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BackgroundMortality and morbidity related to rheumatoid arthritis (RA) has remarkably improved over the last twenty years since using biologics DMARDs1. However, their effectiveness remains questionable in Afro-descendants (AD) due to their large under-representation in RA clinical trials2,3. Martinique is a French Caribbean region with a majority of AD population4, with free access to healthcare, including biotherapies, and a unique university hospital and rheumatology unit.ObjectivesTo evaluate effectiveness of Tocilizumab (TCZ), an interleukin-6 inhibitor, in an afro descendant RA population.MethodsRetrospective cohort of 171 patients who received at least 1 infusion of Tocilizumab (IV TCZ) at Martinique University Hospital Center between 2008 and 2019. Inclusion Criteria: Patients over 18 y/o meeting RA 2010 ACR/EULAR criteria, having received at least 4 courses of IV TCZ starting at 8mg/kg every 4 weeks, with available baseline clinical/biological data. Exclusion criteria: Patients having received subcutaneous TCZ (SC TCZ) prior to IV TCZ, not living in Martinique. Primary endpoint was proportion of patients in remission (R) and low disease activity (LDA) according to DAS28 CRP at 12, 24, 36 weeks. Secondary endpoint was proportion of patients achieving good (GR) and moderate (MR) EULAR response criteria 5 at 12, 24 and 36 weeks, and TCZ retention at 1 year defined as the proportion of patient receiving TCZ at 1 year follow up.ResultsOut of 171 patients receiving IV TCZ, we identified 138 RA and 80 patients met inclusion criteria: 90% were women, mean age was 56.8 (± 11.8) y/o, mean duration of RA was 11.6 (± 8.9) years, ACPA and Rheumatoid Factor were positive in 72.1% and 73% of cases, 69.6% of patients had erosions and 77.8% had received at least 1 biologic prior to IV TCZ. At baseline, 8 patients were in R, 8 had LDA but presented steroid dependency over 10 mg per day of prednisone and mean dose of prednisone was 6.9 (+/- 6.7) mg per day.At 12, 24, 36 weeks, R was achieved in 44.8%, 55.2% and 51.2% of patients and LDA in 37.3%, 17.2% and 20.9%, respectively (Figure 1). At 12, 24, 36 weeks, GR was achieved in 44.8 %, 60.3% and 48.8% of patients respectively, MR was achieved in 20.9%, 20.7% and 27.9% of patients respectively (Figure 1) and mean dose of prednisone per day was 5.1 (± 4.9) mg, 4.9 (± 5.6) mg and 3.3 (± 5.1) mg respectively. At 1 year, 78.8% of patients were still on TCZ. During follow up: 15 patients experienced 19 infectious events; 6 patients liver cytolysis; 12 patients neutropenia. No patient died.ConclusionThis is the first study evaluating efficacy and safety of TCZ in an AD RA cohort. TCZ is safe and effective in our AD population with comparable data observed in other ethnicities6,7.References[1]Lacaille, D., Avina-Zubieta, J. A., Sayre, E. C. & Abrahamowicz, M. Improvement in 5-year mortality in incident rheumatoid arthritis compared with the general population—closing the mortality gap. Ann. Rheum. Dis.76, 1057–1063 (2017).[2]Strait, A. et al. Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials: A Systematic Review. JAMA Netw. Open2, e1914745 (2019).[3]Dunbar-Jacob, J. et al. Factors associated with attrition of African Americans during the recruitment phase of a clinical trial examining adherence among individuals with rheumatoid arthritis: Attrition of African Americans. Arthritis Care Res.51, 422–428 (2004).[4]Levinson, D. Ethnic Groups Worldwide : a ready handbook. (1998).[5]Fransen, J. & van Riel, P. L. C. M. The Disease Activity Score and the EULAR Response Criteria. Rheum. Dis. Clin. N. Am.35, 745–757 (2009).[6]Gottenberg, J.-E. et al. Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. BMJ l67 (2019) doi:10.1136/bmj.l67.[7]Mori, S. et al. Retention of tocilizumab with and without methotrexate during maintenance therapy for rheumatoid arthritis: the ACTRA-RI cohort study. Rheumatology58, 1274–1284 (2019).Disclosure of InterestsNone declared

