Spontaneous Intracranial Hemorrhage Research Articles

Fibroblast growth factor receptor 1 gene mutation as a potential risk factor for spontaneous intracranial hemorrhage in pediatric low-grade glioma patients.

Fibroblast growth factor receptor 1 (FGFR1) mutations have been associated with poorer prognoses in pediatric central nervous system tumor patients. A recent study highlighted a link between FGFR1 mutations and spontaneous intracranial hemorrhage (ICH), demonstrating that all patients with an FGFR1 alteration experienced hemorrhage at some point during their course of treatment. The current study examined 50 out of 67 pediatric patients with low-grade gliomas (LGGs) who had genomic testing between 2011 and 2022 at our institution to determine whether a correlation exists between FGFR1 mutations and spontaneous ICH. We found that of the 50 patients with genomic data, 7 (14%) experienced ICH, and an additional spontaneous hemorrhage was recorded; however, no genomic testing was performed for this case. Five of the seven patients (71.4%) had an FGFR1 modification. In our patient population, 6 expressed a detectable FGFR1 mutation (66.7% [4/6] had N546K alteration, 16.7% [1/6] FGFR1 exons duplication, and 16.7% [1/6] had a variant of unknown significance [VUS]). The patient with the FGFR1 VUS had no reported spontaneous hemorrhage. Statistical analysis found a significant association between FGFR1 and spontaneous intracranial hemorrhage (P-value = < .0001). In the patient population, all cases of PTPN11 alterations (n = 3) co-occurred with FGFR1 mutations. Our case series highlights this link between the FGFR1 mutation and spontaneous intracranial hemorrhage in pediatric LGGs.

Analysis of short-term ventilation weaning for patients in spontaneous supratentorial intracranial hemorrhage.

Prolonged ventilation is a complication of spontaneous supratentorial hemorrhage patients, but the predictive relationship with successful weaning in this patient cohort is not understood. Here, we evaluate the incidence and factors of ventilation weaning in case of spontaneous supratentorial hemorrhage. We retrospectively studied data from 166 patients in the same hospital from January 2015 to March 2021 and analyzed factors for ventilation weaning. The clinical data recorded included patient age, gender, timing of operation, initial Glasgow Coma Scale (GCS), Intracranial hemorrhage (ICH) score, alcohol drinking, cigarette smoking, medical comorbidity, and the blood data. Predictors of patient outcomes were determined by the Student t test, chi-square test, and logistic regression. We recruited and followed 166 patients who received operation for spontaneous supratentorial hemorrhage with cerebral herniation. The group of successful weaning had 84 patients and the group of weaning failed had 82 patients. The patient's age, type of operation, GCS on admission to the Intensive care unit (ICU), GCS at discharge from the ICU, medical comorbidity was significantly associated with successful weaning, according to Student t test and the chi-square test. According to our findings, patients with stereotaxic surgery, less history of cardiovascular or prior cerebral infarction, GCS >8 before admission to the hospital for craniotomy, and a blood albumin value >3.5 g/dL have a higher chance of being successfully weaned off the ventilator within 14 days.

The impact of sex on epidemiology, management, and outcome of spontaneous intracerebral hemorrhage (sICH)

ObjectiveData on sex differences in spontaneous intracerebral hemorrhages are limited. MethodsAn automated comprehensive scoping literature review was performed using PubMed and Scopus. Articles written in English about spontaneous intracerebral hemorrhage and sex were reviewed. ResultsMales experience spontaneous intracerebral hemorrhage more frequently than females, at younger ages, and have a higher prevalence of deep bleeds compared to females. Risk factors between sexes vary and may contribute to differing incidences and locations of spontaneous intracranial hemorrhage. Globally, females receive less aggressive care than males, likely impacting survival. ConclusionsEpidemiology, risk factors, and treatment of spontaneous intracranial hemorrhage vary by sex, with limited and oftentimes conflicting data available. Further research into the sex-based differences of spontaneous intracranial hemorrhage is necessary for clinicians to better understand how to evaluate and guide treatment in the future.

Natural history and clinical manifestation of Pediatric Brain Arteriovenous Malformations.

