Are monoclonals the only panacea for treatment of aquaporin-4 positive NMOSD? Experience from a low-&middle-income (LMIC) region.

OBJECTIVE: A plethora of monoclonals have ushered up for NMOSD treatment. However, their limited availability and cost concerns poses a challenge for usage in developing nations. We compared relapse rates and disabilities among aquaporin-4 positive(AQP4+ve) patients on conventional immunosuppressants and rituximab in a tertiary referral center in southern India. METHODS: This was a chart review of AQP4+ve patients registered under national demyelination registry maintained at institute. AQP4+ve patients were included if they were on azathioprine, MMF, methotrexate for six months; cyclophosphamide for three months and rituximab for one month. RESULTS: 207 records were screened, 154 fulfilled inclusion criteria. Drugs used were azathioprine (70), MMF (34) and rituximab (33). All three drugs were non-inferior to each other in terms of ARR reduction. Median EDSS at last follow-up was significantly lower for azathioprine(2;IQR:0-5) and rituximab(2;IQR:0.5-5) than MMF(3.5;IQR:2-5.6), however azathioprine was associated with highest switch rate(34.3%) and was the only drug which required change because of intolerance. Failure rate was least for rituximab(27.3%).Patients on azathioprine and MMF required higher mean duration of concurrent steroids(7.8±7.7 and 4.56±2.17 months respectively) when compared to rituximab(2.77±1.38) and had more relapses due to steroid withdrawal. CONCLUSION: Initial treatment with azathioprine, MMF and rituximab is comparable in terms of ARR reduction. Findings suggest that choice may be guided by adverse event profile of drug, rather than efficacy per se. Concurrent treatment duration with steroids should also guide clinical decision. Switch to second immunomodulation in event of initial failure adds to efficacy benefit, irrespective of the drug chosen.

A Real-World Experience of Rituximab: A Panacea in Therapy of Multiple Sclerosis in Low- and Middle-Income Setting.

BACKGROUND: Anti-CD20 monoclonal antibodies have received increasing attention in the past few years in the treatment of multiple sclerosis (MS). OBJECTIVES: This study describes the (i) efficacy and safety of rituximab in people living with MS and (ii) assesses clinical and imaging outcomes following rituximab in MS. METHOD: This is a chart review from the MS registry maintained at the institute from a University Hospital in South India. RESULT: Eighty-three (M:F, 26:57) people living with MS received rituximab as immunomodulation between 2007 and 2022 with a median follow-up duration of 18 months. Fifty-nine (71%) were classified as relapsing-remitting MS, 16 (19%) were secondary progressive MS, and 8 (10%) were primary progressive MS. Seventy-two (87%) MS patients did not experience any relapse after receiving rituximab. In relapsing-remitting MS patients, the mean annualized recurrence rate dropped from 1.24 ± 1.19 to 0.16 ± 0.37. Infusion-related reaction occurred in 5 (6% of adverse events), urinary infections in 7 (8.4%), systemic infections in 3 (3%), Pneumocystis carinii pneumonia occurred in 1 (1%), and herpes zoster infection in 1 (1%) patient. Mortality was observed in 3 (3.5%) patients. While being on rituximab, 18 (22%) patients had mild COVID-19 illness and they all made complete recovery without any sequalae. CONCLUSIONS: Rituximab is a safe, well-tolerated, easily accessible, inexpensive, and effective therapeutic option for people with MS. Rituximab showed both clinical and radiological improvement after a median follow-up of 1.5 years. None of our patients showed any severe COVID infection nor side effects after receiving COVID vaccination.

Outcomes of COVID-19 disease and its effect on disability in patients with multiple sclerosis and other allied demyelinating disorders.

BACKGROUND: Coronavirus disease of 2019 (COVID-19) pandemic has posed challenges for clinicians with respect to questions regarding vulnerability of patients with chronic autoimmune diseases like Multiple Sclerosis (MS) and other demyelinating central nervous system (CNS) disorders. OBJECTIVES: We assessed outcomes of COVID-19 disease among patients with CNS demyelinating disorders and its effect on neurological disability. METHODS: This was an electronic survey in which a structured questionnaire was distributed to patients registered with neuroimmunology and MS clinics at All India Institute of Medical Sciences, New Delhi, India. The patients were enquired for their primary disease characteristics, occurrence and course of COVID-19 infection and its effect on their underlying disability, if any. Patients visiting clinics in person were also assessed and data from both sources was pooled. RESULTS: 61 patients with these disorders reported to have contracted COVID-19 infection (mean age- 35.60+10.28 years, females-75.4%, MS-85.2%). None of them suffered from severe/critical COVID-19 despite heterogeneity of disease modifying therapy (DMT) use. DMTs were not associated with increased risk of lymphopenia during illness. 3.3% patients reported fresh relapse and 16.4% had worsening of their neurological disability during/after COVID-19 infection with half of them not attaining their baseline status on follow-up. None of demographic or biochemical parameters were predictive of this neurological worsening. CONCLUSION: Our study suggests that patients with these disorders might not be at heightened risk of severe COVID-19. Adverse effect of COVID-19 infection on neurological disability needs further exploration.

