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

INTRODUCTION: Post-authorisation studies are important to confirm whether the outcomes of clinical trials are reproduced in usual clinical practice. AIMS: To evaluate the effectiveness and safety of fingolimod in clinical practice in the province of Alicante. PATIENTS AND METHODS: A retrospective multi-centre study was conducted with remitting multiple sclerosis patients treated with fingolimod. Demographic, clinical and pharmacological data were collected. We report on the effectiveness of the drug -annualised relapse rate (ARR) and percentage of patients free from attacks- at one and at two years after treatment in relation to the previous year, and data concerning side effects are also provided. RESULTS: The sample consisted of 89 patients. Previous treatment was with immunomodulators (interferon beta or glatiramer acetate) in 54 patients and natalizumab in 32. Fifty patients changed due to failure with the immunomodulator and 31 owing to positive serology for JC virus (JCV+). Overall ARR decreased by 67.3% the first year (p < 0.0001) and by 84.1% the second (p = 0.0078). It diminished in patients with immunomodulator failure (85.6% the first year, p < 0.0001; 88.9% the second year, p = 0.0039) and increased in a non-significant manner in JCV+ patients in the first year. The percentage of patients free from relapses in the overall population increased from 32.6% to 68.1% in the first year (p < 0.0019) and to 82.6% in the second (p = 0.0215). This increase was not observed in JCV+ patients. Side effects were reported by 13 patients, which led to the drug being withdrawn in two of them. CONCLUSION: In clinical practice in the province of Alicante, levels of effectiveness and safety of fingolimod proved to be slightly higher than those found in clinical trials.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en la provincia de Alicante.Introduccion. Los estudios postautorizacion son importantes para confirmar si los resultados de los ensayos clinicos se reproducen en la practica clinica habitual. Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en la provincia de Alicante. Pacientes y metodos. Estudio multicentrico retrospectivo de pacientes con esclerosis multiple remitente tratados con fingolimod. Se recogen las caracteristicas demograficas, clinicas y farmacologicas. Se describe la efectividad del farmaco ­tasa anualizada de brotes (TAB) y porcentaje de pacientes libres de brotes­ al año y a los dos años de tratamiento en relacion con el año previo y datos de efectos secundarios. Resultados. Se incluyo a 89 pacientes. El tratamiento previo fue inmunomodulador (interferon beta o acetato de glatiramero) en 54 pacientes y natalizumab en 32. Cincuenta pacientes cambiaron por fracaso con el inmunomodulador y 31 por serologia positiva del virus JC (VJC+). La TAB global disminuyo el 67,3% el primer año (p < 0,0001) y el 84,1% el segundo (p = 0,0078). Disminuyo en los pacientes con fracaso del inmunomodulador (el 85,6% el primer año, p < 0,0001; el 88,9% el segundo año, p = 0,0039) y aumento de forma no significativa en los pacientes VJC+ en el primer año. El porcentaje de pacientes libres de brotes en la poblacion global aumento del 32,6 al 68,1% en el primer año (p < 0,0019) y al 82,6% en el segundo (p = 0,0215). Este aumento no se observo en los pacientes VJC+. Trece pacientes tuvieron efectos secundarios, que obligaron a la retirada del farmaco en dos de ellos. Conclusion. En la practica clinica de la provincia de Alicante, el fingolimod mostro una efectividad y una seguridad ligeramente superiores a las de los ensayos clinicos.

Mapping of Friedreich's ataxia locus by identification of recombination events in patients homozygous by descent.

The Friedreich's ataxia locus (FRDA) maps on chromosome 9q13. Genetic data, obtained from a small number of recombination events, indicated that the FRDA locus might be located centromeric to the D9S15/D9S5 linkage group, the most probable order being cen-FRDA-D9S5-D9S111-D9S15-D9S110-qter. Recently, new centromeric markers have been reported. Analysis of these markers allowed us to localize the recombination breakpoint in some of the recombinant families. However, only one proximal recombination has been found with these markers. To increase the genetic information from FRDA families, we have analyzed the centromeric markers FR1, FR2, FR7, FR8, and FR5 in patients homozygous by descent. These were ascertained because parents were consanguineous or because they were homozygous for the entire haplotype D9S15 or D9S111-D9S5-D9S411E-D9S202. Haplotype divergence for, at least, two contiguous markers was observed in two patients homozygous for the core D9S111-FR2 haplotype and in one third-degree consanguineous family homozygous for haplotype D9S411E-FR5. Interpretation of divergence as the result of ancient meiotic crossovers allowed the definition of three new recombination events which place the FRDA locus within the interval defined by markers D9S411E and FR8. A consanguineous family with first-cousin parents showed homozygosity only at D9S202 and FR2. Further investigations are needed to discern whether two different mutations are segregating in the family or whether two recombinations, one distal and one proximal, have taken place.

