion patterns of BMD and to correlate the same with reading frame rule and different phenotypes.Setting: A tertiary care teaching hospital.Design: This is a prospective hospital-based study.Materials and Methods: Thirty-two exons spanning different "hot spot" regions using Multiplex PCR techniques were studied in 347 patients. Two hundred and twenty-two showed deletions in one or more of the 32 exons. Out of these, 46 diagnosed as BMD patients were analyzed.Results: Forty-six BMD patients showed deletions in both regions of the dystrophin gene. Out of these 89.1% (41/46) were in-frame deletions. Deletions starting with Exon 45 were found in 76.1% (35/46) of the cases. Mutations in the majority of cases i.e. 39/46 (84.8%) were seen in 3' downstream region (Exon 45-55, distal rod domain). Few, i.e. 5/46 (10.8%) showed deletions in 5' upstream region (Exons 3-20, N-terminus and proximal rod domain) of the gene, while in 2/46 (4.4%) large mutations (>40 bp) spanning both regions (Exons 3-55) were detected.Conclusion: This significant gene deletion analysis has been carried out for BMD patients particularly from Western India using 32 exons. [ABSTRACT FROM AUTHOR]

Introduction/aims: Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and follow-up is limited. The aim of this study is to explore the long-term clinical, investigative, and therapeutic profile of patients with acquired HPNDs., Methods: This study retrospectively analyzed patients from a single tertiary care center with HPND (January 2012 to January 2022). Patients were recruited according to published inclusion and exclusion criteria. Details of clinical features, diagnostic tests, therapeutic interventions, and follow-up were recorded. This study included patients with follow-up of 2 or more years., Results: A total of 32 patients (M = 26, F = 6) were studied. The common clinical features included myokymia, neuropathic or shock-like pain, cramps, sleep disturbances, encephalopathy, cerebellar ataxia, and seizures. A total of 81.25% of patients responded favorably to corticosteroids and membrane stabilizers. Among the nonresponders, five received intravenous immunoglobulin (IVIG), and one received plasma exchange (PLEX). Two patients required rituximab due to poor responses to the above treatments. The mean duration of response was 6 weeks (4-24 weeks) from the initiation of treatment. All patients had favorable outcomes, reaching clinical remission within 1-5 years from the initiation of treatment. Only two patients had relapses. Immunotherapy could be stopped in 78% of patients within 3 years and 100% by 5 years., Discussion: Chronic immunosuppression starting with corticosteroids is required for satisfactory outcomes of HPNDs. These disorders usually run a monophasic course, and relapses are uncommon., (© 2023 Wiley Periodicals LLC.)

Competing Interests: There are no conflicts of interest.

Peripheral neuropathies are traditionally categorized into demyelinating or axonal. It has been proposed that dysfunction at nodal/paranodal region may be a key for better understanding of pathophysiology in patients with immune mediated neuropathies. In last few years, antibodies targeting node and paranode of myelinated nerves have been increasingly detected in patients with immune mediated neuropathies. These patients have clinical phenotype similar common inflammatory neuropathies like Guillain Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy with some additional atypical neurological and systemic features, and they respond poorly to conventional first line immunotherapies like IVIG. This review summarizes the structure of the node, concept and pathophysiology of nodopathies. We provide an overview of clinical phenotypes in patients with specific nodal/paranodal antibodies, along with electrophysiological and other diagnostic features and suggest therapeutic line of management based on current evidence., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Competing Interests: None

Competing Interests: There are no conflicts of interest.