Background:Spondyloarthritis is a polymorphic disease and the absence of diagnostic marker has led to propose diagnostic criteria for recognition. All the criteria, established in Caucasian populations, place at the center of the approach sacroiliac imaging and genetic terrain (HLA B27). For this reason, these criteria are not appropriate in populations lacking HLA B27. SPA is known to be rare in African populations and this rarity correlates with that of HLA B27.Prevalence of B27 in French West Indies is 2% (identical to the African populations).Objectives:We report clinical manifestations of SpA seen at the Fort de France University Hospital, with an emphasis on the so-called “non-radiographic SpA” (NRSPA).Methods:Adult patients with spondyloarthritis seen over a period of three consecutive months, were invited to participate in a survey and filled-in a self-administered questionnaire. The consulting rheumatologist specified the rheumatologic and extra-articular involvement, BASDAI score, HLAB27 data, markers of inflammation and imaging.Results:There were 93 patients, 47 with radiographic sacroilitis (RSPA) and 46 patients without but all - these 46 - had magnetic sacroilitis. This population is Afro-Caribbean for 98%. Mean age at onset of clinical signs is 38.5 ± 15.0 years and median age is 37.0 (13-77). An evocative family history is noted in 37%. All these 93 patients suffer from rachialgia.But the axial complaint is often secondary to the peripheral involvement. 3 patients have a mechanical spinal complaint. All the others have intermittent inflammatory complaint evolving by flares affecting all the spinal stages. 15/93 patients have isolated axial complain without peripheral disease. Enthesopathies are seen in 70%.Peripheral inflammatory joint complain is observed in 78 patients (84%), it is a bilateral and symmetrical chronic polyarticular pattern affecting (70/78) the small joints of the hands, forefeet and wrists. Ankle bi-arthritis is almost systematic and is observed in 71/78 patients; 8 patients with RSPA had no polyarthritis but oligo (6) or monoarthritis (2). Peripheral inflammatory joint is more frequent in NRSPA than in RSPA (98% vs 70%). Ultrasound individualises grade II synovitis (78/78), rarely with a Doppler effect (5/78). On average, more painful and swollen joints are observed in NRSPA than in RSPA. Extra articular and immunological aspects and activity scores are in table 1.Good sensitivity of peripheral arthritis to NSAIDs and MTX is noted in 94 and 91%.Conclusion:NRSpA are not uncommon in the Afro-Caribbean population, but are distinct from Caucasian SpA by several points: female predominance, rarity of B27 and syndesmophytes, frequency of polyalgic pattern, frequency of peripheral arthritis, rarity of extra-articular manifestations, more frequent but less marked inflammation, good response of arthritis to NSAIDs and MTX. Appropriate classification criteria for Afro-descendant populations is an urgent unmet need.References:[1](López-Medina C, et al. RMD Open 2019;5:e001108).Table 1.Extra articular manifestations, activity scores and immunological aspects of the patients.ItemResults (%)NRSPA n=46Results (%)RSPA n=47Dactylitis11 (23 %)13 (27 %)Uvéïtis5 (11 %) (p 0.02)15 (32%)Psoriasis1 (2 %)1 (2 %)IBD4 (9 %) (p 0.02)10 (21 %)Balanitis00Non gonococcal urethritis00Non gonococcal cervicitis00High CRP (at least 2 measure)21 (45%) (p 0.03)30 (63%)Mean CRP mg/l6 ± 4 17 ± 7BASDAI4.1 ± 0.24 ± 0.2EVA pain4.5 ± 0.44,5 ± 0.2HAQ0.6 ± 0.30,5 ± 0.2EVA Global4.9 ± 0.84,8 + 0.8EVA Spine5 ± 0.54,1 + 0.9FIRST score >55 /46 patients (10.9%)6 / 47 patients (12.5%)HLA B27 presence4/46 (8.7%) (p 0.01)14/47 (29.8%)Sexemale 10 (21.3%) (p 0.001)male 19 (51.3%)ACPA00Latex Waaler-Rose1 (low titer, > 65 years)1 (low titer, > 65 years)ANA2 (low titer, < 1/320°)3 (low titer, < 1/320°)Disclosure of Interests:None declared

