Spinocerebellar ataxia type 6 in eastern India: Some new observations.

INTRODUCTION: Spinocerebellar ataxias (SCAs) are hereditary, autosomal dominant progressive neurodegenerative disorders showing clinical and genetic heterogeneity. They are usually manifested clinically in the third to fifth decade of life although there is a wide variability in the age of onset. More than 36 different types of SCAs have been reported so far and about half of them are caused by pathological expansion of the trinucleotide, Cytosine Alanine Guanine (CAG) repeat. The global prevalence of SCA is 0.3-2 per 100,000 population, SCA3 being the commonest variety worldwide, accounting for 20-50 per cent of all cases, though SCA 2 is generally considered as the commonest one in India. However, SCA6 has not been addressed adequately from India though it is common in the eastern Asian countries like, Japan, Korea and Thailand. OBJECTIVE: The present study was undertaken to identify the prevalence of SCA6 in the city of Kolkata and the eastern part of India. MATERIALS AND METHODS: 83 consecutive patients were recruited for the study of possible SCAs and their clinical features and genotype were investigated. RESULTS: 6 of the 83 subjects turned out positive for SCA6, constituting therefore, 13.33% of the patient pool. DISCUSSION: SCA6 is prevalent in the eastern part of India, though not as frequent as the other common varieties. CONCLUSIONS: Further community based studies are required in order to understand the magnitude of SCA6 in the eastern part, as well as in other regions of India.

Study of visuospatial skill in patients with dementia.

OBJECTIVES: To assess the visuospatial function in different types of dementia with the visual object and space perception (VOSP) battery and to relate the degree of visuospatial dysfunction with different types and stages of dementia. MATERIALS AND METHODS: A sample of 53 participants with dementia and equal number of age-, sex-, and education-matched controls were recruited for the study. Participants were evaluated for visuospatial skill using VOSP test battery. The scores of dementia patients were compared with controls and within dementia cohort scores were compared based on stage of dementia. RESULTS: The dementia group scored low in all of the subtests of the VOSP battery in comparison to controls. Alzheimer's disease (AD), dementia of Lewy bodies (DLB), and vascular dementia (VaD) patients performed more poorly than controls in all subtests examining object perception and space perception. The three semantic variants of frontotemporal dementia (FTD) patients scored low in all four subtests of object perception, whereas behavioral variant FTD (bvFTD) patients performed normally. The scores deteriorated with the advancement of dementia in all patients from the dementia groups. CONCLUSIONS: Visuospatial function is significantly impaired in dementia patients particularly in AD, DLB, and VaD patients from the beginning, and the impairment is severe in advanced disease stages.

Genetic and Clinical Profile of Patients of Duchenne Muscular Dystrophy: Experience from a Tertiary Care Center in Eastern India.

OBJECTIVE: To study the genetic pattern, clinical profile and to find any correlation between them in patients of Duchenne muscular dystrophy. METHODS: Patients were selected from Neurogenetic clinic on the basis of clinical features, elevated serum CPK level and electromyographic features. After history and clinical examination, molecular genetic testing was performed by Polymerase Chain Reaction (PCR) technique. RESULTS: Among 100 patients, 73 patients had genetically confirmed disease while 8 cases were proven by biopsy, and thus a total 81 cases were further taken up for the study. Mean age of onset of clinical symptoms was 3.9 yrs; Valley sign and calf hypertrophy were most consistent features, while about 51% had facial weakness. Out of 73 genetically confirmed cases 53 (72.6%) showed deletion in distal exons and 12 (16.4%) showed deletion in both proximal and distal exons while 8 (10.9%) had only proximal deletion. There was no correlation between genetic pattern and clinical features. CONCLUSIONS: The positivity of PCR- based diagnosis is higher in our study possibly related to highly selective group of patients. Phenotype and genotype correlation was not seen.

Clinical profile and genetic correlation of patients with spinocerebellar ataxia: A study from a tertiary care centre in Eastern India.

BACKGROUND: Progressive cerebellar ataxia inherited by autosomal dominant transmission is known as Spino Cerebellar Ataxia (SCA). AIMS AND OBJECTIVES: To look for various clinical profile and molecular genetics of patients with SCAs and their phenotype-genotype correlation of patients with SCAs. MATERIALS AND METHODS: This was a cross-sectional study conducted at Bangur Institute of Neurosciences, Kolkata from June 2010 to April 2013. We selected patients from the neurogenetic clinic of our institute and performed genetic test for SCA 1, 2, 3, 6 and 12. The diagnosis was based on suggestive clinical features and positive genetic study, done by polymerase chain reaction. RESULTS: 83 patients were tested for trineucleotide repeats and turned out 45 positive for the mentioned SCAs. We found 13(28.9%) SCA-1, 18(40%) SCA-2, 7(15.6%) SCA-3, 6(13.3) SCA-6 and 1(2.2%) SCA-12 patients. Half of the remaining 38 patients had positive family history. The mean age of onset were 38.46 years in SCA-1, 29.55 years in SCA-2, 38.43 years in SCA-3, 47.33 years in SCA-6. Slow saccades were observed in 7(53.8%) SCA-1, 17(94.4%) SCA-2, 4(57.1%) SCA-3, 3(50%) SCA-6 patients. Hyporeflexia was noticed in 5(27.8%) SCA-2 patients. Pyramidal tract involvement was found in 8(61.5%) SCA-1, 4(22.2%) SCA-2, 4(57.1%) SCA-3 and 1(16.7%) SCA-6 patients. CONCLUSION: Our study showed SCA-2 is the most common variety of SCA and genotypic-phenotypic correlation was observed in SCA-1,2,6 and 12 patients.

