Movement disorders: Indian scenario: a clinico-genetic review.
TL;DR: Common problems of MDs in India with regard to epidemiology, clinical features and genetics are highlighted.
Abstract: 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.
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TL;DR: The core neuroanatomical features of resilience against PD and evidence for ethnicity-based differential prevalence are presented and similar neural correlates of resilience are envisaged in the Anglo-Indian population.
Abstract: Disease genetics in admixed populations like Hispanic-Americans, African-Americans, etc. are gaining importance due to high disease burden in them. Furthermore, epidemiological studies conclusively prove ethnicity-based differential prevalence of Parkinson's disease (PD), since the American-Caucasians are more susceptible than Asian-Indians and Africans. Contradictorily, Anglo-Indians, an admixture of Europeans and Asian-Indians are five-times less susceptible than Indians. We evaluated the neural basis of this phenomenon using the cytomorphological features of susceptibility to nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The nigral dopaminergic neuronal numbers, their size and tyrosine hydroxylase (TH), PitX3 and Nurr1 expression were compared in MPTP-susceptible C57BL/6J mice, MPTP-resistant CD-1 mice and their crossbreds using stereology, morphometry and densitometry. Apoptotic index was evaluated by TUNEL-assay and caspase-3 expression. Striatal volume, TH and glial derived neurotrophic factor (GDNF) expression were studied. The normal CD-1 and crossbreds had significantly more, although smaller, nigral dopaminergic neurons than C57BL/6J, and a larger striatum. The crossbreds had higher TH, Nurr1 and PitX3 levels. MPTP administration caused loss of ~50-60 % nigral dopaminergic neurons in C57BL/6J and ~15 % in CD-1, but none in crossbreds. MPTP-induced cellular shrinkage in C57BL/6J was contrasted by nuclear enlargement without somal alterations in resistant strains. MPTP lowered the striatal TH and GDNF in C57BL/6J. Elevated striatal GDNF in CD-1 and crossbreds could be of compensatory nature and complemented the reduced nigral caspase-3 expression to attenuate and/or block apoptosis. Similar neural correlates of resilience are envisaged in the Anglo-Indian population. Thus, we present the core neuroanatomical features of resilience against PD and evidence for ethnicity-based differential prevalence.
23 citations
Cites background from "Movement disorders: Indian scenario..."
...However, in the Asian-Indian population, studies report absence of mutations in SNCA/α-synuclein gene while mutations in DJ-1, PINK1 and LRRK2 genes are rare [39, 40]; hence, we did not choose a genetic model of the disease....
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TL;DR: Genetic variability in LRRK2 has been unequivocally established as a major risk factor for familial and sporadic forms of PD in ethnically diverse populations.
Abstract: BACKGROUND Genetic variability in LRRK2 has been unequivocally established as a major risk factor for familial and sporadic forms of PD in ethnically diverse populations. OBJECTIVES To resolve the role of LRRK2 in the Indian population. METHODS We performed targeted resequencing of the LRRK2 locus in 288 cases and 298 controls and resolved the haplotypic structure of LRRK2 in a combined cohort of 800 cases and 402 controls in the Indian population. We assessed the frequency of novel missense variants in the white and East Asian population by leveraging exome sequencing and densely genotype data, respectively. We did computational modeling and biochemical approach to infer the potential role of novel variants impacting the LRRK2 protein function. Finally, we assessed the phosphorylation activity of identified novel coding variants in the LRRK2 gene. RESULTS We identified four novel missense variants with frequency ranging from 0.0008% to 0.002% specific for the Indian population, encompassing armadillo and kinase domains of the LRRK2 protein. A common genetic variability within LRRK2 may contribute to increased risk, but it was nonsignificant after correcting for multiple testing, because of small cohort size. The computational modeling showed destabilizing effect on the LRRK2 function. In comparison to the wild-type, the kinase domain variant showed 4-fold increase in the kinase activity. CONCLUSIONS Our study, for the first time, identified novel missense variants for LRRK2, specific for the Indian population, and showed that a novel missense variant in the kinase domain modifies kinase activity in vitro. © 2018 International Parkinson and Movement Disorder Society.
