Incidence of multiple sclerosis relapses and pseudo-relapses following COVID-19 vaccination.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic created an urgency for an effective vaccine. The FDA approved vaccines offered by Pfizer-BioNTech (BNT162b2), ModernaTX (mRNA-1273) and Janssen/Johnson & Johnson (Ad26.COV2.S) have shown minimal side effects (SE) in general population studies. Multiple sclerosis (MS) patients were not specifically represented in the above studies. The MS community is interested in how these vaccines behave in people with MS. In this study, we compare the SE experienced by MS to that of the general population after SARS-CoV-2 vaccination and evaluate their risk of relapses or pseudo-relapses. METHODS: A retrospective, single-site, cohort study of 250 MS patients who received the initial cycle of FDA approved SARS-CoV-2 vaccines with 151 of whom also received an additional booster dose. SE resulting immediately after COVID-19 vaccination were collected as part of the standard clinical care during patient visits. RESULTS: Out of the studied 250 MS patients, 135 received the first and second doses of BNT162b2 with less than 1% and 4% pseudo-relapses respectively and 79 received the third BNT162b2 dose with a pseudo-relapse rate of 3%. 88 received the mRNA-1273 vaccine with a pseudo-relapse frequency of 2% and 5% after the first and second doses respectively. 70 patients had the mRNA-1273 vaccine booster with a 3% pseudo-relapse rate. 27 received the Ad26.COV2.S first dose, 2 of whom received a second Ad26.COV2.S booster dose, with no reports of MS worsening. No acute relapses were reported in our patient population. All patients experiencing pseudo-relapse symptoms returned to baseline within 96 h. CONCLUSION: COVID-19 vaccine is safe in patients with MS. Cases of temporary worsening of MS symptoms following SARS-CoV-2 are rare. Our findings support those reported by other recent studies and the CDC recommendation for MS patients to receive the FDA-approved COVID-19 vaccines, including the boosters.

Causas no inflamatorias de consulta urgente en esclerosis múltiple / Non-inflammatory causes of emergency consultation in patients with multiple sclerosis

Objetivos: Describir consultas urgentes de pacientes con esclerosis múltiple (EM) distintas a brotes: causas, dificultades diagnósticas, características clínicas y tratamientos empleados.Material y métodosEstudio retrospectivo de los pacientes que acudieron a un Hospital de Día de EM en 2 años por sospecha de brote y que recibieron un diagnóstico alternativo. Se evaluaron variables demográficas, características clínicas de los pacientes, diagnósticos finales y tratamientos. Los pacientes con diagnóstico final de brote e inicialmente diagnosticados de pseudobrote se evaluaron específicamente. Con una finalidad exploratoria se compararon las características de los pacientes que consultaban por causas no inflamatorias con una cohorte de pacientes aleatoriamente seleccionados que habían sufrido un brote en el mismo periodo de tiempo.ResultadosSe incluyeron un total de 50 pacientes inicialmente diagnosticados de pseudobrotes (33 mujeres, con edad media 41,4 ± 11,7 años). Cuatro pacientes (8% del total) fueron inicialmente diagnosticados de pseudobrote aunque posteriormente fueron diagnosticados de un verdadero brote. La fiebre y el vértigo fueron los principales factores de confusión. Las causas no inflamatorias de consulta urgente fueron: neurológicas: 43,5% (20); infecciosas: 15,2% (7); psiquiátricas: 10,9% (5); vértigo: 8,6% (4); traumatológicas: 10,9% (5), y otras: 10,9% (5).ConclusionesLa mayor parte de las consultas urgentes no inflamatorias fueron causadas por síntomas relacionados con la EM. El seguimiento estrecho de brotes y pseudobrotes es necesario para detectar diagnósticos incorrectos, evitar tratamientos innecesarios y aliviar los síntomas de los pacientes. (AU)

Objectives: To describe non-relapse-related emergency consultations of patients with multiple sclerosis (MS): causes, difficulties in the diagnosis, clinical characteristics, and treatments administered.MethodsWe performed a retrospective study of patients who attended a multiple sclerosis day hospital due to suspected relapse and received an alternative diagnosis, over a 2-year period. Demographic data, clinical characteristics, final diagnosis, and treatments administered were evaluated. Patients who were initially diagnosed with pseudo-relapse and ultimately diagnosed with true relapse were evaluated specifically. As an exploratory analysis, patients who consulted with non-inflammatory causes were compared with a randomly selected cohort of patients with true relapses who attended the centre in the same period.ResultsThe study included 50 patients (33 were women; mean age 41.4 ± 11.7 years). Four patients (8%) were initially diagnosed with pseudo-relapse and later diagnosed as having a true relapse. Fever and vertigo were the main confounding factors. The non-inflammatory causes of emergency consultation were: neurological, 43.5% (20 patients); infectious, 15.2% (7); psychiatric, 10.9% (5); vertigo, 8.6% (4); trauma, 10.9% (5); and miscellaneous, 10.9% (5).ConclusionsMS-related symptoms constituted the most frequent cause of non-inflammatory emergency consultations. Close follow-up of relapse and pseudo-relapse is necessary to detect incorrect initial diagnoses, avoid unnecessary treatments, and relieve patients’ symptoms. (AU)

Non-inflammatory causes of emergency consultation in patients with multiple sclerosis.

