Primary intracerebral hemorrhage: pathophysiology

We here review the pathophysiology of primary intracerebral hemorrhage to compare and contrast bleeds due to hypertension and congophilic angiopathy. Hypertension is characterized by early proliferation of arteriolar smooth muscle, followed later by apoptotic smooth muscle cell death and collagen deposition. Eventually excess or deficient collagen deposition can lead respectively to arteriolar occlusion, ectasia or both. Collagen has no contractile capability and is brittle, unable to withstand breakage due to pulse pressure. Arterioles physiologically bring down both blood pressure and pulse pressure, but excessive dilatation results in Charc?t-Bouchard aneurysms, which are fusiform, not saccular structures. The distribution of hypertensive hemorrhage reflects the high pulse pressure of arterioles immediately downstream from major end arteries with minimal intervening branching. Cerebrovascular amyloidosis is a stagnant beta-fibrillosis of arterioles, arising from failure of brain egress of beta-amyloid, after amyloid precursor protein cleavage within brain parenchyma. The lobar distribution of changes reflect an impairment of amyloid removal from brain interstitial fluid and Virchow-Robin spaces. Both diseases cause similar brittle arterioles with poor contractile capability, likely accounting for early growth of hematomas when they rupture. Fibrin globes form in concentric spheres and attempt to seal off the site of bleeding. The size of the final sphere of blood at cessation of bleeding determines the clinical spectrum, from asymptomatic to fatal. Since arteriolar bleeding is slower than arterial bleeding, several hours exist where intervention may be useful with recombinant factor VIIa or other therapies. We speculate on the importance of pulse pressure in the etiology of hemorrhage and resolve the debate over the existence of Charcot-Bouchard aneurysms. The high pulse pressure and brisk interstitial fluid pumping in Virchow-Robin spaces deep within the brain selectively protects against amyloidosis, while leaving these basal arterioles vulnerable to hypertensive damage. Hypertensive hemorrhages occur deep within the centrencephalon, while amyloid hemorrhages occur in a lobar distribution, where pulse pressure and bulk flow are less, away from the major feeding vessels of the brain. The brain distributions of hypertensive and of amyloid hemorrhages are thus different and complementary.     

自发性脑出血的病理生理学进展

自发性脑出血(spontaneous intracerebral hemorrhage, ICH)是一种常见的神经科急症,占入院卒中患者的10% ～30%[1].ICH患者长期预后不良,发病后6个月仅有20%患者能恢复功能性自立[1].在中国脑出血的发病率几乎占到所有卒中事件的30%[2].这些年尽管人们对ICH病理生理学的了解不断深入,但是近10年间ICH的临床死亡率仅降低了6%[3].本文就ICH的病理生理学新进展作一综述.     

Arterial hypertension and intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is still a devastating stroke, with high mortality. Arterial hypertension (AHT) is the most common cause of primary ICH, causing changes in the wall of small vessels, leading to its rupture. Recent studies have attempted to understand the basic mechanisms of tissue damage around the hematoma. These days there is a debate regarding biochemical changes in this area, usually recognized as edema. Detection with the gradient-echo T2 weighted MRI of old and silent microhemorrhages in a patient with ICH as a radiological expression of a microangiopathy of small vessel poses questions regarding its predictive value of risk of bleeding recurrence. The object of our review is to analyze the present data that explains the interaction between chronic hypertension and primary ICH.     

Acute treatment costs of intracerebral hemorrhage and ischemic stroke in Argentina

