Parkinson’s disease (PD) is a progressive neurological disorder that significantly impacts quality of life. Over the past 25 years, deep brain stimulation (DBS) has emerged as an effective treatment option for individuals with advanced PD.. However, in India, DBS remains underutilized primarily due to financial constraints and a general lack of awareness, compounded by biases towards certain treatment centers. Additionally, the absence of definitive guidelines for implementing DBS in India further hampers its accessibility and adoption. Based on expert consensus, we propose a stepwise, five-point approach to optimize clinical outcomes for deep brain stimulation (DBS). This approach focuses on key areas including patient selection, indications for DBS in cases of medically refractory levodopa-induced motor complications or resistant tremor, and precise target selection. We emphasize the necessity of ensuring psychiatric stability and highlight the importance of a multidisciplinary approach, a comprehensive preoperative evaluation by multidisciplinary team of specialists including movement disorder experts, functional neurosurgeons etc critical for better, long-term outcomes. Furthermore, we recommend that DBS procedures be performed at specialized centers to ensure the highest standards of care and expertise.

BACKGROUND:REM sleep behavior disorder (RBD) is now increasingly recognized in progressive supranuclear palsy (PSP), with unclear clinical relevance. OBJECTIVES:To determine the frequency of pRBD and non-motor symptoms in PSP and association between the two. METHODS:We enrolled 150 consecutive patients with PSP and 150 age- and sex-matched controls. Probable RBD (pRBD) was identified using the REM Sleep Behavior Disorder Screening Questionnaire. Clinical, cognitive, and NMS scores were measured using validated rating scales. Group comparisons and regression analyses were performed. RESULTS:The mean age at study was 69.1 ± 7.5 years, pRBD was identified in 18.7% of patients with PSP and in none of the controls. Patients with pRBD had a greater NMS burden (p < 0.001) and poorer quality of life (p = 0.041). Attention/memory (β = 0.196, p = 0.015) and gastrointestinal symptoms (β = 0.255, p = 0.003) independently predicted pRBD. CONCLUSIONS:pRBD is a common non-motor feature of PSP and is associated with greater non-motor symptom burden and poorer quality of life.

BACKGROUND:The new classification of progressive supranuclear palsy (PSP) subtypes necessitates identifying radiological biomarkers to support the clinical diagnosis. OBJECTIVE:The goal was to test if magnetic resonance imaging (MRI) morphometry, diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), or [18F]fluorodeoxyglucose (18FFDG)-positron emission tomography (PET) differentiates PSP subtypes from each other or Parkinson's disease (PD). METHODS:Midbrain/pons (M/P) area ratio, middle/superior cerebellar peduncle (MCP/SCP) width ratio, magnetic resonance parkinsonism indices (MRPI and MRPI2) and midbrain antero-posterior (AP) diameter were measured. Region of interest-based DTI, SWI, and 18FFDG-PET analyses were performed. RESULTS:Four PSP subtypes (n = 85) and 24 PD were studied. MRI morphometry and DTI could differentiate PSP-Richardson syndrome (PSP-RS) from PSP-parkinsonism, PSP-postural instability, and PD (area under curve >0.7). SWI did not differentiate among PSP subtypes or PD. 18FFDG-PET distinguished PSP from PD. CONCLUSIONS:MRI morphometry and DTI differentiated PSP-RS from the other common PSP subtypes and PD and may be tested as a radiological marker of PSP-RS in larger studies.

Monogenic Parkinson’s disease refers to the Parkinson’s disease phenotype caused by mutations in genes that generally follow a mendelian pattern of inheritance. Though this is a rare entity in comparison to idiopathic Parkinson’s disease, they provide an opportunity to understand the pathophysiological basis of this neurodegenerative disease. Monogenic forms include those caused by pathogenic variants in PRKN, PINK1 and DJ1, which have an autosomal recessive mode of inheritance and those in LRRK2, SNCA and VPS35, which have an autosomal dominant inheritance pattern. Some of these mutation carriers (PRKN, PINK1, DJ1, LRRK2, SNCA, VPS35) have a simple parkinsonian phenotype resembling idiopathic Parkinson’s disease, whereas certain other monogenic forms (e.g. ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, SYNJ1) can have a complex or atypical parkinsonian phenotype. Despite significant overlap in various clinical features and insufficient data in literature, characteristic phenotype can be identified for several monogenic forms of Parkinson’s disease. Establishing genotype-phenotype correlation helps in creation of specific disease cohorts for enrolling in future clinical trials involving gene-based target therapies. In this review article, we provide a pragmatic clinical approach to evaluate a suspected case of monogenic Parkinson’s disease.

