Dopamine ß hydroxylase (DBH) polymorphisms do not contribute towards the clinical course of Wilson's disease in Indian patients.

BACKGROUND: Wilson's disease (WD) is a rare copper metabolism disorder with hepatic and neurological symptoms. Dopamine ß hydroxylase (DBH) encodes a copper-dependent mono-oxygenase that converts dopamine to norepinephrine, thereby regulating the endogenous dopamine content in the neurons. Polymorphisms of DBH have been reported to be associated with several neurological diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia and attention-deficit hyperactivity disorder, which have overlapping neurological symptoms with WD. The present study aimed to assess the role of DBH polymorphisms on the clinical course of WD. METHODS: In total, 141 WD patients from India were included in the present study. Three polymorphisms of DBH (rs1611115 in the promoter, rs1108580 in exon 2 and rs129882 in 3'-UTR) were screened for their association with the clinical attributes (hepatic and neurological features) and age of onset of WD using a polymerase chain reaction-restriction fragment length polymorphsm method and sequencing approach. The distribution of genotype or allele frequencies was tested using 2 × 2 contingency chi-squared and logistic regression analysis (additive, dominant and recessive model). RESULTS: The genotypic and allelic frequencies of these single nucleotide polymophisms did not vary significantly along with the clinical symptoms (hepatic and neurological) or the age of onset of WD. No significant association was observed when we analyzed our samples with respect to harboring different kinds of ATP7B mutations (nonsense/in-del and missense). CONCLUSIONS: The data obtained in the present study suggest that the selected DBH variants are unlikely to have any significant contribution towards modifying the clinical symptoms of Indian WD patients.

Neurological Emergencies in Pregnancy.

On one side, pregnancy is a bliss, a beautiful journey for most women while on other, it increases the risk of several diseases which may cause considerable morbidity and mortality in young women in the most productive period of their lives. Neurological emergencies in pregnancy often have grave prognosis and so, must be promptly diagnosed and treated. This article reviews the clinical features and management of some of the common severe neurological emergencies in pregnancy.

Epidemiology of dementia and its burden in the city of Kolkata, India.

OBJECTIVES: Increase in aging population is expected to lead to increasing prevalence of dementia in India. In this study, we aimed to determine prevalence, incidence, and mortality of dementia and its subtypes and assess dementia burden in terms of disability-adjusted life years (DALY). METHODS: A community study was conducted over 5 years (2003-2008) in Kolkata, India, on 100,802 (males 53,209) randomly selected subjects to assess prevalence and capture data on incident cases and deaths. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, based on Global Burden of Disease 2010 approach. RESULTS: During 2003-2004, there were 103 (men 55) cases of dementia. The prevalence was 1.53% (age adjusted 1.12%) at age ≥65 years. In those ≥55 years age, average annual incidence rate of dementia was 72.57 per 100,000. All-cause standardized mortality ratio in dementia cases was 4.74 (men 6.19, women 3.03). The burden of dementia in 2007-2008 revealed that overall YLL was 47.13 per 100,000 and YLD ranged from 1.87 to 16.95 per 100,000 depending on the clinical severity of dementia. The overall DALY lost per 100,000 due to dementia for the year 2007-2008 was 74.19. CONCLUSIONS: This community study revealed a low prevalence and incidence of dementia with consequent low DALY-derived burden of illness compared with many industrialized nations. YLL formed major component of DALY indicating premature mortality to be an outcome of dementia burden. Copyright © 2016 John Wiley & Sons, Ltd.

Correlates of functional outcome among stroke survivors in a developing country--a prospective community-based study from India.

Stroke survivors (SS) are rising with higher incidence of stroke in developing countries. In addition to physical impairment, other factors such as cognition, social interaction, and depression determine the functional outcome after stroke. Considering the paucity of data from developing countries, we planned to determine the change in various functional parameters among SS. This community-based prospective study was carried out in Kolkata, India among 283 SS between 2006 and 2010. Functional outcome was assessed at baseline and at 3 annual follow-up visits using validated tools. A stepwise regression analysis was performed with demographic and stroke-related covariates against various measures of functional outcome. Result showed that mean Barthel Index score at baseline was 76.4 ± 30.8. Bengali version of mental status examination and Geriatric Depression Scale scores trended down over time with a negative regression coefficient of -.2061 (standard error [SE], .0937) and -.4488 (SE, .2145). Other outcomes did not change. Female gender, depression, and cognitive dysfunction had an unfavorable impact, whereas education correlated positively. In conclusions female gender and neuropsychiatric disturbances showed poor functional outcome compared with education, which correlates with better outcome. This information will be helpful for patients in developing countries for planning stroke rehabilitation.