Background Although fractures of the proximal femur (FPF) are supposedly less frequent in Black populations (studies of incidence are rare) the life expectancy in Africa is low, which could partially explain this notion. There is only one retrospective study on the incidence of FPF in the islands of the Caribbean, thus we performed an incidence study in the insular, circumscribed, 90% Afro-Caribbean population of Martinique. The goals of this study were: (1) to estimate the incidence of FPF; (2) and to prospectively describe the main characteristics. Hypothesis The incidence of fractures of the proximal femur in Martinique is lower than in Western countries. Patients and methods The raw and standardized incidence ratio of FPF in relation to the world population was estimated based on data from the Medical Information System Program (Programme de medicalisation des systemes d’information [PMSI]) for all of Martinique for a period of 4 years (January 1, 2010 to December 31, 2013). Characteristics were based on all patients over the age of 60 who presented to the Fort-de-France University Hospital (CHU) for a FPF between December 1, 2011 and April 31, 2012. Patients with light-skin phenotype, high-energy fractures and secondary fractures were excluded from the study. Results The standardized incidence ratio in relation to the world population was estimated ( n = 794) as 22.5/100,000 patient-years [20.6–24.4]: 22.6 and 22.4/100,000 in men and women respectively. The characteristics of eighty-seven patients (including 56 women), mean age 85.3 (± 7.2) (62–100) years old were evaluated: 52 femoral neck fractures (60%) and 33 fractures of the greater trochanter (38%). The 2-month mortality rate was 21%, and 1/3 of the surviving patients could function independently. The risk of death increased in relation to the initial risk of moderate to severe dementia. Discussion The incidence of FPF in Martinique is lower than in Western countries and includes, as expected, an elderly, female population. Unlike a previous study performed in Guadeloupe, there was a majority of femoral neck fractures. A Caribbean multi-insular study is needed to confirm these results and to obtain precise data on bone density. Level of evidence IV; descriptive prospective epidemiological study.

Resume Background Les fractures de l’extremite superieure du femur (FESF) sont reputees moins frequentes dans les populations noires (rares etudes d’incidence), mais l’esperance de vie en Afrique est faible, ce qui peut expliquer en partie cette notion. Une seule etude d’incidence retrospective a ete realisee dans les iles de la Caraibe, aussi nous avons mene au sein de la population martiniquaise, captive et a plus de 90 % d’ascendance afro-caribeenne, une etude d’incidence. Les objectifs etaient : d’estimer l’incidence des FESF et de decrire les principales caracteristiques de maniere prospective. Hypothese L’incidence des FESF en Martinique est plus faible que dans les pays occidentaux. Patients et methodes L’incidence brute et standardisee sur la population mondiale a ete estimee sur les donnees du programme de medicalisation des systemes d’information (PMSI) sur l’ensemble de la Martinique sur une duree de 4 ans (01/01/2010 au 31/12/2013). Les caracteristiques ont ete decrites a partir de tous les patients âges de plus de 60 ans, ayant recouru au CHU de Fort-de-France pour une FESF entre le 01/12/2011 et le 31/04/2012. Ont ete exclus pour l’etude des caracteristiques les patients a peau claire, les traumatismes a haute energie et les fractures secondaires. Resultats L’incidence standardisee sur la population mondiale a ete estimee ( n = 794) a 22,5/100 000 patients-annees [20,6–22,4] : 22,6 et 22,4/100 000 chez les hommes et femmes respectivement. Quatre-vingt-sept patients (dont 56 femmes), d’âge moyen 85,3 (± 7,2) (62–100) ans, ont ete inclus pour l’analyse des caracteristiques : 52 cas de fractures cervicales (60 %) et 33 fractures per-trochanteriennes (38 %). A deux mois, le taux de deces etait de 21 %, et 1/3 des patients vivants etaient autonomes. Le risque de deces augmentait avec un risque initial de demence modere a severe. Discussion Les FESF en Martinique, d’incidence plus faible que dans les pays occidentaux, concernent comme attendu une population âgee et de predominance feminine. On observe une predominance des fractures cervicales, contrairement a une etude menee precedemment en Guadeloupe. Une etude caribeenne multi-insulaire est necessaire pour confirmer ces resultats et preciser les donnees de densite osseuse. Niveau de preuve IV ; etude epidemiologique descriptive prospective.

