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Background: The current study was planned at a tertiary centre in northern India to develop and validate a Diagnostic and Statistical Manual-5 (DSM-5)-based diagnostic tool and design a severity score for attention deficit hyperactivity disorder (ADHD) in children aged 6-18 years. An existing DSM-IV-based tool, INDT (International Clinical Epidemiology Network [INCLEN] diagnostic tool) for ADHD has been modified and named All India Institute of Medical Sciences (AIIMS)-modified INDT ADHD tool.Method: The first phase was development of the tool and the second phase was validation of the same against the gold standard of diagnosis by the DSM-5. A severity score was developed for ADHD in concordance with the Conners rating scale.Results: The tool was validated in 66 children with a sensitivity and specificity of 100 per cent and 90 per cent, respectively. A cut-off score of 12 was decided for labelling severity of ADHD, which corresponded to 63 in the Conners rating scale.Conclusion: This diagnostic tool for ADHD based on DSM-5 has acceptable psychometric properties. The severity score will be useful for prognostication, monitoring treatment response, and designing intervention trials. [ABSTRACT FROM AUTHOR]

Rare diseases form the bulk of the financial expenditure of any developing or developed economy. Among the various rare diseases, paediatric neuromuscular disorders form a major portion, with a worldwide survey estimating a prevalence of 1 in 3500 individuals. In a lower middle-income country (LMIC) like India, malnutrition still accounts for most of the under-5 mortality. However, the economic burden of rare paediatric neuromuscular disorders cannot be underestimated. The treating physician should have a basic understanding of how to approach a child presenting with weakness and how to utilise the available tests which are affordable in an LMIC setting. History and examination still form the core, and with new diagnostic methods like next-generation sequencing, more and more rare disorders are getting diagnosed. It is important for the treating physician to know about basic supportive care, recent advancements, and available treatment options for these conditions. With exciting new treatment options being available for these disorders, the perception of these diseases as being not treatable is gradually changing. This review aims to be of guidance to clinicians from an LMIC setting like India and to empower them to manage such rare paediatric neuromuscular disorders. [ABSTRACT FROM AUTHOR]

Diagnostic and Statistical Manual of mental disorder-IV (DSM-IV) TR based INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD) is an established instrument for the diagnosis of ASD in Indian subcontinent and low-middle income countries (LMIC). The introduction of DSM-5 necessitated revision of existing INDT-ASD tool to incorporate the DSM-5 related changes. This study was undertaken to develop and validate the DSM-5 based All India Institute of Medical Sciences (AIIMS)-Modified-INDT-ASD Tool. The modifications were done using Delphi method and included: (a) rearrangement of questions from the previous tool; and (b) addition of new questions on sensory symptoms. The modified tool was validated against DSM-5 diagnostic criteria. In addition, receiver operating characteristic (ROC) curves were used to determine the cut-off for total score as compared to Childhood Autism Rating Scale (CARS) score to grade the severity of ASD. Two-hundred-twenty-five children (159 boys, median age = 47months) were enrolled. The modified tool demonstrated sensitivity of 98.4% and specificity of 91.7% to diagnose ASD. A score ≥14 on the tool was suggestive of severe ASD (CARS>36.5) with a sensitivity and specificity of 80% and 80.7% respectively [Area under the curve = 0.89]. AIIMS-Modified-INDT-ASD Tool is a simple and structured instrument based on DSM-5 criteria which can facilitate diagnosis of ASD with acceptable diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Introduction: The role of heavy metals in the etio-pathogenesis of ASD is controversial. Paucity of studies from Indian subcontinent with different sociocultural and environmental background prompted the present study. Methods: Sixty children aged three to 12 years with Autism Spectrum Disorder (ASD) and 60 age matched controls were enrolled. Detailed history including possible exposure history to various heavy metals was taken. Severity of ASD was assessed using Childhood Autism Rating Scale 2. Blood level of metals was estimated by Inductively coupled plasma - atomic emission spectroscopy (ICP-AES). Results: Mean blood mercury levels in the two groups of ASD and controls was comparable (p = 0.28). Median blood cadmium and arsenic levels were higher in controls possibly due to higher ground water use and insecticide exposure. (7/60 versus 17/60, p = 0.04) and (2/60 versus 7/60, p = 0.08) while mean blood zinc level was lower in controls. Lead was significantly higher in greater proportion of children with ASD. (11/60 vs 1/60, p = 0.002). Children with ASD had significantly higher pica (26/60 versus 10/60, p = 0.001) and higher median number of days of antibiotics during infancy (24.5 (0-120) versus 15 (0-60), p = 0.004). None of the heavy metal tested had significant correlation with the severity of ASD. Conclusions: Mean blood mercury, lead, zinc, arsenic and cadmium did not show significant association with diagnosis of ASD. High levels of toxic metals in both children with ASD and controls points towards an urgent need to contain environmental pollution by heavy metals. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to retrospectively collect and then describe the clinico-radiographical profile of confirmed cases of leukodystrophy who presented over a 5-year period to a tertiary care teaching hospital in North India. Materials and Methods: The case records of 80 confirmed cases of leukodystrophy were reviewed and the cases have been described in terms of their clinical presentation and neuroimaging findings. Results: The cases have been grouped into five categories: Hypomyelinating, demyelinating, disorders with vacuolization, cystic, and miscellaneous. The commonest leukodystrophies are megalencephalic leukoencephalopathy with subcortical cysts (MLC), Pelizaeus-Merzbacher disease (PMD), and metachromatic leukodystrophy (MLD). A notable proportion of hypomyelinating disorders were uncharacterized. Conclusions: Leukodystrophies at this point of time have no definite cure. They have a progressively downhill clinical course. Early diagnosis is imperative for appropriate genetic counseling. A simplified approach to diagnose common leukodystrophies has also been provided. It is important to develop a registry, which can provide valuable epidemiological data to prioritize research in this field, which has many unanswered questions. [ABSTRACT FROM AUTHOR]

