Parkinson Disease: Muthane UB

Muthane UB, Ragothaman M, Gururaj G. · Departments of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. · J Assoc Physicians India. · Pubmed #18173026 No free full text.

Abstract: Improving economy and health in developing countries like India, has increased the life span and changed the emphasis from communicable to noncommunicable diseases. This is likely to increase the prevalence of movement disorders and, age-related diseases like Parkinson's disease (PD). We review Indian epidemiological studies to describe: a) Prevalence of movement disorders, b) methodological issues and c) potential of epidemiological research in a country with multiple ethnic races and environmental risks for PD. Most Indian epidemiological studies do not specifically assess PD and figures are from studies evaluating all neurological diseases. Well-designed Indian studies on PD and essential tremors estimate prevalence rates in Parsis who are ethnically different from Indians. We compare Indian prevalence studies with other parts of the world to examine the role of ethnicity in PD. Lack of accurate epidemiological data on PD and movement disorders creates an urgent need for properly designed and conducted epidemiological studies in India. This will help find out their load, identify areas of focus, create public health policies for elderly Indians and, possibly, provide etiological clues to the pathogenesis of PD.

Ragothaman M, Murgod UA, Gururaj G, Louis ED, Subbakrishna DK, Muthane UB. · Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. · J Assoc Physicians India. · Pubmed #18702384 No free full text.

Abstract: BACKGROUND: The elderly population in developing countries is likely to increase by 200-280%. Age related diseases like Parkinsonism are also likely to increase in ageing population. The prevalence and awareness of Parkinsonism (and possible PD) amongst them are unknown. METHODS AND MATERIAL: The objective was to know the awareness and occurrence of Parkinsonism (and possible PD) in Old Age Homes in Bangalore, South India. The study design was prospective, direct clinical evaluation, and it was old age homes in Bangalore, South India setting. There were six hundred and twelve residents of the old age homes in Bangalore. A movement disorder neurologist examined 612 elderly residents living in Old age Homes in Bangalore city, India. RESULTS: Parkinsonism was diagnosed in 109 (17.8%) of 612 residents. Possible PD was diagnosed in 9 (1.5% of 612) while in 100 (16.3% of 612) definite PD was diagnosed.94 (86.2%) had bilateral Parkinsonian signs (Stage > or = 2 of Hoehn & Yahr), only 4 (3.7%) of them or the caregivers knew they had PD. CONCLUSIONS: Knowledge about the disease was very low in the elderly residents although the occurrence of Parkinsonism was very high. Improving awareness of PD amongst the elderly and their caregivers might reduce their disability and improve their quality of life.

Punia S, Behari M, Govindappa ST, Swaminath PV, Jayaram S, Goyal V, Muthane UB, Juyal RC, Thelma BK. · Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 21, India. · Neurosci Lett. · Pubmed #17052850 No free full text.

Abstract: Recent discovery of pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene in Parkinson's disease (PD) patients in different ethnic groups have raised a hope of diagnostic screening and genetic counseling. We investigated the six most commonly reported mutations in LRRK2 gene among Indian PD patients, using PCR-RFLP method. Mutations G2019S, R1441C, R1441G, and R1441H were screened in 1012 individuals (PD, 800; controls, 212) while mutations I2012T and I2020T were screened in 748 PD patients. We did not observe any of these six mutations in this study sample except in a single female young onset PD patient who showed a heterozygous G2019S mutation. The absence of mutations was reconfirmed by sequencing of probands from several autosomal dominant PD families. Our observations suggest that these mutations may be a rare cause of PD among Indians and therefore of little help for diagnostic screening and genetic counseling for Indian PD patients.

Ragothaman M, Govindappa ST, Rattihalli R, Subbakrishna DK, Muthane UB. · Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. · Mov Disord. · Pubmed #16874759 No free full text.

