IMPETUS Stroke: Assessment of hospital infrastructure and workflow for implementation of uniform stroke care pathway in India.

BACKGROUND: India accounts for 13.3% of global disability-adjusted life years (DALYs) lost due to stroke with a relatively younger age of onset compared to the Western population. In India's public healthcare system, many stroke patients seek care at tertiary-level government-funded medical colleges where an optimal level of stroke care is expected. However, there are no studies from India that have assessed the quality of stroke care, including infrastructure, imaging facilities, or the availability of stroke care units in medical colleges. AIM: This study aimed to understand the existing protocols and management of acute stroke care across 22 medical colleges in India, as part of the baseline assessment of the ongoing IMPETUS stroke study. METHODS: A semi-structured quantitative pre-tested questionnaire, developed based on review of literature and expert discussion, was mailed to 22 participating sites of the IMPETUS stroke study. The questionnaire assessed comprehensively all components of stroke care, including human resources, emergency system, in-hospital care, and secondary prevention. A descriptive analysis of their status was undertaken. RESULTS: In the emergency services, limited stroke helpline numbers, 3/22 (14%); prenotification system, 5/22 (23%); and stroke-trained physicians were available, 6/22 (27%). One-third of hospitals did not have on-call neurologists. Although non-contrast computed tomography (NCCT) was always available, 39% of hospitals were not doing computed tomography (CT) angiography and 13/22 (59%) were not doing magnetic resonance imaging (MRI) after routine working hours. Intravenous thrombolysis was being done in 20/22 (91%) hospitals, but 36% of hospitals did not provide it free of cost. Endovascular therapy was available only in 6/22 (27%) hospitals. The study highlighted the scarcity of multidisciplinary stroke teams, 8/22 (36%), and stroke units, 7/22 (32%). Lifesaving surgeries like hematoma evacuation, 11/22 (50%), and decompressive craniectomy, 9/22 (41%), were performed in limited numbers. The availability of occupational therapists, speech therapists, and cognitive rehabilitation was minimal. CONCLUSION: This study highlighted the current status of acute stroke management in publicly funded tertiary care hospitals. Lack of prenotification, limited number of stroke-trained physicians and neurosurgeons, relatively lesser provision of free thrombolytic agents, limited stroke units, and lack of rehabilitation services are areas needing urgent attention by policymakers and creation of sustainable education models for uniform stroke care by medical professionals across the country.

Area Postrema Syndrome: An Initial Presentation of Double-Seropositive AQP4 and MOG Antibodies.

Objectives: Area postrema syndrome (APS) is one of the core clinical features of neuromyelitis optic spectrum disorder (NMOSD). APS is mostly associated with neuromyelitis optica (NMO) and rarely reported in myelin oligodendrocyte glycoprotein antibody disease. We herein report a case of APS as an initial presentation of double-seropositive aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) antibodies. Methods: The patient fulfilled the NMOSD diagnostic criteria. Brain MRI, CSF studies, electrophysiologic test, and serum NMO and MOG antibody testing were performed. Results: An elderly woman initially presented to a gastroenterology outpatient department with a history of nausea, vomiting, and hiccups for 3 weeks. A detailed medical evaluation, including upper gastrointestinal endoscopy, was performed, which showed normal findings with no improvement with symptomatic therapy. A neurologic examination showed bilateral nystagmus, postural imbalance, and gait ataxia. An MRI examination of the brain showed T2/fluid attenuated inversion recovery hyperintensity in the dorsal medulla involving area postrema. Both anti-NMO and anti-MOG antibodies were found to be positive in serum. She was treated with intravenous methyl prednisolone with complete symptomatic resolution. Discussion: Double-seropositive APS-onset NMOSD has not been previously reported in literature. An early diagnosis and treatment result in the resolution of APS-related symptoms and prevent further progression of the disease.

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.

Stroke in Tuberculous Meningitis and Its correlation with Magnetic Resonance Angiography Manifestations.

Objective The primary objective of the study was to assess the location of cerebral infarction and look for corresponding magnetic resonance angiography (MRA) changes in patients with tuberculous meningitis (TBM). We also evaluated the predictors of ischemic stroke in TBM and the impact of these infarctions on patient's outcome. Methods This was a single-center prospective study between September 2018 and September 2020. Demographic and laboratory parameters were noted. Cranial magnetic resonance imaging and MRA were performed at the time of admission to the hospital. Results Among 120 patients with TBM, 46 had stroke. Nineteen (15.8%) patients died, of which 12 (10%) suffered from stroke. The most common site of infarction was the basal ganglia (54.3%). The commonest site of MRA abnormalities was the middle cerebral artery (39.1%). British Medical Research Council (BMRC) stage 3, cerebrospinal fluid (CSF) sugar, CSF adenosine deaminase (ADA) level, basal exudates, hydrocephalus, and hyponatremia were found to be predictors of stroke in TBM, while BMRC stage 3, CSF cell count, CSF ADA level, and anemia were found to be significantly associated with mortality in TBM patients with stroke. Conclusion The basal ganglia were the most common site of ischemic stroke in TBM, and middle cerebral artery was the most often involved intracranial blood vessel. BMRC stage 3 was significantly associated with both stroke and mortality in TBM patients with stroke.