[Genetic analysis of Friedreich's ataxia using polymorphic DNA markers]. / Análisis genético de la ataxia de Friedreich con marcadores de ADN polimórficos.

Friedreich's ataxia (FA) is a progressive degenerative disease involving both central and peripheral nervous system. It is an autosomal recessive hereditary disorder, which begins around puberty and has an unknown genetic basis and biochemical defect. The recent mapping of FA locus in human chromosome 9 by means of the analysis of the molecular genetic linkage has permitted to evaluate FA genetics with polymorphic genetic markers (RFLPs) that are secreted linked with the FA gene. The normal and mutant allele secretion of FA was evaluated in ten Spanish families with one or two members with FA by means of several cloned probes (MCT112, DR47, D9S1 and HHH220), localized in chromosome 9 and strongly linked to FA gene, with the aim of achieving a predictive diagnosis of relatives in the pediatric age and to detect healthy carriers. In 9 out of 10 families some totally or partially informative RFLP were found. In 5 of 6 relatives in pediatric age the future development of the disease could be ruled out. By contrast, the carrier status could only be identified in three relatives. In a family with two affected children a genetic recombinant for D9S1 was found. Remarkably, one of them had a better clinical evolution and preserved tendon reflexes in lower limbs.

[Daily defined doses of parkinsonian drugs in Alcoi]. / Dosis diarias definidas de fármacos antiparkinsonianos en Alcoi.

BACKGROUND: Some authors have suggested that the use of DDD (defined daily doses) of L-dopa may be useful as an indicator of the frequency of Parkinson's disease. AIM: To determine the measurement for L-dopa and selegiline in Alcoi. MATERIAL AND METHODS: We have obtained the intakes for L-dopa and selegiline between January and December, 1990 and we have calculated the DDD/1,000 inhab/day. RESULTS: During the study period, we have found that the mean intakes were 18,000.969 mg and 53,800 mg for L-dopa and selegiline, respectively. And so, the L-dopa intake in Alcoi was 0.60 DDD/ 1,000 inh, and the selegiline intake was 0.21 DDD/1,000 inh. DISCUSSION: Comparing the other data of the literature, specially in scandinavian countries, the obtained intake for L-dopa was low, and that could indicate that the frequency of the disease in Alcoi was lower.

[Descriptive epidemiology of transitory ischemic attack: a study in Muro d'Alcoi]. / Epidemiología descriptiva del accidente isquémico transitorio: estudio en Muro d'Alcoi.

A door-to-door survey of transient ischemic attack was conducted in Muro de Alcoi using a randomized sample. We randomly choose 646 people of the 4.525 included in the census. The prevalence ratio found for TIA and stroke were 12.3 per 1,000 people (95% CI 3.9-20.7). The age-specific prevalence rates for male and for women were 12.4 per 1,000 (95% CI 0.3-24.5) and 12.3 per 1,000 (95% CI 0.4-24.2) respectively. The work suggests that methodology of ascertainment strongly influences in the obtained rates, and reinforces the data of our previous whole population work in the same area.

[Descriptive epidemiology of the vascular risk factors in Bañeres. Study group 'Bañeres Project']. / Epidemiología descriptiva de los factores de riesgo vascular en Bañeres. Grupo de Estudio 'Proyecto Bañeres'.

INTRODUCTION: Epidemiological studies of the risk factors of cerebrovascular disease are of great interest, particularly the identification of factors which may be modified. Previous studies carried out in the Alcoi region of Alicante province, showed a high prevalence of cerebrovascular disease. The town of Bañeres was therefore chosen for confirmation of this data and identification of the frequency of vascular risk factors. OBJECTIVE: To compare the group of patients with cerebrovascular disease with the remainder of the population interviewed. PATIENTS AND METHODS: In a door-to-door study in Bañeres 1,832 people were interviewed as part of the Bañeres Project. The population aged over 45 years was interviewed and filled in a questionnaire for diagnosis of transient ischemic accidents. RESULTS: Arterial hypertension: estimated prevalence 500/1,000 inhabitants, relative risk 3.24; diabetes mellitus: estimated prevalence 195/1,000, relative risk 2.18; coronary artery disease: estimated prevalence 58/1,000, relative risk 1.88; peptic ulcer: estimated prevalence 75/1,000, relative risk 1.23; smoking: estimated prevalence 110/1,000, relative risk 0.46; complete arrhythmia: prevalence 73/1,000, relative risk 5.23. Family histories of cerebrovascular accident, arterial hypertension, diabetes and coronary artery disease were not significant. CONCLUSIONS: Arterial hypertension, diabetes mellitus and arrhythmia were significantly more prevalent amongst patients with vascular disease in our setting. We found no association with the other risk factors analyzed.

