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Les troubles neurocognitifs conduisant vers un déficit cognitif, fonctionnel et comportemental sont repérés tardivement et sous-diagnostiqués dans les pays occidentaux. Or de nombreuses mesures s’inscrivant dans une démarche d’accompagnement et de prévention secondaire et tertiaire visent à préserver la qualité de vie, prévenir les complications et crises comportementales en anticipant les stades avancés des maladies. Le diagnostic de certaines pathologies doit en outre conduire vers des soins spécifiques et une information sur la recherche. Pour la première fois, les représentants du Collège de médecine générale, de la Fédération des centres mémoire ressources recherche, de la Société française de gériatrie et de gérontologie, de la Fédération française de neurologie, de la Société de psychogériatrie de langue française et la gouvernance du plan « maladies neurodégénératives » proposent une stratégie graduée et personnalisée de diagnostic des troubles neurocognitifs impliquant la médecine générale et les spécialistes des troubles cognitifs. Cette stratégie émane d’un travail s’inscrivant dans le cadre de la mesure 1 du plan « maladies neurodégénératives » et de la nouvelle action conjointe européenne « Act on dementia », puis d’un séminaire tenu au Collège de médecine générale conduit en mars 2017.

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

To identify a new idiopathic basal ganglia calcification (IBGC)-causing gene.

BACKGROUND Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE To describe the disease course of CLIPPERS. DESIGN A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING Academic research. PATIENTS Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES The therapeutic management of CLIPPERS was evaluated. RESULTS Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a genetic component. Until now, the more consistent association with the disease is found with the major histocompatibility complex, especially HLA‐DRB1*1501‐DQB1*0602 haplotype. In this report, we demonstrate the interaction of Cytotoxic T Lymphocyte‐associated antigen 4 (CTLA‐4[CD152]) gene with DRB1*15 haplotype in multiple sclerosis genetic susceptibility. Our data were obtained from two European independent family‐based studies including 610 multiple sclerosis family trios. Ann Neurol 2003;54:119–122

The management of individuals with multiple sclerosis must be considered under the following headings: administration and follow-up of adequate disease-modifying treatment, symptomatic relief and neurorehabilitation. Neurorehabilitation deserves a four-step strategy: multidisciplinary assessment, identification of areas of potential functional improvement, setting of goals of shortlong-term duration, and measurement of outcomes. The patient's perspective is important to evaluate through questionnaires about quality of life. Well organized disability services with multidisciplinary specialists are probably cost effective and efficient. Determining the actual economic impact of multiple sclerosis and defining the most cost-effective type of care for persons with multiple sclerosis is a need in all countries faced with the limitation of healthcare resources. In persons with multiple sclerosis the range of main symptoms includes the loss of mobility and spasticity, pain, tremor, abnormal eye movements, paroxysmal symptoms, bladder and bowel dysfunction, sexual disturbances, fatigue and depression. Current palliative treatments, which are reviewed, are partly successful depending on the type of symptoms under consideration.

BOTH experimental and clinical studies suggest that lymphotoxin (LT) plays an important role in multiple sclerosis (MS) by inducing oligodendrocyte (OL) depletion. However, the mechanism of LT cytotoxicity is unknown. Because of the role of ceramide as a cell death mediator for a large variety of cytotoxic molecules, we have investigated the possible role of this second messenger in LT-induced cytotoxicity on SV40 immortalized new-born mice OL. Human recombinant LT exposure (50 ng/ml) resulted in intracellular ceramide accumulation which peaked at 48 h (∼170 increase) and paralleled LT-induced cytotoxicity. Moreover, fumonisin B1, a potent and specific ceramide synthase inhibitor, not only inhibited ceramide accumulation but also protected OL from LT cytotoxicity. These results suggest that LT-induced ceramide synthase stimulation and subsequent increased intracellular ceramide concentration are implicated in oligodendrocyte death.

OBJECTIVE: To study the effect of the levorotatory form of 5-hydroxytryptophan on the cerebellar symptoms of Friedreich's ataxia. DESIGN: Cooperative double-blind study of the levorotatory form of 5-hydroxytryptophan vs placebo. SETTING: Twelve centers in research hospitals. Patients: Twenty-six patients were included; 19 completed the study (mean±SD age of patients, 25.9±8.1 years). Of these 19 patients, eight were treated with placebo and 11 were treated with the drug. MAIN OUTCOME MEASURES: A semiquantitative scale for kinetic and static ("postural") cerebellar functions and quantitative measurements of time in standard tests that evaluated stance, speech, writing, and drawing. RESULTS: In the active treatment group, a significant decrease of the kinetic score was observed (P=.03), indicating an improvement in coordination. CONCLUSIONS: These results demonstrated that the levorotatory form of 5-hydroxytryptophan is able to modify significantly the cerebellar symptoms in patients with Friedreich's ataxia. However, the effect is only partial and not clinically major.

