Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

<p>Abstract</p> <p>Background</p> <p>Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control.</p> <p>Methods</p> <p>We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL).</p> <p>Results</p> <p>The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ)(15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05).</p> <p>Conclusions</p> <p>There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.</p

Spinal trigeminal neurons demonstrate an increase in responses to dural electrical stimulation in the orofacial formalin test

Primary headaches are often associated with pain in the maxillofacial region commonly classified under the term “orofacial pain” (OFP). In turn, long-lasting OFP can trigger and perpetuate headache as an independent entity, which is able to persist after the resolution of the main disorder. A close association between OFP and headache complicates their cause and effect definition and leads to misdiagnosis. The precise mechanisms underlying this phenomenon are poorly understood, partly because of the deficiency of research-related findings. We combined the animal models of OFP and headache—the orofacial formalin test and the model of trigeminovascular nociception—to investigate the neurophysiological mechanisms underlying their comorbidity. In anesthetized rats, the ongoing activity of single convergent neurons in the spinal trigeminal nucleus was recorded in parallel to their responses to the electrical stimulation of the dura mater before and after the injection of formalin into their cutaneous receptive fields. Subcutaneous formalin resulted not only in the biphasic increase in the ongoing activity, but also in an enhancement of neuronal responses to dural electrical stimulation, which had similar time profile. These results demonstrated that under tonic pain in the orofacial region a nociceptive signaling from the dura mater to convergent trigeminal neurons is significantly enhanced apparently because of the development of central sensitization; this may contribute to the comorbidity of OFP and headache

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.Observatoire Français de la Sclérose en Plaque

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. OBJECTIVE: To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. METHODS: Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. RESULTS: A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. CONCLUSION: MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated.journal article2016 Nov2016 09 01importe

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Risks and success conditions for the French sanitary service of health students

International audienceAbstract Background French sanitary service of health students was a pledge of the French Presidency. It is mainly presented as a massive information campaign on good practices in health made by “thousands of health students going into the enterprises and schools”. We tried to skip this orientation and to go to actions in favor of people’s empowerment and ability in health choices. Objectives Our program was designed to change students’ ideas on prevention, by focusing on reflexivity, motivational approaches, education and ethic in health promotion, of peer-to-peer effects and concrete use of educational tools for teen-agers groups. We developed students’ autonomy and ability to negotiate their project with the prevention structures. Training was 11 workshops (2 hours each), of 15 to 20 students (mixing medical, pharmaceutical, dental and midwives), and e-learning. Then they had 5 months to negotiate with their place of intervention (secondary schools and apprenticeship centers) and create their own new project. Intervention lasted for one week, full time, in various teen-agers settings, so that to reduce social and territorial inequities in health. Results After a first test (28 students in 6 settings), 250 students acted in 72 teen-agers’ facilities. Problem occurs in 1 case (lack of negotiation and preparation before the intervention) and satisfaction of both students and facilities are high. At the same times, we had to face constraints due to double bind policies of the state authorities (i.e. as asking for more training time and reducing training financing, asking to send students in deprived or isolated areas and reimbursing scarcely the costs). Conclusions An educational program on training and students’ autonomy works if we take care on five points: learning of educational process in health, control of peer-to-peer effects, reduction of health inequities, and reinforcement of local health promotion policies. This also needs state policies that are ready to play the game. Key messages Training of health students to develop their autonomy and ability in health education works. Inconsistency in State policies is the major problem

Manifestations neurologiques de la maladie de Fabry

La maladie de Fabry (MF), sphingolipidose lysosomale liée au chromosome X, est responsable d’une atteinte multisystémique, continuum de sévérité clinique en fonction du niveau d’activité α-galactosidase A. L’atteinte du système nerveux périphérique, avec des crises douloureuses et des acroparesthésies chroniques, souvent révélatrice, est en rapport avec une atteinte des fibres nerveuses de petit calibre (fibres δ), ce qui est confirmé par la normalité de l’électroneuromyographie et l’élévation des seuils à la douleur ou aux stimulations thermiques. Les atteintes cochléo-vestibulaires et du système nerveux autonome sont plus tardives. Outre de rares méningites aseptiques, les atteintes centrales sont dues à des lésions vasculaires ischémiques survenant dans 25 % des cas etaugmentant avec l’âge. Elles intéressent préférentiellement le territoire vertébro-basilaire et leurphysiopathologie n’est pas encore élucidée. L’IRM encéphalique montre l’existence de nombreuseslésions silencieuses, augmentant avec l’âge, dans les territoires vascularisés par des artères perforantes de petit calibre ainsi que des calcifications des pulvinars secondaires à l’hyperperfusion cérébrale observée dans la MF. Celle-ci pourrait être due à la microangiopathie secondaire aux dépôts de glycosphingolipides. L’enzymothérapie substitutive semble pouvoir améliorer les anomalies du métabolisme régional encéphalique, mais aussi les manifestations douloureuses liées à l’atteintepériphérique