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BACKGROUND: Anti-glutamate decarboxylase 65 antibody-associated cerebellar ataxia (anti-GAD65Ab-associated CA) is the most widely studied immune-mediated CA. There are few case series evaluating the clinical, radiological, treatment profile, and outcome of anti-GAD65Ab-associated CA. OBJECTIVE: To study the clinical, radiological profile, associated neoplasm, treatment outcome, and prognosis in patients diagnosed with anti-GAD65Ab-associated CA. METHODS: A retrospective descriptive analysis of a cohort of patients diagnosed with anti-GAD65Abassociated CA was performed and analyzed. RESULTS: Thirteen patients were selected for the analysis with female predominance (70%). The mean age at presentation was 47.5 ± 11.1 years (range, 29-65 years), and the median duration of the symptoms was 4 months. All 13 patients (100%) had gait ataxia. Ten patients had limb ataxia along with gait ataxia (75%). Seven patients had cerebellar dysarthria (54%). Four patients (31%) had gazeevoked jerky nystagmus. Five patients (39%) were diagnosed with type 2 diabetes mellitus, and one patient had hypothyroidism in addition to type 2 diabetes mellitus. Brain magnetic resonance imaging was normal in seven (54%) patients, and pure cerebellar atrophy was observed in six patients. One patient was detected with a colon neoplasm. All 13 patients received intravenous methylprednisolone, followed by oral steroids over 3 months. Six patients (50%) received plasma exchange along with intravenous methylprednisolone. Favorable outcomes (modified Rankin scale score =2) were observed in five patients and poor outcomes in two; six patients were lost to follow-up after the first admission. CONCLUSION: Anti-GAD65Ab-associated CA presents as subacute to chronic progressive CA with a favorable outcome with immunotherapy. Anti-GAD antibodies should be assessed in serum or cerebrospinal fluid in patients presenting subacute to chronic sporadic CA. The occurrence of a systemic neoplasm is rare in anti-GAD65Ab-associated CA. [ABSTRACT FROM AUTHOR]

De Sanctis-Cacchione syndrome (DCS) formerly known as xerodermic idiocy is characterised by cutaneous photosensitivity, microcephaly, mental retardation, short stature, hypogonadism, spasticity, peripheral neuropathy and sensorineural deafness. Here in, we present the case of a four and half years old male child with features of severe acute malnutrition (SAM) with a typical bird like facies and sunken eyes who had history of photosensitive pruritic pigmentary skin lesions on sun exposed areas from a very early age of six months. Gross developmental delay, ataxia, microcephaly, short stature, hypogonadism and cachectic wasting were identified on examination and hypertransaminasemia and hypothyroidism were recorded from biochemical profile. Subsequent visual evoked response and brainstem evoked response audiometry revealed anterior visual pathway dysfunction and bilateral profound sensorineural hearing loss. Magnetic resonance imaging of brain yielded subdural effusion with mass effect in addition to cerebro-cerebral atrophy and demyelination. Skin biopsy further detected dysplastic changes and early signs of squamous cell carcinoma (SCC). Although few cases are reported sporadically throughout the world, to our best of knowledge till date only 11 such cases have been reported completely in Indian medical literature which makes our case report the 12th one with distinctive novel association of subdural effusion. [ABSTRACT FROM AUTHOR]

Objective: The course of various cerebellar ataxia disorders in our population is relatively unexplored, especially beyond the hereditary spinocerebellar ataxias (SCA). This study was conducted to objectively assess the severity and progression of various disorders causing the cerebellar ataxia. Materials and Methods: This longitudinal prospective study evaluated the etiologies and the corresponding severity and progression of the cerebellar ataxia. Clinical examination and the relevant investigations were performed. The severity of ataxia was assessed using the Scale for Assessment and Rating of Ataxia (SARA) - at initial presentation and another at 6 months of follow-up, and the change in SARA scores were calculated to find the disease progression. Results: Out of 145 patients studied, SCA predominated followed by Autoimmune/paraneoplastic disorders, Multiple System Atrophy-Cerebellar (MSA-C), Wilson's disease, and Multiple sclerosis. On follow-up, human immunodeficiency virus (HIV) associated progressive multifocal leukoencephalopathy was the most rapidly advancing disease, followed by MSA-C, Friedreich's ataxia, and Huntington's disease, all of which progressed faster than SCA. SCA 3 emerged as the most progressive SCA followed by SCA 1, SCA 6, SCA 2, and SCA 12. The autoimmune etiologies showed favorable response to treatment, although with some variability across the different disorders. In the paraneoplastic category, anti Tr associated ataxia improved better than other disorders. Multiple sclerosis and other treatable disorders also responded to treatment. Conclusion: Cerebellar ataxia is the predominant clinical feature in a wide variety of disorders. While some are progressive, others are responsive to treatment, the extent of which differed according to the etiology. [ABSTRACT FROM AUTHOR]