Disease burden of stroke in Kolkata, India: derivation of disability-adjusted life years by a direct method.

BACKGROUND/AIMS: The disability-adjusted life year (DALY) is a new time-based measure of disease burden incorporating both disability and mortality. Our study aims to determine the DALYs lost due to stroke using a direct methodology and the implications. METHODS: A population-based, house-to-house, 2-stage, prospective study on stroke was conducted over 7 years in Kolkata, India, on 100,802 randomly selected subjects to capture the incident cases of first-ever stroke and those with fatal stroke. The data were utilized to estimate years of life lost due to premature mortality (YLLs), years lived with disability (YLDs) and DALYs lost. RESULTS: Over 7 years, there were 763 incident cases of first-ever stroke; of these, 320 had a fatal stroke within 30 days and 443 were stroke survivors. The overall DALYs lost due to stroke were computed as 795.57 per 100,000 person-years (730.43 in men and 552.86 in women). The overall YLL and YLD values were 593.14 and 202.43 per 100,000 person-years, respectively. The YLLs comprised 74.5% of the total DALYs. CONCLUSIONS: This is the first study in India where DALYs lost due to stroke were derived by a direct method. High YLL values demand urgent measures for controlling premature stroke death.

Depression among stroke survivors: a community-based, prospective study from Kolkata, India.

OBJECTIVE: Post-stroke depression (PSD) is a disabling entity among stroke survivors (SS). Longitudinal studies on PSD, essential to determine its prognosis, are lacking from developing countries. This prospective study was undertaken to assess the prevalence, natural history, and correlates of depression among SS in an Indian community. METHODS: From a community based stroke registry, SS were assessed annually for cognition, disability, and depression using Bengali validated scales. PSD was diagnosed if score on geriatric depression scale was greater than or equal to 21. Complex sample strategy was considered when calculating prevalence of post stroke depression. An age- and sex-matched case-control study was undertaken to determine the odds of depression in SS. RESULTS: Prevalence of PSD was 36.98% (95% confidence interval [CI]: 31.89%-42.06%) among 241 patients assessed at baseline. About 17% developed depression annually and a similar proportion had spontaneous improvement. Peak rate of PSD was beyond 3 months and continued up to 18 months after stroke. Compared to the non-depressed group, PSD subjects were significantly older, had higher age at first stroke, less education, lower socioeconomic status, and greater cognitive impairment and disability. Education had a protective role. Mortality in PSD was nearly twice that in non-depressed patients, though not significant statistically (hazard ratio: 1.84; 95% CI: 0.90-3.77). Compared with controls, odds ratio of PSD was 19.95 (95% CI: 10.09-39.47). CONCLUSIONS: Approximately one-third of SS develop PSD, similar to developed countries. Prevalence remains stable annually. Delayed peak of PSD suggested later realization of underlying disability. Predictors of PSD have been described and higher literacy was protective in this study.

Early and delayed fatality of stroke in Kolkata, India: results from a 7-year longitudinal population-based study.

There is no previously published well-designed study on long-term outcome of stroke from India. The present study has examined the case fatality rate and survival pattern in patients with stroke in a stratified, randomly selected sample from a large Indian metropolitan area. This prospective study was conducted over 7 years (March 2003 to February 2010) using a validated questionnaire administered by a field team and headed by a neurologist. A cross-sectional house-to-house survey was repeated twice yearly. A verbal autopsy was performed to assess cases of death. The Kaplan-Meier method was applied for survival analysis. A cohort of 763 stroke cases were followed up. The overall stroke fatality was approximately 59% at 5 years and 61% at 7 years. Early fatality was 33% within 7 days and 42% within 30 days. Men were at greater risk of death than women. Logistic regression analysis revealed male sex and diabetes to be important predictors of fatality. The majority of deaths were attributable to the index stroke (70%), followed by recurrent stroke (19%) and cardiovascular causes (7%). Beyond the first year, recurrent stroke was by far the most common cause of death. Median survival time exceeded the 84-month observation period when 30-day fatalities were excluded. Early stroke fatality is higher in this study compared with reports from developed countries, but long-term survival is similar. Beyond 1 year, the causes of stroke fatality are similar to that reported in other Asian populations. Access to acute stroke care and appropriate preventive strategy are urgently needed to reduce early stroke fatality in India.