Background: Hereditary muscle disorders are clinically and genetically heterogeneous. Limited information is available on their genetic makeup and their prevalence in India., Objective: To study the genetic basis of prevalent hereditary myopathies., Material and Methods: This is a retrospective study conducted at a tertiary care center. The study was approved by the institutional ethics board. The point of the collection was the genetic database. The genetic data of myopathy patients for the period of two and half years (2019 to mid-2021) was evaluated. Those with genetic diagnoses of DMD, FSHD, myotonic dystrophies, mitochondriopathies, and acquired myopathies were excluded. The main outcome measures were diagnostic yield and the subtype prevalence with their gene variant spectrum., Results: The definitive diagnostic yield of the study was 39% (cases with two pathogenic variants in the disease-causing gene). The major contributing genes were GNE (15%), DYSF (13%), and CAPN3 (7%). Founder genes were documented in Calpainopathy and GNE myopathy. The uncommon myopathies identified were Laminopathy (0.9%), desminopathy (0.9%), and GMPPB-related myopathy (1.9%). Interestingly, a small number of patients showed pathogenic variants in more than one myopathy gene, the multigenic myopathies., Conclusion: This cohort study gives hospital-based information on the prevalent genotypes of myopathies (GNE, Dysferlinopathy, and calpainopathy), founder mutations, and also newly documents the curious occurrence of multigenicity in a small number of myopathies.

Competing Interests: There are no conflicts of interest.

Background: Trigeminal neuralgia (TN) is a painful condition, often leading to poor quality of life., Objective: The aim of this review was to discuss the various treatment modalities for the medical management of TN., Materials and Methods: We reviewed the available literature on TN in clinical databases including PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews, with a specific focus on the pharmacological treatment and newer drugs under development for the treatment of TN., Results: Carbamazepine (CBZ) is the gold standard of treatment for TN. The first-line drugs for the treatment of TN are CBZ and oxcarbazepine (OXC). A proportion of cases (30%) are initially resistant to the first-line drugs. Alternative drugs need to be considered if the first-line drugs are not well tolerated or become ineffective with prolonged therapy. The second-line drugs comprise lamotrigine, baclofen, gabapentin, and pregabalin used as monotherapy or in combination with CBZ/OXC. Botulinum toxin A may be a promising presurgical option. Newer drug like vixotrigine has shown good results in phase two randomized control trials. About 50% of cases develop treatment resistance to oral drugs over the subsequent years of therapy and require surgical options., Conclusion: The first-line drugs for the treatment of TN (irrespective of the age group or type) are CBZ and OXC. Combination therapy with second-line or other drugs may become necessary with poor response to CBZ/OXC, or if adverse events occur. Patients should be offered surgical options if there is poor response or tolerance to the medical therapy., Competing Interests: None

Background: GNE myopathy is widely regarded as a distal myopathy. Involvement of proximal musculature in this condition has not been systematically studied., Methods: The phenotype of genetically confirmed patients with GNE myopathy was analyzed. Fourteen groups of muscles were evaluated with Medical Research Council (MRC) grading and the average muscle scores (AMS:1-10) were calculated., Results: Fully documented AMS data was available in 31 of 65 patients. It showed a consistent pattern of severe weakness of hip adductors, hip flexors, knee flexors, and foot dorsiflexors, with milder weakness of the hip extensors and abductors. The knee extensors were largely unaffected. The proximal weakness appeared early in the course of the disease. Proximal muscle weakness was also present in the remaining 34 patients in whom the data were limited. A variant in exon 13 (c.2179G > A) was very common (81.5%)., Conclusions: The GNE phenotype in this Indian cohort exhibited mixed proximal and distal involvement. Weakness of adductors and flexors of the hip formed an integral part of the phenotype., (© 2020 Wiley Periodicals LLC.)

