Idiopathic acute transverse myelitis: outcome and conversion to multiple sclerosis in a large series

Background: in 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM) to delimit and unify this group of patients. This study aimed to describe the conversion rate to multiple sclerosis (MS) and variables associated with conversion, and to analyze functional outcome and prognostic factors associated with functional recovery in patients who fulfilled the current TMCWG criteria for definite and possible IATM. Methods: eighty-seven patients diagnosed with IATM between 1989 and 2011 were retrospectively reviewed. Two patients with positive neuromyelitis optica IgG serum antibodies were excluded. Epidemiological, clinical, laboratory, magnetic resonance imaging (MRI) data and outcome of 85 patients were analyzed. Results: eleven (13%) patients converted to MS after a median follow-up of 2.9 years (interquartile range 1.0-4.8). Early-age onset of symptoms was related to conversion to MS. Only 9.4% of patients with IATM were unable to walk unassisted at the end of follow-up. Urinary sphincter dysfunction (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.04-10.92) and longitudinally extensive transverse myelitis (LETM) on MRI (OR 12.34, 95% CI 3.38-45.00) were associated with a poorer outcome (Rankin ≥ 2). Conclusions: at least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI

Cost associated with a relapse-free patient in multiple sclerosis: a real-world health indicator

Background: The efficacy and safety of disease-modifying therapies (DMTs) in multiple sclerosis (MS) are well known; however, owing to their high costs, determining real-world outcomes is essential to evaluate the cost-effectiveness of different therapeutic strategies. This study aimed to investigate the variability in the annual cost of DMTs associated with a relapse-free patient in a representative population cohort of relapsing-remitting MS (RRMS), and whether this could serve as an appropriate health indicator. Methods: We analyzed the patients followed up in our MS clinic during the years 2016 and 2019, and selected patients belonging to our health district diagnosed with RRMS. The treatment cost associated with a relapse-free patient was the ratio between the total cost of DMTs and the number of relapse-free patients, treated and not treated, during the year of the study. Results: A total of 158 patients with RRMS in 2016 and 183 in 2019 were included in our study. In 2016, 101 patients with RRMS (63.9%) received treatment with DMTs and 120 patients (75.9%) remained relapse-free. The mean cost of DMTs per patient in 2016 was 7414.3 (95% confidence interval [CI]: 6325.2-8503.4) considering all the patients (treated and not treated). In 2019, 126 patients (68.9%) received DMTs and 151 patients (82.5%) remained relapse-free. The mean cost of DMTs per patient in 2019 was 6985.4 (95% CI: 5986.9-7983.9) considering all the patients. The cost per year of DMTs to achieve a relapse-free patient was 9762.2 in 2016 and 8465.8 in 2019. Conclusions: The treatment cost per year to achieve a relapse-free patient was stable during successive measurements in the same population. Therefore, it may be considered a good real-world health indicator for patients with RRMS treated with DMTs

Baseline MxA mRNA expression predicts interferon beta response in multiple sclerosis patients

Background Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta. Methods Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups. Results 104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers. Conclusion The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment

The age at onset of relapsing-remitting multiple sclerosis has increased over the last five decades

Background: Patients with relapsing-remitting multiple sclerosis (RRMS) most commonly experience their first symptoms between 20 and 40 years of age. The objective of this study was to investigate how the age at which the first symptoms of RRMS occur has changed over the past decades. Methods: Patients who were followed up in our unit after an initial diagnosis of RRMS using the Poser or McDonald criteria and who experienced their first symptoms between January 1970 and December 2019 were included in the study. The cohort was divided into five groups according to the decade in which the first symptoms appeared. The age at disease onset was compared across decades. Changes in age were also determined after excluding patients with early-onset disease (50 years of age) to avoid bias. Results: The cohort included 1,622 patients with RRMS, 67.6% of whom were women. Among them, 5.9% and 4% had early-onset and late-onset disease, respectively. The mean age ± standard deviation at onset was 31.11 ± 9.82 years, with no differences between men and women. The mean ages at onset were 23.79 ± 10.19 years between 1970 and 1979, 27.86 ± 9.22 years between 1980 and 1989, 30.07 ± 9.32 years between 1990 and 1999, 32.12 ± 9.47 between 2000 and 2009, and 34.28 ± 9.83 years between 2010 and 2019. The ages at disease onset were progressively higher in the later decades; this trend was statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.264 and R2 of 0.070 (p < 0.001). The results were similar when analysing men and women separately. We conducted an analysis of 1,460 patients (mean age at onset: 31.10 ± 7.99 years), after excluding patients with early-onset and late-onset disease. In this specific subgroup, the mean ages at disease onset were 28.38 ± 8.17 years between 1970 and 1979, 29.22 ± 7.51 years between 1980 and 1989, 30.06 ± 8.02 years between 1990 and 1999, 31.46 ± 7.77 years between 2000 and 2009, and 33.37 ± 7.97 years between 2010 and 2019. The trend was also statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.193 and R2 of 0.037 (p < 0.001)

