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Autoimmune autonomic disorders encompass a spectrum of disorders mediated by immune responses directed against the autonomic nervous system, including the peripheral and central autonomic pathways. While centrally mediated autoimmune autonomic disorders primarily can cause autonomic hyperactivity, peripherally mediated disorders are more common and can cause either locally confined or global autonomic failure. These disorders are often underrecognized owing to vague and varied clinical signs and symptoms. The discovery of specific autoantibodies in the past decade has caused a growing recognition of autoimmune causes for these disorders. The management is also complex, as these disorders often manifest with generalized symptoms, are difficult to diagnose, invoke challenges involving robust establishment of an autoimmune syndrome, and are rare. This article presents an overview of autonomic disorders that have a suspected autoimmune etiology, as well as recent advancements in their diagnosis and management.

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) 5, CTP showing penumbra–ischemic core ratio >1.8, absolute difference in volume >10 ml, and ischemic core volume

SQSTM1 (Sequestosome 1) also known as p62, plays several important physiological roles in the cell. It regulates autophagy and mitochondrial homeostasis and can further lead to metabolic reprogramming. Pathogenic variants in SQSTM1 gene are known to cause Neurodegeneration with ataxia, dystonia, and gaze palsy in autosomal recessive inheritance fashion. We report here, the generation of induced pluripotent stem cell (iPSC) line (IGIBi010-A) carrying a novel homozygous frameshift variant in SQSTM1 i.e. p.Leu251SerfsTer4. In future, this iPSC line will be used as a resource to elucidate the molecular pathway, targeting strategies for disease biology derived by variation in SQSTM1 gene.

Friedreich’s ataxia is a spinocerebellar degenerative disease caused by microsatellite (GAA.TTC)n repeat expansion in the first intron of FXN gene. Here, we developed iPSC lines from an FRDA patient (IGIBi016-A) and non-FRDA healthy control (IGIBi017-A). Both iPSC lines displayed typical iPSC morphology, expression of pluripotency markers, regular karyotypes (46, XY; 46, XX), capacity to grow into three germ layers, and FRDA hallmark -GAA repeat expansion and decreased FXN mRNA. Through these iPSC lines, FRDA phenotypes may be replicated in the in vitro assays, by creating neuron subtypes, cardiomyocytes and 3D organoids, for molecular and cellular biomarkers and therapeutic applications.

Friedreich’s ataxia is a neurodegenerative disorder caused by the hyper expansion of (GAA-TTC)n triplet repeats in the first intron of the FXN gene. Here, we generated iPSC lines from two individuals with FRDA, both of whom have homozygous GAA repeat expansion in the first intron of FXN gene. Both iPSC lines demonstrated characteristics of pluripotency, including expression of pluripotency markers, stable karyotypes and ability to develop into all three germ layers, and presence of GAA repeat expansion with reduced FXN mRNA expression. These iPSC lines will serve as invaluable tools for investigating the pathophysiology and phenotypes of FRDA.

The PPP2R2B gene, expressed highly in the brain, harbours trinucleotide CAG repeats in the 5′UTR region, in the range of 7–42 repeats. Individuals carrying CAG repeats greater than 43 have been associated to manifest a neurodegenerative disease condition termed as Spinocerebellar Ataxia type 12 (SCA12). An iPSC line from an adult male diagnosed with SCA12 presenting symptoms of gait (Gait Dominance) was generated. It showed pluripotency and trilineage markers without any chromosomal abnormality. This line can be utilized as an essential resource in enhancing our understanding of the molecular pathogenic mechanisms underlying SCA12 by facilitating generation of various neuronal cell types.

Friedreich's ataxia (FRDA) is a rare neurodegenerative disorder caused by over expansion of GAA repeats in the first intron of FXN gene. Here, we generated two iPSC lines from FRDA patients with biallelic expansion of GAA repeats in the first intron of FXN gene. IGIBi014-A and IGIBi015-A both iPSC lines demonstrated characteristics of pluripotency, normal karyotypes (46, XY), the capacity to differentiate into all three germ layers, and the ability to sustain the GAA repeat expansion with decreased FXN mRNA expression. These cell lines will be utilized to comprehend the pathophysiology of the illness and the FRDA's predictive phenotypes.

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.

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.

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.

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.

