大鼠脑出血模型中神经细胞凋亡与自由基水平的相关性

目的研究脑出血后血肿周围组织不同自由基水平对于细胞凋亡的影响。方法成年SD大鼠随机分为4组：假手术组、模型组、1mg/kg依达拉奉组、3mg/kg依达拉奉组，各组又根据造模后处死动物的不同时间（6h，12h，24h，48h，72h，7d，14d）分为七个亚组，假手术组中每个亚组1只大鼠，其余三组中每个亚组6只大鼠。左尾壳核立体定向注入白体血80μL，制作大鼠脑出血动物模型。分光光度计法检测血肿周围丙二醛（malonaldehyde，MDA）及羟自由基含量，末端转移酶标记技术（terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling，TUNEL）检测血肿组织周围细胞凋亡数，并分析血肿周围组织自由基水平和凋亡相关性。结果（1）模型组羟自由基及MDA含量较假手术组明显增加，四组问进行统计学分析，具有显著性差异。（2）模型组和两种剂量的依达拉奉组均于6h即可观察到TUNEL阳性细胞，24h明显增加，72h时达到高峰，7d时明显减少，14d时于血肿周边仍可见少量阳性细胞。（3）凋亡细胞数与脑组织产生自由基能力（r=0．2003）及MDA含量（r=0．6563）具有相关性。结论脑出血后细胞凋亡数和自由基水平变化趋势相同，二者具有相关性，提示自由基可能参与诱导出血后神经元及胶质细胞凋亡。     

大鼠实验性脑出血后脑水肿与MMP-9表达的关系及依达拉奉干预效应的研究

目的 探讨脑出血后脑水肿和MMP-9表达的动态变化及依达拉奉的干预效应.方法 采用立体定向技术制作大鼠脑出血模型,干湿重法测量脑组织含水量和免疫组化法测定脑组织MMP-9的表达.结果 与假手术组比较,脑出血12h时脑组织含水量明显增加(P＜0.05), 72h时达到高峰,随后逐渐下降, 7d时仍高于假手术组(P＜0.05).出血组大鼠脑含水量与血肿周围MMP-9阳性细胞数呈正相关(r=0.846, P=0.034),且差异有统计学意义.(3)治疗组脑含水量和MMP-9阳性细胞数与假手术组比较差异有统计学意义,与出血组比较差异亦有统计学意义(P＜0.05).结论 MMP-9参与了脑出血后脑水肿的形成,依达拉奉对脑水肿有抑制作用.     

依达拉奉对脑缺血再灌注损伤保护作用机制的研究

目的 探讨依达拉奉对脑缺血再灌注损伤的保护机制.方法 将45只健康雄性Wistar大鼠随机分为假手术组、生理盐水对照组、依达拉奉干预组各15只,采用线栓法制作大鼠大脑中动脉缺血模型,脑缺血2h再灌注即刻及12h干预组给予依达拉奉3mr/kg,对照组给予等量生理盐水分别腹腔注射.于24h后断头取脑,免疫组化法测细胞色素C(Cyt C)、半胱氨酸蛋白酶-3(Caspase-3),TUNEL法检测神经细胞凋亡,化学比色法测MDA、SOD,TTC染色测梗死体积.结果 假手术组无梗死现象,免疫反应阳性细胞及凋亡细胞亦少见.依达拉奉十预组与生理盐水对照组相比,Cyt C阳性细胞数、Caspase-3阳性细胞数及凋亡细胞数均明显减少,MDA含量减少,SOD活性有所恢复,差异均有统计学意义.生理盐水对照组可见明显大脑中动脉供血区梗死灶,依达拉奉干预组亦可见到梗死灶,与对照组比梗死体积占全脑体积的百分比明显缩小(t=6.576,P＜0.01).结论 依达拉奉有自由基清除作用,减少了Cyt C的释放,抑制了细胞凋亡,并缩小了梗死体积;依达拉奉可能通过线粒体途径抑制细胞凋亡.对脑缺血再灌注损伤有保护作用.     

