Producción CientíficaThe aim of this study was to ascertain the prevalence of multiple sclerosis (MS) in a northern Spanish region and to compare it with that from the most recent epidemiological studies in the country. MS prevalence was studied for a period of 2 years using multiple sources of information in the province of Valladolid, with a sample comprising a total population of 92,632. Patients were classified according to the Poser criteria. The crude prevalence of definite and probable MS was 58.3 per 100,000 (95% confidence interval: 43.7–75.7). The same methods have been used in ascertaining similar prevalence rates in Vélez-Málaga, Osona, and Gijón and a slightly lower rate in Teruel. Our survey confirms Spain as a high-risk area for MS, with prevalence rates over 50 per 100,00

Fernández Buey, Nieves

Fernández Herranz, Rosario

Tola Arribas, Miguel Ángel

Yugueros Fernández, María Isabel

Journal of Neurology

Repositorio Documental de la Universidad de Valladolid

IntroductionSurveys on the prevalence of multiple sclerosis (MS)carried out in large populations in Spain before 1992used various diagnostic criteria and were based almostexclusively on hospital records [1, 2, 6, 8, 14, 16, 18, 25,28, 29]. These studies defined Spain as an area of low tomedium risk for MS, according to Kurtzke [12]. Usingevery reasonable information source available for popu-lations under 100,000, prevalence rates between 32 and65 per 100,000 in northern and southern Spain havebeen obtained [3, 7, 17, 30]. Dean and Middleton usedthe same methods and reported similar figures for Sicilyand Cyprus, at a latitude similar to that of Spain, [4, 15,26].Except for a previous survey in Salamanca andZamora [25], there are no recent data on the frequency ofMS in our region, located 200km north of Madrid. Nev-ertheless, the number of followed-up patients in ourhealth area suggested the prevalence of MS here to besimilar to that recently reported for the north and southof our country.Study population and methodsThe area investigated includes six health zones, each ofwith its own health center and with a single outpatientclinic of specialties run by the Neurology Department ofthe Hospital Universitario of Valladolid. These six areasare within the city of Valladolid and comprise a total areaof 197 km2 (41°39 ¢ N–4°44 ¢ W) and a population of 92,632(November 1996). The region has a continental climatewith a mean temperature of 12.4°C. Its average altitude is698 m above sea level (Fig.1). Economic activity is fun-damentally industrial, largely car and machinery manu-facturing, and services. The population level in Valladolidis stable, having increased only slightly over the past 15years. There is a high racial uniformity and migratorymovements are rare.The survey was carried out over a 2-year period fromSeptember 1995 to August 1997. The day of 1 March1997 was chosen as the prevalence day since this was thedate when all the patients began to be checked for the sec-ond time to confirm they were still alive and living in thearea. Poser’s classification of MS was used, and onlythose persons with probable or definite MS were includedAbstract The aim of this study wasto ascertain the prevalence of multi-ple sclerosis (MS) in a northernSpanish region and to compare itwith that from the most recent epi-demiological studies in the country.MS prevalence was studied for a period of 2 years using multiplesources of information in the prov-ince of Valladolid, with a samplecomprising a total population of92,632. Patients were classified ac-cording to the Poser criteria. Thecrude prevalence of definite andprobable MS was 58.3 per 100,000(95% confidence interval: 43.7–75.7).The same methods have been used inascertaining similar prevalence ratesin Vélez-Málaga, Osona, and Gijónand a slightly lower rate in Teruel.Our survey confirms Spain as a high-risk area for MS, with prevalencerates over 50 per 100,000.Key words Multiple sclerosis ·Prevalence · SpainORIGINAL COMMUNICATIONJ Neurol (1999) 246 :170–174© Steinkopff Verlag 1999Miguel Angel TolaMaría Isabel YuguerosNieves Fernández-BueyRosario Fernández-HerranzPrevalence of multiple sclerosis in Valladolid, northern SpainReceived: 4 March 1998Received in revised form: 13 May 1998Accepted: 10 June 1998M. A. Tola Arribas (Y) · M. I. Yugueros ·N. Fernández-Buey · R. Fernández-HerranzDepartment of Neurology, Hospital Universitario de Valladolid,Mailing address: C/ Embajadores 20 6B,S-47013 Valladolid, SpainFax: +34-83-39-0357[22]. Disability was assessed using the Expanded Disabil-ity Status Scale (EDSS) of Kurtzke [10]. A disability of0–3 was considered mild disability, 4–6 moderate disabil-ity, and 7–9.5 severe disability. A progression index wasdefined as the ratio of the disability status (EDSS) to theduration of the disease in years [21]. The type of progres-sion