Neurosurgical management of spontaneous cerebral hemorrhage

Intracerebral hemorrhage (ICH) accounts for 10 to 20% of strokes, but carries the highest rate of morbidity and mortality. Until now, there is no proven benefit in the literature for surgical treatment of ICH, and management of ICH varies greatly in neurosurgical centers. Surgery can be performed through standard craniotomy, or with a stereotactic procedure for deep-seated ICH. Conscious patients with minimal neurological deficit and small ICH are nonsurgical candidates. Patients with a Glasgow Coma Score lower than 4, with large deep-seated ICH are also non surgical candidates. In other situations, the following arguments could lead to the decision of surgery: superficial (so-called lobar) ICH, size above 3 cm in diameter, midline shift, secondary neurological worsening, young patient, underlying vascular malformation. Acute hydrocephalus from ventricular hemorrhage may be treated with external ventricular drainage if the associated deep-seated ICH is small in size. Indications of surgery are more frequent for cerebellar ICH, as the risks for brainstem compression and hydrocephalus from ventricular obstruction are important.     

Intensive care management [corrected] of patients with intracerebral hemorrhage

Approximately 10-15% of acute strokes are caused by non-aneurysmatic intracerebral hemorrhage (ICH) and incidences are expected to increase due to an aging population. Studies from the 1990s estimated mortality of ICH to be as high as 50%. However, these figures may partly be attributed to the fact that patients suffering from ICH frequently received only supportive therapy and the poor prognosis may therefore be more a self-fulfilling prophecy. Recently it has been shown that treatment in a specialized neurological intensive care unit alone was associated with better outcomes after ICH. In recent years considerable efforts have been undertaken in order to develop new therapies for ICH and to assess them in randomized controlled trials. Apart from admission status, hemorrhage volume is considered to be the main prognostic factor and impeding the spread of the hematoma is thus a basic therapeutic principle. The use of activated factor VIIa (aFVIIa) to stop hematoma enlargement has been assessed in two large randomized controlled trials, however the promising results of the dose-finding study could not be confirmed in a phase III trial. Although hemostatic therapy with aFVIIa reduced growth of the hematoma it failed to improve clinical outcome. Similar results were found in a randomized controlled trial on blood pressure management in acute ICH. The link between reduction of hematoma growth and improved outcome is therefore still lacking. Likewise the value of surgical hematoma evacuation remains uncertain. In the largest randomized controlled trial on surgical treatment in ICH so far, only a small subgroup of patients with superficial hemorrhages seemed to benefit from hematoma evacuation. Whether improved intensive care can contribute to improved outcome after ICH will be shown by data obtained in the coming years.     

Phase II study of two-weekly temozolomide in patients with high-grade gliomas.

Palliative chemotherapy has an increasing role in the management of recurrent high-grade gliomas. Temozolomide is a well-tolerated agent that results in objective responses and stabilisation of disease. Theoretically, temozolomide may be more effective when given in a prolonged schedule rather than the standard 5 days-monthly schedule. This Phase II study examined the efficacy and toxicity of temozolomide when given in a two-weekly schedule. Twenty-five patients received 150 mg/m2 temozolomide daily for seven days alternating with seven days of no treatment. One cycle of temozolomide was a total of two weeks treatment in every 28 days. Of the 25 evaluable patients, there was one complete response (4%), four partial responses (16%) and 10 patients had disease stablisation (40%). The progression free survival at 6 months was 56%. Two-weekly temozolomide was well tolerated with only four episodes of Grade 3 thrombocytopenia. Overall, two-weekly temozolomide is an active and well tolerated schedule, but does not appear to improve on the activity of temozolomide using the standard 5-day schedule.     

Coil Embolization of Aneurysm Followed by Stereotactic Aspiration of Hematoma in a Patient with Anterior Communicating Artery Aneurysm Presenting with SAH and ICH

Even though intracerebral hematoma (ICH) due to ruptured cerebral aneurysm has been treated by aneurysm clipping at the same time of removal of ICH through craniotomy, such management strategy is controversial in an aged patients with poor clinical grade. In this regards, stereotactic aspiration of hematoma following coil embolization can be an alternative treatment modality. Thus, the authors report a case of an aged patient who underwent stereotactic aspiration of ICH following coil embolization for the ruptured aneurysm with a brief review of literature.     

