Validation of Indian Council of Medical Research Neurocognitive Tool Box in Diagnosis of Mild Cognitive Impairment in India: Lessons from a Harmonization Process in a Linguistically Diverse Society.

BACKGROUND/AIMS: In a linguistically diverse country such as India, challenges remain with regard to diagnosis of early cognitive decline among the elderly, with no prior attempts made to simultaneously validate a comprehensive battery of tests across domains in multiple languages. This study aimed to determine the utility of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB) in the diagnosis of mild cognitive impairment (MCI) and its vascular subtype (VaMCI) in 5 Indian languages. METHODS: Literate subjects from 5 centers across the country were recruited using a uniform process, and all subjects were classified based on clinical evaluations and a gold standard test protocol into normal cognition, MCI, and VaMCI. Following adaptation and harmonization of the ICMR-NCTB across 5 different Indian languages into a composite Z score, its test performance against standards, including sensitivity and specificity of the instrument as well as of its subcomponents in diagnosis of MCI, was evaluated in age and education unmatched and matched groups. RESULTS: Variability in sensitivity-specificity estimates was noted between languages when a total of 991 controls and 205 patients with MCI (157 MCI and 48 VaMCI) were compared due to a significant impact of age, education, and language. Data from a total of 506 controls, 144 patients with MCI, and 46 patients with VaMCI who were age- and education-matched were compared. Post hoc analysis after correction for multiple comparisons revealed better performance in controls relative to all-cause MCI. An optimum composite Z-score of -0.541 achieved a sensitivity of 81.1% and a specificity of 88.8% for diagnosis of all-cause MCI, with a high specificity for diagnosis of VaMCI. Using combinations of multiple-domain 2 test subcomponents retained a sensitivity and specificity of >80% for diagnosis of MCI. CONCLUSIONS: The ICMR-NCTB is a "first of its kind" approach at harmonizing neuropsychological tests across 5 Indian languages for the diagnosis of MCI due to vascular and other etiologies. Utilizing multiple-domain subcomponents also retains the validity of this instrument, making it a valuable tool in MCI research in multilingual settings.

Clinical Evaluation of a Novel Intrarectal Device for Management of Fecal Incontinence in Bedridden Patients.

PURPOSE: The primary objective of the study was to evaluate the safety and efficacy of a stool management kit (SMK) for containment of fecal incontinence in hospitalized bedridden patients. DESIGN: A single-group quasi-experimental study. SUBJECTS AND SETTING: Twenty bedridden adults who had at least 1 episode of fecal incontinence in the prior 24 hours participated in the study. The study setting was the neurological unit of the All India Institute of Medical Sciences in New Delhi, India. METHODS: The study was carried out in 2 phases. The device was placed in situ for up to 24 hours in 10 patients during phase I of the study and up to 120 hours in an additional 10 patients during phase II. Participants were assessed for anorectal injury and peripheral device leakage on a 4- to 6-hourly basis. Sigmoidoscopy was performed to evaluate for any mucosal trauma or alteration of anorectal pathology after retrieval of the device. RESULTS: The device was successfully placed in all patients following the first attempt to place the device; 80% of patients retained the device until planned removal. The SMK diverted fecal matter without anal leakage in 174 (93.5%) out of 186 assessment points in a group of 20 patients. The devices remained in situ for 21 ± 0.2 and 84.5 ± 38.9 hours during phase I and phase II, respectively. None experienced anorectal bleeding, sphincter injury, or mucosal ulceration with device usage. Post-device sigmoidoscopy revealed erythema at the site of diverter placement in 2 participants. CONCLUSION: Study findings suggest that the SMK successfully diverted liquid to semiformed fecal exudate without peripheral device leakage in 93.5% of bedridden patients. No serious adverse events occurred. Additional research is needed to compare its effectiveness with that of currently available intrarectal balloon devices.

Seasonal differences and circadian variation in stroke occurrence and stroke subtypes.

