Experience with tocilizumab in patients with neuromyelitis optica spectrum disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system involving astrocytes, B lymphocytes, anti-aquaporin 4, and such inflammatory mediators as interleukin-6. Several immunosuppressants are used in their treatment. Tocilizumab, an interleukin-6 receptor antagonist, may be a treatment option. METHOD: We performed an observational, retrospective study analysing parameters of effectiveness (annualised relapse rate, disability, and radiological progression) and safety of tocilizumab in patients with NMOSD in whom previous immunosuppressant treatment had failed. We aimed to evaluate the effectiveness and safety of tocilizumab in clinical practice in patients with NMOSD not responding to other immunosuppressants. RESULTS: Five patients with NMOSD were analysed. Sixty percent of patients were women; mean age at diagnosis was 50±5.3 years and mean progression time was 4.5±3.6 years. Previously administered immunosuppressants were rituximab (in all 5), cyclophosphamide (2), and azathioprine (1). Mean time of exposure to tocilizumab was 2.3±1 years. Mean annualised relapse rate was 1.8±1.3 in the year prior to the introduction of tocilizumab and 0.2±0.4 the year after (P<.05), representing a reduction of 88.9%. CONCLUSIONS: In our experience, tocilizumab is safe and effective in patients with NMOSD showing no response to other immunosuppressants.

13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (II). / XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II).

INTRODUCTION: For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. AIM: This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed. CONCLUSIONS: Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS.

TITLE: XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II).Introducción. Desde hace más de una década, tras el Congreso ECTRIMS, se celebra en España la reunión post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) se reúnen para revisar las novedades presentadas en el ECTRIMS. Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias de la reunión post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 virtualmente. Desarrollo. En esta segunda parte se destaca la importancia del género y la edad en la compresión de la patología de la enfermedad y la optimización de su manejo. Se exponen los avances realizados en la EM pediátrica desde un punto de vista neuropsicológico y de neuroimagen. Por su parte, cobran especial protagonismo los hallazgos que contribuyen a realizar un enfoque del tratamiento más personalizado y a elegir la mejor estrategia de tratamiento (farmacológica y no farmacológica) para cada paciente. De igual forma, se abordan los resultados relacionados con las estrategias posibles que promuevan la remielinización. Aunque no hay grandes avances en el tratamiento de formas progresivas, se destacan algunos métodos cuantitativos para la clasificación de estos pacientes. Además, se incluyen los resultados sobre herramientas potenciales de evaluación y tratamiento de los déficits cognitivos, y algunos aspectos relevantes observados en el espectro de los trastornos de la neuromielitis óptica. Por último, se detallan los resultados de las ponencias consideradas como noticias de última hora en el ECTRIMS-ACTRIMS. Conclusiones. Se presentaron avances principalmente sobre el conocimiento de la EM pediátrica, las estrategias de remielinización y la evaluación cognitiva en la EM.

XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I) / 13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (I)

Introducción: Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo: En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo: En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones: Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.(AU)

Introduction: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). Aim: This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. Development: This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. Conclusions: There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.(AU)

XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II) / 13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (II)

Introducción: Desde hace más de una década, tras el Congreso ECTRIMS, se celebra en España la reunión post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) se reúnen para revisar las novedades presentadas en el ECTRIMS. Objetivo: En el presente artículo, publicado en dos partes, se resumen las ponencias de la reunión post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 virtualmente. Desarrollo: En esta segunda parte se destaca la importancia del género y la edad en la compresión de la patología de la enfermedad y la optimización de su manejo. Se exponen los avances realizados en la EM pediátrica desde un punto de vista neuropsicológico y de neuroimagen. Por su parte, cobran especial protagonismo los hallazgos que contribuyen a realizar un enfoque del tratamiento más personalizado y a elegir la mejor estrategia de tratamiento (farmacológica y no farmacológica) para cada paciente. De igual forma, se abordan los resultados relacionados con las estrategias posibles que promuevan la remielinización. Aunque no hay grandes avances en el tratamiento de formas progresivas, se destacan algunos métodos cuantitativos para la clasificación de estos pacientes. Además, se incluyen los resultados sobre herramientas potenciales de evaluación y tratamiento de los déficits cognitivos, y algunos aspectos relevantes observados en el espectro de los trastornos de la neuromielitis óptica. Por último, se detallan los resultados de las ponencias consideradas como noticias de última hora en el ECTRIMS-ACTRIMS. Conclusiones: Se presentaron avances principalmente sobre el conocimiento de la EM pediátrica, las estrategias de remielinización y la evaluación cognitiva en la EM.(AU)

Introduction: For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. Aim: This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020. Development: This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed. Conclusions: Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS.(AU)

13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (I). / XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).

