Cause Of Intracerebral Hemorrhage Research Articles

Risk Factors for Intracerebral Hemorrhage: Genome-Wide Association Study and Mendelian Randomization Analyses.

The genetic and nongenetic causes of intracerebral hemorrhage (ICH) remain obscure. The present study aimed to uncover the genetic and modifiable risk factors for ICH. We meta-analyzed genome-wide association study data from 3 European biobanks, involving 7605 ICH cases and 711 818 noncases, to identify the genomic loci linked to ICH. To uncover the potential causal associations of cardiometabolic and lifestyle factors with ICH, we performed Mendelian randomization analyses using genetic instruments identified in previous genome-wide association studies of the exposures and ICH data from the present genome-wide association study meta-analysis. We performed multivariable Mendelian randomization analyses to examine the independent associations of the identified risk factors with ICH and evaluate potential mediating pathways. We identified 1 ICH risk locus, located at the APOE genomic region. The lead variant in this locus was rs429358 (chr19:45411941), which was associated with an odds ratio of ICH of 1.17 (95% CI, 1.11-1.20; P=6.01×10-11) per C allele. Genetically predicted higher levels of body mass index, visceral adiposity, diastolic blood pressure, systolic blood pressure, and lifetime smoking index, as well as genetic liability to type 2 diabetes, were associated with higher odds of ICH after multiple testing corrections. Additionally, a genetic increase in waist-to-hip ratio and liability to smoking initiation were consistently associated with ICH, albeit at the nominal significance level (P<0.05). Multivariable Mendelian randomization analysis showed that the association between body mass index and ICH was attenuated on adjustment for type 2 diabetes and further that type 2 diabetes may be a mediator of the body mass index-ICH relationship. Our findings indicate that the APOE locus contributes to ICH genetic susceptibility in European populations. Excess adiposity, elevated blood pressure, type 2 diabetes, and smoking were identified as the chief modifiable cardiometabolic and lifestyle factors for ICH.

Neuropsychiatric symptoms with focus on apathy and irritability in sporadic and hereditary cerebral amyloid angiopathy

BackgroundNeuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA.MethodsWe included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences.ResultsWe included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.β = 1.4[95%CI:0.6–2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1–2.9]; presymptomatic D-CAA:1.2[0.1–2.2], control median:0[IQR:0–3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.β=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.β=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women.DiscussionAccording to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.

Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue.

The risk factors and causes of intracerebral hemorrhage (ICH) and the degree of functional recovery after ICH are distinct between young and elderly patients. The increasing incidence of ICH in young adults has become a concern; however, research on the molecules and pathways involved ICH in subjects of different ages is lacking. In this study, tandem mass tag (TMT)-based proteomics was utilized to examine the protein expression profiles of perihematomal tissue from young and aged mice 24h after collagenase-induced ICH. Among the 5,129 quantified proteins, ICH induced 108 and 143 differentially expressed proteins (DEPs) in young and aged mice, respectively; specifically, there were 54 common DEPs, 54 unique DEPs in young mice and 89 unique DEPs in aged mice. In contrast, aging altered the expression of 58 proteins in the brain, resulting in 39 upregulated DEPs and 19 downregulated DEPs. Bioinformatics analysis indicated that ICH activated different proteins in complement pathways, coagulation cascades, the acute phase response, and the iron homeostasis signaling pathway in mice of both age groups. Protein-protein interaction (PPI) analysis and ingenuity pathway analysis (IPA) demonstrated that the unique DEPs in the young and aged mice were related to lipid metabolism and carbohydrate metabolism, respectively. Deeper paired-comparison analysis demonstrated that apolipoprotein M exhibited the most significant change in expression as a result of both aging and ICH. These results help illustrate age-related protein expression changes in the acute phase of ICH.

A comprehensive review on the development of sporadic cerebral arteriovenous malformations: from Padget to next-generation sequencing.

