COVID-19 pandemic & neurosciences in India- the CoINstudy: Impact of the pandemic on research related to the neurosciences.

Background & objectives We aimed to assess the impact of COVID-19-related disruptions on ongoing and future projects related to neuroscience research and young researchers in India. Methods We conducted a countrywide online survey using a structured, self-administered questionnaire involving medical trainees, post-doctoral fellows, PhD students, early career faculty members and basic neuroscience researchers. The purpose was to assess the impact of the COVID-19 pandemic on the respondents' ongoing/planned research activities and capture their concerns related to future research. Results Five hundred and four valid responses were analyzed. More than three-fourths of the respondents were in their early careers - 64.1 per cent were resident doctors, and 19.8 per cent were early career consultants. Maximum responses were received from respondents working in neurology (228; 45.2%), followed by psychiatry (192; 38.1%) and neurosurgery (49; 9.7%). More than three-fourths [83.5%, 95% confidence interval (CI): 0.8-0.867] of the respondents reported that the pandemic had affected their research. About one-third of the respondents (171; 33.9%) reported delays in completing research studies. Respondents adapted to the pandemic's circumstances by making methodological changes in their research (155; 30.8%). Most respondents (301; 59.6%) reported being diverted from their traditional work settings to COVID-19-related clinical services. Respondents conducting prospective studies and randomized controlled trials and those diverted to COVID-related services were significantly more likely to report the adverse research impact. Interpretation & conclusions In our survey, an overwhelming majority of the respondents reported that the pandemic adversely impacted their study. This trend was independent of sex, designation, and research output of individual subjects. The serious impact of the COVID-19 pandemic on neurosciences research warrants the attention and concerted efforts of the research supervisors, institutional heads, funding agencies and other stakeholders.

Myeloblastic meningeal neoplasm: an unusual natural history.

Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who presented with chronic headache, raised intracranial pressure and progressive vision loss of 2 years duration with no systemic manifestations. He had a history of myeloid sarcoma of the left thigh 15 years ago, treated with external beam radiotherapy and in complete remission for more than 13 years. However, the progressive blindness remained unexplained for 2 years, and he was eventually diagnosed with isolated meningeal relapse without marrow or systemic involvement. Imaging revealed subarachnoid haemorrhage, diffuse leptomeningeal enhancement and involvement of lower dorsal cord and conus, and cerebrospinal fluid cytology showed myeloid blasts. He was managed with intrathecal chemotherapy and craniospinal irradiation, after which he had mild improvement in vision.

Mortality in Two Waves of COVID-19: A Comparative Analysis of a Tertiary Care Hospital in India.

Background COVID-19 has spread as two distinct surges of cases in many countries. Several countries have reported differences in disease severity and mortality in the two waves. Objective Compare the in-hospital mortality in the two COVID-19 waves at a tertiary care hospital in India. Methods We conducted a retrospective data collection. Distinct periods of surges in cases and admissions were defined as the first wave spanning from March 2020 to December 2020 and the second wave from April 2021 to June 21, 2021. The primary outcome of this study was to compare mortality rates in terms of total hospital mortality rate (TMR) and case fatality rate (CFR). Results Mortality rates of wave 2 were approximately 10 times that of wave 1 (TMR of 20.3% in wave 2 versus 2.4% in wave 1 and CFR of 1.5% versus 17.7% in wave 1 and 2, respectively). Mortalities in wave 2 had a larger proportion of severe disease at presentation, faster progression of symptoms to death, and more patients without any chronic comorbid condition dying due to the direct effect of COVID-19 acute respiratory distress syndrome (ARDS). Conclusion Our data matches the worldwide reported pooled hospital mortality figures and shows the comparative difference in disease severity between the two waves.

