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

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

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

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

Genética de la esclerosis múltiple: papel del HLA-DRB1 en la susceptibilidad y expresión fenotípica

[spa] La esclerosis múltiple (EM) es una enfermedad debida a factores genéticos y ambientales. Se ha demostrado que existe agregación familiar y que los genes del haplotipo HLA-DR2 son los que mayoritariamente se asocian con la susceptibilidad a padecer la enfermedad. Si el fenotipo clínico se ve modificado en las formas familiares de EM respecto a las esporádicas o debido a determinados genes es un tema de constante estudio. HIPÓTESIS: Si existen diferencias clínicas entre formas familiares y esporádicas, éstas nos podrán orientar hacia qué factores genéticos están implicados en la enfermedad y si influyen en su expresión fenotípica. El sistema HLA, como principal marcador genético, podría verse implicado en factores clínicos y paraclínicos de la enfermedad y ser un marcador pronóstico de progresión de discapacidad. OBJETIVOS: 1. Analizar la prevalencia de esclerosis múltiple familiar en nuestra serie y comparar características clínicas entre EM familiar y esporádica. 2 y 3. Evaluar las frecuencias de los diferentes alelos y genotipos HLA-DRB1 en una amplia población con EM esporádica y correlacionarlos con la susceptibilidad a padecer la enfermedad comparando con controles sanos así como evaluar el impacto de los alelos y genotipos en el fenotipo clínico con especial interés en la progresión de la discapacidad. 4. Correlacionar los alelos y genotipos HLA-DRB1 con la presencia de bandas oligoclonales (BOC) en líquido cefalorraquídeo (LCR).METODOLOGÍA: Se analizan 1110 pacientes con EM en un estudio observacional retrospectivo en el que se comparan características clínicas entre formas familiares y esporádicas, así como la progresión de la discapacidad. Se realiza también un estudio de casos y controles analizando mediante PCR-SSP el gen HLA-DRB1 y comparando las frecuencias de los alelos y de los genotipos (combinación de ambos alelos parentales) entre 380 pacientes con EM esporádica y 1088 controles sanos. Se correlacionan los alelos y genotipos con la progresión de la discapacidad y con la presencia de BOC en LCR.RESULTADOS: La prevalencia de EM familiar en nuestra cohorte es del 7,84%. Se objetiva una edad de inicio inferior en la EM familiar respecto a la esporádica así como en las generaciones más jóvenes de EM familiar. Se halla asociación entre la susceptibilidad a padecer EM y el alelo HLA-DRB1*15 así como con los genotipos HLA-DRB1*03/15, HLA-DRB1 *04/15, HLA-DRB1*08/15 y HLA-DRB1*03/03. Los pacientes con los alelos HLA-DRB1*01 y HLA-DRB1*04 así como los genotipos HLA-DRB1*01/04 y HLA-DRB1*15/15 evolucionan peor en cuanto a la progresión de la discapacidad. El alelo HLA-DRB1*15 se asocia con la presencia de BOC en LCR.CONCLUSIONES: 1.a) La prevalencia cruda de esclerosis múltiple familiar en nuestra cohorte es similar a la de otras poblaciones estudiadas.1. b) La edad de inicio es inferior en las formas familiares de esclerosis múltiple si la comparamos con la de las formas esporádicas de la enfermedad. No se han hallado diferencias en cuanto a la progresión de la discapacidad comparando formas familiares y esporádicas de esclerosis múltiple. 2.a) El alelo HLA-DRB1*15 se asocia con una mayor susceptibilidad a padecer esclerosis multiple. 2.b) Los alelos HLA-DRB1*01 y HLA-DRB1*04 confieren peor pronóstico evaluado como el tiempo hasta alcanzar una discapacidad severa. 3.a) Los genotipos que incluyen el alelo DRB1*15 junto con el DRB1*03, DRB1*04 o el DRB1*08 en el otro alelo parental así como los homocigotos para el alelo DRB1*03 se asocian con una mayor susceptibilidad a padecer esclerosis multiple. 3.b) Los genotipos DRB1*01/04 y DRB1*15/15 se asocian con peor pronóstico en cuanto al tiempo hasta alcanzar una discapacidad severa. 4) El alelo HLA-DRB1*15 se asocia con la presencia de BOC en LCR en los pacientes con esclerosis múltiple.[eng] Both polygenic inheritance and enviromental factors have been demonstrated to be involved in multiple sclerosis (MS) with the disease susceptibility. The most frequent genetic region associated with MS susceptibility is the HLA-DR2 haplotype. We hypothesized that familial forms of MS may have a particularly different clinical phenotype. The HLA genes could influence the clinical phenotype and they could be disability progression markers of MS. OBJECTIVES: 1. To analyze the prevalence of familial MS in our cohort and to compare clinical characteristics between familial and sporadic MS. 2,3. To investigate the frequencies of the HLA-DRB1 alleles and genotypes in our population, their influence on the genetic susceptibility and their impact on the clinical phenotype with special interest in the disability progression of MS. 4. To investigate the association between HLA-DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF).METHODS: A cohort of 1110 MS patients is studied to compare familial and sporadic MS. The HLA-DRB1 typing is performed by PCR-SSP in 380 sporadic MS patients and compared with 1088 healthy controls. The HLA-DRB1 alleles and genotypes are correlated with clinical variables and the presence of OCB in CSF. RESULTS: The crude point prevalence of familial MS in our cohort is 7.84%. A lower age at onset in the younger generations of familial MS is found as well as in familial MS comparing to sporadic MS. The HLA-DRB1*15 allele and the genotypes HLA-DRB1*03/15, HLA-DRB1 *04/15, HLA-DRB1*08/15 and HLA-DRB1*03/03 have a significantly higher frequency when compared with controls. The patients with HLA-DRB1*01 and HLA-DRB1*04 alleles as well as the genotypes HLA-DRB1*01/04 and HLA-DRB1*15/15 have a worse prognosis when considering disability progression. The HLA-DRB1*15 allele is associated with OCB-positive patients.CONCLUSIONS: The prevalence of familial MS is similar to other populations. There is a lower age at onset in familial versus sporadic MS. HLA-DRB1*15 is associated with MS in our population as well as the genotypes HLA-DRB1*03/15, HLA-DRB1 *04/15, HLA-DRB1*08/15 and HLA-DRB1*03/03. The HLA-DRB1*01 and HLA-DRB1*04 alleles and the genotypes DRB1*01/04 and DRB1*15/15 are associated with a worse prognosis. HLA-DRB1*15 allele is associated with OCB-positive MS patients

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

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.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.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.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

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