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Abstract 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.

Pramipexole, a dopaminergic agonist, has rarely been implicated as a cause of hyponatremia in patients with Parkinson’s disease (PD). Pramipexole-induced stimulation of anti-diuretic hormone results in euvolemic hyponatremia. This is often neglected, and hyponatremia may lead to worsening of the motor symptoms with PD and an unnecessary increase in dopaminergic medications, causing disabling dyskinesias. This case report describes a patient with young-onset PD who developed newonset hyponatremia due to pramipexole-induced syndrome of inappropriate anti-diuretic hormone within 3 months of starting the drug.

Abstract Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Background: Minimum clinically important difference (MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for outcomes powers trials adequately to detect meaningful treatment effects, aids in their interpretation and guides development of new outcome measures. Objectives: To provide a comprehensive summary of MCID thresholds of various symptom severity scales reported in movement disorder. Methods: We conducted systematic review of the literature and included studies of one or more movement disorders, and reporting MCID scales. Results: 2763 reports were screened. Final review included 32 studies. Risk of bias (RoB) assessment showed most studies were of good quality. Most commonly evaluated scale was Unified Parkinson's Disease Rating Scale (UPDRS) (11 out of 32). Four studies assessing MDS-UPDRS had assessed its different sub-parts, reporting a change of 2.64,3.05,3.25 and 0.9 points to detect clinically meaningful improvement and 2.45,2.51,4.63 and 0.8 points to detect clinically meaningful worsening, for the Part I, II, III and IV, respectively. For Parts II + III, I + II + III and I + II + III + IV, MCID thresholds reported for clinically meaningful improvement were 5.73, 4.9, 6.7 and 7.1 points respectively; while those for clinically meaningful worsening were 4.7, 4.2, 5.2 and 6.3 points, respectively. MCID thresholds reported for other scales included Abnormal Involuntary Movement Scale (AIMS), Toronto Western Spasmodic Torticollis Rating Scale (TWSRS), and Burke-Fahn-Marsden Dystonia Scale (BFMD). Conclusion: This review summarizes all the MCID thresholds currently reported in Movement disorders research and provides a comprehensive resource for future trials, highlighting the need for standardized and validated MCID scales in movement disorder research.

Abstract Background Parkinson’s disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery. Methods In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-synTotal) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson’s disease patients was done by 99mTc-TRODAT-single-photon emission computed tomography. Results We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-synTotal concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99mTc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112). Conclusions In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD. Graphical Abstract

BackgroundParkinson's disease (PD) is an increasingly common neurodegenerative condition, which causes movement dysfunction and a broad range of non-motor symptoms. There is no molecular or biochemical diagnosis test for PD. The miRNAs are a class of small non-coding RNAs and are extensively studied owing to their altered expression in pathological states and facile harvesting and analysis techniques.MethodsA total of 48 samples (16 each of PD, aged-matched, and young controls) were recruited. The small extracellular vesicles (sEVs) were isolated and validated using Western blot, transmission electron microscope, and nanoparticle tracking analysis. Small RNA isolation, library preparation, and small RNA sequencing followed by differential expression and targeted prediction of miRNA were performed. The real-time PCR was performed with the targeted miRNA on PD, age-matched, and young healthy control of plasma and plasma-derived sEVs to demonstrate their potential as a diagnostic biomarker.ResultsIn RNA sequencing, we identified 14.89% upregulated (fold change 1.11 to 11.04, p < 0.05) and 16.54% downregulated (fold change −1.04 to −7.28, p < 0.05) miRNAs in PD and controls. Four differentially expressed miRNAs (miR-23b-3p, miR-29a-3p, miR-19b-3p, and miR-150-3p) were selected. The expression of miR-23b-3p was “upregulated” (p = 0.002) in plasma, whereas “downregulated” (p = 0.0284) in plasma-derived sEVs in PD than age-matched controls. The ROC analysis of miR-23b-3p revealed better AUC values in plasma (AUC = 0.8086, p = 0.0029) and plasma-derived sEVs (AUC = 0.7278, p = 0.0483) of PD and age-matched controls.ConclusionWe observed an opposite expression profile of miR-23b-3p in PD and age-matched healthy control in plasma and plasma-derived sEV fractions, where the expression of miR-23b-3p is increased in PD plasma while decreased in plasma-derived sEV fractions. We further observed the different miR-23b-3p expression profiles in young and age-matched healthy control.

