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1.
Mult Scler ; 29(2): 236-247, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36515394

RESUMEN

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. OBJECTIVE: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. METHODS: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). RESULTS: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09-0.22) for the waiting group and 0.40 (95% CI 0.32-0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30-0.46) and 0.44 (95% CI 0.37-0.52), respectively. CONCLUSIONS: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Factores Inmunológicos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico
2.
Mult Scler ; 28(7): 1112-1120, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34766866

RESUMEN

BACKGROUND: The Brief Computerized Cognitive Assessment in Multiple Sclerosis (BCCAMS) is a short neuropsychological battery for persons with multiple sclerosis (PwMS). OBJECTIVES: The main objective of the study is to validate the BCCAMS. METHODS: PwMS and healthy subjects (HS) were evaluated using the BCCAMS which include two computerized tests, the Computerized Speed Cognitive Test and the Computerized Episodic Visual Memory Test (CEVMT), a newly developed visuospatial memory test, and the French learning test. The Minimal Assessment of Cognitive Function in MS (MACFIMS), including the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) tests, was also administered. Regression-based norms of the BCCAMS were calculated in 276 HS. BCCAMS was compared with BICAMS and MACFIMS for detection of cognitive impairment (CI). RESULTS: Out of 120 PwMS, CI was detected using the BCCAMS, BICAMS (one impaired test), and MACFIMS (two impaired tests) in 59.1%, 50%, and 37.9%, respectively. The BCCAMS produced the same predictive value as that of the BICAMS battery for detecting CI in the MACFIMS. CONCLUSION: This study validated the BCCAMS as a validated computerized short assessment for information processing speed and learning in MS.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Memoria Episódica , Esclerosis Múltiple , Cognición , Trastornos del Conocimiento/diagnóstico , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas , Reproducibilidad de los Resultados
3.
Eur J Neurol ; 28(6): 2026-2036, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33650261

RESUMEN

BACKGROUND AND PURPOSE: Disease-modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. METHODS: We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. RESULTS: Of the 21,189 patients with MS (age 47.1 ± 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 ± 2.4), 6,631 (31.3%; 95% confidence interval [CI] 30.7-31.9) were not receiving any DMT. Although patients with a relapsing-remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing-remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio [OR] 0.52 [95% CI 0.44-0.61]) and lower EDSS score (OR 0.78 [95% CI 0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. CONCLUSION: A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.


Asunto(s)
Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Humanos , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/terapia , Recurrencia Local de Neoplasia , Estudios Retrospectivos
4.
Mult Scler ; 26(2): 253-255, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-30663514

RESUMEN

Anti-Glial fibrillary acidic protein (GFAP) encephalomyelitis is a recently described entity and while the spectrum of this disease has been explored, further research is needed to fully describe its phenotype. Area postrema syndrome (APS) is usually associated with neuromyelitis optica spectrum disorders (NMOSDs), whereas no case of APS has been previously reported with anti-GFAP encephalomyelitis. In this article, we report a case of APS in a 41-year-old woman in the context of anti-GFAP encephalomyelitis. This case was not associated with additional anti-AQP4 IgG and therefore extends the clinico-radiological spectrum of anti-GFAP encephalomyelitis.


Asunto(s)
Área Postrema , Autoanticuerpos/inmunología , Encefalomielitis/inmunología , Proteína Ácida Fibrilar de la Glía/inmunología , Adulto , Autoantígenos/inmunología , Encefalomielitis/complicaciones , Encefalomielitis/patología , Femenino , Humanos , Náusea/inmunología , Síndrome , Vómitos/inmunología
5.
Mult Scler ; 26(8): 936-944, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31148523

RESUMEN

OBJECTIVES: We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis. MATERIAL AND METHODS: We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0. RESULTS: Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0-4.0)) compared to SM patients (2.0, (1.0-3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01-1.95, p = 0.046). CONCLUSION: SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.


Asunto(s)
Autoanticuerpos , Progresión de la Enfermedad , Glicoproteína Mielina-Oligodendrócito/inmunología , Mielitis , Sistema de Registros , Índice de Severidad de la Enfermedad , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mielitis/diagnóstico , Mielitis/inmunología , Mielitis/patología , Mielitis/fisiopatología , Pronóstico , Estudios Retrospectivos , Adulto Joven
6.
Neurology ; 103(3): e209624, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38991174

RESUMEN

BACKGROUND AND OBJECTIVES: Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes. METHODS: Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method. RESULTS: We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%. DISCUSSION: The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.