Research in amyotrophic lateral sclerosis (ALS), a neurodegenerative condition, has seen advancement in several key areas of research in 2020. These include a thrust to move the classification of ALS from a neuromuscular condition to a neurodegenerative condition, due to research suggesting involvement of cortical areas, and early cortical hyperexcitability. A new criterion for ALS, called the Gold Coast criterion, has been described. The Gold Coast criteria have removed the categories of possible, probable, and definite ALS, to make the diagnosis of ALS more inclusive and permit enhanced eligibility of patients in clinical trials for ALS. New biomarkers, both imaging and protein based, have been described. Advances in therapy have also occurred, with a large phase II clinical trial reporting benefits with sodium phenylbutyrate-taurursodiol.

Gluten ataxia is a rare immune-mediated neurological disorder caused by the ingestion of gluten. The diagnosis is not straightforward as antibodies are present in only up to 38% of patients, but often at lower titers. The symptoms of ataxia may be mild at the onset but lead to permanent damage if remain untreated. It is characterized by damage to the cerebellum however, the pathophysiology of the disease is not clearly understood. The present study investigated the neurochemical profile of vermis and right cerebellum and structural changes in various brain regions of patients with gluten ataxia (n = 6, age range 40–65 years) and compared it with healthy controls (n = 10, 40–55 years). Volumetric 3-D T1 and T1-weighted magnetic resonance imaging (MRI) in the three planes (axial, coronal, and sagittal) of the whole brain and single-voxel 1H- magnetic resonance spectroscopy (MRS) of the vermis and right cerebellum were acquired on 3 T human MR scanner. The metabolite concentrations were estimated using LC Model (6.1–4A) while brain volumes were estimated using the online tool volBrain pipeline and CERES and corrected for partial volumes. The levels of neuro-metabolites (N-acetyl aspartate + N-acetyl aspartate glutamate, glycerophosphocholine + phosphocholine, and total creatine) were found to be significantly lower in vermis, while N-acetyl aspartate + N-acetyl aspartate glutamate and glycerophosphocholine + phosphocholine was lower in cerebellum regions in the patients with gluten ataxia compared to healthy controls. A significant reduction in the white matter of (total brain, cerebellum, and cerebrum); reduction in the volumes of cerebellum lobe (X) and thalamus while lateral ventricles were increased in the patients with gluten ataxia compared to healthy controls. The reduced neuronal metabolites along with structural changes in the brain suggested neuronal degeneration in the patients with gluten ataxia. Our preliminary findings may be useful in understanding the gluten-induced cerebral damage and indicated that MRI and MRS may serve as a non-invasive useful tool in the early diagnosis, thereby enabling better management of these patients.

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.

(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: Movement disorders are one of the prominent nonataxic symptoms in patients of spinocerebellar ataxia (SCA). The type of movement disorder may provide clinical clue to the type of SCA. Objective: The objective of this study is to evaluate various movement disorders in patients of genetically proven SCAs and to establish a probable clinico-genetic correlation. Methods: Ninety-Five patients of genetically proven SCAs were assessed for the presence of various movement disorders. Results: Patients with SCA (75.8% males) with at least one movement disorder contributed 43.16%. Age for onset of movement disorder was 43.39 ± 13.43 years. SCA-12 (38.95%) was the most common subtype. Among the patients with at least one movement disorder, action tremor of hands contributed majority (90.2%). Dystonia and parkinsonism were present in 17.07% and 12.2% of patients (with movement disorder), respectively. Action tremor of hands was present in 34 patients with SCA-12 (91.89%), and 20 patients (54.05%) had onset of hand tremor preceding the onset of ataxia. Majority of patients with SCA-12 (81%) were of the same ethnic origin belonging to Agrawal community. Patients with movement disorder had a later onset (45 ± 13.88 years) of ataxic symptoms compared to those without a movement disorder (32.8 ± 11.92) (P =

Background: Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population. Methods: A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method. Results: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-β1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2–3.8;P= 0.006), G800A (OR, 4.4; 95% CI; 2.1–9.3;P< 0.001) and T869C (OR, 2.6; 95% CI; 1.5–4.5;P= 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D' =0.51, r2 = 0.23). Conclusion: Our results suggest that TGF-β1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population.

Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by an expanded (GAA) trinucleotide repeat in the FXN gene. The extended repeats expansion results in reduced transcription and, thereby, decreased expression of the mitochondrial protein, frataxin. Given the ongoing drug trials, identification of reliable and easily accessible biomarkers for monitoring disease progression and therapeutic intervention is a foremost requirement. In this study, comparative proteomic profiling of PBMC proteins from FRDA patients and age- and gender-matched healthy controls was done using 2D-Differential in-Gel Electrophoresis (2D-DIGE). Protein–protein interaction (PPI) was analyzed using BioGRID and STRING pathway analysis tools. Using biological variance analysis (BVA) and LC/MS, we found eight differentially expressed proteins with fold change ≥1.5; p ≤ 0.05. Based on their cellular function, the identified proteins showed a strong pathological role in neuroinflammation, cardiomyopathy, compromised glucose metabolism, and iron transport, which are the major clinical manifestations of FRDA. Protein–protein network analysis of differentially expressed proteins with frataxin further supports their involvement in the pathophysiology of FRDA. Considering their crucial role in the cardiac and neurological complications, respectively, the two down-regulated proteins, actin α cardiac muscle 1 (ACTC1) and pyruvate dehydrogenase E1 component subunit β (PDHE1), are suggested as potential prognostic markers for FRDA.

Use of complementary and alternative medicine (CAM; 補充與替代醫學 bǔ chōng yǔ tì dài yī xué) in Parkinson disease (PD) ranged 40–70%. The objective of this study was to determine the frequency, types and factors associated with the use of CAM in Indian PD patients. PD patients, fulfilling UKPD-Society brain-bank diagnostic-criteria, attending Movement-disorders clinic of a tertiary-care teaching hospital in India from 1st May to 15th December 2012 were enrolled. Information on socio-demographic, clinical data and treatment along with factors (source of information, benefits, harms, reason for use and cost) associated with CAM use were recorded. Out of 233 consecutive PD patients, 106 (46%) used CAM. Mean ± SD age of CAM users was 56 ± 11.2 years. Among CAM users, 72% were males, with mean age-onset 49 ± 11.16 years (P = 0.042) and 73% receiving levodopa therapy (p = 0.006). Longer duration PD, higher education (graduates and above), urban residence, and fairly good perceived health were other factors seen among CAM users. Reasons for using CAM were ‘feel good factor’ (73%), 9% took CAM due to side effects from allopathic-medicines. Commonly used CAM were Ayurvedic, homeopathic medicines, and acupuncture (針灸 zhēn jiǔ) [74/106 (70%)]. Median CAM cost in Indian Rupees (INR) was 1000/month (USD16, range: 0-400USD/month in year 2012). Almost half of PD patients use CAM. Three-quarters of Indian CAM using PD patients believe that CAM is harmless, using it at a substantial cost. CAM-users are educated, young, urban dwellers, longer duration PD and receiving levodopa. Commonly used CAM was Ayurvedic, Homeopathic medicines and acupuncture.

Objective: To evaluate neuropsychiatric co-morbidities (depression, psychosis and anxiety) in non-demented patients with Parkinson′s disease (PD). Background: Non-motor symptoms like neuropsychiatric co-morbidities are common in Parkinson′s disease and may predate motor symptoms. Currently there is scarcity of data regarding neuropsychiatry manifestations in Indian patients with PD. Methods: In this cross-sectional study consecutive 126 non-demented patients with PD (MMSE ≥25) were enrolled. They were assessed using Unified Parkinson′s disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Schwab and England (S&E) scale of activity of daily life. Mini-international neuropsychiatric interview (MINI) was used for diagnosis of depression, psychosis and anxiety. Beck′s depression inventory (BDI), Brief psychiatric rating scale (BSRS) and Hamilton rating scale for anxiety (HAM-A) scales were used for assessment of severity of depression, psychosis and anxiety respectively. Results: Mean age and duration of disease was 57.9 ± 10.9 years and 7.3 ± 3.6 years respectively. At least one of the neuropsychiatric co-morbidity was present in 64% patients. Depression, suicidal risk, psychosis and anxiety were present in 43.7%, 31%, 23.8% and 35.7% respectively. Visual hallucinations (20.6%) were most frequent, followed by tactile (13.5%), auditory (7.2%) and olfactory hallucinations (1.6%). Patients with depression had higher motor disability (UPDRS-motor score 33.1 ± 14.0 vs 27.3 ± 13.3; and UPDRS-total 50.7 ± 21.8 vs 41.0 ± 20.3, all p values

Objectives : To determine an association between socioeconomic status and in-hospital outcome in Indian patients with stroke. Materials and Methods : Retrospective hospital-based cohort study. The hospital stroke register was used for this study. The independent variables were demographic job status, education, cardiovascular risk factors, comorbidities and the score on the Glasgow Coma Scale (GCS). The outcome variables were mortality and Barthel′s index (BI) score at discharge. Results : Data of 599 consecutive patients comprising 370 men (54.3%) and 229 women (33.6%) was available for analysis. Their mean age was 55.63±15.36 years. Age, diagnosis (ischemic or hemorrhagic), midline shift, smoking and GCS were significantly associated with mortality and BI score (P