依达拉奉对脑出血大鼠脑代谢的改善作用及其机制研究

目的探讨自由基清除剂依达拉奉对脑出血大鼠脑组织葡萄糖代谢率及神经行为学的影响,并通过检测血肿周围脑含水量及细胞凋亡水平变化,探索依达拉奉改善脑出血后脑代谢水平的作用机制。方法采用自体血立体定向注射建立大鼠脑出血模型,治疗组于建模后皮下注射依达拉奉10 mg/(kg·3 d),对照组注射同体积生理盐水。各组分别于造模后3 d行神经行为学评分及脑含水量测定,并采用小动物正电子发射断层显像/X线计算机体层成像(PET/CT)检测血肿周围葡萄糖代谢率变化,脑组织切片行原位末端脱氧核苷酸转移酶介导的生物素脱氧尿嘧啶核苷酸缺口末端标记法(TUNEL)染色,判定血肿周围细胞凋亡水平变化。结果依达拉奉干预脑出血大鼠后3 d,前肢抬起及转角实验较对照组均明显改善,脑含水量亦明显降低。依达拉奉组血肿周围脑组织葡萄糖代谢率较对照组明显改善,脑代谢降低区域体积较对照组明显减少。血肿周围脑组织TUNEL染色显示,依达拉奉组凋亡细胞明显少于对照组。结论依达拉奉可明显改善脑出血大鼠脑代谢水平及神经功能障碍,减轻脑出血后继发性损伤,其机制可能与减轻血肿周围脑水肿、抑制神经细胞凋亡有关。     

自由基清除剂预处理对大鼠脑缺血再灌注损伤后脑组织细胞凋亡及其相关蛋白表达的影响

目的探讨自由基清除剂依达拉奉预处理对大鼠脑缺血再灌注损伤后神经细胞凋亡及其相关蛋白Bcl-2、Bax、热休克蛋白70(HSP70)表达的影响。方法将45只雄性SD大鼠随机分为假手术组、对照组、依达拉奉预处理组,每组15只。采用线栓法制作大鼠缺血2h再灌注24h模型。预处理组大鼠建模前12h腹腔注射依达拉奉(3mg/kg),对照组给予等容量生理盐水。再灌注24h后断头取脑,应用免疫组织化学法检测Bcl-2、Bax、HSP70蛋白表达,末端脱氧核糖核酸转移酶介导的原位缺口末端标记法检测凋亡细胞。结果依达拉奉预处理组和对照组大鼠缺血周围脑组织中凋亡细胞和Bcl-2、Bax及HSP70阳性细胞数比假手术组均明显增加(P<0.01);与对照组比较,其凋亡细胞和Bax阳性细胞数均明显减少(P<0.01),而Bcl-2和HSP70阳性细胞数明显增加(P<0.01)。结论细胞凋亡在缺血再灌注损伤中起着重要作用;依达拉奉可能通过上调Bcl-2、HSP70蛋白表达、下调Bax蛋白表达减轻大鼠脑缺血再灌注后的细胞凋亡,增加脑缺血再灌注损伤耐受性,从而起到神经保护作用。     

依达拉奉对糖尿病脑缺血再灌注大鼠细胞凋亡及缺氧诱导因子表达的影响

目的 探讨依达拉奉对糖尿病急性脑缺血再灌注大鼠细胞凋亡及缺氧诱导因子表达的影响.方法 选取健康雄性SD大鼠70只,采用腹腔内一次性注入新鲜配制的1%链尿佐菌素(STZ)及线栓法建立糖尿病大鼠大脑中动脉闭塞再灌注模型.随机分成依达拉奉干预脑缺血再灌注组(干预组)30只、非依达拉奉干预脑缺血再灌注组(非干预组)30只、假手术组5只和正常组5只.前两组又分为缺血2h再灌注1h、6h、12h、24h、48h、72h亚组,每亚组5只.用TUNEL法检测细胞凋亡的变化,用免疫组化法检测缺氧诱导因子(HIF-1α)的表达水平.结果 依达拉奉干预组各个时间点脑皮质区凋亡细胞数及缺氧诱导因子表达量均低于非依达拉奉干预组(P<0.05).结论 依达拉奉可明显减少糖尿病急性脑缺血再灌注大鼠脑神经细胞凋亡数,同时可减少缺氧诱导因子的表达.在糖尿病脑缺血再灌注过程中具有明显神经保护作用.     