An epileptic seizure is defined as transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in brain. There are diverse etiologies for acute seizure in infants and children. The present review provides a broad approach to diagnosis and treatment plan for acute seizure in children. The approach to a child with acute seizure is discussed with special emphasis on clinical approach based on history and focused examination with judicious choice of investigation and further management plan. The review also emphasizes on recognizing common nonepileptic events that masquerade as true seizure among infants and children. [ABSTRACT FROM AUTHOR]

Objective: This is a retrospective chart review of consecutive children with acquired demyelinating disorders presenting to a north Indian tertiary care hospital over 4 years. The aim of this review is to describe all the patients (with single event as well as those with recurrences) with detailed description of those who recurred. Materials and Methods: Overall 35 cases were reviewed and their clinical presentations, diagnosis, management, and follow-up are being presented. Results: Out of 35 cases, 24 did not show any recurrences (seven acute disseminated encephalomyelitis (ADEM) and 17 clinically isolated syndromes). Amongst the 11 patients with recurrent demyelination, majority were multiple sclerosis (8/11, 72.7%) followed by neuromyelitisoptica (NMO; 2/11), and multiphasic ADEM (1/11). The median disease duration and follow-up since onset for those with recurrent episodes is 4 years (2.5-4.5 years). Steroids caused significant improvement in acute episodes of demyelination. However, recurrent demyelinating disorders like multiple sclerosis and NMO required long-term immunomodulation. Azathioprine currently is the most favored long-term immunomodulator used in NMO. Interferon-β and glatiramer acetate are currently recommended for multiple sclerosis. However, azathioprine may be a suitable alternative in a resource-limited setting. Conclusion: The consensus definitions for these groups of disorders need further validation in the pediatric age group. Studies with larger population size are required to characterize features that predict future recurrences. [ABSTRACT FROM AUTHOR]

Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures. This was a randomized open-label study conducted at an Indian hospital from August 2008 to April 2009. One hundred forty-one consecutive children aged 6-14 years who presented convulsing to the emergency room were included. After stabilization, the children were randomized to receive either intravenous or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). The primary outcome measure was clinical seizure remission within 10 min of drug administration. The study was registered with clinicaltrials.gov (NCT00735527). Seventy patients were randomized to receive intravenous and 71 to receive intranasal lorazepam. The patients in the two groups were comparable at baseline. Clinical seizure remission within 10 min of drug administration was found in 80% of the intravenous group as compared to 83.1% of intranasal group. The lower limit of 95% confidence interval for effect size was approximately −9.7%, with an a priori cutoff for noninferiority of −10%. Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children. [ABSTRACT FROM AUTHOR]

Fukuyama congenital muscular dystrophy (FCMD) is the most common congenital muscular dystrophy in Japan and there are isolated reports of non-Japanese patients with FCMD. We report an Indian patient with congenital muscular dystrophy and characteristic radiological findings similar to those with FCMD. [ABSTRACT FROM AUTHOR]

