Lobar Hemorrhage Research Articles

Neuroradiological Findings in Cerebral Amyloid Angiopathy with a Particular Consideration of the Boston Criteria 2.0: An Imaging Review

In the elderly, cerebral amyloid angiopathy (CAA) is the most common cause for intracranial lobar hemorrhages. CAA is caused by the accumulation of amyloid-β fibrils in cortical and leptomeningeal vessels. In 2022, the Boston Criteria 2.0 became the new diagnostic standard for CAA, following the Modified Boston Criteria of 2010. The diagnostic criteria are a composite of clinical, imaging and histopathological findings. In the latest version of the Boston Criteria, neuroradiological imaging findings were even expanded compared to the previous version. Crucially, the correct application of the diagnostic criteria is necessary to avoid over- and underdiagnosis. The aim of this review is to demonstrate the diagnostic criteria for CAA with an emphasis on typical imaging findings which are part of the Boston Criteria 2.0 and other imaging findings suggestive of CAA.

Risk factors for intracerebral hemorrhage by five specific bleeding sites: Japan Public Health Center-based Prospective Study.

Evaluating the risk factors for intracerebral hemorrhage is indispensable for primary prevention. However, the pathogenesis varies depending on the bleeding site, and few prospective studies have explored risk factors in detail for each site. The Japan Public Health Center-based Prospective Study is a prospective study comprising a population-based sample of Japanese adults in 1990 (Cohort I) and in 1993 (Cohort II). A total of 34,137 participants (11,907 men and 22,230 women) were enrolled in this study and followed up until 2009 for Cohort I and until 2012 for Cohort II. The association between risk factors (age, sex, blood pressure, serum cholesterol, triglycerides, blood glucose, body mass index, smoking, and drinking status) and intracerebral hemorrhage by its bleeding site (lobes, putamen, thalamus, cerebellum, and brainstem) was assessed using Cox proportional hazards analysis. During a median 20-year follow-up, 571 intracerebral hemorrhage events occurred. Hypertension was associated with an increased risk of total intracerebral hemorrhage, but not lobar hemorrhage. The multivariable hazard ratio (95% confidence intervals) was 2.09 (1.75-2.50) for total intracerebral hemorrhage. In contrast, a low serum total cholesterol level was associated only with lobar hemorrhage (1.73 (1.01-2.96)). Heavy drinking was associated with the risk of total and putamen hemorrhage, and obesity was associated with the risk of putamen hemorrhage. The present study identified different risk factors depending on the bleeding site of intracerebral hemorrhage.

Surgical Management for Primary Intracerebral Hemorrhage.

The incidence of primary intracerebral hemorrhage (ICH) is increasing, particularly in younger patients, in part, because of increased prescription of anticoagulants. The ICH incidence rate from 2016 to 2018 in the United States was nearly 79 per 100,000 person-years and as high as 367 per 100,000 person-years among those 75 years or older. Worldwide, ICH comprises 28% of all new strokes, but a higher disease burden than ischemic stroke because of its higher morbidity and mortality. While mortality seems to be decreasing, functional outcomes are not improving. After negative trials of open surgical evacuation, recent trials of medical management strategies including intensive blood pressure control and prothrombotic agents intended to reduce hematoma expansion failed to demonstrate efficacy. Concomitantly, continued interest in minimally invasive surgical approaches arose from appreciation of secondary iatrogenic injury incurred to subcortical white matter tracts from open surgical techniques. A positive trial of minimally invasive surgery for lobar hemorrhage has recently been reported, bringing new optimism and demanding a reconsideration of surgical management of ICH. In this narrative review, we summarize the landmark studies, review recent literature, and consider the outstanding questions surrounding surgical management of ICH.

Factors associated with cognitive impairment before intracerebral haemorrhage: community-based neuropathological study.

