COVID-19 Infection in Multiple Sclerosis Patients Treated with Rituximab Compared to Natalizumab and Healthy Controls: A Real-World Multicenter Study.

INTRODUCTION: The impact of coronavirus disease 2019 (COVID-19) infection on patients with multiple sclerosis (MS) undergoing various immunomodulating therapies can vary. Individuals on B-cell therapy, such as rituximab, may be more susceptible to infection compared to those treated with natalizumab. OBJECTIVE: The objective of this study was to determine the incidence and severity of COVID-19 infection in patients receiving rituximab, natalizumab, and healthy controls. METHODS: This retrospective multicentric study included data derived from a centralized MS registry of four centers in South India. Data of patients on rituximab and natalizumab recruited between 2020 February and 2022 December were extracted from the registry and analyzed. The outcomes studied were the occurrence of COVID-19 infection, hospitalization, intensive care unit admission, death, post-COVID-19 relapses, and post-vaccine relapses. These outcomes were compared between the treatment groups and the matched controls. RESULTS: COVID-19 infection occurred in 49.1% (26/53) of those on rituximab, 19.2% (5/26) of those on natalizumab, and 11.5% (6/52) of healthy controls. In addition, 8/53 (15.1%) in the rituximab group and 1/26 (3.8%) in the natalizumab group were hospitalized. All 6/52 (11.5%) in the control group had mild infection, and none were hospitalized. No deaths occurred in any group. On statistical analysis, the occurrence of COVID-19 infection in the rituximab group was significantly higher when compared to natalizumab ( P = 0.0141) and healthy controls ( P < 0.001). Hospitalizations were significantly higher in the rituximab group when compared to healthy controls ( P < 0.006). CONCLUSION: MS patients treated with rituximab were more likely to experience COVID-19 infection compared to those treated with natalizumab and healthy controls. Hospitalization was more frequently seen in patients treated with rituximab compared to healthy controls.

Inpatient Burden of Neurological Disorders: A Route Map for Allocation of Resources and Postgraduate Training.

Introduction There are limited data regarding the profile of inpatient neurological disorders in India. Understanding the spectrum of diseases and the profile of patients admitted in an inpatient setting will help to streamline services, allocate resources, develop management protocols, design curricula, and improve training programs of postgraduate students in neurology training. Objective The objective of this study is to study the profile of inpatient neurological disorders in 1000 consecutive patients admitted to a tertiary care neurological center. Methods Data from 1000 consecutive inpatients admitted to the Neurology Department at St. John's Medical College Hospital, Bengaluru from January 2018 to October 2018 were collected from the medical records. The data obtained from the case records were entered into a Microsoft Excel spreadsheet for descriptive analysis. Results The average age of the patients was 48 years (±18.18) and 606 of the 1000 patients were males. Strokes, including arterial and venous strokes, formed the major inpatient caseload, accounting for 48.7% of cases. Of these, 84% had ischemic arterial strokes, 7.4% had intracranial hemorrhage, and 8.4 % had cerebral sinus venous strokes; 19.3% of patients were admitted for seizures while 8.2% of patients were admitted for headache. Meningitis was diagnosed in 5.2% of patients; 4.8% of patients had central nervous system demyelinating and autoimmune diseases. A number of other diagnoses comprised less than 2.5% each and included movement disorders, peripheral nerve, spine and nerve roots disorders, neuromuscular diseases, neurodegenerative diseases, and medical and functional illness. Conclusion The most common disorders in the inpatient setting are stroke, seizure, headache, meningitis, and autoimmune/demyelinating disorders. These disorders should receive priority while planning the allocation of resources, educational curriculum, training, and teaching programs.