丹参酮ⅡA对脑出血大鼠脑组织HIF-1α和VEGF表达的影响

目的探讨丹参酮ⅡA对脑出血大鼠的干预作用以及对HIF-1α和VEGF表达的影响。方法将大鼠随机分为假手术组、脑出血组、丹参酮ⅡA干预I组和II组,除假手术组外,其余大鼠均通过注射胶原酶的方法建立脑出血模型,丹参酮IIA干预Ⅰ组和Ⅱ组分别腹腔注射丹参酮IIA30 mg/kg,每天一次和30 mg/kg,每天两次,共给药15 d。给药完成后,对各组大鼠进行神经功能缺损评分,称重法计算脑组织的含水量,免疫组化法与实时荧光定量PCR检测脑组织中HIF-1α和VEGF的蛋白表达与mRNA表达。结果与脑出血组相比,丹参酮IIA干预组大鼠的神经功能缺损评分显著升高,脑组织含水量显著下降,脑组织中HIF-1α和VEGF的蛋白表达与mRNA表达显著升高。结论丹参酮IIA对脑出血大鼠脑组织具有保护作用,其作用机制可能与HIF-1α和VEGF因子的表达有关。     

Treatment and prevention of primary intracerebral hemorrhage

Intracerebral hemorrhage (ICH), which constitutes 10 to 15% of all strokes and affects approximately 65,000 people each year in the United States, has the highest mortality rate of all stroke subtypes. Hypertension, cerebral amyloid angiopathy, and anticoagulation underlie the majority of cases of ICH. Warfarin not only increases the risk but also increases the severity of ICH by causing hematoma expansion. With the advent of gradient-echo magnetic resonance imaging, patients with underlying cerebral amyloid angiopathy or hypertensive vasculopathy can be identified, and measures can be taken to prevent ICH. Initiating an antihypertensive regimen in a patient with nonlobar microbleeds suggestive of hypertensive vasculopathy, and withholding warfarin in patients with lobar microbleeds suggestive of cerebral amyloid angiopathy, are emerging prevention strategies. Although a treatment for cerebral amyloid angiopathy does not exist, agents targeting beta-amyloid metabolism and bioactivity are promising candidates. Strategies for preventing warfarin-associated hemorrhage include strict monitoring of anticoagulation levels and using agents such as direct thrombin inhibitors. The future of ICH management lies in therapies targeted at the pathophysiological steps in ICH. Potential treatments include glutamate receptor antagonists for preventing glutamate excitotoxicity, matrix metalloproteinase and thrombin inhibitors for preventing perihematomal edema, and recombinant activated factor VII for preventing hematomal expansion.     

Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: Design,Methods, and Rationale

The December 2003 report from the National Institute of Neurological Disorders and Stroke (NINDS) Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) recommended clinical trials for evaluation of blood pressure management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertensive response in ICH. To address important gaps in knowledge, we conducted a pilot study funded by the NINDS, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) I Trial, during 2004–2008 to determine the appropriate level of systolic blood pressure (SBP) reduction. We now have initiated a multi-center, randomized Phase III trial, the ATACH II Trial, to definitively determine the efficacy of early, intensive, antihypertensive treatment using intravenous (IV) nicardipine initiated within 3 h of onset of ICH and continued for the next 24 h in subjects with spontaneous supratentorial ICH. The primary hypothesis of this large (N = 1,280), streamlined, and focused trial is that SBP reduction to ≤140 mm Hg reduces the likelihood of death or disability at 3 months after ICH, defined by modified Rankin scale score of 4–6, by at least 10% absolute compared to standard SBP reduction to ≤180 mm Hg. The ATACH II trial is a natural extension of numerous case series, the subsequent ATACH I pilot trial, and a preliminary, randomized, and controlled trial in this patient population funded by the Australian National Health and Medical Research Council. Both trials recently confirmed the safety and tolerability of both the regimen and goals of antihypertensive treatment in acutely hypertensive patients with ICH, as proposed in the present trial. The underlying mechanism for this expected beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 73% of the patients with acute ICH. The Australian trial provided preliminary evidence of attenuation of hematoma expansion with intensive SBP reduction. The ATACH II trial will have important public health implications by providing evidence of, or lack thereof, regarding the efficacy and safety of acute antihypertensive treatment in subjects with ICH. This treatment represents a strategy that can be made widely available without the need for specialized equipment and personnel, and therefore, can make a major impact upon clinical practice for treating patients with ICH.

