Escalate: Linezolid as an add on treatment in the intensive phase of tubercular meningitis. A randomized controlled pilot trial.

Most drugs used in the treatment of Tuberculous Meningitis have limited CNS penetration thereby limiting efficacy. CSF penetration of linezolid is 80-100%.The study was a prospective, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients were randomized in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD Linezolid for 4 weeks along with standard four drug ATT [HRZE/S]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. 29 patients were recruited and 27 completed three months of follow up. There was no significant difference in terms of mortality with Odds ratio (95% CI) of 2 (0.161-24.87; p = 1) at one month and 0.385 (0.058-2.538; p = 0.39) at three months. There was a significant improvement in GCS in Linezolid group at one month and mRS within the Linezolid group at one and three months. No major safety concerns were observed. The sample size is underpowered to draw any definitive conclusions but improvement in mRS and GCS as well as mortality change make a case for a large sample size trial.

Biosimilar Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Real World Study.

Background and Purpose: There is an unmet need for a more effective thrombolytic agent in acute ischemic stroke (AIS) management. Various studies and meta-analysis suggest tenecteplase (TNK) as non-inferior over alteplase (rTPA). The present single-center study compares biosimilar TNK and rTPA in a tertiary care setting. Methods: Data of patients who presented with AIS and underwent intravenous thrombolysis (IVT) were recruited retrospectively from January 2018 to July 2021. Primary efficacy outcome was a modified Rankin score (mRS) at 90 days dichotomized at < = 2. Qualitative and quantitative variables were assessed using Chi-square test and Student's t-test, respectively. Results: A total of 160 patients, 103 in the rTPA and 57 in TNK group, were analyzed. The baseline characteristics were well matched apart from hypertension. Large artery atherosclerosis was the most frequent subtype of stroke among the two groups. Good functional outcome was seen in 47.92% of patients TNK and 64.77% of patients in rTPA group (p = 0.069). No difference was seen in the rates of any ICH (p = 0.29) and mortality at 3 months (p = 0.32) among the two groups. Conclusion: This present study observed no difference in the efficacy and safety between biosimilar TNK and rTPA. Our findings are in concordance with published trials showing equivalence between the two molecules.

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

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

Study Protocol: IMPETUS: Implementing a Uniform Stroke Care Pathway in Medical Colleges of India: IMPETUS Stroke.

Introduction: In India, a national program for stroke (national programme for the control of cardiovascular diseases, diabetes, cancer, and stroke) and stroke management guidelines exist. Its successful implementation would need an organized system of stroke care in practice. However, many challenges exist including lack of awareness, prehospital notification systems, stroke ready hospitals, infrastructural weaknesses, and rehabilitation. We present here a protocol to investigate the feasibility and fidelity of implementing a uniform stroke care pathway in medical colleges of India. Methods and Analysis: This is a multicentric, prospective, multiphase, mixed-method, quasi-experimental implementation study intended to examine the changes in a select set of stroke care-related indicators over time within the sites exposed to the same implementation strategy. We shall conduct process evaluation of the implementation process as well as evaluate the effect of the implementation strategy using the interrupted time series design. During implementation phase, education and training about standard stroke care pathway will be provided to all stakeholders of implementing sites. Patient-level outcomes in the form of modified Rankin Scale score will be collected for all consecutive patients throughout the study. Process evaluation outcomes will be collected and reported in the form of various stroke care indicators. We will report level and trend changes in various indicators during the three study phases. Discussion: Acute stroke requires timely detection, management, and secondary prevention. Implementation of the uniform stroke care pathway is a unique opportunity to promote the requirements of homogenous stroke care in medical colleges of India.

Cyclophosphamide therapy as an adjunct in refractory post-tubercular arachnoiditis.

INTRODUCTION: There is no satisfactory treatment for post tubercular arachnoiditis (TB arachnoiditis). We did this study to investigate the efficacy and safety of cyclophosphamide as adjuvant therapy for post TB arachnoiditis refractory to corticosteroids and anti-tubercular therapy (ATT). METHODS: This was a retrospective case series of patients of refractory post TB arachnoiditis leading to paraparesis and vision loss who received cyclophosphamide as an adjuvant therapy along with standard ATT and corticosteroids. These patients were treated with intravenous cyclophosphamide (dose 500 mg/m2) once a month for 4 consecutive months after informed written consent and were assessed clinically and radiologically before and after cyclophosphamide therapy. RESULTS: We had 4 patients with refractory post TB arachnoiditis of whom three became independently ambulatory. There was significant clinical as well as radiological improvement in all the patients. CONCLUSIONS: Cyclophosphamide therapy could be an effective therapy for patients with refractory post TB arachnoiditis. Well-designed randomized controlled studies are essential to study the safety and efficacy of cyclophosphamide in this condition.

