Publication of neurology clinical trials registered with clinical trial registry of India: A cross-sectional study.

OBJECTIVES: Unbiased and full disclosure of trial results is vital to evidence-based medicine. Non-publication and selective publication leads to publication bias and unrealistic risk-benefit ratio. In the present study, we aim to determine the publication rate of clinical trials related to neurology registered with the Clinical Trial Registry of India (CTRI), compare the characteristics of published and unpublished trials, and evaluate the adherence of investigators to ethics-approved criteria and outcomes. MATERIALS AND METHODS: A cross-sectional search using the keyword "neurology" was carried out in CTRI registry. Two independent investigators searched Pubmed, Medline, Scopus, and Google Scholar for published manuscripts. The final literature search occurred in November 2021. RESULTS: Out of 325 trials, 102 trials were published (31.4%). Ninety-one trials were beyond 3 years of expected time of trial completion and were still unpublished. Randomized trials had a slightly higher publication rate than non-randomized ones (56% vs. 46%, p = .223); however the difference was not statistically significant. Majority of trials sponsored by pharmaceutical companies were not published, while majority of those sponsored by non-pharmaceutical institutions were published (34.5% vs. 69.3%, p < .001). Feedback to CTRI about trial status was particularly poor (31.5% - informed vs. 68.5% - not informed, p < .001). 52 (50.9%) and 65 (63.7%) of the 102 published trials had changed the registered inclusion and exclusion criteria, respectively, in the CTRI registry compared to those in the published manuscript. In 29 (28.3%) of the 102 trials, the primary outcome did not match with that registered in the CTRI and in 73 (57.8%) trials, the secondary outcomes did not match. CONCLUSION: A large proportion of neurology registered trials are still unpublished, with a majority of pharmaceutical company-sponsored trials not being published. There is scope for improving the provisions in CTRI for enlisting trial results, that may prevent publication bias and also ensure the investigators adhere to the pre-specified ethics approved trial procedures and outcomes.

Feasibility of combining functional near-infrared spectroscopy with electroencephalography to identify chronic stroke responders to cerebellar transcranial direct current stimulation-a computational modeling and portable neuroimaging methodological study.

Feasibility of portable neuroimaging of cerebellar transcranial direct current stimulation (ctDCS) effects on the cerebral cortex has not been investigated vis-à-vis cerebellar lobular electric field strength. We studied functional near-infrared spectroscopy (fNIRS) in conjunction with electroencephalography (EEG) to measure changes in the brain activation at the prefrontal cortex (PFC) and the sensorimotor cortex (SMC) following ctDCS as well as virtual reality-based balance training (VBaT) before and after ctDCS treatment in 12 hemiparetic chronic stroke survivors. We performed general linear modeling (GLM) that putatively associated the lobular electric field strength with the changes in the fNIRS-EEG measures at the ipsilesional and contra-lesional PFC and SMC. Here, fNIRS-EEG measures were found in the latent space from canonical correlation analysis (CCA) between the changes in total hemoglobin (tHb) concentrations (0.01-0.07Hz and 0.07-0.13Hz bands) and log10-transformed EEG bandpower within 1-45 Hz where significant (Wilks' lambda>0.95) canonical correlations were found only for the 0.07-0.13-Hz band. Also, the first principal component (97.5% variance accounted for) of the mean lobular electric field strength was a good predictor of the latent variables of oxy-hemoglobin (O2Hb) concentrations and log10-transformed EEG bandpower. GLM also provided insights into non-responders to ctDCS who also performed poorly in the VBaT due to ideomotor apraxia. Future studies should investigate fNIRS-EEG joint-imaging in a larger cohort to identify non-responders based on GLM fitting to the fNIRS-EEG data.

Evidence of neuroplasticity with robotic hand exoskeleton for post-stroke rehabilitation: a randomized controlled trial.