Objective: Although previous studies have described phenomenological diagnoses, they lacked description of aetiological spectrum in patients visiting movement disorders (MD) service. Herein, we classify the MD phenomenology and describe aetiology wise distribution of each phenomenology in patients visiting a tertiary care movement disorders service., Methods: Collected information included demographic profile (age of onset, age at presentation, gender, duration of illness before presentation), predominant MD phenomenology [such as parkinsonism, dystonia, ataxia, tremor, chorea, ballism, myoclonus, tics, stereotypy, restless legs syndrome (RLS) and others], diagnostic evaluations and detected aetiology., Results: This observational study included 1140 MD patients over a span of 5 years. The median (IQR) age of onset was 49 (35-60) years and age at presentation was 54 (40-65) years, with median duration of illness being 36 (18-72) months. Nearly two-third of patients were males (M:F=731:409). Parkinsonism (n=494, 43.3 %) was the most common MD phenomenology observed, followed by dystonia (n=219, 19.2 %), ataxia (n=125, 11 %), tremor (n=118, 10.4 %), myoclonus (n=73, 6.4 %), chorea (n=40, 3.5 %), spasticity (n=22, 1.9 %), tics (n=8, 0.7 %), and RLS (n=8, 0.7 %). Thirty-three (2.9 %) patients were grouped under miscellaneous MDs. Overall, neurodegenerative disorders (57.4 %) were the most common cause of MDs. Parkinson's disease, genetic dystonia, essential tremor, genetic ataxias, hemifacial spasm, and Huntington's disease were the most common aetiologies for parkinsonism, dystonia, tremor, ataxia, myoclonus, and chorea, respectively., Conclusion: Parkinsonism was the most common phenomenology observed in MD patients, and was followed by dystonia, ataxia and tremor. Neurodegenerative disorders were the most common aetiology detected., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The objective of this study is to analyse detailed clinical presentations, imaging findings, and outcome in a series of 17 cases (n = 17) with neurological complications following acute varicella infection. Methods: It is an observational study on the patients who presented to the neurology outpatient department of our institute with neurological abnormalities following acute varicella infection within the last 3 months. Results: Neuroimaging, either computed tomography or magnetic resonance imaging, cerebrospinal fluid analysis, electroencephalography and nerve conduction studies were performed in all the patients along with other specialized investigations as per clinical context. The age of presentation varied from childhood to middle age (median age was 23 years) and range of clinical spectrum was also wide. Peripheral nervous system involvement was more common in the form of Guillain--Barré syndrome (29.4%) and isolated lower motor neuron facial nerve palsy (23.5%) compared to central nervous system (CNS) involvement. CNS involvement was documented in the form of ataxia (11.76%), myelopathy (17.6%), stroke (5.88%) and encephalitis (5.88%). Conclusion: Chickenpox is a common viral disease and most patients recover without any complication. Although rare, neurological complications following acute varicella infection may have myriad presentations ranging from lower motor neuron facial palsy to life-threatening encephalitis. Compared to other studies, varicella encephalitis and ataxia were not so common in our study group. Response to therapy was uniformly good except in the patients presenting with ataxia. Response was particularly good to central and peripheral demyelinating disorders. [ABSTRACT FROM AUTHOR]

Background: Various neurological manifestations have been described in relation to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and coronavirus disease 2019 (COVID‐19). However, the development of cerebellar ataxia after recovery from COVID‐19 is rare. We present a case of cerebellar ataxia 3 weeks after recovery from COVID‐19. Case Presentation: A 70‐year‐old male patient from an urban area of India presented with ataxia. He was hypertensive and had been receiving treatment for post‐traumatic epilepsy for the previous 3 years. He had previously had laboratory‐confirmed COVID‐19 infection with mild symptoms that resolved within 2 weeks. However, 3 weeks after symptom improvement, he developed severe pan‐cerebellar ataxia. Investigations were suggestive of post‐infectious cerebellar ataxia. Other causes of ataxia were excluded. He responded well to pulse methylprednisolone therapy and was discharged with mild tremor and ataxia. Conclusion: Post‐infectious cerebellar ataxia is an unusual presentation after COVID‐19. The clinician should be aware of such complications following COVID‐19 infection as early diagnosis and proper management leads to better outcomes in many patients. [ABSTRACT FROM AUTHOR]