The Evaluation of Laboratory Parameters as Predictors of Disease Severity and Mortality in COVID-19 Patients: A Retrospective Study From a Tertiary Care Hospital in India.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects and alters various laboratory parameters that are predictors of disease severity and mortality, and hence, their prompt identification can aid in patient triaging and resource allocation. Objectives A retrospective study was conducted on 7416 admitted coronavirus disease 2019 (COVID-19) patients from 20 March 2020 to 9 August 2021 to identify crucial laboratory biomarkers as predictors of disease severity and outcome; also, their optimal cutoffs were also calculated. A comparison of laboratory markers between both COVID-19 waves was also performed. Results The majority of patients had mild disease (4295/7416, 57.92%), whereas 1262/7416 (17.02%) had severe disease. The overall fatal outcome was reported in 461 (6.22%) patients. Predictors for mortality were age (>52 years), albumin/globulin (A/G) ratio (≤1.47), chloride (≤101 mmol/L), ferritin (>483.89 ng/mL), lactate dehydrogenase (LDH) (>393 U/L), procalcitonin (>0.10 ng/mL), interleukin-6 (IL-6) (>8.8 pg/mL), fibrinogen (>403 mg/dL), international normalized ratio (INR) (>1.18), and D-dimer (>268 ng/mL). Disease severity predictors were neutrophils (>81%), lymphocyte (≤25.4%), absolute lymphocyte count (ALC) (≤1.38×103/µL), absolute eosinophil count (AEC) (≤0.03×103/µL), total bilirubin (TBIL) (≥0.51 mg/dL), A/G ratio (≤1.49), albumin (≤4.2 g/dL), ferritin (≥445.4 mg/dL), LDH (≥479 U/L), IL-6 (≥28.6 pg/mL), C-reactive protein/albumin (CRP/ALB) ratio (≥1.78), D-dimer (≥237 ng/mL), and fibrinogen (≥425 mg/dL). The majority of patients admitted in the second wave were older and had severe disease, increased fatality, and significantly deranged laboratory parameters than first wave patients. Conclusion Our findings suggested that several biomarkers are crucial for both severe disease and mortality in COVID-19 patients. Ferritin, LDH, IL-6, A/G ratio, fibrinogen, and D-dimer are important biomarkers for both severity and mortality, and when combined, they provide valuable information for patient monitoring and triaging. In addition to these, older age, INR, chloride, and procalcitonin are also significant risk factors for mortality. For severe COVID-19, TBIL, CRP/ALB, albumin, neutrophil percentage, lymphocyte percentage, ALC, and AEC are also important biomarkers. According to the study, the majority of the baseline laboratory parameters associated with COVID-19 mortality and severe disease were significantly higher during the second wave, which could be one of the possible causes for the high mortality rate in India during the second wave. So, the combination of all these parameters can be a powerful tool in emergency settings to improve the efficacy of treatment and prevent mortality, and the planning of subsequent waves should be done accordingly.

A comparative analysis of demographic, clinical and imaging features of myelin oligodendrocyte glycoprotein antibody positive, aquaporin 4 antibody positive, and double seronegative demyelinating disorders - An Indian tertiary care center prospective study.

Objectives: The aim of the study was to study the demographical, clinical, radiological features, and outcome of anti-myelin oligodendrocyte glycoprotein (MOG) antibody spectrum disorder and compare these features with patients negative for anti-MOG antibody. MOG antibody-associated disease (MOGAD) and aquaporin-4 (AQP4) antibody-related diseases are immunologically distinct pathologies. Our aim was to compare the clinical and radiological features of MOG antibody-related diseases with AQP4 antibody-related diseases and seronegative demyelinating diseases (Non-multiple sclerosis). Materials and Methods: This was a prospective and cohort study conducted at an apex tertiary care institute in the northern part of India from Jan 2019 to May 2021. We compared clinical, laboratory, and radiological findings of patients with MOGAD, AQP4 antibody-related diseases, and seronegative demyelinating disease. Results: There were a total of 103 patients - 41 patients of MOGAD, 37 patients of AQP4 antibody-related diseases and 25 seronegative demyelinating disease. Bilateral optic neuritis was the most frequent phenotype in patients with MOGAD (18/41) whereas myelitis was the most common phenotype in the AQP4 (30/37) and seronegative groups (13/25). Cortical, juxtacortical lesions, anterior segment optic neuritis, optic sheath enhancement, and conus involvement in myelitis were radiological findings that separated MOGAD from AQP4 related diseases. Nadir Expanded Disability Status Scale (EDSS) and visual acuity were similar across the groups. Last follow-up EDSS was significantly better in the MOG antibody group as compared to AQP4 antibody group (1 [0-8] vs. 3.5 [0-8]; P = 0.03). Encephalitis, myelitis, and seizures were more common in the younger population (<18 vs. >18 years) in MOGAD (9 vs. 2, P = 0.001; 9 vs. 7, P = 0.03; 6 vs. 0, P = 0.001). Conclusion: We identified several clinical and radiological features that can help physicians to distinguish MOGAD from AQP4-immunoglobulin G+neuromyelitis optica spectrum disorder. Differentiation is vital as treatment response might vary among both groups.

Prevalence and determinants of post-stroke sleep disorders: a cross-sectional hospital-based study.