Neuropathies form an integral part of the symptomatology of leprosy. Neuropathies of leprosy take various forms and shapes. At one end is the cutaneous nerve involvement adjacent to the anaesthetic skin patch and the other is of symmetrical pansensory neuropathy and the devastating sensory ataxia of leprous ganglionits. Lepra reactions add to the spectrum. Hosts immunological status largely decides the clinical manifestations seen in nerves and skin. A wide array of diagnostic techniques like ultrasonography, magnetic resonance neurography, serological markers, molecular tests, skin biopsy and in selected cases, the nerve biopsy with special stains and electron microscopy are obtainable to help the clinical diagnosis. The unsuspecting clinician, lack of community awareness and limited availability of diagnostic tests are important adverse factors in the total outcome. Multi drug therapy is efficacious and corticosteroids reduce the impact of nerve damage in leprosy. The efficacy, dose and duration of corticosteroid therapy are presently inexact and other immune suppressants like azathioprine are being evaluated. Chronic disabilities and residual deficits require attention of multiple specialties. In the coming time, focus on prevention could lead to favourable results. This review will discuss the classification systems, common and uncommon clinical features, diagnostic armamentarium and therapeutic and preventive aspects of neuropathies of leprosy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Chronic immune polyradiculopathies (sensory, motor, and mixed) are uncommon., Methods: In this single-center, retrospective study, the inclusion criteria for participants were progressive sensory ataxia and/or areflexic limb weakness; tibial somatosensory evoked potential (SSEP) abnormalities of the N22 and P40 potentials with normal sensory and motor nerve conduction studies or root involvement, according to magnetic resonance imaging (MRI); and albuminocytological dissociation., Results: Eight patients were included in our study. Two had weakness, two had sensory ataxia, and four had both weakness and ataxia. Patients with weakness had abnormal SSEPs and patients with sensory ataxia also had absent F waves. Electromyography showed chronic denervation. MRI scans confirmed thickening and enhancement of roots. The patients responded to corticosteroid treatment., Discussion: The overlapping clinicoelectrophysiological findings and similarities in radiological and therapeutic responses suggest that these entities are clinical variants of the same disease. The terms CIS(m)P, CI(s)MP, and CISMP (for chronic immune sensory motor polyradiculopathy) could be used to denote the predominant clinical involvement., (© 2020 Wiley Periodicals LLC.)

Objective: Inherited myopathies comprise more than 200 different individually rare disease-subtypes, but when combined together they have a high prevalence of 1 in 6,000 individuals across the world. Our goal was to determine for the first time the clinical- and gene-variant spectrum of genetic myopathies in a substantial cohort study of the Indian subcontinent. Methods: In this cohort study, we performed the first large clinical exome sequencing (ES) study with phenotype correlation on 207 clinically well-characterized inherited myopathy-suspected patients from the Indian subcontinent with diverse ethnicities. Results: Clinical-correlation driven definitive molecular diagnosis was established in 49% (101 cases; 95% CI, 42-56%) of patients with the major contributing pathogenicity in either of three genes, GNE (28%; GNE-myopathy), DYSF (25%; Dysferlinopathy), and CAPN3 (19%; Calpainopathy). We identified 65 variant alleles comprising 37 unique variants in these three major genes. Seventy-eight percent of the DYSF patients were homozygous for the detected pathogenic variant, suggesting the need for carrier-testing for autosomal-recessive disorders like Dysferlinopathy that are common in India. We describe the observed clinical spectrum of myopathies including uncommon and rare subtypes in India: Sarcoglycanopathies ( SGCA/B/D/G ), Collagenopathy ( COL6A1/2/3 ), Anoctaminopathy ( ANO5 ), telethoninopathy ( TCAP ), Pompe-disease ( GAA ), Myoadenylate-deaminase-deficiency-myopathy ( AMPD1 ), myotilinopathy ( MYOT ), laminopathy ( LMNA ), HSP40-proteinopathy ( DNAJB6 ), Emery-Dreifuss-muscular-dystrophy ( EMD ), Filaminopathy ( FLNC ), TRIM32-proteinopathy ( TRIM32 ), POMT1-proteinopathy ( POMT1 ), and Merosin-deficiency-congenital-muscular-dystrophy-type-1 ( LAMA2 ). Thirteen patients harbored pathogenic variants in >1 gene and had unusual clinical features suggesting a possible role of synergistic-heterozygosity/digenic-contribution to disease presentation and progression. Conclusions: Application of clinically correlated ES to myopathy diagnosis has improved our understanding of the clinical and genetic spectrum of different subtypes and their overlaps in Indian patients. This, in turn, will enhance the global gene-variant-disease databases by including data from developing countries/continents for more efficient clinically driven molecular diagnostics., (Copyright © 2020 Chakravorty, Nallamilli, Khadilkar, Singla, Bhutada, Dastur, Gaitonde, Rufibach, Gloster and Hegde.)