自由基清除剂依达拉奉对大鼠脑出血的治疗作用

目的 探讨自由基清除剂依达拉奉对实验性脑出血的保护作用及其作用机制.方法 240只SD雄性大鼠随机分为4组:假手术组、手术模型组、依达拉奉术前给药(A)组和依达拉奉术后给药(B)组.参考Rosenberg的脑出血模型的制作方法建立大鼠脑出血模型,采用干重法评价脑水肿程度,Bederson评分法评价神经功能缺损,并观察依达拉奉对血肿周围脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)的影响.结果 手术模型组及依达拉奉A、B组脑组织中水的含量高于假手术组,而依达拉奉A、B组低于模型组,其差异有统计学意义(P＜0.01);依达拉奉A、B组大鼠肢体神经功能缺损的恢复明显快于模型组;与假手术组[(70.7±2.7)U/mg]相比,造模后20 min模型组及依达拉奉A、B组大鼠脑组织SOD活性即开始下降[分别为(62.5±2.5)、(65.2±5.3)、(61.6±4.2)U/mg],180 min时降至最低(P＜0.01),而与同时点模型组比较,依达拉奉各组SOD活性有不同程度升高,其差异有统计学意义(P＜0.01).与假手术组[(2.9±0.2)nmol/mg]相比,造模后20min模型组及依达拉奉A、B组大鼠脑组织MDA含量开始增加[分别为(3.4±0.2)、(3.1±0.2)、(3.2±0.5)nmol/mg],与同时点模型组比较,依达拉奉各组MDA含量有不同程度降低,80、110、180min时差异有统计学意义(P＜0.01).结论 依达拉奉可抑制大鼠实验性脑出血脑细胞的过氧化作用,减轻脑水肿,改善神经功能,具有脑保护作用.     

依达拉奉对大鼠急性脊髓损伤后神经细胞凋亡的影响

目的:观察依达拉奉对大鼠急性脊髓损伤后细胞凋亡的影响,探讨脊髓保护的作用机制。方法:120只SD雄性大鼠,Allen法建立脊髓损伤模型,随机分为依达拉奉组、假手术组和对照组（均n=40）。依达拉奉组给予依达拉奉10mg·kg^-1,每日2次腹腔注射,连续6d;对照组给予等量同次数的生理盐水腹腔灌注;假手术组仅行椎板切除,不损伤脊髓,不给药。在伤后第1、7、14、28天观察各组大鼠活动情况行BBB评分,取受伤脊髓节段检测抑制羟自由基能力、caspase-3蛋白表达、原位脱氧糖核苷酸末端转移酶介导的原位末端标记法（TUNEL法）标记凋亡细胞。结果:依达拉奉组抑制羟自由基能力明显高于假手术组和对照组（P<0.05）;依达拉奉组caspase-3与对照组比各时间点的表达明显降低（P<0.05）;依达拉奉组与对照组比各时间点凋亡细胞显著减少（P<0.05）。结论:依达拉奉能减少急性脊髓损伤部位的羟自由基,下调caspase-3表达,抑制脊髓神经细胞凋亡,对继发性脊髓损伤有保护作用。     

依达拉奉对大鼠脑创伤后神经细胞凋亡信号通路的影响

目的 探讨依达拉奉对脑创伤后神经细胞凋亡信号通路的影响.方法 135只雄性SD大鼠随机分为对照组(25只)、创伤组(60只)和依达拉奉组(50只).Marmarou's法建立SD大鼠弥漫性脑创伤模型;依达拉奉组大鼠伤后即刻经尾静脉注射依达拉奉10 mg/kg,每天1次,共3 d;分别于伤后1 h、6 h、24 h、48h和72 h采用硫代巴比妥酸法检测大脑皮质中丙二醛(MDA)含量;免疫组化法和Western Blot法检测皮质区磷酸化细胞外信号调节激酶(ERK1/2)及细胞色素C(CytC)的表达;原位缺口末端标记法(TUNEL)检测神经细胞凋亡.伤后24 h、48 h、72 h对大鼠综合运动功能进行评定.结果 与对照组比较,创伤组大鼠脑组织MDA水平(6 h、24 h、48 h、72 h)、磷酸化ERK1/2(1 h、6 h、24 h、48 h)和CytC(6 h、24 h、48 h、72 h)表达明显增高,细胞凋亡数(6 h、24 h、48 h、72 h)增多;综合运动能力评分下降(均P＜0.05).与创伤组比较,依达拉奉组大鼠脑组织MDA含量、磷酸化ERK1/2和CytC表达、神经细胞凋亡数下降;大鼠的运动功能评分回升(均P＜0.05).结论 依达拉奉通过清除氧自由基、抑制ERK1/2信号途径活化、减少神经细胞凋亡而发挥对脑创伤的保护作用.     

