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.

Utility of the RIPS Scale and 2CAN Score for In-Hospital Stroke Prediction.

Background: In-hospital strokes are a small but sizeable proportion of all strokes. Identification of in-hospital strokes is confounded by stroke mimics in as many as half of in-patient stroke codes. A quick scoring system based on risk factors and clinical signs during the initial evaluation of a suspected stroke might be helpful to distinguish true strokes from mimics. Two such scoring systems based on ischemic and hemorrhagic risk factors are the risk for in-patient stroke (RIPS) and the 2CAN score. Materials and Methods: This prospective clinical study was conducted at a quaternary care hospital in Bengaluru, India. All hospitalized patients aged 18 years and above for whom a "stroke code" alert was recorded during the study period of January 2019 to January 2020 were included in the study. Results: A total of 121 in-patient "stroke codes" were documented during the study. Ischemic stroke was the most common etiological diagnosis. A total of 53 patients were diagnosed to have ischemic stroke, 4 had intracerebral hemorrhage, and the rest were mimics. Receiver operative curve analysis was performed and at a cut-off of RIPS ≥3, it predicts stroke with a sensitivity of 77% and a specificity of 73%. At a cut-off of 2CAN ≥3, it predicts stroke with a sensitivity of 67% and a specificity of 80%. RIPS and 2CAN significantly predicted stroke. Conclusions: There was no difference in the use of either RIPS or 2CAN for differentiating stroke from mimics, and hence they may be used interchangeably. They were statistically significant with good sensitivity and specificity, as a screening tool to determine in-patient stroke.

Delay in the diagnosis of dementia in urban India: Role of dementia subtype and age at onset.

BACKGROUND: Early diagnosis of dementia is crucial for timely intervention. However, frequently, there is a substantial delay in diagnosis. Therefore, it is essential to recognise and address the barriers to early diagnosis. These have not been systematically studied in India. We at a specialist memory clinic in India investigated the time from symptom onset to diagnosis of dementia and factors contributing to the delay. METHODS: In this cross-sectional study, consecutive patients with dementia (n = 855) seen at a private hospital underwent a standard clinical assessment and investigations. The primary outcome variable was time from symptom onset to diagnosis (TTD). The association of age, education, gender, dementia subtype, and age of onset on TTD were examined using a univariate analysis of covariance. RESULTS: The median TTD was 24 months; 43% were diagnosed after 24 months. There was a significant association between TTD and age at onset (young onset-median 36 months vs. late onset-24 months) and dementia subtype. Patients with vascular dementia were diagnosed significantly earlier as compared to patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) [median 18, 24, and 30 months, respectively]. There was no effect of gender or education on the TTD. CONCLUSION: About 40% of patients with dementia were diagnosed more than 2 years after symptom onset, particularly young onset dementias and FTD. Our study findings highlight the gaps in diagnosing patients with dementia in urban India and have significant implications for developing and implementing multifaceted interventions to improve the early diagnosis of dementia.

Perry Syndrome with a Novel Mutation and a Rare Presentation: First Report from India.

Objective: To characterize the first patient of Perry syndrome reported from India. Methods: A 62-year-old gentleman presented with acute encephalopathy, hypercapnia, central hypoventilation, and seizures. He required ventilatory support for persistent respiratory failure even after the resolution of the encephalopathy. History revealed symptoms of orthostatic hypotension, episodes of shallow breathing, unsteadiness of gait, anxiety and depression, and significant weight loss for the previous two years. His mother and elder brother had succumbed to a similar illness. Investigations for neuromuscular diseases, including myasthenia and Pompes disease, were negative. Genetic tests for muscular dystrophies and myopathies, investigations for infectious, autoimmune, and para-neoplastic diseases were negative. Neuroimaging and electrophysiological studies were unremarkable. During his hospital stay, he developed rigidity and bradykinesia. Results: In view of the prominent respiratory failure, Parkinsonism, unexplained weight loss, and family history, he was tested for Perry syndrome. A heterozygous missense variation in Exon 2 of the DCTN1 gene that results in the substitution of Proline for Alanine at codon 45 (pA45P) was detected. This variant was not detected in his clinically unaffected brother. The clinical presentation and genetic test indicate Perry syndrome, a rare autosomal dominant fatal disease, which has never been reported from India. The patient improved with Levodopa and neurorehabilitation but eventually succumbed to his illness three years later. Conclusion: Perry syndrome, though rare, should be considered in the differential diagnosis of patients with a family history of Parkinsonism and central hypoventilation.

