Latest advances in intracerebral hemorrhage

Despite the fact that intracerebral hemorrhage (ICH) is the deadliest and least treatable of all stroke subtypes, historically researchers have directed most of their efforts toward ischemic strokes. However in the past few years this tendency has been changing, and several studies are showing very interesting results that allow us to believe that in the following years ICH management will change dramatically, paralleling the recent revolution that ischemic stroke treatment experienced in the past decade. Studies offering a better understanding of risk factors, pathophysiology, and treatment will help in primary and secondary prevention and also in developing therapeutic strategies to reduce brain damage. This review comments on some of the most relevant publications during the past year in any field related to ICH.     

Recent advances in the management of acute intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is the most deadly form of stroke, and its acute treatment has suffered from a lack of guidance by reliable clinical trial data. In the past year, however, important clinical trials have helped point toward effective acute management. Studies have shown that magnetic resonance imaging is as accurate as computed tomography in diagnosing acute ICH, although this study is not always feasible in critically ill patients. Ultra-early hemostatic therapy has shown promise in limiting early hematoma expansion and rebleeding. The role of early surgery in patient management has been partially clarified. Finally, a novel treatment for intraventricular hemorrhage has shown promise in speeding clot resolution. All of these advances provide grounds for optimism that multimodal, evidence-based treatment of acute ICH will be reality in the near future.     

Perihematomal edema: Implications for intracerebral hemorrhage research and therapeutic advances

In humans, perihematomal edema (PHE) is considered to be a radiological marker of secondary injury following intracerebral hemorrhage (ICH). There is also evidence that PHE might contribute to poor outcome in ICH patients. Given the rising interest in secondary injury after ICH as a therapeutic target, PHE is becoming increasingly used as a proof-of-concept surrogate measure to assess the potential efficacy of various therapeutic interventions in clinical trials. We review the pathophysiology of PHE and its evolution, its prognostic significance and relationship to clinical outcomes, and variabilities in its detection and measurement methodologies to determine the advantages versus shortcomings of using PHE as a translational target or radiological marker to examine the efficacy of interventions aiming to mitigate secondary injury in ICH.     

Oligodendrocytes in intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a cerebrovascular disorder with high mortality and disability rates. Although a lot of effort has been put in ICH, there is still no effective treatment for this devastating disease. Recent studies suggest that oligodendrocytes play an important role in brain repair after ICH and thus may be targeted for the therapies of ICH. Here in this review, we first introduce the origin, migration, proliferation, differentiation, and myelination of oligodendrocytes under physiological condition. Second, recent findings on how ICH affects oligodendrocyte biology and function are reviewed. Third, potential crosstalk between oligodendrocytes and other cells in the brain is also summarized. Last, we discuss the therapeutic potential of oligodendrocyte‐based treatments in ICH. Our goal is to provide a comprehensive review on the biology and function of oligodendrocytes under both physiological and ICH conditions.     

Spontaneous intracerebral hemorrhage

To determine the prognostic value of etiology and localization in spontaneous intracerebral hemorrhage, 896 patients with spontaneous intracerebral hemorrhage, as proven by CT, operation or autopsy, were retrospectively studied using univariate data analysis. Etiologies were hypertension in 63.5%, cerebrovascular malformations in 8.5% and abnormal hemostasis in 15% of the patients. In 23% no etiology was determined. Main localizations were cerebral lobes in 49.2%, basal ganglia in 34.4%, brain stem in 6.9%, cerebellum in 6.7% and primary intraventricular in 2.3% of the patients. Ventricular extension was present in 47.0%. A higher case fatality correlated with: 1) ventricular extension ( P <0.00001), 2) increasing age ( P =0.00005), 3) surgical treatment ( P =0.00010), 4) localization in basal ganglia ( P =0.0108) and 5) hypertension as only etiology ( P =0.01471). A lower case fatality was found in patients with cerebrovascular malformations ( P =0.00006) and when the hemorrhage was localized to the cerebral lobes ( P =0.0050). We conclude that etiology and localization are of prognostic value in spontaneous intracerebral hemorrhage.     