BACKGROUND: India is a subtropical country with clear seasonal variations in weather conditions. Seasonal and circadian variation in occurrence of subtypes of cerebrovascular disease has been of interest in several studies from different countries and climate zones, but discrepant results have made the conclusions unclear. The aim of the present study was to observe the seasonal and circadian variation in the occurrence of stroke and its subtypes among our population. METHODS: This was a cross-sectional observational study based on new cases and past cases of stroke on follow-up, conducted between January 2011 and December 2012 in the Department of Neurology, at the All India Institute of Medical Sciences, New Delhi, India. The date and time of onset of the stroke was recorded. The categorization of months into season was in accordance with the Indian Meteorological Department guidelines. The time of onset was distributed into 6 hourly intervals. Statistical calculations were performed using Stata version 12.1 and SPSS version 20. RESULTS: A total of 583 patients were included for the study. The rate of occurrence of stroke was highest in the late morning 0600-1159 hours (P value <.001) compared with other times of the day, regardless of gender or age for both ischemic and hemorrhagic strokes. It was lowest in late evening (1800-2359 hours) quadrant compared with other quadrants. Although there was no significant difference found by dichotomizing the groups into two 6-month periods, there was an increasing trend in number of patients with stroke during the months November-February. There was no difference in stroke occurrence between the types of stroke or within each type among different seasons with different temperatures. Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of ischemic strokes also did not show any association with season or circadian rhythm. CONCLUSIONS: There is a significant increase in occurrence of strokes between 0600 and 1159 hours and lowest between 1800-2359 hours. No significant variation in stroke occurrence or subtype for any of the seasons was observed.

History of neurology at All India Institute of Medical Sciences.

All India Institute of Medical Sciences (AIIMS), New Delhi is considered as the apex healthcare institute of the country. The Department of Neurology was established in the 1960's and continues to be a leader in the country, in providing quality health care, in teaching, and also in conducting cutting edge research. The article traces the history of the Department of Neurology at AIIMS from its inception to the present day.

A Systematic Review of the Statistical Methods Adopted for Analyzing Follow-Up Data in Cohort Multiple Randomized Controlled Trial.

BACKGROUND: The cohort multiple randomized controlled trial (cmRCT) can tackle some of the weaknesses of an RCT which has triggered the interest of researchers considerably over time. Several challenges persist regarding the methods of analyzing such valued data. The paucity of international recommendations concerning the statistical methods for analyzing trial data has led to a variety of strategies further complicating the result comparison. Our aim was to review the different cmRCT analysis methods since cmRCT was first proposed in 2010. METHODOLOGY: A search for full-length studies presenting statistical analysis of the data collected adopting a cmRCT design was conducted on PubMed, Cochrane Library, EMBASE, JSTOR, Scopus, MEDLINE, and ClinicalTrials.gov. RESULTS: Out of 186 studies screened, we selected 22 for the full-text screening and 11 were found eligible for data extraction. All 11 studies were conducted in high-income countries, reflecting the design being underutilized in other settings. All of the studies were found to have used intention-to-treat (ITT) analysis with four of them utilizing instrumental variables (IV) analysis or a complier average causal effect (CACE). Randomization was noted often to be interchangeably used for random selection. Sample size calculation was not clearly specified in the majority of the studies. CONCLUSION: Clarity regarding the distinction between an RCT and a cmRCT is warranted. The fundamental difference in design, which leads to certain biases that need to be taken care of by adopting IV or CACE analysis, has to be understood before taking up a cmRCT.

Minimal Clinically Important Difference of Scales Reported in Stroke Trials: A Review.

There is a growing awareness of the significance of using minimum clinically important differences (MCIDs) in stroke research. An MCID is the smallest change in an outcome measure that is considered clinically meaningful. This review is the first to provide a comprehensive summary of various scales and patient-reported outcome measures (PROMs) used in stroke research and their MCID values reported in the literature, including a concise overview of the concept of and methods for determining MCIDs in stroke research. Despite the controversies and limitations surrounding the estimation of MCIDs, their importance in modern clinical trials cannot be overstated. Anchor-based and distribution-based methods are recommended for estimating MCIDs, with patient self-evaluation being a crucial component in capturing the patient's perspective on their health. A combination of methods can provide a more comprehensive understanding of the clinical relevance of treatment effects, and incorporating the patient's perspective can enhance the care of stroke patients.

