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Background and purpose The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29-0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score >1.5). Conclusions Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual. NHMRC [1129189, 1157717, 1140766]; Merck; Biogen; Novartis; Roche; Bayer; Schering; Sanofi Genzyme; Teva Pharmaceutical Industries

Resume La sclerose en plaques est une maladie inflammatoire chronique du systeme nerveux central d’etiologie auto-immune. Son phenotype et son evolution peuvent differer d’un patient a l’autre. L’epidemiologie et la presentation de la sclerose en plaques ont connu des modifications remarquables au cours des dernieres decennies notamment dans les pays du Maghreb. Une augmentation de la prevalence et de l’incidence surtout chez la femme a ete notee. Une severite particuliere de la maladie a ete decrite chez les patients d’origine maghrebine par rapport aux Caucasiens. Dans des etudes recentes, la progression du handicap, comparee entre les patients vivant en Afrique du Nord, les immigrants nord-africains et les Caucasiens, etait plus severe chez les patients d’origine nord-africaine. En outre, la severite de la maladie chez les Nord-Africains vivant en France, en particulier chez ceux de la deuxieme generation, a ete demontree. En effet, l’evolution de la maladie serait due a une interaction complexe entre les facteurs genetiques et environnementaux. Au cours des dix dernieres annees, les chercheurs ont valide de nombreux facteurs genetiques et expositions environnementales qui augmentent la susceptibilite a la sclerose en plaques. L’allele HLA-DRB1 * 15/01 a ete associe a un risque plus important de developper la maladie. A la predisposition genetique, s’ajoutent les facteurs environnementaux. L’infection par le virus de l’Epstein-Barr, le tabagisme, et l’alimentation etaient associes au phenotype de la maladie. Ainsi, Son heterogeneite clinique pourrait resulter d’interactions gene-environnement. Des etudes supplementaires sont necessaires pour evaluer l’effet des facteurs environnementaux et genetiques sur la sclerose en plaques aux pays du Maghreb, afin d’etablir les mecanismes en cause et etudier les strategies preventives sous nos latitudes.

International audience; Objective: To explore the associations of patient and disease characteristics with the duration of therapeutic lag for relapses and disability progression.Background: Therapeutic lag represents the delay from initiation of therapy to attainment of full treatment effect. Understanding the determinants of therapeutic lag provides valuable information for personalised choice of therapy in multiple sclerosis (MS).Design/Methods: Data from MSBase, a multinational MS registry, and OFSEP, the French national registry, were used. Patients diagnosed with MS, minimum 1-year exposure to MS treatment, minimum 3-year pre-treatment follow up and yearly review were included in the analysis. By studying incidence of relapses and 6-month confirmed disability progression, the duration of therapeutic lag was calculated by identifying the first local minimum of the first derivative after treatment start in subgroups stratified by patient and disease characteristics. Pairwise analyses of univariate predictors were performed. Combinations of determinants that consistently drove differences in therapeutic lag in pair by pair analyses were included in the final model.Results: Baseline EDSS, ARR and sex were associated with duration of therapeutic lag on disability progression in univariate and pairwise bivariable analyses. In the final model, therapeutic lag was 27.8 weeks shorter in females with ARR6 compared to those with EDSS>=6 (26.6, 18.2–34.9 vs 54.3, 47.2–61.5). Baseline EDSS, ARR, sex and MS phenotype were associated with duration of therapeutic lag on relapses in univariate analyses. Pairwise bivariable analyses of the pairs of determinants suggested ependently associated with therapeutic lag. In the final model, therapeutic lag was shortest in those with RRMS and EDSS

Background:Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear.Objective:The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms.Methods:This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores.Results:The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p Conclusion:Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.