Background : Neurodevelopmental abnormalities are common in congenital heart disease (CHD), more so in cyanotic CHDs. Perioperative factors have been known to affect neurodevelopmental outcomes. Aim : We aimed to determine the neurodevelopmental outcomes following open-heart surgery in cyanotic CHD. Methods : In this prospective observational study, eligible infants and children < 21 months with cyanotic CHD planned for open-heart surgery underwent preoperative neurodevelopmental assessment using Developmental Assessment Scale for Indian Infants (DASII) to look for any motor and/or mental delay. A second neurodevelopmental assessment was performed after 9 months ± 2 weeks of cardiac surgery. Follow-up DASII was conducted through interactive video conferencing in 23 of 60 patients due to COVID-19 pandemic. The univentricular and biventricular repair groups were compared in terms of their neurodevelopmental outcomes. Perioperative factors were compared between neurodevelopmental "delay" and "no delay" groups. Results: Of the 89 children enrolled, preoperative motor and mental delay were present in 29 and 24 children, respectively. Follow-up DASII could be performed in 60 children. At follow-up, motor delay was present in seven and mental delay in four children. Overall, there was a significant improvement in both motor and mental developmental quotient at follow-up. There was no significant difference in either motor or mental domains between univentricular and biventricular groups. Among the perioperative variables, only the postoperative length of stay in intensive care unit was significantly different between neurodevelopmental "delay" and "no delay" groups (P = 0.04). Conclusion : Neurodevelopmental delay occurred substantially among unoperated children with cyanotic CHD. The neurodevelopmental status improved significantly following open-heart surgery among the survivors. Delay was associated with length of stay in intensive care following cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disability affecting at least 5 million children in South Asia. Majority of these children are without access to evidence-based care. The UK Pre-school Autism Communication Therapy (PACT) is the only intervention to have shown sustained impact on autism symptoms. It was systematically adapted for non-specialist community delivery in South Asia, as the 'Parent-mediated Autism Social Communication Intervention for non-Specialists (PASS)' and extended 'PASS Plus' interventions. RCTs of both showed feasibility, acceptability and positive effect on parent and child dyadic outcomes. Methods: The Communication-centred Parent-mediated treatment for Autism Spectrum Disorder in South Asia (COMPASS) trial is now a scale-up two-centre, two-arm single (rater) blinded random allocation parallel group study of the PASS Plus intervention in addition to treatment as usual (TAU) compared to TAU alone, plus health economic evaluation embedded in the India health system. Two hundred forty children (approximately 120 intervention/120 TAU) with ASD aged 2–9 years will be recruited from two tertiary care government hospitals in New Delhi, India. Accredited Social Health Activists will be one of the intervention delivery agents. Families will undertake up to 12 communication sessions over 8 months and will be offered the Plus modules which address coexisting problems. The trial's primary endpoint is at 9 months from randomisation, with follow-up at 15 months. The primary outcome is autism symptom severity; secondary outcomes include parent–child communication, child adaptation, quality of life and parental wellbeing. Primary analysis will follow intention-to-treat principles using linear mixed model regressions with group allocation and repeated measures as random effects. The cost-effectiveness analysis will use a societal perspective over the 15-month period of intervention and follow-up. Discussion: If clinically and cost-effective, this programme will fill an important gap of scalable interventions delivered by non-specialist health workers within the current care pathways for autistic children and their families in low-resource contexts. The programme has been implemented through the COVID-19 pandemic when restrictions were in place; intervention delivery and evaluation processes have been adapted to address these conditions. Trial registration: ISRCTN; ISRCTN21454676; Registered 22 June 2018. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to evaluate ENDIT score and develop a novel outcome prediction score for outcome of pediatric convulsive status epilepticus (CSE) at the hospital and 3 months postdischarge. Methods: Children and adolescents aged 1 month to 14 years, presenting with CSE to a tertiary care teaching center in North India from January 2017 to March 2019, were screened for enrollment. In‐hospital and 3‐month postdischarge outcome were defined as poor if Pediatric Cerebral Performance Category Scale (PCPCS) score dropped by ≥2 levels. Results: Overall, 61 patients were enrolled for final analysis after applying exclusion and inclusion criteria. The area under the receiver operating characteristic (ROC) curve for ENDIT score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge was 0.74 (95% confidence interval [CI] = 0.58‐0.89), 0.7 (95% CI = 0.57‐0.83), and 0.72 (95% CI = 0.6‐0.82), respectively. Based on predictors in the present cohort that were significantly different between good and poor outcome cases at the hospital and 3 months postdischarge, a new six‐point score named PEDSS (pre–status epilepticus PCPCS, background electroencephalographic abnormalities, drug refractoriness, semiology, and critical sickness) was developed. The area under ROC curves for PEDSS score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge were 0.93 (95% CI = 0.87‐0.99), 0.8 (95% CI = 0.7‐0.9), and 0.89 (95% CI = 0.8‐0.96), respectively. The best cutoff PEDSS scores for predicting mortality and poor outcome at the hospital and at 3 months postdischarge were ≥4, ≥3, and ≥3, respectively. Significance: The PEDSS score has high predictive accuracy for mortality and differentiating good from poor outcome at the hospital and 3 months postdischarge in pediatric CSE. Future studies should be planned to validate it in various geographical and health care settings and in adults. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disability affecting at least 5 million children in South Asia. Majority of these children are without access to evidence-based care. The UK Pre-school Autism Communication Therapy (PACT) is the only intervention to have shown sustained impact on autism symptoms. It was systematically adapted for non-specialist community delivery in South Asia, as the ‘Parent-mediated Autism Social Communication Intervention for non-Specialists (PASS)’ and extended ‘PASS Plus’ interventions. RCTs of both showed feasibility, acceptability and positive effect on parent and child dyadic outcomes. Methods: The Communication-centred Parent-mediated treatment for Autism Spectrum Disorder in South Asia (COMPASS) trial is now a scale-up two-centre, two-arm single (rater) blinded random allocation parallel group study of the PASS Plus intervention in addition to treatment as usual (TAU) compared to TAU alone, plus health economic evaluation embedded in the India health system. Two hundred forty children (approximately 120 intervention/120 TAU) with ASD aged 2–9 years will be recruited from two tertiary care government hospitals in New Delhi, India. Accredited Social Health Activists will be one of the intervention delivery agents. Families will undertake up to 12 communication sessions over 8 months and will be offered the Plus modules which address coexisting problems. The trial’s primary endpoint is at 9 months from randomisation, with follow-up at 15 months. The primary outcome is autism symptom severity; secondary outcomes include parent–child communication, child adaptation, quality of life and parental wellbeing. Primary analysis will follow intention-to-treat principles using linear mixed model regressions with group allocation and repeated measures as random effects. The cost-effectiveness analysis will use a societal perspective over the 15-month period of intervention and follow-up. Discussion: If clinically and cost-effective, this programme will fill an important gap of scalable interventions delivered by non-specialist health workers within the current care pathways for autistic children and their families in low-resource contexts. The programme has been implemented through the COVID-19 pandemic when restrictions were in place; intervention delivery and evaluation processes have been adapted to address these conditions. Trial registration: ISRCTN; ; Registered 22 June 2018. [ABSTRACT FROM AUTHOR]