Early neurological deterioration in acute ischemic stroke.

BACKGROUND AND AIMS: Early neurological deterioration (END) in acute ischemic stroke (AIS), patients is defined as clinical worsening or recurrence during first 72 h after onset of AIS. We have conducted this study to determine the association between END and functional outcome at 3 months of onset of AIS along with associated risk factors of END in AIS cases. METHODOLOGY: This study was conducted after approval of Institute Ethics Committee. Two hundred three consecutive patients were admitted from September 2020 to January 2022 at a tertiary care hospital. One hundred ninety patients were included in the study; patients were divided into two groups: (1) early neurological deterioration (END) and (2) non-early neurological deterioration (non-END). Patients were followed-up either telephonically or in person at approximately 3 months using modified Rankin Scale 0-6. All the clinically significant prognostic markers and p < 0.10 variables were considered significant in univariate analysis; P < 0.05 were considered statistically significant for the multivariate analysis. RESULTS: Out of 190 cases included in the cohort 34/190 (17.8%) cases showed END with mean age (56.56 (± 16.6)) and males (20/34 (58.8%)). END was independently associated with high blood glucose at admission (OR = 1.015; P = 0.002; 95%CI = 1.005-1.024) and low serum albumin (OR = 0.208; P = 0.002; 95%CI = 0.077-0.562). Patients with END showed poor functional outcome (mRS > 2) at end of 3 months (32 (94.1%); P < 0.001) and death was also statistically significant (22 (64.7%); P < 0.001) as compared to AIS cases having non-END. CONCLUSION: Our study showed END may be associated with poor functional outcome in AIS patients. Higher blood glucose at admission and low serum albumin may be statistically significant causing END. Future prospective cohort with larger sample size may confirm the findings.

Effectiveness of Yoga in Modulating Markers of Immunity and Inflammation: A Systematic Review and Meta-Analysis.

Chronic inflammation is central to the pathogenesis of many chronic inflammatory conditions. This review aims to analyze whether the practice of yoga, or yogic meditation and breathing, has any effect on the levels of inflammatory cytokines and other inflammatory markers in patients with various chronic inflammatory diseases such as rheumatoid arthritis, neoplastic disorders, and asthma, as well as in healthy subjects, compared to usual care or sham interventions. A comprehensive search of databases (PubMed, CENTRAL, Embase, and CINAHL) was performed. Randomized controlled trials (RCTs) that evaluated the effects of yoga as an intervention on inflammatory markers were analyzed. A total of 26 studies were included. Only two studies had a low risk of bias (RoB); 24 other studies had a high RoB. Most studies (n=24) reported a favorable outcome with yoga, irrespective of the type of yoga used, the condition studied, and the duration of the intervention. The commonly reported inflammatory markers included IL-6 (n=17), tumor necrosis factor-alpha (TNF-a) (n=13), and C-reactive protein (CRP) (n=10). Most studies showed a significant reduction in inflammatory markers in the yoga group (YG) compared to the control group (CG). Few studies also showed significant improvement in markers of cellular immunity (interferon gamma (IFN-g), IL-10, and transforming growth factor-beta (TGF-b); n=2 each) and improved mucosal defense (IgA, IL-6, and IL-2; n=2 each). A meta-analysis of IL-6, TNF-a, and CRP showed yoga had a favorable effect on the levels of these markers, but it was not statistically significant. Current evidence suggests that yoga can be a complementary intervention for various chronic inflammatory conditions. However, the quality of the evidence is poor, along with considerable heterogeneity. In the future, investigators should describe the intervention better, with a uniform assortment of outcome measures and treatment conditions, to generate high-quality evidence.

Safety and Efficacy of Injection Tenecteplase in 4.5 to 24 Hours Imaging Eligible Window Patients with Acute Ischemic Stroke (EAST-AIS) - Study Protocol.