Cognitive dysfunction in stroke survivors: a community-based prospective study from Kolkata, India.

The frequency of cognitive dysfunction among community stroke survivors (SS) is not known in India. This prospective study investigated the prevalence of poststroke mild cognitive impairment (psMCI) and poststroke dementia (psDem), the annual progression rate to dementia, and pertinent risk factors in a sample population of SS in Kolkata, India between September 2006 and July 2010. From a community-based stroke registry, 281 SS were assessed at baseline year after excluding attrition due to various causes. Validated cognitive tools were applied by trained field workers under supervision of a neuropsychologist. The assessment was repeated annually for consecutive three years. The mean follow-up period was 1.89 years (range, 1-3 years). The period prevalence rate of psDem was 13.88% (95% confidence interval [CI], 9.91%-18.90%) at baseline, and the average annual progression rate to dementia was 3.53% (95% CI, 2.09%-5.58%). Compared with subjects without dementia, those with psDem were significantly older at first-ever stroke and more likely to have cortical atrophy. The period prevalence rate of psMCI was 6.05% (95% CI, 1.45%-13.64%) at baseline, and 10.6% (95% CI, 4.57%-20.88%) of these subjects converted to psDem annually. Survival analysis of psDem patients showed a greater risk of death in psDem SS as compared to nondemented SS (hazard ratio, 2.65; 95% CI, 1.72-6.15). Our data suggest that the overall prevalence of psDem is higher than that of psMCI, possibly related to nonexclusion of prestroke dementia, but that the average annual progression rate of SS to psDem and that of psMCI to psDem are comparable. Older age at first-ever stroke and cortical atrophy are associated with increased risk for dementia among SS.

Movement disorders: Indian scenario: a clinico-genetic review.

Movement disorder (MD) is an important branch of neurology and has great potentiality in management because of improved diagnosis and therapeutic strategies. Over the last three decades, emphasis has been laid on the evaluation of various MDs in India by a limited number of interested neurologists and basic scientists. In this review, we want to highlight common problems of MDs in India with regard to epidemiology, clinical features and genetics.

Refractory epilepsy.

Refractory Epilepsy (R.E.) is a condition where all antiepileptic drugs (AEDs) fail to provide adequate seizure control. To diagnose R.E., false cases of refractoriness need to be carefully excluded. There are several predictors of refractoriness. The treatment options in R.E. are resective surgery, ketogenic diet and vagal nerve stimulation. The roles of newer AEDs are also promising. The future therapeutic possibilities include deep brain stimulation, AED containing polymers, stem cells and gene therapy.

Association of TOR1A and GCH1 Polymorphisms with Isolated Dystonia in India.

Isolated dystonia is a common movement disorder often caused by genetic mutations, although it is predominantly sporadic in nature. Common variants of dystonia-related genes were reported to be risk factors for idiopathic isolated dystonia. In this study, we aimed to analyse the roles of previously reported GTP cyclohydrolase (GCH1) and Torsin family 1 member A (TOR1A) polymorphisms in an Indian isolated dystonia case-control group. A total of 292 sporadic isolated dystonia patients and 316 control individuals were genotyped for single-nucleotide polymorphisms (SNPs) of GCH1 (rs3759664:G > A, rs12147422:A > G and rs10483639:C > G) and TOR1A (rs13300897:G > A, rs1801968:G > C, rs1182:G > T and rs3842225:G > Δ) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct Sanger sequencing. The statistical significance of allelic, genotypic and haplotypic associations of all of the SNPs were evaluated using the two-tailed Fisher exact test. The minor allele (A) of rs3759664 is significantly associated with isolated limb dystonia as a risk factor (p = 0.005). The minor allele (C) of rs1801968 is strongly associated with isolated dystonia (p < 0.0001) and most of its subtypes. The major allele of rs3842225 (G) may act as a significant risk factor for Writer's cramp (p = 0.03). Four different haplogroups comprising of either rs1182 or rs3842225 or in combination with rs1801968 and rs13300897 were found to be significantly associated with isolated dystonia. No other allelic, genotypic or haplotypic association was found to be significant with isolated dystonia cohort or its endophenotype stratified groups. Our study suggests that TOR1A common variants have a significant role in isolated dystonia pathogenesis in the Indian population, whereas SNPs in the GCH1 gene may have a limited role.