Outcome of Guillain-Barré syndrome following intravenous immunoglobulin compared to natural course.

BACKGROUND AND PURPOSE: Intravenous immunoglobulin (IVIg) is recommended in Guillain-Barré syndrome (GBS), but its efficacy may vary in different subtypes. We report the outcomes of patients with GBS following IVIg treatment compared to the natural course (NC). We also compare the effect of IVIg treatment in different subtypes of GBS. METHODS: From a cohort of 528 GBS subjects, we have extracted 189 patients who received IVIg and compared their outcomes with 199 age- and peak disability-matched patients who did not receive IVIg, plasmapheresis, or corticosteroid. Disability was assessed using the 0-6 Guillain-Barré Syndrome Disability Scale (GBSDS). Clinical and neurophysiological subtypes were recorded. The primary outcome was functional disability at 6 months, which was categorized as complete (GBSDS ≤ 1), partial (GBSDS 2-3), or poor (GBSDS > 3). The secondary outcomes were in-hospital death, duration of hospitalization, and mechanical ventilation. RESULTS: In-hospital death (2.6% vs. 2%, p = 0.74) and 3-month poor recovery (20.7% vs. 18%) were similar in the IVIg and NC groups. At 6 months, however, a lesser proportion of patients in the IVIg group had poor recovery (2.2% vs. 8.3%, p = 0.026). The outcomes of IVIg and NC were compared in 72 acute motor axonal neuropathy (AMAN) and 256 acute inflammatory demyelinating polyradiculoneuropathy (AIDP) patients. IVIg therapy did not alter the outcome in AMAN but resulted in a lesser proportion of poor recovery at 6 months in AIDP (0.8% vs. 6.6%, p = 0.03). CONCLUSIONS: IVIg is beneficial in AIDP variants of GBS but not in the AMAN subtype. A customized treatment may be cost-effective until a randomized controlled trial is conducted in AMAN.

Neurological manifestations of hepatitis E virus infection: An overview.

Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.

Adjunctive Antioxidant Therapy in Neurologic Wilson's Disease Improves the Outcomes.

Oxidative stress has been reported in Wilson's disease with neurological manifestation (WDNM), but there is a paucity of studies on the role of adjunctive antioxidant therapy. This study aims to evaluate the efficacy of adjunctive vitamin C and E treatment in reducing oxidative stress and improving clinical outcomes. Forty-nine patients with WDNM were included and their clinical details were noted. Glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured using spectrophotometer at baseline and follow-up. All patients received zinc with or without chelating therapy, and 32 of them prescribed vitamin C (500 mg/day) and E (400 mg/day). Clinical outcomes at 6, 12, and 24 months were categorized as improved, static, or worsened based on improvement in Burke-Fahn-Marsden (BFM) score (>10%) and/or severity grade (> 1). Baseline parameters were similar between two groups; except BFM score was higher in the antioxidant group. At follow-up, the antioxidant group had higher GSH, TAC, and lower MDA levels compared with baseline. Patients on antioxidant treatment experienced improvement more frequently at 6 (53.1% vs. 29.4%), 12 (62.5% vs. 29.4%), and 24 months (68.8% vs. 35.3%) compared with those without antioxidant treatment. In WDNM, adjunctive vitamin C and E treatment reduce oxidative stress and improve clinical outcome.

Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy.

