Analysis of different hematoma expansion shapes caused by different risk factors in patients with hypertensive intracerebral hemorrhage.

OBJECTIVE: To elucidate the relationship between the risk factors and hematoma expansion(HE)shapes. PATIENTS AND METHODS: From February 2013 to November 2018, 60 patients diagnosed as basal ganglia ICH were divided into the filled type hematoma expansion group (FTE group) and the expanded type hematoma expansion group (ETE group). we performed follow-up CT and three-dimensional reconstruction for the patients and compared the hematoma before and after the expansion of size and extent. RESULTS: The regression analysis showed that the irregular sign (odds ratio, 3.64; 95 % CI, 1.46-9.12), black hole sign (odds ratio, 3.85; 95 % CI, 1.40-10.60), blend sign (odds ratio, 2.86; 95 % CI, 1.03-7.95), and early use of dehydration (odds ratio, 4.59; 95 % CI, 1.59-13.19) were possible risk factors for the ETE group, while the high systolic blood pressure (odds ratio, 1.51; 95 % CI, 1.04-2.30), early use of dehydration (odds ratio, 3.27; 95 % CI, 1.10-9.69) and low density low-density band (odds ratio, 4.52; 95 % CI, 1.54-13.28) were possible risk factors for the FTE group. CONCLUSIONS: The irregular sign, black hole sign, blend sign and early use of dehydration may be the main risk factors for ETE, whereas early use of dehydration, high systolic blood pressure, and low density low-density band may be the main risk factors for FTE.

Intensive Blood Pressure Reduction and Perihematomal Edema Expansion in Deep Intracerebral Hemorrhage.

Background and Purpose- It is unknown whether blood pressure (BP) reduction influences secondary brain injury in spontaneous intracerebral hemorrhage (ICH). We tested the hypothesis that intensive BP reduction is associated with decreased perihematomal edema expansion rate (PHER) in deep ICH. Methods- We performed an exploratory analysis of the ATACH-2 randomized trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2). Patients with deep, supratentorial ICH were included. PHER was calculated as the difference in perihematomal edema volume between baseline and 24-hour computed tomography scans divided by hours between scans. We used regression analyses to determine whether intensive BP reduction was associated with PHER and if PHER was associated with poor outcome (3-month modified Rankin Scale score 4-6). We then used interaction analyses to test whether specific deep location (basal ganglia versus thalamus) modified these associations. Results- Among 1000 patients enrolled in ATACH-2, 870 (87%) had supratentorial, deep ICH. Of these, 780 (90%) had neuroimaging data (336 thalamic and 444 basal ganglia hemorrhages). Baseline characteristics of the treatment groups remained balanced (P>0.2). Intensive BP reduction was associated with a decrease in PHER in univariable (ß= -0.15; 95% CI, -0.26 to -0.05; P=0.007) and multivariable (ß=-0.12; 95% CI, -0.21 to -0.02; P=0.03) analyses. PHER was not independently associated with outcome in all deep ICH (odds ratio, 1.14; 95% CI, 0.93-1.41; P=0.20), but this association was modified by the specific deep location involved (multivariable interaction P=0.02); in adjusted analyses, PHER was associated with poor outcome in basal ganglia (odds ratio, 1.42; 1.05-1.97; P=0.03) but not thalamic (odds ratio, 1.02; 95% CI, 0.74-1.40; P=0.89) ICH. Conclusions- Intensive BP reduction was associated with decreased 24-hour PHER in deep ICH. PHER was not independently associated with outcome in all deep ICH but was associated with poor outcome in basal ganglia ICH. PHER may be a clinically relevant end point for clinical trials in basal ganglia ICH.

What did Joseph Stalin really die of? A reappraisal of his illness, death, and autopsy findings.