10 citations
Cites background from "Movement disorders: Indian scenario..."
..., G2019S) primarily identified in the white population—and excluded the role of these LRRK2 variants in the Indian PD population.(23,25,50,51) Here, we performed the first comprehensive study using targeted sequencing in Indian PD patients, which led to the identification of populationspecific novel variants and underscores the relevance of allelic heterogeneity in PD....
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TL;DR: The relevance, importance, and translational impediments of contemporary advances to implement public health principles into practice has neither been attempted nor impacted on disease burden or the authors' preparedness to prevent eventualities.
Abstract: It is now recognized worldwide that anticipation and prevention of diseases have significant advantages for the health and healthy ageing of the population. Early recognition of the disease in a vulnerable population such as in children aged 60 years enhances our preparedness for any eventualities and future burden of the diseases to society. It is also recognized that current public health practices alone cannot bring about the desired outcome. When tackling public health-related issues, such problems must be recognized and state-of-the-art principles and innovations from genomic sciences, information technologies, and medical specialties must be encompassed and embraced. These will enhance strategies for preparedness and provide us with a better understanding of how to identify, manage, and control disease burdens. The ever expanding landscape of genomics research also includes experimental and computational approaches for effectively utilizing DNA sequence information. From these perspectives, the intricacies of Mendelian single gene disorders are the least challenging compared to intricacies of multi-dimensional host factors for infectious diseases or complex disorders such as cancer. The concepts of public health in India are on firm footing; however, integration of contemporary advances to implement public health principles into practice has neither been attempted nor impacted on disease burden or our preparedness to prevent eventualities. At the same time, translational genomics is gradually paving the way for personalized medicine. Principles of personalized medicine remain to be fully understood and practiced despite the pharmacogenomics-based future of drug development, and treatment has not been as exciting as the advances in genomics we are witnessing today. The relevance, importance, and translational impediments of these advances will be discussed.
9 citations
01 Jan 2019
TL;DR: A chronicle of Indian Movement Disorders is written based on personal interviews with various senior Movement Disorder specialists of India as mentioned in this paper, which is a right time to look back into the history of Indian Neurology with specific reference to the Movement Disorders and pen down these chronicles since the inception of modern neurology in India.
Abstract: Movement Disorders are currently growing to be one of the major subspecialties of neurology worldwide, primarily by developments of research and therapeutics in this field. As any specialty grows, it leads to the formation of its society and the publication of journal to disseminate the knowledge. The International Parkinson’s Disease and Movement Disorders Society (IPMDS, formerly known as Movement Disorders Society) played its role with inception since 1980s. Further development of Movement Disorders subspecialty leads each region and country to have their own national societies and publications. Similarly, the seeds of Movement Disorders were sown in India in mid-1980s but it took a major stride in last few years with the formation of Movement Disorders Society of India (MDSI) in 2014 and following this, it is now at the crux of starting its journal—Annals of Movement Disorders (AOMD). This would be a right time to look back into the history of Indian Neurology with specific reference to the Movement Disorders and pen down these chronicles since the inception of modern neurology in India. The current chronicles of Indian Movement Disorders is penned based on personal interviews with various senior Movement Disorder specialists of India. However, it should also be remembered that many of the chronicles are limited by the memories of people and their biases with whom the interviews are conducted.
3 citations
Cites background from "Movement disorders: Indian scenario..."
...Das contributed on the epidemiology of various movement disorders.[18] The other important contribution of Indian literature has been on SCA-12....
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TL;DR: The most frequent diagnosis was Parkinson's disease, followed by essential tremor and dystonia, and most patients were over 60 years of age, white, married and teachers.