INTRODUCTION: Post-stroke sleep disorders (PSSD) are an important part of post-stroke disability. PSSD is neglected as a part of stroke rehabilitation. We aimed to study the prevalence and determinants of PSSD in a hospital based, single center setting. METHODS: In a cross-sectional study, adult patients (≥ 18 years) with stroke (one month to one year after the onset), were enrolled in the study. Demographic, clinical, radiological, and motor and functional disabilities were assessed. Sleep quality was assessed with Pittsburg Sleep Quality Index (PSQI) and STOP BANG questionnaire (for obstructive sleep apnea [OSA]). Patients with poor sleep quality (PSQI > 5) were analyzed for risk factors. RESULTS: A total of 103 patients were recruited in the study period (January 2021 to June 2022). The self-reported prevalence of PSSD was 16% which increased to 72% when the PSQI was administered. High risk of OSA was present in 33%. In bivariate analysis, factors associated with PSQI > 5 were involvement of ≥ 2 lobes, lower body mass index (BMI), worse modified Rankin Scale (mRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Stroke Specific Quality of Life (SSQoL). In multivariate analysis, only depression was associated with PSQI > 5 (OR: 1.3 (1.0; 1.7); p-value = 0.03). CONCLUSION: PSSD had a prevalence of 72%. In multivariate analysis, the factor associated with PSQI > 5 was worse HAM-D score.

Social Cognition in Parkinson's Disease: A Case-Control Study.

Background: Social cognition is the study of how people make sense of themselves and others. Impairment in several domains of social cognition is increasingly being recognized in Parkinson's disease (PD). Objectives: We aimed to study multiple domains of social cognition in Indian PD patients using a culturally appropriate, validated instrument. Methods: We recruited 52 individuals with PD and 31 healthy volunteers (HV) and used the Social Cognition Rating Tools in Indian Setting (SOCRATIS) tool to assess theory of mind (ToM), attributional biases and social cue perception. Quality of life (QoL) was assessed using the PDQOL scale. Results: Baseline characteristics were comparable between PD and HV. The mean (SD) FOT index (first order ToM index) was 0.86(0.18) in PD and 0.99(0.07) in HV [P < 0.001]. The PD group showed higher Externalizing Bias [EB, 4.42(3.91)], compared to HV [1.58(3.22), P = 0.001]. The mean (SD) Faux Pas Composite Index (FPCI ALT) was 0.69(0.09) in PD and 0.78(0.13) in HV [P < 0.001]. Social cognition indices were not associated with QoL in PD. Clinical parameters-age, gender, HAM-D, MOCA, education, levodopa equivalent daily dose of medication, number of PD drugs and trihexyphenidyl use did not predict social cognition. Conclusion: PD patients were less successful than age, gender matched controls in understanding social situations and other's thought processes and had higher tendency to attribute undesirable events to external causes. Deficits in social cognition did not impair the quality of life.

Development of sensitive magnetic nanoparticle assisted rapid sandwich assay(s-MARSA) to monitor Parkinson's disease and Schizophrenia pharmacotherapy.

Parkinson's disease and Schizophrenia fall under low dopamine neurodegenerative and high dopamine psychiatric disorders respectively. Pharmacological interventions to correct mid-brain dopamine concentrations sometimes overshoots the physiological dopamine levels leading to psychosis in Parkinson's disease patients and, extra-pyramidal symptoms in schizophrenia patients. Currently no validated method is available to monitor side effects in such patients, Apolipoprotein E is one of the CSF biomarkers identified in the recent past that shows an inverse relation to mid-brain dopamine concentration. In this study, we have developed s-MARSA for the detection of Apolipoprotein E from ultra-small volume (2 µL) of CSF. s-MARSA exhibits a broad detection range (5 fg mL-1 to 4 µg mL-1) with a better detection limit and could be performed within an hour utilizing only a small volume of CSF sample. The values measured by s-MARSA strongly correlates with the values measured by ELISA. Our method has advantages over ELISA in having a lower detection limit, a broader linear detection range, shorter analysis time, and requiring a low volume of CSF samples. The developed s-MARSA method holds promise for the detection of Apolipoprotein E with clinical utility for monitoring pharmacotherapy of Parkinson's and Schizophrenia patients.

Clinical and radiological spectrum of anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis: single-center observational study.