Little is known about whether clinical, radiological or neuropathological features are associated with cognitive impairment before intracerebral haemorrhage. We conducted a community-based cohort study of 125 adults with intracerebral haemorrhage (lobar n = 71, non-lobar n = 54) with consent to brain autopsy. We compared small vessel disease biomarkers on diagnostic CT head and neuropathological findings including neurofibrillary tangles and amyloid plaques in adults without cognitive impairment versus cognitive impairment without dementia versus dementia before intracerebral haemorrhage, stratified by lobar and non-lobar intracerebral haemorrhage. In non-lobar intracerebral haemorrhage, severe cortical atrophy was less common in those without cognitive impairment (8/36, 22%) and cognitive impairment without dementia (0/9, 0%) versus dementia (5/9, 56%); P = 0.008. Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder neurofibrillary tangle pathology measured by median Braak stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [interquartile range, 2-3] versus cognitive impairment without dementia 4 [2-6] versus dementia 5.5 [4-6]; P = 0.004; non-lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [1-2] versus dementia 5 [3-6]; P < 0.001). Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder amyloid plaque pathology measured by median Thal stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [2-3] versus dementia 2.5 [2-3.5]; P = 0.033; non-lobar intracerebral haemorrhage: no cognitive impairment 1 [0-1] versus cognitive impairment without dementia 0 [0-2] versus dementia 3 [2-3]; P = 0.002). Our findings suggest that irrespective of intracerebral haemorrhage location, adults with cognitive impairment before an intracerebral haemorrhage have more Alzheimer's disease neuropathologic change.

Antithrombotics alter intracerebral hemorrhage presentation without affecting minimally invasive endoscopic evacuation

ObjectivesIntracerebral hemorrhages are associated with significant morbidity and mortality. While the ENRICH trial supports the efficacy of surgical evacuation for lobar hemorrhages, the impact of antithrombotic therapies on minimally invasive surgery outcomes remains unexplored. This study evaluates the effects of chronic anticoagulants and antiplatelets on the technical and longterm outcomes of minimally invasive intracerebral hemorrhage evacuation. Materials and MethodsA prospectively collected registry of patients undergoing minimally invasive surgery for intracerebral hemorrhage from a single institution was analyzed (December 2015-September 2022). Data included key demographics, comorbidities, antithrombotic/reversal status, presenting clinical/radiographic characteristics, procedural metrics, and clinical outcomes. Patients were divided into control (neither therapy), antiplatelet-only, and anticoagulant-only groups, with antiplatelet/anticoagulant reversals conducted per current American Heart Association/American Stroke Association guidelines. Variables significant in univariate analyses (p<0.05) were advanced to multivariable regression models. ResultsAmong 226 intracerebral hemorrhage patients treated with minimally invasive surgery, 41% (N=93) had antithrombotic medication history; 28% (N=64) received antiplatelets, and 9% (N=21) received anticoagulants. Patients on both therapies (N=6) were excluded. The antiplatelet group presented more frequently with lobar hemorrhages (56% vs. 37%; p=0.022), while patients on anticoagulants showed increased rates of intraventricular hemorrhage co-presentation (62% vs. 46%; p=0.011) compared to controls. Despite univariate analyses showing a higher postoperative hematoma volume (3.9 vs. 2.9 milliliters; p=0.020) and lower evacuation percentage (88% vs. 92%; p=0.019) for the antiplatelet group, and longer procedures for patients on anticoagulants (2.3 vs. 1.7 hours; p=0.042) compared to control, multivariable analyses indicated that antiplatelets and anticoagulants had no significant impact on these technical outcomes. Longitudinally, antithrombotics were not associated with increased rebleeding, less frequent discharge to home, lower 30-day mortality, or worse, 6-month Modified Rankin Scale scores. ConclusionsPatients on chronic antiplatelets and anticoagulants exhibited characteristic intracerebral hemorrhage phenotypes without worse technical or long-term outcomes after minimally invasive intracerebral hemorrhage evacuation, suggesting the procedure's safety for these patients.

Association of Antithrombotic Drug Use With Incident Intracerebral Hemorrhage Location.

Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.