Joseph Stalin was one of the most important world leaders during the first half of the 20th century. He died suddenly in early March 1953 after a short illness, which was described in a series of medical bulletins in the Soviet newspaper Pravda. Based on both the clinical history and autopsy findings, it was concluded that Stalin had died of a massive hemorrhagic stroke involving his left cerebral hemisphere. However, almost 50 years later, a counter-narrative developed suggesting a more nefarious explanation for his sudden death, namely, that a "poison," warfarin, a potent anticoagulant, had been administered surreptitiously by one or more of his close associates during the early morning hours prior to the onset of his stroke. In the present report, we will examine this counter-narrative and suggest that his death was not due to the administration of warfarin but rather to a hypertension-related cerebrovascular accident resulting in a massive hemorrhagic stroke involving his left cerebral hemisphere. The counter-narrative was based on the misunderstanding of certain specific autopsy findings, namely, the presence of focal myocardial and petechial hemorrhages in the gastric and intestinal mucosa, which could be attributed to the extracranial pathophysiologic changes that can occur as a consequence of a stroke rather than the highly speculative counter-narrative that Stalin was "poisoned" by the administration of warfarin.

Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage.

BACKGROUND: Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. METHODS: Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. RESULTS: Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients without concurrent ischemic lesions. CONCLUSIONS: Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

Serum Copper Homeostasis in Hypertensive Intracerebral Hemorrhage and its Clinical Significance.

This study was to investigate the alterations of serum copper homeostasis after hypertensive intracerebral hemorrhage (ICH), which is not yet clear. We recruited 85 hypertensive ICH patients and determined their serum levels of total copper (TCu), small molecule copper (SMC), and ceruloplasmin (Cp). Sera from 32 healthy persons and 12 primary hypertension patients were collected and analyzed as well. Serum TCu levels in ICH patients were tested at three time points (on admission, day 3, and day 7) and found to be higher than that in hypertension patients (p < 0.05). The serum SMC levels in hypertension patients and ICH patients at three time points were higher than that in healthy controls (p < 0.05). Higher serum SMC levels on days 3 and 7 were associated with death in the hospital. Additionally, higher serum SMC levels on the seventh day were associated with poor outcome at discharge. High serum Cp levels on admission, as well as low serum Cp levels on the seventh day, were associated with death in the hospital (p = 0.002 and p = 0.034, respectively). Our findings indicated that declines in serum Cp and increases in serum SMC are correlated with lethal or poor outcome in hypertensive ICH patients, possibly as a result of contributions to secondary injury of brain after hemorrhage due to impairment of iron transport and enhanced oxidative stress.

N-Terminal Pro-Brain Natriuretic Peptide Concentrations After Hypertensive Intracerebral Hemorrhage: Relationship With Hematoma Size, Hyponatremia, and Intracranial Pressure.

INTRODUCTION:: The role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with hypertensive intracerebral hemorrhage (HICH) is poorly understood. This study aimed to investigate the secretion pattern of NT-proBNP in patients with HICH and to assess its relationship with hematoma size, hyponatremia, and intracranial pressure (ICP). METHODS:: This prospective study enrolled 147 isolated patients with HICH. Blood samples were obtained from each patient, and values of serum NT-proBNP, hematoma size, blood sodium, and ICP were collected for each patient. RESULTS:: The peak-to-mean concentration of NT-proBNP was 666.8 ± 355.1 pg/mL observed on day 4. The NT-proBNP levels in patients with hematoma volume >30 mL were significantly higher than those in patients with hematoma volume <30 mL ( P < .05). In patients with severe HICH, the mean concentration of NT-proBNP was statistically higher than that in patients with mild-moderate HICH ( P < .05), and the mean level of NT-proBNP in hyponatremia group was significantly higher than that in normonatremic group ( P < .05). In addition, the linear regression analysis indicated that serum NT-proBNP concentrations were positively correlated with ICP ( r = .703, P < .05) but negatively with blood sodium levels only in patients with severe HICH ( r = -.704, P < .05). The serum NT-proBNP levels on day 4 after admission were positively correlated with hematoma size ( r = .702, P < .05). CONCLUSION:: The NT-proBNP concentrations were elevated progressively and markedly at least in the first 4 days after HICH and reached a peak level on the fourth day. The NT-proBNP levels on day 4 were positively correlated with hematoma size. There was a notable positive correlation between plasma NT-proBNP levels and ICP in patients with severe HICH. Furthermore, only in patients with severe HICH, the plasma NT-proBNP levels presented a significant correlation with hyponatremia, which did not occur in patients with mild-moderate HICH.

The Relationship of Hematoma Growth to Red Blood Cell Distribution Width in Patients with Hypertensive Intracerebral Hemorrhage.