     

Intracerebral hemorrhage in COVID-19: A narrative review

Coronavirus Disease 19 (COVID-19) pandemic affects the worldwide healthcare system and our understanding of this disease grows rapidly. Although COVID-19 is a mainly respiratory disease, neurological manifestations are not uncommon. The aim of this review is to report on the etiology, clinical profile, location, and outcome of patients with intracerebral hemorrhage (ICH) and COVID-19. This review includes 36 studies examining ICH in the clinical presentation of COVID-19. Overall, 217 cases with intracranial hemorrhage, of which 188 ICHs, were reported. Generally, a low incidence of both primary and secondary ICH was found in 8 studies [106 (0.25%) out of 43,137 hospitalized patients with COVID-19]. Available data showed a median age of 58 years (range: 52–68) and male sex 64%, regarding 36 and 102 patients respectively. Furthermore, 75% of the patients were on prior anticoagulation treatment, 52% had a history of arterial hypertension, and 61% were admitted in intensive care unit. Location of ICH in deep structures/basal ganglia was ascertained in only 7 cases making arterial hypertension an improbable etiopathogenetic mechanism. Mortality was calculated at 52.7%. Disease related pathophysiologic mechanisms support the hypothesis that SARS-CoV2 can cause ICH, however typical ICH risk factors such as anticoagulation treatment, or admission to ICU should also be considered as probable causes. Physicians should strongly suspect the possibility of ICH in individuals with severe COVID-19 admitted to ICU and treated with anticoagulants. It is not clear whether ICH is related directly to COVID-19 or reflects expected comorbidity and/or complications observed in severely ill patients.     

Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases

Intracerebral hemorrhage (ICH) is characterized by parenchymal hematoma formation with surrounding inflammation. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of neurological diseases defined by inflammation and cell death. To investigate the expression profile and pathogenic aspects of MMPs in ICH, we examined MMP expression in vivo using a collagenase-induced rat model of ICH. ICH increased brain MMP-2, -3, -7, and -9 mRNA levels relative to sham-injected (control) animals in the vicinity of the hematoma, but MMP-12 (macrophage metalloelastase) was the most highly induced MMP (>80-fold). Immunohistochemistry showed MMP-12 to be localized in activated monocytoid cells surrounding the hematoma. In vitro studies showed that thrombin, released during ICH, induced MMP-12 expression in monocytoid cells, which was reduced by minocycline application. Similarly, in vivo minocycline treatment significantly reduced MMP-12 levels in brain. Neuropathological studies disclosed marked glial activation and apoptosis after ICH that was reduced by minocycline treatment. Neurobehavioral outcomes also were improved with minocycline treatment compared with untreated ICH controls. Thus, select MMPs exhibit increased expression after ICH, whereas minocycline is neuroprotective after ICH by suppressing monocytoid cell activation and downregulating MMP-12 expression.     

Glioma therapy up-date

The prognosis for patients with malignant brain tumors has always been poor and until recently chemotherapy had not shown to be very effective. Temozolomide is a novel second-generation alkylating agent that has shown efficacy for the treatment of high-grade gliomas. Temozolomide is well-tolerated by most patients and has favorable pharmacodynamic and pharmacokinetic properties. In patients with newly diagnosed glioblastoma multiforme, radiation therapy with concurrent and adjuvant temozolomide significantly improves overall survival compared to treatment with only radiation. The benefit of temozolomide is greatest in patients with tumors that have a methylated 06-methyl-guanine DNA methyl transferase gene promoter that results in decreased repair of temozolomide-induced DNA damage. This chapter will briefly review the diagnosis and treatment of patients with malignant brain tumors and then will focus on the role of temozolomide in glioma therapy.     

Cerebral venous sinus thrombosis associated with cerebral hemorrhage: is anticoagulant treatment safe?

The current recommended treatment for cerebral venous sinus thrombosis (CVST) is anticoagulation, and the presence of intracranial hemorrhage (ICH) is not a contraindication. We present a case of ICH associated with CVST in which heparin treatment was associated with rebleeding, and we review current evidence of anticoagulation safety in patients with ICH associated with CVST. A 65-year-old man presented with right hemiparesis and loss of consciousness. Brain computed tomography showed a left frontoparietal hemorrhage. Angiographic studies with magnetic resonance imaging showed the presence of a partial superior saggital sinus thrombosis. With a diagnosis of CVST, intravenous heparin was administered. After 24 hours the patient had a symptomatic increase in ICH size, and 2 days later the patient developed a status epilepticus with new evidence of rebleeding. Anticoagulant treatment was stopped and the patient experienced neurological improvement, with no new episodes of rebleeding. Evidence for the safety of anticoagulants in CVST comes from 2 small trials involving a total of 79 patients, but only 18 had some degree of bleeding in baseline computed tomography. A meta-analysis suggested that in CVST patients who are treated with anticoagulants, the risk of ICH is low, but acknowledged that an impact of up to 9% of new ICH cannot be ruled out. As there is not enough evidence for the safety of anticoagulant therapy in patients with early ICH associated with CVST, the therapeutic decision must be individualized and the rebleeding risk should be weighed in those patients.     