This article discusses a case of congenital myasthenia syndrome (CMS) caused by a novel DPAGT1 gene mutation. CMS is a group of myasthenia syndromes that result from impaired transmission at the neuromuscular junction due to defective proteins. DPAGT1 is a gene responsible for glycosylation, and mutations in this gene can lead to CMS. The patient in this case was a 10-year-old girl who presented with proximal weakness and limited craniobulbar involvement. Next-generation sequencing revealed a compound heterozygous pathogenic mutation in DPAGT1, confirming the diagnosis of CMS. The patient showed significant improvement with treatment using pyridostigmine. This article provides valuable insights into the genetic basis and clinical presentation of CMS caused by DPAGT1 gene mutations. [Extracted from the article]

Background: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden.Methods and Findings: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population.Conclusions: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions. [ABSTRACT FROM AUTHOR]

Background: The economic burden of autism is substantial and includes a range of costs, including healthcare, education, productivity losses, informal care and respite care, among others. In India, approximately, 2 million children aged 2-9 years have autism. Given the likely substantial burden of illness and the need to identify effective and cost-effective interventions, this research aimed to produce a comprehensive cost of illness inventory (COII) suitable for children with autism in South Asia (India) to support future research.Methods: A structured and iterative design process was followed to create the COII, including literature reviews, interviews with caregivers, pilot testing and translation. Across the development of the COII, thirty-two families were involved in the design and piloting of the tool. The COII was forward translated (from English to Hindi) and back translated. Each stage of the process of development of the COII resulted in the further refinement of the tool.Results: Domains covered in the final COII include education, childcare, relocation, healthcare contacts (outpatient, inpatient, medical emergencies, investigations and medication), religious retreats and rituals, specialist equipment, workshops and training, special diet, support and care, certification, occupational adjustments and government rebates/schemes. Administration and completion of the COII determined it to be feasible to complete in 35 minutes by qualified and trained researchers. The final COII is hosted by REDCap Cloud and is a bilingual instrument (Hindi and English).Conclusions: The COII was developed using experiences gathered from an iterative process in a metropolitan area within the context of one low- and middle-income country (LMIC) setting, India. Compared to COII tools used for children with autism in high-income country settings, additional domains were required, such as complimentary medication (e.g. religious retreats and homeopathy). The COII will allow future research to quantify the cost of illness of autism in India from a broad perspective and will support relevant economic evaluations. Understanding the process of developing the questionnaire will help researchers working in LMICs needing to adapt the current COII or developing similar questionnaires. [ABSTRACT FROM AUTHOR]

Acute-onset ophthalmoplegia is a perplexing diagnosis in a young child. When the full-blown picture of ophthalmoplegia, ataxia, and areflexia is evident, the diagnosis of Miller-Fisher syndrome (MFS), a variant of Guillain-Barre syndrome (GBS), is almost certain. However, the same is not true for isolated external ophthalmoplegia as it is etiologically heterogeneous. Only anecdotal case reports of childhood-onset acute ophthalmoplegia exist in the literature. Adult series suggest that acute onset external ophthalmoplegia is often immune-mediated and is secondary to anti-GQ1b antibodies. We present a 30-month-old boy with acute-onset bilateral external ophthalmoplegia with highly elevated serum anti-GQ1b antibodies. The child had a rapid and complete recovery with intravenous immunoglobulin. A review of all published cases of childhood anti-GQ1b antibody syndrome was performed. The case highlights that anti-GQ1b antibody syndrome should be considered even in young children with acute-onset external ophthalmoplegia. The disease has a favorable prognosis. The majority improve on conservative management. Treatment with steroids or IVIG may be considered in some after weighing the risks and benefits. [ABSTRACT FROM AUTHOR]

Background: Trace elements have been implicated in pathogenesis of epilepsy. Studies till date have shown altered levels of serum trace elements in children with epilepsy.Objective: The objective of the current was to estimate serum levels of trace elements in children with well-controlled and drug refractory epilepsy and compare it with controls.Methodology: In a tertiary care teaching hospital of North India, serum selenium, copper, zinc, and iron were estimated in well-controlled and drug refractory epileptic children aged 2-12 years and compared with age and gender matched controls.Results: A total of 106 children with epilepsy (55 drug refractory and 51 well controlled) and 52 age and gender matched controls were included in the study. Serum selenium and copper were significantly decreased in cases compared to controls. After classifying epilepsy into well-controlled and drug refractory cases, only in the latter the significant difference for serum selenium and copper levels remained compared to controls. Additionally, in the drug refractory cases, serum iron levels were significantly reduced compared to controls.Conclusions: Serum trace elements are altered in children with epilepsy (more so in the drug refractory group) compared to controls. Monitoring of serum trace elements in children with epilepsy should be considered. Up to one-third of epilepsy is drug refractory of which only another third are amenable to surgery. It is worth investigating the therapeutic potential of altered micronutrient status in these patients. [ABSTRACT FROM AUTHOR]