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.

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.

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.

Cerebral Hyperperfusion Syndrome following Staged Bilateral Internal Carotid Artery Stenting.

Cerebral Hyperperfusion syndrome is a relatively rare event following carotid revascularization. It can occur after both carotid endarterectomy and carotid artery stenting. It is characterized by focal neurodeficit, seizures and headache in the absence of ischemia. It occurs due to ipsilateral cerebral edema secondary to hyperperfusion. CT and MRI of the brain are the main modalities used for diagnosis and to rule out infarct. Prompt recognition and treatment can prevent permanent injury to the brain. We present a case of cerebral hyperperfusion syndrome in an elderly gentleman after a staged bilateral internal carotid artery stenting.

Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study.

BACKGROUND AIMS: Spinal cord injury (SCI) is a medically untreatable condition for which stem cells have created hope in the last few years. Earlier pre-clinical reports have shown that transplantation of bone marrow (BM) mesenchymal stromal cells (MSC) in SCI-simulated models can produce encouraging results. In a clinical pilot study, we investigated the growth kinetics of BM MSC from SCI patients, their safety and functional improvement post-transplantation. METHODS: Thirty patients with clinically complete SCI at cervical or thoracic levels were recruited and divided into two groups based on the duration of injury. Patients with <6 months of post-SCI were recruited into group 1 and patients with >6 months of post-SCI were included into group 2. Autologous BM was harvested from the iliac crest of SCI patients under local anesthesia and BM MSC were isolated and expanded ex vivo. BM MSC were tested for quality control, characterized for cell surface markers and transplanted back to the patient via lumbar puncture at a dose of 1 x 10(6) cells/kg body weight. RESULTS: At the time of writing, three patients had completed 3 years of follow-up post-BM MSC administration, 10 patients 2 years follow-up and 10 patients 1 year follow-up. Five patients have been lost to follow-up. None of the patients have reported any adverse events associated with BM MSC transplantation. CONCLUSIONS: The results indicate that our protocol is safe with no serious adverse events following transplantation in SCI patients. The number of patients recruited and the uncontrolled nature of the trial do not permit demonstration of the effectiveness of the treatment involved. However, the results encourage further trials with higher doses and different routes of administration in order to demonstrate the recovery/efficacy if any, in SCI patients.

Lower risk of Parkinson's disease in an admixed population of European and Indian origins.

We studied whether the occurrence of Parkinson's disease (PD) in the Anglo-Indians, an admixed population of European and Asian Indian origin, differs from Indians living in the same environment. Epidemiological studies show considerably higher prevalence of PD amongst white compared to non-white populations. Normal Indians contain a approximately 40% lower number of melanized nigral neurons compared to Caucasians from the UK. Anglo-Indians are an admixed population of European and Indian origin. We used the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria (steps 1 and 2) to diagnose PD in 84 of 493 residents (Indians, 409; Anglo-Indians, 84) living in elderly homes in Bangalore, India. Of these 84, 80 were Indians (19.5%) and 4 were Anglo-Indians (4.8%). Occurrence of PD is nearly five times higher amongst Indians compared to the Anglo-Indians (odds ratio, 3.9; 95% confidence interval, 1.3-12.9). We conclude that an admixture population of European and Indian origins, rather than averaging, might result in reduced occurrences of PD. Hence, studying an admixed population could provide crucial insights into understanding genetic mechanisms in the etiopathogenesis of PD.