Retrospective study of ivosidenib for patients with recurrent IDH mutant gliomas.

2040 Background: IDH mutant gliomas are the most common primary malignant brain tumors in adults under the age of 50 and accounts for approximately 12% of all glioma diagnoses each year. While lower grade gliomas (LGG) encompassing WHO grades II and III are less aggressive than their higher-grade counterparts, treatment is not curative, and most patients develop tumor recurrence in which there are a paucity of effective treatment options. Mutations in IDH1/ 2 occur upwards of 80% of patients with LGG and drive specific epigenetic programs to dysregulate and impair differentiation leading to tumorigenesis. As such, pharmacologic blockage of IDH mutant enzymes is being actively investigated as potential treatment option. Ivosidenib (AG-120), a second-generation IDH inhibitor, is an FDA approved medication for treatment of IDH-mutated acute myeloid leukemia and has demonstrated safety and clinical activity in patients with progressive IDH mutant gliomas. We explored the efficacy of Ivosidenib in IDH mutant gliomas. Methods: We retrospectively analyzed patients with IDHm gliomas treated with ivosidenib in our institution. We included patients with an IDH1 mutation who received at least one cycle of ivosidenib. Data collected included patient demographics, tumor histology, tumor location, grade, 1p/19q co-deletion, MGMT, CDKN2A, TERT, EGFR, P53, PTEN mutational status, prior treatment history, duration of treatment, toxicities, radiographic response, PFS, and OS. Descriptive statistics were used to summarize patients' characteristics. The distribution of mPFS was estimated by the Kaplan-Meier method. Results: Between April 2010 and December 2023, we identified 33 patients that received ivosidenib. 7 patients received ivosidenib in combination with bevacizumab, 3 patients received ivosidenib in combination with radiation, and 1 patient received ivosidenib and nivolumab. The median age was 52 (range 31-81). 21 (63%) were male. The median lines of medical therapy and radiation/surgery prior to starting ivosidenib were 3.03(range 0-6) and 1.5(range 0-4), respectively. 27(81%) were grade 2, 5(15%) were grade 3, and 1(3%) were grade 4. 19(57%) had 1p/19q co-deletion. As of 12/31/2023, 48%(16) patients were alive. The median PFS was 7.52 months (1-26) and median OS 12.7 months (3-25). 11(33%) patients experienced partial response (PR), 20(60%) experienced stable disease (SD) and 2(6%) demonstrated progressive disease (PD) at 12-week assessment. Nine patients experienced adverse events: grade 1 fatigue (3), grade 1 diarrhea (1), grade 2 fever (1), grade 2 weakness (1), and grade 3 confusion (1). One patient experienced grade 4 lobar hemorrhage thought to be related to concurrent bevacizumab use. Conclusions: Treatment with Ivosidenib therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre-treated recurrent IDH mutant gliomas.

The potential for minimally invasive intracerebral hemorrhage evacuation in routine healthcare: applicability of the ENRICH trial criteria to an unselected cohort

ObjectiveFollowing the favorable outcomes demonstrated by the Early MiNimally-invasive Removal of IntraCerebral Hemorrhage (ENRICH) trial in supratentorial intracerebral hemorrhage (ICH) patients treated with minimally invasive surgery (MIS), and considering the increasing interest in MIS, we aimed to assess the potential eligibility rate for ICH patients in Sweden.MethodsAll patients with spontaneous ICH in the Swedish Stroke Register (RS) during 2017–2020 in Skane county (1.37 million) were assessed. Baseline imaging was used for radiological characterization. Clinical data were obtained from RS. MIS eligibility in the total ICH population meeting ENRICH criteria were estimated and extrapolated to the Swedish population (10.5 million).ResultsOf 1,314 ICH patients, 5.9% met the ENRICH criteria for MIS (ICH volume 30–80 ml). Considering the ENRICH trial results indicating the effectiveness of MIS was mainly attributable to intervention for lobar hemorrhages, we determined that 2.8% of our ICH cohort in Sweden would be eligible for MIS. The estimated rate of neurosurgery for ICH could increase from the current 1.46–1.90 patients/100,000 population/year (in absolute numbers from 154 to 200 interventions out of 2,400 ICHs in Sweden annually).ConclusionsWe show that 2.8% of the Skane ICH population would be eligible for MIS if ENRICH criteria are employed for patients with lobar ICH, corresponding to a 29% increase of current surgical rates for ICH in Sweden. As MIS for ICH is not yet standard practice in Sweden, consideration for its implementation within the neurosurgical organization becomes essential to accommodate the anticipated increase in patient demand.