Drooling is a challenging situation to manage especially in neurologically impaired pediatric population. Numerous surgical procedures have been described in literature but none of them is standardized. We evaluate the effectiveness of bilateral submandibular duct rerouting and sublingual gland excision in drooling paediatric patients. Prospective interventional study was conducted from November 2007 to September 2009 in twenty-eight pediatric patients with drooling who had failed conservative treatment modalities. Patients underwent bilateral submandibular duct transposition and sublingual gland excision. Patients were assessed pre-operatively, at 7, 30 and 90 days after surgery for drooling severity, frequency as per Thomas-Stonell and Greenberg classification and also number of bibs changed per day. Result was categorized using Wilkie and Brody criteria for assessing effectiveness of the surgery. Twenty-eight patients were successfully operated. All patients were followed-up for a duration of at least 3 months. The success rate achieved in term of control of drooling was 95.2 % at 3 months follow up. Statistically significant difference ( p < 0.001) was noted in pre-operative and postoperative mean values for severity and frequency of drooling and also bibs/day. Transient, minor complications (n = 5/28, 17.8 %) were encountered following this surgical procedure. Bilateral submandibular duct rerouting and sublingual gland excision in drooling paediatric patients is a simple and effective surgery with minor operative morbidity. Concomitant sublingual gland excision bilaterally helps in reducing the incidence of ranula formation significantly. [ABSTRACT FROM AUTHOR]

Sir, Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome and can affect multiple organ systems. Except for the recent study by Sudarshan et al., no population-based studies or large observational studies in TSC have been published from India.[[2]] We diagnosed 85 cases of TSC from 2015 to 2019, details of which are summarized in [Table 1]. [Extracted from the article]

X-linked myopathy with excessive autophagy (XMEA) is a rare, recently characterized type of autophagic vacuolar myopathy caused by mutations in the VMA21 gene. It is characterized by slowly progressive weakness restricted to proximal limb muscles and generally has a favorable outcome. The characteristic histological and ultrastructural features distinguish this entity from other mimics, notably Danon disease. XMEA is an under recognized disease and should be considered in the differentials of slowly progressive myopathy in children. Awareness of this rare entity is also important for the pathologists in order to distinguish it from other causes of vacuolar myopathy in view of its favourable prognosis. We report the first genetically confirmed case of XMEA from India in an 8-year-old boy which was diagnosed based on the characteristic light microscopic and ultrastructural findings on muscle biopsy and subsequently confirmed by mutation analysis. The differential diagnostic considerations are also discussed. [ABSTRACT FROM AUTHOR]

Background: Valproate is a commonly used anticonvulsant drug. Uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT) contributes to around 50% of valproate metabolism and its polymorphisms may be important for explaining the considerable variation in valproate levels in patients with epilepsy. Aim: This study was aimed to analyze the genetic polymorphisms of UGT1A6 in Indian children with epilepsy and their potential influence on the pharmacokinetics of valproate. Setting and Design: This cross-sectional study was carried out in the Department of Pediatrics, All India Institutes of Medical Sciences (AIIMS), New Delhi, between March 2011 and July 2012. Materials and Methods: Children aged 3-12 years diagnosed with epilepsy on valproate monotherapy for at least 1 month were enrolled. They underwent a detailed clinical examination. The UGT1A6 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Random samples were checked by genetic sequencing. The steady-state plasma concentrations of valproate were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A6 polymorphisms. Results: A total of 80 children were studied. The prevalence of UGT1A6 T19G was as follows: TT (45%), TG (38.8%), and GG (16.3%); that of UGT1A6 A541G was: AA (48.8%), AG (38.8%), and GG (12.5%); and that of UGT1A6 A552C was: AA (43.8%), AC (40%), and CC (16.3%). The association between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes could not be studied reliably in this small study population. Conclusions: The frequencies of UGT1A6 geneotypes and alleles were reported in the study population. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of delayed myelination with dysthyroidism, specifically Allan-Herndon-Dudley syndrome (AHDS). AHDS is an X-linked disorder that presents with developmental delay, feeding difficulties, seizures, and other symptoms due to a defect in the MCT8 transporter, which leads to central hypothyroidism and peripheral hyperthyroidism. The article describes the case of a 5½-year-old boy with intellectual disability, stiffness of limbs, and abnormal twisting movements. The boy had a mutation in the SLC16A2 gene, which is associated with AHDS. The article also discusses the differential diagnoses and treatment options for this condition. [Extracted from the article]

Abstract: Background: Information on peripheral neuropathy in children with cystic fibrosis is scanty. The etiology can be multifactorial (micronutrient deficiency, chronic hypoxia, impaired glucose tolerance, immunological, vasculopathic, critical illness). Methods: Forty five cystic fibrosis children aged 1–18years on vitamin E supplementation for at least 6months underwent detailed neurological examination, serum vitamin E, vitamin B12, folate, copper levels and detailed nerve conduction studies. Results: The mean age of the study population was 8.35years (±4.9years) with 62.2% being males. Overall 22 out of 45 (48.88%,CI: 33.7–64.2) had electrophysiological evidence of peripheral neuropathy which was predominantly axonal (86.4%), sensory (50%), and polyneuropathy (95.45%). There was no significant association between status of serum micronutrients and electrophysiological evidence of peripheral neuropathy. Conclusion: Patients with cystic fibrosis have electrophysiological evidence of peripheral neuropathy (predominantly axonal, sensory and polyneuropathy). There is significant association of higher chronological age with occurrence of peripheral neuropathy. [Copyright &y& Elsevier]