Background and purpose – Stroke is the third leading cause of death in Argentina, yet little information exists on the acute treatment provided for stroke or its costs. This study estimates the national costs of the acute treatment of first‐ever intracerebral hemorrhage (ICH) and ischemic stroke (IS) in Argentina. Methods – Retrospective hospital‐based inception study design using data on resource use and costs from high‐volume stroke centers in Argentina, and published population‐based incidence data. Treatment provided at two large urban hospitals were evaluated in all patients admitted with a first‐ever stroke between 1 January 2004 and 31 August 2006, and costs were assigned using appropriate unit cost data for all resource use. Cost estimates in Argentinian pesos were converted to US dollars ($) using the 2005 purchasing power parity index. National costs of acute treatment for incident strokes were estimated by extrapolation of average costs estimates to national incidence data. Assumptions of the average cost of stroke treatment on a national scale were examined in sensitivity analysis. Results – The acute care of 167 patients with stroke was thoroughly evaluated from hospital admission to hospital discharge. Mean length of hospital stay was 35.4 days for ICH and 13.0 days for IS. Ninety‐one percent of the patients with ICH and 68% of the patients with IS were admitted to an ICU for a mean length of stay (LOS) of 12.9 ± 20.3 and 3.6 ± 5.9 days respectively. Mean total costs of initial hospitalization were $12,285 (SD ±14,336) for ICH and $3888 (SD ±4018) for IS. Costs differed significantly by Glasgow Coma Scale (GCS) score at admission, development of pneumonia and infections during hospitalization, and functional outcome at hospital discharge. Aggregate national healthcare expenditures for acute treatment of incident ICH were $194.2m (range 97.1–388.4) and $239.9m for IS (range 119.9–479.7). Conclusion – The direct hospital costs of incident ICH and IS in Argentina are substantial and primarily driven by stroke severity, in‐hospital complications and clinical outcomes. With the expected increase in the incidence of stroke over the coming decades, these results emphasize the need for effective preventive and acute medical care.     

非高血压性自发性颅内出血病因及治疗研究

目的 分析非高血压性自发性颅内出血的病因,并对其治疗进行探讨.方法 对60例非高血压性自发性蛛网膜下腔出血(SAH)和42例脑实质内出血患者进行分析,均行DSA检查并采取相应治疗措施.结果 60例SAH的患者中,动脉瘤52例(86.67%),脑动静脉畸形(CAVM)1例(1.67%),动脉瘤合并CAVM 1例(1.67%),血液病1例(1.67%),造影阴性5例(83.33%);在42例脑实质出血(包括脑室出血)的患者中,动脉瘤15例(35.71%),CAVM 9例(21.43%),moyamoya病3例(7.14%),右侧椎动脉变细1例,海绵窦血栓性静脉炎1例,13例(30.95%)造影未发现异常.结论非高血压性SAH的主要原因为动脉瘤破裂,自发性脑实质出血的主要原因为动脉瘤和脑动静脉畸形破裂,临床DSA检查是确诊其病因的重要手段之一,自发性颅内出血病因的早期诊断和对因治疗具有重要临床意义.     

Leukoaraiosis, intracerebral hemorrhage, and arterial hypertension

To investigate whether the observed association of leukoaraiosis with intracerebral hemorrhage is direct or mediated by risk factors, we compared 116 patients with intracerebral hemorrhage confirmed by computed tomography and 155 controls without intracerebral hemorrhage, evaluating the prevalence of leukoaraiosis and vascular risk factors. Leukoaraiosis was observed in 21 (18%) of the 116 patients and in 12 (8%) of the 155 controls (p less than 0.01). Only two (6%) of the 31 patients with lobar hemorrhage had leukoaraiosis on computed tomograms, compared with 17 (24%) of the 71 patients with basal ganglionic hemorrhage (p less than 0.05). Leukoaraiosis was significantly correlated with intracerebral hemorrhage after controlling for age and sex by using multiple logistic regression analysis, while the correlation disappeared after controlling for hypertension. Our results indicate that leukoaraiosis is not an independent risk factor for intracerebral hemorrhage.     