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage

BackgroundTrials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known.MethodsIn this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients’ assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment.ResultsA total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and −0.013 (95% Bayesian credible interval, −0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration.ConclusionsAmong patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.)

Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage (P10-2.004)

Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage (P10-2.004)

Abstract 149: Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage

Background: Blood pressure (BP) reduction is associated with better neuroimaging and clinical outcomes in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Because this evidence comes from studies that overwhelmingly enrolled deep hemorrhages, the impact of BP reduction in patients with lobar ICH remains understudied. Methods: We re-analyzed data from the pivotal Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) study. We included all patients with available neuroimaging data. Participants were randomized to either intensive (systolic BP target 110-139 mmHg) or standard (systolic BP target 140-179 mmHg) acute BP lowering. The main outcome measures were hematoma expansion &gt; 6 mL in the first 24 hours (HE), poor functional outcome (3-month mRS 4-6) and renal adverse events (RAE) until day 7 or hospital discharge. We fitted multivariable logistic regression models to test for association between the intervention and our outcomes of interest. Covariates included sex, age, race and ethnicity, and baseline ICH volume. Results: Among 1,000 patients enrolled in ATACH-2, 875 (87.5%) with complete data were included (88.9% deep hemorrhages and 11.1% lobar hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced as in the original study (all comparisons p &gt;0.05). Multivariable logistic regression showed that intensive BP reduction decreased the risk of HE (OR 0.60, 95%CI 0.39-0.90; p=0.02) and increased the risk of RAE (OR 2.53, 95%CI 1.40-4.77; p=0.003) in patients with deep, but not lobar ICH (HE, OR: 0.89; 95% CI= 0.31 - 2.52; p=0.83 and RAE, OR: 0.46; 95% CI= 0.04 - 5.10; p=0.53). Intensive BP reduction was not associated with improved mRS in either deep (OR: 0.96; 95 % CI= 0.68 - 1.37; p= 0.82) nor lobar (OR: 0.66; 95% CI= 0.16 - 2.42; p= 0.54) ICH. Conclusion: The impact of intensive blood pressure lowering differs in deep and lobar ICH. These results emphasize the need for a better understanding about biologic differences in ICH, which may have therapeutic implications.

Abstract WMP81: Overweight Patients Had Higher Odds of Favorable Outcome After Both Deep and Lobar Intracerebral Hemorrhage