BACKGROUND: A novel electromechanical robotic-exoskeleton was designed in-house for the rehabilitation of wrist joint and Metacarpophalangeal (MCP) joint. OBJECTIVE: The objective was to compare the rehabilitation effectiveness (clinical-scales and neurophysiological-measures) of robotic-therapy training sessions with dose-matched conventional therapy in patients with stroke. METHODS: A pilot prospective parallel randomized controlled study at clinical settings was designed for patients with stroke within 2 years of chronicity. Patients were randomly assigned to receive an intervention of 20 sessions of 45 min each, five days a week for four weeks, in Robotic-therapy Group (RG) (n = 12) and conventional upper-limb rehabilitation in Control-Group (CG) (n = 11). We intended to evaluate the effects of a novel exoskeleton based therapy on the functional rehabilitation outcomes of upper-limb and cortical-excitability in patients with stroke as compared to the conventional-rehabilitation. Clinical-scales- Modified Ashworth Scale, Active Range of Motion, Barthel-Index, Brunnstrom-stage and Fugl-Meyer (FM) scale and neurophysiological measures of cortical-excitability (using Transcranial Magnetic Stimulation) -Motor Evoked Potential and Resting Motor threshold, were acquired pre- and post-therapy. RESULTS: No side effects were noticed in any of the patients. Both RG and CG showed significant (p < 0.05) improvement in all clinical motor-outcomes except Modified Ashworth Scale in CG. RG showed significantly (p < 0.05) higher improvement over CG in Modified Ashworth Scale, Active Range of Motion and Fugl-Meyer scale and FM Wrist-/Hand component. An increase in cortical-excitability in ipsilesional-hemisphere was found to be statistically significant (p < 0.05) in RG over CG, as indexed by a decrease in Resting Motor Threshold and increase in the amplitude of Motor Evoked Potential. No significant changes were shown by the contralesional-hemisphere. Interhemispheric RMT-asymmetry evidenced significant (p < 0.05) changes in RG over CG indicating increased cortical-excitability in ipsilesional-hemisphere along with interhemispheric changes. CONCLUSION: Robotic-exoskeleton training showed improvement in motor outcomes and cortical-excitability in patients with stroke. Neurophysiological changes in RG could most likely be a consequence of plastic reorganization and use-dependent plasticity. Trial registry number: ISRCTN95291802.

Educating Caregivers to Reduce Complications and Improve Outcomes of Stroke Patients (ECCOS) - A Cluster-Randomized Trial.

OBJECTIVES: Stroke constitutes a significant public health problem in developing countries. Caregivers provide an important support system for patient care but usually lack knowledge and skill to attend their stroke patients. We assessed whether a caregiver-directed educational intervention would reduce hospital-acquired complications and improve stroke patients' outcomes. MATERIALS AND METHODS: We randomly assigned two Neurology inpatient wards to receive either standard care or an educational intervention. The coprimary outcomes included incidence of hospital-acquired complications and in-hospital mortality. Secondary outcomes included the modified Rankin Scale and mortality at three months. RESULTS: Among 164 patients recruited, 82 received intervention, and standard care each. The mean (Standard deviation) Glasgow coma scale of patients was 11.01 (3.4), and National Institute of Health Stroke Scale was 19.17 (8.54). The incidence of complications (72 in the intervention versus 81 in the control group; p=0.56) was not different. Ten patients (12.2%) in the intervention group and 16 (19.5%) in the control group (p=0.20) died in-hospital. Twenty patients (27.8%) in the intervention and twelve (18.2%) in the control group attained modified Rankin Scale 0-2 at three months (p=0.12). The mortality at three months (20 [24.4%] in the intervention versus 25 [30.5%] in the control group) was not different (p=0.38). The intervention group had fewer complications (42 versus 68 in the control group; p=0.01) during the initial ten days of hospital stay, but adjusted analysis revealed no difference. CONCLUSION: A structured educational intervention did not reduce the incidence of hospital-acquired complications, mortality, or morbidity. However, there was a trend towards fewer complications in the initial days of hospital stay. Extended hospital stay, caregiver fatigue, and dilution of the intervention over time might be reasons for the apparent lack of effect. CLINICAL TRIAL REGISTRATION-URL: http://www.ctri.nic.in. Unique identifier: CTRI/2018/11/016312.