依达拉奉对局灶性脑缺血再灌注损伤大鼠caspase-3、Bcl-2表达的影响

目的 对局灶性脑缺血再灌注损伤大鼠,给予自由基清除剂依达拉奉后,观察再灌注不同时间点脑组织caspase-3和Bcl-2蛋白表达情况,探讨依达拉奉对脑缺血再灌注损伤的保护作用.方法 制作局灶性脑缺血再灌注模型.随机分为正常组、假手术组、脑缺血组、依达拉奉组.假手术组于术后,脑缺血组和依达拉奉组于缺血1h后再灌注2h、6h、12h、24h、48h不同时间点,依达拉奉组于再灌注后30min腹腔内及皮下各注射依达拉奉1 次(3mg/kg.wt),30min 后重复1次.按时间点处死大鼠,灌注固定、取脑,行免疫组化染色,观察和计数不同脑区的caspase-3和Bcl-2蛋白表达阳性细胞数.结果 脑缺血组再灌注后2h在大脑额、顶叶皮质和海马均可见到caspase-3和Bcl-2阳性细胞,caspase-3表达高峰在12h;Bcl-2表达高峰在6h.依达拉奉组各时间点caspase-3阳性细胞较脑缺血组明显减少,而Bcl-2阳性细胞数明显增加 (均为P＜0.05).结论 依达拉奉可抑制caspase-3,提高Bcl-2的蛋白表达,对脑缺血再灌注损害有明显的保护作用.     

依达拉奉干预对大鼠脑出血模型细胞凋亡相关通路的影响

目的研究脑出血后自由基对于细胞凋亡通路的影响。方法将动物随机分为4组，假手术组、模型组、依达拉奉组1（1mg／kg）、依达拉奉组2（3mg／kg），通过立体定向技术，采用二次注血／退针方法向成年SD大鼠左尾壳核注入自体血80ul，制造大鼠脑出血动物模型。通过免疫组化半定量检测脑出血后肿瘤坏死因子-α（Tumournecrosis factor-alpha，TNF-a）的表达，并通过Westernblot检测脑组织中Caspase-3、8的表达水平。结果出血后模型组和药物干预组TN卜a表达水平有差异。半定量检测Caspase-3、Caspase-8蛋白水平，脑出血后二者均有激活，总体水平模型组和两种剂量药物干预组较假手术高，且模型组表达量高于药物干预组。结论脑出血后自由基可能对于TNF-α表达及分泌具有诱导作用，Caspase-3、Caspase-8蛋白表达水平升高，认为死亡受体通路可能参与脑出血后细胞凋亡，并与自由基水平有关。     

中药补阳还五汤对脑出血大鼠脑组织水通道蛋白4表达的影响

目的探讨中药补阳还五汤对脑出血大鼠脑组织水通道蛋白4(AQP4)表达的影响。方法 55只雄性SD大鼠随机分为假手术组(5只)、脑出血模型组(25只)和补阳还五汤治疗组(25只)。采用自体血注入法制作右侧纹状体出血大鼠模型。假手术组不注入自体血。补阳还五汤治疗组于术前给予1 ml/100 g补阳还五汤浓缩液灌胃3 d,假手术组和脑出血模型组同期给予等量生理盐水替代。在相应时间点分别对大鼠进行神经功能缺损评分后处死大鼠。采用免疫组化法检测脑组织AQP4蛋白的表达,采用原位杂交法检测脑组织AQP4 mRNA的表达。结果补阳还五汤治疗组及脑出血模型组大鼠神经功能缺损评分明显高于假手术组(均P<0.05)。补阳还五汤治疗组大鼠术后3 d和7 d时神经功能缺损评分明显低于脑出血模型组(均P<0.05)。补阳还五汤治疗组及脑出血模型组大鼠脑组织AQP4蛋白和mRNA表达水平明显高于假手术组(均P<0.05)。补阳还五汤治疗组大鼠术后3 d和7 d时脑组织AQP4蛋白和mRNA表达水平明显低于脑出血模型组(均P<0.05)。各组大鼠均未见明显不良反应。结论补阳还五汤可抑制脑出血大鼠脑组织中AQP4的表达,并有助于其神经功能恢复。补阳还五汤治疗脑出血有效可能与其抑制AQP4的表达,减轻脑水肿有关。     