Purpose The aim of this study was to evaluate the efficacy of the modified Atkins diet in a randomized controlled trial in children with refractory epilepsy. Methods Children aged 2-14 years who had daily seizures despite the appropriate use of at least three anticonvulsant drugs were enrolled. Children were randomized to receive either the modified Atkins diet or no dietary intervention for a period of 3 months. The ongoing anticonvulsant medications were continued unchanged in both the groups. Seizure control at 3 months was the primary end point. Analysis was intention to treat. Adverse effects of the diet were assessed by parental reports (ClinicalTrials.gov Identifier: NCT00836836). Key Findings Among a total of 102 children, 50 were in the diet group and 52 in the control group. Four children discontinued the diet before the study end point, and three children in the control group were lost to follow-up. The mean seizure frequency at 3 months, expressed as a percentage of the baseline, was significantly less in the diet group: 59 ± 54 (95% confidence interval [ CI] 44-74.5) versus 95.5 ± 48 (95% CI 82-109), p = 0.003. The proportion of children with >90% seizure reduction (30% vs. 7.7%, p = 0.005) and >50% seizure reduction was significantly higher in the diet group (52% vs. 11.5%, p < 0.001). Constipation was the most common adverse effect among children on the diet (23, 46%). Significance The modified Atkins diet was found to be effective and well tolerated in children with drug-refractory epilepsy. [ABSTRACT FROM AUTHOR]

Fungi are a relatively uncommon cause of brain abscess in neonates and early infancy. They are usually associated with predisposing factors like prematurity, low birth weight, use of broad-spectrum antibiotics, and prolonged stay in the intensive care unit. Candida tropicalis (C. tropicalis) is rapidly emerging as a nosocomial threat in the neonatal intensive care settings. This case report describes a neonate with C. tropicalis brain abscess who was diagnosed early and managed aggressively with a favorable outcome. Inadvertent use of intravenous antibiotics can have serious complications such as invasive fungal infection. Correct microbiological diagnosis is the key to successful treatment of deep-seated pyogenic infection. Fungal etiology should always be studied in relevant clinical settings. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux (GER) disease is a significant comorbidity of neuromuscular disorders. It may present as paroxysmal dyskinesia, an entity known as Sandifer syndrome. A 6-week-old neonate presented with very frequent paroxysms of generalized stiffening and opisthotonic posture since day 22 of life. These were initially diagnosed as seizures and he was started on multiple antiepileptics which did not show any response. After a normal video electroencephalogram (VEEG) was documented, possibility of dyskinesia was kept. However, when he did not respond to symptomatic therapy, Sandifer syndrome was thought of and GER scan was done, which revealed severe GER. After his symptoms got reduced to some extent, a detailed clinical examination revealed abnormal facies with flaccid quadriparesis. Muscle biopsy confirmed the diagnosis of a specific congenital myopathy. On antireflux measures, those episodic paroxysms reduced to some extent. Partial response to therapy in GER should prompt search for an underlying secondary etiology. [ABSTRACT FROM AUTHOR]

Hyperekplexia, an underdiagnosed motor paroxysm of infancy, mimics epilepsy closely. It is hallmarked by episodic and excessive startle response, brief episodes of intense, generalized hypertonia, or stiffness in response to unexpected auditory and/or tactile stimuli right from birth. Though a seemingly benign entity with an excellent prognosis, hyperekplexia has been occasionally associated with recurrent apneas, feeding difficulties, and sudden infant death syndrome (SIDS). We describe three unrelated children with hyperekplexia (two SLC6A5; one GLRA1). All three children had the onset of motor paroxysms from the neonatal period and were initially labeled as drug-resistant epilepsy leading to a variable diagnostic delay, the longest being 2.5 years. An excellent response to oral clonazepam with a good neurodevelopmental outcome was observed. The lack of habituation on the nose-tapping test is a simple clinical clue to the diagnosis. Early differentiation from epilepsy minimizes treatment cost, allays caregiver anxiety, and empowers them with abortive measures. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The present study aimed to determine the pattern of prescription of antiepileptic drugs (AEDs) in a cohort of patients with epilepsy (PWE) attending a tertiary care center of North India. MATERIALS AND METHODS: Demographic variables including age, gender, age at onset, type and frequency of seizures, and prescription of all AEDs (dose and duration) were noted. Descriptive analysis of the use of AEDs was done, and their different combinations were studied. RESULTS: A total of 1187 prescriptions were evaluated. Demography showed 65.7% of males; mean age of 21.9 years (range: 2–77 years), generalized seizures (53%), and focal seizures (47%). Only 21.8% of the patients were seizure free with no seizure in 1 year of treatment. The five most frequently prescribed AEDs out of 12 AEDs were sodium valproate (VPA) (49.6%), clobazam (CLB) (39.3%), levetiracetam (LEV) (28.4%), carbamazepine (CBZ) (27.3%), and phenytoin (PHT) (26.5%). Monotherapy was effective in 36.6% of the patients. Sodium VPA (39.4%), PHT (25.6%), and CBZ (20.1%) were commonly used as monotherapy. Polytherapy was required in 63.4% of the patients, and most commonly prescribed combinations were PHT + CLB (n = 53), sodium VPA + CLB (n = 62), CBZ + CLB (n = 45), PHT + sodium VPA + CLB (n = 28), and CBZ + sodium VPA + CLB (n = 31). CONCLUSIONS: Polytherapy is a very common practice in our tertiary care center. Sodium VPA, a highly prescribed AED, results in good control of generalized seizures, whereas focal seizures are well controlled by CBZ alone as well as in combination. The present study highlights the commonly prescribed combinations of AEDs resulting in control of different types of seizures. [ABSTRACT FROM AUTHOR]

Objective: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1‐related epilepsy and explored genotype‐phenotype correlations associated with frequently encountered variants. Methods: A cross‐sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. Results: Twenty‐seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two‐thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray‐white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%‐50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. Significance: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence‐based practice is still unavailable. [ABSTRACT FROM AUTHOR]