Abstract: Medicines and surgical interventions improve the quality of life of Parkinson's disease (PD) patients. These are still expensive options and are unaffordable to those living in developing countries. Managing PD in Indians who have a low annual gross national income (GNI; 450-540 US dollars) and for whom only a few (3%) have health insurance is a challenge. We interviewed 175 consecutive PD patients regarding health insurance and money spent for treatment. The annual income of nearly half the patients was less than rupees 50,000 (1,148.63 US dollars). Patients in this study spend nearly 16% to 41.7% of the average Indian GNI to buy medicines. Costs of treating PD in India are lower than those in developed nations but are still out of reach for most Indian patients.

Juyal RC, Das M, Punia S, Behari M, Nainwal G, Singh S, Swaminath PV, Govindappa ST, Jayaram S, Muthane UB, Thelma BK. · National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India. · Neurogenetics. · Pubmed #16816977 No free full text.

Abstract: The depletion of dopamine levels in the brain due to degeneration of dopaminergic neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease (PD). The cumulative contribution of genetic variations in genes from the dopaminergic pathway has been widely implicated to confer susceptibility to idiopathic PD. We present in this paper an extensive association analysis of a total of 20 markers including single nucleotide polymorphism/short tandem repeat/variable number tandem repeat/duplication markers from five candidate genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine transporter) with PD among two independent sample sets. The allelic, genotypic, and haplotypic association of these markers with PD was tested in South Indian (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120 bp duplication marker of DRD4 gene showed promising results with PD in both of the sample sets. A significant allelic association in SI [odds ratio, OR (95% confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for 120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120 bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)= 1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report on the association of dopaminergic gene polymorphisms with PD from the Indian sub-continent.

Muthane UB, Chickabasaviah YT, Henderson J, Kingsbury AE, Kilford L, Shankar SK, Subbakrishna DK, Lees AJ. · Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. · Mov Disord. · Pubmed #16673400 No free full text.

Abstract: The role of genetic and environmental factors in etiopathogenesis of Parkinson's disease (PD) is debated. The prevalence of PD is higher among white than nonwhite populations, yet it is five times higher in nonwhites living in the United States than in Nigeria. We compare counts of melanized nigral neurons between neurologically normal Nigerians and British brains. Neuronal counts were estimated in an age-matched sample of 23 Nigerian and 7 British brains from neurologically normal individuals who had no Lewy bodies and Lewy neurites on alpha-synuclein immunostaining. Two investigators blind to age and ethnicity performed counts of melanized neurons in a single 7-mum hemisections showing the substantia nigra pars compacta. No significant difference exits in the number of neurons between the Nigerian and the British subjects (P = 0.1, NS). Differences in melanized nigral neuronal numbers may not explain differences in the prevalence of PD between white and nonwhite populations, suggesting factors other than neuronal numbers contribute to differential susceptibility of black vs. white races to PD.

Chaudhary S, Behari M, Dihana M, Swaminath PV, Govindappa ST, Jayaram S, Goyal V, Maitra A, Muthane UB, Juyal RC, Thelma BK. · Department of Genetics, University of Delhi, South Campus, Benito Juarez Road, New Delhi 110021, India. · Parkinsonism Relat Disord. · Pubmed #16500134 No free full text.

Abstract: We observed a mutation frequency of 8.5% in Parkin gene among Indian PD patients based on sequencing and gene dosage analysis of its exons. We identified nine point mutations of which seven are novel and hitherto unreported. These mutations accounted for 14.3% familial PD, 6.9% young onset and 5.9% late onset sporadic PD. Of the 20 PD patients with mutations only two had homozygous mutations and one was a compound heterozygote. Homozygous exonic deletions were absent but heterozygous exon rearrangements were observed in 9.2% of patients (19% familial PD and 4.5% young onset sporadic PD).

Chaudhary S, Behari M, Dihana M, Swaminath PV, Govindappa ST, Jayaram S, Singh S, Muthane UB, Juyal RC, B K T. · Department of Genetics, University of Delhi South Campus, New Delhi, India. · Pharmacogenet Genomics. · Pubmed #16141799 No free full text.