A randomized controlled clinical trial to compare the safety and efficacy of edaravone in acute ischemic stroke

Background and Objective:

Edaravone has potent antioxidant and free radical scavenger properties. Few Japanese studies had demonstrated its neuroprotective role in acute ischemic stroke (AIS). This study aims to evaluate the efficacy of edaravone in terms of functional outcome in a group of Indian patients of AIS.

Materials and Methods:

Fifty patients of AIS were randomly divided into two groups. The study group received 30 mg of edaravone twice daily for 14 days by infusion, while control group received normal saline infusion as placebo. Outcome assessment was done by the Modified Rankin Scale (MRS). MRS score ≤2 at 90 days was considered as a favorable outcome.

Results:

Of 25 patients, 18 (72%) had favorable outcomes (MRS ≤2) at 90 days in edaravone group, while 10 (40%) of 25 patients in placebo group had favorable outcome (P < 0.005). Two patients expired (one in each group) during treatment. The mean Barthel index increased from 41.20 ± 32.70 at baseline to 82.40 ± 18.32 at day 90 in edaravone group as compared with placebo group in which scores were 44.20 ± 22.76 at baseline and 68.20 ± 21.30 at day 90 (P < 0.005).

Conclusions:

We therefore conclude that edaravone effectively improves functional outcome in AIS.     

姜黄素对脑出血大鼠血肿周围脑组织氧化损害保护作用的研究

目的:探讨姜黄素对脑出血(ICH)后脑组织氧化损害的保护作用。方法:120只SD大鼠随机分为姜黄素治疗组(Cur治疗组,n=40)、脑出血对照组(ICH对照组,n=40)和假手术组(n=40)。每组分为手术前、术后6h、12h、24h、48h、72h、96h、120h等8个时点,每个时点5只大鼠。采用立体定向自体血注入大鼠尾状核建立ICH模型,观察各组术前及术后各时点血肿周围脑组织超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量及含水量变化。结果:ICH对照组术后各时间点SOD活性明显低于假手术组(P<0.05),而术后各时间点MDA含量显著高于假手术组(P<0.05),ICH对照组术后各时点含水量与SOD活力呈明显负相关(r=-0.626,P<0.05),与MDA含量呈明显正相关(r=0.648,P<0.001)。Cur治疗组术后12～120h各时点的SOD活力显著高于ICH对照组(P<0.05),12～96h各时点MDA含量明显低于ICH对照组(P<0.001),Cur治疗组术后各时点含水量与SOD活力呈显著负相关r=-0.458,P<0.05),与MDA含量呈显著正相关(r=0.407,P<0.05)。结论:脑出血大鼠血肿周围脑组织具有显著的氧化损害,此损害与脑水肿形成有关。Cur治疗脑出血大鼠使氧化损害明显减轻,Cur对抗脑出血后脑水肿形成可能与抑制自由基产生和清除自由基有关。     

Therapeutic Temperature Modulation for Fever After Intracerebral Hemorrhage

Background

We sought to determine whether therapeutic temperature modulation (TTM) to treat fever after intracerebral hemorrhage (ICH) is associated with improved hospital complications and discharge outcomes.

Methods

We performed a retrospective case–control study of patients admitted with spontaneous ICH having two consecutive fevers ≥38.3 °C despite acetaminophen administration. Cases were enrolled from a prospective database of patients receiving TTM from 2006 to 2010. All cases received TTM for fever control with goal temperature of 37 °C with a shiver-control protocol. Controls were matched in severity by ICH score and retrospectively obtained from 2001 to 2004, before routine use of TTM for ICH. Primary outcome was discharge-modified Rankin score.