Fatigue, chronic fatigue syndrome and migraine: Intersecting the lines through a cross-sectional study in patients with episodic and chronic migraine.

Objectives: Fatigue is a common symptom occurring in a variety of disorders. Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue as the core symptom. The risk of CFS is nearly 1.5 times higher in migraine while headaches have been reported in 59% of cases with CFS. However, details of its occurrence and severity remain largely unexplored. The primary objective of our study was to determine the occurrence and severity of fatigue and CFS in patients with episodic and chronic migraine. The secondary objectives were to define their relationship with other common comorbidities. Materials and Methods: 60 migraine patients (30 each, episodic [EM] and chronic migraine [CM]) were recruited from Neurology Outpatient Department, GIPMER a tertiary referral center in New Delhi, India. Patients' headache severity was analyzed using the Headache impact test-6 (HIT-6) score while fatigue and other migraine accompaniments were assessed using Fatigue severity scale (FSS), Chalder fatigue scale, CDC diagnostic criteria for CFS, American College of Rheumatology Diagnostic Criteria for fibromyalgia, Hamilton Depression Scale, the Generalized Anxiety Disorder 7-Item Scale, and Epworth sleepiness Scale (ESS). Comparative analysis was further done among migraine patients with and without fatigue and CFS. Results: The mean HIT-6 score was significantly higher in CM versus EM. The CM group had a higher mean FSS score (47.87 vs. 37.3 in EM; P = 0.004), a percentage of patients with severe fatigue (60% vs. 20% in EM; P = 0.004), and a higher percentage of patients with pathological fatigue (83.3% vs. 63.3% in EM; P = 0.04). Around 23.33% of CM patients fulfilled the criteria of CFS. Fatigue correlated positively with severity, frequency, attack duration and chronicity of the migraine episodes, along with depression, anxiety, and excessive daytime sleepiness. Conclusion: Fatigue and related comorbid disorders are significantly more common in CM than in EM, expanding the morbidity of the condition and underscores the need to address these accompanying symptoms for devising a holistic treatment plan.

Impact of JME on quality of life: Does a well-controlled epilepsy also hamper the psychological wellbeing?

PURPOSE: Epilepsy is a stigmatizing disorder and its diagnosis can have important psychosocial consequences on individuals, severely impacting their quality of life(QOL). There are numerous studies which have seen an adverse impact on the psychosocial aspects of life in patients with intractable epilepsy. The aim of this study was to assess the QOL in adult and adolescent patients with JME, which is largely a well-controlled form of epilepsy. METHODOLOGY: This was a hospital based cross-sectional observational study comprising of 50 JME patients. QOLIE-31-P and QOLIE-AD-48 questionnaires were used to assess QOL in adults & adolescents(11-17 years) respectively. The Mini international neuropsychiatric interview-version 7.0.2 and Brief psychiatric rating scale were used for screening of underlying psychopathology and if, the screening tests were positive then they were further evaluated and classified using DSM V and ICD 10. RESULTS: The mean QOLIE-31-P score was 64.65 ± 15.74. Majority of the adult patients had fair QOL (poor, fair and good QOL scores in 18 %, 54 % and 28 % respectively). Subscale scores in poor category were for the medication effects and pertaining to seizure worry.Among adolescent patients, the mean QOLIE 48 AD score was 69.15 ± 13.13. 50 % had fair QOL. Amongst those with poor QOL, majority of poor scores were for the attitude towards epilepsy. The QOL scores were significantly poorer in patients with uncontrolled seizures. 78 % of the patients had comorbid anxiety and depression, however syndromic psychiatric diagnosis was seen in 10.25 % and 2.56 % for anxiety and depression respectively. Presence of psychiatric symptoms did not influence QOL scores. CONCLUSION: QOL, in well controlled JME, is fair in majority of patients. QOL might improve if seizure worry is addressed and patients are educated about medication effects at the time of initial diagnosis. Vast majority of patients may experience minor psychiatric issues, which do need addressal for formulating a holistic and individualized treatment plan.

Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.