Abstract: Background Knowing the epidemiological profile is relevant for improving healthcare practices. Movement disorders are neurological disorders characterized by the presence of involuntary movements. They have a negative impact on patients' quality of life. Objectives To outline the frequencies of the different diagnoses seen among patients, along with their demographic characteristics, at a hospital in Sao Paulo (SP), Brazil, and to highlight the clinical aspects of those with Parkinson's disease. Design and setting Retrospective descriptive epidemiological analysis at a specialized outpatient clinic in a state public hospital in Sao Paulo. Methods Patients treated at this clinic over a four-year period were analyzed. Diagnoses, demographic variables and associations with clinical aspects of Parkinson's disease were evaluated. Results Out of the 680 medical records analyzed, 58.4% related to females. Most patients were over 60 years of age, white, married and teachers. The most frequent diagnosis was Parkinson's disease, followed by essential tremor and dystonia. Parkinson's disease presented in the mixed clinical form; the most common initial symptom was tremor. The akinetic-rigid clinical form occurred in younger individuals and mostly presented with postural instability and freezing of gait in the early years of disease. Conclusions Parkinson's disease, essential tremor and dystonia were the most frequent diagnoses. Characteristics like sex, frequency of other pathological conditions and the clinical and demographic aspects of Parkinson's disease were consistent with the data in the relevant literature.
2 citations
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7 citations
Journal Article•
TL;DR: The sensitivity and specificity of the new Wilson Index was more than the Nazer index in predicting mortality with liver involvement and has to be validated on a larger scale.
Abstract: Background Wilson's disease is a common metabolic disease of the tropics, which is treatable, if diagnosed early. In the paediatric group, the manifestations are mainly hepatic. Aims The objective was to study the varied presentations of the disease and to evaluate the diagnostic values of conventional tests in children. The prognostic importance of different indices in liver disorders was also assessed. Method The prospective work was carried out in the Paediatric Medicine Department of Nilratan Sircar Medical College & Hospital (NRSMCH) over a span of three years on children 1 through 12 years of age who fulfilled the prerequisite inclusion criteria. Results The mean age of the 34 children was 7.7 +/- 2.13 years. Predominant liver involvement was seen in 17 patients, neurological disturbance in 7 and purely hematological manifestations in 2 cases; the remaining 8 children were incidentally diagnosed whilst screening the siblings of affected subjects. In our series the sensitivity of various diagnostic tests was: 24 hour urinary copper excretion--100%, serum ceruloplasmin less than 20 mg/ dL--82.3%, K-F rings--32.35%. Eighteen of the 23 followed up cases (78.2%) responded to medical treatment. The sensitivity and specificity of the new Wilson Index was more than the Nazer index in predicting mortality with liver involvement. Conclusion The superiority of the new Wilson Index over the Nazer index has to be validated on a larger scale. As the outcome of management was very promising, a high index of suspicion in pertinent cases can not only check mortality, but also prevent florid manifestations.
7 citations
"Movement disorders: Indian scenario..." refers background in this paper
...2% of cases responded to medical treatment.[36] WD was diagnosed in 8....
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TL;DR: The results suggest that, unlike Parkin, pathogenic DJ-1 mutations seem to be restricted in certain populations and are unlikely to be of clinical importance in the eastern part of India.
Abstract: Objectives: Mutations in the DJ-1 gene have been described in autosomal recessive Parkinson's disease (PD) of European ancestry, Ashkenazi Jews, and Afro-Caribbean patients. Up to date, there is a lack of information about the prevalence of DJ-1 mutations among Indian PD patients. Materials and methods: In this study, we examined for DJ-1 mutations in Eastern Indian PD patients. Exons (no. 2-7) and intron boundaries of the DJ-1 gene were screened in 300 individuals (PD, 150; controls, 150) by direct sequencing. Results: A total of six intronic variants (IVS4+30T>G, IVS4+45G>A, IVS4+46G>A, IVS4-98G>A, IVS5+31G>A and IVS5+69G>C) were detected including one novel intronic change (IVS5+69G>C). Clinical features of the two patients exhibiting IVS5+69G>C (novel change) were compared and both were found to have early onset PD. IVS4+30T>G, IVS4+45G>A, and IVS4+46G>A were found to be present equally both in the patient and control cohorts. We did not find any DJ-1 mutations in our study. Conclusion: Our r...
