An intravascular perspective on hyper-acute neutrophil,T-cell and platelet responses: Similarities between human and experimental stroke

In stroke patients, local sampling of pial blood within the occluded vasculature before recanalization by mechanical thrombectomy emerged as powerful tool enabling insights into ultra-early stroke pathophysiology. Thereby, a strong intravascular inflammatory response hallmarked by hyper-acute neutrophil recruitment, altered lymphocyte composition and platelet activation could be observed. These human findings mirror experimental stroke. Here, neutrophil and T-cell activation are driven by platelets involving engagement of platelet glycoprotein receptor (GP)Ib, GPVI and CD84 as well as α-granule release orchestrating infarct progression. Thus, targeting of early intravascular inflammation may evolve as a new therapeutic strategy to augment the effects of recanalization.     

Association between tissue hypoxia,perfusion restrictions,and microvascular architecture alterations with lesion-induced impairment of neurovascular coupling

Functional magnetic resonance imaging (fMRI) has been mainly utilized for the preoperative localization of eloquent cortical areas. However, lesion-induced impairment of neurovascular coupling (NVC) in the lesion border zone may lead to false-negative fMRI results. The purpose of this study was to determine physiological factors impacting the NVC. Twenty patients suffering from brain lesions were preoperatively examined using multimodal neuroimaging including fMRI, magnetoencephalography (MEG) during language or sensorimotor tasks (depending on lesion location), and a novel physiologic MRI approach for the combined quantification of oxygen metabolism, perfusion state, and microvascular architecture. Congruence of brain activity patterns between fMRI and MEG were found in 13 patients. In contrast, we observed missing fMRI activity in perilesional cortex that demonstrated MEG activity in seven patients, which was interpreted as lesion-induced impairment of NVC. In these brain regions with impaired NVC, physiologic MRI revealed significant brain tissue hypoxia, as well as significantly decreased macro- and microvascular perfusion and microvascular architecture. We demonstrated that perilesional hypoxia with reduced vascular perfusion and architecture is associated with lesion-induced impairment of NVC. Our physiologic MRI approach is a clinically applicable method for preoperative risk assessment for the presence of false-negative fMRI results and may prevent severe postoperative functional deficits.     

Young adult stroke: neuropsychological dysfunction and recovery

Etiology, neuropsychological deficits, aphasia type, and recovery were retrospectively studied in 254 young adults with stroke. Cardiac embolism was the most common cause of stroke in patients younger than 40, while atherosclerosis was the most frequent etiology among those aged 41-50 years. In 166 aphasic patients, Broca's aphasia was the most common while Wernicke's and transcortical aphasias were rare. Compared with an older aphasic population, young patients had significantly more nonfluent aphasias and fewer comprehension deficits. These differences were related to stroke localization: the majority of infarcts localized by computed tomography in 37 patients involved either the entire middle cerebral artery territory or its superior or deep branches, explaining the preponderance of nonfluent aphasia. Prognosis of aphasia in our patients was better than has been reported for non-age-selected aphasia populations. Roughly one third of our patients recovered completely, one third improved, and one third had an unresolved language deficit. Complete recovery and significant improvement were observed even greater than 6 months after stroke. In some patients, recovery was much better than might have been predicted from lesion site and size depicted on computed tomograms.     

Mild cognitive impairment in adult: A neuropsychological review

Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This is clinically relevant overt dementia can be prevented if treatment strategies are devised for MCI. Neuropsychological deficits in this condition are very common and are important clinically for treatment and outcomes. We aimed to review various neuropsychological deficits in MCI. Further, we have presented the current evidence for nosological status, neuroanatomical basis, and clinical outcome of this heterogeneous construct. All published papers on the topic of neuropsychological deficits in MCI on Medline and other databases were reviewed. A wide range of memory and executive function deficits are common in MCI patients. However, several studies are limited by either improper designs or inadequate sample sizes. Several neuropsychological impairments like memory function and executive functions can be diagnosed in MCI. The evidence base for the exact neuroanatomical basis of MCI is not robust yet. However, given the wide range of outcomes, controversies and debates exist regarding the nosological significance of the deficits. Hence, more studies are needed to specifically locate the impairments and further delineate the construct of MCI.     

