Treatment patterns and persistence on disease modifying therapies for multiple sclerosis and its associated factors.

BACKGROUND: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. OBJECTIVES: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. METHODS: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. RESULTS: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. CONCLUSIONS: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.

Seasonality and clinical characteristics of MS in an equatorial country.

BACKGROUND: Month and season of birth have been associated with risk of multiple sclerosis (MS), but there is relatively little evidence regarding their influence on the timing and severity of disease at onset. OBJECTIVE: To assess whether month and season of birth influence the age and phenotype at onset of MS as well as its severity in a cohort of Colombian patients. METHODS: This study is an analysis on MS cases only, drawn from a previously published case-control study. MS cases confirmed with current diagnostic criteria cared for at least once in our center were included. We assessed the influence of the month and season of birth in the age at MS onset, MS severity score, and age-related MS severity score using multiple and pairwise comparisons. Age at onset was also studied using Kaplan-Meier survival estimates compared with the log-rank test. The likelihood of progressive MS onset was evaluated with OR estimated from logistic regression models adjusted for age at onset and sex. RESULTS: 668 MS cases were included. No significant differences were found in the age at MS onset according to month of birth or season of birth. Neither month of birth nor season of birth conferred significant differences in MS severity score or age-related MS severity score. No significant association was found between month (ORs ranging from 0.62 to 3.11, none significant) or season of birth (OR 0.91; 95 %CI: 0.46-1.84) with primary progressive MS. CONCLUSION: The month or season of birth do not appear to influence the age onset and phenotype of MS in our country.

Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study / Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto.

Introduction: Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective: To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods: We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results: Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions: We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

Introducción: El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo: Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos: Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados: Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones: Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

Pruebas funcionales en esclerosis múltiple y su comparabilidad con los valores de administración autónoma: estudio piloto / Multiple sclerosis functional tests and their comparability with self-administered values: A pilot study

Introducción. El deterioro neurológico en la esclerosis múltiple es variable para cada paciente y su cuantificación se dificulta con el tiempo. El Multiple Sclerosis Outcome Assessment Consortium estableció medidas clínicas sensibles, costo-efectivas y reproducibles para medir los resultados de los estudios clínicos. Sin embargo, sus valores de referencia se desconocen y, en la atención habitual, su uso no está extendido por limitaciones de tiempo y entrenamiento. Objetivo. Establecer la factibilidad de la administración autónoma de las pruebas de marcha de 25 pies, símbolos y dígitos, y clavijas y nueve hoyos en individuos sanos. Materiales y métodos. Se realizó un estudio piloto descriptivo. Se incluyeron individuos sanos entre los 18 y los 80 años. Las pruebas de Timed 25-Foot Walking Test (T25-FWT) [caminata cronometrada de 25 pies], Symbol Digit Modality Test (SDMT) [símbolos y dígitos] y Nine-Hole Peg Test (9-HPT) [clavijas y nueve agujeros] fueron administradas por un médico capacitado, quien también instruyó a los sujetos sobre la administración autónoma de las pruebas. La correlación y la concordancia entre la prueba guiada y la autónoma se evaluaron con los coeficientes de Pearson y Spearman, y el análisis gráfico de Bland-Altman. Resultados. Se incluyeron 38 voluntarios sanos. La mediana de edad fue de 36 (rango: 23-55 años) y el 55,26 % eran mujeres. El coeficiente de correlación entre la prueba de administración guiada y la autónoma fue de 0,37 para la T25-FWT (p=0,01), de 0,54 para la SDMT (p<0,001) y de 0,64 y 0,65 para la 9-HPT, en las manos dominante y no dominante, respectivamente (p<0,001). Ambas formas de administración fueron concordantes para las pruebas T25-FWT (IC95%: -1,49 a 1,43), 9-HPT con la mano dominante (IC95%: -5,23 a 4,09), 9-HPT con la mano no dominante (IC95%: -7,75 a 7,14) y SDMT (IC95%: -20,94 a 24,10). Conclusiones. Los resultados de este estudio ayudan a determinar los valores de normalidad poblacional obtenidos con las pruebas T25-FWT, 9-HPT y SDMT; además, establecen la posibilidad de practicarlas de forma autónoma.