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia.

BACKGROUND/AIMS: The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD). MATERIALS AND METHODS: We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l'Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively. RESULTS: We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD. CONCLUSIONS: BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment.

Adrenomyeloneuropathy with bulbar palsy: A rare association.

Adrenomyeloneuropathy (AMN) is a variant of adrenoleukodystrophy (ALD), an X-linked recessive peroxisomal disorder associated with accumulation of very long chain fatty acids (VLCFA). Mutations of this gene lead to abnormal peroxisomal ß-oxidation, which results in the harmful accumulation of VLCFAs in affected cells. Neurological symptoms occur due to progressive demyelination and destruction of cerebral white matter and primary adrenal insufficiency. Bulbar palsy in a case of AMN is very unusual. We report a case of a 22-year-old male with AMN who developed adrenal insufficiency at the age of 4 years successfully treated by gluco- and mineralocorticoids followed by features of myeloneuropathy with bulbar palsy. AMN with prominent bulbar symptoms emphasizes the diverse clinical manifestation of this disease.

Clinical features, MRI brain, and MRS abnormalities of drug-naïve neurologic Wilson's disease.

BACKGROUND: Magnetic resonance imaging (MRI) helps in the diagnosis of neurologic Wilson's disease (WD). The literature regarding MR spectroscopy (MRS) and diffusion-weighted imaging (DWI) in WD is limited. OBJECTIVES: To evaluate the clinical features and neuroimaging findings in drug-naïve neurologic WD and to find correlation between clinical stage and disease duration with different imaging findings. MATERIALS AND METHODS: The study subjects included consecutive and follow-up neurologic WD patients attending movement disorder clinic. The initial clinical and MRI features before commencement of chelation therapy were noted. Of 78 patients, 34 underwent DWI study and MRS was done in 38 patients and in 32 control subjects. RESULTS: Dystonia, dysarthria, tremor, and behavioral abnormality were common presenting features. All patients had MRI abnormality with major affection of basal ganglia. The clinical severity and anatomical extent of MRI abnormalities were positively correlated (P < 0.001; r s = 0.709). Presence of diffusion restriction was inversely related to duration of disease (P < 0.001; r s = 0.760). WD patients had reduced N-acetylaspartate/creatine (Cr) and choline (Cho)/Cr ratio (P < 0.001) as compared with control subjects in MRS study. CONCLUSION: Dystonia, dysarthria and tremor are common neurological features of WD. In this study, MRI abnormalities were positively correlated with disease severity; diffusion restriction was inversely correlated with the duration of the disease process. MRS was also a sensitive tool for diagnosing patient of neurologic WD.

Deletional mutations of dystrophin gene and carrier detection in eastern India.

OBJECTIVE: To determine the pattern of deletions of the dystrophin gene, the major class of mutations among the Duchenne and Becker muscular dystrophy patients of eastern India and to analyze the carrier frequency of the female members of the proband's family. METHODS: Deletional mutations occurring in patients have been characterized by multiplex polymerase chain reaction. Carrier state of mothers and sisters of probands were analyzed by either of two methods: 1) typing polymorphic short tandem repeat markers in or around the regions of deletion, by radioactive polymerase chain reaction and 2) quantitative real time amplification of the region of deletion. RESULTS: Deletions were detected in 67 (62.04%) out of 108 male patients, about 76.12% of these being localized in the central hot spot region of the gene, i.e., between exon 42 to exon 53 and 17.91% at the proximal hot spot i.e., between exon 1 to exon 20. In the present study were found 43 types of deletions, out of which 25 (58%) were new deletions, which were not described earlier among the Indian patients. Distribution pattern of deletions in different hot spot regions has been compared with that of other countries and statistical analysis reveals significant difference between countries (p<0.001). Correlation of the pattern of deletion with clinical phenotype of patients has been discussed. Interesting case of germline mosaicism and its implications in counseling has also been discussed. CONCLUSION: About half the mothers of affected probands were not carriers of the deletion, underscoring the need to use real time techniques for carrier detection.