INTRODUCTION: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). AIM: This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. CONCLUSIONS: There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.

TITLE: XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).Introducción. Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo. En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones. Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.

Experience with tocilizumab in patients with neuromyelitis optica spectrum disorders. / Experiencia con tocilizumab en pacientes con espectro de la neuromielitis óptica.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system involving astrocytes, B lymphocytes, anti-aquaporin 4, and such inflammatory mediators as interleukin-6. Several immunosuppressants are used in their treatment. Tocilizumab, an interleukin-6 receptor antagonist, may be a treatment option. METHOD: We performed an observational, retrospective study analysing parameters of effectiveness (annualised relapse rate, disability, and radiological progression) and safety of tocilizumab in patients with NMOSD in whom previous immunosuppressant treatment had failed. We aimed to evaluate the effectiveness and safety of tocilizumab in clinical practice in patients with NMOSD not responding to other immunosuppressants. RESULTS: Five patients with NMOSD were analysed. Sixty percent of patients were women; mean age at diagnosis was 50±5.3 years and mean progression time was 4.5±3.6 years. Previously administered immunosuppressants were rituximab (in all 5), cyclophosphamide (2), and azathioprine (1). Mean time of exposure to tocilizumab was 2.3±1 years. Mean annualised relapse rate was 1.8±1.3 in the year prior to the introduction of tocilizumab and 0.2±0.4 the year after (P <.05), representing a reduction of 88.9%. CONCLUSIONS: In our experience, tocilizumab is safe and effective in patients with NMOSD showing no response to other immunosuppressants.

Development and validation of a brief electronic screening test for cognitive impairment in multiple sclerosis (SCI-MS Test).

OBJECTIVE: Although cognitive impairment (CI) is common in multiple sclerosis (MS), it is difficult to suspect in patients with low disability and there is a lack of brief and effective CI screening tools with a define cut-off point to be used during routine clinic visits. This study aims to validate the Electronic Screening Cognitive Impairment in Multiple Sclerosis (SCI-MS) test for CI among MS patients. METHODS: Cross-sectional, observational study that included adult patients, diagnosed with MS, Expanded Disability Status Scale (EDSS) score ≤6.5, without relapses within the last 2 months and no depression symptoms. The SCI-MS test consists of two modules: questionnaire (SCI-MS-Q) and pictogram matching tool (SCI-MS-P) measured for score and time. At inclusion, patients completed the Beck Depression Inventory (BDI-II test), the Brief Repeatable Battery of Neuropsychological Test (BRB-N) and the SCI-MS. The SCI-MS feasibility, test-retest reliability and predictive validity were assessed. RESULTS: A total of 194 patients (59.3% female) were included: mean (SD) age of 42 (9) years, mean time since diagnosis of 10 (7) years, 89.7% relapsing-remitting MS, and median (Q1-Q3) EDSS of 2.0 (1.0-3.5). According to BRB-N, 26.8% of patients had CI. Internal consistency was high (Cronbach alpha: 0.97). The intra-class correlation coefficient was 0.88 for the SCI-MS-Q, 0.09 for the SCI-MS-P score and 0.48 for the SCI-MS-P time, corresponding to AUC of the ROC curves of 0.571, 0.574 and 0.714, respectively. For a clinically significant cut-off point of ≥60 seconds, the reached CI sensitivity of SCI-MS-P time was 0.75 and the specificity 0.51. CONCLUSION: SCI-MS showed good psychometric properties. SCI-MS-P time of pictogram completion had an acceptable diagnostic accuracy of CI in MS patients with low disability. SCI-MS-P time of pictogram completion tool is an easy and quick score that can help neurologists to early identify CI in MS patients that should be further assessed to confirm CI diagnosis and to describe its characteristics and mainly affected domains.

[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Navarra, Gipuzkoa and La Rioja]. / Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Navarra, Gipuzkoa y La Rioja.