[Multiple sclerosis incidence in the Alcoi Health district. 12-year-long study (1986-1997)]. / Incidencia de la esclerosis múltiple en el área sanitaria de Alcoi. Estudio de 12 años (1986-1997).

INTRODUCTION: To date, epidemiological studies on multiple sclerosis in Spain have been basically prevalence studies, and the data on incidence recorded have been the result of different methodologies, with no definition of the criteria for inclusion. OBJECTIVE: To carry out a study of incidence with prospective collection/review of cases over a prolonged period of time. PATIENTS AND METHODS: Over 12 years, between 1 March 1986 and 31 December 1997, we collected data prospectively for patients with a definite diagnosis of multiple sclerosis. The year of incidence was considered to be when the patient fulfilled clinical criteria for diagnosis of the disease. RESULTS: On 31 December 1997 in the Alcoi Health District there were 54 patients with clinically defined multiple sclerosis (a prevalence of 41.28 cases per 100,000 inhabitants). Of these, 45 patients were diagnosed during the period studied, with an average incidence of 2.82 cases per 100,000 inhabitants per year. Only 15 patients were confirmed before 1986. CONCLUSIONS: This is the most prolonged study of the incidence of multiple sclerosis carried out in Spain. The figures found for incidence are in contrast to those found in previous years for prevalence and incidence. Analysis of the data suggests that the incidence of multiple sclerosis in the Alcoi district has changed and has increased since the second half of the 1980s.

[The prevalence of multiple sclerosis in the Alcoi Health district]. / Prevalencia de la esclerosis múltiple en el área sanitaria de Alcoi.

INTRODUCTION: The epidemiological studies done in Spain in recent years show higher figures for the prevalence of multiple sclerosis than before. Spain is therefore now in the area with a high risk of contracting the disease. OBJECTIVE: We have made a new study to confirm the current prevalence of the disorder in the Alcoi Health District. PATIENTS AND METHODS: Between 1 March 1986 and the prevalence day, 31 December 1997 we recorded the patients with definite or probable multiple sclerosis, as defined on Poser's criteria, after intensive fieldwork and reevaluation of all possible patients by a neurologist from the Neurology Unit. On the prevalence day there were 130,786 inhabitants in the district. RESULTS: On the prevalence day we found 54 patients with definite multiple sclerosis and no patient with probable multiple sclerosis. The rate of prevalence was 41.28 cases per 100,000 inhabitants (95% CI: 31-53.6). During the study we counted an incidence of 45 cases with an average rate of 2.82 cases per 100,000 inhabitants per year. We also describe the clinical characteristics of the patients. CONCLUSIONS: The rate of prevalence found is much higher than that described for the district in studies using similar methodology. This increase, together with the discrepancy between the incidence found and the prevalence, makes us consider that possibly the prevalence has increased in recent years.

[Oculographic findings in the Arnold-Chiari malformation type I]. / Hallazgos oculográficos en la malformación de Arnold Chiari tipo I.

The paper deals with 5 adults carriers of this syndrome diagnosed by means of nuclear magnetic resonance (NMR). Neither the conventional radiography nor the plain computerized tomography showed indicative clues of the deformity. However electronystagmography prove in all cases a vertical down beating nystagmus. In one instance the nystagmus become rotatory at lateral glance. In all cases appeared an altered smooth pursuit and a lack of suppression fixation of the vestibular nystagmus. The AA. emphasize the diagnostic value of the electronystagmography (which tracings could spare several other, sometimes expensive, examinations) and suggest a prompt MRI.

Friedreich's ataxia: an epidemiological study in Valencia, Spain, based on consanguinity analysis.