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of disorders that cause muscle weakness and also have extramuscular manifestations involving various organ systems; namely the lung, skin, heart, and joints. Previously classified broadly as dermatomyositis (DM) and polymyositis now the spectrum of the disease has evolved into more clinical subtypes. There are now five clinicoserological subtypes recognized worldwide DM, antisynthetase syndrome (AS), overlap myositis (OM), immune mediated necrotizing myopathy (IMNM), and inclusion body myositis. Each of these subtypes has a unique phenotype and specific antibodies associated. With the evolving treatment options from the use of immunosuppressive medications to the use of targeted therapy with biologic agents, and further understanding of the pathogenesis of inflammatory myositis, we may have more effective treatment options. We discuss in this review, various myositis-associated antibodies associated with each clinicoserological subtype of IIM and their role. We also describe the evolving therapies and the evidence for the newer biologic therapies in the treatment of IIMs., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2019 Annals of Indian Academy of Neurology.)

COVID-19 pandemic is ongoing and information on the neurological aspects of this viral infection is being gathered. Neuromuscular manifestations have been reported uncommonly in these early stages of the analysis. This manuscript studies the available information on the neuromuscular manifestations of COVID-19., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2020 Annals of Indian Academy of Neurology.)

Background: Several studies on clinical practice for Duchenne muscular dystrophy (DMD) have been conducted in Western countries. However, there have been only a few similar studies in Asia and Oceania. Here, we investigate the steroid therapy-related clinical practice for DMD among the local experts. In 2015, we conducted a DMD expert survey in Asia and Oceania to acquire information regarding patients with DMD and to assess current clinical practice with the cooperation of Asian and Oceanian Myology Centre, a neuromuscular disease research network., Results: We obtained survey responses from 87 out of 148 clinicians (62%) from 13 countries and regions. In China, 1385 DMD patients were followed-up by 5 respondent neurologists, and 84% were between 0 and 9 years of age (15% were 10-19 years, 1% > 19 years). While in Japan, 1032 patients were followed-up by 20 clinicians, and the age distribution was similar between the 3 groups (27% were 0-9 years, 35% were 10-19 years, 38% were >19 years). Most respondent clinicians (91%) were aware of DMD standard of care recommendations. Daily prednisolone/prednisone administration was used most frequently at initiation (N = 45, 64%). Inconsistent opinion on steroid therapy after loss of ambulation and medication for bone protection was observed., Conclusions: Rare disease research infrastructures have been underdeveloped in many of Asian and Oceanian countries. In this situation, our results show the snapshots of current medical situation and clinical practice in DMD. For further epidemiological studies, expansion of DMD registries is necessary., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Hypothalamic-pituitary-gonadal axis regulates the reproductive system. The overall health and wellbeing of a woman is subject to fluctuations in the sex hormones throughout her lifespan. Menopause, either natural or surgically induced, is often associated with cognitive complaints, especially memory disturbances. Sex hormones, besides affecting the reproductive function, affect the central nervous system in many ways. Here, we aim to review the role of sex hormones in cognition and the current evidence on use of or against menopausal hormonal therapy as a cognition enhancer in women with cognitive disturbances, including those with Alzheimer's disease., Competing Interests: Conflict of interestBoth the authors declare that they do not have any conflict of interest.

Aim: This questionnaire-based national survey is aimed at understanding the patterns of practice of various aspects of central nervous system (CNS) tuberculosis (TB) among neurologists., Settings and Design: Neurology department of a tertiary medical college., Materials and Methods: A questionnaire was sent through email to all practicing neurologists in India. The responses were analyzed., Statistical Analysis: Inferential statistics., Results: In all, 144 responses were received (out of the 853 questionnaires sent). The major discrepancies were in the primary antitubercular drug regimen (HRZE + HR), duration for tubercular meningitis (TBM) [12 months] and tuberculoma (12-18 months) to develop, follow-up (varied), linezolid use (varied), proportion of drug-resistant cases (<25%), and not taking histological aids (91%). The cerebrospinal fluid (CSF) TB polymerase chain reaction (PCR) utility (75%), not using CSF adenosine deaminase [ADA] (58%), the strategy to stop antitubercular drugs, and the use of steroids (77%) were according to guidelines., Conclusion: The present survey, for the first time, provides ground-level evidence of various aspects of CNS TB as practiced by neurologists in India. The major diversity was observed in therapeutics such as the choice of antitubercular drugs, its duration, linezolid use beyond the recommended duration, and knowledge of drug resistance. The monitoring aspects of CNS TB also showed variations. The investigational aspects of CNS TB such as using TB PCR, not using CSF ADA, and regular neuroimaging revealed a good clinical practice. Other CSF parameters require uniformity. This survey thus helps to identify areas of future work in CNS TB in India., Competing Interests: There are no conflicts of interest