6 citations
"Movement disorders: Indian scenario..." refers background in this paper
...[45] In India, candidate gene studies have been performed on SNCA,[46,47] Parkin,[48‑52] PINK1,[53] DJ‑1,[54,55] and LRRK2[47,56‑59] only [Table 2], with the maximum study being reported on Parkin....
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...[45] In India, candidate gene studies have been performed on SNCA,[46,47] Parkin,[48‐52] PINK1,[53] DJ‐1,[54,55] and LRRK2[47,56‐59] only [Table 2], with the maximum study being reported on Parkin....
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TL;DR: MDs are clinically important neurological disorders which are often caused by drugs and interestingly drugs used for its management are also associated with high incidence of ADRs, Hence these ADRs should be carefully monitored.
Abstract: Background : Movement disorders (MD) are neurological conditions that affect the speed, fluency, quality, and ease of movement and commonly include Parkinson's disease, tremor and dystonias. Drugs are important causes of MD, and the incidence and prevalence of such disorders are possibly underappreciated because of the lack of recognition. Objectives : To assess the incidence of all adverse drug reactions (ADRs) and estimate the prevalence of drug-induced MD among patients attending the clinic. Materials and Methods : This prospective observational study was conducted at an outpatient referral MD clinic of a tertiary care hospital for 1 year. The demographic data, drug intake, diagnosis, and ADRs experienced by the subjects were recorded. Causality assessment was done by Naranjo's scale. Results : Incidence of ADR among patients who attended this clinic was 19.7% (151 out of 768 patients experienced at least one ADR). A total of 299 ADRs were detected out of which 30.8% were gastrointestinal, 28.4% psychiatric, and 26% MD effects. The commonly implicated suspect drugs were levodopa (37.8%) and trihexyphenidyl (25.1%). The prevalence of drug-induced MD was 10.15% and drug-induced dyskinesias and dystonias were the most common. Conclusion : MDs are clinically important neurological disorders which are often caused by drugs and interestingly drugs used for its management are also associated with high incidence of ADRs. Hence these ADRs should be carefully monitored.
6 citations
"Movement disorders: Indian scenario..." refers background in this paper
...Dyskinesia and dystonias were common and the drugs such as levodopa and trihexyphendiyl were commonly held responsible.[11]...
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02 Apr 2012
TL;DR: Neuropsychological dysfunction involving right hemisphere more than the left involving stage II and above is revealed in patients with PD and PD Plus syndromes.
Abstract: Background: Cognitive dysfunction is an important cause of disability in Parkinson’s disease (PD) and Parkinson’s Plus syndrome (PD Plus). The development of dementia in PD has significant impact on the natural history of disease with rapid progression of disability and increased mortality. The present study aimed to evaluate the clinical and neuropsychological profile in patients with PD and PD Plus syndromes. Methods: Forty-one patients with a diagnosis of probable PD, and Parkinson’s Plus syndromes with minimum of fifth standard education were enrolled. They were evaluated with the UPDRS, Hoehn & Yahr staging, MMSE and AIIMS comprehensive neuropsychological battery in Hindi (adult form) using the eight lobar scales for the right and left hemisphere. Patients were then compared with age and gender matched controls. Results: Parkinson’s disease (85.4%) comprised * Correspondence to: Dr Deepika Joshi, Professor, Department of neurology, Institute of medical sciences, Banaras hindu university, Varanasi, India. Email: drdeepikajoshi73@gmail.com. the majority of cases followed by PSP (12.2%) and CBGD (2.4%). The MMSE scores were significantly reduced in the patients as compared to controls. Neuropsychological testing revealed that the mean T scores of the lobar scales (both right and left hemispheres) in patient group (LF – 77.33; LSM 76.57; LPO – 79.26; LT82.74; RF – 95.14; RSM – 92.05; RPO – 73.86; RT74.45) were higher & remarkably significant as compared to the controls (p<0.0005) particularly stage II and above. Conclusion: Our study revealed neuropsychological dysfunction involving right hemisphere more than the left. The AIIMS test battery was more sensitive for cognitive evaluation in this study, as about 70% patients who had impaired cognitive function with this battery had scored normal on MMSE.
2 citations