[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Asturias and Cantabria]. / Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Asturias y Cantabria.

AIM: To evaluate the effectiveness and safety of fingolimod in routine clinical practice in the region of Asturias and Cantabria (Spain). PATIENTS AND METHODS: We conducted a retrospective multicentre study of patients with relapsing-remitting multiple sclerosis treated with fingolimod, in accordance with the product data sheet. Effectiveness was evaluated in patients with at least one year's treatment. The following were calculated: annualised relapse rate (ARR), the percentage of patients free from relapses and free from gadolinium-enhancing lesions, and those who improved/maintained their score on the Expanded Disability Status Scale (EDSS). Both total population and according to previous treatment: immunomodulator (interferon beta-1 or glatiramer acetate) or natalizumab, were analysed. RESULTS: A total of 138 patients started treatment with fingolimod; 60% previously received an immunomodulator; 28% were given natalizumab; and 9% had no treatment. Ninety-nine patients were treated with fingolimod for at least one year. After one year of treatment, fingolimod decreased the ARR by 67% (1.26 to 0.42; p < 0.0001), increased the percentage of patients free from relapses from 24% to 69% (p < 0.0001) and the percentage of patients free from gadolinium-enhancing lesions from 70% to 85% (p < 0.0106). Altogether, 77% of the patients improved/maintained their score on the EDSS. Similar results were observed in patients previously treated with an immunomodulator. The effectiveness of the patients previously treated with natalizumab remained the same following treatment with fingolimod. CONCLUSIONS: Routine clinical practice in the regions of Asturias and Cantabria shows that fingolimod yields similar results to those observed in clinical trials, on comparing the clinicoradiological variables used in them.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Asturias y Cantabria.Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica habitual en la region de Asturias y Cantabria (España). Pacientes y metodos. Estudio retrospectivo y multicentrico de pacientes con esclerosis multiple recurrente remitente tratados con fingolimod, segun la ficha tecnica. La efectividad se evaluo en los pacientes con al menos un año de tratamiento. Se calculo la tasa anualizada de brotes (TAB), el porcentaje de pacientes libres de brotes y libres de lesiones captantes de gadolinio, y los que mejoraron/mantuvieron la puntuacion en la escala expandida del estado de discapacidad (EDSS). Se analizo la poblacion total y segun el tratamiento previo: inmunomodulador (interferon beta-1 o acetato de glatiramero) o natalizumab. Resultados. Un total de 138 pacientes iniciaron tratamiento con fingolimod; el 60% recibio previamente inmunomodulador; el 28%, natalizumab; y el 9%, ningun tratamiento. Noventa y nueve pacientes estuvieron al menos un año en tratamiento con fingolimod. Despues de un año de tratamiento, el fingolimod disminuyo la TAB en un 67% (1,26 a 0,42; p < 0,0001), aumento el porcentaje de pacientes libres de brotes de un 24% a un 69% (p < 0,0001), y el porcentaje de pacientes libres de lesiones captantes de gadolinio de un 70% a un 85% (p < 0,0106). El 77% de los pacientes mejoro/mantuvo la puntuacion en la EDSS. Resultados similares se observaron en pacientes tratados previamente con inmunomodulador. La efectividad de los pacientes tratados previamente con natalizumab se mantuvo tras el tratamiento con fingolimod. Conclusiones. La practica clinica habitual en las regiones de Asturias y Cantabria muestra que el fingolimod tiene resultados similares a los observados en los ensayos clinicos, al comparar las variables clinicorradiologicas utilizadas en estos ultimos.

[Genetic epidemiology of multiple sclerosis]. / Epidemiología genética de la esclerosis múltiple.

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.

[Spinal cord infarction and recurrent venous thrombosis in association with estrogens and the 20210A allele of the prothrombin gene]. / Mielopatía aguda isquémica y trombosis venosa recurrente asociada a estrógenos y alelo 20210A del gen de la protrombina.

The acute spinal cord infarction is a rare cause of acute-onset paraplegia. Furthermore, it is specially uncommon that the infarction occurs in patients with apparent low predisposition to vascular disease. The 20210A allele of the prothrombin gene (causing a threefold-increased risk in venous thromboembolism) was recently associated with unexplained spinal cord infarction in young women under treatment with estrogens (contraceptive pill). We report a case of anterior spinal artery syndrome resulting from an ischaemic infarction at the anterior aspect of the spinal cord in a healthy 50-year-old woman, carrying this mutation, being the first published case under treatment with transdermal estradiol. She referred the typical sudden-onset back pain associated to clinical anterior spinal artery syndrome with sphincter dysfunction and nontraumatic paraplegia. A possible multiple sclerosis was ruled out and the steroids or immunoglobulin therapy induced no clinical improvement. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord infarction from T10 to T11, with increased signal in T2-weighted image (T2). Because she referred a previous thrombophlebitis and suffered a deep-vein thrombosis one month after paraplegia, a complete coagulation study was performed. Antithrombin, proteins C and S, homocysteine, factor V Leiden, lupus anticoagulant and anticardiolipin antibodies were all normal or negatives. In opposite, the 20210A variation was positive (heterozygous) and the factor VIIIc level was very high (280 U/dl eight months later). We argue the relative importance of both findings. The patient had no a substantial recovery over a period of 20 months.Certainly, the prothrombin 20210A seems to be associated with unexplained ischemic myelopathy among the young women with estrogens.

Interferon beta-1b treatment in patients with relapsing--remitting multiple sclerosis under a standardized protocol in Spain.

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.

HLA and multiple sclerosis. Studies of a spanish population. / HLA y esclerosis múltiple. Estudios en la población española.

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.

[Haemophilus influenzae type B meningitis: typical and atypical presentation]. / Meningitis por Haemophilus influenzae tipo B: presentación típica y atípica.

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.

Multiple sclerosis in Gijon health district, Asturias, northern Spain.

The objective of this study was to ascertain the prevalence and incidence of Multiple Sclerosis (MS) in a population of 33,775 in two primary health care centres in the sanitary district of Gijon, Asturias, northern Spain. Many information sources were used but the unique advantage of Gijon was that the city has a centralized computerized register of all diagnoses made for all consultations in the clinics and hospitals in the area. The HLA distribution in the population was already known and the Poser classification of MS was used. The crude MS prevalence was 65/100,000, a similar prevalence to that found in southern and eastern Spain, Sicily and Greek-speaking Cyprus. The mean incidence was 3.7/100,000 per year. The study demonstrated the advantage of a centralized and computerized medical recording system and demonstrates that northern Spain is a moderately high or medium MS risk zone.

[Prognostic factors in multiple sclerosis in a population-based series in Asturias]. / Factores pronósticos de la esclerosis múltiple en una serie de base poblacional de Asturias.

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.

The germline repertoire of T cell receptor beta-chain genes in multiple sclerosis patients from Spain.

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.

[Treatment with ubiquinone in Kearns-Sayre syndrome. Improvement in ocular motility and visual evoked potentials]. / Tratamiento con ubiquinona en el síndrome de Kearns-Sayre. Mejoría de la motilidad ocular y los potenciales evocados visuales.

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.

[Epidemiology of multiple sclerosis in Asturias]. / Epidemiología de la esclerosis múltiple en Asturias.

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 antigens in multiple sclerosis of northern Spanish population.

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.