A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) is increasingly being used in Indian multiple sclerosis (MS) patients. There are no reports on its safety and efficacy, especially with respect to the occurrence of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To describe the patient characteristics, treatment outcomes, and adverse events, especially the occurrence of PML in NTZ-treated patients. METHODS: A multicentre ambispective study was conducted across 18 centres, from Jan 2012 to Dec 2021. Patients at and above the age of 18 years treated with NTZ were included. Descriptive and comparative statistics were applied to analyze data. RESULTS: During the study period of 9 years, 116 patients were treated with NTZ. Mean age of the cohort was 35.6 ± 9.7 years; 83/116 (71.6%) were females. Relapse rate for the entire cohort in the year before NTZ was 3.1 ± 1.51 while one year after was 0.20±0.57 (p = 0.001; CI 2.45 -3.35). EDSS of the entire cohort in the year before NTZ was 4.5 ± 1.94 and one year after was 3.8 ± 2.7 (p = 0.013; CI 0.16-1.36). At last follow up (38.3 ± 22.78 months) there were no cases of PML identified. CONCLUSIONS: Natalizumab is highly effective and safe in Indian MS patients, with no cases of PML identified at last follow up.

Neurology Exit Examination System in India: A Survey of Examiners' Perceptions and Recommendations.

Background: The traditional Neurology exit examination in India has remained unchanged over the last few decades. In developed countries, objective evaluation methods have replaced the traditional ones. A need for such methods has not been explored in India. Objective: We aimed to study the perceptions and key recommendations of Neurology examiners on the existing examination pattern. Material and Methods: We conducted an online survey of examiners perceptions and recommendations using a set of 10 multiple-choice questions and an open-ended question. Results: 46 examiners provided completed responses suitable for analysis. Nearly equal proportions (30%) of the examiners had 10 years, 10-25 years and >25 years' experience. 92% were not satisfied with current system, 95% did not find adequate time for correction of theory scripts, 90% felt that theory questions were random, and 95% had legibility issues. 84% felt that the practical exams do not test true learning, 98% felt the examination stress impairs the performance and 85% felt that there are no objective criteria to pass the candidate. 83% felt the current system-needed changes. The key suggestions provided by the examiners to improve the system included objective assessments like MCQ, OSCE, OSLER and DOPS, inclusion of larger number of short answer type questions and periodic internal assessments of the candidates. Conclusions: A vast majority of examiners favoured changes to the current examination system and provided key recommendations. A larger study is needed to extrapolate these findings to the rest of India.

Headaches associated with acute SARS-CoV-2 infection: A prospective cross-sectional study.

OBJECTIVES: The prevalence and characteristics of COVID-19-related headaches are not known in Indian patients. We aim to determine the prevalence and characteristics of headache in COVID-19-infected individuals and make a comparison with those without headaches. METHODS: This prospective cross-sectional observational study was conducted from 1 October to 31 October 2020. Data were collected using a detailed questionnaire. We compared the data of those with and without headaches to identify the differences between the groups. RESULTS: During the study period of 1 month, among 225 COVID-19-infected patients, 33.8% patients had headaches. The mean age of patients with headache was 48.89 ± 15.19 years. In all, 53.9% were females. In 65.8%, headache occurred at the onset of viral illness; 44.7% described the headache as dull aching; 39.5% had bifrontal headache; and 32.9% had holocranial headache. In total, 78.9% had complete resolution of headache within 5 days. A comparison between those with and without headaches showed that those with headaches were more younger (48.89 ± 15.19 vs 54.61 ± 14.57 years, p = 0.007) and of female gender (41/76(53.9%) vs 41/149 (27.5%), p = 0.001). Primary headache disorders were more common in the headache group. Levels of inflammatory markers such as leukocyte count (7234.17 ± 3054.96 vs 8773.35 ± 5103.65, p = 0.017), erythrocyte sedimentation rate (39.28 ± 23.29 vs 50.41 ± 27.61, p = 0.02) and ferritin (381.06 ± 485.2 vs 657.10 ± 863.80, p = 0.014) were lower in those with headaches. CONCLUSIONS: Headaches are a common and early symptom of acute SARS-CoV-2 infection more frequently seen in young females and in those with a history of primary headache disorders. The lower level of inflammatory markers in those with headaches suggests that these headaches are probably due to the local spread of virus through the trigeminal nerve endings, resulting in activation of the trigeminovascular system.