Validation of ICH and ICH-GS Scores in an Indian Cohort: Impact of Medical and Surgical Management.

OBJECTIVE: Prognostic scores help in predicting mortality and functional outcome post intracerebral hemorrhage (ICH). We aimed to validate the ICH and ICH-GS scores in a cohort of Indian patients with ICH and observe the impact of any surgical intervention on prognostication. METHODS: This was an ambispective observational study of primary ICH cases enrolled between January 2014 and April 2018. Observed mortality on ICH and ICH GS scores for the entire cohort and individually for the medically and surgically managed patients was compared to the published mortality in the original derivation cohorts. RESULTS: 617 patients, (464 retrospective and 153 prospective) of ICH were included. In hospital mortality and 30-day mortality was 28.7% and 28.5% respectively. There was a significant association of increasing mortality with increasing ICH and ICH-GS scores. Area under receiver operating characteristic curve for 30-day mortality was 75.9% and 74.1% for ICH and ICH-GS scores respectively. However, mortality observed at individual scores was significantly less than previously reported. Among the surgically intervened patients (n = 265), both the expected mortality at baseline and discriminative ability of ICH and ICH-GS scores for 30-day mortality was significantly reduced following surgical intervention (ROC in surgically intervened groups: 59.9 (52.6-67.2) and 63(56-70) for ICH and ICH-GS scores respectively). CONCLUSIONS: Although ICH and ICH-GS scores are valid in Indian population, mortality at individual scores is lower than previously reported. Mortality prediction using ICH and ICH GS scores is significantly modified by surgical interventions. Thus, newer prognostic tools which incorporate surgical intervention need to be developed and validated in future.

Coronary Artery Disease in Patients with Ischemic Stroke and TIA.

BACKGROUND AND OBJECTIVES: Ischemic stroke (IS) and coronary artery disease (CAD) share common risk factors and one may be the harbinger of the other. We aimed to study prevalence of symptomatic and asymptomatic CAD in a cohort of consecutive patients with IS and assess its relationship with intracranial and extracranial large artery cerebrovascular disease (LAD). METHODS: All consecutive eligible IS and Transient Ischemic Attack (TIA) patients were recruited into the study. Both clinically suspected and asymptomatic patients (N = 259) underwent myocardial Stress-rest Gated Technetium-99m (Tc99m) MIBI Myocardial Perfusion SPECT scan performed on a dual head SPECT-CT to estimate evidence of myocardial ischemia. RESULTS: Three hundred patients completed the study. Forty one patients were previously diagnosed cases of definitive CAD. Twelve patients were clinically suspected to have CAD and 247 patients were asymptomatic. Among these, 12 patients (4.81%) had a positive SPECT. The overall prevalence of CAD was 17.67% (n = 53). Presence of diabetes was an independent predictor of CAD (OR 1.98, 95% CI 1.07-3.67. P .02). No significant association was found between the presence of LAD and CAD in all subgroup comparisons. However, there was a suggestion of higher LAD among patients with known CAD compared with others. CONCLUSIONS: CAD is prevalent in patients with ischemic stroke. No definitive relationship was found between CAD and intracranial or extracranial LAD. Population based stratification tools are needed to further assess the need to detect subclinical CAD in patients with stroke.

Ischemic Stroke Profile, Risk Factors, and Outcomes in India: The Indo-US Collaborative Stroke Project.