Introduction. Neurological impairment in multiple sclerosis is highly variable among patients and over time it is difficult to quantify. The Multiple Sclerosis Outcome Assessment Consortium established sensitive, cost-effective, clinically significant, and reproducible measures of different functional systems to measure outcomes in clinical trials. However, their use in clinical care routines is not widespread due to time and training constraints. Objective. To evaluate the self-administration feasibility of the timed 25-foot walking, symbol-digit-modality, and 9-peg hole tests in healthy individuals. Materials and methods. We performed a descriptive pilot study. Healthy individuals between 18 and 80 years of age were included. The Timed 25-Foot Walking Test (T25- FWT), the Symbol Digit Modality Test (SDMT), and the Nine-Hole Peg Test (9-HPT) (using the dominant and non-dominant hand) were administered by a trained physician, who also instructed the subjects about test self-administration. The correlation and agreement, between the guided and self-administered tests were assessed with Pearson and Spearman coefficients and the Bland-Altman method. Results. Thirty-eight healthy volunteers were included. The median age was 36 (range: 23-55) years old, and 55.26% were female. The correlation coefficient between guided and selfadministered tests was 0.37 for the T25-FWT (p=0.01), 0.54 for the SDMT (p<0.001), and 0.64 and 0.65 for the 9-HPT, in the dominant and non-dominant hands, respectively (p<0,001). Both forms of administration were concordant for the T25-FWT (95%CI: -1,49 to 1,43), the 9-HPT with dominant hand (95%CI: -5,23 to 4,09), the 9-HPT with non-dominant hand (95%CI: -7,75 to 7,14) and the SDMT (95% CI: -20,94 to 24,10). Conclusions. We provide a proof of concept related to the feasibility of the selfadministration of the T25-FWT, the 9-HPT, and the SDMT, as a tool to improve monitoring in routine clinical practice.

COVID-19 en pacientes con esclerosis múltiple: estudio observacional retrospectivo en un centro de referencia colombiano

Introducción: En Colombia, la información sobre la frecuencia de presentación de la enfermedad por CO-VID-19 y sus desenlaces en personas con esclerosis múltiple (EM) es prácticamente inexistente. El objetivo de este estudio es describir la frecuencia, las características y los factores relacionados con la infección por COVID-19 en una muestra de pacientes con EM en Colombia. Materiales y métodos: Análisis descriptivo y retrospectivo de pacientes diagnosticados con criterios de esclerosis múltiple que acudieron a nuestro centro entre junio y octubre del año 2021. Los pacientes proporcionaron información sobre la infección por SARS-CoV-2 y su vacunación. Se analizaron los factores relacionados con la infección por COVID-19 mediante modelos de regresión logística binomial uni y multivariable. Resultados: Se analizaron 240 pacientes, de los cuales el 71 % eran mujeres, con una edad promedio de 34 años. La mayoría estaban en tratamiento con terapias modificadoras de la enfermedad y más del 80 % estaban vacunados. Sesenta y nueve pacientes declararon haber tenido COVID-19. En los modelos multivariables, la edad (OR 0,96; IC 95 % 0,93-0,99) fue el único factor asociado con una menor probabilidad de infección por COVID-19. Discusión: La infección por COVID-19 en pacientes con EM en Colombia parece ser independiente de las variables clínicas y de tratamiento y parece estar asociada con la menor edad. Conclusiones: Se requieren más estudios para evaluar el comportamiento del COVID-19 en pacientes con EM en el contexto colombiano.

Introduction: The information about the frequency of COVID-19 and its outcomes in people with Multiple Sclerosis (MS) in Colombia is practically non-existent. We aimed to describe the frequency characteristics and factors associated with of COVID-19 in a sample of patients with MS. Materials and methods: Descriptive and retrospective analysis of patients diagnosed with Multiple Sclerosis criteria who attended our center between June and October 2021. Patients provided information about SARS-CoV-2 infection and their vaccination. COVID-19 determinants were analyzed using uni-and multivariable binomial logistic regression models. Results: 240 patients were analyzed, of whom 71% were women, with a mean age of 34 years. The majority of patients were on disease-modifying therapies and over 80 % were vaccinated. 69 patients reported having had COVID-19. In multivariable models, age (OR 0.96; 95 % CI 0.93-0.99) was the only factor associated with a lower odds of COVID-19 infection. Discussion: COVID-19 infection in patients with MS in Colombia appears to be independent of clinical and treatment variables, and it appears to be associated with younger age. Conclusions: More studies are needed to assess the behavior of COVID-19 in MS patients from Colombia.