Resume Introduction L’infarctus musculaire diabetique est une complication exceptionnelle du diabete sucre. Elle concerne les patients ayant une maladie mal controlee et deja compliquee. Elle se manifeste par des douleurs musculaires avec gonflement touchant surtout les muscles de la cuisse, associees parfois a la fievre et une alteration de l’etat general. Observations Nous rapportons cinq cas d’infarctus musculaire diabetique survenant chez trois patientes originaires des Antilles presentant une forme atypique. Le diagnostic a donc ete pose sur la biopsie musculaire, permettant d’eliminer un diagnostic frequent en milieu tropical (contrairement aux zones temperees) et de pronostic redoutable, la pyomyosite. Conclusion L’existence d’infarctus musculaire diabetique chez trois patientes, complication pourtant consideree comme exceptionnelle dans la litterature au sein d’une population de petite taille, nous semble plus liee a la frequence du diabete aux Antilles qu’a un caractere proprement ethnique.

Resume Les auteurs rapportent 2 observations d'arthrite reactionnelles a anguillule (Strongyloides stercoralis), parasite dont la prevalence reste elevee aux Antilles. Ils soulignent quelques particularites cliniques, biologiques et therapeutiques de ces arthrites : affection rare, se presentant volontiers comme une spondylarthropathie, absence d'HLA B27, resistance aux AINS, contre-indication des corticoides, efficacite spectaculaire des anti-parasitaires specifiques. Le cadre nosologique et les criteres diagnostiques des rhumatismes parasitaires sont brievement discutes.

Resume Nous rapportons le resultat d'une etude prospective ouverte visant a apprecier l'efficacite d'un traitement par le methotrexate a la dose de 7,5 mg par semaine dans une population de 16 lupus erythemateux systemiques corticodependants qui necessitaient des doses quotidiennes de prednisone superieures a 15 mg. Une efficacite precoce du methotrexate a ete objectivee sur notre population des la fin du troisieme mois sur les quatre parametres evolutifs etudies: index d'activite sur echelle visuelle analogique ; dose quotidienne de prednisone ; nombre d'articulations douloureuses, et indice fonctionnel de Lee. Une amelioration a ete effective chez 13 patients, qui presentaient surtout des manifestations articulaires et cutanees du lupus erythemateux systemique, ce qui a permis une reduction de leur corticotherapie en dessous de 10 mg par jour. Un echappement secondaire est survenu dans quatre cas et n'a pas ete sensible a l'augmentation de la posologie du methotrexate a 10 mg par semaine. Seuls quatre cas d'intolerance mineure au traitement ont ete notes. Cette etude suggere un effet benefique du traitement par le methotrexate a faibles doses dans les manifestations articulaires et cutanees du lupus corticodependant et souligne son role d'epargne cortisonique.

Dengue fever (DF) is an epidemic viral mosquito-borne infection limited to tropical and subtropical countries. Biological therapies have been frequently used for the last 15 years in the treatment of inflammatory rheumatic conditions like rheumatoid arthritis. However, no data is available regarding the characteristics of this infection in patients on biological therapy. Yet, numerous patients on biotherapy have holidays in countries where DF exists. Moreover, the mosquitoes Aedes albopictus , vector of this viral disease, is now found in some developed countries such as southern Europe and the USA, allowing the possibility of a DF outbreak. We conducted a survey of individuals on biotherapy and described a case series of the patients experiencing DF. Our 8 patients on biotherapy (anti-TNF, n =6; rituximab, n =2) for a rheumatic condition did not experience severe DF.