Introduction: New-onset refractory status epilepticus (NORSE) is uncommon and almost 50% of cases are cryptogenic. We report the rare development of NORSE following carotid artery stenting (CAS), a procedure which is increasingly being used to treat the carotid stenosis., Materials and Methods: Patients who developed NORSE following CAS for the prevention of stroke over a period of 5 years were analyzed retrospectively. The degree of internal carotid artery stenosis (ICA) was estimated as per the NASCET criteria., Results: We analyzed five patients (age: 56-83 years). NORSE was reported within 30 min to 14 days post-CAS. Status epilepticus was focal in two patients, generalized in two, and one had nonconvulsive status epilepticus. All patients were treated with multiple antiepileptic drugs. Four patients recovered and survived and one succumbed. Two patients had comorbid hypertension and two had diabetes and hypertension. Four patients had hemiparesis due to the contralateral middle cerebral artery territory infarction and one patient had syncope. Two patients had postinfarction gliosis., Conclusions: We report a new cause of NORSE, following CAS. Stroke resulting in gliosis and cerebral hyperperfusion syndrome are the proposed mechanisms., Competing Interests: There are no conflicts of interest.

Background: The majority of people afflicted with epilepsy live in developing countries. Poor adherence to prescribed medication is considered the main cause of unsuccessful drug treatment for epilepsy. Our study aims to evaluate the factors influencing medication adherence in epilepsy patients at a public hospital in Mumbai, India., Method: This cross-sectional study was carried out on a cohort of 313 epilepsy patients regularly attending an out-patient clinic at a tertiary-care hospital. A semi-structured questionnaire was used to assess demographic information, the level of medication adherence, and various factors that could influence adherence. Brief Illness Perception Questionnaire and WHO QoL-BREF Scale were also administered to the study population., Results: Patients on anti-epilepsy medication reported an overall good quality of life and a good level of adherence. 90.1% of study participants reported being adherent with their treatment regimen. The main factors found to impact medication adherence were the duration of non-availability of medications in the public sector, and the monthly cost of the medications in the private sector. Other therapy-related, health system-related, socioeconomic, and psychosocial variables were not found to be significant determinants of medication nonadherence in our setting., Conclusion: Ensuring that anti-epilepsy drugs remain available in the public sector, and/or making them more affordable in the private sector are the main interventions likely to improve medication adherence in clinical settings such as ours., (© Journal of the Association of Physicians of India 2011.)