Objective: Rare variants in the TREM2 gene have been reported to significantly increase the risk of Alzheimer’s disease in Caucasian populations. Hitherto, this association was not studied in North African populations. In this work, we aimed to study the association between TREM2 exon 2 variants and the risk of late-onset Alzheimer’s disease (LOAD) in a Tunisian population. Subjects and Methods: We sequenced exon 2 of TREM2 in a Tunisian cohort of 172 LOAD patients and 158 control subjects. We used the Fisher exact test to compare the distribution of allelic frequencies between the two groups. Results: We identified 4 previously reported nonsynonymous variants (p.Asp39Glu, p.Arg62His, p.Thr96Lys, and p.Val126Gly) and 1 novel synonymous variant (p.Gln109Gln), none of which was significantly associated with the risk of Alzheimer’s disease. Moreover, the rare TREM2 variant (p.Arg47His), which was considered to be a risk factor for Alzheimer’s disease in European descent populations, was not detected in our cohort. Conclusion: These findings do not support a major role for TREM2 in the pathogenesis of LOAD in the Tunisian population.

CONTEXT: Cervical root avulsion secondary to traumatic plexus injury is a rare etiology of superficial siderosis (SS) of the central nervous system (CNS). We describe the case of an isolated progressive compressive myelopathy revealing this complication and discuss the pathogenesis of such a presentation, its clinical and imaging peculiarities with a literature review. FINDINGS: We report on the case of a 48-year-old man with history of left brachial plexus injury at the age of 2 years. Since the age of 38 years, he had presented with a progressive paraplegia, bladder and erectile dysfunction, neuropathic pain and sensory level. The diagnosis was made by spinal cord and brain magnetic resonance follow-up imaging revealing hypointensity T2-weighted gradient echo linear dark rim around the entire neuraxis and cervical dural pseudomeningoceles. These MRI findings were suggestive of extensive hemosiderin deposition consolidating the diagnosis of SS of CNS. CONCLUSION/CLINICAL RELEVANCE: Our case report illustrates diagnosis difficulties in unusual or paucisymptomatic presentations of SS. A history of brachial plexus trauma with nerve root avulsion should prompt gradient-echo T2-weighted imaging to bring out such a complication. Superficial siderosis of the CNS should be included in the panel of differential diagnosis of the parethospastic syndromes and compressive myelopathy.

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis., National Health and Medical Research Council of Australia; Roche; Merck; Biogen; Novartis; Bayer Schering; Sanofi Genzyme; Teva

Turkoglu, Recai/0000-0001-9724-851X; Ferraro, Diana/0000-0003-4818-3806; McCombe, Pamela/0000-0003-2704-8517; Altintas, Ayse/0000-0002-8524-5087; Jokubaitis, Vilija G./0000-0002-3942-4340; Slee, Mark/0000-0003-4323-2453; Lugaresi, Alessandra/0000-0003-2902-5589; van Pesch, Vincent/0000-0003-2885-9004; Vucic, Steve/0000-0002-8323-873X WOS: 000481049900001 PubMed: 31397221 Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested. Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis. Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed. Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion. Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression. National Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia [1083539, 1129189, 1140766]; BiogenBiogen; RocheRoche Holding; Bayer ScheringBayer AG; Sanofi Genzyme; Teva; MerckMerck & Company; NovartisNovartis The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was financially supported by National Health and Medical Research Council of Australia (project grants 1083539 and 1129189 and fellowship 1140766). The MSBase Foundation is a not-for-profit organisation that receives support from Merck, Biogen, Roche, Novartis, Bayer Schering, Sanofi Genzyme and Teva. The study was conducted separately and apart from the guidance of the sponsors.

Patients with the ‘aggressive’ form of MS accrue disability at an accelerated rate, typically reaching EDSS >= 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive MS, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive MS is essential to optimise treatment in this MS subtype. We evaluated whether patients who will develop aggressive MS can be identified based on early clinical markers, and to replicate this analysis in an independent cohort. Patient data were obtained from MSBase. Inclusion criteria were (a) first recorded disability score (EDSS) within 12 months of symptom onset, (b) at least 2 recorded EDSS scores, and (c) at least 10 years of observation time. Patients were classified as having ‘aggressive MS’ if they: (a) reached EDSS >= 6 within 10 years of symptom onset, (b) EDSS >=6 was confirmed and sustained over >=6 months, and (c) EDSS >=6 was sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalisation). Predictors were evaluated using Bayesian Model Averaging (BMA). Independent validation was performed using data from the Swedish MS Registry. Of the 2,403 patients identified, 145 were classified as having aggressive MS (6%). BMA identified three statistical predictors: age > 35 at symptom onset, EDSS >= 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive MS (AUC = .80, 95% CIs = .75, .84). The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish MS Registry cohort, 34 (6%) met criteria for aggressive MS. The combination of all three signs was also predictive in this cohort (AUC = .75, 95% CIs = .66, .84). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive MS.