Anticoagulant-associated intracerebral hemorrhage

The incidence of anticoagulant-associated intracerebral hemorrhage (AAICH) quintupled during the 1990 s, probably due to increased warfarin use for the treatment of atrial fibrillation. Anticoagulant-associated intracerebral hemorrhage now accounts for nearly 20% of all intracranial hemorrhage (ICH). Among patients using warfarin for atrial fibrillation, the annual risk of ICH in trials is 0.3 to 1.0%. Predictors of potential anticoagulant-associated hemorrhage are increasing age, prior ischemic stroke, hypertension, leukoaraiosis, the early period of warfarin use, higher intensity anticoagulation, and antiplatelet use in addition to anticoagulation. Compared with other intracranial hemorrhage patients, anticoagulated patients have a greater risk of hematoma expansion, subsequent clinical deterioration and death, necessitating vigorous reversal of their coagulopathy. Recommended methods of warfarin reversal are administration of intravenous vitamin K and either prothrombin complex concentrates or fresh frozen plasma. Reversal of unfractionated heparin is accomplished with intravenous protamine sulfate. Surgical treatment of intracranial hemorrhage may be life saving in select cases, but has not reduced morbidity or mortality in large randomized trials.     

Spontaneous intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (sICH) is defined as bleeding within the brain parenchyma, and occurs twice as commonly as subarachnoid hemorrhage, but is equally as deadly. Risk factors for sICH include hypertension, advanced age, leukoaraiosis, prior ICH, renal failure, use of anticoagulant drugs, and cerebral amyloid angiopathy. When a patient is clinically suspected of having sICH, head computed tomography scan is the standard diagnostic tool. However, newer magnetic resonance neuroimaging techniques may aid in determining the underlying pathology and aid in prognosis. Supportive care and blood pressure management are important in the care of patients with sICH. Ongoing research is aimed at determining a safe blood pressure goal that may also prevent expansion of hemorrhage. Hemostatic medications and neuroprotectants have thus far not shown clinical improvement. Although several neurosurgical trials have failed to demonstrate benefit for surgical evacuation of sICH, multiple research trials are ongoing investigating acute blood pressure control, deep or basal ganglionic hemorrhage evacuation via minimally invasive approach (MISTIE; http://mistietrial.com/default.aspx), lobar ICH evacuation (STICH; II http://research.ncl.ac.uk/stich/), and intraventricular thrombolysis with tissue plasminogen activator (tPA) (CLEAR III; http://biosgroup-johnshopkinsmedicine.health.officelive.com/default.aspx).     

Recurrent intracerebral hemorrhage

Objective: In order to study the clinical manifestation and risk factor of recurrent intracerebral hemorrhage(ICH).Methods:The 256 patients were analysed who admitted to our hospital for intracerebral hemorrhage between 1995 and 1997.The 15(5 .86%)patients had a recurrent ICH.There were 9 men and 6 women and the mean age of the patients was 63.5 ± 6.4years at the first bleeding episode and 67.8± 8. 5 years at the second. The mean interval between the two bleeding episodes was 44.6 ± 12.5 months. The 73.3%patients were hypertensive .′The site of the first hemorrhage was ganglionic in 8 patients , ]ohar in six paients and brainstem in one .The recurrent hemorrhage occurred at a different location from the previous ICH.The most common pattern of recurrence was “ganglionic -ganglionic” (7 patients), lobar - ganglionic (3 patients), lobar-lobar(three patients), which was always observed in hypertensive patients. The outcome after the recurrent hemorrhage was usually poor. By comparison with 24 patients followed up to average 47.5± 18.7 months with isolated ICH without recurrence .Only lobar hematoma and a younger age were risk factors for recurrences whereas sex and previous hypertension were not. The mechanism of recurrence of ICH were multiple(hypertension, cerebral amyloid angiopathy).Contral of blood pressure and good living habit after the first hemorrhage may prevent ICH recurrences.     

Latest advances in epilepsy surgery

Recent advances in epilepsy surgery are a result of improved methods of assessment and diagnosis, a better understanding of seizures, the possibility of surgery at a younger age and the development of new surgical techniques. These factors have led to a wider selection of candidates for epilepsy surgery and shorter treatment trials with anti-epilepsy drugs before surgery is considered. The psychosocial indications for surgery, however, are often not examined thoroughly enough. Epilepsy surgery shows the best results following temporal lobe excision, with 68% of patients becoming seizure-free and 24% showing an improvement. Extra-temporal surgery results in 45% of patients seizure-free and 35% improved. The results of epilepsy surgery in children are similar to those of adults, with 67% of children becoming seizure-free and 21% showing improvement, following successful extensive cortical excision for non-inflammatory lesions. The beneficial psychosocial-economic effects of epilepsy surgery are, however, seldom documented and more research is needed into methods of quantifying, in broader perspectives, the outcome of surgery.     

