Permanent Cerebral Vessel Occlusion via Double Ligature and Transection

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia) ¹. Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex ², is the most common site of human stroke ³, and ischemia within its territory can result in extensive dysfunction or death ^1,4,5. Survivors of ischemic stroke often suffer loss or disruption of motor capabilities, sensory deficits, and infarct. In an effort to capture these key characteristics of stroke, and thereby develop effective treatment, a great deal of emphasis is placed upon animal models of ischemia in MCA.Here we present a method of permanently occluding a cortical surface blood vessel. We will present this method using an example of a relevant vessel occlusion that models the most common type, location, and outcome of human stroke, permanent middle cerebral artery occlusion (pMCAO). In this model, we surgically expose MCA in the adult rat and subsequently occlude via double ligature and transection of the vessel. This pMCAO blocks the proximal cortical branch of MCA, causing ischemia in all of MCA cortical territory, a large portion of the cortex. This method of occlusion can also be used to occlude more distal portions of cortical vessels in order to achieve more focal ischemia targeting a smaller region of cortex. The primary disadvantages of pMCAO are that the surgical procedure is somewhat invasive as a small craniotomy is required to access MCA, though this results in minimal tissue damage. The primary advantages of this model, however, are: the site of occlusion is well defined, the degree of blood flow reduction is consistent, functional and neurological impairment occurs rapidly, infarct size is consistent, and the high rate of survival allows for long-term chronic assessment.     

Prehospital Thrombolysis: A Manual from Berlin

In acute ischemic stroke, time from symptom onset to intervention is a decisive prognostic factor. In order to reduce this time, prehospital thrombolysis at the emergency site would be preferable. However, apart from neurological expertise and laboratory investigations a computed tomography (CT) scan is necessary to exclude hemorrhagic stroke prior to thrombolysis. Therefore, a specialized ambulance equipped with a CT scanner and point-of-care laboratory was designed and constructed. Further, a new stroke identifying interview algorithm was developed and implemented in the Berlin emergency medical services. Since February 2011 the identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of this ambulance, a stroke emergency mobile (STEMO). On arrival, a neurologist, experienced in stroke care and with additional training in emergency medicine, takes a neurological examination. If stroke is suspected a CT scan excludes intracranial hemorrhage. The CT-scans are telemetrically transmitted to the neuroradiologist on-call. If coagulation status of the patient is normal and patient''s medical history reveals no contraindication, prehospital thrombolysis is applied according to current guidelines (intravenous recombinant tissue plasminogen activator, iv rtPA, alteplase, Actilyse).Thereafter patients are transported to the nearest hospital with a certified stroke unit for further treatment and assessment of strokeaetiology. After a pilot-phase, weeks were randomized into blocks either with or without STEMO care. Primary end-point of this study is time from alarm to the initiation of thrombolysis. We hypothesized that alarm-to-treatment time can be reduced by at least 20 min compared to regular care.     

早期强化步行基本功训练对脑卒中的预后分析

目的：分析早期强化步行基本功训练对脑卒中预后的影响。方法：选取我院2008年10月一2011年10月收治的176例恢复期脑卒中患者,按照随机数字表分为观察组及对照组,各88例,均接受常规药物治疗和康复训练,观察组在此基础上接受早期强化步行基本功训练,对比两组患者的预后。结果：两组患者治疗后FMA—LE、BBS及MBI评分均见上升,观察组较对照组上升程度更为明显（P〈0．05）,T2时期观察组评分亦见升高,而对照组评分与T1时期相比无明显统计学差异（P〉0．05）;两组患者治疗后步长、步宽及步速均见上升,观察组较对照组上升程度更为明显（P〈0．05）,T2时期观察组步态参数亦见升高,而对照组步态参数与T1时期相比无明显统计学差异（P〉0．05）。结论：早期强化步行基本功训练能够有效改善脑卒中患者下肢运动功能和平衡能力,保证治疗后步行功能,避免生活质量下降,该康复方法值得广泛推广。     

重复经颅磁刺激对脑卒中后患者神经功能缺损的改善

目的:探讨重复经颅磁刺激在脑卒中康复的应用及效果.方法:选择2010年9月至2012年9月在我院神经内科收治的58例脑卒中患者分为两组,即A组和B组,A组患者给予常规药物治疗和康复训练,B组患者在上述治疗的基础上加用低频重复经颅磁刺激治疗,比较两组患者美国国立卫生院神经功能缺损评分情况、日常生活活动(ADL)评分和不良反应发生情况.结果:治疗后,随着时间的推移,两组患者美国国立卫生院神经功能缺损评分得分逐渐下降(P＜0.05).B组患者2周后和6周后两个时点美国国立卫生院神经功能缺损评分得分明显低于A组患者的,差异有显著性(P＜0.05),而随着时间的推移,两组患者日常生活活动(ADL)评分得分逐渐上升(P＜0.05).B组患者2周后和6周后两个时点日常生活活动(ADL)评分得分明显高于A组患者的,差异有显著性(P＜0.05).两组患者在不良反应发生方面差异无显著性(P＞0.05).结论:低频重复经颅磁刺激治疗脑卒中单侧肢体功能障碍患者临床疗效确切,安全可靠,不良反应少.     

