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Background: Early identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) can be challenging for clinicians, as diagnostic criteria for SPMS are primarily based on physical disability and a holistic interpretation., Objective: To establish a consensus on patient monitoring to identify promptly disease progression and the most useful clinical and paraclinical variables for early identification of disease progression in MS., Methods: A RAND/UCLA Appropriateness Method was used to establish the level of agreement among a panel of 15 medical experts in MS. Eighty-three items were circulated to the experts for confidential rating of the grade of agreement and recommendation. Consensus was defined when ≥66% agreement or disagreement was achieved., Results: Consensus was reached in 72 out of 83 items (86.7%). The items addressed frequency of follow-up visits, definition of progression, identification of clinical, cognitive, and radiological assessments as variables of suspected or confirmed SPMS diagnosis, the need for more accurate assessment tools, and the use of promising molecular and imaging biomarkers to predict disease progression and/or diagnose SPMS., Conclusion: Consensus achieved on these topics could guide neurologists to identify earlier disease progression and to plan targeted clinical and therapeutic interventions during the earliest stages of SPMS., Competing Interests: The authors declare the following potential conflicts of interest regarding the research, authorship, and/or publication of this article: JM-L has received grants and consulting or speaking fees from Almirall, Biogen Idec, Celgene, Genzyme, Merck, Novartis, Roche, and Teva. BC has received research support or personal compensation from any commercial entity (for-profit business) for employment, consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Sanofi, Roche, Merck, Teva, Novartis, Celgene, and Almirall. AR-A has received personal compensation from any commercial entity (for-profit business) for serving on a scientific advisory board or speaking from Merck, Biogen Idec, Roche, Genzyme, Teva, Mylan, and Celgene. SE has received speaker honoraria and consultant fees from Biogen, Novartis, Sanofi Genzyme, Merck, Almirall, Roche, and Teva. GI has received speaking and/or advisory board honoraria from Bayer, Biogen Idec, Novartis, Sanofi, Merck Serono, Almirall, Roche, Actelion, Celgene, and Teva. CD has received speaking and/or advisory board honoraria from Sanofi, Novartis, AbbVie, and Bial. JR has received speaking honoraria and personal compensation for participating on advisory boards from Biogen Idec, Genzyme, Merck Serono, Novartis, Teva, and Sanofi-Aventis. MH has received research support or personal compensation from any commercial entity (for-profit business) for employment, consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Novartis, Roche, Merck, Teva, and Genzyme-Sanofi. CC has received personal compensation from any commercial entity (for-profit business) for employment, consulting, serving on a scientific advisory board, speaking, or other activities from Teva, Sanofi-Genzyme, Merck, Novartis, Biogen, and Roche. JP-G is a consultant for Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva, Roche, and Almirall. He has participated as a speaker/moderator in meetings and/or symposia organized by Almirall, Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva, and Roche. He has received grants for research projects from Almirall, Biogen Idec, Novartis, and Sanofi-Genzyme. JA has received honoraria for lecturing, travel expenses for attending meetings, or financial support for research from Biogen Idec, Merck Serono, Genzyme, and Novartis. DU has received honoraria for lecturing, courses, advisory boards, or financial support for research from Biogen, Merck, Novartis, Roche, Sanofi, Teva, Bayer, and Almirall. LC-F has received honoraria for lecturing, travel expenses for attending meetings, or financial support for research from Merck, Bayer, Biogen, Novartis, Sanofi-Genzyme, Almirall, Roche, Celgene, Biopas, Ipsen, and Teva. AG-M has received compensation for lecturing, scientific advisory board and consulting from Novartis, Merck, Roche, Emerald, Biogen and Sanofi, and research support from Teva. CO-G has received honoraria for speaking and/or consultancy from Biogen, Sanofi-Genzyme, Merck, Roche, Teva, and Novartis., (Copyright © 2022 Meca-Lallana, Casanova, Rodríguez-Antigüedad, Eichau, Izquierdo, Durán, Río, Hernández, Calles, Prieto-González, Ara, Uría, Costa-Frossard, García-Merino and Oreja-Guevara.)

