Different clinical response to interferon beta and glatiramer acetate related to the presence of oligoclonal IgM bands in CSF in multiple sclerosis patients.

OBJECTIVE: To study the efficacy of interferon beta (IFNß) and glatiramer acetate (GA) related to the presence of oligoclonal M bands (OCMB) in the cerebrospinal fluid in relapsing-remitting multiple sclerosis (RRMS). METHOD: This is an observational, multicenter and retrospective study with prospectively collected data of patients that started treatment with IFNß or GA. Treatment decision was made blinded to the OCMB status. Time to first attack after starting therapy was compared by using Kaplan-Meier curves, and adjustment by Cox regression analysis was performed. RESULTS: Two hundred and fifty-six patients entered in the study (141-55% received IFNß; 115-45% received GA). After a mean follow-up of 41 and 65 months, 54.7% of patients remained free from further attacks (RF). The proportion of RF patients was higher in the GA group than in the IFNß group (72.2 vs. 40.4%, p < 0.001). The IFNß patients with OCMB+ presented the poorest response, 31.3% RF vs. 48.1% in IFNß without OCMB, p = 0.03. CONCLUSION: OCMB in CSF could be a biomarker of treatment response in multiple sclerosis.

Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Neuromyelitis optica spectrum disorders: Comparison according to the phenotype and serostatus.

OBJECTIVE: To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO. METHODS: This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays. RESULTS: Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10-77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presented more often with longitudinally extensive transverse myelitis (LETM) (p < 0.001), and had lower relapse rates (p = 0.015), but similar disability outcomes. Nonwhite ethnicity and optic neuritis presentation doubled the risk for developing NMO compared with white race (p = 0.008) or LETM presentation (p = 0.008). Nonwhite race (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.4-13.6) and older age at onset were associated with worse outcome (for every 10-year increase, HR 1.7, 95% CI 1.3-2.2). Patients with NMO and MOG-IgG (n = 9) had lower female:male ratio (0.8:1) and better disability outcome than AQP4-IgG-seropositive or double-seronegative patients (p < 0.001). CONCLUSIONS: In patients with AQP4-IgG, the similar outcomes regardless of the clinical phenotype support the unified term NMOSD; nonwhite ethnicity and older age at onset are associated with worse outcome. Double-seronegative and AQP4-IgG-seropositive NMO have a similar clinical outcome. The better prognosis of patients with MOG-IgG and NMO suggests that phenotypic and serologic classification is useful.

On the diagnosis of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic arteriopathy related to Notch3 mutations, is difficult to diagnosis. The goal of this study was to determine the value of clinical, immunohistochemical, and molecular techniques for the diagnosis of CADASIL. Clinical features and the immunohistochemical and molecular findings in 200 subjects with suspected CADASIL in whom 93 biopsies and 190 molecular studies are reported. Eighteen pathogenic mutations of the Notch3 gene, six of them previously unreported, were detected in 67 patients. The clinical features did not permit differentiation between CADASIL and CADASIL-like syndromes. The sensitivity and specificity of the skin biopsies was 97.7% and 56.5%, respectively, but increased to 100% and 81.5%, respectively, in cases with proven family history. In conclusion, a clinical diagnosis of CADASIL is difficult to determine and confirmatory techniques should be used judiciously.

Esclerosis multiple como primera manifestacion en el territorio oral y facial: Presentación de cuatro casos / Multiple sclerosis as first manifestation in oral and facial area: Presentation of four cases

La esclerosis múltiple (EM) es una enfermedad inflamatoria crónica del sistema nervioso central de etiología no conocida caracterizada por la aparición de sintomatologia neurológica diversa en forma de brotes o de deterioro progresivo y de lesiones en cualquier localización de la sustancia blanca cerebral que pueden dejar como secuelas la desmielinización definitiva de la zona. Esta enfermedad afecta a gente joven siendo más frecuente su aparición entre los 20 y 40 años, en climas templados y fríos y con una relación hombre-mujer de 0,46 / 0,67. La importancia de esta enfermedad radica en que es la primera causa de invalidez permanente en adultos jóvenes. Presentamos 4 casos de EM cuyo síntoma de inicio de la enfermedad fue la aparición de parestesias en el territorio maxilo-facial afectando a una o más ramas del trigémino y de tiempo de evolución que oscilaba entre 15 días y un año. Todos los pacientes fueron diagnosticados clínicamente siendo confirmado el diagnostico, tanto con la resonancia magnética como con el estudio del liquido cefalorraquídeo (LC) y los potenciales evocados(PE). Las manifestaciones en el territorio oral y facial fueron la primera manifestación de la enfermedad en todos los casos

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, whose etiology is unknown, and which is characteristic by the appearance of a diverse neurological symptomatology consisting of outbreaks or gradual deterioration and lesions in any location of the brain’s white matter which may provoke the after-effect of a definitive demyelination of the area. The disease affects young people, with its appearance being most frequent between 20 and 40 years of age, in temperate and cold climates, and with a man-woman rate of 0.46 / 0.67. The magnitude of this disease lies in the fact that it is the primary cause for permanent disablement among young adults. We are presenting 4 cases of MS whose initial symptom of the disease was the appearance of paraesthesia in the maxillofacial area, affecting one or more ramifications of the trigeminal nerve, and a progression time varying from 15 days to one year. All the patients were clinically diagnosed, with their diagnostics being confirmed both with magnetic resonance imaging as well as through the study of their cerebrospinal fluid (CSF) and the Evoked potentials ( EPs). Manifestations in the oral and facial area were the first manifestation of the disease in all cases

Multiple sclerosis as first manifestation in oral and facial area: presentation of four cases.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, whose etiology is unknown, and which is characteristic by the appearance of a diverse neurological symptomatology consisting of outbreaks or gradual deterioration and lesions in any location of the brain s white matter which may provoke the after-effect of a definitive demyelination of the area. The disease affects young people, with its appearance being most frequent between 20 and 40 years of age, in temperate and cold climates, and with a man-woman rate of 0.46/0.67. The magnitude of this disease lies in the fact that it is the primary cause for permanent disablement among young adults. We are presenting 4 cases of MS whose initial symptom of the disease was the appearance of paraesthesia in the maxillofacial area, affecting one or more ramifications of the trigeminal nerve, and a progression time varying from 15 days to one year. All the patients were clinically diagnosed, with their diagnostics being confirmed both with magnetic resonance imaging as well as through the study of their cerebrospinal fluid (CSF) and the evoked potentials (EPs). Manifestations in the oral and facial area were the first manifestation of the disease in all cases.