Single nucleotide polymorphism of CD40 in the 5′-untranslated region is associated with ischemic stroke

Objectives

Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods

We conducted a case–control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results

Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR = 1.273, 95% CI = 1.016–1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR = 2.350, 95% CI = 1.601–3.449; for TT/CT: OR = 2.148, 95% CI = 1.479–3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR = 6.538, 95%CI = 1.655–25.833; for TT/CT: OR = 3.469, 95%CI = 1.031–11.670), respectively.

Conclusions

The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.     

Regularity of Daily Activities in Stroke

Various studies have been performed using the Social Rhythm Metric (SRM), though none has been developed with stroke patients. Stroke is a pathology that provokes a strong physical and social impact caused by an abnormality in cerebral circulation. Consequently, we performed two studies to validate the SRM and translate it into Portuguese, and to evaluate the regularity of the daily activities of stroke patients. Both healthy individuals and patients with unilateral cerebral lesions were evaluated. Subjects were of both sexes and between 45 and 65 yrs of age. Participants underwent clinical evaluation and recorded the time of 17 daily activities on the SRM for two weeks. Data were analyzed by the Pearson correlation and Fisher tests. After conceptual translation into Portuguese, corrections were made to arrive at the final version. Normative SRM scores varied from 3.2 to 7.0, suggesting that the activities presented in SRM adequately represented the daily routines of the patients. A correlation was found in SRM between the weeks (r=0.84; p=0.0001), indicating instrument reliability. The mean (±SD) score of the stoke patients was 4.8 (±1.0), and the correlation between the SRM and level of neurological damage showed that patients with lower SRM values were more physically compromised (r=?0.29; p=0.04), suggesting that SRM may be a clinical predictor. Activities related to eating and the sleep‐wake cycle were rated by most patients. In all, 71% of the patients did not work, while 84% of healthy individuals did (p=0.001). Only 64% of patients left home compared to 90% of the healthy subjects (p=0.001), and 59% of patients recorded the activity of going home compared to 82% of healthy individuals (p=0.001). According to the results, there is evidence of the validity and reliability of the SRM, enabling it to be reliably used in chronobiological studies of stroke patients. Given that a less regular lifestyle may be associated with neurological compromise and a decrease in social activities, we suggest new studies with the repeated application of this instrument over the clinical evolution of the disease to better define improvement or worsening of the patient's condition in terms of their social and health aspects.     

Circadian Rhythms in the Efficacy of Intravenous Alteplase in Patients With Acute Ischemic Stroke and Middle Cerebral Artery Occlusion

Circadian rhythm interactions of hemostatic factors can modify tissue plasminogen activator (tPA) effects. We assess the relationship of the time frame of intravenous tPA administration with the outcome of patients with acute ischemic stroke (AIS). We studied 135 consecutive patients with AIS and transcranial duplex documented middle cerebral artery (MCA) occlusion treated with intravenous tPA. Complete recanalization was defined as total improvement on thrombolysis in brain ischemia (TIBI) grades 2?h after tPA infusion. Clinical response was evaluated by the modified Rankin scale at 90 days. We determined plasminogen activator inhibitor-1 (PAI-1) levels in 33 patients with available plasma samples before treatment. Our results are follows: 92 (68.1%) patients were treated in the diurnal (9:00–21:00) and 43 (31.8%) in the nocturnal period (21:00–9:00). Complete recanalization was recorded in 52/135 (38.5%) patients. Both the rate of complete recanalization (45.6% vs. 23.2%; p?=?.01) and good clinical outcome (64.1% vs. 44.2%; p?=?.02) were significantly higher in the group of diurnal tPA administration compared with those treated in the nocturnal period. The adjusted odds ratio (OR) of diurnal tPA treatment for complete MCA recanalization was 2.37 (95% confidence interval [CI], 1.02–5.52; p?=?.045). Diurnal tPA infusion significantly improved the overall distribution of scores on the modified Rankin scale, as compared with nocturnal treatment (OR, 2.07; 95% CI, 1.16–4.64 by ordinal regression analysis). Low PAI-1 levels were associated with complete recanalization but did not significantly differ between the two time frames. In conclusion, diurnal administration of tPA is associated with complete MCA recanalization and better functional outcome at 90 days in patients with AIS. (Author correspondence: mgomis.germanstrias@gencat.cat, meritxellgomis@gmail.com)     

Impact of unilateral spatial neglect on chronic patient's post-stroke quality of life

Abstract

Background: Unilateral spatial neglect (USN) is the prevalent feature in patients with right-sided stroke. It is diagnosed through the behavior inattention test (BIT) and has a negative impact on patients affecting both their functional capacity and quality of life.