BACKGROUND AND PURPOSE: The Indo-US Collaborative Stroke Project was designed to characterize ischemic stroke across 5 high-volume academic tertiary hospitals in India. METHODS: From January 2012 to August 2014, research coordinators and physician coinvestigators prospectively collected data on 2066 patients with ischemic stroke admitted <2 weeks after onset. Investigator training and supervision and data monitoring were conducted by the US site (Massachusetts General Hospital, Boston). RESULTS: The mean age was 58.3±14.7 years, 67.2% men. The median admission National Institutes of Health Stroke Scale score was 10 (interquartile range, 5-15) and 24.5% had National Institutes of Health Stroke Scale ≥16. Hypertension (60.8%), diabetes mellitus (35.7%), and tobacco use (32.2%, including bidi/smokeless tobacco) were common risk factors. Only 4% had atrial fibrillation. All patients underwent computed tomography or magnetic resonance imaging; 81% had cerebrovascular imaging. Stroke etiologic subtypes were large artery (29.9%), cardiac (24.9%), small artery (14.2%), other definite (3.4%), and undetermined (27.6%, including 6.7% with incomplete evaluation). Intravenous or intra-arterial thrombolysis was administered in 13%. In-hospital mortality was 7.9%, and 48% achieved modified Rankin Scale score 0 to 2 at 90 days. On multivariate analysis, diabetes mellitus predicted poor 3-month outcome and younger age, lower admission National Institutes of Health Stroke Scale and small-artery etiology predicted excellent 3-month outcome. CONCLUSIONS: These comprehensive and novel clinical imaging data will prove useful in refining stroke guidelines and advancing stroke care in India.

Changes in psychiatric comorbidity during early postsurgical period in patients operated for medically refractory epilepsy--a MINI-based follow-up study.

PURPOSE: The purpose of this study was to assess axis-I DSM-IV psychiatric disorders in patients at baseline and 3 months after surgery for medically refractory temporal lobe epilepsy. METHOD: The Mini International Neuropsychiatric Interview (MINI) and Quality of Life in Epilepsy Inventory-10 (QOLIE-10) were evaluated before and 3 months after surgery in 50 consecutive patients (21 females, 29 males) with medically refractory temporal lobe epilepsy (persistent seizures>2/month, despite treatment with ≥2 appropriate drugs in adequate doses for ≥2 years) who underwent surgery [anterior temporal lobectomy with amygdalo-hippocampectomy (for mesial temporal sclerosis in 40), electrocorticography-guided lesionectomy (for other lesions in 10)]. RESULTS: Twenty-six patients (52%) had an axis-I psychiatric disorder [26% depressive disorder, 28% anxiety disorder] at baseline, while 30 (60%) patients had an axis-I psychiatric disorder [28% depressive disorder, 28% anxiety disorder] at 3 months after surgery. Twenty percent developed a new psychiatric disorder, while 12% showed improvement postsurgery. Mean QOLIE-10 scores improved from 23.78 to 17.80 [24 (48%) patients showed ≥5-point improvement]. Thirty-four (68%) patients had no seizure, 6 (12%) had non-disabling seizures, while 2 (4%) had disabling seizures after surgery. High frequency of seizures prior to surgery (p<0.038) and seizure occurrence after surgery (p<0.055) predicted the presence of psychiatric disorders after surgery. No clinical characteristic could predict development of new psychiatric disorder after surgery. CONCLUSION: Psychiatric dysfunction in the early postsurgery period is seen in nearly half of patients undergoing surgery for temporal lobe epilepsy, is mild in nature, and does not adversely affect quality of life but may cause significant clinical problems when it arises de novo postsurgery.

Paraneoplastic cerebellar degeneration as the first evidence of malignancy: a case report.

Paraneoplastic cerebellar degeneration (PCD) is an immune-mediated paraneoplastic disorder affecting the cerebellum. PCD associated with ovarian malignancy is a rare occurrence with fewer than 100 cases reported in published work. PCD patients express anti-Yo antibody, one of the anti-onconeuronal antibodies which is most likely associated with gynecologic or breast malignancies. In this report, we present the case of a 65-year-old postmenopausal woman presenting with acute symptoms of PCD as a first sign of ovarian malignancy.

Novel inflammatory biomarkers and their correlation to Chlamydia pneumoniae titres in acute ischemic stroke.