Summary Objectives To describe the EEG characteristics of patients with Unverricht-Lundborg disease (ULD) and their changes during the long-term evolution of the disease. Methods A retrospective study including all patients with ULD confirmed by molecular biology and more than 15 years’ duration of disease progression at the time of inclusion. EEGs were recorded at inclusion, 2 years and 5 years of follow-up. Patients who discontinued treatment during follow-up had an EEG monitoring 1 year after reintroduction of therapy. Results Forty-seven EEGs were performed in 17 patients. The mean age at onset was 12.0 ± 5.5 years. The mean duration of follow-up was 26.5 ± 6.9 years. The average background rhythm was 8.2 c/s, and was normal in 30 EEGs (64%), slow in 17 (36%) and disorganized in 11 (23%). Epileptic abnormalities were found in 22 EEGs (47%). Myoclonic jerks were found in 13 EEGs (28%). After re-adaptation of antiepileptic medication in patients who had previously stopped treatment, control EEG showed a normal background rhythm with no epileptic abnormalities throughout the monitoring period. Conclusion This study shows that the progressive disappearance of EEG abnormalities is rather due to antiepileptic treatment than a gradual spontaneous tendency to decrease over time.

Non-motor symptoms (NMS) of Parkinson Disease (PD) are common and can cause severe disability. They are often under-recognized and remain untreated. Tools to evaluate these symptoms in Arabic-speaking patients are still lacking. The objective of this study was to evaluate an Arabic version of the non-motor symptoms scale (NMSS) of PD as an instrument for measuring NMS in Arabic-speaking patients. Sixty-two PD patients clustered around Hoehn & Yahr Stages 2–3 were evaluated by the Arabic version of NMSS. They also underwent a battery of standard psychometric assessment measures that included the scales for outcomes of Parkinson’s disease-autonomic (SCOPA-AUT), the Pittsburgh sleep quality index (PSQI), the Beck depression inventory, the geriatric depression scale (GDS), the mini-mental state examination (MMSE), the visual analogical scale for pain(VAS) and the neuro-psychiatric inventory (NPI). The metric properties of the NMSS were studied as well as its correlation with other standard tests evaluating NMS. The mean NMSS score was 82 ± 56 (skewness 0.88). There were highly significant correlations between the NMSS and the SCOPA-AUT as well as the NMSS and PSQI scores. Significant positive correlations between NMSS and GDS, BECK and VAS were also observed. The sleep/fatigue domain significantly correlated with the PSQI, the cardiovascular/urinary/sexual function/gastrointestinal domains significantly correlated with the SCOPA-AUT, the mood/cognition domain significantly correlated with the GDS and BECK findings. The mean Cronbach’s alpha coefficient was 0.87, showing a satisfactory internal consistency. The Arabic version of NMSS can be considered a comprehensive and reliable measure for non-motor symptoms in Arabic-speaking PD patients.

Background Few epidemiological data are available on multiple sclerosis (MS) patients in North Africa (NA). Studies of immigrants from NA showed a more aggressive course compared to European patients. Objective The aim of this study is to describe clinical and long term course characteristics of MS in Tunisia and to compare it to European cohorts. Method A total of 437 MS patients from three hospital based cohorts in Tunisia and having prospective follow up between 2010 and 2012 were analyzed. We considered as endpoints the time to reach EDSS scores of 3, 4 and 6 in the different clinical forms of MS and the beginning of a secondary progressive (SP) phase. Results Sex ratio was 2.34. Mean age of onset was 30.3 years. The course was relapsing–remitting (RR) in 91% of patients and primary progressive (PP) in 9%. The most frequent isolated onset symptoms were respectively motor (28%), optic neuritis (20%) and sensory (16%) dysfunction. Median time to SP onset was 19.1 years. Median times from onset of multiple sclerosis to assignment of a score of 3, 4 and 6 were 8, 10.7 and 15 years respectively. Benign form of MS represented 31.5%. Median interval from the onset of the disease to EDSS score of 3, 4 and 6 was shorter in PP-MS than in RR-MS. However, there was no difference between these two groups for the median time from the assignment of EDSS 4 to the assignment EDSS 6. Conclusions Our study shows that Tunisian MS patients have a quite similar clinical feature to European patients. Still, larger MS multicenter cohort studies in NA with longer follow-up duration could clearly respond to the issue.