Lesch-Nyhan syndrome is a rare neurometabolic condition characterized by progressive choreoathetosis, intellectual disability, and peculiar manifestations like self-mutilation. Occasional case reports in adults have suggested an association between Lesch-Nyhan syndrome and hypercoagulability; however, no such report of either a venous or arterial stroke in children with Lesch-Nyhan Syndrome exists in literature. We present a 3-year-old boy with global developmental delay, dystonic posturing, choreoathetoid movements, and self-mutilation involving fingers and lips. He had acute worsening of sensorium, recurrent seizures, and opisthotonous posturing. A diagnosis of Lesch-Nyhan Syndrome was confirmed by extremely low hypoxanthine-guanine phosphoribosyltransferase enzyme levels. In view of an acute neurological deterioration, magnetic resonance imaging brain and magnetic resonance venogram were done that showed sagittal and left transverse venous sinus thrombosis. This case is the first case report of cerebral venous sinus thrombosis in a child with Lesch-Nyhan Syndrome. It further strengthens the association between hypercoagulability and Lesch-Nyhan syndrome. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 10‑month‑old boy who altered sensorium along with right hemiparesis. Topics include considered clinical diagnosis of left middle cerebral artery territory AIS kept and MRI brain confirmed; examines sonography and Doppler of neck vessels, left internal carotid artery are not visualized; and the diagnosis of congenital thrombotic thrombocytopenic purpura, hemolytic uremic syndrome (HUS) considered and clinical exome sequencing are ordered.

The article describes the case of a 10-year-old girl presented with a history of right focal seizures, weakness in the right side of the body, and a week-long absence of speech but without a history of associated medical conditions. Her magnetic resonance imaging (MRI) results suggest the presence of multiple collaterals which led to the diagnosis of moya-moya. A discussion of the cerebrovascular condition moyamoya is also presented.

Background & objectives: Although the need for a combination of antiepileptic drugs (AEDs) in the treatment of epilepsy is well justified, but an associated increase in adverse effects (AEs) lends a restriction to polytherapy. The aim of this study was to evaluate AEs and drug load (prescribed daily dose/defined daily doses) of AEDs in patients with epilepsy (PWE). Methods: Consecutive PWEs attending Epilepsy clinic in a tertiary care hospital in New Delhi, India, were enrolled in the study. Demographic variables, such as age, gender, diagnosis, age at onset of seizures, frequency of seizures, use of all AEDs and adverse event profile (AEP) score were noted. Routine laboratory tests including lipid profile, fasting blood glucose, haematological parameters and liver and kidney function tests were done. Results: A total of 697 consecutive patients were included in this study. Of them, 64.4 per cent were male; mean age was 29.6 ± 10.6 yr. Generalized seizures and focal seizures were recorded in n=386 (55.4%) and n=311 (44.6%), respectively. Monotherapy and polytherapy with two and greater than or equal to three AEDs were prescribed in 264 (37.9%), 243 (34.9%) and 190 (27.2%) patients, respectively. The average AED load, duration of treatment as well as AEP score were found to be significantly higher in combination of greater than or equal to three AEDs as compared to both monotherapy and combination of two AEDs, whereas no significant difference was observed between monotherapy and combination of two AEDs. Patients on monotherapy were in good control of seizures as compared to polytherapy. There was no significant change in biochemical parameters between the groups. Interpretation & conclusions: Polytherapy with combination of greater than or equal to three AEDs was associated with higher AEs and lower seizure control as compared to both monotherapy and combination of two AEDs. AEs did not correlate with AED load, seizure type, gender and age of the patients but were associated with both numbers of AEDs as well as seizure frequency in PWE. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID)/Global developmental delay (GDD) is a diverse group of disorders in terms of cognitive and non-cognitive functions and can occur with or without associated co-morbidities. It affects 1–3% of individuals globally and in at least 30–50% of cases the etiology remains unexplained. The widespread use of chromosomal microarray analysis (CMA) in a clinical setting has allowed the identification of submicroscopic copy number variations (CNVs), throughout the genome, associated with neurodevelopmental phenotypes including ID/GDD. In this study we investigated the utility of CMA in the detection of CNVs in 106 patients with unexplained ID/DD, dysmorphism with or without multiple congenital anomalies (MCA). CMA study was carried out using Agilent 8 × 60 K chips and Illumina Human CytoSNP-12 chips. Pathogenic CNVs were found in 15 (14.2%) patients. In these patients, CNVs on single chromosome were detected in 10 patients while 5 patients showed co-occurrence CNVs on two chromosomes. The size of these CNVs ranged between 322 kb to 13 Mb. The yield of pathogenic CNVs was similar for both mild and severe ID/GDD cases. One patient described in this paper is considered to harbour a likely pathogenic CNV with deletion in 17q22 region. Only few cases have been described in literature for 17q22 deletion and patient reported here was found to have an atypical deletion in 17q22 region (Case 90). This study re-affirms the view point that CMA is a powerful diagnostic tool in the evaluation of idiopathic ID/GDD patients irrespective of the degree of severity. Identifying pathogenic CNVs helps in counseling and prenatal diagnosis if desired. [ABSTRACT FROM AUTHOR]

The article describes the case of a 7-year-old female child who was admitted to a private institution with severe abdominal pain and generalized tonic-clonic seizures. She was diagnosed with primary diffuse leptomeningeal (PDL) supratentorial primitive neuroectodermal tumor (sPNET) based on the biopsy and pathological findings obtained after performing various tests on the girl. The girl received a palliative chemotherapy treatment after being referred to the oncology department. [ABSTRACT FROM AUTHOR]

The article presents a case study of 7‑year‑old boy with Japanese B encephalitis. Topics discussed include production of anti-N-methyl-D-aspartate (NMDA) rector that leads to proliferation of encephalitis conditions in the patient; analysis of Cerebrospinal fluid (CSF) for herpes simplex virus presence through magnetic resonance imaging (MRI); and consideration of the disease as parainfectious autoimmune processes.