癫(癎)患者磁共振弥散张量成像及其与智能损害的关系

目的 采用磁共振弥散张量成像技术研究癫(癎)患者智能损害的相关脑区及病理改变,探讨其可能的发生机制.方法 对44例癫(癎)患者和20名健康人进行韦氏成人量表和磁共振弥散张量成像检查.结果 癫(癎)组患者的全量表智商(FIQ,98.19±17.76)、语言智商(VIQ,100.52±17.63)、操作智商(PIQ,95.10±16.72)均显著低于对照组(VIQ:109.77±13.54、PIQ:108.11±12.17、FIQ:109.81±10.57).癫(癎)智能缺损患者胼胝体膝部平均扩散率(MD值)高于癫(癎)智能正常组,双侧内囊前肢、左侧内囊膝部、左侧外囊、双侧枕叶白质和双侧壳核的各向异性(FA)值低于癫(癎)智能正常组,差异有统计学意义(P＜0.05).相关分析发现,右枕叶FA值与FIQ呈正相关;右侧额叶MD值与VIQ呈负相关;右侧枕叶FA值与VIQ呈正相关;两侧枕叶FA值均与PIQ正相关.结论 本组癫(癎)患者在FIQ、VIQ、PIQ均存在损害.癫(癎)患者伴有智能缺损的胼胝体膝部平均扩散率增加,双侧内囊前肢、左侧内囊膝部、左侧外囊、双侧枕叶白质和双侧壳核各向异性减低;枕叶的各向异性减低与FIQ减低有关,额叶平均扩散率增加与VIQ减低有关,皮质下白质在认知中可能起较重要的作用.     

Gambling and Problem Gambling in Canada in 2018: Prevalence and Changes Since 2002

Objective:The purpose of this study was to provide an updated profile of gambling and problem gambling in Canada and to examine how the rates and pattern of participation compare to 2002.Method:An assessment of gambling and problem gambling was included in the 2018 Canadian Community Health Survey and administered to 24,982 individuals aged 15 and older. The present analyses selected for adults (18+).Results:A total of 66.2% of people reported engaging in some type of gambling in 2018, primarily lottery and/or raffle tickets, the only type in which the majority of Canadians participate. There are some significant interprovincial differences, with perhaps the most important one being the higher rate of electronic gambling machine (EGM) participation in Manitoba and Saskatchewan. The overall pattern of gambling in 2018 is very similar to 2002, although participation is generally much lower in 2018, particularly for EGMs and bingo. Only 0.6% of the population were identified as problem gamblers in 2018, with an additional 2.7% being at-risk gamblers. There is no significant interprovincial variation in problem gambling rates. The interprovincial pattern of problem gambling in 2018 is also very similar to what was found in 2002 with the main difference being a 45% decrease in the overall prevalence of problem gambling.Conclusions:Gambling and problem gambling have both decreased in Canada from 2002 to 2018 although the provincial patterns are quite similar between the 2 time periods. Several mechanisms have likely collectively contributed to these declines. Decreases have also been reported in several other Western countries in recent years and have occurred despite the expansion of legal gambling opportunities, suggesting a degree of inoculation or adaptation in large parts of the population.     

Alzheimer's disease and depression: neuropsychological impairment and progression of the illness

The authors longitudinally evaluated the cognitive functions of patients with probable Alzheimer's disease who also met criteria for major depression and compared them with matched patients with Alzheimer's disease who were not depressed. They found no significant difference in the pattern of neuropsychological deficits between the two groups; composite scores on attention, language, memory, learning, and visuospatial functions did not differentiate the two groups at baseline or at 1-year follow-up. The results of this preliminary report suggest that depression does not modify the neuropsychological features and the rate of progression of Alzheimer's disease.     

CADASIL: new cases and new questions

We described the first two unrelated Polish families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In the morphological examination with light microscopy, two kinds of changes were observed: (1) panarteritis nodosa-like changes with eosinophilic fibrinoid necrosis of the vessel wall and perivascular inflammatory infiltrates and (2) basophilic granular material in the tunica media characteristic of CADASIL. At electron microscopy, we found deposits of granular osmophilic material (GOM) within the wall of arteries, veins and capillary vessels. Our findings imply two questions requiring further investigation: Why in the genetically determined vascular disorder are the features of systemic inflammatory vascular disease present? Why in capillary walls deprived of smooth muscle cells are deposits of GOM present?     