MRI features of intracerebral hemorrhage within 2 hours from symptom onset.

BACKGROUND AND PURPOSE: MRI has been increasingly used in the evaluation of acute stroke patients. However, MRI must be able to detect early hemorrhage to be the only imaging screen used before treatment such as thrombolysis. Susceptibility-weighted imaging, an echo-planar T2* sequence, can show intracerebral hemorrhage (ICH) in patients imaged between 2.5 and 5 hours from symptom onset. It is unknown whether MRI can detect ICH earlier than 2.5 hours. We describe 5 patients with ICH who had MRI between 23 and 120 minutes from symptom onset and propose diagnostic patterns of evolution of hyperacute ICH on MRI. METHODS: As part of our acute imaging protocol, all patients with acute stroke within 24 hours from symptom onset were imaged with a set of sequences that included susceptibility-weighted imaging, diffusion- and perfusion-weighted imaging, T1- and T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR), and MR angiography using echo-planar techniques. Five patients with ICH had MRI between 23 and 120 minutes from the onset of symptoms. RESULTS: ICH was identified in all patients. Distinctive patterns of hyperacute ICH and absence of signs of ischemic stroke were the hallmark features of this diagnosis. The hyperacute hematoma appears to be composed of 3 distinct areas: (1) center: isointense to hyperintense heterogeneous signal on susceptibility-weighted and T2-weighted imaging; (2) periphery: hypointense (susceptibility effect) on susceptibility-weighted and T2-weighted imaging; and (3) rim: hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, representing vasogenic edema encasing the hematoma. CONCLUSIONS: MRI is able to detect hyperacute ICH and show a pattern of evolution of the hematoma within 2 hours from the onset of symptoms.     

替莫唑胺治疗难治性垂体腺瘤一例报告并文献复习

目的 探讨难治性垂体腺瘤有效的综合治疗方法.方法 采用手术、伽玛刀及再次手术治疗1例难治性垂体腺瘤患者,然后根据其原代肿瘤细胞培养结果,选用替莫唑胺治疗2个疗程,总结分析其疗效.结果 由于肿瘤生长迅速,常规手术、放疗、药物等治疗方法均难以控制难治性垂体腺瘤生长.根据切除肿瘤病理(Ki-67 LI,MGMT表达水平)及原代肿瘤细胞替莫唑胺敏感实验结果选用替莫唑胺治疗,患者肿瘤停止快速生长,并有肿瘤液化坏死.结论 对于常规手术、放疗及药物治疗无效的难治性垂体腺瘤,替莫唑胺化疗可能是一种替代治疗方法.

Abstract：

Objective To explore the effective treatment for refractory pituitary adenomas.Method Based on MGMT expression and sensitive test of the primary pituitary adenoma cells to temozolomide, we treated a refractory pituitary adenoma patient.Results MGMT expression in this case was at low level,and primary pituitary adenoma cells were sensitive to temozolomide in vitro.The tumor volume decreased after the first cycle temozolomide therapy.Conclusions Temozolomide may be a salvage therapy for those refractory pituitary adenomas with low MGMT expression.     

Intracerebral hemorrhage after thrombolytic therapy managed with ventricular drainage.

Intracerebral hemorrhage (ICH) after thrombolytic treatment for acute myocardial infarction (AMI) is a serious complication causing significant morbidity and mortality. Drainage of the haematoma by craniotomy is associated with poor outcome. We present a patient who received tissue plasminogen activator (t-PA) for acute myocardial infarction; he subsequently developed an ICH with ventricular system extension. The patient was managed by insertion of an external ventricular drain. The hemorrhage was successfully evacuated by insertion of the external ventricular drain. This was unexpected as ICH are usually viscous and difficult to aspirate in the acute phase. This suggests that ICHs following thrombolytic therapy remain liquid for up to 10 h. External ventricular drains can be used in the management of patients with ICH complicating thrombolytic therapy for management of acute myocardial infarction or ischemic stroke. This reduces the need for craniotomy and associated morbidity and mortality.     