BACKGROUND: Young stroke patients constitute 15%-30% of all stroke patients in India as against 3.0%-8.5% reported from the West. The mechanisms for stroke in the young may include unconventional risk factors such as infections. We aimed to investigate the role (if any) of Chlamydia pneumoniae antibodies in young patients with acute ischemic stroke (AIS). Several proinflammatory cytokines and biomarkers are released early after the onset of brain ischemia. We assessed the role of heat shock protein (hsp) 65, neopterin, and myeloperoxidase upregulation after AIS in predicting stroke severity. We also assessed relationship of upregulated inflammatory biomarkers with C pneumoniae antibody titres (IgG, IgA, and IgM). METHODS: Eighty acute stroke patients and healthy age- and sex-matched controls were recruited. Blood samples were drawn within 1 week from the onset of stroke. Detection of IgA, IgG, and IgM antibodies to C pneumoniae was done with a validated microimmunofluorescence technique from 5 mL of serum in all subjects. Inflammatory biomarkers such as neopterin, myeloperoxidase and hsp 65 were estimated with sandwich enzyme linked immunosorbent assay (ELISA) method. RESULTS: hsp 65 and neopterin were significantly elevated in all stroke patients with respect to healthy controls (odds ratio [OR], 4.9; 95% confidence interval [CI], 23.5-67.8; P = .001 and OR, 4.4; 95% CI, 2.08-9.4; P = .04, respectively). Eighty-one percent of cases were seropositive for IgA versus 32% of controls (P = .003), and IgG was positive in 52.7% versus 17.3% of controls (P = .05). Myeloperoxidase levels were similar in patients and controls. Correlation and multiple regression indicated a high level of predictability and sensitivity of hsp 65 to IgA. C. pneumoniae antibody titres when all other variables were constant (F [4,90] = -6.8, P = .001). Patients with high NIHSS scores (>15) had elevated levels of hsp 65 (mean, 13.2 ng/mL) suggesting correlation with stroke severity. CONCLUSIONS: The study demonstrated high levels of hsp 65 and neopterin levels in AIS correlated to significantly elevated IgA titres of C pneumoniae. Elevated levels of hsp 65 were associated with stroke severity.

The Pitfalls of NIHSS: Time for a New Clinical Acute Stroke Severity Scoring System in the Emergency?

Stroke is the second leading cause of death and a major cause of disability worldwide. Stroke severity scales serve as reliable means to track a patient's neurological deficit, predict outcome, and guide treatment decisions in clinical practice. The National Institute of Health Stroke Scale (NIHSS) was introduced over 30 years ago, marking a significant milestone in the field of stroke. Over the years, there have been notable advancements in acute stroke care. Despite several modifications made to NIHSS, none has yet succeeded in effectively capturing all the complex effects of a stroke. This review focuses on the pitfalls of NIHSS and emphasizes the need for a quick and comprehensive clinical and upgraded version of the stroke severity rating scale.

Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research.

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.

Outcomes of COVID-19 disease and its effect on disability in patients with multiple sclerosis and other allied demyelinating disorders.

BACKGROUND: Coronavirus disease of 2019 (COVID-19) pandemic has posed challenges for clinicians with respect to questions regarding vulnerability of patients with chronic autoimmune diseases like Multiple Sclerosis (MS) and other demyelinating central nervous system (CNS) disorders. OBJECTIVES: We assessed outcomes of COVID-19 disease among patients with CNS demyelinating disorders and its effect on neurological disability. METHODS: This was an electronic survey in which a structured questionnaire was distributed to patients registered with neuroimmunology and MS clinics at All India Institute of Medical Sciences, New Delhi, India. The patients were enquired for their primary disease characteristics, occurrence and course of COVID-19 infection and its effect on their underlying disability, if any. Patients visiting clinics in person were also assessed and data from both sources was pooled. RESULTS: 61 patients with these disorders reported to have contracted COVID-19 infection (mean age- 35.60+10.28 years, females-75.4%, MS-85.2%). None of them suffered from severe/critical COVID-19 despite heterogeneity of disease modifying therapy (DMT) use. DMTs were not associated with increased risk of lymphopenia during illness. 3.3% patients reported fresh relapse and 16.4% had worsening of their neurological disability during/after COVID-19 infection with half of them not attaining their baseline status on follow-up. None of demographic or biochemical parameters were predictive of this neurological worsening. CONCLUSION: Our study suggests that patients with these disorders might not be at heightened risk of severe COVID-19. Adverse effect of COVID-19 infection on neurological disability needs further exploration.