Cerebral arteriovenous malformations (AVMs) are a leading cause of intracerebral hemorrhage in both children and young adults. With the continued advancement of science and technology, the understanding of the pathophysiology behind the development of these lesions has evolved. From early theory published by Harvey Cushing and Percival Bailey in 1928, Tumors Arising from the Blood-vessels of the Brain: Angiomatous Malformations and Hemangioblastoma, which regarded AVMs as tumors arising from blood vessels, to the meticulous artistry of Dorcas Padget's embryological cataloguing of the cerebral vasculature in 1948, to the proliferative capillaropathy theory of Yaşargil in 1987, to Ramey's 2014 hierarchical model of vascular development, there have been multiple hypotheses of congenital, developmental, and genetic two-hit theories in the pathogenesis of AVMs. Most recent evidence implicates somatic KRAS mutations in the cerebral endothelium, producing an important understanding of the pathogenesis of this disease, which is critical to the development of targeted therapeutics. The authors present the historical progression of their understanding of AVM pathogenesis. They focus on the foundation laid by early pioneers, discussing embryological anatomy and vasculogenesis, the prominent theories of AVM development that have emerged over time, and culminate in an overview of the most current understanding of the pathogenesis of these complex vascular lesions and the clinical implications of our scientific progress.

Abstract TP28: The Effects of Social Isolation on Cerebral Amyloid Angiopathy

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) deposition in the cortical and leptomeningeal vessels, and it is a largely untreatable cause of intracerebral hemorrhage and dementia. Studies estimate a 10-50% prevalence of CAA in the general elderly population, positioning it as one of the strongest vascular contributors to age-related cognitive impairment. With aging, the prevalence of social isolation (SI) also increases. Isolated individuals have an increased risk of Aβ-related cognitive decline and heightened inflammatory response to stress. Yet, whether and how SI exacerbates CAA-induced cognitive decline is unknown. Methods: TgSwDI mice harboring Swedish, Dutch, and Iowa mutations of human amyloid precursor protein were used as a mouse model of CAA. Male and female C57BL6 wildtype (WT) and CAA mice were randomly assigned to paired housing (PH) or SI at 3 months. Neurobehaviors were measured at baseline and every 3 months using the novel object recognition test (NORT), tail suspension test (TST), and fear conditioning (FC). At 12 months, microglia phenotype, vascular structure, and Aβ burden were assessed using flow cytometry and immunostaining. Results: Both WT and CAA isolated animals displayed significantly greater immobility in TST at 9 months post-SI, suggesting a depression-like behavior (n=10-15/grp, p&lt;0.0001). Isolated CAA mice displayed exacerbated cognitive deficits in NORT and FC while WT mice showed intact cognition (n=10-15/grp, p&lt;0.05). Specifically, SI-induced cognitive deficits were more prominent in the female CAA mice compared to males (n=5-8/grp, p&lt;0.01). Sex differences were also observed in CAA mice in frequencies of Aβ-containing endothelial cells (CD31 + ) and vessel-associated microglia (VAM, CD45 int CD11b + CD31 + ) as well as in microglial phagocytosis of Aβ (n=3/grp, p&lt;0.05). SI increased the frequency of Aβ-containing microglia in isolated CAA mice compared to their PH littermates. Conclusion: SI induced behavioral deficits in both WT and CAA mice but exacerbated cognitive decline only in the CAA SI mice. SI also influences microglial phagocytosis of Aβ. Further research is needed to determine the cellular and molecular mechanism underlying SI-induced changes in CAA.

Analysis of differentially expressed genes in hypertension and hypertensive cerebral hemorrhage via RNA-sequencing

Hypertension (HT) is a major cause of intracerebral hemorrhage (ICH), and hypertensive cerebral hemorrhage (HCH) has a serious impact on life quality of patients and gives society a heavy burden. This study investigated the key genes involved in HT and HCH. Three patients with HT, three with HCH, and three healthy individuals were recruited in the present study. Shared and specific differentially expressed genes (DEGs) in HT and HCH were identified using RNA sequencing and bioinformatics analysis. Functional annotation and protein–protein interaction (PPI) network construction of HT- and HCH-specific DEGs were conducted. Estimation of cell infiltration, drug prediction, and real-time qPCR (RT-qPCR) validation were performed. Compared with the controls, 502 and 1649 DEGs were identified in the HT and HCH groups, respectively. Among them, 378 DEGs were HT-specific and 633 DEGs were HCH-specific, and a total of 1771 DEGs were identified between HT and HCH. In addition, there were fewer immune cell types that differed significantly among the three groups. The RT-qPCR validation results in human subjects and cell models were generally consistent with the sequencing results. Our study may make a contribution for the understanding of the specific mechanisms of HT and HCH. Highlights Hypertension (HT) is a major cause of intracerebral hemorrhage (ICH), and hypertensive cerebral hemorrhage (HCH) has a serious impact on life quality of patients. A total of 502 and 1649 DEGs were obtained in HT and HCH, and 1771 DEGs were obtained between HT and HCH. Doxycycline, fasudil and propylthiouracil were predicted as potential drugs for HT and HCH. Our study may make a contribution for the understanding of the specific mechanisms of HT and HCH and representing a potential novel strategy for HT and HCH treatment.