Asunto(s)
Glicoproteína Mielina-Oligodendrócito , Recurrencia , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Anciano , Adulto Joven , Autoanticuerpos/sangre , Francia/epidemiología , Estudios de Cohortes , Estudios de Seguimiento , Neuritis Óptica
7.
Artículo en Inglés | MEDLINE | ID: mdl-34728496

RESUMEN

BACKGROUND AND OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a disabling neurologic disorder resulting from the infection of the CNS by JC polyomavirus in immunocompromised individuals. For the last 2 decades, increasing use of immunotherapies leads to iatrogenic PML. Iatrogenic PML is often associated with signs of inflammation at onset (inflammatory PML) and/or after treatment withdrawal immune reconstitution inflammatory syndrome (PML-IRIS). Although immune reconstitution is a key element for viral clearance, it may also be harmful and induce clinical worsening. A C-C chemokine receptor type 5 (CCR5) antagonist (maraviroc) has been proposed to prevent and/or limit the deleterious immune responses underlying PML-IRIS. However, the data to support its use remain scarce and disputed. METHODS: We conducted a multicenter retrospective cohort study at 8 university hospitals in France and Switzerland by collecting clinical, biological, and radiologic data of patients who developed inflammatory PML (iPML) or PML-IRIS related to immunosuppressive therapies used for chronic inflammatory diseases between 2010 and 2020. We added to this cohort, a meta-analysis of individual case reports of patients with iPML/PML-IRIS treated with maraviroc published up to 2021. RESULTS: Overall, 27 cases were identified in the cohort and 9 from the literature. Among them, 27 met the inclusion criteria: 16 treated with maraviroc and 11 with standard of care (including corticosteroids use). Most cases were related to MS (92.6%) and natalizumab (88%). Inflammatory features (iPML) were present at onset in 12 patients (44.4%), and most patients (92.6%) received corticosteroids within the course of PML. Aggravation due to PML-IRIS was not prevented by maraviroc compared with patients who received only corticosteroids (adjusted odds ratio: 0.408, 95% CI: 0.06-2.63). Similarly, maraviroc did not influence time to clinical worsening due to PML-IRIS (adjusted hazard ratio = 0.529, 95% CI: 0.14-2.0) or disability at the last follow-up (adjusted odds ratio: 2, 95% CI: 0.23-17.3). DISCUSSION: The use of CCR5 blockade did not help to keep deleterious immune reconstitution in check even when associated with corticosteroids. Despite maraviroc's reassuring safety profile, this study does not support its use in iPML/PML-IRIS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence showing that adding maraviroc to the management of iatrogenic iPML/PML-IRIS does not improve the outcome.


Asunto(s)
Antagonistas de los Receptores CCR5/farmacología , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/prevención & control , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/prevención & control , Maraviroc/farmacología , Adulto , Antagonistas de los Receptores CCR5/administración & dosificación , Femenino , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/inducido químicamente , Leucoencefalopatía Multifocal Progresiva/inducido químicamente , Masculino , Maraviroc/administración & dosificación , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Adulto Joven
8.
Mult Scler Relat Disord ; 48: 102692, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33352358