Background: COVID-19 infection is associated with neurological manifestations, including various types of movement disorders (MD). A thorough review of individual patients with COVID-19-induced MD would help in better understanding the clinical profile and outcome of these patients and in prognostication. Objective: We conducted an individual patient-systematic review to study the clinical and imaging profile and outcomes of patients with COVID-19-associated MD. Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was conducted by two independent reviewers. Individual patient data COVID from case reports and case series on COVID-19-associated MD, published between December 2019 and December 2022, were extracted and analyzed. Results: Data of 133 patients with COVID-19-associated MD from 82 studies were analyzed. Mean age was 55 ± 18 years and 77% were males. A mixed movement disorder was most commonly seen (41%); myoclonus-ataxia was the most frequent (44.4%). Myoclonus significantly correlated with age (odds ratio (OR) 1.02 P = 0.03, CI 1-1.04). Tremor had the longest latency to develop after SARS-CoV-2 infection [median (IQR) 21 (10-40) days, P = 0.009, CI 1.01-1.05]. At short-term follow-up, myoclonus improved (OR 14.35, P value = 0.01, CI 1.71-120.65), whereas parkinsonism (OR 0.09, P value = 0.002, CI 0.19-0.41) and tremor (OR 0.16, P value = 0.016, CI 0.04-0.71) persisted. Conclusion: Myoclonus-ataxia was the most common movement disorder after COVID-19 infection. Myoclonus was seen in older individuals and usually improved. Tremor and parkinsonism developed after a long latency and did not improve in the short-term.

Objective: To determine the feasibility, reliability, and acceptability of video teleconference (VTC)-based neuropsychological assessment using Addenbrooke's cognitive examination-III (ACE-III). Methods: This study was performed from January 2022 to April 2022, during the third wave of the COVID-19 pandemic in India. We administered ACE-III using video-teleconferencing and compared the scores to face-to-face (FTF) testing for the eligible participants. We also conducted a participant's satisfaction survey of VTC-administered ACE-III compared to FTF-administered ACE-III, using a 7-point Likert scale. Results: We screened 37 participants and 24 (64.9%) successfully underwent ACE-III testing through VTC. We included 20 patients (mean age: 62.7 ± 10 years, mean education: 12.0 ± 4.6 years, 85% men) for final analysis, (who completed both VTC and FTF-administered ACE-III). Nine patients had major neurocognitive disorder (dementia), eight had mild neurocognitive disorder (MCI), and three had subjective cognitive decline (SCD). The two tests were administered at a median gap of 36 (18,74.5) days. The Intraclass correlation coefficients (ICC) of ACE-3 total scores (0.97) and the subdomain scores was high (>0.8). There was “very low” to “no” bias on the Bland–Altman plots, across all domains. The mean overall satisfaction score was 4.1, indicating that VTC is “as good as” FTF. Conclusions: Results support the feasibility and acceptability of remote administration of ACE-III via VTC. There is a good agreement between the ACE-III scores across VTC and in-person conditions.

Introduction: Parkinson's disease (PD) is a neurological condition that impacts the physical and psychological functioning of the patients. The physical and cognitive changes come with social stigma and threats to roles previously associated with their identities. Objectives: The current paper attempts to study the influence of the disease on the personal identity of the patients. Methods: A systematic review was done on PD and personal identity following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The Consolidated Criteria for Reporting Qualitative Research checklist was used to assess the quality of the papers. The selected papers were synthesized to understand the relationship between PD and personal identity. Results: The emerging themes were: (1) dissociation of old personal identity: (1.1) Influence of physical symptoms, (1.2) influence of society and stigma, and (1.3) threats to roles associated with identity and (2) changing family dynamics. A Model of Personal, Family, and Disease Dynamics was also developed based on clinical first-hand experience with the patients and the review. Conclusion: The personal identity of the PD patients shifts drastically as a result of their physical and psychosocial experiences. This also results in changed family dynamics, with the patient feeling sidelined due to loss of control and responsibilities in the family.