Introduction: Intracerebral Hemorrhage (ICH) leads to high rates of morbidity and mortality. Malnutrition is common in stroke patients and leads to worse outcomes. Body mass index (BMI) is a widely available marker of nutrition status, however studies on BMI and post-ICH outcomes are limited and have conflicting results. We aim to clarify this relationship by examining the relationship between BMI, nutritional lab markers, ICH severity, and functional outcome at discharge stratified by ICH location. Methods: We leveraged data from an ongoing longitudinal ICH study of adults with spontaneous primary ICH. Patients were divided into underweight, normal weight, overweight, and obese according to World Health Organization BMI criteria. Albumin, B12, total bilirubin, cholesterol, CRP, ferritin, iron, folate, hbA1c, HDL, LDL, hemoglobin, MCV, INR, ALT, triglycerides, and vitamin D were abstracted from health records. Associations between BMI, lab markers, ICH volume, and favorable outcome (mRS 0-2) were analyzed using univariate and multivariable logistic regression stratified by deep versus lobar hemorrhage location, with normal weight as the reference. Results: 1,370 patients (719 with deep hemorrhage, 651 with lobar hemorrhage) were included. There was no association between BMI and ICH volume in patients with deep or lobar hemorrhage. Multivariable analyses adjusting for age, education, diabetes mellitus, coronary artery disease, alcohol use, ICH volume, and intraventricular hemorrhage showed that overweight, but not underweight or obese, subjects had higher odds of favorable outcome on discharge in the deep (OR 3.16, 95% CI 1.36-7.34) and lobar (OR 3.15, 95% CI 1.67-5.94) groups. Albumin (OR 2.27, 95% CI 1.05-4.90) and hemoglobin (OR 1.31, 95% CI 1.09-1.59) were the only labs associated with favorable outcome in the deep hemorrhage group while no markers were associated with favorable outcome in the lobar hemorrhage group. Albumin and hemoglobin were not associated with being overweight. Conclusion: Overweight patients had three times higher odds of favorable outcome after both deep and lobar hemorrhages. This was not driven by ICH severity or explained by lab markers. Future biomarker studies are needed to better understand this relationship.

Abstract TMP81: Effect of Post Thrombolytic Intracerebral Hemorrhage Volume on 90-day Outcomes in Acute Ischemic Stroke Patients

Background and Purpose: Post thrombolytic intracerebral hemorrhage (ICH) is associated with higher rate of death or disability in acute ischemic stroke patients. We investigated the relationship between post thrombolytic ICH volume and change in volume and death or disability at 90 days in acute ischemic stroke patients. Methods: We analyzed 110 patents recruited in the Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY) trial who received intravenous tissue plasminogen activator (tPA) followed by mechanical thrombectomy (if indicated) and 3K3A-APC or placebo. ICH volume was measured at Day 2 and Day 7 using susceptibility weighted sequence (SWI) on magnetic resonance imaging (MRI). We also calculated the post thrombolytic ICH volume change between Day 2 and Day 7. Outcomes were determined by using utility weighted modified Rankin scale (UW-mRs) at 90-days. We adjusted for age, gender, National Institute of Health Stroke Scale (NIHSS) score (&lt;10,10-19 and ≥20), location of hemorrhage (single basal ganglia hemorrhage, single lobar, single cerebellum, and multiple sites hemorrhage) in multivariate regression analysis. Results: A total of 88 (80%) of 110 patients had post thrombolytic ICH (mean volume 28.3 ml ± SD 62ml). The strata of ICH volume were not associated with UW-mRs at 90 days: &lt;20 cc (regression coefficient-0.05, p= 0.58), 20-39 cc (-0.23, p=0.15), or 40 cc (-0.33, p= 0.086) compared with no ICH after adjusting for potential confounders. Change in ICH volume mean volume 27.43ml ±59.01, 52 had increase in volume) between Day 2 and day 7 was not associated with UW-mRS at 90 days (regression coefficient -11.87, p= 0.796). Conclusions: We did not observe any independent effect of post thrombolytic ICH volume on death or disability in acute ischemic stroke patients. Strategies to prevent ICH expansion such as antifibrinolytic medications and reduction in ICH volume such as surgical evacuation may not reduce death or disability in acute ischemic stroke patients with post thrombolytic ICH.

A case of young onset cerebral amyloid angiopathy associated with dural grafting

A 47-year-old man was admitted to our hospital because of sudden-onset motor aphasia and right hemiplegia. His past medical history was notable for left craniotomy and hematoma evacuation following a traumatic brain hemorrhage approximately 40 years earlier, for which dural grafting was performed. He also had a history of three lobar hemorrhages in the left hemisphere since the age of 42 years. Brain CT imaging revealed an acute left frontal lobar hemorrhage. His initial brain MRI conducted at our hospital demonstrated hemorrhagic findings with left hemisphere dominance, including acute and old lobar hemorrhage, cortical superficial siderosis, and cerebral microbleeds. Cerebrospinal fluid analyses demonstrated reduced levels of cerebral amyloid-β 42, and elevated total tau. His apolipoprotein E genotype was ε3/ε3. Whole-exome sequencing did not detect mutations in genes associated with Alzheimer's disease, including presenilin 1, presenilin 2, and amyloid precursor protein. These findings led to a clinical diagnosis of iatrogenic cerebral amyloid angiopathy (CAA) using recently proposed diagnostic criteria, which do not require pathological evaluation of the brain. Iatrogenic CAA should be considered as a cause of lobar hemorrhage in young patients, especially those with a past history of neurosurgery.