Background: Movement disorders constitute a major burden among the neurological disorders. Overall prevalence and distribution of disorders requiring medical resources remain unknown. Objective: To understand the pattern of movement disorders burden in India. Materials and Methods: Retrospective electronic database review of new patients attending movement disorders clinics in three cities from 2012 to 2018 was done. Results: 14,561 patients (M:F-9,578:4,983) with mean age at assessment of 60.5 ± 14.9 years (Range: 1–98 years) were analyzed. The major broad syndromic diagnosis included: Parkinsonism (n = 9560, 64.9%), Dystonia (n = 2159, 14.8%), Tremors (n = 1129, 7.7%), Ataxia (n = 475, 3.3%), Chorea (n = 402, 2.7%), Peripheral induced movement disorders (n = 400, 2.7%), Gait Disorders (n = 156, 1.1%), Tics (n = 112, 0.8%), Restless Leg Syndrome (n = 89, 0.6%), and Myoclonus (n = 58, 0.4%). The syndromic diagnosis also included the functional disorders (0.6%). Conclusion: This large database from India show the burden of different movement disorders in tertiary clinics. In addition, it also gives insight into disorders requiring more resources for evaluation and management. [ABSTRACT FROM AUTHOR]

Autosomal dominant leukodystrophy is an adult onset neurodegenerative disorder presenting with progressive symptoms of ataxia and autonomic dysfunction in fourth or fifth decade in life. It has clinical similarity with multiple sclerosis, but shows characteristic magnetic resonance imaging findings of diffuse bilaterally symmetrical leukodystrophy which can distinguish this disorder. It is a rare disorder with no known treatment till date, and has never been described from the Indian subcontinent. We present an Indian family with autosomal dominant adult-onset demyelinating leukodystrophy with multiple members affected over four generations, and demonstrate a cheap and accurate molecular method of real-time polymerase chain reaction to detect the LMNB1 gene duplication, which is the genetic basis of this devastating disorder. [ABSTRACT FROM AUTHOR]

Background: Anti α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis is a rare autoimmune encephalitis. They present with memory, confusion or behavioral changes.Objective: The aim of this study was to describe unusual clinical features in a patient with AMPAR-associated encephalitis.Case: A 42-year-old female presented to us with bulbar and gait disturbances of three weeks duration and behavioral changes for ten days. She was found to have memory impairment along with psychosis. She had left eye ptosis, restricted eye movements, sluggish deep tendon reflexes, and bilateral cerebellar signs. Her serum and CSF (cerebrospinal fluid) AMPAR2 antibodies were strongly positive; CT (computed tomography) chest showed evidence of Thymoma. She was treated with steroids with significant improvement initially but expired within 3 months of diagnosis.Conclusion: This is the first report of AMPAR associated encephalitis from India presenting with unique clinical features affecting both the CNS (central nervous system)--(psychosis, ataxia, cognition) and PNS--peripheral nervous system involvement (ptosis, restricted eye movements, bulbar disturbances). [ABSTRACT FROM AUTHOR]

A case study of an eight‑year‑old boy born to consanguineous marriage is brought with developmental delay, recurrent falls, seizures, behavioral abnormality, and unresponsiveness with fever in the last 20 days. Topics include riboflavin and child has a significant improvement in development, which may be due to medications or spontaneous health recovery; and child presenting with developmental delay, and muscle enzymes, a diagnosis of childhood myocerebrohepatopathy should be considered.

Background Fragile X-associated Tremor/Ataxia syndrome (FXTAS) is a clinically heterogeneous disorder characterized predominantly by tremor, followed by late onset gait ataxia, autonomic dysfunction and/or cognitive impairment. We aimed to screen FMR1 -CGG repeats in our cohort of progressive late-onset cerebellar ataxia/tremor cohort to characterize the occurrence of FXTAS in India. Methods We have screened FMR1 -CGG repeats in 109 patients and 173 healthy control subjects. Our cohort comprised: a)group of patients with predominant cerebellar ataxia and/or tremor. b.)suspected cases of MSA and c.)patients who presented SCA12-like neurological manifestations (late onset predominant tremor and/or ataxia). All the cases were ruled out for known triplet-repeat-expansion (TRE) SCA mutations. Results We have found three FMR1 -premutation carriers among the cases. Two of them (with CGG-96 and CGG-102) were under evaluation for their SCA12-like manifestations and another (CGG-78) had progressive gait ataxia. Overall the frequency of FXTAS in our cohort was found to be 3.3% among cases of late onset cerebellar-ataxia/tremor; however, incidences were higher among cases with SCA12-like syndrome (9%, 2/23). Conclusion Finding FXTAS in patients with SCA12-like manifestation suggests that TRE in the 5′UTR of the gene is the common cue connecting two disorders with common phenotype of tremor/ataxia. This knowledge might shed light upon their sharing of molecular neuropathology. [ABSTRACT FROM AUTHOR]