Patients with Neurological Illnesses and Their Experience During the Lockdown: A Teleinterview-based Study.

Background: Governments have imposed lockdowns in the wake of the COVID-19 pandemic. Hospitals have restricted outpatient clinics and elective services meant for non-COVID illnesses. This has led to patients facing unprecedented challenges and uncertainties. This study was carried out to assess patients' concerns and apprehensions about the effect of the lockdown on their treatments. Materials and Methods: An ambispective, observational cross-sectional single centre study was conducted. Patients were contacted telephonically and requested to answer a structured questionnaire. Their responses were documented and summarized as frequency and proportions. Results: A total of 727 patients were interviewed. Epilepsy (32%) was the most common neurological illness in our cohort followed by stroke (18%). About half the patients and/or their caregivers reported health-related concerns during the lockdown. The primary concern was how to connect with their treating neurologist if need arose. Forty-seven patients (6.4%) had drug default. Among patients on immunomodulatory treatments, only eight patients had drug default. High compliance rates were also observed in the stroke and epilepsy cohorts. Of the 71 patients who required emergency care during the lockdown, 24 could reach our hospital emergency. Fourteen patients either had a delay or could not seek emergency care. Two-thirds of our patients found the telemedicine experience satisfactory. Conclusion: The ongoing pandemic will continue to pose challenges to both physicians and patients. Patients in follow-up may need to be contacted regularly and counselled regarding the importance of maintaining drug compliance. Telemedicine can be used to strengthen the healthcare delivery to patients with non-COVID illnesses.

Clinical Utility of Intravascular Ultrasound (IVUS) in Carotid Artery Interventions: A Systematic Review and Meta-analysis.

BACKGROUND: Carotid plaque morphology plays an important role in determining outcome of carotid artery stenting (CAS). Intravascular ultrasound (IVUS) and its extension VH (Virtual Histology)-IVUS evaluate plaque characteristics in real time and guide decision making during stenting. To date, there is no consensus about indications of IVUS and its validated methods. This systematic review and meta-analysis aims to evaluate the clinical utility of IVUS in carotid artery interventions (CAS) and develop a future consensus for research and practice parameters. METHODS: A systematic review and meta-analysis was performed of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings and also its performance compared with other imaging modalities were included in review. Pooled prevalence with 95% confidence intervals (CI) was calculated. The statistical analysis was conducted in R version 3.6.2. RESULTS: A total of 2015 patients from 29 studies were included. Proportional meta-analysis was performed on 1566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4% (95% CI 3%-5%) while asymptomatic stroke had a pooled prevalence of 46% (95% CI 31%-62%) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n=33/396 vs 11/396). IVUS led to stent type or size change in 8 of 48 cases which were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80% to 85% reported in 2 studies. CONCLUSIONS: This systematic review and meta-analysis showed, though IVUS fared better to computed tomography (CT)/magnetic resonance (MR) angiography for better stent selection during CAS, with low to moderate risk of bias in the studies included. However, large scale, preferably randomized controlled studies are needed to predict its role in determining clinical outcome.

Pallidal Deep Brain Stimulation for KMT2B Related Dystonia in An Indian Patient.

Outcomes of pallidal stimulation in KMT2B dystonia have been infrequently reported prospectively. We report the six-month outcomes of bilateral GPi DBS in an Asian Indian patient with early-onset generalized dystonia associated with a novel heterozygous variant in the KMT2B gene.

Artificial Intelligence shaping the future of neurology practice.

Neurology practice has faced many challenges since Jean-Martin Charcot established its sacred tenets. Artificial Intelligence (AI) promises to revolutionize the time-tested neurology practice in unimaginable ways. AI can now diagnose stroke from CT/MRI scans, detect papilledema and diabetic retinopathy from retinal scans, interpret electroencephalogram (EEG) to prognosticate coma, detect seizure well before ictus, predict conversion of mild cognitive impairment to Alzheimer's dementia, classify neurodegenerative diseases based on gait and handwriting. Clinical practice would likely change in near future to accommodate AI as a complementary tool. The clinician should be prepared to change the perception of AI from nemesis to opportunity.