Decreased perihematomal edema in thrombolysis-related intracerebral hemorrhage compared with spontaneous intracerebral hemorrhage

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a highly morbid disease process. Perihematomal edema is reported to contribute to clinical deterioration and death. Recent experimental observations indicate that clotting of the intrahematomal blood is the essential prerequisite for hyperacute perihematomal edema formation rather than blood-brain barrier disruption. METHODS: We compared a series of patients with spontaneous ICH (SICH) to a series of patients with thrombolysis-related ICH (TICH). All patients were imaged within 3 hours of clinical onset. We reviewed relevant neuroimaging features, emphasizing and quantifying perihematomal edema. We then analyzed clinical and radiological differences between the 2 ICH types and determined whether these factors were associated with perihematomal edema. RESULTS: TICHs contained visible perihematomal edema less than half as often as SICHs (31% versus 69%, P<0.001) and had both lower absolute edema volumes (0 cc [25th, 75th percentiles: 0, 6] versus 6 cc [0, 13], P<0.0001) and relative edema volumes (0.16 [0.10, 0.33] versus 0.55 [0.40, 0.83], P<0.0001). Compared with SICHs, TICHs were 3 times larger in volume (median [25th, 75th percentiles] volume 69 cc [30, 106] versus 21 cc [8, 45], P<0.0001), 4 times more frequently lobar in location (62% versus 15%, P<0.001), 80 times more frequently contained blood-fluid level(s) (86% versus 1%, P<0.001), and were more frequently multifocal (22% versus 0%, P<0.001). CONCLUSIONS: The striking qualitative and quantitative lack of perihematomal edema observed in the thrombolysis-related ICHs compared with the SICHs provides the first substantial, although indirect, human evidence that intrahematomal blood clotting is a plausible pathogenetic factor in hyperacute perihematomal edema formation.     

Oral-anticoagulant-related intracerebral hemorrhage

BACKGROUND: The characteristics, management and outcomes of patients who suffer intracerebral hemorrhage (ICH) while taking oral anticoagulants (OAC) are relatively unreported. DESIGN: Retrospective cohort study of consecutive cases with ICH associated with OAC. SETTING: A university-affiliated tertiary care hospital in Ontario, Canada. PATIENTS/PARTICIPANTS: 368 charts of individuals with a discharge diagnosis of ICH (ICD-9 code 431) between January 1993 and May 1998 were reviewed. MAIN RESULTS: 20 (5.4%, 95% confidence interval (CI): 3.1-7.7%) of the 368 ICHs occurred in people taking OAC. The median age of patients on OAC was 74 years (S.D.+/-9.8), and 70% (95% CI: 49-91%) were female. The median INR at presentation was 3.4 (intraquartile (IQR) range 2.2-4.4). Nine of 20 (45%) patients had INR values which exceeded the target range. The case fatality rate was 45% (95% CI: 23-67%). Approximately 2.8 years after the initial ICH, 9 of the 11 patients who survived the initial ICH were still alive, and 6 had restarted OAC. CONCLUSIONS: ICH is a serious complication in patients taking OAC, and the case-fatality rate is high. Given the increasing use of OAC in patients with cardiovascular disease, the relative benefits and risks of this therapy must be weighed carefully.     

Anticoagulant-related intracerebral hemorrhage

Twenty-four patients had intracerebral hemorrhage while they were being treated with anticoagulants. Hypertension was present in 67% of the cases, head trauma was an uncommon preceding event, and simultaneous bleeding in other organs occurred in only one instance. Neurologic abnormalities progressed for several hours in 58%. Seizures occurred at onset in 12.5%. The location of the hemorrhage was as follows: cerebellum (nine cases), lobar white matter (six), basal ganglia (five), thalamus (two), and hemisphere, unspecified (two). In 61%, the hemorrhages occurred within 6 months of therapy. In 75%, the prothrombin time was beyond 1 1/2 times the control value. Mortality was 62.5%. Survivors had smaller hematomas than did patients with fatal hemorrhage.     

Warfarin-associated intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulant therapy (OAT), with mortality in excess of 50%. Major risk factors are advanced patient age, elevated systolic blood pressure, intensity of anticoagulation, and previous cerebral ischemia. A number of acute treatments are available, but all have significant side effects and no randomized clinical trials assessing clinical outcome have been performed. Future trials will have to address choice and dose of agent, the timing of its administration, and the risk of side effects.     