OBJECTIVE: The objective was to describe the clinical presentations, radiologic features, and outcomes of patients with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibody (MOG). BACKGROUND: During the past decade, the spectrum of the myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) has expanded. Recently, patients with MOG antibody encephalitis (MOG-E) who do not fulfill the criteria for ADEM have been reported. In this study, we aimed to describe the spectrum of MOG-E. METHODS: Sixty-four patients with MOGAD were screened for encephalitis-like presentation. We collected the clinical, radiological, laboratory, and outcome data of the patients who presented with encephalitis and compared it with the non-encephalitis group. RESULTS: We identified sixteen patients (nine males and seven females) with MOG-E. The median age of the encephalitis population was significantly lower than the non-encephalitis group (14.5 years (11.75-18) vs. 28 years (19.75-42), p = 0.0004). Twelve out of sixteen patients (75%) had fever at the time of encephalitis. Headache and seizure were present in 9/16 (56.2%) and 7/16 (43.75%) patients, respectively. FLAIR cortical hyperintensity was present in 10/16 (62.5%) patients. Supratentorial deep gray nuclei were involved in 10/16 (62.5%) patients. Three patients had tumefactive demyelination, and one patient had a leukodystrophy-like lesion. Twelve of 16 (75%) patients had a good clinical outcome. Patient with leukodystrophy pattern and other with generalized CNS atrophy showed a chronic progressive course. CONCLUSION: MOG-E can have heterogeneous radiological presentations. FLAIR cortical hyperintensity, tumefactive demyelination, and leukodystrophy-like presentations are novel radiological presentations associated with MOGAD. Though majority of MOG-E have a good clinical outcome, few patients can have chronic progressive disease even on immunosuppressive therapy.

A teenager with ophthalmoparesis and dysphagia.

The pharyngeal-cervical-brachial (PCB) variant is a rare presentation of Guillain-Barré syndrome (GBS), and there is a handful of case reports that overlap with the Miller-Fisher syndrome (MFS) variant of GBS. This overlap produces varied symptoms that may be confusing and challenging for physicians to diagnose timely and start appropriate treatment. In this article, we present a case report and review of the rare overlap of the PCB variant with the MFS variant of GBS.

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.

Carotid Artery Stenting for a Nonagenarian Presenting as Stuttering Stroke.

Carotid artery stenting (CAS) is performed in patients with minor strokes and transient ischemic attacks (TIAs) to prevent further strokes. However, most operators do not intervene in older adults. We had a 92-year patient with recurrent minor strokes with two possible proximate causes - cardioembolism and significant symptomatic left carotid stenosis. This patient continued to have recurrent ischemic events in the left carotid territory despite optimum management of the cardioembolic source with dual antiplatelets and anticoagulation and was successfully treated with left CAS. The role of carotid revascularization in older patients with high-grade symptomatic carotid stenosis and cardiac comorbidities is discussed.

Polymicrobial Pyomyositis in a Patient with Suspected Myeloma on 18F-FDG PET-CT.

Pyomyositis is an infective involvement of systemic skeletal muscles. We discuss the case of 43-year-old male who presented with quadriparesis, anemia, and hypercalcemia, leading to suspicion of multiple myeloma, and on FDG PET-CT, incidentally, pyomyositis was found. FDG PET-CT thus helped in diagnosing an occult infection which helped in the treatment of the patient.

Chronic T Cell Encephalitis Responsive to Immunotherapy.

Chronic encephalitis manifesting as an epilepsy syndrome most commonly presents as Rasmussen's syndrome, usually characterized by epilepsia partialis continua, hemiparesis, and progressive cortical deficits such as aphasia, hemianopia, and cognitive decline. It is characterized by progressive hemispheric cortical atrophy on imaging and is usually seen in childhood. Adult-onset of the syndrome is rare, and only a few cases have been reported with bilateral symptoms. We present a patient with pseudobulbar affect and frontal lobe dysfunction who developed multifocal myoclonic jerks, right hemibody focal motor seizures, and right hemiparesis with bilateral cerebellar signs. Magnetic resonance imaging showed progressive hemispheric atrophy and bilateral features in Positron emission tomography-computed tomography (PET CT). Brain biopsy revealed chronic T-cell infiltrate. We discuss this case as the patient had several features that were atypical for Rasmussen's encephalitis (or syndrome).

Late-onset cobalamin C disease: rare but treatable.

Cobalamin C disease is the most common inborn error of cobalamin metabolism, resulting from mutations in methylmalonic aciduria and homocystinuria type C protein (MMACHC) gene. There is associated elevation of homocysteine and methylmalonic acid and decreased synthesis of methionine. It is a multisystem disorder characterised by cognitive impairment, psychiatric manifestations, haematological manifestations and thromboembolic phenomena. Its variable clinical presentation and wide age distribution at presentation necessitates a high index of diagnostic suspicion. The diagnosis is suggested by amino acid chromatography and confirmed by sequencing analysis of the MMACHC gene Parenteral hydroxycobalamin and betaine can bring significant clinical and biochemical improvement and is the recommended long-term therapy.

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.