Results

Forty patients were enrolled in each group. Median admission ICH Score, ICH volume, and GCS were similar. TTM was initiated with a median of 3 days after ICH onset and for a median duration of 7 days. Mean daily T _max was significantly higher in the control group over the first 12 days (38.1 vs. 38.7 °C, p ≤ 0.001). The TTM group had more days of IV sedation (median 8 vs. 1, p < 0.001) and mechanical ventilation (18 vs. 9, p = 0.003), and more frequently underwent tracheostomy (55 vs. 23 %, p = 0.005). Mean NICU length of stay was longer for TTM patients (15 vs. 11 days, p = 0.007). There was no difference in discharge outcomes between the two groups (overall mortality 33 %, moderate or severe disability 67 %).

Conclusions

Therapeutic normothermia is associated with increased duration of sedation, mechanical ventilation, and NICU stay, but is not clearly associated with improved discharge outcome.     

Mild Prolonged Hypothermia for Large Intracerebral Hemorrhage

Background

Perihemorrhagic edema (PHE) develops after intracerebral hemorrhage (ICH). It can worsen the clinical situation by its additional mass effect. Therapeutic hypothermia (TH) might be an effective method to control PHE, but has not been sufficiently studied in ICH patients.

Methods

We report data on n = 25 consecutive patients with large supratentorial ICH (volume > 25 ml) who were treated by mild TH of 35 °C for 8–10 days. Body temperature was controlled by endovascular cooling catheters. We followed the clinical course during hospital stay and measured volumes of ICH and PHE in regularly performed serial cranial computed tomography. Outcome was assessed after 3 and 12 months. These data were compared to a historical group of n = 25 patients with large ICH.

Results

While PHE continuously increased in the historical control group up to day 10, PHE volumes in the hypothermia group remained stable. There was a significant difference from day 3 after symptom onset. Shivering (36 %) and pneumonia (96 %) were the most frequent complications during TH. Mortality rate was 8.3 % in TH versus 16.7 % in the control group after 3 months and 28 versus 44 % after 1 year.

Conclusions

These data support the promising results of our first case series on TH in large ICH. TH prevents the development of PHE and its complications. Side effects of TH appeared often, but could be treated sufficiently. Therefore, TH might represent a new therapy for PHE after large ICH, but has to be further tested in randomized trials.     

Recombinant activated factor VII for acute intracerebral hemorrhage US phase IIA trial

Background and Purpose

Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven^®) for preventing early hematoma growth in acute ICH.

Methods

In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 μg/kg of rFVIIa (n=8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs).

Results

Mean age was 65 years (range 34–91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17±19 mL; nearly three-quarters were located in the basal ganglia (n=29). The mean interval from onset to treatment was 178±41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 μg/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 μg/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [n=2], 20 μg/kg [n=1], 40 μg/kg [n=1], and 80 μg/kg [n=2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred.

Conclusions

Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.     

Coagulopathy Disproportionately Predisposes to Lobar Intracerebral Hemorrhage

Background

Anticoagulation increases the risk of intracerebral hemorrhage (ICH), yet whether different underlying disease processes are equally affected is unknown. We tested the hypothesis that coagulopathy, measured by admission international normalized ratio (INR), disproportionately increases the risk for lobar hemorrhages.

Methods

Patients with primary ICH were enrolled into a registry between December 2006 and February 2012 with prospective data acquisition and systematic follow up. Logistic regression was used to test whether lobar versus deep ICH location was independently associated with INR, and then whether INR had an influence on mortality. Spearman’s correlation coefficient was used to test for an association between INR and hematoma volume separately in the lobar and deep ICH groups.

Results

221 patients were studied. Patients with lobar ICH were older (71 vs. 62 years old, p < 0.001) and more likely to have prior ICH (10 vs. 0 %, p < 0.001). INR >1.4 was observed on admission more frequently in lobar versus deep ICH (19 vs. 8 %, p = 0.02). Lobar ICH location was independently associated with INR >1.4 (OR: 2.51, 95 % CI: 1.03–6.14, p = 0.043). ICH volume correlated with INR in lobar ICH (p = 0.009), but not deep ICH (p = 0.8). Death at 1 month was independently associated with INR >1.4 (OR: 7.6, 95 % CI: 2.4–24.1, p = 0.001) after correction for the ICH Score.

Conclusions

Abnormal coagulation occurs disproportionally in lobar versus deep ICH, and is associated with larger ICH volumes and higher mortality. These findings suggest a unique risk interaction between coagulopathy and underlying brain pathology due to cerebral amyloid angiopathy.