Objective: To develop an automated algorithm to detect, quantify, and differentiate between tremor using pen-on-paper spirals. Methods: Patients with essential tremor (n = 25), dystonic tremor (n = 25), Parkinson’s disease (n = 25), and healthy volunteers (HV, n = 25) drew free-hand spirals. The algorithm derived the mean deviation (MD) and tremor variability from scanned images. MD and tremor variability were compared with 1) the Bain and Findley scale, 2) the Fahn–Tolosa–Marin tremor rating scale (FTM–TRS), and 3) the peak power and total power of the accelerometer spectra. Inter and intra loop widths were computed to differentiate between the tremor. Results: MD was higher in the tremor group (48.9 ± 26.3) than in HV (26.4 ± 5.3; p < 0.001). The cut-off value of 30.3 had 80.9% sensitivity and 76.0% specificity for the detection of the tremor [area under the curve: 0.83; 95% confidence index (CI): 0.75, 0.91, p < 0.001]. MD correlated with the Bain and Findley ratings (rho = 0.491, p = 0 < 0.001), FTM–TRS part B (rho = 0.260, p = 0.032) and accelerometric measures of postural tremor (total power, rho = 0.366, p < 0.001; peak power, rho = 0.402, p < 0.001). Minimum Detectable Change was 19.9%. Inter loop width distinguished Parkinson’s disease spirals from dystonic tremor (p < 0.001, 95% CI: 54.6, 211.1), essential tremor (p = 0.003, 95% CI: 28.5, 184.9), or HV (p = 0.036, 95% CI: -160.4, -3.9). Conclusion: The automated analysis of pen-on-paper spirals generated robust variables to quantify the tremor and putative variables to distinguish them from each other. Significance: This technique maybe useful for epidemiological surveys and follow-up studies on tremor.

Stem cells have proved to be the “wonder treatment” for various genetic diseases and holds great potential for the treatment of numerous, but presently incurable maladies. However, stem cells may not be the answer for all such diseases. With the rampant growth of clinics offering stem cell therapy for almost every incurable disease, it is prudent that the indications, ethical considerations, and potential side effects of this treatment are known to the physicians and patients. In this article, we have summarized the available evidence on stem cell therapy in spinocerebellar ataxias.

Abstract Primary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value

Background and Purpose: We aimed to explore the characteristics, clinical features, predictors of seizure, and associated clinical outcomes in patients with cerebral venous thrombosis (CVT). Methods: We enrolled patients with CVT from January 2014 to July 2020. Prospectively patients were recruited from December 2018. We analyzed predictors of seizures and associated good functional outcomes (modified Rankin Scale, mRS: 0–2) using multivariable logistic regression. Results: We enrolled 153 patients with CVT in which 77 (50%) had presented with a seizure. The median age was 31 years (IQR 16-46), and the majority were men (73.2%). Focal to bilateral tonic-clonic was the most common seizure type (27%), followed by generalized seizures (22%). None of the patients had status epilepticus. Antiseizure medications (ASM) were used in 71% of patients at diagnosis, 42% having received them prophylactically. Supratentorial parenchymal involvement was seen in 72% of seizure patients compared to 38% in those without, and superior sagittal sinus was most commonly involved. Percentage of patients who achieved good clinical outcome (mRS 0-2) at 3 months did not vary significantly between both groups. The only predictor for seizures with CVT was the presence of a parenchymal lesion (OR-3.75, 95% CI 1.79-7.85), whereas seizure occurrence (OR- 12.55, 95% CI- 1.53-102.59) was associated with statistically significant risk for recurrent seizures, by multiple logistic regression analysis. Seizure occurrence was not associated with adverse functional outcomes. Conclusion: Seizures at presentation occurred in 50% of patients with CVT which was associated with a parenchymal lesion in the brain. There was no association between seizure at presentation and clinical outcome.

Objective: Neurological emergencies saw a paradigm shift in approach during the coronavirus disease-2019 (COVID-19) pandemic with the challenge to manage patients with and without COVID-19. We aimed to compare the various neurological disorders and 3 months outcome in patients with and without SARS-CoV-2 infection. Methods: In an ambispective cohort study design, we enrolled patients with and without SARS CoV-2 infection coming to a medical emergency with neurological disorders between April 2020 and September 2020. Demographic, clinical, biochemical, and treatment details of these patients were collected and compared. Their outcomes, both in-hospital and at 3 months were assessed by the modified Rankin Scale (mRS). Results: Two thirty-five patients (235) were enrolled from emergency services with neurological disorders. Of them, 81 (34.5%) were COVID-19 positive. The mean (SD) age was 49.5 (17.3) years, and the majority of the patients were male (63.0%). The commonest neurological diagnosis was acute ischemic stroke (AIS) (43.0%). The in-hospital mortality was higher in the patients who were COVID-19 positive (COVID-19 positive: 29 (35.8%) versus COVID-19 negative: 12 (7.8%), P value:

Introduction: In India, a national program for stroke (national programme for the control of cardiovascular diseases, diabetes, cancer, and stroke) and stroke management guidelines exist. Its successful implementation would need an organized system of stroke care in practice. However, many challenges exist including lack of awareness, prehospital notification systems, stroke ready hospitals, infrastructural weaknesses, and rehabilitation. We present here a protocol to investigate the feasibility and fidelity of implementing a uniform stroke care pathway in medical colleges of India. Methods and Analysis: This is a multicentric, prospective, multiphase, mixed-method, quasi-experimental implementation study intended to examine the changes in a select set of stroke care-related indicators over time within the sites exposed to the same implementation strategy. We shall conduct process evaluation of the implementation process as well as evaluate the effect of the implementation strategy using the interrupted time series design. During implementation phase, education and training about standard stroke care pathway will be provided to all stakeholders of implementing sites. Patient-level outcomes in the form of modified Rankin Scale score will be collected for all consecutive patients throughout the study. Process evaluation outcomes will be collected and reported in the form of various stroke care indicators. We will report level and trend changes in various indicators during the three study phases. Discussion: Acute stroke requires timely detection, management, and secondary prevention. Implementation of the uniform stroke care pathway is a unique opportunity to promote the requirements of homogenous stroke care in medical colleges of India.

Background: Spinocerebellar ataxia is a neurodegenerative disease. Information on comparative assessment of quality of life (QoL) among SCAs, particularly SCA 12, is scarce. We aimed to compare health-related QoL in SCA 1, 2 and 12. Methods: We conducted a cross-sectional study among individuals with genetically-confirmed SCAs. Ataxia severity was assessed using Brief Ataxia Rating Scale (BARS), independence in activities of daily living (ADL) using Katz index (Katz ADL) and depression using Beck's Depression Inventory-II (BDI-II). QoL was assessed via Short Form Health Survey version 2.0 (SF-36). Results: We enrolled 89 individuals (SCA1 = 17, SCA2 = 43, SCA12 = 29; 56% males). Mean age at onset (41.0 ± 11.6 for SCA12 versus 24.9 + 7.0 for SCA1 and 28.8 ± 9.8 years for SCA2) was significantly higher among SCA12. SCA12 had lower BARS (mean score 4.1 ± 4.5 versus 10.6 ± 4.6 for SCA1 and 12.5 ± 4.5 for SCA2). SCA12 scored better on all SF-36 subdomains including Physical (PCS) and Mental Component Summary (MCS) scores. PCS score amongst SCA12 was 44.4 ± 9.0 versus 30.4 ± 9.1 for SCA1 and 33.3 ± 8.9 for SCA2. MCS score for SCA12 was 51.4 ± 11.4 versus 41.8 ± 11.5 for SCA1 and 41.8 ± 11.2 for SCA2. SCA12 had lower mean BDI scores (5.0 ± 6.0) versus SCA1 (9.5 ± 11.6) and SCA2 (10.9 ± 10.3). BARS and BDI emerged as significant predictors of most SF-36 subdomains. Conclusions: Our study suggests that despite older age and comparable disease duration, SCA12 patients experience better QoL, less severe depression and ataxia versus SCA1 and SCA2. Severity of ataxia and depression are significant predictors of QoL among the three SCA types.

Spinocerebellar ataxia (SCA) is a clinically heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum and its associated connections. Genetic defects causing SCA include trinucleotide repeat expansions in the coding and non-coding regions of the genes, gene rearrangements, and conventional mutations. Various non-ataxic manifestations, such as dementia, peripheral neuropathy, and movement disorders (MDs) are described in SCA. MDs are the most common non-ataxic manifestations of SCA, and their prevalence and type vary according to the underlying genetic defects as well as the geographical and ethnic differences. In addition to the size of the repeat expansions, genetic modifiers contribute to the phenotypic pleiotropy of SCA. When present in association with ataxia, MDs may provide an important diagnostic clue for genotyping. However, patients with SCA presenting with MDs can be a diagnostic challenge when cerebellar ataxia is subtle or absent. Certain MDs may be more frequent in particular SCA subtypes compared to others. Similarly, MD may be an infrequent but pertinent manifestation in specific subtypes of SCA. Knowledge about MDs in SCA can help clinicians choose the genetic tests appropriately. Our paper comprehensively reviews the spectrum of MDs in SCA, and attempt to guide clinicians in choosing appropriate genetic tests for SCA in patients presenting with isolated or prominent MDs.