A Brazilian series utilizing the SMASH-U system for etiologic classification of intracerebral hemorrhage.

Understanding the causes of intracerebral hemorrhage (ICH) is crucial for effective treatment and preventing recurrences. The SMASH-U scale is a suggested method for classifying and predicting the outcomes of ICH. To describe the SMASH-U classification and outcomes by etiology in patients admitted to a comprehensive stroke center in São Paulo, Brazil. A retrospective analysis was conducted on patients admitted to the hospital or outpatient clinic between April 2015 and January 2018. Two stroke neurologists evaluated the SMASH-U classification, and patients with incomplete medical records were excluded. Out of the 2000 patients with a stroke diagnosis evaluated, 140 were included in the final analysis. The mean age was 57.9 (± 15.5) years, and 54.3% were male. Hypertension was the most frequent etiology, accounting for 41.4% of cases, followed by amyloid angiopathy (18.5%) and structural lesions (14.1%). Structural lesions were more common among women and patients under 45 years old. Favorable outcomes were observed in 61% of patients with structural lesions, compared to 10% of patients with medication-related etiologies. This study provides important evidence regarding the etiological classification of Brazilian patients with ICH. Hypertension and amyloid angiopathy were the most frequent causes, while structural lesions and systemic diseases were more common in younger patients.

CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small Vessel Disease

Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

The Neuropathological Correlates of White Matter Hyperintensities in Cerebral Amyloid Angiopathy

AbstractBackgroundCerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage and cognitive impairment in older individuals. Hallmark manifestations of CAA on MRI include cortical hemorrhages, as well as perivascular spaces (PVS) in the white matter centrum semiovale and white matter hyperintensities (WMH) in a subcortical multi‐spot pattern. We performed an ex vivo MRI‐neuropathological study to: 1) determine the relationship between WMH volume and CAA severity, and 2) assess the histopathological substrate of confluent WMH, WMH in a multi‐spot pattern (WM_MS), and normal‐appearing white matter (NAWM).MethodNineteen autopsy cases with pathologically confirmed CAA (age 75±8y; 7F) and five non‐CAA controls (age 88±5y; 3F) were included. Formalin‐fixed hemispheres underwent 3T MRI, including a T2‐weighted (500µm isotropic resolution, to obtain manual WMH segmentations) and a T2*‐weighted sequence (1mm isotropic resolution, to automatically segment hemisphere volume using SynthSeg). After scanning, five pre‐defined standard areas were sampled from each brain, then processed to obtain manually assessed arteriolosclerosis scores and AI‐derived cortical and leptomeningeal CAA area measurements. In the CAA cases, specific areas with ex vivo MRI‐observed WM_MS (n = 7), confluent WMH (n = 9), and NAWM (n = 9) were sampled. Sections were stained with LH&amp;E (to determine WM rarefaction, % PVS area, and degree of arteriolosclerosis), and CD68 (a marker of activated microglia, to assess density of CD68‐positive cells).ResultTotal normalized WMH volume did not differ between CAA cases (0.037±0.024) and non‐CAA controls (0.027±0.026) (Mann‐Whitney U test 36, p = 0.31). Within the CAA cases, a multivariable regression model corrected for age at death revealed that normalized WMH volume was associated with cortical CAA area (p = 0.010) and arteriolosclerosis (p = 0.066), but not leptomeningeal CAA area (p = 0.94). Targeted neuropathological assessment revealed that WM rarefaction, arteriolosclerosis score, and density of CD68‐positive cells were higher in areas with WMH compared to WM_MS and NAWM. In contrast, % PVS area was higher in WM_MS compared to WMH and NAWM.ConclusionThe observed differences in neuropathological correlates between WMH in a multi‐spot pattern and confluent WMH in CAA suggest different pathophysiological mechanisms. Future studies are needed to determine these mechanisms as well as the causal relationship between cortical CAA severity and WMH burden.

GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals.

Arteriovenous malformations (AVMs) are fast-flow vascular malformations and refer to important causes of intracerebral haemorrhage in young adults. Getting deep insight into the genetic pathogenesis of AVMs is necessary. Herein, we identified two vital missense variants of G protein-coupled receptor (GPCR) associated sorting protein 1 (GPRASP1) in AVM patients for the first time and congruously determined to be loss-of-function variants in endothelial cells. GPRASP1 loss-of-function caused endothelial dysfunction in vitro and in vivo. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral haemorrhage, AVMs and exhibited vascular anomalies in multiple organs. GPR4 was identified to be an effective GPCR binding with GPRASP1 to develop endothelial disorders. GPRASP1 deletion activated GPR4/cAMP/MAPK signalling to disturb endothelial functions, thus contributing to vascular anomalies. Mechanistically, GPRASP1 promoted GPR4 degradation. GPRASP1 enabled GPR4 K63-linked ubiquitination, enhancing the binding of GPR4 and RABGEF1 to activate RAB5 for conversions from endocytic vesicles to endosomes, and subsequently increasing the interactions of GPR4 and ESCRT members to package GPR4 into multivesicular bodies or late endosomes for lysosome degradation. Notably, the GPR4 antagonist NE 52-QQ57 and JNK inhibitor SP600125 effectively rescued the vascular phenotype caused by endothelial Gprasp1 deletion. Our findings provided novel insights into the roles of GPRASP1 in AVMs and hinted at new therapeutic strategies.

Association between systolic blood pressure variability and severity of cerebral amyloid angiopathy in incident intracerebral hemorrhage

IntroductionThe role of systolic blood pressure (SBP) variability in the pathogenesis of cerebral amyloid angiopathy (CAA) as an underlying cause of intracerebral hemorrhage (ICH) is unknown. We studied SBP variability before ICH according to CAA severity at autopsy.MethodsWe collected office (primary care or hospital clinic) BP readings during 10 years before first-ever ICH onset in adults who died and had brain research autopsy in the Lothian IntraCerebral Hemorrhage, Pathology, Imaging, and Neurological Outcome (LINCHPIN), prospective, population-based, inception cohort study. A neuropathologist assessed CAA severity using a histopathological rating scale, masked to BP readings. Functional principal component analysis was used to model SBP levels by time before ICH, and logistic regression models assessed associations of SBP variability indices with CAA severity (moderate-severe vs. absent-mild) adjusted for age, gender, and mean SBP.ResultsAmong 72 adults (median age 81 [interquartile range 76–86], 56% female, median number of SBP readings 11 [3–19]), patients with moderate-severe CAA had similar mean SBP (143 vs. 145 mmHg, P = 0.588) but lower SBP variability (SBP standard deviation [SD] 14 vs. 17 mmHg, P = 0.033) compared with patients with absent-mild CAA, and their SBP trajectories seemed to differ over 10 years before ICH. The odds of moderate-severe CAA were higher with lower maximum SBP (adjusted OR per 10 mmHg lower: 1.53, 95% confidence interval [CI] 1.09–2.15; P = 0.015) and lower SBP range (1.29 [1.03–1.61]; P = 0.028), but not SBP SD (1.95 [0.87–4.38]; P = 0.11).DiscussionCompared with absent-mild autopsy-verified CAA, moderate-severe CAA is associated with lower maximum and range of pre-morbid SBP.

Normotensive state during acute phase of hypertensive intracerebral hemorrhage.