AIM: Hypertension is a primary risk factor for intracerebral hemorrhage (ICH) and is thought to be responsible for about 55% of all ICH cases. Thus, the primary goal of the study was to examine whether the status of vascular rheological factors upon admission to the hospital was associated with hypertensive ICH growth and early outcomes. MATERIAL AND METHODS: Over a 2-year period, the present study evaluated 60 ICH patients who were admitted within the first 12 hours of symptom onset. Brain computed tomography scans were performed at admission and then 24 hours later as a control. Hematoma growth was classified as an volume increase more than 6.5 ml or > 33%, and good outcome was defined using the modified Rankin Scale (mRS) score (? 2 at 3 months). RESULTS: The mean age of the study population was 65.07 ± 11.659 years, with 34 men and 26 women. The leading vascular risk factor was hypertension (86.7%). There were significant associations between the initial red blood cell distribution width (RDW) and hematoma growth (p=0.038). Therefore, hematoma growth in the first 24 hours after symptom onset was significantly related to a poor clinical outcome at 3 months (p = 0.050). CONCLUSION: The study identified significant relationships between the initial RDW and poor outcome as well as the initial RDW and hypertensive hematoma growth. Additionally, this study demonstrated that these parameters are easily obtainable and could be used to effectively evaluate outcomes in ICH patients.

Relationship of plasma matrix metalloproteinase-9 and hematoma expansion in acute hypertensive cerebral hemorrhage.

In the present study, we aimed to investigate the relationship of plasma matrix metalloproteinase-9 (MMP-9) and hematoma expansion (HE) in acute hypertensive cerebral hemorrhage (AHCH) (HE-in-AHCH). Patients with hypertensive cerebral hemorrhage, confirmed by head computed tomography (CT) within 12 h of onset, were prospectively collected. Venous blood was sampled within 4 h of the confirmation to determine the serum MMP-9 concentration. The blood pressure and National Institute of Health Stroke Score of the patients were recorded on hospital admission. CT re-scanning was performed within 42-54 h of the first head CT examination or immediately after worsening of the patients' consciousness disorder. The relationship between MMP-9 level and HE was analyzed. A total of 186 patients were included. Of these patients, 41 had HE (22.0%). Multivariate logistic regression analysis showed that, in addition to the short interval between onset and the first CT examination, and the irregularity of hematoma shape, increasing MMP-9 level was an independent risk factor for HE-in-AHCH (OR value = 15.65, 95% CI: 5.30-46.15). Moreover, increasing plasma MMP-9 level was identified as an independent risk factor in patients with HE-in-AHCH.

Experimental hypertension increases spontaneous intracerebral hemorrhages in a mouse model of cerebral amyloidosis.

Hypertension and cerebral amyloid angiopathy (CAA) are major risk factors for intracerebral hemorrhage (ICH); however the mechanisms of interplay between the two are not fully understood. We investigated the effect of hypertension in a transgenic mouse model with Alzheimer's-like pathology (Tg2576) treating them with angiotensin II and L-N(G)-nitroarginine methyl ester. A similar increase in systolic blood pressure was observed in both Tg2576 and control mice; however Tg2576 mice developed signs of stroke with a markedly shorter latency. Cerebral deposition of amyloid beta promotes the hypertension-induced ICH, thus supporting the notion that hypertension is a risk factor for ICH among patients with CAA.

Real-time ultrasound-guided endoscopic surgery for putaminal hemorrhage.

OBJECT: Endoscopic surgery plays a significant role in the treatment of intracerebral hemorrhage. However, the residual hematoma cannot be measured intraoperatively from the endoscopic view, and it is difficult to determine the precise location of the endoscope within the hematoma cavity. The authors attempted to develop real-time ultrasound-guided endoscopic surgery using a bur-hole-type probe. METHODS: From November 2012 to March 2014, patients with hypertensive putaminal hemorrhage who underwent endoscopic hematoma removal were enrolled in this study. Real-time ultrasound guidance was performed with a bur-hole-type probe that was advanced via a second bur hole, which was placed in the temporal region. Ultrasound was used to guide insertion of the endoscope sheath as well as to provide information regarding the location of the hematoma during surgical evacuation. Finally, the cavity was irrigated with artificial cerebrospinal fluid and was observed as a low-echoic space, which facilitated detection of residual hematoma. RESULTS: Ten patients with putaminal hemorrhage>30 cm3 were included in this study. Their mean age (±SD) was 60.9±8.6 years, and the mean preoperative hematoma volume was 65.2±37.1 cm3. The mean percentage of hematoma that was evacuated was 96%±3%. None of the patients exhibited rebleeding after surgery. CONCLUSIONS: This navigation method was effective in demonstrating both the real-time location of the endoscope and real-time viewing of the residual hematoma. Use of ultrasound guidance minimized the occurrence of brain injury due to hematoma evacuation.

Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke.

Astrocytes express laminin and assemble basement membranes (BMs) at their endfeet, which ensheath the cerebrovasculature. The function of astrocytic laminin in cerebrovascular integrity is unknown. We show that ablation of astrocytic laminin by tissue-specific Cre-mediated recombination disrupted endfeet BMs and led to hemorrhage in deep brain regions of adult mice, resembling human hypertensive hemorrhage. The lack of astrocytic laminin led to impaired function of vascular smooth muscle cells (VSMCs), where astrocytes have a closer association with VSMCs in small arterioles, and was associated with hemorrhagic vessels, which exhibited VSMC fragmentation and vascular wall disassembly. Acute disruption of astrocytic laminin in the striatum of adult mice also impaired VSMC function, indicating that laminin is necessary for VSMC maintenance. In vitro, both astrocytes and astrocytic laminin promoted brain VSMC differentiation. These results show that astrocytes regulate VSMCs and vascular integrity in small vessels of deep brain regions. Therefore, astrocytes may be a possible target for hemorrhagic stroke prevention and therapy.

Volume quantification of acute infratentorial hemorrhage with computed tomography: validation of the formula 1/2ABC and 2/3SH.

OBJECTIVE: To compare the accuracy of formula 1/2ABC with 2/3SH on volume estimation for hypertensive infratentorial hematoma. METHODS: One hundred and forty-seven CT scans diagnosed as hypertensive infratentorial hemorrhage were reviewed. Based on the shape, hematomas were categorized as regular or irregular. Multilobular was defined as a special shape of irregular. Hematoma volume was calculated employing computer-assisted volumetric analysis (CAVA), 1/2ABC and 2/3SH, respectively. RESULTS: The correlation coefficients between 1/2ABC (or 2/3SH) and CAVA were greater than 0.900 in all subgroups. There were neither significant differences in absolute values of volume deviation nor percentage deviation between 1/2ABC and 2/3SH for regular hemorrhage (P>0.05). While for cerebellar, brainstem and irregular hemorrhages, the absolute values of volume deviation and percentage deviation by formula 1/2ABC were greater than 2/3SH (P<0.05). 1/2ABC and 2/3SH underestimated hematoma volume each by 10% and 5% for cerebellar hemorrhage, 14% and 9% for brainstem hemorrhage, 19% and 16% for regular hemorrhage, 9% and 3% for irregular hemorrhage, respectively. In addition, for the multilobular hemorrhage, 1/2ABC underestimated the volume by 9% while 2/3SH overestimated it by 2%. CONCLUSIONS: For regular hemorrhage volume calculation, the accuracy of 2/3SH is similar to 1/2ABC. While for cerebellar, brainstem or irregular hemorrhages (including multilobular), 2/3SH is more accurate than 1/2ABC.

Recurrent hypertensive cerebral hemorrhages in a boy caused by a reninoma: rare manifestations and distinctive electron microscopy findings.

Recurrent cerebral hemorrhages caused by hypertension secondary to reninoma are extremely rare in children. Because of its detrimental effects on children's health, the importance of early diagnosis of and treatment for reninoma should be emphasized. Here, the authors present a 10-year-old boy with intermittent headaches and neurologic deficiency symptoms caused by hypertension. A reninoma in the right kidney was detected and successfully treated with laparoscopic partial nephrectomy. Two cell types were revealed in the tumor tissue under electron microscopy: renin secreting tumor cells and mast cells. This rare case expands our knowledge of hypertension in children and provides direct evidence that mast cells may infiltrate reninoma.

[Edema in nervous tissue studied on model of hemorrhagic stroke in vitro].

The development of edema in the survival olfactory cortex slices under the long-term action of autoblood has been studied by monitoring the bioelectric activity of nervous cells. The level of disorder in electrogenesis of cells was revealed by comparing the focal potentials with their control values; the degree of the nervous tissue swelling in various periods of autoblood action was determined by weighing. In the model of hemorrhagic stroke, the dependence of edema growth on the level of activity of ionotropic glutamate receptors has been determined using the pharmacological blockade technique.