Incidence of and risk factors for new-onset urinary and fecal incontinence after acute stroke

Background:Understanding the risk factors for incontinence after acute stroke allows for early identification and treatment of patients who are likely to experience this complication. Objectives:The purpose of this study was to estimate the incidence of urinary and fecal incontinence (UI and FI) after stroke in adults and examine the association of risk factors. Methods:Screening data from a prospective study were analyzed. Included were 652 consecutive patients admitted to an acute stroke unit over a 15-month period beginning May 2021. Those with pre-existing UI or FI were excluded from the analysis. Bivariate analyses examined unadjusted relationships between both UI and FI and age, sex, stroke severity, premorbid disability, stroke type, and stroke anatomical site. Regression analyses were performed to build iterative models. Results:A total of 418 patients had an acute stroke without pre-existing incontinence. The median age of stroke survivors was 76 years (IQR 66–84), 58% were men, and 76% had an ischemic stroke. Within the first 7 days after stroke, 128 (29%) had UI and 115 (26%) had FI. Increasing age, premorbid disability, and stroke severity increased the risk of both new-onset UI and FI after stroke. Those with intraventricular hemorrhage were 2.9 times more likely to develop UI. Women were 1.7 times more likely to have UI after stroke than men. Intraventricular hemorrhage increased the risk of new-onset FI after stroke by 2.9 times, while lobar hemorrhage increased the risk by 2.2 times. Conclusions:Urinary and fecal incontinence continue to be relatively common after acute stroke, although incidence rates are lower than 20th century estimates. Patients are more likely to require incontinence assessment, monitoring and care if they are older, had higher premorbid disability, and have experienced more severe stroke or intraventricular hemorrhage. Given that more than a quarter of stroke patients develop incontinence following stroke, continence care and rehabilitation programs remain essential components of stroke services.

Abstract 117: Digitally Subtracted Angiogram &amp; Biopsy Negative Recurrent Spontaneous Bilateral Anterior Cerebral Artery Territory Intracranial Hemorrhage