BACKGROUND AND AIMS: Tenecteplase is used as the standard of care treatment for thrombolysis in acute ischemic stroke (AIS) patients within 4.5 h of symptom onset. Documented reports were less certain to claim the benefits of it in an extended window period. EAST-AIS (CTRI/2022/03/040718) trial is designed to determine the success rate of thrombolysis in an extended window period for good clinical outcomes. STUDY DESIGN: It is a randomized, placebo-controlled trial of tenecteplase administered within 4.5-24 h of stroke onset (with or without large vessel occlusion) based on evidence of salvageable tissue through baseline computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) scan. Criteria of patient inclusion are as follows: patients of both genders (male and female), age >18 years, pre-stroke modified Ranking Scale (mRS) <2, baseline NIHSS >5, CTP showing penumbra-ischemic core ratio >1.8, absolute difference in volume >10 ml, and ischemic core volume <70 ml. The sample size for the study is 100 patients: 50 in the tenecteplase arm (0.25 mg/kg body weight; maximum- 25 mg) and 50 in the placebo arm (controls). STUDY OUTCOMES: The study's primary objective is safety endpoints along with the efficacy of tenecteplase assessed using the mRS score at 90 days of stroke onset. CONCLUSION: The result obtained from EAST-AIS will determine the safety and efficacy of tenecteplase injection administered 4.5-24 h following the symptom onset for AIS patients within the territory of Internal Carotid Artery (ICA), Middle Cerebral Artery (MCA), or Anterior Cerebral Artery (ACA) occlusion.

Effect of endovascular therapy in large anterior circulation ischaemic strokes: A systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: The benefit of endovascular treatment in large anterior circulation ischaemic strokes with low ASPECTS score (<6) is uncertain. Recent randomised studies have demonstrated the benefit of endovascular treatment (EVT) in large ischaemic strokes. The present meta-analysis aims to assess the combined effect of these studies on efficacy and safety of endovascular treatment in this group of patients. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases MEDLINE, PubMed, EMBASE, SCOPUS, Google Scholar, Tripdatabase were searched for randomised controlled trials with at least 50 participants from inception until February 16, 2023. The primary efficacy outcome analysed was the relative risk of functional independence defined as mRS - 0-2 at 90 days. Secondary efficacy outcomes included early neurological improvement, death due to any cause at 90 days and proportion of patients requiring decompressive hemicraniectomy. The primary safety outcome was the risk of developing symptomatic intracerebral haemorrhage (sICH). RESULTS: A total of three studies (RESCUE Japan-LIMIT, SELECT 2 and ANGEL ASPECTS) involving 1011 patients; 510 in the EVT arm and 501 in the medical management (MM) arm met the defined criteria (ASPECTS-3-5). The combined RR for the primary outcome of mRS 0-2 was 2.53 [1.84-3.47] (p = <0.0001) favouring EVT over MM. The primary safety outcome of sICH was not significant in the EVT arm with a combined RR of 1.84 [0.94-3.60] (p = 0.5157). Mortality rates were similar in both arms (26.67% in EVT arm vs 27.94% in MM arm) with a combined RR of 0.95 [0.78; 1.16] (p = 1.000). CONCLUSION: In patients with Large vessel occlusion (LVO) and low ASPECTS (3-5), EVT was associated with higher likelihood of achieving functional independence and early neurologic improvement but did not provide any mortality benefit.

Minimal Clinically Important Difference (MCID) in Patient-Reported Outcome Measures for Neurological Conditions: Review of Concept and Methods.

The concept of the minimal clinically important difference (MCID) emerged from the recognition that statistical significance alone is not enough to determine the clinical relevance of treatment effects in clinical research. In many cases, statistically significant changes in outcomes may not be meaningful to patients or may not result in any tangible improvements in their health. This has led to a growing emphasis on the importance of measuring patient-reported outcome measures (PROMs) in clinical trials and other research studies, in order to capture the patient perspective on treatment effectiveness. MCID is defined as the smallest change in scores that is considered meaningful or important to patients. MCID is particularly important in fields such as neurology, where many of the outcomes of interest are subjective or based on patient-reported symptoms. This review discusses the challenges associated with interpreting outcomes of clinical trials based solely on statistical significance, highlighting the importance of considering clinical relevance and patient perception of change. There are two main approaches to estimating MCID: anchor-based and distribution-based. Anchor-based approaches compare change scores using an external anchor, while distribution-based approaches estimate MCID values based on statistical characteristics of scores within a sample. MCID is dynamic and context-specific, and there is no single 'gold standard' method for estimating it. A range of MCID thresholds should be defined using multiple methods for a disease under targeted intervention, rather than relying on a single absolute value. The use of MCID thresholds can be an important tool for researchers, neurophysicians and patients in evaluating the effectiveness of treatments and interventions, and in making informed decisions about care.