Background Lumbar canal stenosis (LCS) is a clinicopathological and radiological disease first described in 1949, causing a neurovascular compression leading to back pain, radicular, sensory or motor deficit which treatment is difficult. Objectives The objectives of our study were appraisal of a protocolized treatment for 3 months and identification of predictive factors for failure of medical treatment. This is a prospective nonrandomized study with no control group. All patients satisfying inclusion criteria were included after clinical and radiological evaluation. Methods Clinical inclusion criteria were neurogenic claudication, radiculopathy at rest with or without back pain, mono or multirooted sensory, motor or reflex abnormalities of the lower limbs. Radiological inclusion criteria were: anteroposterior dural sac diameter 2 , reduction in the anteroposterior diameter of the spinal canal >25% on myelography in supine extended position. Results Included patients had at least one clinical and one radiological criteria. Treatment was 2 epidural injections of 125 mg hydrocortancyl 15 days apart, combined with NSAIDs or analgesic, associated with physiotherapy sessions over 2 months. 147 patients were included. Mean age was 62±13 years. F/M sex ratio is 1.3. Mean BMI was 27.5±4.3, overweight was present in 72.1%. At baseline, mean duration for back pain and radicular pain were 9.3±10.5 and 4.4±5.7years. Primary objective was evolution of the Oswestry [1] score (a low back pain disability questionnaire) at 3 months as compared to baseline. Secondary objective was the evolution of pain. At the end of treatment, the mean value for the Oswestry score decreased from 41.2 to 39.7 (p=0.17). Mean VAS for lumbar pain decreased from 53.6 to 42.1 (p BMI, duration of back and radicular pain, mean lumbar radicular VAS and mean Oswestry score at inclusion were not significantly different in improved and non improved patients. Predictors of good response to treatment were the initial presence of impulsivity cough and nocturnal pain. Conclusions In conclusion with this approach there was no significant decrease in Oswestry score, however there was a significant decrease in mean VAS lumbar and radicular pain. No predictor of poor response has been highlighted. Predictors of good response were the initial presence of impulsivity at cough and nocturnal pain. These results show the limits of medical treatment in the management of SCL. References Niskanen RO, The Oswestry Low Back Pain Disability Questionnaire. a two-year follow-up of spine surgery patients. Scand J Surg, 2002 91 (2):. P. 208-11. Disclosure of Interest None declared

Introduction L'apolipoproteine E (ApoE) est impliquee dans le metabolisme lipidique et l'atherosclerose. La distribution des alleles du gene codant pour l'ApoE (e2, e3, e4) varie selon les populations et determinerait le risque de coronaropathie. Chez les sujets afro-caribeens (AC), ce risque est moins eleve qu'attendu malgre une augmentation de la prevalence des pathologies metaboliques. Objectifs : analyser la distribution des alleles de l'ApoE selon le statut coronarien et leurs effets sur le profil metabolique. Patients et methodes Deux SNP (rs7412, rs 429358) ont ete genotypes chez 295 sujets apres signature d'un consentement eclaire lors de leur hospitalisation dans des services de medecine. Donnees anthropometriques et cardiometaboliques colligees. Equilibre de Hardy-Weinberg verifie. Analyse statistique avec le logiciel SPSS. Resultats Frequences des alleles e2, e3, e4 dans la population globale : 15,3 %, 51,2 %, 33,5 % respectivement. Cent cinquante-trois sujets etaient coronariens et 142 non coronariens. La distribution des alleles n'etait pas differente entre ces 2 groupes. Les porteurs de l'allele e4 etaient plus frequemment obeses ( p = 0,03) et dyslipidemiques ( p = 0,028) compares aux porteurs des alleles e2 et e3. La frequence de l'hypertension arterielle et du diabete n'etait pas differente selon le genotype. Chez les sujets non traites par hypolipemiants, l'allele e2 etait associe a des concentrations basses de cholesterol total compare aux alleles e3 et e4 ( p = 0,007). L'allele e4 etait associe a des concentrations elevees de HDL-CT compare aux alleles e2 et e3. Les concentrations du LDL-Cholesterol, de l'Apolipoproteine B et A-1 n'etaient pas differentes en fonction de l'allele. Conclusion Contrairement aux donnees de la litterature, les porteurs de l'allele e4 ne presentent pas de profil lipidique a risque cardiovasculaire. Les polymorphismes de l'ApoE ne semblent pas determiner de profil metabolique a haut risque cardiovasculaire et ne sont pas associes aux coronaropathies chez les sujets afro-caribeens. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Strongyloidiasis is an parasitic intestinal disease, frequent in tropical countries and fairly rare in temperate areas under certain conditions. Disseminated forms can provoke multivisceral damage.A 75 year-old woman, hospitalized for occlusion, developed multivisceral (cerebral, renal, cardiac pulmonary and hepatic) damage over 48 hours, attributed to strongyloidiasis. The diagnosis was confirmed by isolation of larvae in the tracheal and gastric aspiration fluids. Treatment combined ivermectin and albendazole.Disseminated stronglyloidiasis is essentially observed in immunodepressed patients, under corticosteroids or HTLV1 carriers, although an HIV status does not appear to intervene. Larvae can be found in all the organs. Death occurs by multivisceral failure in 50 to 70% of cases. Broncho-alveolar washing and examination of the gastric fluids is the key to diagnosis. Treatment relies on thiabendazole, ivermectin or albendazole, and the symptomatic management of all the visceral deficiencies.