The approach to drug treatment of vertigo is almost exclusively symptomatic. There are 3 major goals for drug treatment of vertigo. The first one is to eliminate the hallucination of motion. Drugs with vestibular ‘suppressant’ properties are used for this purpose. The major vestibular suppressants are anticholinergic and antihistamine drugs. The second goal is to reduce the accompanying neurovegetative and psychoaffective signs (nausea, vomiting, anxiety). Antidopaminergics are used for this purpose. The third goal is to enhance the process of ‘vestibular compensation’ to allow the brain to find a new sensory equilibrium in spite of the vestibular lesion. Until now, the pharmacological manipulation of vestibular compensation has been assessed in animals but not in humans with vestibular lesions. Vestibular suppressant drugs delay rather than enhance compensation. A variety of other drugs is also used in the treatment of vertigo, including benzodiazepines, histaminergic agents, sympathomimetics and calcium antagonists. Their mechanism of action is poorly understood. The data base derived from clinical trials evaluating antivertigo medications is often questionable because of methodological limitations. This explains why habits of prescription are mainly empirical, and why striking differences can be noticed from one country to another. We can hope that new treatments may emerge from the present interest in receptor subclasses and neuromodulators of the vestibular system, and we must be ready to evaluate these potential new pharmacological agents with reliable clinical methods in humans.

Multiple sclerosis (MS) is a demyelinating auto-immune disease of the central nervous system with a suspected genetic component.Previous publications have demonstrated that MS susceptibility is influenced by Major Histocompatibility Complex (MHC) genes and recent studies have focused on additional susceptibility genes. The accumulation of activated T-cells in demyelinating MS lesions, the possible auto-immune mechanism of this disease and the functional relationship between MHC and T cell receptor (TCR) molecules support the hypothesis that TCR genes are good candidates to influence MS development. Published results in this domain are conflicting and still a matter of controversy.In the present study we analysed the influence of Vβ, Cβ, PλG3 and Vγ gene polymorphisms defined by Restriction Fragments Length Polymorphism (RFLP) on 48 pairs of monozygotic and dizygotic twins with at least one of each pair affected, and also in 63 unrelated MS patients for Vγ gene polymorphism. These results have been compared with those in the non affected twins and with data from a control group (Beall et al., 1989) regarding Cβ and Vβ polymorphisms and with a local control population for Vγ. No significant correlation between Cβ, Vy or PλG3 polymorphisms and MS was found, only a non significant tendency to reduced PAG3 allele sharing among dizygotic non concordant twin pairs was observed. However one Vβ11, 25 kb allele and a haplotype defined by Vβ11 and Cβ alleles showed a correlation with MS susceptibility of borderline significance.These observations are in favor of a slight effect of a genetic factor in the TCRβ gene region in MS genetic susceptibility whereas this is not the case for Vγ genes.

OBJECTIVE To assess the feasibility of synthesis of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET), a new positron emission tomographic (PET) tracer described in several studies but not yet considered standard in management of glioma, in routine practice and to determine FET uptake in a homogeneous group of patients with suspected high-grade glioma. DESIGN Prospective nonrandomized trial. PATIENTS Twelve patients with suspicion of high-grade glioma. RESULTS The mean (SD) FET uptake ratio was 3.15 (0.72) for the 12 patients and 3.16 (0.75) for the 11 patients with glioblastoma. CONCLUSION The initial results are promising and indicate that FET PET is a valuable and applicable tool for the imaging of high-grade glioma.Arch Neurol. 2010;67(3):370-372--

Depuis une dizaine d’années, la stratégie thérapeutique de la SEP a évolué. En France, en 2013, le nombre de patients atteints de SEP était de 99,123, pour la plupart suivis dans des centres experts.

La cryothérapie, dispositif très demandé par les patients, a montré un possible effet dans la SEP mais il n’existe pas de validation.

L’efficacité des immunomodulateurs dans la sclérose en plaques (SEP) a été démontrée lors d’essais cliniques randomisés. Leur utilisation dans des conditions de vie réelle reste à déterminer.

VAV1plays a role in regulating proinflammatory cytokines, which underlie the susceptibility for developing experimental autoimmune encephalomyelitis and multiple sclerosis.