Randomized, double-blind, parallel-group, 48-week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs. 10 cm(2)) in Alzheimer’s disease

Aim: Determine whether patients with Alzheimer’s disease demonstrating functional and cognitive decline, following 24-48 weeks of open-label treatment with 9.5 mg/24 h (10 cm(2)) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Methods: Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm(2)) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-IADL) scale and the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Results: Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAScog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. Conclusions: The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated. Copyright © 2012 S. Karger AG, Base

Mechanical Thrombectomy for Tandem Occlusions of the Internal Carotid Artery—Results of a Conservative Approach for the Extracranial Lesion

Background: Mechanical thrombectomy (MT) is of clinical benefit for patients with extracranial-intracranial tandem lesions of anterior circulation. However, the optimal approach to the cervical lesion of the internal carotid artery (ICA) during MT has yet to be established. Data on a conservative approach for the proximal lesion during the acute phase are scarce.Methods: A retrospective study on an institutional, prospective database was conducted. We included patients with anterior circulation stroke presenting with a tandem lesion that was approached conservatively during MT.Results: Thirty-five 35 patients were included, of whom 25 (71.4%) had an atheromatous ICA lesion and 10 (28.6%) a dissection. Despite implementing a conservative strategy, acute percutaneous transluminal angioplasty (PTA) and/or stenting was necessary in 8 (22.9%) and 3 patients (8.6%), respectively. Of 27 surviving patients, 7 (25.9%) underwent delayed treatment of the ICA lesion. No new embolic events occurred between MT and delayed treatment. A favorable clinical outcome (mRS ≤ 2) was achieved in 15/35 patients (45.7%) and was associated with higher baseline ASPECTS (OR 1.62, 95% CI 1.08–2.45, p = 0.002) and successful recanalization (OR 9.39, 95% CI 1.92–45.80, p = 0.0005). Successful recanalization (TICI ≥ 2B) itself was observed in 54.3% of patients and was more likely with acute treatment of the proximal ICA lesion (OR 6.3, 95% CI 11–35.67, p = 0.03) and, more importantly, by the use of distal access catheters (OR 16.25, 95% CI 3.06–86.41, p = 0.0001).Conclusion: A conservative approach for ICA lesions during MT is feasible and offers favorable outcomes and successful recanalization for a significant proportion of patients. However, acute treatment of the cervical lesion is often necessary (31.4%) to make the distal occlusion accessible. Clinical outcome is influenced by the size of the baseline ischemic core and by successful recanalization; the latter is strongly favored by the use of distal access catheters to pass the proximal lesion. The fact that acute treatment of the ICA lesion favored intracranial recanalization but had no effect on clinical outcome is probably due to sample size, emphasizing the need for large scale, randomized studies to determine the optimal treatment strategy for this pathology

Fronto-Subcortical Circuits for Cognition and Motivation: Dissociated Recovery in a Case of Loss of Psychic Self-Activation

In humans and non-humans primates, extensive evidence supports the existence of subcortico-cortical circuits for cognition and behavior. Lesions studies are critical to understand the clinical significance of these functionally segregated circuits. Mapping these circuits from lesion studies is difficult given the heterogeneous etiology of the lesions, the lack of long-term and systematic testing of cognitive and behavioral disturbances, as well as the scarcity of neuroimaging data for identifying the precise location and extent of subcortical lesions. Here, we report the long-term follow-up study of a patient who developed a loss of psychic self-activation associated to a dysexecutive syndrome following resuscitation from cardiac arrest. Neuroimaging revealed extensive bilateral lesions in the putamen, with a relative spare of the caudate, and exhibiting a dorsoventral gradient that was predominantly rostrally to the anterior commissure and spared most of the ventral striatum. In comprehensive neuropsychological and neuropsychiatric assessments, we observed dissociation between the improvement of the self-activation deficits and the stability of the dysexecutive syndrome. The pattern of recovery after this lesion lends support to current models proposing the existence of two main subcortico-cortical circuits: a dorsal circuit, mostly mediating cognitive processes, and a ventral circuit, implicated in motivation

Glucose modifies the effect of endovascular thrombectomy in patients with acute stroke: a pooled-data meta-analysis