The article presents a case study of a 3-year-old boy who developed high-grade fever, focal status epilepticus and laboured breathing. A chest x-ray, bilateral pleural effusion and non-structural protein (NSP) antigen testing were performed. The patient was diagnosed with Dengue fever which triggered hemiconvulsion hemiplegia.

The article presents a case study of a 5-month-old boy with Pelizaeus-Merzbacher disease (PMD). Topics discussed include observation of several symptoms such as pendular nystagmus in the patient, analysis of hypomyelination through brain's magnetic resonance imaging (MRI), confirmation for PMD diagnosis through proteolipid protein 1 (PLP1) gene triplication at Xq22, initiation of PMD with genetic mutation of the PLP1 gene and consideration of hypomyelinating leukodystrophy as PMD among infants.

Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor's information) were noted. Results: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis. [ABSTRACT FROM AUTHOR]

The article presents a case study related to 9‑year‑old boy presented with bilateral lower‑motor‑neuron facial‑palsy, progressive hearing‑loss, and radiating‑pains in legs for 2 months. Topics include neuroimaging revealed bilateral VII and VIII cranial‑nerve enhancement with arachnoiditis, the cerebrospinal fluid (CSF) was meningitic, the CSF serology was positive for Lymes disease, and the child received ceftriaxone and methylprednisolone pulse for arachnoiditis with marginal improvement.

Background: Tuberculous meningitis (TBM) is the most common form of neurotuberculosis and the fifth most common form of extrapulmonary TB. Early diagnosis and prompt treatment are the cornerstones of effective disease management. The accurate diagnosis of TBM poses a challenge due to an extensive differential diagnosis, low bacterial load and paucity of cerebrospinal fluid (CSF) especially in children. Methodology/Principal Findings: We describe the utility of ELISA and qPCR for the detection of Mycobacterium tuberculosis (M. tb) proteins (GlcB, HspX, MPT51, Ag85B and PstS1) and DNA for the rapid diagnosis of TBM. CSF filtrates (n = 532) derived from children were classified as 'Definite'TBM (M. tb culture positive, n = 29), 'Probable and Possible' TBM (n = 165) and 'Not- TBM' including other cases of meningitis or neurological disorders (n = 338). ROC curves were generated from ELISA and qPCR data of 'Definite' TBM and Non-Tuberculous infectious meningitis (NTIM) samples and cut-off values were derived to provide ≥95% specificity. devR qPCR, GlcB, HspX and PstS1 ELISAs showed 100% (88;100) sensitivity and 96-97% specificity in 'Definite' TBM samples. The application of these cut-offs to 'Probable and Possible' TBM groups yielded excellent sensitivity (98%, 94;99) and specificity (98%, 96;99) for qPCR and for GlcB, HspX and MPT51 antigen ELISAs (sensitivity 92- 95% and specificity 93-96%). A test combination of qPCR with GlcB and HspX ELISAs accurately detected all TBM samples at a specificity of ~90%. Logistic regression analysis indicated that these tests significantly added value to the currently used algorithms for TBM diagnosis. Conclusions: The detection of M. tb GlcB/HspX antigens/devR DNA in CSF is likely to improve the utility of existing algorithms for TBM diagnosis and also hasten the speed of diagnosis. [ABSTRACT FROM AUTHOR]

Background: Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutation in the gene encoding for calpain-3 resulting in total or partial loss of protein. Diagnosis of LGMD2A, the most prevalent form of LGMD, is established by analyzing calpain-3 protein deficiency or CAPN3 gene mutation. Since there is no data from India regarding the incidence of LGMD2A, this study was undertaken. Aims: To study the frequency of LGMD2A in Indian population on the basis of protein analysis by immunoblotting and to correlate pathological and clinical features with protein analysis. Settings and Design: One hundred and seventy-one muscle biopsies of clinically suspected LGMD, unclassified muscular dystrophy or myopathy were analyzed in a tertiary national referral centre for neurosciences. Materials and Methods: Histopathological, immunohistochemical and enzyme histochemical analysis of muscle biopsies was performed followed by protein analysis for calpain-3 and dysferlin by immunoblotting. Results: Immunoblot identified 75 patients (43.8%) with calpain-3 deficiency, of which 36 (45%) had complete loss and 39 (55%) had partial loss of calpain-3 protein. In patients with LGMD phenotype alone, the incidence of LGMD2A was 47%. The biopsies of these patients displayed variety of morphological changes ranging from dystrophic pattern with presence of active fibre necrosis, regeneration and lobulated fibres to end stage muscle disease. The mean age of presentation and disease onset was 24 and 18 years respectively. Conclusions: This series of 75 patients is probably the first confirmed cases of LGMD2A (calpainopathy) from India. Our study suggests that LGMD2A is the most frequent form of LGMD in India, similar to the Western data, thus, highlighting the importance of immunoblotting for an accurate diagnosis. [ABSTRACT FROM AUTHOR]