Resume Introduction Le syndrome du canal carpien (SCC) est le plus repandu des syndromes canalaires du membre superieur. Il est frequent chez les patients hemodialyses. Le role de la fistule arterioveineuse a ete incrimine mais conteste. L’objectif de cette etude etait de confirmer cette relation. Methodes Nous avons realise un examen electroneuromyographique systematique chez tous les patients hemodialyses chroniques par fistule arterioveineuse (FAV) entre janvier 2003 et decembre 2010. Nous avons uniquement inclus, pour cette etude, les patients ayant une FAV unilaterale. Resultats Ainsi, 134/155 patients examines ont ete inclus. Un SCC a ete retrouve chez 106 patients et etait infraclinique dans 42 % des cas. Il etait significativement plus frequent ( p p = 0,08). La survenue du SCC etait, par ailleurs, uniquement correlee a la duree de la dialyse ( p = 0,005). Cette duree etait significativement plus courte chez le diabetique ayant un SCC. Conclusion L’existence d’une correlation positive entre le cote de la FAV et le developpement d’un SCC confirme le role pathogene de cette derniere. Le risque augmente chez ces patients avec la duree de l’hemodialyse et la presence de diabete.

Cerebral malaria is characterized by various non-specific neurologic features with usually diffuse cerebral edema on magnetic resonance imaging. We report on an exceptional case of cerebral malaria with isolated parkinsonism and bilateral substantia nigra involvement. We discuss the pathophysiology leading to involvement of substantia nigra and treatment options.

Mycoplasma pneumoniae is a common cause of respiratory tract infection. Extra-pulmonary complications of M. pneumoniae infection include neurologic complications involving the central nervous system. Myelitis is one of the most severe complications of central nervous system. We report a unique case of acute transverse myelitis associated with M. pneumoniae infection in a 3-year-old boy with particular imaging and clinical course features. Intravenous corticosteroids were prescribed with an 8 wk tapering of oral corticosteroids resulting in full recovery. We postulate an immune-mediated mechanism.

Objective:To compare multiple sclerosis (MS) disability progression among North Africans (NAs) living in France (NAF) and in Tunisia (NAT) and Caucasian patients born and living in France (CF).Methods:Patients with MS admitted to the day hospital in the Neurology Department at Pitié-Salpêtrière Hospital (France) and Razi Hospital (Tunisia) were questioned on their place of birth and the place of birth of their parents. To compare delay to outcomes, log-rank tests were used. Univariate and multivariate Cox models were used to determine factors influencing time to Expanded Disability Status Scale (EDSS) 6.Results:We consecutively included 462 patients: 171 CF, 151 NAT, and 140 NAF. Sex ratio, disease forms, and delay from disease onset to diagnosis were similar between the groups. NAF differed from other groups, with a shorter median time to reach EDSS 3, 4, and 6, and a more frequent incomplete recovery after first relapse (p < 0.0001). Furthermore, the NA second-generation group showed the youngest median age at onset (26.5 ± 8.8 years, p = 0.001), the shortest median time to EDSS 6 in relapsing-remitting patients, and an increased mean number of relapses during the first 5 years of the disease (6.1 ± 3.7, p = 0.01) compared to CF. The Cox proportional hazard models demonstrate that (1) NA ethnicity is a significant predictor of fast progression even when adjusting for major covariates and (2) treatment did not influence the models.Conclusion:Our study further supports severity of MS in NAs and unravels the particular severity in NAs living in France, mainly for the second generation.

