Resequencing the complete SNCA locus in Indian patients with Parkinson's disease.

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.

De Novo Movement Disorders Associated with COVID-19- A Systematic Review of Individual Patients.

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.

Zonisamide add-on in tremor-dominant Parkinson's disease- A randomized controlled clinical trial.

INTRODUCTION: and objective: Tremor is a disabling symptom of PD that usually responds poorly to available standard pharmacological agents. This study aimed to assess the effect of Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo. METHODS: This was a randomized, placebo-controlled, double-blind study. Parkinson's disease patients were allocated either to the intervention group (standard treatment along with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor analysis were done and follow-up assessments of the same were done after 12 weeks of intervention. Percentage change from baseline in the UPDRS tremor score was the primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis values were the secondary outcomes. RESULTS: There was no significant difference in the percentage change from baseline UPDRS tremor scores between the two groups (placebo: 8.33 [-19.89-23.86] vs drug: 26.14 [-35.58 to -16.07], p-value: 0.164, CI: 0.157-0.171). Best-case analysis for missing values showed a significant improvement in the drug group, compared to the placebo group (p-value: < 0.001, CI: <0.001 - <0.001). CONCLUSION: Zonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor score. Larger studies are required to confirm this finding.

Comparison of Disease Profiles and Three-Month Outcomes of Patients with Neurological Disorders with and without COVID-19: An Ambispective Cohort Study.

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: <0.001). The 3 months telephonic follow-up could be completed in 73.2% of the patients (142/194). Four (12.1%) deaths occurred on follow-up in the COVID-19 positive versus fifteen (13.8%) in the COVID-19 negative patients (P value: 1.00). The 3-month mRS was worse in the COVID-19 positive group (P value <0.001). However, this was driven by higher in-hospital morbidity and mortality in COVID-19 positive patients. Conclusion: Patients with neurological disorders presenting with COVID-19 infection had worse outcomes, including in-hospital and 3 months disability.

Hyponatremia in ICU.

Background: Hyponatremia is defined as serum sodium level <135 meq/L. It is the most common electrolyte abnormality seen in hospital admissions worldwide. The proportion is even higher in the ICU setting. A wide variety of factors influence the outcome of the hyponatremic patient. Present study is designed to approach to analyse etiology, clinical features, co-morbid factors, severity of hyponatremia, rate of correction, and impact of treatment on outcome of these diverse group of patients in ICU. Aims: 1) To find proportion of patients presenting with hyponatremia and requiring medical ICU admission in a tertiary care set up. 2) To study the etiology and clinical features of hyponatremia in patients requiring ICU admission. 3) To compare and study the effect of various factors on the outcome of hyponatremic patients in the ICU. Methods: This study was a cross-sectional observational study in tertiary care hospital. All indoor general medicine ward admissions over a period of 18 months were screened for the presence of hyponatremia and patients requiring Medical ICU care and satisfying inclusion criteria were studied. Serial serum electrolytes and urine sodium were tested for all patients in the ICU satisfying the inclusion criteria. Type of fluid given and daily correction of serum sodium of all patients were noted. Outcome was measured in terms of mortality, duration of stay in ICU, number of days required for sodium correction and complications of treatment if any. Patients were followed up till hospital discharge or death.. Results: In this study, 5.2% of total admissions had hyponatremia. Among the ICU admissions, the different symptoms attributed to hyponatremia included nausea (69.3%), malaise (80%), drowsiness (61.3%), confusion (41.3%), lethargy (24%), frequent falls (1.3%), convulsions (2.7%), altered sensorium (41.3%) and delirium (9.3%). SIADH was the most common cause of hyponatremia in these patients (32%). Serum sodium levels of patients on admission ranged from 82 - 133 meq/L, with average serum sodium being 124meq/L. Overall mortality among the hyponatremic ICU admissions was 26/75, 34.6%, which was higher than the total ICU mortality of 26% in same duration (p = 0.1). There was a significant increase in duration of stay in ICU in patients with various co-morbidities (p=0.003). There was a significant association between Glasgow Coma Scale (GCS) and serum sodium levels, (p = 0.002). Blood pressure and hydration status did not significantly influence outcome. Lower serum sodium on admission was associated with a lower survival (p= 0.041). Sodium correction of < 5 m eq/day was associated with an increased mortality(p = 0.04), whereas sodium correction of > 10 m eq/day was not associated with increased mortality, but an increased risk of EPM, which was seen in one patient. Conclusion: Most common cause of hyponatremia in ICU patients is SIADH. Longer duration of stay is seen in the presence of different co-morbidities. A lower GCS and a lower serum sodium on admission is associated with lower survival. Type of fluid used for hyponatremia correction did not influence the outcome. Under correction of hyponatremia in first 24 hours or inadequate correction was associated with a poorer outcome. Overcorrection was not associated with any survival benefit, but was associated with risk of EPM.