AIM: To evaluate the effectiveness and safety of fingolimod in clinical practice in Navarra, Gipuzkoa and La Rioja regions. PATIENTS AND METHODS: We conducted a retrospective multi-centre study with recurrent multiple sclerosis patients treated with fingolimod, following the product data sheet. The following data were evaluated: annualised relapse rate (ARR), percentage of patients free from relapses, disability using the Expanded Disability Status Scale (EDSS) and the percentage of patients without gadolinium-enhancing lesions. RESULTS: A total of 113 patients were treated with fingolimod: 6% were naive, and 58% and 35% were patients previously treated with an immunomodulator and natalizumab, respectively. Fingolimod lowered the ARR after the first (67%; 1 to 0.3; p < 0.0001) and second (89%; 1 to 0.1; p < 0.0001) years of treatment, and thus the number of patients free from relapses during the treatment increased. The baseline EDSS was 3 and after treatment with fingolimod was 2.5 in both years. The percentage of patients without gadolinium-enhancing lesions after the first year of treatment was 77%. Similar results were observed in naive patients and in those previously treated with an immunomodulator. In patients previously treated with natalizumab no changes were observed following the treatment. CONCLUSIONS: The use of fingolimod in clinical practice showed an effectiveness similar to that observed in clinical trials. There were no changes in the ARR after changing from natalizumab, and only one patient presented a 'relapse' after withdrawal of natalizumab. Fingolimod acts like a safe drug, with scarce side effects and a low percentage of drop-outs.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Navarra, Gipuzkoa y La Rioja.Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en las regiones de Navarra, Gipuzkoa y La Rioja. Pacientes y metodos. Estudio retrospectivo y multicentrico de pacientes con esclerosis multiple recurrente tratados con fingolimod, siguiendo la ficha tecnica. Se evaluo la tasa anualizada de brotes (TAB), el porcentaje de pacientes libres de brotes, la discapacidad usando la escala expandida del estado de discapacidad (EDSS) y el porcentaje de pacientes sin lesiones captantes de gadolinio. Resultados. Un total de 113 pacientes fueron tratados con fingolimod: el 6%, naive, y el 58% y 35%, pacientes tratados previamente con inmunomodulador y natalizumab, respectivamente. El fingolimod disminuyo la TAB tras el primer (67%; 1 a 0,3; p < 0,0001) y segundo (89%; 1 a 0,1; p < 0,0001) año de tratamiento, y aumento asi el porcentaje de pacientes libres de brotes durante el tratamiento. La EDSS basal fue 3 y despues del tratamiento con fingolimod fue 2,5 en ambos años. El porcentaje de pacientes sin lesiones captantes de gadolinio tras el primer año de tratamiento fue del 77%. Resultados similares se observaron en los pacientes naive y en los tratados previamente con inmunomodulador. En los pacientes tratados previamente con natalizumab no se observaron cambios tras el tratamiento. Conclusiones. El uso del fingolimod en la practica clinica mostro una efectividad similar a la eficacia observada en ensayos clinicos. No hubo cambios en la TAB al cambiar desde natalizumab, y solo un paciente tras suspender el natalizumab presento 'rebrote'. El fingolimod se comporta como un farmaco seguro, con escasos efectos adversos y con un bajo porcentaje de abandonos.

Tabaco y esclerosis múltiple / Smoking and multiple sclerosis

Introducción. La esclerosis múltiple (EM) es una enfermedad autoinmune de etiología compleja, hoy por hoy desconocida, en la que factores genéticos y ambientales determinan la susceptibilidad. En los últimos años, el efecto del tabaco ha sido uno de los factores ambientales que ha emergido en la EM, y se ha asociado tanto a un aumento de la susceptibilidad como a un aumento de la progresión. Objetivo. Revisar la evidencia actual sobre el papel del tabaco en la EM. Desarrollo. Se incluye una actualización de los estudios publicados que han analizado distintos aspectos del tabaco en laEM: vías patogénicas implicadas, asociación del tabaco y riesgo de EM, interacción con otros factores de riesgo y efecto del tabaco en el curso de la enfermedad. Conclusiones. Los estudios observacionales demuestran que el tabaquismo incrementa de forma significativa el riesgo de EM (odds ratio ~ 1,5) y es un factor de riesgo independiente. Sin embargo, la EM es una enfermedad compleja y el aumento de riesgo por el tabaco puede diferir en función de la interacción con otros factores genéticos y ambientales. El papel del tabaco como factor de progresión es más controvertido, con resultados contradictorios y estudios de gran variabilidad, lo que dificulta establecer una conclusión firme. Los mecanismos por los que el tabaquismo modifica el riesgo y posiblemente la progresión de la enfermedad no son aún conocidos (AU)