Introduction La sclerose laterale amyotrophique (SLA) a ete longtemps consideree comme une maladie purement motrice. Une deterioration cognitive et comportementale et un pattern fronto-temporale ont ete decrits chez ces malades. Objectifs Etudier le profil cognitif de patients tunisiens atteints de SLA et determiner la frequence de l’atteinte executive et son eventuelle correlation avec la forme de debut de la maladie. Patients et methodes Il s’agit d’une etude retrospective incluant des patients atteints de SLA suivis au service de neurologie du CHU Razi. Les donnees cliniques ont ete precisees. Nous avons recueilli les resultats du Mini-Mental State Examination (MMSE) et de la Batterie Rapide d’Efficience Frontale (BREF) quand cela etait possible. La BREF etait consideree comme alteree si score Resultats Nous avons inclus 66 patients. L’âge moyen etait de 56 ans, le sex-ratio etait de 1,6.le debut etait spinal dans 76,9 % des cas. Quatorze patients avaient des plaintes fonctionnelles cognitives. Le score MMSE moyen etait de 26/30. Le score moyen de la BREF etait de 15/18. Elle etait alteree dans 33 % cas. Il n’existait pas de correlation significative entre l’existence de troubles cognitifs et la forme de debut de la maladie. Discussion Dans notre etude, une atteinte executive a ete observee chez 33 % des cas. En effet, il existe un dysfonctionnement cognitif chez 30 a 50 % des patients SLA, affectant particulierement les fonctions executives. Les formes a debut bulbaire sont considerees comme un facteur de risque, cela a ete infirme dans notre etude probablement en rapport avec la taille reduite de l’echantillon. Conclusion Les troubles cognitifs sont frequents dans notre serie. Un depistage precoce de la deterioration cognitive chez ces patients est primordial. L’utilisation de tests adaptes est necessaire pour une meilleure individualisation.

Introduction Le phenomene d’Uhthoff est frequent au cours de la sclerose en plaques (SEP). Peu d’etudes se sont interessees a ce phenomene en Afrique. Objectifs Evaluer l’incidence et les caracteristiques cliniques du phenomene d’Uhthoff chez les patients tunisiens suivis pour une SEP. Patients et methodes Nous avons utilise un questionnaire pour les patients SEP au service de Neurologie a l’hopital Razi (Tunisie) du 1 octobre au 30 novembre 2016 concernant des symptomes neurologiques transitoires et brefs declenches et/ou aggraves par une augmentation de la temperature corporelle. Nous avons inclus les patients presentant un phenomene d’Uhthoff. Leurs symptomes ont ete classes : moteur (faiblesse, trouble de l’equilibre), sensitif, visuels (flou visuel, diplopie) et vesicosphincteriens (fuite). Resultats Quarante-cinq patients inclus avec un âge moyen de 40,2 ans. Le phenomene d’Uhthoff etait note chez 62,2 % des patients avec predominance des symptomes moteurs (67,8 %) suivis par ceux visuels (46,4 %) et sensitifs (32,1 %). Quinze patients avaient deux types de symptomes ou plus. Les symptomes survenaient apres un delai de 5 a 60 minutes (19,6 minutes) et disparaissaient completement apres 5 minutes a 3 heures (45,8 minutes). La marche etait le principal facteur declenchant (64,2 %). Discussion La frequence du phenomene d’Uhthoff n’a pas ete etudiee dans les pays Afrique. En effet, notre etude a objective une frequence importante conformement aux pays asiatiques (48,1 %) et occidentaux (80 %). Le principal facteur connu est l’exercice comme la marche qui etait le plus frequent dans notre etude. Le bloc de conduction transitoire a ete propose comme principal mecanisme physiopathologique sous-jacent. Conclusion Le phenomene d’Uhthoff etait frequent dans notre population tunisienne, ce qui augmente le retentissement de la maladie sur la vie quotidienne de nos patients.