RESUMEN

BACKGROUND: The Minimal Assessment of Cognitive Function in Multiple sclerosis (MACFIMS) is an internationally recognised battery of neuropsychological tests for patients with multiple sclerosis (MS). OBJECTIVES: To establish regression-based norms for the MACFIMS in French-speaking healthy subjects (HS) and validate its use in persons with multiple sclerosis (PwMS). METHODS: 136 PwMS, including 43 with relapsing-remitting MS, 46 with secondary progressive MS and 45 with primary progressive MS, as well as 276 HS were enrolled. Regression-based norms and validity were established for the seven tests of the MACIMS: the Symbol Digit Modalities Test (SDMT), the Paced Auditory Serial Addition Test (PASAT), the French learning test (FLT) a French-adapted memory test (or the California Verbal Learning Test (CVLT) at re-testing), the Judgment of Line Orientation Test (JLO), the 'épreuve de classement de cartes de Champagne' (ECCC), a French adaptation of the DKEF-sorting test, the Brief Visuospatial Memory Test (BVMT-R) and the Controlled Oral Word Association Test (COWAT). RESULTS: Regression-based norms of MACFIMS tests were established in the HS population. The MACFIMS battery was able to identify cognitive impairment (CI) (at least two abnormal tests in different domains) in 32.7% of PwMS. The domains with more frequent impairment were (in descending order): learning followed by IPS, delayed memory, verbal fluency and working memory. CONCLUSION: This study established the regression-based norms for French subjects of the French adaptation of the MACFIMS and its validity in PwMS.


Asunto(s)
Trastornos del Conocimiento , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Cognición , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Pruebas Neuropsicológicas
9.
JAMA Neurol ; 77(1): 94-102, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31479149

RESUMEN

Importance: Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated. Objective: To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013. Design, Setting, and Participants: This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018. Exposures: Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation. Main Outcomes and Measures: Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016). Results: In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016. Conclusions and Relevance: The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.


Asunto(s)
Factores Inmunológicos/efectos adversos , Leucoencefalopatía Multifocal Progresiva/epidemiología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/efectos adversos , Adolescente , Adulto , Femenino , Francia/epidemiología , Humanos , Huésped Inmunocomprometido , Incidencia , Virus JC , Leucoencefalopatía Multifocal Progresiva/inmunología , Leucoencefalopatía Multifocal Progresiva/prevención & control , Masculino , Sistema de Registros , Factores de Riesgo , Adulto Joven
10.
Mult Scler Relat Disord ; 27: 223-225, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30414563

RESUMEN

Combined central and peripheral demyelination (CCPD) is a rare chronic inflammatory disorder of the nervous system. In this article, we report on a CCPD patient with a very unusual pattern of central demyelination, comprising recurrent cerebral tumefactive demyelinating lesions (three times, each one in a new area of the brain) and one episode of longitudinally extensive transverse myelitis. This patient could not be classified as having multiple sclerosis, or neuromyelitis optica spectrum disorder, or any other well-known inflammatory disorder of the central nervous system, associated with demyelinating neuropathy. A diagnosis of idiopathic inflammatory demyelinating disorder (IIDD) was made while waiting for more knowledge concerning the diseases currently characterized as IIDD.


Asunto(s)
Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico , Polirradiculoneuropatía/diagnóstico , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico por imagen , Enfermedades Autoinmunes Desmielinizantes SNC/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mielitis Transversa/diagnóstico , Mielitis Transversa/fisiopatología , Polirradiculoneuropatía/diagnóstico por imagen , Polirradiculoneuropatía/fisiopatología , Recurrencia
11.
Ann Clin Transl Neurol ; 6(7): 1332-1337, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31353859

RESUMEN

Biotin is thought to improve functional impairment in progressive multiple sclerosis (MS) by upregulating bioenergetic metabolism. We enrolled 19 patients suffering from progressive MS (5 primary and 14 secondary Progressive-MS). Using cerebral multinuclear magnetic resonance spectroscopy (MMRS) and clinical evaluation before and after 6 months of biotin cure, we showed significant modifications of: PME/PDE, ATP, and lactate resonances; an improvement of EDSS Neuroscore. Our results are consistent with metabolic pathways concerned with biotin action and could suggest the usefulness of MMRS for monitoring.


Asunto(s)
Biotina/metabolismo , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/metabolismo , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/diagnóstico por imagen , Esclerosis Múltiple Crónica Progresiva/metabolismo
12.
Neurology ; 93(7): e635-e646, 2019 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-31300547

RESUMEN

OBJECTIVE: In this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques. METHODS: A total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated. RESULTS: The confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001). CONCLUSIONS: After 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.


Asunto(s)
Crotonatos/uso terapéutico , Dimetilfumarato/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Toluidinas/uso terapéutico , Adulto , Progresión de la Enfermedad , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Hidroxibutiratos , Masculino , Persona de Mediana Edad , Nitrilos , Recurrencia , Resultado del Tratamiento
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