Transient Ischemic Attack after Eating Spicy Foods in Children: Think of Moya Moya Disease.

Moya Moya disease is an important cause for childhood strokes and morbidity. An early diagnosis and treatment can prevent strokes and disability. Here we report the case of an eight-year-old boy who had transient episodes of headache and hemiparesis secondary to Moya Moya disease. He was misdiagnosed as hemiplegic migraine, seizure disorder, paroxysmal non-kinesigenic dyskinesia and dissociative disorder during the past three years. The diagnosis was significantly delayed as an important clinical cue was overlooked. A detailed history showed that symptoms were precipitated on eating spicy food. This clinical pointer prompted evaluation for Moya Moya disease. MRI and MR angiogram confirmed Moya Moya disease.

COVID-19-related strokes are associated with increased mortality and morbidity: A multicenter comparative study from Bengaluru, South India.

BACKGROUND: COVID-19-related strokes are increasingly being diagnosed across the world. Knowledge about the clinical profile, imaging findings, and outcomes is still evolving. Here we describe the characteristics of a cohort of 62 COVID-19-related stroke patients from 13 hospitals, from Bangalore city, south India. OBJECTIVE: To describe the clinical profile, neuroimaging findings, interventions, and outcomes in COVID-19-related stroke patients. METHODS: This is a multicenter retrospective study of all COVID-19-related stroke patients from 13 hospitals from south India; 1st June 2020-31st August 2020. The demographic, clinical, laboratory, and neuroimaging data were collected along with treatment administered and outcomes. SARS-CoV-2 infection was confirmed in all cases by RT-PCR testing. The data obtained from the case records were entered in SPSS 25 for statistical analysis. RESULTS: During the three-month period, we had 62 COVID-19-related stroke patients, across 13 centers; 60 (97%) had ischemic strokes, while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ± 13.20 years, with 34 (77.4%) males. Twenty-six percent (16/62) of patients did not have any conventional risk factors for stroke. Diabetes mellitus was seen in 54.8%, hypertension was present in 61.3%, coronary artery disease in 8%, and atrial fibrillation in 4.8%. Baseline National Institutes of Health Stroke Scale score was 12.7 ± 6.44. Stroke severity was moderate (National Institutes of Health Stroke Scale 5-15) in 27 (61.3%) patients, moderate to severe (National Institutes of Health Stroke Scale 16-20) in 13 (20.9%) patients and severe (National Institutes of Health Stroke Scale 21-42) in 11 (17.7%) patients. According to TOAST classification, 48.3% was stroke of undetermined etiology, 36.6% had large artery atherosclerosis, 10% had small vessel occlusion, and 5% had cardioembolic strokes. Three (5%) received intravenous thrombolysis with tenecteplase 0.2 mg/kg and 3 (5%) underwent mechanical thrombectomy, two endovascular and one surgical. Duration of hospital stay was 16.16 ± 6.39 days; 21% (13/62) died in hospital, while 37 (59.7%) had a modified Rankin score of 3-5 at discharge. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality. A comparison to 111 historical controls during the non-COVID period showed a higher proportion of strokes of undetermined etiology, higher mortality, and higher morbidity in COVID-19-related stroke patients. CONCLUSION: COVID-19-related strokes are increasingly being recognized in developing countries, like India. Stroke of undetermined etiology appears to be the most common TOAST subtype of COVID-19-related strokes. COVID-19-related strokes were more severe in nature and resulted in higher mortality and morbidity. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality.

Recurrent Ischemic Strokes: "Discontinuation of Antiplatelet Drugs Appears to be an Important Preventable Cause".