Epidemiological studies performed directly on the population show a prevalence of Friedreich's ataxia (FA) from 1 to 4.7 cases/100,000 inhabitants. An indirect epidemiological approach can be achieved using genetic methods like consanguinity studies to determine the frequency of a mutated gene and the incidence of certain diseases in the population. We obtained consanguinity data of a series of FA patients in Valencia, Spain and the figures on consanguinity in the general population that were estimated according to the Archive of Dispensations given by the Catholic church for consanguineous marriages. From these data, the frequency of the FA gene was calculated as 1/127. From these data, applying the Hardy-Weinberg principle, the frequency of the carriers was 1/64 and the incidence was 6.18/100,000 live births. Assuming a life expectancy of FA of 45 years, the prevalence was 3.83/100,000 inhabitants. These figures are in the same range as those obtained in population studies.

A family segregating a Friedreich ataxia phenotype that is not linked to the FRDA locus.

Friedreich ataxia is an autosomal recessive neurodegenerative disorder. The genetic homogeneity to the FRDA locus on chromosome 9q13-21.1 has been observed in families from different ancestries. We report a Spanish family with two affected and three unaffected children. The segregated classical Friedreich ataxia did not show the expected linkage. The analysis focusses on flanking markers FR1, FR2, FR7 and FR5, excluding linkage 1 cM around the FRDA locus. The unique clinical hallmark in this family was the absence of cardiomyopathy after a long-term follow-up in the two affected children. In both patients serum vitamin E levels were normal. The present observations support the existence of a second locus in Friedreich ataxia, and we suggest that this form could be clinically characterized by the absence of muscular heart disease.

[The presence of oligoclonal bands in the cerebrospinal fluid in various neurologic diseases]. / Aparición de bandas oligoclonales en LCR de diferentes enfermedades neurológicas.

The polyacrylamide gel electrophoresis of spinal fluid from 488 patients suffering neurological diseases and from a control group are reviewed. One hundred and eleven cases (22.7%) showed oligoclonal bands (OB). The highest percentage of OB appeared in the group of patients with definite multiple sclerosis (84%), followed by those with probable multiple sclerosis (46%) and inflammatory infectious diseases (43%); the group of patients with a possible multiple sclerosis (7%), vascular malignancies (11%) and other diseases (4%) showed a lower incidence of OBs. No OBs were found in groups of patients with degenerative diseases, dementia or the control group. These results confirm the great usefulness of this test to support the diagnosis of multiple sclerosis, although it also shows that it is not a specific test so it should always be evaluated within a clinical context.

Early-onset ataxia with cardiomyopathy and retained tendon reflexes maps to the Friedreich's ataxia locus on chromosome 9q.

Absence of lower limb tendon reflexes has been considered an essential diagnostic criterion for Friedreich's ataxia (FA). However, preservation of knee and ankle jerks has been reported in a few patients. Linkage analysis to FA locus (FRDA) on chromosome 9q13-21.1 was performed in 11 patients from 6 families with FA phenotype, including cardiomyopathy, but retained reflexes (FARR). A maximal lod score of 3.38 at recombination fraction theta equal to 0.00 was obtained demonstrating that FARR maps to the FRDA locus. These results suggest that FARR is a variant phenotype of FA.

[Abnormal movements of vascular origin]. / Movimientos anormales de origen vascular.

Three patients with hemichorea and ten with dystonia of vascular origin are reported. Five were secondary to ischemic infarcts, two to lacunar infarcts, three to intraparenchymal hematoma, and in the remaining three the type of lesion could not be determined. The patients with chorea, as opposed to those with dystonia, presented abruptly immediately after the stroke, and had a regressive evolution and good therapeutic response. The type of dyskinesia was not useful to identify the precise localization of the lesion or to determine its nature. In addition, in 5 patients multiple lesions were found and 5 had release of archaic reflexes or cortical atrophy in CT; this shows the importance of the overall functional impairment and focal lesions in the genesis of dyskinesia. There were sensory deficits in 7 patients. In 2 patients lesions were not found in the CT in spite of the presence of previous hemiparesis; this suggests that this technique has limitations to discover focal cerebral lesions in patients with focal or hemicorporal dyskinesia.

[Findings of computed tomography in the acute form of Marchiafava-Bignami disease]. / Hallazgos de la tomografía computadorizada en la forma aguda de la enfermedad de Marchiafava-Bignami.

We report a case of Marchiafava-Bignami's disease with acute evolution. Pathological examination was carried out and a cavitary lesion with discontinuous longitudinal extension was found throughout the corpus callosum. CT had shown a narrow hypodense area symmetrically localized just anterior to the frontal horns of the lateral ventricles, corresponding to the genus of the corpus callosum. The literature is reviewed, the anatomical-radiological correlations are discussed, and the possibility of the diagnosis of this condition during life is commented.