Burden among stroke caregivers: results of a community-based study from Kolkata, India.

BACKGROUND AND PURPOSE: Stroke causes significant caregiver (CG) stress, which is under-reported in India. This study assesses the financial, physical, psychological, and family burden on CG of stroke patients in an urban community. METHODS: Cross-sectional survey of stroke patients and CG were selected from a community-based registry using validated scales through face-to-face interviews. RESULTS: Data were available from 199 stroke survivors and a similar number of CG. Increased workload, related anxiety and depression, and sleep disturbance were reported by 70%, 76%, and 43% of CG, respectively, whereas >80% reported financial worry, which was greater among slum dwellers and less educated families. CG of patients with dementia and depression experienced greater stress. Female CG received more appreciation and family bonding was well-maintained. CONCLUSIONS: Financial stress was prominent and common among the socioeconomically weaker section. Psychological stress is similar to that of other studies. Women CG received greater appreciation. Family bonding was well-preserved in contrast to that of a western report.

A longitudinal study of epilepsy in Kolkata, India.

PURPOSE: This study aimed to determine the prevalence, incidence, and mortality rates of epilepsy in the city of Kolkata, India. This is the first such longitudinal study in a heterogeneous urban Indian population. METHODS: A two-stage door-to-door survey of a stratified random sample was undertaken within the municipal limits of Kolkata. Trained field workers detected and interviewed the cases using a simple screening questionnaire, and the detailed follow-up was done by neurologists. The survey was conducted annually for five consecutive years from March 2003 through February 2008. RESULTS: A total of 52,377 (52.74% men) individuals were screened. There were 309 prevalent and 66 incident cases of active epilepsy. The prevalence and average annual incidence rate (AAIR) with 95% confidence interval (CI), age-standardized to World Standard Population, were 572.8 (509.79-641.54) per 100,000 and 27.27 (21.03-34.80) per 100,000 per year, respectively. The age-specific incidence rates of epilepsy showed bimodal distribution. During the 5-year period, 20 cases of active epilepsy died. The average annual mortality rate (AAMR) was 7.63 (95% CI 4.45-11.26) per 100,000 population per year. Compared to the general population of Kolkata, the all-cause standardized mortality ratio (SMR) for persons with epilepsy was 2.58 overall (men 3.67; women 1.77). There was no significant difference between slum and nonslum dwellers in epidemiologic parameters. CONCLUSIONS: The AAIR of epilepsy is comparable to that observed in developed countries, but AAMR is higher. The all-cause SMR for epilepsy relative to the general population is, however, similar to that of developed nations.

"Clinical Profile of Genetically Proven Huntington's Disease Patients from Eastern India".

BACKGROUND AND AIMS: To study the clinical profile of genetically proven Huntington's disease (HD) patients from eastern India. METHODS: This cross sectional study selected patients of HD after genetic confirmation of expanded CAG repeats in Huntingtin (HTT) gene. We performed detail clinical evaluation including cognitive and neuropsychological assessment, and imaging of brain. RESULTS: This study included 75 patients (male: 57.3%; female: 42.7%). Mean age at onset was 37.12 (range 16-62) years; juvenile variety (onset below 20 years) was detected in 5.3%. Paternal transmission was commoner. Manifestations at onset were motor in 81.3% patients, behavioral in 10.7% and cognitive impairment in 8%. After chorea, next common movement disorder was dystonia. Frontal lobe dysfunction was found in 77.3% patients. Behavioral disturbances were observed in 77.3% patients and commonly manifested as depression, irritable behavior and anxiety. Among the three onset groups (motor/behavioral/cognitive), there was no significant difference regarding age at onset, gender distribution, pattern of inheritance (paternal/maternal), and at the time of evaluation, all groups had essentially similar pattern of clinical features. Mean CAG repeat of the patients was 48.25 (range 40-79). Our study showed some differing clinical characteristics compared to previous studies from the Indian subcontinent. CONCLUSION: Clinical features in our study showed differences from previous studies from the Indian subcontinent. We had more cognitive-onset patients. However, behavioral onset was lower in our study. Motor, behavioral and cognitive onset groups of HD were comparable regarding demographics, family history, CAG repeat lengths and major clinical features at the time of evaluation.

