Les troubles cognitifs dans les syndromes cliniquement isolés: Etude cas-témoins / Cognitive impairment in clinically isolated syndromes: A control-case study

ntroduction - L'atteinte cognitive est fréquente dans la Sclérose en Plaques (SEP) mais son diagnostic se fait souvent tardivement, au stade de désinsertion sociale et professionnelle. Les études portant sur les aspects cognitifs dans les formes pré-coces de la SEP tels que les syndromes cliniquement isolés (SCI) et les syndromes radiologiquement isolés (SRI) sont rares.Objectifs - Analyserles fonctions cognitives d'un premier événement démyélinisant et identifier les domainesqui seraient les plus précocement atteints.Patients et méthodes - Le profil cognitif d'une populationhomogène de 13 patients présentant unSCI a été évalué, eta été comparé à 15 témoins sains appareillés en fonction de l'âge, du sexe et du niveau d'éducation. Une batterie de tests neu-ropsychologiques(BCCogSEP, batterie courte d'évaluation cognitive de la SEP),vali-dée dans la SEP, a été utilisée. Ses composants explorent les capacités mnésiques et verbales, l'attention, la vitesse de traitement de l'information (VTI) et les fonctions exécutives.Résultats - Lesperformances cognitives globales étaient amoindries dans le groupe SCI, comparativement au groupe témoin. Sur les 13 patients atteints de SCI, cinq (38%) présentaient une altération cognitive globale qui a été objectivée par l'at-teinte d'au moins deux ou trois tests de la batterie. La PASAT (Paced Auditory Serial Addition Test)était le test le plus altéré (84,6% d'atteinte). La VTI et la mémoire de travail étaient les fonctions les plus atteintes chez les patients.Conclusion - Les dysfonctions cognitives peuvent se voir très précocement et peuvent grever lourdement le pronostic de la SEP.

Introduction - Cognitive impairment is common in multiple sclerosis (MS) but its diagnosis is often made late, at the stage of social and professional disinsertion. Studies of the cognitive aspects in early forms of MS such as clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) are rare. Objectives - To analysis the cognitive functions of a first demyelinating event and identify the areas that would be most affected early. Patients and methods - The cognitive profile of a homogeneous population of 13 patients with a CIS was evaluated, and compared with 15 healthy controls, matched according to age, sex and level of education. A battery of neuropsychological tests (BCCogSEP, Short battery for cognitive assessment of MS) validated in MS,was used. Its components explore memory and verbal skills, attention, information processing speed (IPS) and executive functions. Results - The overall cognitive performance was reduced in the CIS group,compared to control group. Five out of thirteen CIS patients (38%) had an overall cognitive impairment, demonstrated by the achievement of at least two or three battery tests. The Paced Auditory Serial Addition Test (PASAT) was the most altered test (84.6% impairment). IPS and working memory were the most affected functions in the patients. Conclusion - Cognitive dysfunctions can be seen very early and can severely affect the prognosis of MS.

LRRK2 G2019S mutation in Parkinson's disease: a neuropsychological and neuropsychiatric study in a large Algerian cohort.

A series of 106 patients with isolated or familial Parkinsonism underwent clinical evaluation and genetic testing for the LRRK2 G2019S mutation which was identified in 34/106 patients (32%). Seventy one of them accepted to be evaluated for neuropsychological and neuropsychiatric studies with the aim to compare mutation carriers with non-carriers. For neuropsychological testing, comparisons between LRRK2 G2019S carriers and non-carriers were made after stratification according to the level of education: median and high school versus low level. Memory was investigated with the five words test, 2 novel tests with verbalized visual material dedicated to illiterate patients, the TNI-93 (nine pictures test), The TMA-93 (associative memory test), and digit spans (forward/backward). Cognitive analyse did not show major differences between the two groups of patients. Nevertheless, behavioral abnormalities, mostly depression and hallucinations, were more frequent in the LRRK2 G2019S carriers, suggesting the presence of a greater involvement of the limbic system in these patients. Sleep disorders which were also more common amongst mutation carriers than non-carriers might be related to depression.

Parkinson's disease-related LRRK2 G2019S mutation results from independent mutational events in humans.

Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (PD) and in sporadic cases; the G2019S mutation is the single most frequent. Intriguingly, the frequency of this mutation in PD patients varies greatly among ethnic groups and geographic origins: it is present at <0.1% in East Asia, approximately 2% in European-descent patients and can reach frequencies of up to 15-40% in PD Ashkenazi Jews and North African Arabs. To ascertain the evolutionary dynamics of the G2019S mutation in different populations, we genotyped 74 markers spanning a 16 Mb genomic region around G2019S, in 191 individuals carrying the mutation from 126 families of different origins. Sixty-seven families were of North-African Arab origin, 18 were of North/Western European descent, 37 were of Jewish origin, mostly from Eastern Europe, one was from Japan, one from Turkey and two were of mixed origins. We found the G2019S mutation on three different haplotypes. Network analyses of the three carrier haplotypes showed that G2019S arose independently at least twice in humans. In addition, the population distribution of the intra-allelic diversity of the most widespread carrier haplotype, together with estimations of the age of G2019S determined by two different methods, suggests that one of the founding G2019S mutational events occurred in the Near East at least 4000 years ago.