Introduction: Genetic factors may play a role in the susceptibility of intracerebral hemorrhage (ICH). The present case-control study hypothesized that genetic polymorphisms in tumor necrosis factor- ...α (TNF-α) gene may affect the risk of ICH.
Materials and Methods: In this study, we investigated the association of four single nucleotide polymorphisms (-308G/A, +488G/A, -857C/T, and -1031T/C) within TNF-α gene promoter and their haplotypes with the risk of ICH in a North Indian population. Genotyping was determined by using the SNaPshot method for 100 ICH patients and 100 age and sex-matched ICH-free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between TNF-α gene polymorphisms and risk of ICH. Haplotypes were reconstructed using PHASE 2.0, and patterns of linkage disequilibrium (LD) analysis were performed using Haploview version 4.2 software.
Results: TNF-α +488G/A gene polymorphism was found to be independently associated with the risk of ICH under dominant GG + GA vs. AA (OR = 3.1; 95% CI = 1.2-8.2; P = 0.001) and allelic G vs. A (OR = 2.2; 95% CI = 1.2-4.2; P = 0.007) models. However, no significant association between -308G/A, -857C/T, and -1031T/C gene polymorphisms and risk of ICH was observed. Haplotype analysis showed that 308A-488G-857C-1031T and 308G-488A-857T-1031T haplotypes were significantly associated with an increased risk of ICH. Strong LD was observed for + 488G/A and -857C/T TNF-α polymorphisms (D' = 0.72, r2= 0.01).
Conclusion: Our findings suggest that the TNF-α +488G/A polymorphism may be an important risk factor for ICH, whereas -308G/A, -857C/T, and -1031T/C gene polymorphisms may not be associated with risk of ICH in North Indian population.
Over 100 genetically distinct causal known loci for hereditary ataxia phenotype poses a challenge for diagnostic work‐up for ataxia patients in a clinically relevant time and precision. In the ...present study using next‐generation sequencing, we have investigated pathogenic variants in early‐onset cerebellar ataxia cases using whole exome sequencing in singleton/family‐designed and targeted gene‐panel sequencing. A total of 98 index patients were clinically and genetically (whole exome sequencing (WES) in 16 patients and targeted gene panel of 41 ataxia causing genes in 82 patients) evaluated. Four families underwent WES in family based design. Overall, we have identified 24 variants comprising 20 pathogenic and four likely‐pathogenic both rare/novel, variations in 21 early onset cerebellar ataxia patients. Among the identified variations, SACS (n = 7) and SETX (n = 6) were frequent, while ATM (n = 2), TTPA (n = 2) and other rare loci were observed. We have prioritized novel pathogenic variants in RARS2 and FA2H loci through family based design in two out of four families.
Objectives
To assess the time and frequency domain measures of cardiac autonomic activity/tone in patients of genetically defined spinocerebellar ataxia (SCA) types 1 and 2, as well as to decipher ...the probable associations among the cardiovascular autonomic parameters and genetic and clinical characteristics.
Materials and methods
Simultaneous 5‐min recording of RR interval (RRI) and blood pressure (BP) for the calculation of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were performed in genotypically confirmed SCA1 (n = 31) and SCA2 (n = 40) patients and healthy controls (n = 40). Additionally, the International Cooperative Ataxia Rating Scale (ICARS) was used for scoring of clinical severity in SCA patients.
Results
Time and frequency domain parameters of HRV, BPV and BRS were depressed in SCA1 and SCA2 subtypes as compared to controls, although there was no statistically significant difference in autonomic tone between the two SCA subtypes. On correlation analysis, autonomic tone parameters were found to be associated with the clinical and genetic features of the SCA subtypes. Also, ICARS was associated with the genotype (CAG repeat length) in SCA2 patents.
Conclusions
Cardiac autonomic tone is depressed in both SCA1 and 2 as compared to healthy controls while the two SCA subtypes do not differ in terms of autonomic tone. Also, a typical association exists between disease characteristics and autonomic indices.
4Clinical efficacy and outcomes can only be studied once patients are placed on the drug and then followed up on an objective quantitative scale (such as UPDRS) serially over a timeline (at least 12 ...weeks) with a reduction in quantified off-time before and after therapy, increase in on-time or improvement in nonmotor symptoms. ...information would have been of additional clinical utility.Although the authors state that all 29 subjects were confirmed PD patients, the results show that some of these patients had other parkinsonian syndromes (as indicated in Figure 3). Patient education and training of Apomorphine use and lack of concordance between patients and treating clinicians have been major barriers as experienced in many other resource-poor countries. Since it is an invasive therapy with definite indications as well as limitations, its acceptance by PD patients as well as neurologists in India for routine use in these patients will be known only in the years to come.