Objectives: To study the self-perceived changes in occupational performance of clients using Canadian occupational performance measure (COPM). (Quantitative Analysis) To analyze the factors influencing the client centered care (Qualitative Analysis). Method: Study design of case studies was used.3 clients diagnosed with neurodegenerative conditions (senile dementia, progressive ataxia, multiple sclerosis) were quantitatively assessed on Canadian Occupational Performance Measure (COPM) and were intervened for 6 weeks using the client cantered practice. Qualitative analysis was carried out based on the data collected through semi structured interview, patient observation, and field notes to formulate themes and categories so as to get an insight into the factors affecting client centred practice. Results1.Quantitative results show increase in performance scores and satisfaction scores.2.Qualitative analysis provides insight into client's perspective(values and beliefs)and also helps understanding the socio- cultural and contextual factors that affect occupational performance and satisfaction. Conclusion For an effective client centred care, it is essential to consider both quantitative and qualitative factors that guide the program [ABSTRACT FROM AUTHOR]

Bhat V, Girimaji SC, Mohan G, Arvinda HR, Singhmar P, Duvvari MR, Kumar A. Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations. Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7. We have previously reported genetic analysis of 35 families, including the identification of the MCPH7 gene STIL. Of the 35 families, three families showed linkage to the MCPH2 locus. Recent whole-exome sequencing studies have shown that the WDR62 gene, located in the MCPH2 candidate region, is mutated in patients with severe brain malformations. We therefore sequenced the WDR62 gene in our MCPH2 families and identified two novel homozygous protein truncating mutations in two families. Affected individuals in the two families had pachygyria, microlissencephaly, band heterotopias, gyral thickening, and dysplastic cortex. Using immunofluorescence study, we showed that, as with other MCPH proteins, WDR62 localizes to centrosomes in A549, HepG2, and HaCaT cells. In addition, WDR62 was also localized to nucleoli. Bioinformatics analysis predicted two overlapping nuclear localization signals and multiple WD-40 repeats in WDR62. Two other groups have also recently identified WDR62 mutations in MCPH2 families. Our results therefore add further evidence that WDR62 is the MCPH2 gene. The present findings will be helpful in genetic diagnosis of patients linked to the MCPH2 locus. [ABSTRACT FROM AUTHOR]

The article describes the case of a 16-year-old boy from Bangalore, India with cortical blindness, left focal motor seizures which progressed to epilepsia partialis continua (EPC), and mild ataxia who died four weeks after the onset of illness. A list of differential diagnoses for the patient is presented, including acute fulminant subacute sclerosing panencephalitis (SSPE) and angiotropic B-cell lymphoma. The teenager had received empirical anti-tuberculous therapy for cervical lymphadenopathy for five months.

Friedreich ataxia (FRDA), the most common type of ataxia worldwide, is an autosomal recessive disease. Homozygous expansion of GAA repeats in the first intron of the frataxin gene constitute the major type of mutation that causes the disease. The prevalence of FRDA in diverse ethnic populations of India has not been widely studied. We have studied the distribution of polymorphic GAA repeats in the frataxin gene among 6 clinically diagnosed patients and 160 ethnically matched normal individuals, to gather information on the prevalence of FRDA in the eastern part of India. Homozygous expansion in the range of 250–730 GAA repeats was detected among the patients. Among normal individuals, we observed a unimodal distribution of GAA repeats, consisting of 10 different alleles ranging from 7 to 16 GAA repeats, where the 9 repeat allele had maximal frequency. Only 5.9% of all chromosomes were found to harbour >12 GAA repeats. Haplotype analysis using closely linked four bi-allelic markers in and around the frataxin gene indicated that 66.7% of the expanded alleles harbour the ATCC haplotype that has been reported worldwide. This haplotype was present in 53.3% of the chromosomes with >12 GAA repeats, and accounted for only 3.8% of chromosomes with 7 to 12 GAA repeats. We found one novel haplotype, ACCT, among the expanded alleles as well as among normal individuals, though at low frequency; this haplotype may be characteristic of Indian populations. [ABSTRACT FROM AUTHOR]

