Clinical features and prognosis of amyotrophic lateral sclerosis in Africa: the TROPALS study.

OBJECTIVE: We describe and compare the sociodemographic and clinical features, treatments, and prognoses and survival times of patients with amyotrophic lateral sclerosis (ALS) in Africa. METHODOLOGY: We conducted a multicentre, hospital-based cohort study in Africa. Patients with ALS diagnosed in the neurology departments of participating hospitals from 2005 to 2017 were included. Subgroup analysis was performed by subcontinent. Survival analyses were conducted using the Cox proportional hazards model. RESULTS: Nine centres from eight African countries participated. A total of 185 patients with ALS were included: 114 from Northern Africa, 41 from Western Africa and 30 from Southern Africa. A male predominance (male to female ratio 2.9) was evident. The median age at onset was 53.0 years (IQR 44.5-64.0 years). The onset was bulbar in 22.7%. Only 47 patients (26.3%) received riluzole, mainly in Northern and Western Africa. The median survival from the time of diagnosis was 14.0 months (95% CI 10.7 to 17.2 months). The median survival was longer in Northern Africa (19.0 months, 95% CI 10.8 to 27.2 months) than in Western (4.0 months, 95% CI 0.8 to 7.1 months) and Southern (11.0 months, 95% CI 5.6 to 16.4 months) Africa (Breslow test, p<0.0001). Both subcontinental location and riluzole treatment independently affected survival. CONCLUSION: More African patients with ALS were male and younger and exhibited a lower proportion of bulbar onset compared with patients with ALS from Western nations. Survival was consistent with that in Western registers but far shorter than what would be expected for young patients with ALS. The research improves our understanding of the disease in Africa.

Characteristics and Prognosis of Oldest Old Subjects with Amyotrophic Lateral Sclerosis.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is an age-related neurodegenerative disease with unclear characteristics and prognosis in the oldest old (80 years and over). The aim of this study was to compare the oldest old and younger ALS patients in terms of clinical and socio-demographic characteristics, and prognosis. METHODS: ALS incident cases from the register of ALS in Limousin (FRALim), diagnosed between January 2000 and July 2013, were included. Descriptive and comparative analyses by age group were carried out. For time to event univariate analysis, Kaplan-Meier estimator and log rank test were used. Univariate and multivariate survival analyses were carried out with Cox's proportional hazard model. RESULTS: Out of 322 patients, 50 (15.5%) were aged 80 or over ("oldest old" ALS) at the time of diagnosis. Among them, the male:female gender-ratio was 1.27, and 32.6% had a bulbar onset (not different from subjects aged less than 80 years). With increasing age, there was a worsening of the clinical state of the patients at time of diagnosis in terms of weight loss, forced vital capacity, ALSFRS-R and manual muscular testing. Access to ALS referral centres decreased with age, and the use of riluzole tended to be lower in the oldest old group. The median survival of oldest old patients appeared to be 10 months shorter than that of subjects aged less than 80 years (7.4 vs. 17.4 months). CONCLUSION: The survival of oldest old ALS patients is particularly short. It relates to prognostic features at baseline and to an independent effect of advanced age.

Epidemiological evidence that physical activity is not a risk factor for ALS.

To elucidate whether physical activity (PA) and sport increase the risk of developing amyotrophic lateral sclerosis (ALS), a literature review of epidemiological studies was conducted according to the Meta-analysis of Observational Studies in Epidemiology guidelines. Six databases (Pubmed, Scopus, ScienceDirect, IngentaConnect, Refdoc and the Cochrane database) were searched to April 2014. Experts were asked to identify studies in press. Studies of interest were examined for their level of evidence and synthetized using Armon's classification for exogenous risk factors for ALS. Of 37 epidemiological works included in the review, two (5.5%) provided class I evidence, and five (13.5%) class II. Others offered evidence of class III (n = 8, 21.6%), IV (n = 16, 43.2%) and V (n = 6, 16.2%). Results were stratified according to type of exposure: (1) PA related to sport and work (n = 14), (2) soccer and American football (n = 9), (3) occupation (n = 12), (4) proxies of PA (n = 2). Among articles which considered "PA related to sport and work", two class I studies and one class II study concluded that PA is not a risk factor for ALS. This evidence establishes (level A) that PA is not a risk factor for ALS. As regards "occupational related activity" a level of evidence of U was obtained (it is unknown whether the professional category "physical worker" is a risk factor for ALS). Football/soccer may be considered as a possible risk factor for ALS (level C) and there is a need for further research taking into account the numerous confounding factors that may arise in this field.

Multicenter evaluation of light transmission platelet aggregation reagents: communication from the ISTH SSC Subcommittee on Platelet Physiology.