Background: Teleneurology consultations can be highly advantageous since neurological diseases and disabilities often limit patient's access to health care, particularly in a setting where they need to travel long distances for specialty consults. Patient satisfaction is an important outcome assessing success of a telemedicine program. Materials and Methods: A cross-sectional study was conducted to determine satisfaction and perception of patients toward an audio call based teleneurology follow-up initiated during the coronavirus disease 2019 pandemic. Primary outcomes were satisfaction to tele-consult, and proportion of patients preferring telemedicine for future follow-up. Results: A total of 261 patients who received tele-consult were enrolled. Satisfaction was highest for domain technological quality, followed by patient?physician dialogue (PPD) and least to quality of care (QoC). Median (interquartile range) patient satisfaction on a 5-point Likert scale was 4 (3?5). Eighty-five (32.6%; 95% confidence interval 26.9?38.6%) patients preferred telemedicine for future follow-up. Higher overall satisfaction was associated with health condition being stable/better, change in treatment advised on tele-consult, diagnosis not requiring follow-up examination, higher scores on domains QoC and PPD (p?0.05). Future preference for telemedicine was associated with patient him-/herself consulting with doctor, less duration of follow-up, higher overall satisfaction, and higher scores on domain QoC (p?

The ongoing COVID-19 pandemic has precipitated a global health crisis. Non-COVID diseases across specialties have been significantly compromised. The greatest challenge has been to continue providing care to non-COVID cases with minimum transmission risk to health care workers, patients, and caregivers. In this specter, better described as a medical holocaust, we present our experiences of dealing with acute neurological patients who could access our facility. We attempted to work on three key areas – initial screening using a more inclusive, dynamic checklist for COVID suspicion over and above the emergency triage, a mandatory initial holding on a separate floor of our inpatient service equipped with infection control strategies similar to a COVID-designated area, and daily screening of health care workers and caregivers for symptoms and possible exposures. It was a steep learning curve, a couple of close shaves, and many more lessons that went into the development of an algorithm that seems to be working well.

Parkinson's disease (PD) is the second most common progressive neuro-degenerative disorder. Research in PD is gradually increasing in India due to increased clinical cases, which could double by 2030 worldwide. Although its prevalence is low in India as compared to other countries, the total burden is much higher due to the large population size. PD is progressively debilitating, with pronounced motor and nonmotor symptoms (NMSs) that severely affect the quality of life (QoL) of patients and their caregivers. The progressive nature of the disease lays great emphasis on doctors to focus on the patients' QoL. As a consequence, Health-related QoL (HRQoL) has gradually become one of the main indicators for assessing health-related outcome. There is a growing need to pay attention to the NMSs and a pressing need to look at the QoL of Indian patients with PD through a culture and value specific lens. Research into the holistic QoL assessment with emphasis on psychological domains may allow for the early evaluation and intervention of depressive and cognitive symptoms in PD. This could result into increased productivity, reduced morbidity, and healthcare cost, which would in turn result into better QoL of Indian PD patients.

CONTEXT: Subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa therapy are reported to produce impulsivity in PD. We tested the hypothesis that STN-DBS enhances impulsive decision-making and that this effect is masked by the beneficial influence of the concomitant reduction in levodopa therapy. AIMS: To compare learning from negative consequences in patients with PD receiving STN-DBS to those without surgery. SETTINGS AND DESIGN: We conducted a prospective study in the Movement Disorder Clinic of a tertiary care university hospital in India, recruiting 26 PD patients treated with STN-DBS (PD-DBS) and 25 matched control patients on medical therapy (PD-MED) alone. METHODS: Impulsivity and decision-making were assessed using the Iowa Gambling Task (IGT) at baseline and 3 months. Dopamine agonist dose was unchanged during the study period. IGT total and block scores were used to assess impulsive decision-making and task learning. STATISTICAL ANALYSIS: General linear mixed model involving repeated measures ANOVA was used to compare IGT total and block scores. RESULTS: There was no independent effect of STN-DBS on the IGT total score (P = 0.198). In the PD-DBS group, block scores worsened after surgery with a negative slope across blocks, suggesting a lack of task learning [TIMEFNx01BLOCKFNx01INTERVENTION [F (4, 46) = 4.810, P = 0.003, partial Eta-squared = 0.095]. In the PD-MED group, block scores were seen to improve from baseline and across the blocks. These contrasting effects remained robust when tested in the Drug ON or OFF states. In the PD-DBS group, better task learning and higher block 5 scores were associated with greater post-operative reductions in total LEDD [TIMEFNx01BLOCKFNx01LEDD [F (4, 46) = 3.818, P = 0.012, partial Eta-squared = 0.077]. CONCLUSIONS: STN-DBS did not independently affect a global measure of decision making. However, STN-DBS and dopaminergic medications were shown to exert subtle yet significant opposing effects on the ability to learn from negative consequences.