Systemic lupus erythematosus presenting with holocord myelitis.

This is a report of a case of a 25-year-old woman, who presented with a rapidly progressive sensory-motor flaccid quadriparesis which had developed over a few days along with bladder and bowel involvement. She had a past history of photosensitive rash and joint pains along with mild-to-moderate grade fever; for which she had never been evaluated. Serological markers for systemic lupus erythematosus (SLE) were strongly positive and helped in establishing the diagnosis of SLE-related holocord myelitis. High-dose intravenous glucocorticoid followed by intravenous pulse cyclophosphamide was used to treat her and there was a significant improvement. In this case report, the diagnosis of SLE was made for the first time in a patient presenting with holocord myelitis.

Efficacy of Low-Frequency Repetitive Transcranial Magnetic Stimulation in Ischemic Stroke: A Double-Blind Randomized Controlled Trial.

OBJECTIVE: To investigate the role of low-frequency repetitive transcranial magnetic stimulation (rTMS) along with conventional physiotherapy in the functional recovery of patients with subacute ischemic stroke. DESIGN: Double-blind, parallel group, randomized controlled trial. SETTING: The outpatient department of a tertiary hospital participants: first ever ischemic stroke patients (N=96) in the previous 15 days were recruited and were randomized after a run-in period of 75±7 days into real rTMS (n=47) and sham rTMS (n=49) groups. INTERVENTION: Conventional physical therapy was given to both the groups for 90±7 days postrecruitment. Total 10 sessions of low-frequency rTMS on contralesional premotor cortex was administered to real rTMS group (n=47) over a period of 2 weeks followed by physiotherapy regime for 45-50 minutes. MAIN OUTCOME MEASURES: The primary efficacy outcomes were change in modified Barthel Index (mBI) score (pre- to postscore) and proportion of participants with mBI score more than 90, measured at 90±7 days postrecruitment. The secondary outcomes were change in Fugl-Meyer Assessment-upper extremity, Fugl-Meyer Assessment-lower extremity, Hamilton Depression Scale, modified Rankin Scale, and National Institute of Health and Stroke Scale (pre- to post-rTMS) scores at 90±7 days post recruitment. RESULTS: Modified intention to treat analysis showed a significant increase in the mBI score from pre- to post-rTMS in real rTMS group (4.96±4.06) versus sham rTMS group (2.65±3.25). There was no significant difference in proportion of patients with mBI>90 (55% vs 59%; P=.86) at 3 months between the groups. CONCLUSION: In patients with subacute ischemic stroke, 1-Hz low-frequency rTMS on contralesional premotor cortex along with conventional physical therapy resulted in significant change in mBI score.

Head to head comparison between neurology residents and a mobile medical application for diagnostic accuracy in cognitive neurology.

BACKGROUND: A novel Mobile Medical Application (App) App was created on iOS platform (Neurology Dx®) to deduce Differential Diagnoses (DDx) from a set of user selected Symptoms, Signs, Imaging data and Lab findings. The DDx generated by the App was compared for diagnostic accuracy with differentials reasoned by participating neurology residents when presented with same clinical vignettes. METHODS: Hundred neurology residents in seven leading Neurology centers across India participated in this study. A panel of experts created 60 clinical vignettes of varying levels of difficulty related to Cognitive neurology. Each neurology resident was instructed to formulate DDx from a set of 15 cognitive neurology vignettes. Experts in Cognitive Neurology made the gold standard DDx answers to all 60 clinical vignettes. The differentials generated by the App and neurology residents were then compared with the Gold standard. RESULTS: Sixty clinical vignettes were tested on 100 neurology residents (15 vignettes each) and also on the App (60 vignettes). The frequency of gold standard high likely answers accurately documented by the residents was 25% compared with 65% by the App (95% CI 33.1-46.3), P < 0.0001. Residents correctly identified the first high likely gold standard answer as their first high likely answer in 35% (95% CI 30.7-36.6) compared with 62% (95% CI 14.1-38.5), P < 0.0001. CONCLUSION: An App with adequate knowledge-base and appropriate algorithm can augment and complement human diagnostic reasoning in drawing a comprehensive list of DDx in the field of Cognitive Neurology (CTRI/2017/06/008838).