BACKGROUND: Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory harmonization. OBJECTIVES: The primary objective was to assess whether sources of activators (mainly adenosine diphosphate [ADP], collagen, arachidonic acid, epinephrine, and thrombin receptor activating peptide6) and ristocetin contribute to poor LTA reproducibility. The secondary objective was to evaluate interindividual variability of results to appreciate the distribution of normal values and consequently better interpret pathologic results. METHODS: An international multicenter study involving 28 laboratories in which we compared LTA results obtained with center-specific activators and a comparator that we supplied. RESULTS: We report variability in the potency (P) of activators in comparison with the comparator. Thrombin receptor activating peptide 6 (P, 1.32-2.68), arachidonic acid (P, 0.87-1.43), and epinephrine (P, 0.97-1.34) showed the greatest variability. ADP (P, 1.04-1.20) and ristocetin (P, 0.98-1.07) were the most consistent. The data highlighted clear interindividual variability, notably for ADP and epinephrine. Four profiles of responses were observed with ADP from high-responders, intermediate-responders, and low-responders. A fifth profile corresponding to nonresponders (5% of the individuals) was observed with epinephrine. CONCLUSION: Based on these data, the establishment and adoption of simple standardization principles should mitigate variability due to activator sources. The observation of huge interindividual variability for certain concentrations of activators should lead to a cautious interpretation before reporting a result as abnormal. Confidence can be taken from the fact that difference between sources is not exacerbated in patients treated with antiplatelet agents.

Clinical management and disease-modifying treatment for amyotrophic lateral sclerosis in African hospital centers: the TROPALS study.

Objective: To assess the availability of health workers and medications for clinical management of amyotrophic lateral sclerosis (ALS) in African hospital centers. Availability and affordability analyses of disease-modifying treatments were performed. Methods: A multicenter observational study involving African hospitals was conducted. A standard questionnaire was developed based on the European Federation of the Neurological Societies (EFNS) guidelines. We collected data on multidisciplinary care and availability of medicines. The availability and affordability were evaluated according to the WHO guidelines. Results: Nine hospital centers from eight African countries participated. We observed a low degree of implementation of multidisciplinary care in ALS management. Riluzole was only available in centers from South Africa, Senegal, Tunisia, and Togo. This treatment was unaffordable and the adjusted price was highly variable among countries. The cost of riluzole was partly or fully covered by patients, which implies a substantial economic burden. Conclusion: Our findings strengthen the need to promote multidisciplinary care in the clinical management of ALS in Africa. Disease-modifying medication should be both available and affordable. Local and international collaboration is needed to improve ALS health care access in Africa.

Exploring the diagnosis delay and ALS functional impairment at diagnosis as relevant criteria for clinical trial enrolment.

Objectives were: i) to describe the phenotypic heterogeneity of incident amyotrophic lateral sclerosis (ALS) patients diagnosed in 2012 in French ALS centres; ii) to look at the associations between ALSFRS-R score and ALSFRS-R slope (ΔFS) at time of diagnosis with diagnosis delay, ALS phenotypes and Airlie House diagnosis criteria (AHDC); iii) to describe the rate of progression on ΔFS, according to diagnosis delay. METHODS: Incident ALS cases diagnosed in French ALS centres were included. The rate of progression was evaluated as follows: ΔFS = (48 - ALSFRS-R at time of diagnosis)/duration from onset to diagnosis (months). Fast and slow progressors were defined by ΔFS >1 and <0.5, respectively. RESULTS: At time of diagnosis, 476 patients were classified into eight phenotypes: bulbar (33.0%), spinal lumbar (28.2%), spinal cervical (23.1%), flail leg (4.4%), ALS/FTD (4.2%), possible flail arm (4.0%), respiratory (2.1%), dropped-head (1.0%). Median ΔFS (n = 358/476) was 1.0 [0.5-2.0]. ΔFS was associated with AHDC (p = 0.009), but not with clinical phenotype (p = 0.902). Stratification on diagnosis delay (<12 months or ≥18 months) allowed to differentiate fast progressors from slow progressors. CONCLUSION: At time of inclusion in therapeutic trial closed to diagnosis, ΔFS or diagnosis delay may discriminate the rate of progression.

Prognostic value of early epileptic seizures on mortality and functional disability in acute stroke: the Dijon Stroke Registry (1985-2010).

We aimed to evaluate the prognostic value of early epileptic seizures after stroke. All consecutive patients with a first-ever stroke were prospectively identified within the population of Dijon, France, thanks to a population-based registry, from 1985 to 2010. Early epileptic seizures were defined as seizures occurring within 14 days after stroke onset. Outcomes were 1-month and 1-year mortality, and severe functional handicap at discharge. Of the 4,411 stroke patients included, data about seizures were available in 4,358 (98.8, 53.5 % women, mean age, 74.1 ± 14.8 years). Among these patients, 134 (3.1 %) had early seizures. Stroke patients with early seizures differed from those without seizures, as there was a higher proportion of hemorrhagic stroke, higher blood glucose level at admission, smoking status, and more frequent impaired. Higher risks of 1-month and 1-year mortality in patients with early seizures (unadjusted HR 1.45, 95 % CI 1.00-2.10; HR = 1.59, 95 % CI 1.21-2.09, respectively) disappeared (HR 0.71, 95 % CI 0.49-1.08 and HR 0.85, 95 % CI 0.64-1.17) after adjustment for stroke severity and other confounding factors. Early seizures were associated with severe handicap in unadjusted analyses (OR 2.07, 95 % CI 1.46-2.95) but the association was no longer significant after multivariable adjustment (OR 1.12, 95 % CI 0.69-1.83). Early epileptic seizures were not associated with higher risks of mortality at 1 month and 1 year or with unfavorable functional outcome after acute stroke. The adverse effects of epileptic seizures may not be distinguishable from stroke severity, which is strongly related to epileptic seizures.