No seasonality in the risk of multiple sclerosis in an equatorial country: A case-control ecological study.

BACKGROUND: Multiple sclerosis risk has been shown to have seasonal variations that are more pronounced in higher latitudes. However, this phenomenon has not been adequately studied near the Equator. OBJECTIVE: To explore the risk of multiple sclerosis associated with month, season of birth, and sunlight exposure variables in Colombia. METHODS: In this case-control study, 668 multiple sclerosis cases were matched to 2672 controls by sex and age. Association of multiple sclerosis with each month/season of birth and sunlight exposure variables was estimated with multilevel mixed-effects logistic regression and ecological regression models, respectively. Seasonality in the births of multiple sclerosis was assessed with a non-parametric seasonality test. RESULTS: We found a higher probability of multiple sclerosis in September (0.25; 95% confidence interval (CI) = 0.21-0.31) and lower in March (0.15; 95% CI = 0.10-0.18), which turned non-significant after a multiple comparisons test. Sunlight exposure variables had no significant effect on the risk of MS, and the tests of seasonality in the births of MS did not show significant results. CONCLUSION: Our results show no seasonality in the risk of multiple sclerosis near the Equator, supporting the hypothesis that this phenomenon is latitude dependent.

Fertility preferences and unmet need for family planning in women with multiple sclerosis.

Background: Most women with multiple sclerosis (MS) have childbearing potential. Although fertility and pregnancy are not affected by MS, the fertility preferences of women with MS can change due to the risk of complications for the mother and/or adverse pregnancy outcomes resulting from the disease or its treatment. Objectives: To describe fertility preferences (FPs) and their associated factors, to estimate the Unmet Need for Family Planning (UNFP), use of contraceptives, and history of exposure to disease-modifying therapies (DMTs) during pregnancy in women with MS. Methods: In a cross-sectional observational study, a random sample of women with MS were surveyed with the FP subset of the Demographic and Health Survey of Colombia. Factors associated with FP were evaluated through bivariate and logistic regression analysis. The proportion of pregnancies exposed to DMTs, UNFP, and use of contraceptives was estimated. Results: Of the 141 women interviewed, 101 women had childbearing potential, of whom 49 did not want to have children, 38 were sterilized, 33 wanted to have more children, 19 were undecided, and 2 stated they were unable to bear children (menopause or hysterectomy). No MS-related variables were associated with the preference to have more children. Age (OR 0.91; 95% CI 0.84-0.98) and the number of children (OR 0.23; 95% CI 0.09-0.58) decreased the likelihood of desire for children. Of 116 sexually active women, 87.06 % (101) were using contraceptives, and among them, four were using fertility awareness methods and withdrawal. The UNFP was estimated at 6.03% and was not significantly different from the general population. Eighty-two pregnancies were identified, of which 48 occurred after diagnosis, and 25 were exposed to DMTs. Conclusion: Fertility preference in women with MS is not associated with clinical variables. A large proportion of women choose not to have children and prefer to use permanent contraceptive methods. Although the frequency of contraceptive use was high, some women have the UNFP and use low-efficacy contraceptive methods, which may result in unplanned pregnancies.

The kappa free light chain index and oligoclonal bands have a similar role in the McDonald criteria.