Introduction: Although multiple sclerosis (EM) has the characteristics of a disorder which is complex to study epidemiologically, many papers have been published on its genetic epidemiology, and these have given a great deal of information regarding the aetiological factors of the disorder., Method: These epidemiological investigations have also studied the incidence and prevalence of EM in each zone, the different geographical distribution, its variation with immigration, relation to race and sex, the existence of possible epidemics or groups and its family aggregation. They have supported the environmental aetiological factor of EM, the geographical gradient of the frequency, possible epidemics or groups, changes with migrations and concordance in identical twins of less than 100%. However, arguments in favour of a genetic aetiological factor have been supported by racial differences in the frequency of this disorder, the existence of resistant ethnic groups in spite of the migrations and the increased concordance in monozygotic twins., Conclusion: The results of studies on the genetic epidemiology of EM support the multifactorial nature of its aetiology, with a polygenic type of genetic susceptibility, although this alone does not justify the development of EM. Some environmental factor, as yet unknown, is necessary for the disease to develop in a genetically susceptible person. Molecular genetic studies are adding further knowledge about this genetic susceptibility, although the genes involved have not yet been conclusively identified because of the complexity of EM.

Introduction: Family and population studies have shown the existence of genetic susceptibility to have multiple sclerosis (MS). The genes of the HLA system have been the only genetic markers for this tendency to have been confirmed in multiple studies in different countries. A relation has also been found between certain HLA genes and the clinical course or paraclinical parameters of MS., Development: In this article we first analyze the structure, function, typing and association of illnesses with the HLA system and their relation with MS. Subsequently we review the articles published or reported on the HLA-MS association in the Spanish population., Conclusion: MS is generally associated with the DR15/DQ6 haplotype (subtypes of DR2/DQ1) in the Spanish population. There may be minor ethnic differences in some regions which explain other associations found. Although the Spanish studies on the association of HLA with clinical and paraclinical factors of MS require confirmation in samples with larger number of patients, the primarily progressive forms and those with a worse prognosis tend to be associated with DR4 and the benign forms with DR2. The DRw 13 (DR6) seems to be a protective allele. The presence of DR2 may be a marker for the development of MS after an optic neuritis.

Objective: A protocol system is being used in Spain for the prescription of innovative drugs including interferon beta-1b (IFNbeta-1b). Petitions for dispensing and reimbursement are based on the inclusion and exclusion criteria of pivotal trials, and are reviewed individually for approval by specialist committees. To estimate the performance of IFNbeta-1b in the clinical setting, data collected by the INSALUD and regional health services of Andalusia and Catalonia, together responsible for the healthcare of nearly 30 million individuals, were compiled in a common database for analysis., Methods: Data comprise demographic and disease characteristics at the time of petition and at follow-up 3 months after treatment initiation and every 6 months thereafter. Efficacy was estimated by mean number of relapses per year, proportion of relapse-free patients, and disease progression as measured by the Expanded Disability Status Scale (EDSS). Safety parameters included adverse events and laboratory analyses., Results: Between September 1995 and database cutoff in mid-1998, petitions of 1419 patients were approved for IFNbeta-1b treatment. Patients were homogenous across the three databases and in the subgroups of patients completing 1 year (n = 940) and 2 years (n = 302) of treatment. There was a marked decrease in the mean number of relapses in the first 12 months of IFNbeta-1b treatment for the 938 patients documented for 12 months, with a mean of 0.4 (+/- 0.7 SD) relapses per patient and year, and a 2-year mean of 0.9 (+/- 1.20 SD) in the 302 patients documented for 24 months. Of the 938 patients followed for > or = 12 months, 505 (53.8%) were documented as being relapse-free during 12 months of treatment, and 146 (48.3%) of the 302 patients followed for > or = 24 months, were relapse-free during 24 months of treatment. There were no differences in mean or median EDSS scores between baseline and months 12 and 24. Skin disorders were the most frequent adverse events, reported in over one-third of all patients; there were 159 injection site events, most frequently erythema (115 events). Systemic AEs pointing towards flu-like symptoms were reported in 288 of 1419 patients (20.3%). Leukopenia was the most frequently reported laboratory event. Elevations in liver transaminases were noted for 12 patients (0.8%) with SGOT increase and 7 (0.5%) with SGPT increase., Conclusion: The protocol system has helped make IFN treatment available to 8-10% of the estimated 15,000-18,000 MS patients in the regions studied. In terms of efficacy, IFNbeta-1b performed in line with the pivotal study results. The safety profile of IFNbeta-1b was consistent with the published findings and the drug labelling, and no new side effects or increased incidence of known side effects was observed.