BACKGROUND: Antiplatelet therapy (APT) is an integral part of secondary stroke prevention. Noncompliance to APT is an important factor in stroke recurrence. In this study, we have evaluated the reasons for noncompliance to APT. OBJECTIVE: The aim of this study was to identify the various causes of nonadherence to APT in recurrent stroke patients. MATERIAL AND METHODS: The study was conducted in a tertiary care hospital in south India with a huge stroke burden. The study period was from October 2017 to September 2018. A total of 60 consecutive patients of recurrent stroke who were nonadherent to antiplatelet therapy were evaluated for various factors that prevented compliance. RESULTS: During the 12-month study period among 604 ischemic stroke patients, 128 (21%) had recurrent strokes. Of this 128, 60 (46.8%) were due to discontinuation of APT. The main factor for nonadherence to APT was lack of awareness about the need for lifelong medication (41/60; 68.3%). 10 patients (16.7%) stopped treatment as they opted for alternative therapy and 4 (6.7%) discontinued antiplatelets due to side effects. A small proportion of the patients (3.3%) cited financial constraints and forgetfulness as the issue, while 1.7% had difficulty in finding assistance to administer medicine. 27 (45%) patients had recurrent stroke within 2-15 days of stopping APT. CONCLUSIONS: The main reason for nonadherence to antiplatelet therapy is lack of awareness about the need for lifelong antiplatelet therapy. Stroke patients should be educated about the importance of lifelong antiplatelet therapy to prevent recurrent strokes.

Essential oil-related status epilepticus: A small case series study.

OBJECTIVE: Essential oils are plant-derived oils and are widely used as an over-the-counter remedy for common ailments. Many essential oils are found to have proconvulsant effects. Here we report a small case series of 3 adults with eseential oil-related status epilepticus. METHODS: This was an observational study conducted in a tertiary care hospital in south India from January 2018 to December 2019. We collected the demographic, clinical, and imaging features of all cases of status epilepticus resulting from exposure to essential oils. Cases of status epilepticus secondary to all other causes were excluded. RESULTS: There were 3 young adults with essential oil-related status epilepticus. Two had de novo generalized tonic-clonic status epilepticus, and 1 with posttraumatic occipital lobe epilepsy had focal-impaired awareness status epilepticus. The first 2 cases presented with histories of ingestion of eucalyptus oil. The third case had focal-impaired awareness status epilepticus after topical application of various balms containing eucalyptus and camphor. CONCLUSIONS: Proconvulsant essential oils of eucalyptus and camphor can cause both generalized and focal status epilepticus. Physicians dealing with patients of status epilepticus should enquire about the exposure to proconvulsant essential oils.

Efficacy and safety of rituximab in multiple sclerosis: Experience from a developing country.

BACKGROUND: Rituximab is increasingly being used in treatment of multiple Sclerosis (MS) in our centers due to its easy availability, efficacy and favorable side effect profile. Here we describe experience with rituximab over a period of 4 years from three MS centers from south India. METHODS: The data of MS patients who were treated with rituximab in three MS centers at Bangalore, India, from December 2015 to December 2019 were collected and evaluated with respect to relapse rate, EDSS score and adverse events. RESULTS: Over the four-year study period 118 MS patients were evaluated, 80 of whom were on rituximab. 58 (72%) had RRMS, 15 (19%) SPMS and 7 (9%) PPMS. Most patients (89%) received rituximab at a dose of 500 mg every 6-12 months. Nine patients (11%), all with progressive MS were on 1 gm to 2 gm every 6 months. Follow up ranged from 1 year to 3 years, with a median of 2 years. 56 (97%) RRMS patients had no relapses during follow up. EDSS score improved by a score of 0.5-2.0 in 68 (85%) patients, remained same in 10 (12.5%) and worsened in 2 patients (2.5%). Most patients (91%) tolerated rituximab infusions well. There were no opportunistic infections or neoplasms. CONCLUSION: Anti B cell therapy with rituximab appears effective, safe and affordable in the treatment of MS in developing countries like India with resource limited settings.