Importance of high-quality evidence regarding the use of Bacopa monnieri in dementia.

Background: Bacopa monnieri (BM), a commonly used herb, has shown neuroprotective effects in animal and in vitro studies; but human studies on patients with Alzheimer's Disease (AD) have been inconclusive. Further high-quality trials are required to conclusively state the utility of BM in AD and other neurodegenerative dementias. Methods: In the present study, we did a narrative review of the current challenges in designing clinical trials of BM in dementia and their evidence-based recommendations. Results: Many facets of the BM trials need improvement, especially effect size and sample size estimation. Current assessment and outcomes measures need a more holistic approach and newer scales for diagnosing and monitoring prodromal AD. The stringent guidelines in CONSORT and STROBE are often considered difficult to implement for clinical trials in ayurvedic medications like BM. However, adherence to these guidelines will undoubtedly improve the quality of evidence and go a long way in assessing whether BM is efficacious in treating AD/prodromal AD patients and other neurodegenerative dementias. Conclusion: Future studies on BM should implement more randomized controlled trials (RCTs) with an appropriate sample size of accurately diagnosed AD/prodromal AD patients, administering a recommended dosage of BM and for a pre-specified time calculated to achieve adequate power for the study. Researchers should also develop and validate more sensitive cognitive scales, especially for prodromal AD. BM should be evaluated in accordance with the same rigorous standards as conventional drugs to generate the best quality evidence.

Comparison of dexamethasone regimens in tubercular meningitis (TBM): a randomized open label clinical trial.

INTRODUCTION: Corticosteroids are used as adjunctive treatment in tuberculous meningitis (TBM). However, there is no universally accepted regimen, type, duration, or route of steroid administration. METHODOLOGY: In a randomized open labelled pilot study, TBM patients were divided into overlap oral dexamethasone (OOD) and direct oral dexamethasone (DOD) arms. The total duration of steroid administration was 8 weeks. The primary outcome was symptomatic resolution at 1 month post randomization. The secondary outcomes were mortality and modified Rankin scale (mRS) at 3 and 6 months after initiation of steroids. RESULTS: Symptomatic resolution after one month of randomization in 53 randomized patients was similar in OOD (71.4% (15/21)) versus DOD ((85.0% (17/20)) arm (p value:0.45). Median mRS was also similar in OOD versus DOD (OOD: 2.5 (IQR: 1.0; 6.0) versus DOD: 1.0 (IQR: (0.0; 4.0); p value: 0.31)) arm at 6 months. The mortality at 6 months was 31.8% (7/22) in the OOD versus 20.0% (4/20) in the DOD arm (p value: 0.49). CONCLUSIONS: In this open label pilot study, the outcomes were similar in OOD versus DOD arms in terms of symptomatic resolution at 1 month, and morbidity, and mortality at 3 and 6 months. Patients with stage I to III TBM may be given injectable steroids for 1 week after which they may be switched to oral steroid. This regime cannot be applied to stage IV TBM and patients with complications like optico-chiasmatic or spinal arachnoiditis or vasculitic infarcts.

Social Cognition in Parkinson's Disease: A Case-Control Study.