Introduction: Stroke is the most common cause of epilepsy in the adult population. Post-stroke seizures (PSSs) are classified into early-onset seizures (ES) and late-onset (LS). ES can significantly affect the clinical outcome and occurrence of LS. Methods: We analyzed data from a prospective cohort of acute ischemic stroke patients between June 2018 and May 2020 in a neurology unit at a tertiary hospital. We screened all acute stroke patients and included consecutive patients older than 18 years of age, presenting with acute, first-ever neuroimaging-confirmed ischemic stroke. We excluded patients with a previous stroke, transient ischemic attacks, hemorrhagic stroke, cerebral venous thrombosis, prior history of seizures, or any other epileptogenic comorbidity. ES were classified as spontaneous seizures occurring within 1 week of the stroke. The main outcome assessed was the occurrence of ES. The secondary outcome was to determine predictors of ES and create an ES prediction score. Results: We screened 432 patients; of them, 291 were enrolled. ES occurred in 37 patients (12.7%). Cortical location (OR: 4.2), large artery disease subtype (OR: 2.9), mRS at presentation (OR: 1.4), use of anticoagulants (OR: 2.6), and hypertension (OR: 0.3) were significantly associated with the occurrence of ES. Patients with ES had a statistically significant worse clinical outcome at 3 months follow-up (P = 0.0072). Conclusion: We could formulate an ES prediction tool using the following components: (a) cortical location, (b) large vessel stroke, (c) mRS at admission, (d) anticoagulant use, and (e) presence of hypertension. This tool might help in treating patients at high risk for ES with prophylactic ASD, thereby preventing seizures and their complications.

Background: Parkinson's disease (PD) is a neurodegenerative disorder which greatly affects patients' quality of life. Despite an exponential increase in PD cases, not much attention has been paid to enhancing their quality of life (QoL). Thus, this systematic review aims to summarize the available literature for the role of repetitive transcranial magnetic stimulation (rTMS) intervention to improve QoL of PD patients. Methods: Literature review was carried out using PubMed, Embase, Web of Science and Scopus databases. The key search words were, “rTMS AND Parkinson AND QoL”, “rTMS AND Parkinson AND Quality of Life”. Cochrane Collaboration software Revman 5.3 was used to assess the quality of studies. Results: Over 707 studies were identified out of which 5 studies were included which consisted of 160 subjects, 89 male and 71 female, with mean age of 65.04 years. PD type varied from idiopathic PD, rigid, akinetic, tremor dominant to mixed type. The overall risk of bias across the studies was low and unclear with high risk of bias in incomplete outcome data domain in one study. Conclusions: The efficacy of rTMS as an adjunct intervention to enhance QoL of PD patients is uncertain due to dire lack of research in this area. The findings of the present review would help researchers conduct a well-defined, randomized, controlled trial by overcoming the present limitations associated with rTMS intervention to improve QoL of PD patients.

Medical training programs are witnessing immense disruptions worldwide due to the ongoing COVID-19 pandemic. Keeping in mind the trainees' future prospects, it is important to provide continuity of teaching and timely certification assessments. Overcoming the obstacles to routine functioning presented by SARS-CoV-2 spread, we recently conducted the DM Neurology exit examination in a hybrid virtual format. We created a curated case repository with history and clinical examination findings followed by structured questions that could be built upon for case discussions. The external examiners assessed the candidates virtually through a video conferencing platform. The end results were well accepted by all key stake holders. The concerns, logistics and experience of conducting the DM Neurology exit exam in a virtual format are summarized here.

Introduction Two pharmacological possibilities exist for an acute ischemic stroke (AIS): recanalization of the occluded artery and neuroprotection from ischaemic injury, the latter’s efficacy being debatable. We sought to determine whether administration of Citicoline immediately after recanalization therapy for AIS would improve clinical and radiological outcome at three months compared to standard treatment alone. Patients and methods CAISR was a single centre, randomized, placebo-controlled, parallel-group trial with blinded endpoint assessment. It was approved by the All India Institute of Medical Sciences Institutional ethics committee and registered at the Clinical Trial Registry of India (CTRI/2018/011900). We recruited participants with AIS undergoing recanalization therapy and randomly assigned them to receive either Citicoline or placebo in 1:1 ratio. Citicoline arm patients received Citicoline 1gm BD intravenously for three days, followed by oral citicoline 1gm BD for 39 days. Placebo arm patients received 100ml intravenous normal saline for three days, followed by multivitamin tablet BD for 39 days. All patients received standard of care. Outcome Blinded assessors did the follow-up assessment at six weeks (MRI Brain-stroke volume) and three months (NIHSS 0–2, mRS 0–2 and Barthel index> = 95). Results The infarct volume decreased from week 1 to week 6 by 2.6 cm3 on placebo versus 4.2 cm3 on Citicoline (p-0.483). The OR for achieving NIHSS 0–2, mRS 0–2 and Barthel index> = 95 with Citicoline was found to be 0.96(95%CI 0.39–2.40), 0.92(95%CI 0.40–2.05) and 0.87(95%CI 0.22–2.98) respectively. Conclusion CAISR was the first to evaluate the role of Citicoline, when used immediately after recanalization therapy, when the penumbral tissue is the most susceptible either to be protected from injury or become ischemic. We did not find any significant difference between the Citicoline or placebo arms with respect to either our primary or secondary outcomes.