Evaluation of intraventricular hemorrhage in pediatric intracerebral hemorrhage

Previous studies of pediatric intracerebral hemorrhage have investigated isolated intraparenchymal hemorrhage. The authors investigated whether detailed assessment of intraventricular hemorrhage enhanced outcome prediction after intracerebral hemorrhage. They prospectively enrolled 46 children, full-term to 17 years, median age 2.7 years, with spontaneous intraparenchymal hemorrhage and/or intraventricular hemorrhage. Outcome was assessed with the King's Outcome Scale for Childhood Head Injury. Twenty-six (57%) had intraparenchymal hemorrhage, 10 (22%) had pure intraventricular hemorrhage, and 10 (22%) had both. There were 2 deaths, both with intraparenchymal hemorrhage and intraventricular hemorrhage volume ≥4% of total brain volume. Presence of intraventricular hemorrhage was not associated with poor outcome, but hydrocephalus showed a trend (P = .09) toward poor outcome. In receiver operating characteristic curve analysis, combined intraparenchymal hemorrhage and intraventricular hemorrhage volume also showed a trend toward better outcome prediction than intraparenchymal hemorrhage volume alone. Although not an independent outcome predictor, future studies should assess intraventricular hemorrhage qualitatively and quantitatively.     

Collagenase-induced intracerebral hemorrhage in rats

Intracranial bleeding is an important cause of brain masses and edema. To study the pathophysiology of intracerebral hemorrhage, we produced experimental hemorrhages in 53 rats and characterized the lesion by histology, brain water content, and behavior. Adult rats had 2 microliters saline containing 0.5 unit bacterial collagenase infused into the left caudate nucleus. Histologically, erythrocytes were seen around blood vessels at the needle puncture site within the first hour. By 4 hours there were hematomas, the size of which depended on the amount of collagenase injected. Necrotic masses containing fluid, blood cells, and fibrin were seen at 24 hours. Lipid-filled macrophages were observed at 7 days and cysts at 3 weeks. Water content was significantly increased 4, 24, and 48 hours after infusion at the needle puncture site and for 24 hours in posterior brain sections. Behavioral abnormalities were present for 48 hours, with recovery of function occurring during the first week. Brain tissue contains Type IV collagen in the basal lamina. Collagenase, which occurs in an inactive form in cells, is released and activated during injury, leading to disruption of the extracellular matrix. Collagenase-induced intracerebral hemorrhage is a reproducible animal model for the study of the effects of the hematoma and brain edema.     

脑出血后早期血肿增大的研究进度

脑出血后早期血肿增大可独立预测其不良预后。本文从早期血肿增大的发生率、对预后的影响、血肿增大相关临床因素、病理生理机制、分子信号及rFVIIa治疗等方面进行综合阐述。     

Oral anticoagulant-associated intracerebral hemorrhage

The incidence of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) is growing due to the increasing use of warfarin and the older age of treated patients. Recent population studies reveal that OAC-ICH currently occurs at a frequency comparable to that of subarachnoid hemorrhage. Most frequently, OAC-ICH are located in deep or lobar regions of the brain, although it may also occur in the brainstem. These hemorrhages are larger than spontaneous hematomas and may be fatal in at least 50% of cases. The primary cause of brain injury in patients with OAC-ICH is the direct mechanical disruption of the brain tissue but secondary damage may occur through the intervention of matrix metalloproteinases, glutamate, cytokines, heme, iron, and the chemical toxicity of products such as thrombin, which are released from the clot. The pathogenesis of OAC-ICH also includes the effects of aging, the level of anticoagulation, genetic factors, and a high prevalence of concurrent cerebrovascular conditions, such as cerebral amyloid angiopathy, leukoaraiosis or previous strokes. The treatment of OAC-ICH is challenging and involves rapid reversal of anticoagulation with hemostatic drug therapies such as vitamin K, fresh frozen plasma, prothrombin complex concentrates or recombinant factor VIIa. These therapies may not always be sufficient to stabilize the patient’s clinical condition and lacking randomized controlled trials, the best hematological approach to reverse oral anticoagulation is debated. Other difficult decisions reviewed in this article are whether anticoagulation should be restarted after OAC-ICH, and when anticoagulant treatment should be resumed. The newer oral anticoagulants, which are increasingly being introduced for thromboembolism prevention, may confer a lower risk of intracranial bleeding than warfarin, although they do not have an antidote and their anticoagulant effect is difficult to monitor.     

Rare neonatal intracerebral hemorrhage

Intracranial hemorrhage in neonates is often found in either the subependymal area or the subdural space. The former is observed particularly in premature infants and is attributable to damage of the germinal matrix layer. The latter usually occurs in the vicinity of the falx and tentorium cerebri of full-term neonates and is thought to be caused by birth injury. Two cases of intracerebral hemorrhage in full-term newborn babies are reported. In both the hematoma was located at the left frontal area under the coronal suture. Angiograms revealed no causative signs, such as arteriovenous malformation, aneurysm or angioma. Observations on CT scans and during surgery led to the conclusion that the hemorrhages were caused by the moulding which forced the frontal bone to slip under the parietal bone at the coronal suture and then press on the fragile cerebral vasculature of the neonates, thus causing contusion.