Intrathecal production of kappa free light chains occurs in multiple sclerosis and can be measured using the kappa free light chain index. Kappa free light chain index values can be determined more easily than oligoclonal bands detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of oligoclonal bands, kappa free light chain index cut-offs 5.9, 6.6 and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome inception cohort. We selected patients with sufficient data to determine oligoclonal bands positivity, MRI dissemination in space and time, IgG index and sufficient quantities of paired CSF and blood samples to determine kappa free light chain indexes (n = 214). We used Kendall's Tau coefficient to estimate concordance, calculated the number of additional diagnoses when adding each positive index to dissemination in space and positive oligoclonal bands, performed survival analyses for oligoclonal bands and each index with the outcomes second attack and 2017 MRI dissemination in space and time and estimated the diagnostic properties of oligoclonal bands and the different indexes for the previously mentioned outcomes at 5 years. Oligoclonal bands were positive in 138 patients (64.5%), kappa free light chain-5.9 in 136 (63.6%), kappa free light chain-6.6 in 135 (63.1%), kappa free light chain-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between oligoclonal bands and kappa free light chain-6.6 (τ = 0.727) followed by oligoclonal bands and kappa free light chain-5.9 (τ = 0.716). Combining dissemination in space plus oligoclonal bands or kappa free light chain-5.9 increased the number of diagnosed patients by 11 (5.1%), with kappa free light chain-6.6 by 10 (4.7%), with kappa free light chain-10.61 by 9 (4.2%) and with IgG index by 3 (1.4%). Patients with positive oligoclonal bands or indexes reached second attack and MRI dissemination in space and time faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [adjusted hazard ratio (95% confidence interval)], the risk for second attack was very similar between kappa free light chain-5.9 [2.0 (0.9-4.3), P = 0.068] and kappa free light chain-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI dissemination in space and time was demonstrated with kappa free light chain-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by kappa free light chain-6.6 [3.4 (1.9-6.3), P < 0.0001]. Kappa free light chains-5.9 and -6.6 had a slightly higher diagnostic accuracy than oligoclonal bands for second attack (70.5, 71.1 and 67.8) and MRI dissemination in space and time (85.7, 85.1 and 81.0). Kappa free light chain indexes 5.9 and 6.6 performed slightly better than oligoclonal bands to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between oligoclonal bands and these indexes, we suggest using dissemination in space plus positive oligoclonal bands or positive kappa free light chain index as a modified criterion to diagnose multiple sclerosis.

Is humoral and cellular response to SARS-CoV-2 vaccine modified by DMT in patients with multiple sclerosis and other autoimmune diseases?

BACKGROUND: The effect of disease-modifying therapies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is unclear. OBJECTIVES: We aim to determine the immunological responses to SARS-CoV-2 in multiple sclerosis (MS) and anti-CD20-treated patients with other autoimmune diseases (AID). METHODS: Humoral and cellular responses we determined before and 30-90 days after vaccination in patients with MS and anti-CD20-treated patients with other AID in two Catalan centers. RESULTS: 457 patients were enrolled. Findings showed that humoral response decreased under anti-CD20s or sphingosine 1-phosphate receptor modulators (S1PRM) and with longer treatment duration and increased after 4.5 months from the last anti-CD20 infusion. Cellular response decreased in S1PRM-treated. Patients on anti-CD20 can present cellular responses even in the absence of antibodies. CONCLUSION: Anti-CD20s and S1PRM modify the immunological responses to SARS-CoV-2 vaccines.

Humoral and Cellular Responses to SARS-CoV-2 in Convalescent COVID-19 Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Information about humoral and cellular responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antibody persistence in convalescent (COVID-19) patients with multiple sclerosis (PwMS) is scarce. The objectives of this study were to investigate factors influencing humoral and cellular responses to SARS-CoV-2 and its persistence in convalescent COVID-19 PwMS. METHODS: This is a retrospective study of confirmed COVID-19 convalescent PwMS identified between February 2020 and May 2021 by SARS-CoV-2 antibody testing. We examined relationships between demographics, MS characteristics, disease-modifying therapy (DMT), and humoral (immunoglobulin G against spike and nucleocapsid proteins) and cellular (interferon-gamma [IFN-γ]) responses to SARS-CoV-2. RESULTS: A total of 121 (83.45%) of 145 PwMS were seropositive, and 25/42 (59.5%) presented a cellular response up to 13.1 months after COVID-19. Anti-CD20-treated patients had lower antibody titers than those under other DMTs (p < 0.001), but severe COVID-19 and a longer time from last infusion increased the likelihood of producing a humoral response. IFN-γ levels did not differ among DMT. Five of 7 (71.4%) anti--CD20-treated seronegative patients had a cellular response. The humoral response persisted for more than 6 months in 41/56(81.13%) PwMS. In multivariate analysis, seropositivity decreased due to anti-CD20 therapy (OR 0.08 [95% CI 0.01-0.55]) and increased in males (OR 3.59 [1.02-12.68]), whereas the cellular response decreased in those with progressive disease (OR 0.04 [0.001-0.88]). No factors were associated with antibody persistence. DISCUSSION: Humoral and cellular responses to SARS-CoV-2 are present in COVID-19 convalescent PwMS up to 13.10 months after COVID-19. The humoral response decreases under anti-CD20 treatment, although the cellular response can be detected in anti-CD20-treated patients, even in the absence of antibodies.

