Sustained efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis independent of disease activity and disability at baseline: real-life data from a Swiss cohort

OBJECTIVES: Therapy for relapsing-remitting multiple sclerosis with natalizumab (Tysabri; Biogen Idec) has been shown to be effective in the reduction of the clinical relapse rate and disability progression. However, real-life longitudinal data, including years before baseline, are rare. METHODS: An observational single-center study was carried out. We analyzed data from 64 consecutive patients with multiple sclerosis. RESULTS: After 1 year of treatment (n = 64), score on the Expanded Disability Status Scale (EDSS) decreased by 0.47 points (P = 0.047) and the annualized relapse rate (ARR) decreased by 82% (P 2) or EDSS score and was not biased by exceptional high disease activity or relapses around baseline. CONCLUSIONS: These real-life data reinforce that natalizumab is effective over years, reduces ARR, and stabilizes EDSS score independent of baseline ARR, baseline EDSS score, or baseline treatment

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses

Combined duloxetine and benzodiazepine-induced visual hallucinations in prodromal dementia with Lewy bodies

Objective: We describe a patient with prodromal dementia with Lewy bodies (DLB) presenting with drug-induced visual hallucinations (VHs). Case report: A 78-year-old woman complained of daytime recurrent VHs characterized by seeing her face and arms covered in fur and viewing moustaches on her daughter's face. VHs started a few days after the beginning of a combination therapy with duloxetine and lorazepam and ceased within 24 h after their discontinuation. Nonamnestic mild cognitive impairment with profound visual perception deficits and very mild extrapyramidal signs, with abnormal brain DaTscan single photon emission tomography, were present. Three years later, cognitive and neurological follow-up assessments supported the diagnosis of DLB. Conclusion: Perturbation of cerebral serotonergic tone induced by duloxetine, associated with reduced attentional control due to benzodiazepine use, may be the physiopathological substrate of transient VHs in prodromal DL

Effects of Lexical–Semantic Treatment on Memory in Early Alzheimer Disease: An Observer-Blinded Randomized Controlled Trial

Background. Episodic memory and semantic abilities deteriorate early in Alzheimer disease (AD). Since the cognitive system includes interconnected and reciprocally influenced neuronal networks, the authors hypothesized that stimulation of lexical–semantic abilities may benefit semantically structured episodic memory. Objective. To investigate the effects of lexical–semantic stimulation (LSS) on verbal communication and episodic memory in early AD. Methods. Forty AD participants were randomized to LSS or unstructured cognitive stimulation (UCS) as control condition. Treatments lasted 3 months, 2 sections a week. The primary outcome measures were the Mini Mental State Examination (MMSE), Boston Naming Test (BNT), Verbal Naming Test (VNT), Phonemic and Semantic Fluency, Story Recall, and Rey Auditory Verbal Learning (RAVL). Secondary outcome measures were neuropsychological tests assessing cognitive functions not stimulated by the intervention, such as attention, executive functions, and visual–spatial abilities, and the instrumental activities of daily living scale. A 6-month follow-up assessment was administered to the LSS group. Results. LSS treatment yielded significant improvements of the MMSE, BNT, VNT, Brief Story Recall, and RAVL delayed recall mean scores. Among secondary outcome measures, only working memory and the speed of a task assessing executive functions (Stroop test) improved after LSS. Unstructured cognitive stimulation intervention did not improve any cognitive domain. Six months after LSS discontinuation, the MMSE mean score remains significantly higher than the baseline value. Conclusion. LSS treatment may improve episodic memory in AD patients and may be regarded as a clinical option to counteract the cognitive decline typical of the disease

High specificity of MMSE pentagon scoring for diagnosis of prodromal dementia with Lewy bodies

BACKGROUND: Patients with dementia with Lewy bodies (DLB) may display a different cognitive pattern from Alzheimer's disease (AD) with more severe impairment performing visuospatial/visuoconstructive tasks. The aim of this study was to investigate whether the analysis of the MMSE pentagon copy could be a useful diagnostic screening tool in prodromal DLB. METHODS: Fifty-three patients with Mild Cognitive Impairment (MCI) were followed over 3-years until a diagnosis of DLB (MCI-DLB: n = 30) and AD (MCI-AD: n = 23) were made according to standard criteria. At the first assessment patients underwent a thorough cognitive assessment including the Qualitative Scoring MMSE Pentagon Test (QSPT), the NPI, the UPDRS as well as questionnaires to determine fluctuations and sleep disorders. RESULTS: The percentage of subjects who were unable to determine the correct number of angles in the pentagon copy test was 45.1% of MCI-DLB and 8.3% of MCI-AD patients (sensitivity 41.1%; specificity 91%). Attentive/executive functions and visual-spatial abilities were worse in the MCI-DLB group, while episodic memory impairment was greater in MCI-AD. Subtle extrapyramidal signs (63%) and RBD symptoms (56%) were the most frequent clinical features supporting the diagnosis of MCI-DLB. CONCLUSIONS: We suggest that a poor performance in determining the number of angles when performing the pentagon copying test, together with the presence of subtle extrapyramidal signs and symptoms of RBD may serve as a predictive tool for early DLB