We report here a case of 18 year old male with tremors of hands, deafness, tendency to fall while walking, drowsiness and double vision of total duration 1(1/2) years. He had internuclear ophthalmoplegia, broken saccades, hypertonia and hyperreflexia of all four limbs, intention tremors, signs of gait and limb ataxia. Pupillary reactions and fundus examination were normal and signs of meningeal irritation or sensory neurological deficit were absent. MRI head and cervical spine with gadolinium enhancement revealed demyelination as evident from multiple oblong foci isointense on T1-weighted images and hyperintense on T2-weighted and fluid attenuated inversion recovery sequences in corpus callosum, sub-cortical white matter, right thalamus, pons and periaqueductal region of midbrain. Ill-defined linear hyperintense signals were observed in cervical spinal cord. No skeletal abnormality was noted in the skull or cervical spine. Oligoclonal bands were present in the cerebrospinal fluid. Brainstem auditory evoked potentials were abnormal, although visual evoked potentials were in normal range. A diagnosis of primary progressive multiple sclerosis (PPMS) was made fulfilling the revised criteria as laid down. In view of its presentation, it is a unique case of PPMS from India. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence, clinical and molecular genetic characteristics of cerebellar ataxia in an ethnic Tamil community in India.Methods: An epidemiological study of cerebellar ataxia was done in two villages in the Indian state of Tamilnadu where its prevalence was observed to be high. All the people were screened and the clinical characteristics of those with ataxia were recorded. Genetic analysis was done in those with ataxia and in two asymptomatic control groups - group I belonging to the affected community and group II belonging to the unaffected community. The clinical and genetic results are correlated. Measures to help the community are suggested.Results: The total population of the two villages was 378. Among them 345 belonged to Vanniyakula Kshatriyar community and 33 to another. Cerebellar ataxia was found in 25 individuals belonging only to the former community (7.2%). The mean age of onset was 39.8 years and the salient features were ataxic gait (100%), dysarthria (100%), pyramidal signs (72%), slow saccades (48%) and bleeding diathesis (12%). Genetic studies were done in 17 of the study group. All showed pathological expansion of CAG repeats above 40, in chromosome 6p, diagnostic of SCA1. 7 of the 18 in the control group (I) and none in control group (II) had CAG repeats above 40.Conclusion: The prevalence of SCA1 is high (7.2%) in this ethnic Tamil community with a large asymptomatic group waiting to manifest. The symptomatic individuals need social support and rehabilitation. Appropriate counseling, prenatal evaluation and therapy will prevent the spread of disease to the next generation. [ABSTRACT FROM AUTHOR]

Cognitive decline and epilepsy are well recognized complication of Down syndrome (DS). Here, we intend to present a case of 28 year old male who presented with progressive mental regression, gait ataxia and myoclonic jerking especially on awakening in morning. His EEG was normal and karyotyping revealed trisomy of chromosome 21. Very few cases had been described in literature of late-onset myoclonic epilepsy in DS. This is first case report from India and our aim is to propose the inclusion of this entity in the spectrum of progressive myoclonic epilepsies but still more cases are yet to be found. [ABSTRACT FROM AUTHOR]

The article pays tribute to Noshir Hormusjee Wadia, a pioneer in Indian neurology.

Introduction: Megalencephalic leucodystrophy with subcortical cysts(MLC) is a rare form of leucodystrophy described in particular ethnic group(Agarwals)in India. It is an autosomal recessive disease due to mutation in MLC -1 gene (22q13.33) characterized by megalencephaly, early onset ataxia followed by slowly progressive spasticity, occasional seizures and mild to moderate cognitive decline. MRI brain shows early and severe cerebral white matter involvement with subcortical cysts in the temporal lobes and fronto-parietal areas. It is non-progressive variety and the prognosis is good. Management is based on physical and psychomotor therapy and treatment of seizures. Identification of MLC-1 mutation is the only way of prenatal diagnosis. Case Summary: We present here a genetically confirmed case of 7yrs old, Agarwal boy, born of non -consanguinous marriage, delivered through caeserian section due to large head size. The child had normal motor and mental milestones till three years of age when he developed slowly progressive gait and limb ataxia and generalized seizures. There is no family history. MRI brain revealed diffuse white matter changes with bilateral temporal and frontal cortical cysts. Genetic testing revealed MLC-1 gene mutation. [ABSTRACT FROM AUTHOR]