Introduction La maladie d’Alzheimer (MA) constitue un probleme de sante publique en Tunisie et dans le monde. L’etude de ses facteurs determinants a ete peu etudiee dans notre population. Objectifs Comparer les caracteristiques de la MA en fonction de l’âge de debut, determiner la correlation entre le genotype APOE et le phenotype clinique. Patients et methodes Dans une etude transversale descriptive et retrospective menee entre 2002 et 2015, nous avons inclus les patients ayant un diagnostic de MA. Nous avons reparti les patients en 2 groupes selon l’âge de debut de la maladie (precoce ou tardif). L’etude du profil genotypique de l’APOE a concerne les patients ayant eu un prelevement d’ADN. Les donnees ont ete comparees entre les sous-groupes classes en fonction du statut APOE. Resultats Un total de 1692 patients MA ont ete inclus. Le sex-ratio etait de 0,72. Un debut precoce a ete retrouve dans 22,1 % des cas. Deux cent quatre-vingt-dix patients ont eu une etude genotypique APOE. Les frequences alleliques etaient de 68,27 % pour ɛ3, 30,17 % pour ɛ4 et 1,55 % pour ɛ2. Une frequence plus elevee du genotype APOEɛ4/ɛ4 a ete retrouvee dans la tranche d’âge de debut 60–69 ans (p = 0,05). Le delire et les myoclonies etaient significativement plus frequents chez les patients ɛ4+. Discussion La frequence elevee de l’APOE ɛ4 dans notre etude, comparativement a la population generale saine, lui confere le statut de facteur de risque majeur de MA dans notre population. Des caracteristiques phenotypiques similaires associees a cet allele ont ete precedemment rapportees. Un impact maximal de l’effet de l’allele ɛ4 sur la tranche d’âge de debut 60–70 ans a ete evoque. Conclusion La presence de l’APOEɛ4 influence la revelation de la MA dans la tranche d’âge 60–69 ans. Son impact sur le phenotype clinique se manifeste par une frequence elevee de delire et de myoclonies.

Background Recent studies on date of birth of multiple sclerosis (MS) patients showed an association between month of birth and the risk of developing MS. This association has not been investigated in an African country. Objective We aimed to determine if the risk of MS is associated with month of birth in Tunisia. Methods Data concerning date of birth for MS patients in Tunisia (n=1912) was obtained. Birth rates of MS patients were compared with all births in Tunisia matched by year of birth (n=11,615,912). We used a chi-squared analysis and the Hewitt's non-parametric test for seasonality. Results The distribution of births among MS patients compared with the control population was not different when tested by the chi-squared test. The Hewitt’s test for seasonality showed an excess of births between May and October among MS patients (p=0.03). The peak of Births of MS patients in Tunisia was in July and the nadir in December. Conclusion Our data does support the seasonality hypothesis of month of birth as risk factor for MS in Tunisia. Low vitamin D levels during pregnancy could be a possible explanation that needs further investigation.

Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy reported in patients with renal failure undergoing periodic haemodialysis. The role of arteriovenous fistula was discussed. The aim of this study was to investigate this relationship.Subjects for this study were hemodialysis patients who underwent systematic electroneuromyography between January 2003 and December 2010. Only patients with unilateral fistulae were included for the study.One hundred and thirty-four out of 155 patients were examined. CTS was noted in 106 patients and was detectable only in ENMG in 42% of cases. It was more frequent (P0.001) and more severe in the side of fistulae (P=0.08). Besides, development of CTS was only correlated with the longer duration of dialysis (P=0.005). This duration was significantly shorter in patients with CTS and diabetes.The positive correlation between CTS and aretriovenous fistulae confirms the pathogenic role of this latter. The risk rises in these patients with the duration of hemodialysis and the presence of diabetes.

