Search

Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy. Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity. Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort. Interpretation: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.

BACKGROUND: The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment reduced the risk of CDMS by 37% (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed treatment. The risk for confirmed disability progression was not significantly lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median FAMS-TOI scores were 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b, although a delay in treatment by up to 2 years did not affect long-term disability outcomes. FUNDING: Bayer Schering Pharma. ispartof: The Lancet Neurology vol:8 issue:11 pages:987-997 ispartof: location:England status: published

The need for optimal care has led to implementation of multiple sclerosis care units, specialised in diagnosis and follow-up of multiple sclerosis patients. Since information on multiple sclerosis prognosis is crucial, accurate diagnosis is one of their major roles.Prospective analysis of first visits during a year (origin and diagnosis) at the Unidad de Neuroinmunología Clínica of Hospital Vall d'Hebron.A total of 437 first visits were analysed; a moderate agreement (kappa = 0.468) between referral diagnoses and diagnosis at follow-up was obtained; agreement was very good (kappa = 0.844) between diagnosis at first visit and diagnosis at follow-up. In the subgroup of 200 patients with a demyelinating disease on follow-up after one year, 37.6% of referrals came from other non-specialised centers and 40.6% from our own center.Specialised care units enhance diagnostic precision; direct influence zone and non-specialised centers referrals are their more important sources of patients.

The ability of natural human interferon beta (n-hIFN beta) to reduce multiple sclerosis (MS) activity was investigated in 60 patients with relapsing-remitting MS (RRMS).Patients were randomized to receive either 9 MIU (33 micrograms) of n-hIFN beta by subcutaneous route, three times per week, on alternate days, during one year, or no treatment (control group) during the first six months and then switched to the same treatment for the following six months. Disease activity was monitored monthly by both magnetic resonance imaging (MRI) and clinical parameters. An intergroup analysis (first 6 months of the study) showed fewer active lesions and lower exacerbation rate in the treatment group than in the control group. Similarly, there were more exacerbation-free patients in the treatment group during this time.When switched to treatment, the control group showed a significant reduction in the number of active lesions (p = 0.00001) and the exacerbation rate decreased by half. Exacerbation-free patients more than doubled (p = 0.006) and the median time to first exacerbation was significantly prolonged (96 vs180 days; p = 0.019). Treatment was extended for 12 additional months at a dose of 6 MIU (22 micrograms) once a week and disease activity persisted under control in 88% of patients. Treatment with n-hIFN beta was well tolerated, adverse events being mild and self-limiting. Sera were analyzed for anti-IFN beta antibodies and neutralizing activity was found in 12% of the patients after two years.The results of this phase II study show, that n-hIFN beta promotes a significant reduction of disease activity in RRMS as shown by both MRI and clinical variables, and that the treatment is well tolerated, with low antigenicity.

The incidence of sarcoidosis in our country is one of the lowest in Europe. Neurosarcoidosis affects only 5% on patients with sarcoidosis. Clinical cases. We describe four patients in which neurologic disfunction was the presenting finding. Initial neurological symptoms include status epilepticus, headache, fever and nerve cranial palsies. MRI showed a spectrum of protean central nervous abnormalities: 1. Hypotalamic infiltrating lesion; 2. Brain parenchyme enhanced masses; 3. Leptomeningeal enhancement, and 4. Focal white-matter lesions. Thoracic CT scan, bronchoscopy, Gallium scintigraphy and pulmonary biopsy yielded to diagnosis in three patients. Biopsy of the meninges was required in one patient because systemic involvement was not found. Histological examination of an intracranial mass was also performed in another patient to rule out tumoral lesions. ACE in serum was normal in all patients. CSF ACE was determine in only one patient and was also normal. Three patients started treatment with corticosteroids but one of them required adjuvant treatment with immunosuppressor. Cranial nerve palsy resolved spontaneously in the last patient.Clinical and radiological polymorphism explained the delay before diagnosis and the problems in ruling out other diseases. MRI is highly useful for the diagnosis and follow up treatment.

Retino-cerebellar hemangioblastomatosis or Von Hippel-Lindau (VHL) disease is a phacomatosis with a dominant autosomal pattern of inheritance, which is characterized by the presence of hemangioblastomas of the central nervous system (cerebellum and spinal medulla), retinal angiomas and tumors (pheochromocytoma, clear cell carcinoma) or cysts of the abdominal viscera.We present the case of a 22 year old female with Von Hippel-Lindau disease, in whom a cystic hemangioblastoma of the basal ganglia of the left hemisphere was diagnosed when she complained of difficulty in carrying out fine movements of the right hand and tremor for some months. The supratenorial site of cystic hemangioblastomas in the clinical context of Von Hippel-Lindau disease is very rare and clinical presentation of a parkinsonian hemisyndrome is exceptional. In our search through the literature we have found tumors with many types of histology (meningiomas, glial tumors, craniopharyngioma, epidermoid cysts) in the origin of tumoral parkinsonism.However, we have found no previous case of cystic hemangioblastomas. We also emphasize that there was full resolution of the condition after total removal of the tumour.