was defined according to the consensus criteria es-tablished by Lublin et al. [13]. The onset of MS was de-termined by interviewing patients and reviewing theirmedical records, and the classification of definite andprobable signs and symptoms of MS proposed by Poserwas used [19].Multiple methods for case ascertainment were used.Records of both Valladolid hospitals (Hospital Universi-tario and Hospital Universitario del Río-Hortega), datafrom the Neurology Service of the Hospital Universitarioand the records from outpatient clinics of specialties werereviewed, searching for the code number 340 (MS). Fur-ther information was obtained from 41 general practition-ers in the area by periodically interviewing medical coor-dinators from each one of the six health zones. Othersources of information included private neurologists (4),internists (14), records of evoked potential studies in Hos-pital Universitario, a home hospitalization unit, welfareworkers, and the local MS patient association. Informa-tion from the city’s two units of magnetic resonance imag-ing (MRI) could not be obtained as their files were not ona data base. Searching for nonidentified patients, twosymposia for relatives and patients were held and reportedby the public media.All possible MS patients were examined by two neu-rologists. A second examination was carried out by thesame physician in all cases. MS had to be confirmed byboth physicians for the diagnosis to be accepted.Adjusted prevalence rates were calculated by the directmethod [11] using 5-year groupings, with the total Span-ish population (1991 census) as a standard. Confidenceintervals (95%) were computed assuming the Poisson dis-tribution [27]. The chi-square test was used to analyze thehomogeneity in the distribution of patients over the sixhealth zones [9]. The survey was reviewed by the Hospi-tal Universitario of Valladolid Research Committee andby the Board of the ONCE Foundation for the cooperationand social integration of the disabled.ResultsAfter an intensive search, 54 definite or probable MS pa-tients were ascertained, all alive and living in the area on1 March 1997 (18 men and 36 women). Fifty-one patientshad definite MS (18 men and 33 women), including 4with laboratory-confirmed MS. Three women had clini-cally probable MS. The crude prevalence rate found in thearea was 58.3 per 100,000 (95% CI: 43.7–75.7). Theprevalence for clinically definite MS alone was 55.1 per100,000. Age- and sex-specific prevalence rates areshown in Table 1. The distribution of cases within thestudy area, analyzed according to the six health zones,was uniform (chi-square = 7.2; d.f. = 5; P = 0.2). Crudeprevalences and age- and sex-adjusted prevalence rates ofthe 1991 Spanish population in the most recent epidemio-logical studies carried out in Spain are shown in Table 2.Forty-five patients were visited or admitted to hospitalduring the study. Five patients were identified by hospitalrecords. One patient was being visited by a private neu-rologist and another patient by an internist. The collabora-171Fig.1 Map of Spain, with theprovince of Valladolid (left)and the study area (right). Theareas of Gijón, Osona, Teruel,and Vélez-Málaga are alsoshowntion of the local MS patient association allowed us to findone patient not identified by other methods. A generalpractitioner reported the case of a woman suffering fromMS for 24 years who had not been visited by a neurologistfor the past 10 years. The remaining methods for case as-certainment detected no patient not already known by thelocal neurologists.Mean age at onset was 27.3 years (men 28.7, women26.6) and mean age on the prevalence day was 36.1 years(men 37.6, women 35.3). The mean period between thefirst symptom and the prevalence day was 8.7 years (men8.8; women 8.6). The mean diagnostic delay was 3 years(range 0–23). Sensory symptoms were the most commonat onset (55%), followed by pyramidal tract symptoms(49%), brainstem symptoms (31%), cerebellar symptoms(24%), and optic neuritis (14%).Cranial MRI was performed in all patients exceptthree, with abnormal results in 98%. In addition, the re-sults of 32% of spinal MRI studies were also abnormal.The median and interquartile EDSS range in clinicallydefinite patients was 3.0 [1.5–5.0; men 3.5 (1.5–5.6),women 2.5 (1.0–4.3)]. The mean EDSS score was 3.4.The mean progression index was 0.4. Among these pa-tients 58% were only slightly or not disabled (EDSS ≤3.0), and 13% were severely disabled (EDSS ‡ 7.0). Ninepatients were alive after 15 years of the disease; one hadlow disability, four moderate, and four severe.The clinical course was relapsing-remitting in 37 pa-tients (68%; 11 men, 26 women), primary-progressive in11 (20%; 4 men, 7 women), and 6 patients with an initialrelapsing-remitting evolution had developed a secondaryprogressive clinical course (3 