BACKGROUND:Parkinson's disease (PD) phenotype may vary with genetic, ethno-geographic, cultural, and environmental factors. OBJECTIVES:The aim was to develop a clinical database of PD in India and assess the influence of age-at-onset (AAO), gender, and motor subtype on the clinical profile of PD. METHODS:A cross-sectional study of PD was conducted across 18 Indian hospitals. Standardized assessments were performed by movement disorder specialists. Data were collected using uniform questionnaires during the recruitment visit. A total of 3300 age- and gender-matched case-control pairs were analyzed for environmental exposures, habits, and co-morbidities. RESULTS:We recruited 7918 PD cases with a mean AAO of 54.2 ± 11.8 years and a median disease duration of 5 years (interquartile range: 2-9). Subgroup analyses based on AAO, gender, and motor phenotype revealed significant differences in motor and non-motor symptoms, exposures, habits, and co-morbidities. Except coffee consumption, previously known associations were observed for exposure to insecticides/pesticides/fungicides (odds ratio [OR]: 1.67), head injury (OR: 3.11), coffee consumption (OR: 1.73), diabetes (OR: 1.48), hypertension (OR: 1.73), and smoking (OR: 0.74) in the Indian population. CONCLUSIONS:This large pan-Indian study highlights the clinical characteristics, environmental exposures, habits, and comorbid diseases associated with PD, which were broadly similar to those observed in European populations. The earlier AAO in Indian PD patients suggests a potentially higher genetic risk, warranting further investigation. A nationwide, community-based, epidemiological study is needed to achieve a comprehensive understanding of all risk factors for PD in India and to validate the risk factors identified in this hospital-based study. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The genomic landscape of the Indian population, particularly for age-related disorders like Parkinson's disease (PD) remains underrepresented in global research. Genetic variability in PD has been studied predominantly in European populations, offering limited insights into its role within the Indian population. To address this gap, we conducted the first pan-India genomic survey of PD involving 4,806 cases and 6,364 controls, complemented by a meta-analysis integrating summary statistics from a multi-ancestry PD meta-analysis (N=611,485). We further leveraged RNA-sequencing data from lymphoblastoid cell lines of 731 individuals from the 1000 Genomes project to evaluate the expression of key loci across global populations. Our findings reveal a higher genetic burden of PD in the Indian population compared to Europeans, accounting for ∼30% of the previously unexplained heritability. Thirteen genome-wide significant loci were identified, including two novel loci, with an additional three loci uncovered through meta-analysis. Polygenic risk score analysis showed moderate transferability from European populations. Our results highlight the importance of genetic loci in immune function, lipid metabolism and SNCA aggregation in PD pathogenesis, with gene expression variability emphasizing population-specific differences. We also established South Asia's largest PD biobank, providing a foundation for patient-centric approaches to PD research and treatment in India.

The outcomes of motor and non-motor features of Parkinson's disease (PD) following DBS vary among its subtypes. We tested whether pre-operative motor subtyping using the modified Tremor/PIGD ratio, could indicate the short-term motor, non-motor and quality of life (QOL) outcomes of STN-DBS.

BACKGROUND:There are limited data on the long-term survival of patients with Parkinson's disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS). OBJECTIVES:The aim of the study was to estimate the long-term survival and its predictors in patients who underwent STN-DBS. METHODS:The baseline demographic and clinical features of patients who underwent STN-DBS for PD at our center and had at least 5 years of follow-up were analyzed. Survival status, the date of demise, and the cause of death were obtained by telephonic interview with family members. RESULTS:A total of 186 patients who underwent STN-DBS between 1999 and 2018 (age at surgery: 56.7 ± 9.3 years) and were contactable in 2024 were included; 85 had died by 2024. Progressive worsening of PD, intercurrent infections, and cardiovascular diseases were the leading causes of death. The median survival after surgery was 13.1 years (interquartile range [IQR]: 8.9-17.1). Baseline postural instability and gait dysfunction subtype (hazard ratio [HR]: 2.3; 95% confidence interval [CI]:1.4-3.8, P = 0.001), higher levodopa-equivalent daily dosage (HR: 2.5; 95%CI: 1.4-4.5; P = 0.002), and higher Unified Parkinson's Disease Rating Scale Part I (UPDRS I) score in the ON state (HR: 2.8; 95% CI: 1.8-4.9; P < 0.001) were independent predictors of shorter survival, whereas higher levodopa response was an independent predictor of longer survival (HR: 0.19; 95% CI: 0.07-0.48; P = 0.001). CONCLUSIONS:STN-DBS offers a median survival of around 13 years; predominant axial features, neurocognitive changes, poor levodopa response, and higher medication requirement at baseline portend shorter survival. These findings could influence surgical candidate selection and long-term care strategies in resource-limited settings.