Cushing's disease associated with unruptured large internal carotid artery aneurysm. Case report.

A 40-year-old woman with Cushing's disease presented with hypertensive cerebral hemorrhage. Neuroimaging detected an unruptured large intracavernous aneurysm, which projected beyond the midline, and thin crescent-shaped adenoma along the aneurysm wall. The aneurysm was treated with endovascular tight packing with coils. Transsphenoidal adenomectomy was then safely performed. The signs of Cushing's disease were resolved, and she was discharged without deficits. The first line therapy for Cushing's disease is transsphenoidal adenomectomy. However, the therapeutic strategy and optimal timing of treatment are unclear for Cushing's disease with large intracavernous aneurysm. The present case shows that transsphenoidal surgery was safely possible with minimal invasiveness after embolization of the intracavernous aneurysm.

Exploring the optimal operation time for patients with hypertensive intracerebral hemorrhage: tracking the expression and progress of cell apoptosis of prehematomal brain tissues.

BACKGROUND: Hypertensive intracerebral hemorrhage (HICH) is a severe disease with high morbidity and mortality. Timely removal of the hematoma through surgical procedures may effectively reduce secondary injuries. However, there has long been a debate over the proper timing of such surgery. In this study, we explored the optimal operation time for HICH patients by observing the pathological changes in perihematomal brain regions during different stages of onset. METHODS: Twenty-five specimens of brain tissue, obtained from perihematomal region of HICH patients in different phases, were subjected to haematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) staining and Caspase-3, matrix metalloproteinases-9 (MMP-9) immunohistochemical staining. The changing roles of necrosis and apoptosis and the expression of MMP-9 and Caspase-3 positive cells were all observed using image analysis. RESULTS: The obvious expression of TUNEL positive cells was recognized within 6 hours of ICH onset, reaching its peak between 6 hours and 24 hours in the early phase. RESULTS: were highly consistent with Caspase-3 and MMP-9 positive cell counts. Necrosis was found 6 hours after ICH onset and aggravated after 12 hours. CONCLUSIONS: In the early phase, apoptosis was seen as a major modality of injury in the brain tissue of the perihematomal region and was strongly correlated with the expression of MMP-9 and Caspase-3. The results of the present study suggest that an operation performed as soon as possible after ICH onset may be optimal for preserving the nervous system function.

Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT).

BACKGROUND AND PURPOSE: The Intensive Blood Pressure Reduction In Acute Cerebral Haemorrhage Trial (INTERACT) study suggests that early intensive blood pressure (BP) lowering can attenuate hematoma growth at 24 hours after intracerebral hemorrhage. The present analyses aimed to determine the effects of treatment on hematoma and perihematomal edema over 72 hours. METHODS: INTERACT included 404 patients with CT-confirmed intracerebral hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to start BP-lowering treatment within 6 hours of intracerebral hemorrhage. Patients were randomly assigned to an intensive (target systolic BP 140 mmHg) or standard guideline-based management of BP (target systolic BP 180 mm Hg) using routine intravenous agents. Baseline and repeat CTs (24 and 72 hours) were performed using standardized techniques with digital images analyzed centrally. Outcomes were increases in hematoma and perihematomal edema volumes over 72 hours. RESULTS: Overall, 296 patients had all 3 CT scans available for the hematoma and 270 for the edema analyses. Mean systolic BP was 11.7 mm Hg lower in the intensive group than in the guideline group during 1 to 24 hours. Adjusted mean absolute increases in hematoma volumes (mL) at 24 and 72 hours were 2.40 and 0.15 in the guideline group compared with -0.74 and -2.31 in the intensive group, respectively, an overall difference of 2.80 (95% CI, 1.04 to 4.56; P=0.002). Adjusted mean absolute increases in edema volumes (mL) at 24 and 72 hours were 6.27 and 10.02 in the guideline group compared with 4.19 and 7.34 in the intensive group, respectively, for an overall difference of 2.38 (95% CI, -0.45 to 5.22; P=0.10). CONCLUSIONS: Early intensive BP-lowering treatment attenuated hematoma growth over 72 hours in intracerebral hemorrhage. There were no appreciable effects on perihematomal edema.