Background Data from African countries regarding diagnosis, prognosis, management, and outcome of patients with cerebral venous thrombosis (CVT) are limited. The aim of the present study is to characterize clinical presentation, predisposing factors, neuroimaging findings, and outcomes of the disease in the Tunisian population. Methods This is a prospective study including patients referred to the Neurology Department of the Military Hospital of Tunis between January 2009 and December 2012. The diagnosis of CVT was confirmed in all patients using magnetic resonance imaging and magnetic resonance venography. The demographic, clinical, radiological, and outcome data were recorded and analyzed. Median follow-up was 16 months (range 6 months to 4 years). Primary outcome was death or dependency as assessed by modified Rankin score more than 2 at the end of follow-up. Results This study included 41 patients with CVT. Mean age was 41.24 years, predominantly women (68%). The mode of onset was acute in 10 patients (24%), subacute in 26 (64%), and chronic in 5 (12%). The most common presenting features were headache, observed in 83% of the patients, followed by seizures, focal motor deficits, papilledema, and mental status changes. Lateral (56%) and superior longitudinal (51%) sinuses were the most commonly involved. Multiple sinuses were involved in 46% of cases. Nineteen patients (46%) had a d -dimer level more than 500 ng/mL. Major causes of CVT were thrombophilia (56%), either genetic or acquired, obstetric and gynecological (50%), and septic (34%). Outcome was favorable in 83% of patients. At the end of follow-up, 32 patients (78%) had complete recovery (modified Rankin Scale [mRs] score 0-1), 2 (5%) had partial recovery (mRs score 2), and 4 (10%) were dependent (mRs score 3-5). One patient (2.5%) had a recurrent sinus thrombosis. Conclusions Our Tunisian population presented distinct risk factors profile with high frequency of thrombophilia, infections, and postpartum state. Oral contraceptive use is not a major risk factor in our population. The overall prognosis was good.

Introduction La Sclerose Laterale Amyotrophique (SLA) est une pathologie neurodegenerative rare, caracterisee par une atteinte des neurones moteurs centraux et peripheriques. Peu de series africaines se sont interessees a ce sujet. Objectifs Decrire les caracteristiques phenotypiques cliniques et evolutives des patients presentant une SLA dans une serie tunisienne. Patients et methodes Il s’agit d’une etude descriptive prospective, realisee au service de neurologie de l’hopital Razi, Tunisie, sur une periode de 13 ans (juin 2002–novembre 2016) incluant tous les patients ayant une SLA definie selon les criteres d’ESCORIAL revises. Les donnees cliniques, evolutives et therapeutiques ont ete recueillies. Resultats Nous avons inclus 130 patients, l’âge moyen etait de 56,2 ans, l’âge moyen de debut etait de 53,1 ans, le delai diagnostique moyen etait de 3 ans, un debut spinal a inaugure le tableau dans 76 % des cas, des formes juveniles etaient retrouvees dans 7,6 %. Le score ALSFRS moyen initial etait de 39,2. Au total, 49,5 % des patients etaient sous Riluzole, 7,6 % des patients avaient recours a la ventilation non invasive. La survie moyenne etait de 4,2 ans. Discussion Dans notre serie caracterisee par un delai diagnostique assez long, une frequence elevee du debut spinal et des formes juveniles et une survie moyenne plus longue. Ces elements sont consideres de bon pronostic. Toutefois nous n’avons pas releve de differences significatives par rapport aux autres etudes quant a l’âge de debut, le sex-ratio et la frequence des formes familiales. Conclusion Notre etude a permis de relever certaines caracteristiques de la SLA dans la population tunisienne. Des etudes multicentriques sont necessaires pour une meilleure caracterisation phenotypique de la SLA en Afrique.

Introduction Les polyradiculoneuropathies inflammatoires chroniques (PRNc) sont des neuropathies demyelinisantes acquises. Elles sont majoritairement idiopathiques mais elles peuvent etre associees a des maladies diverses. Objectifs Etudier le profil epidemiologique, clinique, electrophysiologique, les modalites therapeutiques et evolutives des patients suivis pour PRNc associee. Patients et methodes Il s’agit d’une etude retrospective menee sur 12 ans (janvier 2004–decembre 2015) au service de neurologie de l’hopital Razi de La Manouba incluant tous les patients presentant une PRNc associee. Nous avons collecte pour chaque patient les donnees cliniques, electrophysiologiques, biologiques, etiologiques therapeutique et le profil evolutif. Resultats Nous avons collige 23 patients. L’âge de debut moyen etait de 41,5 ans avec un sex-ratio = 6. Les etiologies etaient l’exposition aux toxiques (8 cas), diabete (7 cas), lymphome (3 cas), hepatite C (2 cas), paludisme (1 cas), amylose (1 cas), gammapathie (1 cas). Le tableau revelateur etait moteur dans 69 %. L’examen a trouve areflexie (56 %) et troubles de la sensibilite (86 %). Le traitement recu etait un immunomodulateur (32 %) associe a un traitement specifique. Discussion Nous avons note une nette predominance masculine. L’origine toxique etait la plus frequente contrairement a la litterature. La prise en charge repose sur un traitement immunomodulateur ou immunosuppresseur associee a un traitement specifique. L’evolution dependra de la pathologie associee. Conclusion Les etiologies d’une PRNc associee sont multiples dominees dans notre serie par le diabete et l’exposition aux toxiques.