Status epilepticus and bilateral middle cerebral artery infarction: A rare presentation after viper bite.

Owing to the antihemostatic property of viper venom, hemorrhagic complications including intracerebral hemorrhage are the most commonly encountered after viper bite. Ischemic strokes have been rarely reported after viper envenomation, and its occurrence has been attributed to multiple mechanisms. Postsnakebite seizures are known to occur after neurotoxic bite. Here, we report the case of a viper bite victim who developed status epilepticus within 3 h after viper bite. He had only mild signs of local envenomation, and prolonged whole blood clotting time was the only manifestation of systemic envenomation. Subsequently, he was found to have developed right hemiparesis and global aphasia. Brain imaging revealed large infarcts in bilateral middle cerebral artery (MCA) territories. We report this as a unique case of viper bite which presented to the emergency room with status epilepticus. Moreover, bilateral MCA infarct, as was found in this case, is genuinely rare in scientific literature. Finally, the absence of overt features of envenomation makes this case stand out from other similar reported occurrences.

Résumé En raison de la propriété antihémostatique du venin de vipère, les complications hémorragiques, y compris l'hémorragie intracérébrale, sont les plus courantes. rencontré après morsure de vipère. Des AVC ischémiques ont rarement été signalés après une envenimation par vipère, et son apparition a été attribuée à mécanismes multiples Les crises d'épilepsie postnakebite se produisent après une piqûre neurotoxique. Ici, nous rapportons le cas d'une victime de morsure de vipère qui état de mal épileptique dans les trois heures suivant la piqûre des vipères. Il ne présentait que de légers signes d'envenimation locale et un temps de coagulation du sang total prolongé était la seule manifestation de l'envenimation systémique. Par la suite, il s'est avéré avoir développé une hémiparésie droite et une aphasie globale. L'imagerie cérébrale a révélé de grands infarctus dans les territoires bilatéraux de l'artère cérébrale moyenne (ACM). Nous rapportons cela comme un cas unique de morsure de vipère présenté à la salle d'urgence avec le statut épileptique. De plus, l'infarctus bilatéral à MCA, comme on l'a constaté dans ce cas, est vraiment rare dans littérature scientifique. Enfin, l'absence de caractéristiques évidentes d'envenimation fait que ce cas se distingue des autres cas similaires.

Chorea-ballism as a dominant clinical manifestation in heteroplasmic mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome with A3251G mutation in mitochondrial genome: a case report.

BACKGROUND: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, the most common maternally inherited mitochondrial disease, can present with a wide range of neurological manifestations including both central and peripheral nervous system involvement. The most frequent genetic mutation reported in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome is A3243G in MT-TL1 gene. Stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature constitute the known presentations in this syndrome. Among the abnormal involuntary movements in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome, myoclonus is the commonest. Other movement disorders, including chorea, are rarely reported in this disorder. CASE PRESENTATION: A 14-year-old South Asian boy from rural Bengal (India), born of a second degree consanguineous marriage, with normal birth and development history, presented with abnormal brief jerky movements involving his trunk and limbs, with recurrent falls for 10 months. We present here a case of heteroplasmic mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome with A3251G mutation, in which the clinical picture was dominated by a host of involuntary abnormal movements including chorea-ballism, myoclonus, and oromandibular dystonia in a backdrop of cognitive decline, seizure, and stroke-like episode. A final diagnosis was established by muscle biopsy and genetic study. Haloperidol was administered to control the involuntary movements along with introduction of co-enzyme Q, besides symptomatic management for his focal seizures. Six months into follow-up his seizures and abnormal movements were controlled significantly with slight improvement of cognitive abilities. CONCLUSION: The dominance of hyperkinetic movements in the clinical scenario and the finding of a point mutation A3251G in MT-TL1 gene make this a rare presentation.