Hypertensive hemorrhage is a leading cause of intracerebral haemorrhage (ICH), although some of these patients may not present with high blood pressure (BP) at the time of ICH. This retrospective study included patients with history of hypertension presenting with ICH. Patients with systolic BP recording of more than 140 mmHg were included in hypertension group (group I). Patients whose BP rose to hypertension range after fluid correction were included in group II and patients with BP <140 mmHg on consecutive 1-week BP recordings were included in group III. Clinical features including volume of ICH of all the three groups were noted. Outcome in the form of mortality was analyzed. Chi-square test was used for categorical variables and independent t-test for continuous variables. P < 0.05 was considered significant. Ninety-two ICH patients with history of hypertension were included in the study. Of them, 20 patients (22%) presented with BP <140 mmHg systolic at the time of ICH. After fluid correction, it rose to hypertensive range in 9 (10%) but remained normal in 11 patients (12%) during consecutive recordings for 1-week post-admission. On comparing normotensive and hypertensive groups, significant difference was seen in survival and volume of ICH. There is a subset of hypertensive patients who may present with normal BP recording during acute ICH. The BP rises subsequently with the correction of hypovolemia in some. The volume of hemorrhage in normotensives is relatively small but whether this translates into better prognosis needs further studies.

Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial

BackgroundCerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients.MethodsThe BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics.DiscussionThe results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers.Trial registrationClinicalTrials.gov NCT05680389. Registered on January 11, 2023

Abstract WP132: Cerebral Amyloid Angiopathy And Risk Of Ischemic And Hemorrhagic Stroke

Introduction: Cerebral amyloid angiopathy (CAA), a condition characterized by beta amyloid deposition in the cerebral vasculature, is a common cause of intracerebral hemorrhage (ICH) in elderly patients. Radiographic features of CAA such as white matter hyperintensities and cerebral microbleeds are also associated with an increased risk of ischemic stroke. However, there are limited population-based data regarding the risk of incident ischemic and hemorrhagic stroke associated with clinically diagnosed CAA. Methods: We performed a retrospective cohort study using inpatient and outpatient claims from 2016 to 2018 from a nationally representative 5% sample of Medicare beneficiaries. The study exposure was a diagnosis of CAA identified using ICD-10-CM code I68.0. Participants with prevalent stroke were excluded. The primary outcome was any stroke (ischemic or hemorrhagic), and secondary outcomes were ICH, subarachnoid hemorrhage (SAH), and ischemic stroke, assessed separately. These outcomes were identified using validated ICD-10-CM diagnosis codes. Cox proportional hazards regression was used to determine the association between CAA and outcomes after adjustment for demographics and vascular comorbidities. Results: Of the 1.3 million Medicare beneficiaries included, 436 had clinically documented CAA without a prior or concurrent stroke. During a median follow-up of 3.0 years (IQR, 2.3-3.0), incident ischemic stroke occurred in 29,545 patients (2.28%), SAH in 3,340 (0.26%), and ICH in 4,338 (0.34%). In adjusted Cox models, CAA was significantly associated with an increased risk of any stroke (HR, 3.4; 95% CI, 2.5-4.7), ICH (HR, 17.1; 95% CI, 11.1-26.3), and SAH (HR, 6.2; 95% CI, 2.7-13.9). There was a nonsignificant association with ischemic stroke (HR, 1.4; 95% CI, 0.8-2.4). Conclusions: In a nationally representative cohort of Medicare beneficiaries, CAA was associated with a significantly increased risk of future ICH and SAH, but was not significantly associated with an increased risk of future ischemic stroke.

Surface regularity: A new factor for predicting the expansion of intracerebral hemorrhage?

BackgroundThe radiology features of CT can be used to predict the development of hemorrhage. Purpose: To explore the relationship between regularity and the expansion of hematoma by using a novel factor: surface regulation. Methods: This is a retrospective study, where 213 patients (71 females, 33.3 %) are retrospectively analyzed. The inclusion criteria are as follows. The diagnosis of spontaneous supratentorial hemorrhage, admission CT scan and a cranial CT scan obtained within 9 h are required, with other potential causes of intracerebral hemorrhage excluded during hospitalization. The exclusion criteria are as follows. Any patients having operative treatment before the cranial CT scan are excluded. Then, they are divided into the hematoma expansion group based on expanded hematoma (relative growth ≥ 33 % or absolute growth ≥ 6 ml) and the non-hematoma expansion group. After other factors are balanced through a 1:2 PS match, 82 samples (31 females, 37.8 %) are modeled to calculate their surface area and volume by using 3D Slicer and their surface regularity [SR=6√πvolume√surfacearea3]. Results: The mean ± SD SR value of Group-HE is calculated to be 0.557 ± 0.131, while that of Group-NHE is calculated to be 0.631 ± 0.101. The effect of surface regulation on the expansion of intracerebral hemorrhage hematoma is found to be statistically significant (OR 0.004, 95 %CI 0.00–0.27, P = 0.011). Conclusions: There is a link between surface regularity and hematoma expansion during the early stages of intracerebral hemorrhage.