Transient paraparesis as a manifestation of left carotid stenosis

Introducción: la paraparesia por afectación vascular cerebral es infrecuente, aunque se observa en infartos de ambas arterias cerebrales anteriores (ACA), en síndromes de insuficiencia vertebrobasilar o en infartos de territorios frontera de la circulación anterior. Caso clínico: varón de 52 años, diestro, con antecedentes de hipertensión arterial, que consultó por dos episodios transitorios de paraparesia, de 5 minutos y 15 horas de duración. Durante el último episodio, se objetivó la presencia de una paraparesia y un Babinski izquierdo. Las exploraciones complementarias practicadas para el estudio de patología medular fueron negativas. Una RM craneal mostró únicamente infartos lacunares bilaterales en territorios profundos. Cuatro meses después, el paciente presentó un episodio de afasia motora y parestesias de la extremidad inferior derecha, autolimitado en 10 minutos. La ecografía Doppler de los troncos supraórticos reveló una estenosis significativa de carótida interna izquierda (CII) y una oclusión de la derecha (CID). La arteriografía de los troncos supraórticos demostró una estenosis del 99% de la CID y del 95% de la CII, con vascularización de ambas ACA dependientes de la CII. Se practicó una endarterectomía carotídea izquierda, y el paciente permaneció asintomático hasta la actualidad. Conclusión: en nuestro paciente, ambas ACA dependían del flujo de la CII. Por ello, consideramos que el cuadro de paraparesia transitoria fue secundario a la estenosis carotídea izquierda, bien por un mecanismo hemodinámico o embólico arteria­arteria

Individualización posológica de natalizumab en la esclerosis múltiple remitente recurrente

La esclerosis multiple (EM) es la enfermedad autoinmune, inflamatoria, cronica y degenerativa mas prevalente a nivel mundial, cuya forma mas frecuente es la EM remitente recurrente (EMRR). Para el manejo de la EMRR grave se aprobo natalizumab, un anticuerpo monoclonal IgG4 que se une a la integrina 41 de la superficie de los leucocitos, impidiendo que migren al sistema nervioso central. Con la dosis fija intravenosa aprobada, de 300 mg cada 4 semanas, se ha comprobado que mas del 90% de los pacientes alcanzan concentraciones sericas preinfusion de NTZ >10 μg/mL, cuando la eficacia se ha demostrado con unos niveles de 2,5-10 μg/mL. Una concentracion plasmatica de NTZ de 2,5 μg/mL asegura una ocupacion del 50% de la biofase y demuestra una eficacia terapeutica, mientras que tasas de ocupacion del 20-40% se han relacionado con un aumento de la actividad de la enfermedad. Palabras clave: Esclerosis multiple, natalizumab, farmacocinétic

Impact of Neuromyelitis Optica Spectrum Disorder on Quality of Life from the Patients' Perspective : An Observational Cross-Sectional Study

Altres ajuts: Medical Department of Roche Farma, Spain (ML41397).Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. Methods: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis. Results: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29. Conclusion: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions

Quantifying the patient´s perspective in neuromyelitis optica spectrum disorder: Psychometric properties of the SymptoMScreen questionnaire

Background: The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. Methods: A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. Results: A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach's alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken's criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). Conclusions: The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD

Perception of Stigma in Patients with Neuromyelitis Optica Spectrum Disorder

Background: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman's rank correlation. Results: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p<0.0001) and psychological (rho=0.608, p<0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p<0.0001), MOS-PES score (rho= 0.457, p<0.0001), and D-FIS score (rho=0.556, p<0.0001). Conclusion: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge

Cognitive Performance and Health-Related Quality of Life in Patients with Neuromyelitis Optica Spectrum Disorder

Background: The frequency of cognitive impairment (CI) reported in neuromyelitis optica spectrum disorder (NMOSD) is highly variable, and its relationship with demographic and clinical characteristics is poorly understood. We aimed to describe the cognitive profile of NMOSD patients, and to analyse the cognitive differences according to their serostatus; furthermore, we aimed to assess the relationship between cognition, demographic and clinical characteristics, and other aspects linked to health-related quality of life (HRQoL). Methods: This cross-sectional study included 41 patients (median age, 44 years; 85% women) from 13 Spanish centres. Demographic and clinical characteristics were collected along with a cognitive z-score (Rao's Battery) and HRQoL patient-centred measures, and their relationship was explored using linear regression. We used the Akaike information criterion to model which characteristics were associated with cognition. Results: Fourteen patients (34%) had CI, and the most affected cognitive domain was visual memory. Cognition was similar in AQP4-IgG-positive and -negative patients. Gender, mood, fatigue, satisfaction with life, and perception of stigma were associated with cognitive performance (adjusted R-2 = 0.396, p < 0.001). Conclusions: The results highlight the presence of CI and its impact on HRQoL in NMOSD patients. Cognitive and psychological assessments may be crucial to achieve a holistic approach in patient care