Introduction Up to 18% of spontaneous intracerebral hemorrhages are cryptogenic despite a thorough workup, usually noted in a lobar location. Although undetected on DSA, a significant proportion of these represent ruptured micro‐AVM/AVF or cavernous malformations that ultimately are amenable to surgical resection if detected on biopsy. However, occult cerebral amyloid angiopathy can also present similarly, and their management is markedly different. Methods We present a case of recurrent bilateral medial frontal hemorrhage in a patient without known cerebrovascular disease that evaded diagnosis despite hematologic evaluation, MRI, CTA, two DSAs, three clot evacuations with pathology, and brain biopsy. Results The patient is a 60‐year‐old previously healthy woman who presented with sudden onset right hemiparesis and speech arrest. CT revealed a left parasagittal hemorrhage. She was brought to the OR for clot evacuation. Pathology from the clot revealed blood vessels of multiple sizes consistent with meningeal vessels or underlying AVM/AVF. A 6‐vessel cerebral angiogram as unremarkable. The patient’s inpatient course was complicated by new onset Afib with RVR and asymptomatic DVT with PE, however no etiology of coagulopathy was detected. MRI brain showed no evidence of cerebral microbleed or other underlying pathology, noting only DWI + FLAIR hyperintensity in the left ACA territory. The patient was diagnosed with ACA territory stroke complicated by PH2‐type hemorrhagic conversion. She was initially placed on IV Heparin, before transition to apixaban uneventfully. She continued to recover in the hospital and was eventually discharged to rehab. She re‐presented 1 month later with worsening behavioral arrest and right hemiparesis. CT head revealed recurrence of left parasagittal ICH. She underwent clot evacuation in the OR again and repeat pathology was unrevealing. A repeat MRI showed only the evident bleed and a subtle hyperintensity in the right occipital cortex suspicious for an interval subacute occipital lobe stroke with laminar necrosis, ostensibly from Afib. She improved clinically and was discharged to rehab with a diagnosis of recurrent hemorrhage attributed to anticoagulant use and recent stroke. She was discharged this time on no anticoagulant or antiplatelets. She re‐presented 1 month later with sudden onset speech arrest, but now with left hemiparesis. CT revealed a right parasagittal hemorrhage. She was brought to the OR for emergent clot evacuation and parenchymal biopsy – which was initially normal. A repeat 6‐vessel DSA was again unremarkable as was repeat brain MRI. The patient’s parenchymal biopsy was sent for specific congo‐red and immunohistochemistry for beta‐amyloid. IHC revealed beta‐amyloid plaques in the parenchyma and vessel walls, confirming a diagnosis of CAA. Conclusion Apparently cryptogenic lobar hemorrhage may be caused by both occult micro‐AVM/fistula and CAA. As in this case, when a patient experiences recurrent DSA negative lobar hemorrhages, biopsy should be pursued. This case was particularly challenging given the anatomical plausibility of parasagittal AVM/fistula given its midline location and venous drainage, considering the patient’s evident predisposition to systemic venous thrombosis hemorrhagic venous infarction mimicking lobar ICH is also possible. We present this case to raise awareness of the potential need for early biopsy, especially in patients who may also require anticoagulation or antiplatelet medications.

Cerebral amyloid angiopathy: Neuropathological diagnosis, link to Alzheimer's disease and impact on clinics.

Cerebral amyloid angiopathy (CAA) is the most frequent cause of lobar hemorrhages in the brains of elderly individuals. It is characterized by the deposition of amyloidogenic proteins in the vessel wall of leptomeningeal and/or intracerebral blood vessels. Different proteins can cause CAA. Most frequently, the amyloid β protein (Aβ) is found to be deposited in CAA and indicates a link to Alzheimer's disease, because Aβ is known to be deposited in amyloid plaques characteristic of Alzheimer's disease. Among other proteins that can also cause CAA, transthyretin (TTR) is the most important one because TTR amyloidosis can be successfully treated. Therefore, it is essential to diagnose TTR-related CAA even in biopsies taken in the context of cerebral hematoma evacuations if possible. The current "Boston criteria version 2.0" for the diagnosis of CAA highlight the importance of autopsy for the definite diagnosis of CAA and biopsies for the diagnosis of probable CAA. Here, we discuss the implications of Aβ-related and non-Aβ-related forms of CAA for their current diagnostic relevance also in the context of neurodegenerative diseases as well as the implications of the Boston criteria version 2.0 for neuropathological diagnosis.

Essential nutrients and cerebral small vessel diseases: a two-sample Mendelian randomization study.