Mild cognitive impairment after lacunar infarction: voxel-based morphometry and neuropsychological assessment

BACKGROUND: The aim of the present study was to investigate whether there were differences in neuroradiological features, including white-matter lesions and gray-matter volumes, between patients with lacunar infarction with and without mild cognitive impairment of the vascular type (MCI-V). METHODS: A total of 40 patients with lacunar infarction were studied within 1 month after stroke. RESULTS: MCI-V was found in 22 patients, who in comparison with patients without cognitive impairment were significantly older and had fewer years of formal education. MRI subcortical hyperintensities especially in the basal ganglia (putamen and thalamus) were significantly more frequent in the MCI-V group. In the voxel-based morphometric study, patients with MCI-V showed more atrophy bilaterally in the middle temporal gyrus, right and left frontal and posterior bilateral occipitoparietal regions including the posterior cingulate as well as in the cerebellum. A region of interest analysis restricted to the parahippocampi and hippocampi showed further reduced bilateral parahippocampal gyrus and right hippocampus volume reductions in this group of patients. Finally, the amount of white-matter lesions among MCI-V showed negative correlations with gray-matter volume in frontal and temporal areas as well as with the thalamus and mesencephalon. CONCLUSIONS: The present findings provide support for an anatomical substrate of the MCI entity in patients with lacunar infarction. Both gray- and white-matter changes seem to contribute to the cognitive impairment of such patients.     

Early depressive symptoms after stroke: neuropsychological correlates and lesion characteristics

OBJECTIVE: To examine the relation between depressive symptoms and specific cognitive functions in patients with a recent stroke and to examine associations with lesion characteristics. METHODS: We studied 126 of 183 consecutive patients within 3 weeks after a first-ever symptomatic stroke (mean interval, 8.3+/-4.3 days). Presence and severity of depressive symptoms was assessed with the Montgomery Asberg Depression Rating Scale. Neuropsychological functioning was examined by means of a detailed neuropsychological examination covering six cognitive domains. We included a healthy control group (N=75) to obtain normative data for the neuropsychological examination. Functional impairment was measured with the modified Barthel Index and the modified Rankin Scale. Symptomatic and preexistent lesion characteristics were determined on CT or MRI. RESULTS: Of the included patients, 40% demonstrated mild and 12% moderate to severe depressive symptoms. Severity of depressive symptoms was related to lesion volume (p=0.008), functional impairment (all p<0.004), and degree of overall cognitive impairment (p=0.005). After adjustment for lesion size, a specific neuropsychological profile emerged in patients with moderate to severe depressive symptoms, affecting primarily memory, visual perception, and language (all p<0.05). No association was found between severity of depressive symptoms and lesion location, presence of preexistent lesions (white matter lesions and silent infarcts), and demographic factors (age, education, and gender). CONCLUSIONS: Moderate or severe symptoms of depression in the early stage poststroke are associated with a specific pattern of cognitive impairment, lesion size, and functional status. We suggest that depressive symptoms early after stroke are, at least in part, a reactive phenomenon secondary to severe cognitive and functional deficits.     

Development of M1 mAChR Allosteric and Bitopic Ligands: Prospective Therapeutics for the Treatment of Cognitive Deficits

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Season of birth and neuropsychological impairment in schizophrenia.

Repeated studies suggest a relationship between winter birth and increased incidence of schizophrenia. Furthermore, there may be seasonal fluctuations in schizophrenia risk factors (e.g., influenza epidemics) and the severity of biological anomalies (e.g., enlarged cerebral ventricles in neuroimaging studies). In order to assess whether winter-born schizophrenics show greater neuropsychological impairment, 112 males meeting Research Diagnostic criteria for schizophrenia were administered the Luria-Nebraska Neuropsychological Battery, a thorough measure of higher cortical functioning deficit. Sixty-four of these 112 patients were also administered the Wechsler Adult Intelligence Scale-Revised, the Benton Visual Retention Test, and the Rey Auditory Verbal Learning Test. Despite the use of several definitions of winter and nonwinter birth, there was no evidence of elevated rates of neuropsychological dysfunction among winter-born patients on any measure. The current study contains certain limitations (e.g., variable medication status at testing), but the results suggest no strong season of birth relationship with neuropsychological impairment in a reasonably large, research-diagnosed sample of schizophrenic patients.     

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