The expansion of the spectrum of limb girdle muscular dystrophies (LGMDs) in recent years means that neurologists need to be familiar with the clinical clues that can help with their diagnosis. The LGMDs comprise a group of genetic myopathies that manifest as chronic progressive weakness of hip and shoulder girdles. Their inheritance is either autosomal dominant (LGMD1) or autosomal recessive (LGMD2). Their prevalence varies in different regions of the world; certain ethnic groups have documented founder mutations and this knowledge can facilitate the diagnosis. The clinical approach to LGMDs uses the age at onset, genetic transmission and clinical patterns of muscular weakness. Helpful clinical features that help to differentiate the various subtypes include: predominant upper girdle weakness, disproportionate respiratory muscle involvement, distal weakness, hip adductor weakness, 'biceps lump' and 'diamond on quadriceps' sign, calf hypertrophy, contractures and cardiac involvement. Almost half of patients with LGMD have such clinical clues. Investigations such as serum creatine kinase, electrophysiology, muscle biopsy and genetic studies can complement the clinical examination. In this review, we discuss diagnostic clinical pointers and comment on the differential diagnosis and relevant investigations, using illustrative case studies., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Systematic and quantitative evaluation of the plantar reflex has been infrequently studied in the past and can help assess the vexing variables encountered in its elicitation. The objective of this study was to determine the effect of type, pattern and force of stimulation in eliciting an accurate plantar response in patients with pyramidal dysfunction and healthy individuals., Patients and Methods: A special instrument was designed to give a predesigned force of stimulus. The plantar surface of foot was divided into nine parts and point and stroke stimulations were studied systematically in pyramidal weakness feet (cases) and healthy control feet (controls) with predefined forces. Results were tabulated and statistically analysed., Results: Stroke stimulation was superior to point stimulation in eliciting plantar response. There was no significant difference in the responses to the three predefined forces used for stroke stimulations. Sensitivity of Babinski sign was 72.9% and specificity was 100%. In pyramidal weakness feet, extensor responses were significantly elicited from lateral starting stroke patterns (67%) and on moving medially they were replaced by flexor responses (44%). Withdrawal responses increased with the stimulations reaching the distal foot and with the curvilinear component of stimulations. Sensitivity responses (related to the sensitivity of an individual) contaminate the plantar response and occasionally make its interpretation difficult. In subjects with bilateral sensitivity with unilateral disease, knowing the sensitivity pattern on the normal side improved the interpretation of plantar response on the abnormal side., Conclusions: Based on this study, the optimal method for eliciting Babinski sign accurately is to stroke the lateral aspect of the sole of the foot in a straight line up to mid foot. This should be performed in both feet three times, and if the weakness is unilateral, it should be performed in the normal leg first to aid interpretation of the affected leg., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: GNE myopathy is an adult onset recessive genetic disorder that affects distal muscles sparing the quadriceps. GNE gene mutations have been identified in GNE myopathy patients all over the world. Homozygosity is a common feature in GNE myopathy patients worldwide., Objectives: The major objective of this study was to investigate the mutation spectrum of GNE myopathy in India in relation to the population diversity in the country., Materials and Methods: We have collated GNE mutation data of Indian GNE myopathy patients from published literature and from recently identified patients. We also used data of people of Indian subcontinent from 1000 genomes database, South Asian Genome database and Strand Life Science database to determine frequency of GNE mutations in the general population., Results: A total of 67 GNE myopathy patients were studied, of whom 21% were homozygous for GNE variants, while the rest were compound heterozygous. Thirty-five different mutations in the GNE gene were recorded, of which 5 have not been reported earlier. The most frequent mutation was p.Val727Met (65%) found mainly in the heterozygous form. Another mutation, p.Ile618Thr was also common (16%) but was found mainly in patients from Rajasthan, while p.Val727Met was more widely distributed. The latter was also seen at a high frequency in general population of Indian subcontinent in all the databases. It was also present in Thailand but was absent in general population elsewhere in the world., Conclusion: p.Val727Met is likely to be a founder mutation of Indian subcontinent.

Background: Charcot-Marie-Tooth (CMT) disease is clinically and genetically heterogeneous. There are no published series describing clinical, electrophysiological, and genetic information on CMT from the Indian subcontinent. Magnetic resonance imaging (MRI) neurography technique provides useful information about the plexus and roots and can be employed in patients with CMT., Settings and Design: A prospective, observational study carried out at a tertiary care hospital in Western India., Subjects and Methods: CMT patients fulfilling the UK Genetic Testing Network criteria were included. They underwent clinical, electrophysiological, radiological, and multigene panel testing., Results: Totally 22 patients (19 males, 3 females; 18 sporadic and 4 familial cases) were studied. Pes cavus (19), hammer toes (16), and scoliosis was seen in 1 patient. Electrophysiology revealed motor predominant neuropathy with 15 demyelinating (10 uniform and 5 multifocal) and 7 axonal patterns. Thickened lumbosacral plexuses on MRI neurography were evident in 6/10 studied patients, all 6 having demyelinating neuropathy. Genetic analysis identified PMP22, GJB1, SH3TC2, HSPB1, SPTLC2, MPZ, AARS, and NEFH gene mutations., Conclusions: This small series documents the pattern of CMT neuropathies as seen in Western India. Clinico-electrophysiological and genetic diagnosis showed general concordance some overlaps and reiterated advantages of gene panel testing in this heterogeneous group of neuropathies. MRI neurography was useful as an additional investigation to detect nerve enlargement in patients with demyelinating neuropathies., Competing Interests: There are no conflicts of interest.