Evaluation of Anticonvulsant Action of Nebivolol in Albino Mice

Background: Epilepsy is a disorder of brain function indicating periodic and unpredictable occurrence of seizures. Hypertension is the main cause of intracerebral hemorrhage which is a triggering factor for development of epilepsy. Nebivolol, a β-blocker is an anti-hypertensive drug, could decrease the glutaminergic transmission with addition of antioxidant property as a contributing factor may possibly provide anticonvulsant effect. Aim and Objective: The aim of the study was to study the anticonvulsant effect of Nebivolol in Albino mice. Materials and Methods: An either sex of Albino mice weighing between 18 and 22 g were used. Forty-eight animals (n = 48) were divided into eight groups with six in each group; four groups each for maximal electroshock (MES) and pentylenetetrazole (PTZ) models, respectively. Hind Limb Flexion, Hind Limb Extension, Clonus, and Postictal Depression were observed using MES model, Seizure latency and Duration of seizures were observed using PTZ model. Results: Nebivolol showed anticonvulsant effect with MES convulsions at both 0.25 mg/kg and 0.5 mg/kg but this effect is not equivalent to that of phenytoin in the present study. In terms of duration of tonic hind limb flexion and post-ictal depression, Nebivolol 0.5 mg/kg dose has comparable results to that of phenytoin. In PTZ model, Nebivolol decreased the seizure duration but did not delay the seizure onset, which were comparable to the standard Diazepam. Conclusion: Nebivolol may possibly be beneficial in treating generalized tonic clonic seizures and absence seizures. However, more extended studies are needed to prove the anticonvulsant effect of Nebivolol and enable its use in clinical practice.

State of the Art in the Role of Endovascular Embolization in the Management of Brain Arteriovenous Malformations—A Systematic Review

As a significant cause of intracerebral hemorrhages, seizures, and neurological decline, brain arteriovenous malformations (bAVMs) are a rare group of complex vascular lesions with devastating implications for patients' quality of life. Although the concerted effort of the scientific community has improved our understanding of bAVM biology, the exact mechanism continues to be elucidated. Furthermore, to this day, due to the high heterogeneity of bAVMs as well as the lack of objective data brought by the lack of evaluative and comparative studies, there is no clear consensus on the treatment of this life-threatening and dynamic disease. As a consequence, patients often fall short of obtaining the optimal treatment. Endovascular embolization is an inherent part of multidisciplinary bAVM management that can be used in various clinical scenarios, each with different objectives. Well-trained neuro-interventional centers are proficient at curing bAVMs that are smaller than 3 cm; are located superficially in noneloquent areas; and have fewer, larger, and less tortuous feeding arteries. The transvenous approach is an emerging effective and safe technique that potentially offers a chance to cure previously untreatable bAVMs. This review provides the state of the art in all aspects of endovascular embolization in the management of bAVMs.

Prediction of intracerebral hemorrhage in patients with out-of-hospital cardiac arrest using post-resuscitation electrocardiogram: An observational cohort study

AimWe evaluated the characteristics of patients with intracerebral hemorrhage in nontraumatic out-of-hospital cardiac arrests (OHCA) after return of spontaneous circulation (ROSC) to identify patients who required brain computed tomography as the next diagnostic workup. MethodsWe conducted a retrospective cohort study on 1303 consecutive patients with nontraumatic OHCA who were admitted to Miyazaki Prefectural Nobeoka Hospital between 2008 and 2020. Among these, 454 patients achieved sustained ROSC. We excluded 126 patients with obvious extracardiac causes. Clinical and demographic characteristics of patients and post-resuscitation 12-lead electrocardiogram were compared. Patients were categorized into the intracerebral hemorrhage (n = 32, 10%) and no intracerebral hemorrhage group (n = 296). All causes of intracerebral hemorrhage were diagnosed based on brain computed tomography images by board-certified radiologists. ResultsWe included 328 patients (mean age, 74 years; women, 36%) who achieved ROSC. Logistic regression analyses showed that female sex, younger age (<75 years), no shockable rhythm changes, tachycardia (≥100 bpm), lateral ST-segment elevation, and inferior ST-segment depression on post-resuscitation electrocardiogram were independently associated with intracerebral hemorrhage. We developed a new predictive model for intracerebral hemorrhage by considering 1 point for each of the six factors. The odds ratio for intracerebral hemorrhage increased 2.36 for each 1-point increase (P < 0.001). A score ≥ 4 had 43.7% sensitivity, 90.8% specificity, 34.1% positive predictive value, and 93.7% negative predictive value. ConclusionOur new predictive model might be useful for risk stratification of intracerebral hemorrhage in patients with OHCA who achieved ROSC.