Introduction Les syndromes neurologiques paraneoplasiques (SNP) sont des manifestations neurologiques associees aux cancers en dehors d’un envahissement tumoral ou de complications secondaires identifiees. Les formes non classiques sont peu connues. Objectifs Decrire les caracteristiques cliniques et biologiques des SNP non classiques et analyser les differentes associations aux anticorps onconeuronaux (AON). Patients et methodes Nous avons realise une etude descriptive transversale, sur 9 ans, au sein du service de neurologie de l’hopital Razi, incluant les patients ayant un SNP non classique selon les criteres de l’Euronet Group de 2004. Resultats Nous avons collige 37 patients ayant un SNP dont 23 presentaient une forme non classique. L’âge moyen etait de 60,9 ans avec sex-ratio = 1,3. L’atteinte du systeme nerveux central etait dominee par les tableaux de SLA like (7 cas). L’atteinte peripherique etait dominee par les polyneuropathies (7 cas). Les anticorps onconeuronaux (AON) etaient positifs dans 12 cas avec une predominance des Ac anti-Yo et anti-Ma2. Des tumeurs etaient identifiees dans 13 cas. Discussion La frequence elevee des SNP non classiques caracterise notre serie. Il s’agit habituellement de polyneuropathies. Les tableaux de SLA like retrouves etaient frequents et polymorphes. Le diagnostic etait oriente par le dosage des AON domines par les Ac anti-Ma2 et anti-Yo contrairement a la litterature ou une predominance des Ac anti-Hu etait rapportee. Conclusion La frequence elevee des SNP non classiques temoigne de l’interet du dosage des AON dans le diagnostic positif. Les differences retrouvees seraient liees a des facteurs genetiques et environnementaux.

Introduction Few epidemiological data on multiple sclerosis (MS) patients are available in North Africa (NA). Studies of immigrants from NA showed a more aggressive course of MS in NA than in European patients. Objective To describe clinical, long term course characteristics and prognostic factors of MS in a Tunisian population. Methods We performed a prospective multicentric study of 437 MS patients in Tunisia between 2010 and 2012. We considered as endpoints the time to reach non-reversible disability levels corresponding to EDSS scores of 3.0, 4.0 and 6.0, and the beginning of a secondary progressive phase. We used Kaplan–Meier analyses and Cox regression models to determine the influence of the clinical variables on the time to disability onset. Results Sex ratio was 2.34. Mean age of onset was 30.3±9.5 years and the duration of illness was 8.4±6.7 years. The course was relapsing-remitting (RR) in 77% of patients, secondary progressive (SP) in 15.5% and primary progressive (PP) in 8.5%. Median time to secondary progressive onset was 19.1 years. Median times from onset of multiple sclerosis to assignment of a score of 3, 4 and 6 were 8, 10.7 and 15 years respectively. A greater number of functional systems involved at onset, progressive from as well as late age, motor, cerebellar and sphincter symptoms at onset were factors predictive of a poor outcome. A longer first inter-attack interval was associated with a better prognosis. Once EDSS 4 was reached, the time course of progressive disability was similar in patients with progressive onset and those with RR MS. Conclusion This is the first multicentric study in our country. The present study showed a similar course of MS in a North African population compared to European cohorts. Similar long term prognosis factors were found.