Background No study describes the frequency of Behcet’s disease (BD) in the populations of African origin and its characteristics. Objectives To retrospectively assess by retrieval of multiple sources, the epidemiology and characteristics of BD in the mainly African descent population of Martinique, a French Island in the Caribbean. Methods In 2011 we consulted 5 different sources. Patients were included if they lived in Martinique, were classified as certain if they fulfilled the international criteria for BD. The diagnosis was considered only as probable if they had recurrent oral ulcers with at least one other international criteria but no other possible diagnosis. The incidence during the 1997-2011 interval and prevalence at December 31, 2010 were calculated. Basic and BD-related characteristics were recorded. Results 48 patients were indicated as BD. Only 36 (female, n=22; male, n=14) fulfilled the criteria. Mean age at diagnosis was 38.5 years old (range: 8-64), 36.6 for women and 41.6 for men. Disease onset was over 50 years old for 7 patients. Mean time between first signs and diagnosis was 4.2 years (range: 0-22). Twenty eight began their disease between 1997 and 2011 allowing a total crude mean annual incidence estimation of 0.72 new cases/10 5 inhabitants (0.79/10 5 for female and 0.59/10 5 for males, 0.37/10 5 for certain cases and 0.35/10 5 for probable). In December 2010, 28 patients were alive, 5 lost to follow up and 3 deceased: the crude prevalence was estimated as 7.04/10 5 inhabitants (Female: 7.49; male: 6.51). Genital ulcers were found in 75.6%. Dermatological manifestations were: pseudofolliculitis (52%), erythema nodosum (13.5%). Pathergy test was done for 6 patients and positive for 4. Nine patients had ophthalmologic involvement: anterior uveitis (55.5%, n=5), panuveitis and posterior uveitis (11.1%, n=1 each), conjunctival ulceration (22.2%, n=2). Parenchymal brain involvement was more frequent than non-parenchymal (7 versus 3 patients) without any cerebral venous thrombosis. Rheumatic manifestations were occurred in 20 patients (55.6%) mainly females (60%): polyarthritis (38.9%), monoarthritis and spondylarthropathy (11.1% each). Deep vein thromboses were seen in 2 cases and superficial in 1, central retinal artery occlusion in 1 patient. The colon was involved in 6 cases and the ileo-cecal region in one. Conclusions In Martinique, BD seems to be a rare disease compared to Mediterranean and most Asian countries. The incidence is comparable to Spain and Switzerland. The prevalence is higher than in most European countries and USA. Black population seems to have particular manifestations of BD: older age at onset and rare uveitis. Disclosure of Interest None Declared

Cogan's syndrome consists of non syphilitic interstitial keratitis associated with vestibuloauditory dysfunction. This syndrome is rare and very few cases have been reported since Cogan's first characterization in 1945. We present the case of a 24-year-oldman with a history of recurrent access of arthralgia and glomerulonephritis. Bilateral corneal disease consists of peripheral whitish patchy opacities in deep stroma. The patient also shows bilateral severe deafness, fever, meningeal and tetrapyramidal syndrome. Ocular involvement responds well to corticosteroids therapy but hearing loss is severe and often irreversible.

We have carried out an epidemiological study of giant cell arteritis (GCA and polymyalgia rheumatica (PR) in the French West Indies from 1982 to 1991. Twenty-five cases were followed. Incidence may be evaluated to 2,6/100 000 (GCA) and to 1,2/100 000 (PR) in population aged over 55. This is markedly lower than the reported incidence in similar socio-economical milieu in Western France.

We retrospectively studied 13 dermatomyositis in Martinique (FWI). Six of them were HTLV1 seropositive and were associated with pyramidal syndrome chronic evolution and inefficiency of usual therapy.