Objective: Here, we aimed to evaluate the impact of USN on the quality of life of patients in the chronic phase of stroke.

Methods: This is a cross-sectional study with stroke patients with USN. After confirming the presence of stroke through neuroimaging examinations and of USN through the BIT, patients’ quality of life was evaluated by using the EUROQOL scale. Spearman’s correlation was used to validate the correlation between patients’ USN and quality of life, with a p?<?.05 representing significant results.

Results: Eighteen individuals were included. When correlating the value of each domain of the EUROQOL scale with the results of the BIT, we observed a negative correlation between mobility (r?=?–0.97; p?=?.000), self-care (r?=?–0.82; p?=?.013), usual activities (r?=?–0.87; p?=?.005); pain or discomfort (r?=?–0.88; p?=?.004), anxiety or depression (r?=?–0.97; p?=?.000), and EUROQOL total score (r?=?–0.97, p?=?.000).

Conclusion: After a correlation between the overall EUROQOL and BIT scores, we suggest that the higher the USN degree is in stroke patients, the worse their perceived quality of life tends to be.     

A Truncated Fragment of Src Protein Kinase Generated by Calpain-mediated Cleavage Is a Mediator of Neuronal Death in Excitotoxicity

Excitotoxicity resulting from overstimulation of glutamate receptors is a major cause of neuronal death in cerebral ischemic stroke. The overstimulated ionotropic glutamate receptors exert their neurotoxic effects in part by overactivation of calpains, which induce neuronal death by catalyzing limited proteolysis of specific cellular proteins. Here, we report that in cultured cortical neurons and in vivo in a rat model of focal ischemic stroke, the tyrosine kinase Src is cleaved by calpains at a site in the N-terminal unique domain. This generates a truncated Src fragment of ∼52 kDa, which we localized predominantly to the cytosol. A cell membrane-permeable fusion peptide derived from the unique domain of Src prevents calpain from cleaving Src in neurons and protects against excitotoxic neuronal death. To explore the role of the truncated Src fragment in neuronal death, we expressed a recombinant truncated Src fragment in cultured neurons and examined how it affects neuronal survival. Expression of this fragment, which lacks the myristoylation motif and unique domain, was sufficient to induce neuronal death. Furthermore, inactivation of the prosurvival kinase Akt is a key step in its neurotoxic signaling pathway. Because Src maintains neuronal survival, our results implicate calpain cleavage as a molecular switch converting Src from a promoter of cell survival to a mediator of neuronal death in excitotoxicity. Besides unveiling a new pathological action of Src, our discovery of the neurotoxic action of the truncated Src fragment suggests new therapeutic strategies with the potential to minimize brain damage in ischemic stroke.     

妊娠相关脑卒中39 例临床分析

目的:探讨妊娠相关脑卒中的发病原因、临床表现、母婴结局、治疗及预防措施。方法:回顾性分析2001年1月-2013年12月我院共收治的妊娠相关脑卒中39例患者的临床资料。结果:39例患者中,发生在妊娠期21例,产褥期18例。经电子计算机断层扫描(CT)、磁共振成像(MRI)、磁共振动脉血管造影(MRA)、磁共振脑静脉血管成像(MRV)、数字减影血管造影术(DSA)和腰椎穿刺等检查明确诊断,诊断出血性脑卒中7例,脑梗死3例,脑静脉窦血栓(CVST)29例,均给予相应的抢救及治疗。16例早期、中期妊娠患者行人工流产术或利凡诺羊膜腔内注射穿刺引产终止妊娠,5例患者行剖宫产终止妊娠。患者治愈出院15例,6例死亡,14例遗留不同程度的肢体活动障碍或语言障碍,家属放弃治疗出院4例。结论:妊娠相关脑卒中危险因素主要包括子痫前期、心源性栓塞、脑血管畸形、脑动脉瘤、水电解质紊乱等代谢障碍性疾病及产褥感染等。其发病急、病死率高,故需提高对本病的认识,定期产前检查,及时发现高危因素,早诊断及时治疗,选择适当的时机及方式终止妊娠是改善妊娠相关脑卒中患者预后的关键。