Outcomes of pallidal stimulation in KMT2B dystonia have been infrequently reported prospectively. We report the six-month outcomes of bilateral GPi DBS in an Asian Indian patient with early-onset generalized dystonia associated with a novel heterozygous variant in the KMT2B gene.

The objective of this paper was to report on a case of steroid-responsive chorea in a patient with κ light-chain monoclonal gammopathy. In addition to subacute-onset generalized chorea, evidence of peripheral neuropathy in this elderly gentleman led us to investigate for paraproteinemia. We treated the patient with intravenous steroids in view of elevated κ light-chain assay and bone marrow biopsy, suggestive of monoclonal gammopathy of undetermined significance. There was a remarkable improvement of paresthesias and chorea at 6 months follow-up with no evidence of evolution to malignancy at 1 year. Autoimmune chorea is a treatable condition if identified and treated timely.

Hereditary ataxias comprise a group of neurological disorders which affect different levels of the neurological axis including the cerebellum, peripheral nerves, cognition, and the extrapyramidal system. These are categorized by the mode of inheritance as autosomal recessive, autosomal dominant, X-linked, and mitochondrial cerebellar ataxia. Definitive curative therapy is not available for these disorders. However, a wide array of emerging treatment options, especially in terms of symptomatic therapy, rescues this group from therapeutic nihilism. Several drugs have been assessed including riluzole, valproate, lithium, etc., as well as rehabilitative, and neuromodulatory strategies. In addition, symptomatic therapies for ancillary symptoms, such as seizures, movement disorders, spasticity, dystonia, etc., should also be targeted. Lastly, molecular therapeutic possibilities are also being explored in animal studies. In this review, we elucidate on the current treatment options available for hereditary ataxias.

AIM: The aim of this study was to detect the diagnostic accuracy of a novel app (Neurology Dx) vis-à-vis neurology residents. METHODS: A multicenter cross-sectional study involving seven leading teaching neurology institutes in India was conducted by recruiting 100 neurology residents. Primary outcome was proportion of correctly identified high likely gold standard differential diagnoses. Secondary outcomes were proportions of correctly identified first high likely, first three high likely, first five high likely, and combined moderate plus high likely gold standard differentials. RESULTS: Four sets comprising 15 movement disorder vignettes each (total 60) were tested on 100 neurology residents (one set for each resident) and also on the app (60 vignettes). Residents correctly identified the gold standard “high likely” differentials with a frequency of 13.6% as against 41.5% by the app (95% confidence interval [CI]: 21.9–34.1). On combining “high” and “moderate likely” differentials, residents could accurately identify gold standard differentials with a frequency of 10.8% as against 37.9% by the app (95% CI: 22.6–31.9). The residents correctly identified first five high likely gold standard differentials with a frequency of 13.5% versus 23.7% by the app (95% CI: 5.3–15.9). The residents correctly identified first three high likely gold standard differentials with a frequency of 13.0% versus 15.8% by the app (95% CI: -1.2–7.9). Residents correctly identified the first “high likely” gold standard differential in 32.3% as against 35% by the app (95% CI: -8.4–15.6). CONCLUSIONS AND RELEVANCE: This study suggests that an app (Neurology Dx) is capable of generating differential diagnoses to complement clinical reasoning of neurology residents (CTRI/2017/06/008838).