Abstract: OBJECTIVES: To investigate the association of (i) seven SNPs and SNP haplotypes in the phase II conjugating enzyme N-acetyl transferase 2 gene; and (ii) slow acetylator phenotype, with the development of young onset (YO) and late onset (LO) Parkinson's disease (PD) among Indians. METHODS: A total of 267 cases (132 YOPD, age at onset < or =40 years; 135 LOPD, age at onset >40 years) and 324 age and sex matched controls (132 for YOPD and 192 for LOPD) were genotyped for NAT2 SNPs. Allelic, genotypic and haplotypic association was tested by chi2 using a case-control approach. Chi2 test of association of acetylation phenotype (by genotype) with PD was also carried out. RESULTS: Of the seven SNPs genotyped, SNP191 was monomorphic and therefore, not included for analysis. With SNPs 590 and 857 a significant allelic [OR (95% CI) 4.147 (2.28-7.54) for A allele and 2.565 (1.34-4.92) for A allele, respectively] and genotypic [OR (95% CI) 0.27 (0.14-0.52) for GG and 0.35 (0.174-0.712) for GG, respectively] association with YOPD was observed. There was a significant allelic and genotypic association of SNP 282 with LOPD [chi2 = 8.92, P = 0.003 and chi2 = 10.2, P = 0.006, respectively]. There was also a significant association of protective and predisposing haplotypes TCGG and TCAG [OR (95% CI) 0.446 (0.31-0.63) and 3.742 (2.0-6.99), respectively] with YOPD and predisposing haplotype TCGA [OR (95% CI) 3.214 (1.43-7.22)] with LOPD. Slow acetylator phenotype was significantly associated with YOPD [OR (95% CI) 2.32 (1.2-4.48)]. CONCLUSION: Specific SNPs and SNP haplotypes in NAT2 and slow acetylator phenotype are significantly associated with YOPD and to a lesser extent with LOPD among Indians.

Sarangmath N, Rattihalli R, Ragothaman M, Gopalkrishna G, Doddaballapur S, Louis ED, Muthane UB. · Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. · Mov Disord. · Pubmed #16078206 No free full text.

Abstract: The prevalence of Parkinson's disease (PD) is low among Indians, except in the Parsis. Data for Indians come from studies using different screening tools and criteria to detect PD. An epidemiological study in India, which has nearly a billion people, more than 18 spoken languages, and varying levels of literacy, requires development and validation of a screening tool for PD. The objectives of this study are to (1) validate a modified version of a widely used screening questionnaire for PD to suit the needs of the Indian population; (2) compare the use of a nonmedical assistant (NMA) with the use of a medical person during screening; and (3) compare the effect of literacy of participants on the validity of the screening tool. The validity of the questionnaire was tested on 125 participants from a home for the elderly. NMAs of similar background and medical personnel administered the modified screening questionnaire. A movement disorder neurologist blind to the responses on the questionnaire, examined participants independently and diagnosed if participants had PD. The questionnaire was validated in the movement disorders clinic, on known PD patients and their family members without PD. In the movement disorders clinic, sensitivity and specificity of the questionnaire were 100% and 89%, respectively. Fifty-seven participants were included for analysis. The questionnaire had a higher sensitivity when NMAs (75%) rather than the medical personnel (61%) administered it, and its specificity was higher with the medical personnel (61%) than with NMAs (55% and 25%). The questionnaire had a higher specificity in literates than illiterates, whereas sensitivity varied considerably. The modified questionnaire translated in a local Indian language had reasonable sensitivity and can be used to screen individuals for PD in epidemiological studies in India. This questionnaire can be administered by NMAs to screen PD and this strategy would reduce manpower costs. Literacy may influence epidemiological estimates when screening PD.

Swaminath PV, Ragothaman M, Muthane UB, Udupa SA, Rao SL, Govindappa SS. · No affiliation provided · Mov Disord. · Pubmed #16700033 No free full text.

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Muthane UB, Prasad BN, Vasanth A, Satishchandra P. · No affiliation provided · J Neurol Sci. · Pubmed #10960299 No free full text.

This publication has no abstract.