Aim and Objectives: Multiple Sclerosis may have varied presentation. The Multiple Sclerosis can present Relapsing Remitting Multiple Sclerosis (RRMS), Primary Progressive Multiple Sclerosis (PPMS), Secondary Progressive Multiple Sclerosis (SPMS), Progressive Relapsing Multiple Sclerosis (PRMS) and Neuromyelitis Optica (NMO). Aim of this study was to define clinical type of Multiple Sclerosis and their radiological spectrum. Method: Forty seven consecutive subjects of Multiple Sclerosis who fulfilled clinical, radiological and electro-physiological criteria of Multiple Sclerosis and NMO were included. They were classified into different types depending upon their clinical presentation and radiological findings. Patient presenting with acute attack received one gram methylprednosolone for five days. Twelve patients of RRMS received mitoxantrone as secondary prophylaxis and three received interferon alpha. Result: We evaluated 47 patients of MS, among which 61.70% (29/47) were females and 38.30% (18/47) were male. Among these patients, RRMS comprised 83% (39/47), PPMS 8.51% (4/47), SPMS 2.12% (1/47) and NMO 6.37 % (3/47). Among these 39 cases of RRMS males were 33.33% (13/39) and females 66.77% (26/39), and among PPMS cases males were 75.00% (3/4) and females 25.00 %(1/4). However only one patient was of SPMS and three were of NMO. These patients presented to us within 3-5 years mean duration of illness in 56.41% (22/39), only one patient presented to us within one year. This might be due to referral bias at our institute. Presenting symptom in RRMS was optic neuritis in 38.46% (15/39), others being sensory deficit in 21% (8/39), paraparesis in 20.51% (8/39), bladder involvement in 17.94% (7/39), hemiparesis in 5.13% (2/39), monoparesis in 5.13% (2/39), quadriparesis in 5.13% (2/39), facial weakness in 5.13% (2/39) and ataxia in 7.69% (3/39). MRI was suggestive of brain involvement in 56% while both brain and spine MRI were abnormal in 44%. VEP was done in 26 patients and was abnormal in 87% (24/26)while BAER was done in 17 patients and was abnormal in 71%(12/17). Oligoclonal bands were done in 9 RRMS patients and were found to be positive in 67 % (6/9). Two out of three patients of NMO had more than three relapses. Conclusion: RRMS was the commonest type of MS at our centre. Incidence of SPMS and NMO was very low. Most common presenting symptom in RRMS cases were optic neuritis. [ABSTRACT FROM AUTHOR]

The article presents the author's comments on the article "High Prevalence of Spinocerebellar Ataxia Type 1 in an Ethnic Tamil Community in India," by R. Rengaraj, M. Dhanaraj, T. Arulmozhi, B. Chattopadhyay and N.P. Battacharyya, published in the September 2005 issue of the journal "Neurology India." As per the author, India is an ethnically and religiously diverse population. The ethnic diversity may have a bearing on the prevalence of spinocerebellar ataxia (SCA) subtypes. The study report a high prevalence of SCA1 in an ethnic Tamil Vanniyakula Kshatriyar community. It seems SCA1 is typically an Indian disease. However this needs to be confirmed by other studies.

Nearly a thousand mutations mapping to 60 different loci have been identified in cerebellar ataxias. However, almost 50% of the cases remain genetically uncharacterized and there is a difference in prevalence as well as in the phenotypic spectrum of ataxia among various geographical regions. This poses a challenge for setting up a genetic panel for screening ataxia. In our ataxic cohort of 1014 families, 61% are genetically uncharacterized (UC). We investigated the potential of whole exome sequencing in conjunction with homozygosity mapping (HM) to delineate the genetic defects in three uncharacterized families with recessive inheritance each manifesting some unusual phenotype: (i) infantile onset ataxia with hearing loss (IOAH), (ii) Juvenile onset cerebellar ataxia with seizures (JCS) and (iii) Friedreich ataxia-like (FA-like). We identified a novel missense mutation in c10orf2 in the family with IOAH, compound heterozygous mutations in CLN6 in the family with JCS and a homozygous frame-shift mutation in SACS in the FA-like patient. Phenotypes observed in our families were concordant with reported phenotypes of known mutations in the same genes thus obviating the need for functional validation. Our study revealed novel variations in three genes, c10orf2, CLN6, and SACS, that have so far not been reported in India. This study also demonstrates the utility of whole exome screening in clinics for early diagnosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)