Fatigue,psychological and cognitive impairment following transient ischaemic attack and minor stroke: a systematic review

Transient ischaemic attack (TIA) and minor stroke are characterized by short‐lasting symptoms; however, anecdotal and empirical evidence suggests that these patients experience ongoing cognitive/psychological impairment for which they are not routinely treated. The aims were (i) to investigate the prevalence and time course of fatigue, anxiety, depression, post‐traumatic stress disorder(PTSD) and cognitive impairment following TIA/minor stroke; (ii) to explore the impact on quality of life (QoL), change in emotions and return to work; and (iii) to identify where further research is required and potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PSYCINFO, CINAHL, the Cochrane libraries and the grey literature between January 1993 and April 2013 was undertaken. Literature was screened and data were extracted by two independent reviewers. Studies were included of adult TIA/minor stroke participants with any of the outcomes of interest: fatigue, anxiety, depression, PTSD, cognitive impairment, QoL, change in emotions and return to work. Random‐effects meta‐analysis pooled outcomes by measurement tool. Searches identified 5976 records, 289 were assessed for eligibility and 31 studies were included. Results suggest high levels of cognitive impairment and depression post‐TIA/minor stroke which decreased over time. However, frequencies varied between studies. Limited information was available on anxiety, PTSD and fatigue. Meta‐analysis revealed that the measurement tool administered influenced the prevalence of cognitive impairment: Mini‐Mental State Examination 17% [95% confidence interval (CI) 7, 26]; neuropsychological test battery 39% (95% CI 28, 50); Montreal Cognitive Assessment 54% (95% CI 43, 66). There is evidence to suggest that TIA/minor stroke patients may experience residual impairments; however, results should be interpreted with caution because of the few high quality studies. Notwithstanding, it is important to raise awareness of potential subtle but meaningful residual impairments.     

Short-term effects of glucose and sucrose on cognitive performance and mood in elderly people

In this study we determined the short-term effects of a glucose drink and a sucrose drink compared to a placebo on cognitive performance and mood in elderly people with subjective, mild memory complaints using a randomized crossover study design. In total, 43 nondiabetic older adults with self-reported memory complaints were included. Drinks consisted of 250 ml with dissolved glucose (50 g), sucrose (100 g), or a mixture of artificial sweeteners (placebo). Multiple neuropsychological tests were performed and were combined by means of z scores into four cognitive domains: episodic memory, working memory, attention and information (processing speed), and executive functioning. Mood was assessed with the short Profile of Mood Status (s-POMS) questionnaire. Blood glucose concentrations were measured at five time points to divide participants into those with a better or poorer blood glucose recovery. Performance on the domain of attention and information processing speed was significantly better after consuming the sucrose drink (domain score of 0.06, SD = 0.91) than after the placebo drink (–0.08, SD = 0.92, p = .04). Sucrose had no effect on the other three domains, and glucose had no effect on any of the domains compared to the placebo. When dividing participants into poorer or better glucose recoverers, the beneficial effect of sucrose on attention and information processing speed was only seen in participants with a poorer recovery. After sucrose consumption, depressive feelings and tension were slightly higher than after the placebo. To conclude, 100 g sucrose, but not 50 g glucose, optimized attention and information processing speed in the short term in this study in elderly people with subjective, mild memory complaints.     

Novel mGluR5 Positive Allosteric Modulator Improves Functional Recovery,Attenuates Neurodegeneration,and Alters Microglial Polarization after Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) causes microglial activation and related neurotoxicity that contributes to chronic neurodegeneration and loss of neurological function. Selective activation of metabotropic glutamate receptor 5 (mGluR5) by the orthosteric agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), is neuroprotective in experimental models of TBI, and has potent anti-inflammatory effects in vitro. However, the therapeutic potential of CHPG is limited due to its relatively weak potency and brain permeability. Highly potent, selective and brain penetrant mGluR5 positive allosteric modulators (PAMs) have been developed and show promise as therapeutic agents. We evaluated the therapeutic potential of a novel mGluR5 PAM, VU0360172, after controlled cortical impact (CCI) in mice. Vehicle, VU0360172, or VU0360172 plus mGluR5 antagonist (MTEP), were administered systemically to CCI mice at 3 h post-injury; lesion volume, hippocampal neurodegeneration, microglial activation, and functional recovery were assessed through 28 days post-injury. Anti-inflammatory effects of VU0360172 were also examined in vitro using BV2 and primary microglia. VU0360172 treatment significantly reduced the lesion, attenuated hippocampal neurodegeneration, and improved motor function recovery after CCI. Effects were mediated by mGluR5 as co-administration of MTEP blocked the protective effects of VU0360172. VU0360172 significantly reduced CD68 and NOX2 expression in activated microglia in the cortex at 28 days post-injury, and also suppressed pro-inflammatory signaling pathways in BV2 and primary microglia. In addition, VU0360172 treatment shifted the balance between M1/M2 microglial activation states towards an M2 pro-repair phenotype. This study demonstrates that VU0360172 confers neuroprotection after experimental TBI, and suggests that mGluR5 PAMs may be promising therapeutic agents for head injury.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-014-0298-6) contains supplementary material, which is available to authorized users.     

血小板参数与缺血性脑卒中患者颈动脉狭窄的相关性分析

目的：探讨血小板参数与缺血性脑卒中患者颈动脉狭窄的相关性。方法选取2012-01-2013-10在我院住院治疗的急性缺血性脑卒中患者98例及同期健康体检者60例,动脉超声检查受检者有无颈动脉颅外段狭窄及其程度,全自动血细胞分析仪检测所有入组对象血小板参数各项值,并进行比较。结果伴颈动脉狭窄卒中组血小板计数（PL T ）最低,而血小板平均体积（MPV）、血小板分布宽度（PDW）最大（P＜0.05）;颈动脉狭窄患者PLT、MPV及PDW较不伴颈动脉狭窄者均有显著差异（P＜0.05）。缺血性脑卒中患者不伴动脉狭窄组血小板参数比较,仅MPV 水平差异有统计学意义（P＜0.05）。相关性分析发现MPV与颈动脉狭窄程度呈正相关（P＜0.05）。结论血小板参数与缺血性脑卒中颈动脉狭窄及程度密切相关。