Brain abscess following intracerebral haemorrhage

We report two cases of brain abscess, which developed at the site of an intracerebral haemorrhage (ICH) in a 75-year-old man and a 32-year-old-man. The patients recovered after surgical treatment and systemic antibiotic therapy. The route of infection could not be detected in either case. The literature contains only 13 reported cases of brain abscess as a complication of ICH. Although the interval from initial ICH to abscess formation ranged from 4 to 20 weeks, almost all patients had episodes of high fever, indicating the presence of systemic infection and bacterial seeding, 0-14 days after the onset of their ICH. Therefore, abscess formation appears to be caused by haematogenous seeding of infection in patients with ICH. Abscess formation should be considered when a patient deteriorates clinically with a febrile episode after an ICH.     

Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.

OBJECTIVE: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. METHOD: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation. RESULTS: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). CONCLUSIONS: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.     

Deep Intracerebral Hemorrhage Caused by Rupture of Distal Lenticulostriate Artery Aneurysm : A Report of Two Cases and a Literature Review

Intracerebral hemorrhage (ICH) is common among various types of storkes; however, it is rare in young patients and patients who do not have any risk factors. In such cases, ICH is generally caused by vascular malformations, tumors, vasculitis, or drug abuse. Basal ganglia ICH is rarely related with distal lenticulostriate artery (LSA) aneurysm. Since the 1960s, a total of 29 distal LSA aneurysm cases causing ICH have been reported in the English literature. Despite of the small number of cases, various treatment methods have been attempted : surgical clipping, endovascular treatment, conservative treatment, superficial temporal artery-middle cerebral artery anastomosis, and gamma-knife radiosurgery. Here, we report two additional cases and review the literature. Thereupon, we discerned that young patients with deep ICH are in need of conventional cerebral angiography. Moreover, initial conservative treatment with follow-up cerebral angiography might be a good treatment option except for cases with a large amount of hematoma that necessitates emergency evacuation. If the LSA aneurysm still persists or enlarges on follow-up angiography, it should be treated surgically or endovascularly.     

An Australian experience with temozolomide for the treatment of recurrent high grade gliomas.

Temozolomide has an evolving role in the treatment of high grade gliomas. Recent studies suggest that temozolomide is well tolerated and efficacious. This study retrospectively analysed the activity and toxicity associated with temozolomide at two Australian centres over a 24 month period. Fifty-six patients with recurrent high grade gliomas were treated with temozolomide. Patients received temozolomide orally at 150-200mg/m(2)daily, days 1-5, every 4 weeks. The median number of treatment cycles was 4 (1-12). Of the 56 patients, 15 (27%) achieved complete or partial response and 18 (32%) achieved minor response or stable disease. There were no episodes of febrile neutropenia and temozolomide was generally well tolerated. In conclusion, temozolomide is an active therapy in patients with recurrent high grade glioma and our results concord with published studies.     

Current intracerebral haemorrhage management.

Primary intracerebral haemorrhage (ICH) refers to spontaneous bleeding from intraparenchymal vessels. It accounts for 10-20% of all strokes, with higher incidence rates amongst African and Asian populations. The major risk factors are hypertension and age. In addition to focal neurological findings, patients may present with symptoms of elevated intracranial pressure. The diagnosis of ICH can only be made through neuro-imaging. A CT scan is presently standard, although MRI is increasingly important in the evaluation of acute cerebrovascular disease. A significant proportion of intracerebral haematomas expand in the first hours post-ictus and this is often associated with clinical worsening. There is evidence that the peri-haematomal region is compromised in ICH. This tissue is oedematous, although the precise pathogenesis is controversial. An association between elevated arterial pressure and haematoma expansion has been reported. Although current guidelines recommend conservative management of arterial pressure in ICH, an acute blood pressure lowering trial is overdue. ICH is associated with a high early mortality rate, although a significant number of survivors make a functional recovery. Current medical management is primarily aimed at prevention of complications including pneumonia and peripheral venous thromboembolism. Elevated intracranial pressure may be treated medically or surgically. Although the latter definitively lowers elevated intracranial pressure, the optimal patient selection criteria are not clear. Aggressive treatment of hypertension is essential in the primary and secondary prevention of ICH.