Acute gastric changes after intracerebral hemorrhage in rats

Severe intracerebral hemorrhage (ICH) produces gastric pathology in about 30% of the patient population, even after the standard treatment of H2 receptor blockers or proton pump inhibitors. This study was undertaken to establish a rat model of ICH-induced gastric ulcer. Adult male Sprague-Dawley rats (300-350 g) were divided into two hemorrhage groups and a sham control group. ICH was produced either by injection of 100 microl of autologous arterial blood or by injection of 4 microl saline containing 0.6 unit of bacterial collagenase VII into the right basal ganglia. Rats were sacrificed at 24, 48, 72 h, and 7 days after ICH to harvest brains and stomachs. Greater degrees of hemorrhage and brain edema were observed in collagenase-induced ICH. Motor behavior decreased significantly after 24 h in both models. The incidence of acute ulceration with destruction of the forestomach epithelium was extremely low at 8.7% in the collagenase injection model and 4.8% in the blood injection rats. Small, pinpoint hemorrhages (petechiae) were noticed in 38% of rats after blood injection and 22% after collagenase injection, in the glandular portion of the gastric mucosa with penetration of red blood cells and inflammatory cells into the gastric mucosa. Enhanced tumor necrosis factor alpha (TNFalpha) and cyclooxygenase 2 (COX-2) expressions were observed in gastric tissues after ICH with more intense staining occurring at 24 and 48 h. Due to the low incidence of ulceration, ICH-induced gastric ulceration in rodents may not appropriate for evaluating the potential human risk of gastric ulceration after ICH.     

Medical treatment of intracerebral hemorrhage

Neurological Sciences - Intracerebral hemorrhage (ICH) occurs as a result of bleeding into the brain parenchyma and formation of a focal hematoma. Treatment for ICH is primarily supportive, and...     

Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice

Oxidative stress and matrix metalloproteinases (MMPs) contribute to hemorrhagic transformation after ischemic stroke and brain injury after intracerebral hemorrhage (ICH). The goal of this study was to develop a new model of spontaneous ICH, based on the hypothesis that acute, superimposed on chronic, hypertension produces ICH. We hypothesized that increases in angiotensin II (AngII)-mediated oxidative stress and activation of MMPs are associated with, and may precede, spontaneous ICH during hypertension. In C57BL/6 mice, chronic hypertension was produced with AngII infusion and an inhibitor of nitric oxide synthase. During chronic hypertension, mice with acute hypertension from injections of AngII developed ICH. Oxidative stress and MMP levels increased in the brain even before developing ICH. Active MMPs colocalized with a marker of oxidative stress, especially on cerebral vessels that appeared to lead toward regions with ICH. Incidence of ICH and levels of oxidative stress and MMP-9 were greater in mice with acute hypertension produced by AngII than by norepinephrine. In summary, we have developed an experimental model of ICH during hypertension that may facilitate studies in genetically altered mice. We speculate that acute hypertension, especially when induced by AngII, may be critical in spontaneous ICH during chronic hypertension, possibly through oxidative stress and MMP-9.     

Acute inflammatory reaction following experimental intracerebral hemorrhage in rat

Previous studies on intracerebral hemorrhage (ICH) indicate that brain edema increases progressively in the first 24 h and remains elevated for several days. The cause of secondary brain injury and edema formation is uncertain. We hypothesized that inflammatory mediators released from the blood after cerebral hemorrhage might cause secondary brain injury and edema formation. This study investigates if, when and where inflammation occurs after ICH in rat. Immunocytochemistry for polymorphonuclear leukocyte marker (myeloperoxidase, MPO), microglia marker (OX42) and intracellular adhesion molecule-1 (ICAM-1) was performed in control, and 1, 3, 7 and 10 days after the injection of 100 microliter autologous blood in the right basal ganglia. Double labeling immunohistochemistry was used to identify ICAM-1 positive cells. The results show that an inflammatory response occurred in and around the blood clot after ICH, characterized by the infiltration of neutrophils and macrophages as well as activation of microglia. ICAM-1 immunoreactivity was observed in blood vessels adjacent to the clot, as well as in activated microglia and neurons in the ipsilateral hemisphere. The present study demonstrates there is an inflammatory response in the brain after ICH. Infiltrating leukocytes and activated microglia may release cytotoxic mediators contributing to secondary brain injury.     

高血压脑出血的外科治疗

目的探讨高血压脑出血手术适应证、手术方式、手术技巧及疗效评价.方法回顾本科10年间收治的687例高血压脑出血病历资料.根据出血部位、出血量、中线移位情况及意识状况,选择手术方法.结果全组687例,死亡率14.8%.日常生活能力(ADL)分级:Ⅰ～Ⅴ级分别为:32.9%、24.9%、16.7%、8.6%、2.1%.结论正确选择手术方式,娴熟的操作技巧是提高治愈率及生存质量的关键;超早期手术和显微镜的应用可显著改善患者生存质量.     