Impact of COVID-19 pandemic on frequency of clinical visits, performance of MRI studies, and therapeutic choices in a multiple sclerosis referral centre.

INTRODUCTION: To evaluate the impact of the COVID-19 pandemic on (1) number of clinical visits, (2) magnetic resonance (MR) scans, and (3) treatment prescriptions in a multiple sclerosis (MS) referral centre. METHODS: Retrospective study covering January 2018 to May 2021. RESULTS: The monthly mean (standard deviation [SD]) of visits performed in 2020 (814[137.6]) was similar to 2018 (741[99.7]; p = 0.153), and 2019 (797[116.3]; p = 0.747). During the COVID-19 period (2020 year), 36.3% of the activity was performed through telemedicine. The number of MR scans performed dropped by 76.6% during the "first wave" (March 14 to June 21, 2020) compared to the mean monthly activity in 2020 (183.5[68.9]), with a recovery during the subsequent two months. The monthly mean of treatment prescriptions approved in 2020 (24.1[7.0]) was lower than in 2019 (30[7.0]; p = 0.049), but similar to 2018 (23.8[8.0]; p = 0.727). Natalizumab prescriptions increased in the "first wave" and onwards, whereas anti-CD20 prescriptions decreased during the COVID-19 period. CONCLUSION: Maintenance of the number of clinical visits was likely due to telemedicine adoption. Although the number of MR dramatically dropped during the "first wave", an early recovery was observed. Treatment prescriptions suffered a slight quantitative decrease during 2020, whereas substantial qualitative changes were found in specific treatments.

Multiple sclerosis is associated with higher comorbidity and health care resource use: A population-based, case-control study in a western Mediterranean region.

BACKGROUND AND PURPOSE: Comorbidities are common in multiple sclerosis (MS), and have been associated with worse outcomes and increased health care resource usage. We studied the frequency of comorbidities and adverse health behaviors (AHBs) in MS patients in the Mediterranean region of Catalonia. METHODS: This population-based, case-control study used primary health care information covering 80% of Catalonia's population. Cases were matched by age/sex with randomly chosen controls (ratio = 1:5). Demographic information, comorbidities, AHBs, annual visits, sick leave days, and medication dispensing were studied. The association of comorbidities with MS and the profile of comorbidities according to sex within MS cases were assessed with multivariate logistic regression models, after adjusting for confounding variables. Health care resource usage was analyzed in MS cases compared to controls, and within MS cases in those with compared to those without comorbidities. RESULTS: Five thousand five hundred forty-eight MS cases and 27,710 controls (70% female, mean age = 48.3 years) were included. Stroke (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.17-1.99), epilepsy (OR = 2.46, 95% CI = 1.94-3.10), bipolar disorder (OR = 1.67, 95% CI = 1.17-2.36), and depression (OR = 1.83, 95% CI = 1.70-1.98) were more frequent in MS. Cases were more prone to smoking but less to alcohol intake. Among cases, psychiatric comorbidities were more frequent in women, whereas cardiovascular diseases and AHBs were more frequent in men. MS patients, particularly with comorbidities, had higher health care resource usage than controls. CONCLUSIONS: Psychiatric comorbidities, stroke, epilepsy, and AHBs are more common in MS patients than in the general population in the western Mediterranean region of Catalonia. The presence of comorbidities increases the health care resource usage in MS patients.

COVID-19 in multiple sclerosis patients: susceptibility, severity risk factors and serological response.