BACKGROUND: Recent studies have shown various neurological adverse events associated with COVID-19 vaccine. OBJECTIVE: We aimed to retrospectively review and report the neurological diseases temporally associated with COVID-19 vaccine. METHODS: We performed a retrospective chart review of admitted patients from 1st February 2021 to 30th June 2022. A total of 4672 medical records were reviewed of which 51 cases were identified to have neurological illness temporally associated with COVID-19 vaccination. RESULTS: Out of 51 cases, 48 had probable association with COVID-19 vaccination while three had possible association. Neurological spectrum included CNS demyelination (n = 39, 76.5 %), Guillain-Barré-syndrome (n = 3, 5.9 %), stroke (n = 6, 11.8 %), encephalitis (n = 2, 3.9 %) and myositis (n = 1, 2.0 %). Female gender had a greater predisposition (F:M, 1.13:1). Neurological events were more commonly encountered after the first-dose (n = 37, 72.5%). The mean latency to onset of symptoms was 13.2 ± 10.7 days after the last dose of vaccination. COVIShield (ChAdOx1) was the most commonly administered vaccine (n = 43, 84.3 %). Majority of the cases with demyelination were seronegative (n = 23, 59.0 %) which was followed by anti-Myelin oligodendrocyte-glycoprotein associated demyelination (MOGAD) (n = 11, 28.2 %) and Neuromyelitis optica (NMOSD) (n = 5, 12.8 %). Out of 6 Stroke cases, 2 cases (33.3 %) had thrombocytopenia and coagulopathy. At discharge, 25/51 (49.0 %) of the cases had favourable outcome (mRS 0 to 1). Among six patients of stroke, only one of them had favourable outcome. CONCLUSION: In this series, we describe the wide variety of neurological syndromes temporally associated with COVID-19 vaccination. Further studies with larger sample size and longer duration of follow-up are needed to prove or disprove causality association of these syndromes with COVID-19 vaccination.

COVID-19 vaccine associated demyelination & its association with MOG antibody.

BACKGROUND: ChAdOx1-S (Covishield™/Vaxzervria, AstraZeneca) and BBV152 (Covaxin) SARS-CoV-2 vaccines are proven to be safe and effective, but rare complications have been reported. OBJECTIVE: To describe reports of central nervous system (CNS) demyelination following ChAdOx1-S and BBV152 vaccinations. METHODS & RESULTS: We report 29 (17 female; mean 38 years) cases of CNS demyelination; twenty-seven occurred in temporal association with ChAdOx1-S vaccine; two in association with BBV152 vaccine. Eleven patients had presentation with myelitis, six patients developed optic neuritis, five had acute demyelinating encephalomyelitis, three presented with brainstem demyelination, and four had multiaxial involvement. Myelin oligodendrocyte glycoprotein (MOG) antibodies were positive in ten patients. One patient with ADEM and tumefactive demyelinating lesions died after a prolonged intensive care unit stay and superimposed infection. As compared to the control group (87); the postvaccinial cases were found to have a significantly higher mean age, presence of encephalopathy (p value:0.0007), CSF pleocytosis (p value: 0.0094) and raised CSF protein (p value: 0.0062). CONCLUSIONS: It is difficult to establish a causal relationship between vaccination and neurological adverse events such as demyelination. The temporal association with the vaccination and the presence of MOG antibodies raises the possibility of an immunogenic process triggered by the vaccine in susceptible individuals.

Modulation of epileptiform EEG discharges in patients with JME.

PURPOSE: To study modulation of epileptiform EEG discharges in patients with JME. METHOD: 50 subjects with JME underwent a sleep deprived EEG recording along with conventional provocative methods and testing with cognitive tasks (CTs). Both categories of tests were evaluated for their effect on occurrence of IEDs. Number of IEDs per unit time was calculated at baseline as well as with each task. Statistical and arbitrary methods were used to assess modulation. By arbitrary method if frequency of IEDs was more than twice that of baseline, it was considered as provocation and if less than half, it was considered as inhibition. To account for spontaneous fluctuation of IEDs, 95% CI was calculated for baseline IEDs in each patient and provocation/inhibition was considered if frequency of IEDs exceeded/remained below limits of CI respectively. RESULTS: There was no significant difference in rates of provocation of IEDs by conventional or CTs. However there was exclusive provocation of IEDs by CTs in 4 patients, 3 of whom were already on AEDs. There was a significant inhibitory effect of CTs as mean baseline discharge frequency was 0.4 ±â€¯1.16 IEDS/min and during CTs was 0.1 ±â€¯0.38 IEDs/min. However when spontaneous fluctuation was accounted for, inhibition was seen in only 22.23% patients by statistical method as compared to 90.91% by arbitrary method. CONCLUSIONS: Inclusion of CTs may assist in provocation of IEDs, thereby increasing yield of routine EEG. Spontaneous fluctuation of IEDs accounts for much observed inhibition by CTs in JME patients.