Introduction. Multiple sclerosis (MS) is a complex autoimmune disease of unknown etiology, in which genetic and environmental factors interact and determine the disease susceptibility. In recent years, smoking effect has been one of the emerging environmental factors in the study of MS and has been associated with an increased susceptibility and an increase in disease progression. Aim. To review the current evidence on the role of smoking in MS. Development. The review includes an update of studies that have analyzed different aspects of tobacco in MS, including the potential pathogenic pathways involved, association of smoking and risk of MS, interactions with other risk factors and the effect of smoking in the disease course. Conclusions. Observational studies show that smoking significantly increases the risk of MS (odds ratio ~ 1.5) and is an independent risk factor. However, MS is a complex disease and this risk may be modified depending on the interaction with other genetic and environmental factors. The role of smoking as a progression factor is more controversial, with confronted results and highly variable studies, making it difficult to draw any conclusion. The mechanisms by which smoking may modify the risk and progression of the disease have to be further investigated (AU)

Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients.

BACKGROUND: Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability; however, it has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). The differential expression of microRNA (miRNA), the small non-coding RNAs that regulate gene expression, in natalizumab-treated patients has been reported and miRNA have also been described as good candidates for disease biomarkers. OBJECTIVE: To characterize the effect of natalizumab therapy on the miRNA expression pattern and to search for miRNAs that can predict PML on an individual basis. METHODS: The expression of 754 microRNAs was measured in blood samples from 19 relapsing-remitting MS patients at three time points during natalizumab therapy, using TaqMan OpenArray panels. Two patients included in this study developed PML after more than 2 years of therapy. RESULTS: We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy (t6). Furthermore, we observed a differential expression of another three miRNAs (miR-320, miR-320b and miR-629) between the PML and non-PML groups after 12 months of treatment (t12); and a positive correlation was found between therapy time and the expression of miR-320. CONCLUSIONS: Natalizumab modified the expression levels of three miRNAs after a 6-month treatment. We suggest miR-320, miR-320b and miR-629 as possible biomarkers for individual PML risk assessment.

Association between synapsin III gene promoter SNPs and multiple sclerosis in Basque patients.

BACKGROUND: Synapsins are a family of neuron-specific phosphoproteins, one of whose subunits is encoded by the SYN3 gene. This gene is located close to one of the multiple sclerosis susceptibility regions (in 22q13.1). Two single-nucleotide polymorphisms (SNPs) (rs133945 and rs133946) in the promoter region of this gene have been proposed as factors protecting against MS. This relationship is not clear because another report failed to found such association. OBJECTIVES: In an attempt to clarify this association, the frequency of these SNPs was analyzed in a population of 221 Spanish MS patients with a cluster of 72 Basque patients and in 373 controls with a cluster of 138 controls of a Basque origin. METHODS: The SNis analysis was performed by 9 PCR. RESULTS: According to our findings, these SNPs are differently distributed in the two populations. This significant bias should therefore be taken into account in association studies. Our data suggest that the C/C genotype in rs133946 and the G/G genotype in rs133945 could be protecting factors against MS in the Basque population.

Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype?

BACKGROUND: Multiple sclerosis (MS) onset before puberty may have a distinct clinical presentation. Pediatric patients with MS may less often meet MRI diagnostic criteria for adults. Whether initial MRI presentation is distinct in prepubertal patients is unknown. METHODS: We queried the UCSF MS database for pediatric patients with MS (onset or=11 years) pediatric MS. The next available brain MRI scan was used to evaluate lesion resolution. RESULTS: Thirteen children with EOPMS (median age 8.90 years, range [3.58-10.98], 38% girls) and 18 with LOPMS (median age 14.47 years, range [11.78-18.00], 61% girls) were identified. While the overall number of T2-bright lesions was similar in the two groups, patients with EOPMS had fewer well-defined ovoid T2-bright lesions (median = 7, range [0-29] vs 21.5, [4-100]; p = 0.004) and more often had confluent lesions (31% of patients vs 0%; p = 0.02) on their first MRI compared with patients with LOPMS. Ninety-two percent of patients with EOPMS had a reduction in the number of T2-bright lesions on the second scan compared to 29% of patients with LOPMS (p = 0.002). CONCLUSIONS: The distinct prepubertal multiple sclerosis (MS) MRI phenotype suggests that underlying biologic processes may differ in earlier-onset pediatric MS compared to later-onset pediatric MS. These findings may delay diagnosis in that age range. MRI criteria for MS diagnosis may need to be revised before puberty.