Preliminary results of a multicenter, randomized study on the effect of natural interferon beta (n-INFN-beta) in relapsing-remitting MS are reported. Sixty patients received either no treatment or n-IFN-beta (9 MIU three times a week, subcutaneously). After 6 months, the n-IFN-beta-treated group showed a 58% median reduction in the number of active lesions detected on monthly magnetic resonance imaging scans as well as a 38% reduction in the exacerbation rate as compared with the control group. Side-effects were mild and self-limiting. The study continues according to the protocol.

The Multiple Sclerosis Quality of Life 54 (MSQOL-54) is a health-related quality of life specific questionnaire for multiple sclerosis (MS) patients. The objective of this study was to develop the Spanish version of the MSQOL-54 and to obtain a conceptually equivalent version to the original one for its use in patients with MS in the first phase of the project.A transcultural adaptation procedure was designed according to the following phases: a) two independent translations made by bilingual native Spanish speaking translators (forward translation); b) a revision of the items by an expert panel; c) a back translation by a bilingual native English speaking person; d) comparison with the original version (expert panel and advise by the original authors), and e) cognitive debriefing (interviews with subjects with MS) to test the comprehension and feasibility of the instrument.Ten interviews were carried out with 5 men and 5 women with MS, aged 21 to 54 years, with different education levels and EDSS scores ranging from 1,0 to 8,0. Most of the patients found the questionnaire easy to fill out and the understanding favorable. Only one item (item 51) was modified after the cognitive debriefing to improve its comprehension. Finally, a final pretest version was obtained.The procedure carried out maximizes the conceptual equivalence between the original MSQOL-54 and the translated version and shows that the Spanish pre-test version is comprehensible and its administration feasible in patients with MS. The psychometric properties must be evaluated in the next phase of the project.

Acute disseminated encephalomyelitis (ADEM) is an uncommon disease characterized by inflammation and demyelination of the central nervous system (CNS). It typically occurs after a viral infection or vaccination and is more frequent in children. Its immediate and longterm prognosis is expected to be good (20% of cases with sequelae). Although ADEM is typically monophasic, occasional relapses may occur. Differential diagnosis, mostly in the early phases, is established with multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the CNS that may have worse prognosis. Traditionally it has been believed that 10% of ADEM patients develop MS. However, this percentage could be higher according to several recently published clinical series. Some clinical and paraclinical patterns are considered to confer risk of developing MS when present in ADEM patients. Our study has aimed to: a) describe a series of 29 patients (22 children and 9 adults) admitted in our hospital and diagnosed of ADEM between 1990 and 2005; b) study those patients considered to have risk patterns of developing MS, and c) compare the child and adult populations of our series. After a median 55 month follow-up, 6 children (27%) and no adults developed MS. In our series, risk patterns for developing MS predicted conversion to MS more accurately in children than in adults. Eight patients (6 children and 2 adults) had sequelae, cognitive in 6 of them. Our work supports that also observed in recent publications: that both conversion to MS or presence of sequelae after an episode of ADEM are more frequent than traditionally considered.

An important controversy on the development of multiple sclerosis (MS) after an isolated episode of optic neuritis (ON) exists. Magnetic resonance imaging (MRI) is the method of election in order to detect demyelinated lesions in MS. The current study was designed to determine the prevalence of brain abnormalities on MRI and to asses the further development of MS after an isolated idiopathic ON in our population.From 1991 to 1995, 60 patients with decrease of visual acuity were studied, 35 (28 women, half age 31 +/- 10 years) completed criteria of idiopathic ON. A brain MRI was performed in all patients after the diagnosis of idiopathic ON and they subsequently were followed in the outpatient clinic from our center for a mean time of 29 +/- 16 months. 24 out of the 35 patients were treated with corticosteroids in different ways.It has been found 43% of the patients with idiopathic ON to have brain lesions by MRI. During the follow-up 14% of the patients developed a clinically definite MS; all of them had a pathological brain MRI at the basal evaluation (p = 0.009). None of the patients that were treated with high-dose of intravenously corticosteroids developed MS.The prevalence of silent cerebral lesions in the MRI after an idiopathic ON is elevated in our population although further development of MS is lower possibly due to the short follow-up carried out. The presence of lesions in the MRI confers a high risk for developing MS after an idiopathic ON.

Esclerosis múltiple; Reacciones adversas; Infecciones respiratorias Esclerosi múltiple; Reaccions adverses; Infeccions respiratòries Multiple sclerosis; Adverse reactions; Respiratory infections Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p