Previous studies have suggested a potential association between nutrients and cerebral small vessel disease (CSVD), but this association has not been fully addressed. We intended to clarify the causal associations between four categories of essential nutrients (amino acids, polyunsaturated fatty acids, minerals and vitamins) and two acute manifestations of CSVD (intracerebral hemorrhage and small vessel stroke) using two-sample Mendelian randomization (MR) analysis. We obtained European-based large-scale genome-wide association studies (GWASs) related to CSVD (6,255 cases and 233,058 controls) and nutrient concentrations. Causality evaluation mainly included the results of the inverse variance-weighted (IVW) method. The simple median method, the weighted median method and the MR-Egger method were adopted for sensitivity analyses. For ICH or SVS, increased levels of phenylalanine (OR = 1.188, p < 0.001) and dihomo-gamma-linolenic acid (DGLA) (OR = 1.153, p = 0.001) showed risk effects, while docosapentaenoic acid (DPA) (OR = 0.501, p < 0.001), zinc (OR = 0.919, p < 0.001), and arachidonic acid (OR = 0.966, p = 0.007) showed protective effects. For lobar hemorrhage or SVS, AA (OR = 0.978, p < 0.001), zinc (OR = 0.918, p < 0.001), and retinol (OR = 0.753, p < 0.001) showed risk effects; DPA (OR = 0.682, p = 0.022), gamma-linolenic acid (OR = 0.120, p = 0.033) and 25(OH)D (OR = 0.874, p = 0.040) showed protective effects. For nonlobar hemorrhage or SVS, DGLA (OR = 1.088, p < 0.001) and phenylalanine (OR = 1.175, p = 0.001) showed risk effects. Our study analyzed the effect of nutrients on CSVD risk from a genetic perspective, with implications for CSVD prevention through nutrient supplementation.

Reversible cerebral vasoconstriction syndrome: A review of pathogenesis, clinical presentation, and treatment.

Reversible segmental narrowing of the intracranial arteries has been described since several decades in numerous clinical settings, using variable nosology. Twenty-one years ago, we tentatively proposed the unifying concept that these entities, based on similar clinical-imaging features, represented a single cerebrovascular syndrome. This "reversible cerebral vasoconstriction syndrome" or RCVS has now come of age. A new International Classification of Diseases code, (ICD-10, I67.841) has been established, enabling larger-scale studies. The RCVS2 scoring system provides high accuracy in confirming RCVS diagnosis and excluding mimics such as primary angiitis of the central nervous system. Several groups have characterized its clinical-imaging features. RCVS predominantly affects women. Recurrent worst-ever (thunderclap) headaches are typical at onset. While initial brain imaging is often normal, approximately one-third to half develop complications such as convexity subarachnoid hemorrhages, lobar hemorrhages, ischemic strokes located in arterial "watershed" territories and reversible edema, alone or in combination. Vasoconstriction evolves over hours to days, first affecting distal and then the more proximal arteries. An overlap between RCVS and primary thunderclap headache, posterior reversible encephalopathy syndrome, Takotsubo cardiomyopathy, transient global amnesia, and other conditions has been recognized. The pathophysiology remains largely unknown. Management is mostly symptomatic: headache relief with analgesics and oral calcium-channel blockers, removal of vasoconstrictive factors, and avoidance of glucocorticoids that can significantly worsen outcome. Intra-arterial vasodilator infusions provide variable success. Overall, 90-95% of admitted patients achieve complete or major resolution of symptoms and clinical deficits within days to weeks. Recurrence is exceptional, although 5% can later develop isolated thunderclap headaches with or without mild cerebral vasoconstriction.

Utilizing the supreme anterior connecting artery in embolization of a parietal lobe arteriovenous malformation.

The supreme anterior connecting artery (SAConnA) is an exceedingly rare anatomical variant. This artery may interconnect bilateral anterior cerebral arteries (ACAs), yet its existence and clinical implications are scarcely discussed in the literature. A 60-year-old man with no significant past medical or family history presented to our emergency department. He exhibited right homonymous hemianopsia and Gerstmann's syndrome. Cranial computed tomography indicated a left parietal lobar hemorrhage, and digital subtraction angiography revealed a flow-related aneurysm in the anterior communicating artery, with the arteriovenous malformation (AVM) receiving blood supply from the anterior, middle, and posterior cerebral arteries. Notably, the angiography also disclosed the presence of a SAConnA. We adopted a treatment approach of staged embolizations followed by resection. During the second session, the SAConnA was utilized for the embolization of feeding arteries within the ACA system. This case demonstrates that SAConnA can be associated with AVMs and can serve as an access route during AVM embolization. SAConnA may be a remnant artery interconnecting bilateral ACAs formed during early embryogenesis.