Background and Purpose: Hyperglycemia is a negative prognostic factor following acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy in patients with large vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of endovascular thrombectomy in acute stroke. Methods: Seven randomized trials compared endovascular thrombectomy with standard care between 2010 and 2017 (HERMES Collaboration). 1764 patients with large vessel stroke were allocated to endovascular thrombectomy (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome [modified Rankin Scale (mRS) range: 0-6; lower scores indicating less disability] at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results: Median (IQR) serum glucose on admission was 120 (104-140) mg/dl [6.6mmol/l (5.7-7.7) mmol/l]. Endovascular thrombectomy (EVT) was better than standard care in the overall pooled-data analysis [common odds ratio (acOR), 2.00 (95% CI 1.69–2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or > 90mg/dl (5.0mmol/l) [(p=0.019 for interaction, acOR 3.81 (95% CI 1.73–8.41) for patients < 90 mg/dl vs 1.83 (95% CI 1.53–2.19) for patients > 90 mg/dl], and glucose < or > 100mg/dl (5.5mmol/l) [(p=0.004 for interaction, acOR 3.17 (95% CI 2.04–4.93) vs acOR 1.72 (95% CI 1.42–2.08)], but not between subgroups above these levels of glucose. Conclusions: Endovascular thrombectomy improved stroke outcomes compared to standard treatment regardless of glucose levels but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100mg/dl (5.0-5.5mmol/l). Whether tight control of glucose improves the efficacy of endovascular thrombectomy following large vessel stroke warrants appropriate testing

Comparaison et places du Ropinirole et du Pramipexole dans le traitemnt du syndrome des jambes sans repos

REIMS-BU Santé (514542104) / SudocSudocFranceF

Dépendance et charge de travail de la maladie d'Alzheimer en institution : une évaluation de quelques outils simples en milieu institutionnel

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Altération des compétences de la cognition sociale dans la sclérose en plaques (une approche neuropsychologique)

La sclérose en plaques (SEP) est une maladie auto-immune du système nerveux central associée à de nombreux symptômes physiques, cognitifs ou psychologiques dont la progression va entraver l'autonomie du sujet. Indépendamment des manifestations comportementales comme l'euphorie, le déni du handicap souvent liées aux stades plus avancés de la maladie, d'autres changements plus subtils sont observés et peuvent avoir des conséquences sur la qualité des interactions sociales. Ces modifications ne sont pas forcément imputables aux déficits cognitifs ou à des paramètres adaptatifs. Elles pourraient également être associées à une altération de la cognition sociale, son fonctionnement reposant en partie sur l'intégrité des réseaux de la substance blanche, principales localisations des lésions dans la SEP. Ce travail a pour objectif d'explorer les capacités socio-cognitives des sujets présentant une SEP à travers trois études. Nous évaluons les capacités d'attribution de pensées à autrui et de reconnaissance des émotions faciales en relation avec les fonctions cognitives et les facteurs psychologiques liés à la maladie. Les résultats mettent en évidence des altérations des compétences socio-cognitives même à des stades précoces de la maladie indépendamment des capacités cognitives ou des troubles de l'humeur quelle que soit la forme de la maladie. Au regard des conséquences psycho-sociales que ces difficultés peuvent engendrer, il semble nécessaire de les prendre en compte lors des bilans d'évaluation pour une meilleure prise en charge de cette maladie, comme cela a été démontré dans d'autres pathologies neurologiques (traumatisme crânien, démences).Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system associated with a wide array of symptoms including physical, cognitive, emotional and behavioral symptoms. Independently of behavioral manifestations as euphoria, denial of disability often linked to advanced MS, other more subtle behavioral changes are observed that may have consequences on the quality of social interactions. These behavioral changes are not necessarily related to cognitive deficits or adaptative parameters but could be also associated with social cognition alterations. Social cognition may rely partly on the integrity of white matter structures, which are the main site of damage related to MS. This work was designed to evaluate socio-cognitive skills of subjects with MS through three studies. The ability to attribute mental states to others and to recognize facial emotional expressions was investigated in different clinical forms of MS in relation with cognitive and psychological factors of this disease. The MS participants performed worse in tests of mental states attribution and emotion facial recognition to controls group even at the beginning of the disease, with and without cognitive deficits or mood disorders. These results provide evidence for deficits in social cognition in MS. With regards to consequences of these deficits on social interaction, it seems necessary to explore systematically theses abilities in order to anticipate social outcomes, as demonstrated in other neurological conditions (head trauma, dementias).ST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF

Dissociation of emotional processes in response to visual and olfactory stimuli following frontotemporal damage

International audienc