Background: Social cognition is the study of how people make sense of themselves and others. Impairment in several domains of social cognition is increasingly being recognized in Parkinson's disease (PD). Objectives: We aimed to study multiple domains of social cognition in Indian PD patients using a culturally appropriate, validated instrument. Methods: We recruited 52 individuals with PD and 31 healthy volunteers (HV) and used the Social Cognition Rating Tools in Indian Setting (SOCRATIS) tool to assess theory of mind (ToM), attributional biases and social cue perception. Quality of life (QoL) was assessed using the PDQOL scale. Results: Baseline characteristics were comparable between PD and HV. The mean (SD) FOT index (first order ToM index) was 0.86(0.18) in PD and 0.99(0.07) in HV [P < 0.001]. The PD group showed higher Externalizing Bias [EB, 4.42(3.91)], compared to HV [1.58(3.22), P = 0.001]. The mean (SD) Faux Pas Composite Index (FPCI ALT) was 0.69(0.09) in PD and 0.78(0.13) in HV [P < 0.001]. Social cognition indices were not associated with QoL in PD. Clinical parameters-age, gender, HAM-D, MOCA, education, levodopa equivalent daily dose of medication, number of PD drugs and trihexyphenidyl use did not predict social cognition. Conclusion: PD patients were less successful than age, gender matched controls in understanding social situations and other's thought processes and had higher tendency to attribute undesirable events to external causes. Deficits in social cognition did not impair the quality of life.

Neuropathic Tremor in Guillain-Barré Syndrome.

Background: Neuropathic Tremor (NT) is a postural/kinetic tremor of the upper extremity, often encountered in patients with chronic neuropathies such as paraprotein-associated and hereditary neuropathies. Objectives: To describe the clinical and electrophysiological features of NT in a previously underrecognized setting- during recovery from Guillain-Barré Syndrome (GBS). Methods: Patients with a documented diagnosis of GBS in the past, presenting with tremor were identified from review of clinical records. Participants underwent structured, videotaped neurological examination, and electrophysiological analysis using tri-axial accelerometry-surface electromyography. Tremor severity was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. Results: We describe the clinical and electrophysiological features of 5 patients with GBS associated NT. Our cohort had a fine, fast, and slightly jerky postural tremor of frequency ranging from 8 to 10 Hz. Dystonic posturing and overflow movements were noted in 4/5 patients. Tremor appeared 3 months-5 years after the onset of GBS, when patients had regained near normal muscle strength and deep tendon jerks were well elicitable. Electrophysiological analysis of tremor strongly suggested the presence of a central oscillator in all patients. Conclusion: NT is not limited to chronic inflammatory or hereditary neuropathies and may occur in the recovery phase of GBS. The tremor is characterized by a high frequency, jerky postural tremor with dystonic posturing. Electrophysiological evaluation suggests the presence of a central oscillator, hypothetically the cerebellum driven by impaired sensorimotor feedback.

Latest Trends in Outcome Measures in Dementia and Mild Cognitive Impairment Trials.

Disease modification trials in dementia and mild cognitive impairment (MCI) have not met with success. One potential criticism of these trials is the lack of sensitive outcome measures. A large number of outcome measures have been employed in dementia and MCI trials. This review aims to describe and analyze the utility of cognitive/clinical outcome measures in Alzheimer's disease (AD) and MCI trials. Methods: A PubMed search was conducted using relevant MeSH terms and exploded keywords. The search was confined to English language publications of human studies from the last five years which describe the latest trends in the use of outcome measures. Results: Despite broad use, the outcome measures employed are heterogeneous, with little data on correlations between scales. Another problem is that most studies are over-reliant on clinician/researcher assessment and cognitive outcomes, and there is a definite lack of stakeholder input. Finetuning of the paradigm is also required for people with early-stage disease, mild to moderate disease, and advanced dementia, as the outcome measures in these subgroups have varying relevance. Disease modification/prevention is an appropriate goal in early disease, whereas palliation and freedom from discomfort are paramount in later stages. The outcome measures selected must be suitable for and sensitive to these particular care goals. Although there is a shift to enrich MCI cohorts using a biomarker-based approach, the clinical relevance of such outcome measures remains uncertain. Conclusions: Outcome measures in dementia/MCI trials remain inhomogeneous and diverse, despite extensive use. Outcome measures fall within several paradigms, including cognitive, functional, quality-of-life, biomarker-based, and patient-reported outcome measures. The success of future disease-modifying trials is reliant to a large extent on the selection of outcome measures which combine all outcomes of clinical relevance as well as clinical meaning. Outcome measures should be tied to the type and stage of dementia and to the specific interventions employed.

Capsule-Deficient Cryptococcal Meningitis: A Diagnostic Conundrum.