Patients with neurologic Wilson disease (NWD) may worsen on treatment, but there is no study evaluating the role of oxidative stress. We report the role of plasma glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in the worsening of NWD following treatment. Fifty-one treatment-naïve NWD patients were subjected to detailed clinical evaluation. The severity of NWD was noted, and dystonia was measured by Burke-Fahn-Marsden (BFM) score. Their hematological, serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at admission and at 3 and 6 months after treatment. The patients were considered worsened if there was one or more grade deterioration in severity scale, >10 % deterioration in BFM score or appearance of new neurologic signs. The median age of the patients was 11 (5-37) years, and 12 were females. Following treatment, 25 patients improved, 12 worsened, and 14 had stationary course. The worsened group at 3 months had lower GSH (1.99 ± 0.17 vs. 2.30 ± 0.30 mg/dl; P = 0.004) and TAC (1.59 ± 0.12 vs. 1.82 ± 0.17 mmol Trolox equivalent/L; P = 0.001) and higher MDA (5.24 ± 0.22 vs. 4.34 ± 0.46 nmol/ml; P < 0.001) levels compared to the improved group. These changes were associated with increased serum free Cu (41.81 ± 3.31 vs. 35.62 ± 6.40 µg/dl; P = 0.02) and 24-h urinary Cu (206.42 ± 41.61 vs. 121.99 ± 23.72 µg/24 h; P < 0.001) in the worsened compared to the improved group. All the patients having worsening were on penicillamine. Worsening following chelating treatment in NWD may be due to oxidative stress which is induced by increased serum free Cu. These results may have future therapeutic implication and needs further study.

Oromandibular Dystonia in Wilson's Disease.

BACKGROUND: Movement disorder is common in Wilson's disease (WD), but there is no report on oromandibular dystonia (OMD). We report on frequency, severity, and MRI correlation of OMD in Wilson's disease with neurological manifestations (WDNM) and its response to treatment. METHODS: Consecutive WDNM patients were included and their clinical, hematological, serum chemistry, and MRI findings were noted. Neurological severity of WD and OMD were assessed. Burke-Fahn-Marsden (BFM) score for dystonia was noted. Patients were treated with penicillamine, zinc, and multiple antidystonic drugs. Clinical improvement at 3 and 6 months was noted. RESULTS: Overall, 61 of 67 (91%) WDNM patients had OMD, whose median age was 13.5 years. Median severity of OMD was 2.5 (range, 1-4). Thirteen patients were anarthric and 12 unable to eat. Severity of OMD correlated with drooling (r = 0.29; P = 0.02), BFM score (r = 0.63; P < 0.001), pancytopenia (r = -0.26; P = 0.04), and serum ceruloplasmin (r = 0.33; P = 0.01), but not with location and number of MRI lesions. Compared to baseline, severity of OMD improved at 6 months (P < 0.001), but not at 3 months. None became asymptomatic. Improvement in OMD paralleled with improvement in severity grade of WDNM (r = 0.26; P = 0.04) and with BFM score (r = 0.31; P = 0.02). CONCLUSION: OMD was a common manifestation of WDNM occurring in 91% patients, and OMD improved partially over the study period.

A study of oxidative stress, cytokines and glutamate in Wilson disease and their asymptomatic siblings.

BACKGROUND: Free copper in Wilson disease (WD) is toxic and may reduce antioxidant, increase oxidative stress marker and thereby cytokine release and excitotoxic injury, but there is paucity of studies in humans. We report oxidative stress markers, cytokines and glutamate in neurologic WD and correlate these with their clinical severity, laboratory findings and extent of Magnetic resonance imaging (MRI) changes. METHODS: 29 patients with neurologic WD and 9 asymptomatic WD siblings were included and their clinical, treatment history, disease severity, biochemical findings and MRI changes were noted. Glutathione (GSH), total antioxidant capacity (TAC) and malonodialdehyde (MDA) were measured by spectrophotometer, cytokines by cytokine bead array and glutamate by the fluorometer. RESULTS: In WD patients, the glutathione (mean±SEM, 2.20±0.06 vs. 2.73±0.04mg/dl, P<0.001) and TAC (1.70±0.03 vs. 2.29±0.02 Trolox_Eq_mmol/l, P<0.001) were reduced, and MDA and glutamate (23.93±0.54 vs. 19.96±0.27µmol/l; P<0.001) were increased (4.7±0.11 vs. 3.03±0.52nmol/ml, P<0.001) compared to controls. The serum IL6 {median (IQRs), 9.42(10.92) vs. 5.2(5.34) pg/ml; P=0.001}, IL8 {12.37(10.92) vs. 5.63(5.52) pg/ml; P<0.001}, IL10 {8.33(8.3) vs. 2.05(1.37) pg/ml; P=0.001} and TNFα {6.14(8.95) vs. 3.61(3.58) pg/ml; P<0.001} were also increased in WD patients compared to controls. These changes were more marked in the neurologic WD compared to asymptomatic WD and in the untreated compared to treated patients. TAC correlated with duration of illness, serum free copper, 24hour urinary copper and serum ceruloplasmin, and glutamate with MDA, TNFα, ceruloplasmin and 24-hour urinary copper. CONCLUSIONS: In WD patients, antioxidants are reduced and MDA, cytokines and glutamate are increased which are more marked in symptomatic neurologic WD than asymptomatic patients.