Background: Limb-girdle muscular dystrophy (LGMD) is the most common adult-onset class of muscular dystrophies in India, but a majority of suspected LGMDs in India remain unclassified to the genetic subtype level. The next-generation sequencing (NGS)-based approaches have allowed molecular characterization and subtype diagnosis in a majority of these patients in India., Materials and Methods: (I) To select probable dysferlinopathy (LGMD2B) cases from other LGMD subtypes using two screening methods (i) to determine the status of dysferlin protein expression in blood (peripheral blood mononuclear cell) by monocyte assay (ii) using a predictive algorithm called automated LGMD diagnostic assistant (ALDA) to obtain possible LGMD subtypes based on clinical symptoms. (II) Identification of gene pathogenic variants by NGS for 34 genes associated with LGMD or LGMD like muscular dystrophies, in cases showing: absence of dysferlin protein by the monocyte assay and/or a typical dysferlinopathy phenotype, with medium to high predictive scores using the ALDA tool., Results: Out of the 125 patients screened by NGS, 96 were confirmed with two dysferlin variants, of which 84 were homozygous. Single dysferlin pathogenic variants were seen in 4 patients, whereas 25 showed no variants in the dysferlin gene., Conclusion: In this study, 98.2% of patients with absence of the dysferlin protein showed one or more variants in the dysferlin gene and hence has a high predictive significance in diagnosing dysferlinopathies. However, collection of blood samples from all over India for protein analysis is expensive. Our analysis shows that the use of the "ALDA tool" could be a cost-effective alternative method. Identification of dysferlin pathogenic variants by NGS is the ultimate method for diagnosing dysferlinopathies though follow-up with the monocyte assay can be useful to understand the phenotype in relation to the dysferlin protein expression and also be a useful biomarker for future clinical trials., Competing Interests: There are no conflicts of interest.

Background: Mechanical thrombectomy (MT) is the most effective treatment in large vessel occlusion (LVO). We have analyzed our initial experience of MT of 137 patients in anterior circulation (AC) and posterior circulation (PC) LVO using Solitaire stent retriever device., Methods: Retrospective cohort analysis of 112 AC and 25 PC acute ischemic strokes was done considering various baseline characteristics, risk factors, National Institute of Health Stroke Scale (NIHSS) change, revascularization rate, complications, and functional outcome at 3 months using modified Rankin score., Results: Out of 137 patients, occlusion was found in M1 segment (44.5%), carotid T occlusion (37.2%), and basilar artery (18.2%). Atrial fibrillation was important risk factor for Carotid T occlusion. 50.4% patients received intravenous thrombolysis. Baseline mean NIHSS in AC was 15.5 (±4.32), and PC was 19 (±5.5). Tandem lesions were noted in 14.6%. There was significant difference in mean door-to-needle time for AC and PC (220 ± 80.6 and 326 ± 191.8 min, respectively). Mean time to revascularization for AC (39.5 ± 14.1) and PC (42.2 ± 19.4) was similar. Procedural success (modified thrombolysis in cerebral infarction ≥2b) observed in AC and PC was 92.9% and 84%, respectively ( P = 0.154). NIHSS at admission between 5 and 15 and immediate postprocedure NIHSS improvement >4 was associated with significant better clinical outcome at 3 months. Overall complication rate was about 15.3% including symptomatic intracranial hemorrhage in 8.1% and 6.6% deaths., Conclusion: MT is safe treatment and equally effective for both AC and PC LVO. With careful patient selection, clinical outcome in PC was comparable to AC despite delayed presentation and higher baseline NIHSS., Competing Interests: There are no conflicts of interest.