Cryptococcosis is a serious systemic mycosis. Its incidence has escalated in the past four decades. Cryptococcus neoformans causes localized or disseminated infection in immunocompromised and immunocompetent patients. The capsulated form is commonly encountered which can be diagnosed on an India ink preparation or antigen detection. However, the noncapsulated forms are very rare and require a high index of suspicion for correct diagnosis. Herein, we present a case of cryptococcal meningitis due to a noncapsulated strain in an apparently immunocompetent patient with no proven immunodeficiencies along with review of world literature. Such cases are a diagnostic challenge for the clinician as well as microbiologist.

Clinical Effectiveness of Non-Immersive Virtual Reality Tasks for Post-Stroke Neuro-Rehabilitation of Distal Upper-Extremities: A Case Report.

A library of non-immersive Virtual Reality (VR) tasks were developed for post-stroke rehabilitation of distal upper extremities. The objective was to evaluate the rehabilitation impact of the developed VR-tasks on a patient with chronic stroke. The study involved a 50-year-old male patient with chronic (13 month) stroke. Twenty VR therapy sessions of 45 min each were given. Clinical scales, cortical-excitability measures, functional MRI (fMRI), and diffusion tensor imaging (DTI) data were acquired pre-and post-therapy to evaluate the motor recovery. Increase in Fugl-Meyer Assessment (wrist/hand) by 2 units, Barthel Index by 5 units, Brunnstrom Stage by 1 unit, Addenbrooke's Cognitive Examination by 3 units, Wrist Active Range of Motion by 5° and decrease in Modified Ashworth Scale by 1 unit were observed. Ipsilesional Motor Evoked Potential (MEP) amplitude (obtained using Transcranial Magnetic Stimulation) was increased by 60.9µV with a decrease in Resting Motor Threshold (RMT) by 7%, and contralesional MEP amplitude was increased by 56.2µV with a decrease in RMT by 7%. The fMRI-derived Laterality Index of Sensorimotor Cortex increased in precentral-gyrus (from 0.28 to 0.33) and in postcentral-gyrus (from 0.07 to 0.3). The DTI-derived FA-asymmetry decreased in precentral-gyrus (from 0.029 to 0.024) and in postcentral-gyrus (from 0.027 to 0.017). Relative reduction in task-specific performance metrics, i.e., time taken to complete the task (31.6%), smoothness of trajectory (76.7%), and relative percentage error (80.7%), were observed from day 1 to day 20 of the VR therapy. VR therapy resulted in improvement in clinical outcomes in a patient with chronic stroke. The research also gives insights to further improve the overall system of rehabilitation.

Mucormycosis in COVID-19 Patients: A Case-Control Study.

(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.

Genetics of Ataxias in Indian Population: A Collative Insight from a Common Genetic Screening Tool.

Cerebellar ataxias (CAs) represent a group of autosomal dominant and recessive neurodegenerative disorders affecting cerebellum with or without spinal cord. Overall, CAs have preponderance for tandem nucleotide repeat expansions as an etiological factor (10 TREs explain nearly 30-40% of ataxia cohort globally). The experience of 10 years of common genetic ataxia subtypes for ≈5600 patients' referrals (Pan-India) received at a single center is shared herein. Frequencies (in %, n) of SCA types and FRDA in the sample cohort are observed as follows: SCA12 (8.6%, 490); SCA2 (8.5%, 482); SCA1 (4.8%, 272); SCA3 (2%, 113); SCA7 (0.5%, 28); SCA6 (0.1%, 05); SCA17 (0.1%, 05), and FRDA (2.2%, 127). A significant amount of variability in TRE lengths at each locus is observed, we noted presence of biallelic expansion, co-occurrence of SCA-subtypes, and the presence of premutable normal alleles. The frequency of mutated GAA-FRDA allele in healthy controls is 1/158 (0.63%), thus an expected FRDA prevalence of 1:100 000 persons. The data of this study are relevant not only for clinical decision making but also for guidance in direction of genetic investigations, transancestral comparison of genotypes, and lastly provide insight for policy decision for the consideration of SCAs under rare disease category.