Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II).

The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) held in October 2012 in France have been summarised in the fifth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2012. This review is the result of the meeting, which is being published in three parts. This second part of the Post-ECTRIMS review discusses the biology of recovery and remyelination in multiple sclerosis (MS) as well as the different repair and endogenous and exogenous remyelination strategies currently being evaluated based on the fact that resident microglia and oligodendroglial progenitor cells have been implicated in the remyelination process. This review also discusses the current state and future use of biomarkers in MS and proposes as markers of neurodegeneration the following: T2 lesion volume and brain atrophy using MRI and the loss of the ganglion cell layer as assessed by optical coherence tomography. A greater future utility for double inversion recovery (DIR) sequences is proposed to correlate cognitive impairment with MS impairment, given its higher diagnostic yield in locating and defining cortical lesions. The availability of novel biomarkers in the future requires strict validation. In this context, this paper proposes possible areas of action to improve the current situation and also presents the latest research results in identifying potential candidates with useful diagnostic characteristics, prognostic characteristics, treatment responses, and safety procedures.

TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (II).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, han sido resumidos en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision que se publica en tres partes. En esta segunda parte de la revision Post-ECTRIMS se analiza la biologia de la recuperacion y remielinizacion en la esclerosis multiple (EM), y se discuten las diferentes estrategias de reparacion y remielinizacion endogena y exogena que actualmente estan siendo evaluadas, sobre la base de que la microglia residente y las celulas precursoras de oligodendrocitos se han visto implicadas en el proceso de remielinizacion. Asimismo, se expone el estado actual y uso futuro de los biomarcadores en EM, y se proponen como marcadores de neurodegeneracion el volumen lesional en T2 y la atrofia cerebral mediante resonancia magnetica, asi como la perdida de capa de celulas ganglionares mediante tomografia de coherencia optica. Se plantea una mayor utilidad futura de las secuencias DIR para correlacionar las alteraciones cognitivas con las alteraciones de la EM, dado su mayor rendimiento diagnostico en localizar y definir lesiones corticales. La disponibilidad de nuevos biomarcadores en un futuro requiere una validacion estricta. En este sentido, se plantean posibles areas de actuacion dirigidas a mejorar la situacion actual, y ademas se presentan los resultados de las investigaciones mas recientes en la identificacion de posibles candidatos con utilidad diagnostica, pronostica, de respuesta al tratamiento y de seguridad.

Association of HLA-DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort.

BACKGROUND AND OBJECTIVE: The HLA-DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA-DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS. METHODS: The HLA-DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA-DRB1 allelic frequencies were compared between OCB-positive and OCB-negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA-DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB. RESULTS: We found 206 OCB-positive and 62 OCB-negative patients. The HLA-DRB1*15 allele in OCB-positive patients had a higher frequency when compared with OCB-negative patients (39.3% in OCB-positive vs. 16.1% in OCB-negative, OR = 1.38 95% CI = 1.18-1.61, P < 0.001). The other alleles did not show differences. When we compared with controls, the HLA-DRB1*15 allele was associated with the disease only in the OCB-positive patients group. None of the 55 genotypes found showed any association with the presence or absence of OCB. CONCLUSIONS: HLA-DRB1*15 allele is associated with OCB-positive patients with MS when studying a Spanish MS population.

HLA-DRB1: genetic susceptibility and disability progression in a Spanish multiple sclerosis population.

BACKGROUND AND OBJECTIVE: The association of HLA-DRB1*15 with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical phenotype is still controversial. The objectives of this study are to investigate the influence of the HLA-DRB1 alleles on the genetic susceptibility to MS and to study their impact on disability progression in a Spanish population. METHODS: HLA-DRB1 typing was performed by PCR-SSP in 380 patients with sporadic MS and 1088 unrelated healthy controls. Allelic frequencies were compared between groups. We studied the correlation between the different alleles and the progression of MS. RESULTS: The HLA-DRB1*15 allele in patients with MS had a statistically significant higher frequency when compared with controls (18.9% in patients vs. 10.1% in controls, Odds ratio (OR)=2.07, 95% CI=1.64-2.60, P<0.001). In the univariate analysis, the DRB1*01 and DRB1*04 alleles were associated with a worse prognosis when considering the time to reach an EDSS of 6, whereas the DRB1*03 was correlated with a better outcome. In the multivariate analysis, the alleles*01 and *04 were demonstrated to be independent factors to have a worse prognosis. CONCLUSIONS: HLA-DRB1*15 is associated with MS when comparing patients with unrelated healthy controls in a Spanish population. The HLA-DRB1*01 and HLA-DRB1*04 alleles are related to a worse prognosis when considering the time taken to reach severe disability.

Anticipation of age at onset in familial multiple sclerosis.

BACKGROUND AND OBJECTIVE: Anticipation of age at onset in the younger generations is a widely known characteristic of many diseases with genetic inheritance. This study was performed to assess whether there is anticipation of age at onset in younger generations of familial multiple sclerosis (MS) in a Spanish population and to compare clinical characteristics of familial and sporadic MS. METHODS: We studied a cohort of 1110 patients diagnosed with MS and followed-up in our MS Unit. Patients were considered as familial MS if they had in their family at least one relative of first or second degree diagnosed with MS. Otherwise, patients were considered to have sporadic MS. We compared the age at onset between relatives from different generations, and we also compared the age at onset of familial and sporadic MS. RESULTS: A lower age at onset in the younger generations was found (median 22 years vs. 30 years, P < 0.001) and a significant lower age at onset of the disease in familial MS comparing to sporadic MS (median 25 years vs. 29 years, P = 0.042). CONCLUSIONS: There is an anticipation of the age at onset of MS in the younger generations of patients with familial MS. There is also a lower age at onset in familial versus sporadic MS.

Single-dose antibiotic prophylaxis in patients at high risk for infection in biliary surgery: a prospective and randomized study comparing cefonicid with mezlocillin.

The usefulness of antibiotic prophylaxis in biliary surgery is well established. When antibiotic prophylaxis is not used, wound infection rates after biliary surgery range from 10% to 25%. With antibiotic prophylaxis, the rates can be reduced to less than 5%. Three questions are still controversial: Do all patients undergoing biliary surgery require antibiotic prophylaxis? What is the ideal antibiotic for use in biliary surgery? What should be the duration of antibiotic prophylaxis? In this study we prospectively evaluated the efficacy of a single dose of antibiotic prophylaxis in biliary surgery, administered to patients at high risk for infection, in a trial comparing cefonicid (a cephalosporin with a long half-life) with mezlocillin (a broad-spectrum ureidopenicillin).

Clinical efficacy, safety and tolerability of intramuscular imipenem/cilastatin in the treatment of mild to moderate infections.

Intramuscular imipenem/cilastatin gave satisfactory results in 20 episodes of infection, which included 16 UTIs (five with bacteraemia). The preparation was well tolerated locally and systemically.