高血压脑出血的手术治疗

目的 分析189例高血压脑出血手术疗效许探讨提高手术疗效与生存质量的相关因素。方法 回顾性分析了189例高血压脑出血病人手术治疗的临床资料，分析不同手术时机、手术方法的治疗效果。结果 死亡21例，其余随访6月～3年，平均1．5年，按照日常生活能力(ADL)量表来评定疗效：Ⅰ～Ⅴ级分别为35．45％(67／189)，22．22％(42／189)，16．93％(32／189)，7．94％(15／189)，6．35％(12／189)。结论 甲期手术解除脑部受压是治疗的关键，采用微创手术治疗是提高生存质量的重要手段。     

自发性脑室内血肿的外科手术治疗

目的 总结自发性脑室内血肿的手术治疗。方法 回顾性分析手术治疗的35例自发性脑室内血肿患者的临床资料。结果 手术治疗的35例自发性脑室内血肿患者恢复良好27例，植物生存3例，死亡5例。结论 局麻下一侧或双侧侧脑室穿刺置管＋尿激酶注入溶解持续引流是一种简便、易行、有效的治疗自发性脑室内血肿的方法。     

高血压脑出血的手术治疗

我院自1998年至2001年手术治疗高血压脑出血24例。现总结报导如下。     

高血压脑出血显微外科治疗

目的分析显微手术治疗高血压脑出血的临床效果。方法对158例高血压脑出血患者中142例采用显微手术治疗，根据患者的出血部位、血肿体积及术中脑压情况，76例采用单纯彻底清除血肿，66例采用单纯清除血肿加去骨瓣压减术，并对两组治疗结果进行相关因素分析。结果两种手术治疗方法，患者恢复情况无显著性差异，丘脑出血、脑室内出血死亡率高、本组发病6h内手术无死亡率。结论高血压脑出血显微手术效果好，要根据患者的出血量、出血部位及术中的脑压选择术式。     

微创手术治疗高血压脑出血

高血压脑出血是目前严重威胁人类健康的一类脑血管疾病,其具有发病突然,进展迅速,死亡率及致残率高的特点。目前对于高血压脑出血的手术治疗一般采取开颅血肿清除术或微创血肿清除术。自2007年6月至2009年6月本院应用微创手术对50例高血压患者进行治疗,取得满意疗效,现报     

睾酮对脑出血大鼠脑、肺TNF-α、IL-1β含量的影响及可能机制

目的探讨睾酮在脑出血大鼠急性脑、肺损伤发生、发展中的作用及可能机制。方法 (1)雄性Wistar大鼠55只,分为对照组、脑出血组和氟他胺预处理组。(2)立体定向技术自体血尾状核注入法制作脑出血大鼠模型;氟他胺预处理组大鼠行氟他胺溶液灌胃(50mg/kg.d)10d后,行脑出血造模;对照组大鼠尾状核注入等量生理盐水。(3)ELISA法测定睾酮及TNF-α、IL-1β含量。(4)HE染色光镜观察大鼠脑、肺病理变化。结果 (1)脑出血组大鼠血清睾酮含量显著升高(P<0.05);而氟他胺预处理组各时相点大鼠血清睾酮含量均显著低于脑出血组(P<0.05);(2)脑出血组大鼠各时相点TNF-α、IL-1β含量较对照组显著增高(P<0.05),而氟他胺预处理组各时相点较脑出血组显著降低(P<0.05)。(3)脑出血组大鼠肺匀浆TNF-α、IL-1β含量亦显著增高(P<0.05),氟他胺预处理组显著降低(P<0.05);(4)脑出血组大鼠脑、肺组织出现明显水肿及炎性改变,氟他胺预处理组大鼠脑、肺组织以上变化明显减轻。结论脑出血大鼠脑损伤同时,出现急性炎性肺损伤,氟他胺预处理后炎性反应明显减轻。提示睾酮含量变化可能与炎性肺损伤密切相关。