(1) Background: During the second wave of COVID-19, India faced a rapid and sudden surge of not only COVID19-delta variant cases but also mucormycosis, making the infection even more fatal. We conducted a study to determine factors associated with the occurrence of mucormycosis in patients with COVID-19. (2) Methods: This case–control study comprised 121 patients; 61 cases (mucormycosis with COVID-19) and 60 controls. Patients were included from April 10, 2021 onwards. Follow-up was conducted after about 90 days and health status was recorded based on the modified Rankin Scale (mRS). (3) Results: Mucormycosis with COVID-19 cases had a median (IQR) age of 49 (43–59) years with 65.6% males and were older (95% CI 1.015–1.075; p = 0.002) than in the control group with median (IQR) 38 (29–55.5) years and 66.6% males. Baseline raised serum creatinine (OR = 4.963; 95% CI 1.456–16.911; p = 0.010) and D-dimer (OR = 1.000; 95% CI 1.000–1.001; p = 0.028) were independently associated with the occurrence of mucormycosis in COVID-19 patients. Additionally, diabetes mellitus (OR = 26.919; 95% CI 1.666–434.892; p = 0.020) was associated with poor outcomes and increased mortality in patients with mucormycosis with COVID-19 as per the multivariable analysis. A total of 30/61 mucormycosis patients had intracranial involvement. (4) Conclusions: The study observed elevated levels of baseline raised creatinine and D-dimer in mucormycosis pa-tients with COVID-19 as compared to the control group. However, future studies may be conducted to establish this cause–effect relationship.

Background: Magnetic resonance guided focused ultrasound (MRgFUS) is a relatively novel technique to treat essential tremor (ET). The objective of this review was to analyze the efficacy and the safety profile of MRgFUS for ET.Methods: A systematic literature review was done. The post procedure changes in the Clinical Rating Scale for Tremor (CRST) score, hand score, disability and quality of life scores were analyzed.Results: We found 29 studies evaluating 617 patients. DTI based targeting was utilized in six cohorts. A significant difference was observed in the pooled standard mean difference between the pre and postoperative total CRST score (p-value < 0.001 and 0.0002), hand score (p-value 0.03 and 0.02); and the disability at 12 months (p-value 0.01). Head pain and dizziness were the most in procedure complications. The immediate pooled proportion of ataxia was 50%, while it was 20% for sensory complications, which, respectively, declined to 31 and 13% on long term follow up. A significant reduction (p = 0.03) in immediate ataxia related complications was seen with DTI targeting.Conclusion: MRgFUS for ET seems to be an effective procedure for relieving unilateral tremor. Use of DTI based targeting revealed a significant reduction in post procedure ataxia related complications as compared to traditional targeting techniques. Analysis of other complications further revealed a decreasing trend on follow up.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our “hub-spoke” model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

CONTEXT: Scant data exist regarding the overall distribution of dystonia phenotypes in individuals presenting with abnormal posturing to a movement disorder center in India. AIM: To identify the proportion of various types of dystonia presenting to a tertiary care, academic movement disorder center in India. SETTINGS AND DESIGN: We conducted a retrospective chart review of consecutive patients presenting to the movement disorder clinic of our tertiary care, university hospital. SUBJECTS AND METHODS: We included subjects evaluated at least once by a movement disorder specialist and documented to have dystonia (n = 170). Dystonia was classified according to the consensus update on phenomenology and classification of dystonia (Axes 1 and 2). We calculated the proportion of patients classified into one of the defined dystonia syndromes: early-onset isolated generalized dystonia, focal or segmental isolated dystonia with onset in adulthood, combined dystonia, and dystonia associated with other neurological or systemic manifestations. RESULTS: Focal or segmental isolated dystonia with onset in adulthood was the most common phenotype. Among focal dystonias, majority were brachial (65.8%), followed by cranial (27.1%) and cervical (15.7%). Task specificity was documented in 51.2% of focal dystonias, all brachial dystonias. Tremor was present in 70.3%. Etiologically (Axis 2), evidence of neurodegeneration was present in 10.0% and structural lesion in 5.9%. CONCLUSION: Writer’s cramp was the most common isolated dystonia identified in this hospital-based series.

Acute flaccid paralysis (AFP) is a complex clinical syndrome with a broad array of potential etiologies that vary with age. We present our experience of acute onset lower motor neuron paralysis. Materials and Methods: One hundred and thirty-three consecutive adult patients presenting with weakness of duration less than four weeks over 12 months period were enrolled. Detailed history, clinical examination, and relevant investigations according to a pre-defined diagnostic algorithm were carried out. The patients were followed through their hospital stay till discharge or death. Results: The mean age was 33.27 (range 13-89) years with male preponderance (67.7%). The most common etiology was neuroparalytic snake envenomation (51.9%), followed by Guillain Barre syndrome (33.1%), constituting 85% of all patients. Hypokalemic paralysis (7.5%) and acute intermittent porphyria (4.5%) were the other important conditions. We did not encounter any case of acute polio mylitis in adults. In-hospital mortality due to respiratory paralysis was 9%. Conclusion: Neuroparalytic snakebite and Guillain Barre syndrome were the most common causes of acute flaccid paralysis in adults in our study.

Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson’s disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD)Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS.Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model’s STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions.Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P