A Causal Classification System for Intracerebral Hemorrhage Subtypes.

Determining the underlying causes of intracerebral hemorrhage (ICH) is of major importance, because risk factors, prognosis, and management differ by ICH subtype. We developed a new causal CLASsification system for ICH Subtypes, termed CLAS-ICH, based on recent advances in neuroimaging. CLAS-ICH defines 5 ICH subtypes: arteriolosclerosis, cerebral amyloid angiopathy, mixed small vessel disease (SVD), other rare forms of SVD (genetic SVD and others), and secondary causes (macrovascular causes, tumor, and other rare causes). Every patient is scored in each category according to the level of diagnostic evidence: (1) well-defined ICH subtype; (2) possible underlying disease; and (0) no evidence of the disease. We evaluated CLAS-ICH in a derivation cohort of 113 patients with ICH from Massachusetts General Hospital, Boston, USA, and in a derivation cohort of 203 patients from Inselspital, Bern, Switzerland. In the derivation cohort, a well-defined ICH subtype could be identified in 74 (65.5%) patients, including 24 (21.2%) with arteriolosclerosis, 23 (20.4%) with cerebral amyloid angiopathy, 18 (15.9%) with mixed SVD, and 9 (8.0%) with a secondary cause. One or more possible causes were identified in 42 (37.2%) patients. Interobserver agreement was excellent for each category (kappa value ranging from 0.86 to 1.00). Despite substantial differences in imaging modalities, we obtained similar results in the validation cohort. CLAS-ICH is a simple and reliable classification system for ICH subtyping, that captures overlap between causes and the level of diagnostic evidence. CLAS-ICH may guide clinicians to identify ICH causes, and improve ICH classification in multicenter studies. ANN NEUROL 2023;93:16-28.

The Outcomes of COVID-19 Patients with Spontaneous Intracerebral Hemorrhage Comorbidity and the Efficacy of Enoxaparin in Decreasing the Mortality Rate in Them: Single Egyptian Center Report

Patients with neurological comorbidities are more likely to develop severe COVID-19. We aimed to detect the outcomes of COVID-19 patients with spontaneous intracerebral hemorrhage comorbidity and the role of enoxaparin in decreasing the mortality rate in these cases, even though enoxaparin is a potential cause of intracerebral hemorrhage. The patients were checked on to detect surveillance outcomes, the relationship between mortality and patient characteristics, and the relationship between enoxaparin and study outcomes. Chest condition and GCS improved in 67.9% of participants. Hematoma course increased in 49.1%. Midline-shift, brain-edema, and COVID symptoms improved in 67.9%. There was a non-significant difference in mortality regarding age and gender. There was a significant difference in mortality regarding treatment with enoxaparin; 75% of the patients who did not receive enoxaparin died. 92.6% of the patients who showed decreases in hematoma course were administered enoxaparin. 76.9% of the patients who showed increases in hematoma-course were administered enoxaparin. Most of the patients who were admitted to the neurosurgical unit with spontaneous intracerebral hemorrhage acquired the COVID-19 infection. Most of the cases included in this study did not progress to severe cases. The dying patients showed deterioration in both neurological and COVID-19 symptoms. The anticoagulant properties of enoxaparin given earlier before and throughout the infection can considerably reduce mortality in COVID-19 individuals with spontaneous intracerebral hemorrhage. It is recommended to use enoxaparin for cases with spontaneous intracerebral hemorrhage and COVID-19 regardless of hematoma size because the rate of improvement was greater than the mortality rate after using enoxaparin in this study.