BACKGROUND AND PURPOSE: Information regarding multiple sclerosis (MS) patients with the 2019 novel coronavirus disease (COVID-19) is scarce. The study objective was to describe the incidence and characteristics of MS patients with COVID-19, to identify susceptibility and severity risk factors and to assess the proportion of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologies according to disease-modifying treatments. METHODS: This was a retrospective study of an MS cohort analysing data collected between February and May 2020. Cases were identified through an email survey and clinical visits. The relationship of demographic and MS characteristics with COVID-19 and of the disease-modifying treatments with SARS-CoV-2 serostatus were examined. RESULTS: Data from 48 suspected cases out of 758 valid respondents and from 45 COVID-19 cases identified through clinical visits were collected. Incidence was 6.3%. Nineteen (20.3%) patients were hospitalized and two (2.2%) died. Multivariable models determined that age (odds ratio [OR] per 10 years 0.53, 95% confidence interval [CI] 0.34-0.85), contact with a confirmed case (OR 197.02, 95% CI 56.36-688.79), residence in Barcelona (OR 2.23, 95% CI 1.03-4.80), MS duration (OR per 5 years 1.41, 95% CI 1.09-1.83) and time on anti-CD20 treatment (OR per 2 years 3.48, 95% CI 1.44-8.45) were independent factors for presenting COVID-19 and age (OR per 10 years 2.71, 95% CI 1.13-6.53) for a severe COVID-19. Out of the 79 (84.9%) with serological test, 45.6% generated antibodies, but only 17.6% of those on anti-CD20 therapies. Lymphopaenia or immunoglobulin levels did not relate to COVID-19. CONCLUSIONS: Multiple sclerosis patients present similar incidence, risk factors and outcomes for COVID-19 as the general population. Patients treated with an anti-CD20 therapy for a longer period of time might be at a higher risk of COVID-19 and less than 20% generate an antibody response. Only age was related to severity.

Delayed diagnosis of multiple sclerosis in a low prevalence country.

Background: Early diagnosis and treatment of multiple sclerosis (MS) is crucial to avoid future disability. The factors that influence diagnostic delay in low prevalence settings have been poorly studied.Objectives: To evaluate the factors associated with a delayed diagnosis of MS after the symptomatic onset.Methods: Clinical records of confirmed MS patients were reviewed. Diagnostic delay was calculated by subtracting the date of onset from the date of diagnosis and categorized as early and delayed, when below and above than 1 year. Logistic regression was performed to evaluate the likelihood of a delayed diagnosis according to age at first symptom, gender, type of the first symptom, progressive vs relapsing onset, diagnostic criteria prevailing at the time of symptom onset, comorbidities, and family history of MS.Results: Data of 525 (95.6%) from a cohort of 549 patients were analyzed. About 69.1% were women. The mean age was 43.2 years. About 86.3% had relapsing-remitting MS. The mean overall diagnostic delay was 3.07 years. About 45.7% of the patients had a delayed diagnosis, and it was dependent on the symptom and the diagnostic criteria prevailing at the onset. Multivariate logistic regression showed onset during the Schumacher (OR = 10.03 [95%CI 1.30-77.1], p = 0.027) and Poser (OR = 4.26 [95%CI 1.25-15.15], p = 0.021) years were associated with delayed MS diagnosis.Conclusions: MS onset before the McDonald diagnostic criteria era is associated with delayed diagnosis.

Multiple sclerosis management during the COVID-19 pandemic.

BACKGROUND: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services. OBJECTIVES: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery. METHODS: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d'Hebron-Centre d'Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care. RESULTS: There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services. CONCLUSION: Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption.

Prevalencia e impacto de las comorbilidades en pacientes con esclerosis múltiple / Prevalence and impact of comorbidities in patients with multiple sclerosis

INTRODUCCIÓN: La esclerosis múltiple es una enfermedad crónica, de origen inflamatorio y degenerativo, del sistema nervioso central. Se caracteriza en la mayoría de los casos por la aparición de manera recurrente de brotes de déficit neurológico focal, que con el tiempo puede tornarse progresivo. Dado el carácter crónico de la enfermedad, los pacientes pueden presentar enfermedades adicionales (comorbilidades), que impactan de diferentes maneras en la historia natural de la enfermedad y en su tratamiento. OBJETIVO: Resumir la evidencia disponible respecto a la influencia de las comorbilidades en la historia natural de la esclerosis múltiple. DESARROLLO: Los pacientes con esclerosis múltiple tienen un riesgo mayor que la población general de desarrollar comorbilidades tanto agudas como crónicas. Se ha demostrado que las comorbilidades pueden retrasar el diagnóstico de esclerosis múltiple después del inicio clínico, incrementar la tasa de brotes y aumentar la tasa de acumulación de la discapacidad. Las comorbilidades también influyen en aspectos relacionados con la elección del tratamiento y la adhesión terapéutica. Finalmente, las comorbilidades también aumentan la tasa de mortalidad y la calidad de vida de los pacientes con esclerosis múltiple. CONCLUSIONES: El cribado, el diagnóstico y el tratamiento de las comorbilidades son un aspecto clave del cuidado de los pacientes con esclerosis múltiple para mejorar su pronóstico a largo plazo en cuanto a discapacidad, calidad de vida y mortalidad