OBJECTIVES: To describe non-relapse-related emergency consultations of patients with multiple sclerosis (MS): causes, difficulties in the diagnosis, clinical characteristics, and treatments administered. METHODS: We performed a retrospective study of patients who attended a multiple sclerosis day hospital due to suspected relapse and received an alternative diagnosis, over a 2-year period. Demographic data, clinical characteristics, final diagnosis, and treatments administered were evaluated. Patients who were initially diagnosed with pseudo-relapse and ultimately diagnosed with true relapse were evaluated specifically. As an exploratory analysis, patients who consulted with non-inflammatory causes were compared with a randomly selected cohort of patients with true relapses who attended the centre in the same period. RESULTS: The study included 50 patients (33 were women; mean age 41.4 ±â€¯11.7 years). Four patients (8%) were initially diagnosed with pseudo-relapse and later diagnosed as having a true relapse. Fever and vertigo were the main confounding factors. The non-inflammatory causes of emergency consultation were: neurological, 43.5% (20 patients); infectious, 15.2% (7); psychiatric, 10.9% (5); vertigo, 8.6% (4); trauma, 10.9% (5); and miscellaneous, 10.9% (5). CONCLUSIONS: MS-related symptoms constituted the most frequent cause of non-inflammatory emergency consultations. Close follow-up of relapse and pseudo-relapse is necessary to detect incorrect initial diagnoses, avoid unnecessary treatments, and relieve patients' symptoms.

Patient- versus physician-reported relapses in multiple sclerosis: insights from a large observational study.

BACKGROUND AND PURPOSE: The patient's perspective is becoming increasingly important for endpoints in studies on multiple sclerosis. However, relapse data generated from the patient's perspective in combination with independent documentation by the physician are scarce. Our objective was to compare self-reported relapses by the patient to physician-documented relapses within a routine clinical practice setting of quarterly visits. METHODS: Two-year data (n = 1921 patients) were extracted from two prospective, non-interventional, multicentre cohort studies in Germany. The number of relapses independently reported by patients and physicians was analysed. In addition, inter-rater reliability and measures of validity were evaluated. Patterns of associations were investigated in subgroup analysis of sociodemographic, clinical and patient-reported outcome measures. RESULTS: Patients and physicians showed good overall agreement [κ = 0.78, 95% confidence interval (CI) 0.76-0.80]. Nevertheless, patients reported, on average, more relapses than physicians during follow-up (0.55 vs. 0.44; P < 0.001). Corresponding annualized relapse rates were 0.38 (95% CI 0.36-0.39) and 0.30 (95% CI 0.29-0.31), respectively. Differences between physicians and patients were particularly pronounced in patient groups with greater disability levels, decreased health-related quality of life or treatment satisfaction. The positive predictive value was 74.01% (95% CI 71.85-76.07), and the negative predictive value was 98.86% (95% CI 98.67-99.03). CONCLUSION: Some disagreement on the occurrence of relapses appears in specific patient subgroups, where factors such as pseudo-relapses or confounding factors may have promoted over- or under-reporting.

Emerging Approaches for Validating and Managing Multiple Sclerosis Relapse.

The autoimmune disease multiple sclerosis (MS) is characterized by relapses in the majority of patients. A definitive clinical diagnosis of relapse in MS can be complicated by the presence of an infection or comorbid disorder. In this mini-review, we describe efforts to develop enhanced imaging techniques and biomarker detection as future tools for relapse validation. There is emerging evidence of roles for meningeal inflammation, sex hormones, comorbid metabolic or mood disorders, and a dysregulated immune profile in the manifestation and severity of relapse. Specific subsets of immune cells likely drive the pathophysiology of relapse, and identification of a patient's unique immunological signature of relapse may help guide future diagnosis and treatment. Finally, these studies highlight the diversity in terms of relapse presentation, immunological signature, and response in patients with MS, indicating that going forward the best approach to assessment and treatment of relapse will be multifactorial and highly personalized.