Abstract Tandem nucleotide repeat (TNR) expansions, particularly the CNG nucleotide configuration, are associated with a variety of neurodegenerative disorders. In this study, we aimed to identify ...novel unstable CNG repeat loci associated with the neurogenetic disorder spinocerebellar ataxia (SCA). Using a computational approach, 15,069 CNG repeat loci in the coding and noncoding regions of the human genome were identified. Based on the feature selection criteria (repeat length >10 and functional location of repeats), we selected 52 repeats for further analysis and evaluated the repeat length variability in 100 control subjects. A subset of 19 CNG loci observed to be highly variable in control subjects was selected for subsequent analysis in 100 individuals with SCA. The genes with these highly variable repeats also exhibited higher gene expression levels in the brain according to the tissue expression dataset (GTEx). No pathogenic expansion events were identified in patient samples, which is a limitation given the size of the patient group examined; however, these loci contain potential risk alleles for expandability. Recent studies have implicated GLS, RAI1, GIPC1, MED15, EP400, MEF2A , and CNKSR2 in neurological diseases, with GLS, GIPC1, MED15, RAI1 , and MEF2A sharing the same repeat loci reported in this study. This finding validates the approach of evaluating repeat loci in different populations and their possible implications for human pathologies.
Background: The data regarding patients eligible for endovascular thrombectomy (EVT), especially in the developing world is lacking.
Objective: To determine the proportion of patients with acute ...ischemic stroke (AIS) who are eligible for EVT in the 0-24-h time window.
Materials and Methods: We performed a retrospective cohort study using prospectively collected AIS data between July 2017 and September 2019. Demographic, clinical, and management information were analyzed. EVT eligibility was explored using the following criteria: National Institutes of Health Stroke Scale (NIHSS) score ≥6, presence of anterior circulation large-vessel occlusion (ACLVO), Alberta stroke program early Computerized Tomography score (ASPECTS) ≥6, baseline modified Rankin Scale (mRS) score 0-2, and within 24 h of time last seen well (TLSW). EVT-eligible patients were further evaluated for in-hospital course and outcomes.
Results: In the study period of 27 months, there were 221 patients with AIS who presented within 24 h. The mean age of the patients was 54.4 (16.0) years and 66.1% (146) were males. A majority (61.5% 136/221) arrived within 6 h of TLSW. Of these, 81.6% (111/136) presented in the time window for thrombolysis (0-4.5 h). The patients with NIHSS ≥6 and ACLVO constituted 41.2% (91/221) of the patients. AIS eligible for EVT constituted 19.5% (43/221) of the patients.
Conclusion: In our study, the proportion of AIS eligible for endovascular thrombectomy was comparable to the developed world. These data predict a large potential for the late-window EVT in India.
There is an unmet need for safe and efficacious treatments for upper-extremity dystonic tremor (DT). To date, only uncontrolled retrospective case series have reported the effect of botulinum ...neurotoxin (BoNT) injections on upper-extremity DT.
To assess the effect of BoNT injections on tremor in patients with upper-extremity DT.
In this placebo-controlled, parallel-group randomized clinical trial, 30 adult patients with upper-extremity DT treated at a movement disorder clinic in a tertiary care university hospital were randomized in a 1:1 ratio to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence. Randomization was masked using opaque envelopes. The participant, injector, outcome assessor, and statistician were blinded to the randomization. Participants were recruited between November 20, 2018, and December 12, 2019, and the last follow-up was completed in March 2020.
Participants received electromyographically guided intramuscular injections of BoNT or placebo into the tremulous muscles of the upper extremity. Injection patterns and doses were individualized according to tremor phenomenologic findings.
The primary outcome was the total score on the Fahn-Tolosa-Marin Tremor Rating Scale 6 weeks after the intervention. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. All patients were offered open-label BoNT injections after 12 weeks and reassessed 6 weeks later.
A total of 48 adult patients with a diagnosis of brachial dystonia with DT were screened. Fifteen were ineligible and 3 refused consent; therefore, 30 patients (mean SD age, 46.0 18.6 years; 26 86.7% male) were recruited, with 15 randomized to receive BoNT and 15 to receive placebo. In the intention-to-treat group, the Fahn-Tolosa-Marin Tremor Rating Scale total score was significantly lower in the BoNT group at 6 weeks (adjusted mean difference, -10.9; 95% CI, -15.4 to -6.5; P < .001) and 12 weeks (adjusted mean difference, -5.7; 95% CI, -11.0 to -0.5; P = .03). More participants in the BoNT group reported global improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 26.7%, 6 40.0%, and 5 33.3%; placebo: 5 33.3%, 10 66.7%, and 0, respectively; P = .047). Subjective hand weakness (BoNT: 6 40.0%; placebo: 4 28.6%, P = .52) and dynamometer-assessed grip strength (mean difference, -0.2 log10kgf/m22/Hz-Hz; 95% CI, -0.9 to 0.4 log10kgf/m22/Hz-Hz; P = .45) were similar in both groups.
In this randomized clinical trial, botulinum neurotoxin injections were superior to placebo in reducing tremor severity in upper-extremity DT. An individualized approach to muscle selection and dosing was beneficial without unacceptable adverse effects.
Clinical Trials Registry of India (http://ctri.nic.in) Identifier: CTRI/2018/02/011721.
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