Background: Most Parkinson's disease (PD) loci have shown low prevalence in the Indian population, highlighting the need for further research. Objective: The aim of this study was to characterize a novel phosphatase tensin homolog-induced serine/threonine kinase 1 (PINK1) mutation causing PD in an Indian family. Methods: Exome sequencing of a well-characterized Indian family with PD. A novel PINK1 mutation was studied by in silico modeling using AlphaFold2, expression of mutant PINK1 in human cells depleted of functional endogenous PINK1, followed by quantitative image analysis and biochemical assessment. Results: We identified a homozygous chr1:20648535-20648535 T>C on GRCh38 (p.F385S) mutation in exon 6 of PINK1, which was absent in 1029 genomes from India and in other known databases. PINK1 F385S lies within the highly conserved Deutsche Forschungsgemeinschaft (DFG) motif, destabilizes its active state, and impairs phosphorylation of ubiquitin at serine 65 and proper engagement of parkin upon mitochondrial depolarization. Conclusions: We characterized a novel nonconservative mutation in the DFG motif of PINK1, which causes loss of its ubiquitin kinase activity and inhibition of mitophagy. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Writer’s cramp is a task-specific focal hand dystonia, which is diagnosed clinically. Quantification of defect in WC is done using clinical scales, while digitized platforms are lacking. To design and test a platform that can differentiate and quantify the abnormal kinematics of writing using a software interface and to validate it in adult-onset isolated writer’s cramp (WC). A native platform was designed using Java and Wacom Intuos pro tablet and the data analyzed using a MATLAB-based platform called Large Data-Based Evaluation of Kinematics in Handwriting (LEKH). We standardized this new platform by comparing the handwriting between patients with WC and age, and gender and education-matched healthy controls, using standard tasks to assess the kinematics. Comparison of the writing of right-handed WC patients (N = 21) and 39 healthy controls (N = 39) showed that patients differed from controls in the frequency of strokes (P < 0.001), number of inversions of velocity (P < 0.001), number of breaks (P = 0.02), air time and paper time (P < 0.001). Using the LEKH platform, the kinematic profile of patients with WC could be differentiated from healthy controls. Studies in larger samples will be needed to derive statistical models that can differentiate the flexion and extension types of WC which can help in muscle selection and to quantify the effects of treatment.

The efficacy of every neuromodulation modality depends upon the characteristics of the electrodes used to stimulate the chosen target. The geometrical, chemical, mechanical and physical configuration of electrodes used in neurostimulation affects several performance attributes like stimulation efficiency, selectivity, tissue response, etc. The efficiency of stimulation in relation to electrode impedance is influenced by the electrode material and/or its geometry. The nature of the electrode material determines the charge transfer across the electrode-tissue interface, which also relates to neuronal tissue damage. Electrode morphology or configuration pattern can facilitate the modulation of extracellular electric field (field shaping). This enables selective activation of neurons and minimizes side effects. Biocompatibility and biostability of the electrode materials or electrode coating have a role in glial formation and tissue damage. Mechanical and electrochemical stability (corrosion resistance) determines the long-term efficacy of any neuromodulation technique. Here, a review of electrodes typically used for implantable neuromodulation is discussed. Factors affecting the performance of electrodes like stimulation efficiency, selectivity and tissue responses to the electrode-tissue interface are discussed. Technological advancements to improve electrode characteristics are also included.

Objective Oculomotor impairment is an important diagnostic feature of progressive supranuclear palsy (PSP) and PSP subtypes. We assessed the role of video-oculography (VOG) in confirming clinically suspected slow saccades in PSP and differentiating PSP from Parkinson’s disease (PD). We also measured the correlation of both saccadic velocity and latency in PSP patients with scores on the PSP Rating Scale, Montreal Cognitive Assessment, and frontal assessment battery. We assessed the frequency of apraxia of eyelid opening (ALO) and reflex blepharospasm in PSP and PD patients.Methods A total of 112 PSP patients with slow saccades but not gaze palsy, 50 PD patients, and 50 healthy controls (HCs) were recruited. The Movement Disorders Society task force-PSP and PD criteria were used for the diagnoses. All the subjects underwent VOG.Results Horizontal and vertical saccadic velocities and latencies differentiated PSP patients from PD patients and HCs (p<0.001). Vertical saccadic velocity and latency accurately differentiated PSP with predominant parkinsonism (PSP-P) patients from PD patients (p<0.001 and 0.012, respectively). A couple of vertical and horizontal saccadic velocities differentiated PSP-Richardson’s syndrome (PSP-RS) patients from PSP-P patients (vertical velocity of left eye: p=0.024; horizontal velocity of right eye: p=0.030). In vertical gaze, the mean velocity cutoff showed good sensitivity and specificity in differentiating PSP patients from HCs and PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse global cognitive and frontal dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.Conclusion VOG is useful for confirming slow saccades in PSP-RS and PSP-P patients and for differentiating PSP-P patients from PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse cognitive dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.

The genetic loci implicated in familial Parkinson’s disease (PD) have limited generalizability to the Indian PD population. We tested mutations and the frequency of known mutations in the SNCA gene in a PD cohort from India. We selected 298 PD cases and 301 age-matched controls for targeted resequencing (before QC), along with 363 PD genomes of Indian ancestry and 1029 publicly available whole genomes from India as healthy controls (IndiGenomes), to determine the frequency of monogenic SNCA mutations. The raw sequence reads were analyzed using an in-house analysis pipeline, allowing the detection of small variants and structural variants using Manta. The in-depth analysis of the SNCA locus did not identify missense or structural variants, including previously identified SNCA mutations, in the Indian population. The familial forms of SNCA gene variants do not play a major role in the Indian PD population and this warrants further research in the under-represented population.