We present 2 cases of Haemophilus influenzae meningitis. The first is a patient with atypical simptomatology: abdominal pain, fever and two days later pain in the back of his legs. Abdominal pathology was not found. The cerebrospinal fluid (CSF) showed polymorphonuclear cells, hyperproteinorachia and lowered glucose. CSF culture revealed Haemophilus influenzae, blood culture was sterile. The second had suffered surgery at maxilar and ethmoid sinuses four years before, and unknown germ meningitis 6 months before. Haemophilus influenzae was isolated from CSF cultures and CSF rhinorrhea was detected by isotopic cisternography.

We sought clinical, paraclinical and genetic (HLA) factors that might have prognostic value in predicting disability produced by multiple sclerosis. An epidemiologically based sample including 146 cases (86% remittent and 14% mainly progressive) was studied. The progression of disability was measured on an index after systematic follow-up of at least 3 years. Our results show that the prognosis is significantly worse for those with a high frequency of attacks (p < 0.001), multiple clinical signs at presentation (p < 0.05) or motor weakness. The best prognosis was associated with those whose symptoms began with sensory alterations (p < 0.05). Late onset correlated significantly with a short interval between the first and second attack (r = 0.24), and this short interval was in turn significantly correlated with higher frequency of attacks in later stages (r = 0.44). We conclude that cases with a short interval between the first two attacks and those with late onset have a poorer prognosis. The following variables also tended to be associated with a more unfavorable prognosis, although the relationship was not statistically significant: female, progressive form, an increase in gammaglobulins in spinal fluid, infratentorial lesions as evidenced by magnetic resonance, and the alleles HLA-DR4, DR7 and DQw8. The allele DQw5 tended to be associated with a better prognosis.

Recently several reports have described contradictory results after studying the association between restriction fragments length polymorphisms (RFLP) of T cell receptor (TcR) beta-chain genes and multiple sclerosis (MS). We studied the allelic, genotypic and haplotypic distribution of RFLPs of TcR beta chain gene segments C beta, V beta 8 and V beta 11 in 97 unrelated multiple sclerosis (MS) patients, 11 with chronic progressive MS and 86 with relapsing/remitting (R/R) MS. We found the distribution of the TcR haplotypes defined by the alleles of the three loci studied in the MS patients was significantly different from that found in control individuals. The distribution of TcR haplotypes in R/R MS patients was also different from that observed in controls. Our data suggest that the TcR beta chain gene complex contains one or more genes involved in genetic susceptibility to develop MS.

In 1985 Ogasahara observed that treatment with ubiquinone produced improvement in the cardiac conduction and the metabolism of the lactic and pyruvic acids in the Kearns-Sayre syndrome. The results of the administration of 150 mg/day of ubiquinone for 3 years in a patient diagnosed with the Kearns-Sayre syndrome is described. The patient improved notably in strength, ocular movement, visual evoked potentials and in the metabolism of lactic and pyruvic acids. Other beneficial effects reported in the literature have been improvement of ataxia and the somato-sensitive evoked potentials. No side effects have been described.

An epidemiological study of multiple sclerosis carried out in Gijón (Principado de Asturias). It had the methodological peculiarity of having been performed in a reduced population of 81,462 individuals selected from the primary health care centers from which they depended. This permitted a better case finding and both a prospective and retrospective investigation. In the prospective period, the incidence found was 0.49/100,000/year, while it was 1.59 in the retrospective period. The reasons for this difference are discussed. The prevalence was 23.32/100,000. We attribute the fact that this rate is higher than that previously reported for Spain to methodological and perhaps geographical reasons.

HLA-A, -B, -C, -DR, -DQ antigens were studied in 43 multiple sclerosis (MS) patients with clinically definite remittent sclerosis from Asturias (North Spain). The prevalence of HLA-B7, B7 and B27 were significantly increased in MS. HLA-B35 was under-represented in these patients. DR2 was increased but not significantly. No association with DQw1 was discovered. The existence of several susceptibility factors in the more common B7/DR2/DQw1 haplotype is discussed.