men, 3 women).Thirty-four patients were born in Valladolid (63%), tenin adjacent provinces (18%), and the rest in other placesin Spain, except two patients born in France and Switzer-land, respectively. A family history of MS were found intwo women.Nine patients were excluded from the survey becausethey had been misdiagnosed. Two of these had a cervicalspondylotic myelopathy; one had an Arnold-Chiari mal-formation; three had hyperintense lesions on cranial MRIthat according to their vascular risk factors, clinicalcourse, and age was of ischemic origin; one was diag-nosed as having Childer disease, though not confirmed bynecropsy; one showed typical hyperintense lesions on cra-nial MRI although his symptoms were considered sec-ondary to a large cervical disk herniation; and one suf-fered from hysteria.DiscussionThe results of our study, together with those obtained inother Spanish regions using a similar methodology [3, 7,17, 30], confirm our country as a high risk area for MS,with prevalence rates between 50 and 60 per 100,000. Webelieve that only a single further study in southern Spainis needed to confirm the survey findings of Fernández etal. [6, 7] in Málaga.Comparison of adjusted prevalence rates to Spanishpopulations, except for the results of Modrego-Pardo et al.in Teruel [17], show few differences among the recentsurveys carried out in Spain. The size of the study area,with a total population of 143,000 inhabitants, health-caredispersion, duration of the survey, and a high emigrationrate can explain the prevalence rate in Teruel.A number of features lend additional credence to thefigures from our study. The study population has a highdemographic stability and racial uniformity. The area hasa good sanitary infrastructure, with well-developed health172Table 1 Age- and sex-specificprevalence rates (MS multiplesclerosis, M men, W women)Age Population MS patients Prevalence/100,000(years)M W Total M W Total M W Total≤ 19 9,044 8,822 17,866 2 2 4 22.1 22.7 22.420–29 9,412 9,579 18,991 6 12 18 63.7 125.3 94.830–39 6,067 6,580 12,647 2 12 14 33 182.4 110.740–49 6,014 6,844 12,858 3 5 8 49.9 73.1 62.250–59 5,794 5,899 11,693 5 4 9 86.3 67.8 77‡ 60 7,921 10,656 18,577 – 1 1 – 9.4 5.4All 44,252 48,380 92,632 18 36 54 40.7 74.4 58.3Table 2 Comparison of the most recent prevalence studies inSpain (MS multiple sclerosis, CI confidence interval)Popu- MS pa- Crude Age- andlation tients prevalence sex-adjusted[CI 95%]a prevalencebVélez-Málaga [7] 36,014 19 52 [31.7–82.2] 61Osona [3] 71,985 42 58 [42.0–78.7] 60Gijón [30] 33,775 22 65 [40.8–98.3] 59Teruel [17] 143,680 46 32 [22.8–41.3] 35Valladolid 92,632 54 58 [43.7–75.7] 53a Crude prevalence per 100,000 populationb Age- and sex-adjusted prevalence per 100,000 in the 1991 Span-ish population173services, and neurological care is focused in a single neu-rology department. Computerization of both hospitalrecords and neurology service data made case ascertain-ment easier. Multiple sources of information as by Fer-nández et al. were used [5], allowing us to identify ninepatients (16%) who were not being visited by local neu-rologists. If we had not used all these information sources,the prevalence figures would have been 48.6 instead of58.3 per 100,000. Finally, the patient distribution in thestudied area was homogeneous, showing easy and uni-form access to neurological services.It has been proposed as a measurement of the reliabil-ity of MS prevalence studies that the ratio of patients hav-ing a low degree of disability (EDSS ≤ 3.0) must be closeto 70% [24]. This estimation has been carried out accord-ing to the concept of onset-adjusted prevalence rate pro-posed by Poser, after his experience on a survey in Iceland[23]. This measures the number of symptomatic MS pa-tients (diagnosed or not) in an ethnically homogeneouspopulation who live to the age of puberty in the same nat-urally defined geographical area [20]. This measurementrequires case ascertainment to be extended at least 2 yearsafter the prevalence date to increase the probability of di-agnosing all the patients in the area. In our study, usingthe traditional concept of prevalence, the ratio of patientswith low disability was 58%. This lower percentage sug-gests that there may be patients who have not consultedhealth services for their symptoms yet.The mean age on the prevalence day (36.1 years), themean duration of the disease (8.7 years), the reduced per-centage of patients with a secondary progressive course,and the low number of patients older than 60 years sug-gest that there are some patients in the area who were notidentified in this study. 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Prevalence of multiple sclerosis in Valladolid, northern Spain

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Repositorio Documental de la Universidad de Valladolid