INTRODUCTION: Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system. In most cases it is characterised by the recurring focal neurological deficit, which may become progressive over time. Given the chronic nature of the disease, patients may present with additional diseases (comorbidities), which affect the natural history of the disease and its treatment in different ways. AIM: To summarise the available evidence regarding the influence of comorbidities on the natural history of multiple sclerosis. DEVELOPMENT: Patients with multiple sclerosis are at greater risk than the general population of developing both acute and chronic comorbidities. It has been shown that comorbidities can delay the diagnosis of multiple sclerosis after clinical onset, increase the rates of relapses and of accumulation of disability. Comorbidities also influence aspects of the choice of treatment and therapy adherence. Finally, comorbidities also increase the mortality rate and reduce the quality of life of patients with multiple sclerosis. CONCLUSIONS: Screening, diagnosis and treatment of comorbidities are a key aspect of caring for patients with multiple sclerosis to improve their long-term prognosis in terms of disability, quality of life and mortality

Multiple sclerosis coverage in the written media of a low prevalence country.

BACKGROUND: Awareness in the community is an important factor across a wide range of diseases and the communication media have an important role in its promotion. However, misinformation and misguide may take place heightening the expectations of people affected by chronic conditions such as multiple sclerosis (MS). This study explores media coverage of MS in a low prevalence country. METHODS: We identified the most important written media at national and local levels and performed a search in their digital archives and social media with the words "Multiple Sclerosis". The articles found were categorized as relevant, and non-relevant. We describe the total number, number of relevant and non-relevant articles published every year, since the earliest found until 2018. We identified the topics covered by the relevant articles and described their distribution and performed a quality evaluation of their content. RESULTS: We reviewed the archives of 20 sources. A total of 976 articles where MS was mentioned were reviewed (relevant: 143 [14.6%]; non-relevant: 833 [85.4%]). We observed a steady increase in the annual publication rate, from the first in 1991 up to 107 in 2018. The most frequent covered topic was disease modifying therapies and MS itself, and the least documented topic was rehabilitation. Most of the relevant articles had low quality scores. CONCLUSION: The media coverage of different topics MS has risen steadily since its first appearance in the early nineties. This should be encouraged, but caution should be held so misinformation is not propagated. We call for the public to discuss misleading information with their healthcare providers.

Characterization of brain anatomical patterns by comparing region intensity distributions: Applications to the description of Alzheimer's disease.

Purpose: This work presents an automatic characterization of the Alzheimer's disease describing the illness as a multidirectional departure from a baseline defining the control state, being these directions determined by a distance between functional-equivalent anatomical regions. Methods: After a brain parcellation, a region is described by its histogram of gray levels, and the Earth mover's distance establishes how close or far these regions are. The medoid of the control group is set as the reference and any brain is characterized by its set of distances to this medoid. Evaluation: This hypothesis was assessed by separating groups of patients with mild Alzheimer's disease and mild cognitive impairment from control subjects, using a subset of the Open Access Series of Imaging Studies (OASIS) database. An additional experiment evaluated the method generalization and consisted in training with the OASIS data and testing with the Minimal Interval Resonance Imaging in Alzheimer's disease (MIRIAD) database. Results: Classification between controls and patients with AD resulted in an equal error rate of 0.1 (90% of sensitivity and specificity at the same time). The automatic ranking of regions resulting is in strong agreement with those regions described as important in clinical practice. Classification with different databases results in a sensitivity of 85% and a specificity of 91%. Conclusions: This method automatically finds out a multidimensional expression of the AD, which is directly related to the anatomical changes in specific areas such as the hippocampus, the amygdala, the planum temporale, and thalamus.