Brain arteriovenous malformations (bAVMs) are aberrant arteriovenous shunts through a vascular nidus with no intervening capillary beds. They are one of the commonest causes of spontaneous intracranial haemorrhage in children and may be associated with significant morbidity and mortality in cases of rupture. Treatment strategies include microsurgical resection, endovascular embolisation, stereotactic radiosurgery, multimodality treatment with a combination thereof, and particularly in high-grade bAVMs, conservative management. Clinicians involved in treating bAVMs need to have familiarity with the natural history pertaining to bAVMs in terms of risk of rupture, risk factors elevating rupture risk as well as understanding the clinical manifestations of bAVMs. This invited review serves to provide a synthesis on natural history and clinical presentation of bAVMs with particular focus in children to inform decision-making pertaining to management.

NLP-based Extraction of Social Determinants of Health in Patients Admitted with Spontaneous Intracranial Hemorrhage (P11-2.005)

NLP-based Extraction of Social Determinants of Health in Patients Admitted with Spontaneous Intracranial Hemorrhage (P11-2.005)

873 Code Brain Ultra-Early Clinical Pathway for Patient Identification and Management in Spontaneous Non-traumatic Intracranial Hemorrhage Single-Institution Study

INTRODUCTION: Spontaneous non-traumatic intracranial hemorrhage causes high morbidity and mortality. Clinical pathways for the management of acute ischemic stroke are well established but fall short in identifying intracranial hemorrhage, preventing early therapy. METHODS: Using Class 1 recommendations from the AHA/ASA Spontaneous Intracranial Hemorrhage Guidelines, our multi-disciplinary stroke team developed a hyper-acute clinical pathway. Once the hemorrhagic stroke patient was identified, protocolized measures were immediately initiated to lower systolic blood pressure to 140 mmHg, institute factor replacement therapies in coagulopathic patients and anti-platelet reversal when appropriate. Key performance indicators and quality metrics were established to compare post-intervention groups to the baseline cohort. RESULTS: Of 180 patients, 113 and 67 patients were treated pre- and post-protocol, respectively. From pre- to post-protocol, diagnosis of hemorrhagic stroke using the alert increased from 59% to 81%. Anti-hypertensive initiation within 60 minutes increased from 79.5% to 88.7%, with the average time from CT result decreasing from 32.7 to 21.7 minutes. Time to reversal agent decreased from 53 to 23 minutes for pro-coagulation agents and 106 to 55 minutes for DDAVP. Reversal agent initiation within 60 minutes of CT result increased from 66.6% to 100% for pro-coagulation agents and 28.5% to 84.6% for DDAVP. CONCLUSIONS: The initiation of this management protocol for hemorrhagic stroke resulted in a higher proportion of patients being rapidly identified and earlier initiation of anti-hypertensive and hemostatic therapies. These processes are the key to important interventions designed to reduce injury extension associated with intracranial hemorrhage, like “time to thrombolysis” measures for acute ischemic stroke.

441 Glasgow Coma Scale Motor Score Predicts Need for Tracheostomy After Decompressive Craniectomy for Traumatic Brain Injury

INTRODUCTION: Traumatic brain injury (TBI) is a common problem worldwide. Severe TBI is sometimes treated with decompressive craniectomy. Many patients who survive require tracheostomy. The decision to proceed with tracheostomy and at what time is often ambiguous. Existing methods for predicting which patients with neurologic insult will require tracheostomy are aimed at stroke and spontaneous intracranial hemorrhage (ICH). METHODS: We performed a retrospective review of adult patients who underwent decompressive craniectomy for severe TBI at the University of Kansas Medical Center between 2007 and 2020. RESULTS: 100% of patients who have GCS motor score of 4 or less on POD 5 required tracheostomy. 80% of patients with GCS motor score of 5 on POD 5 required tracheostomy. Setting the threshold at GCS motor score of 5 on POD 5 for recommending proceeding with tracheostomy results in 86.7% sensitivity, 91.7% specificity, and 90.5% PPV with area under the receiver operator curve of 0.9101. CONCLUSIONS: GCS motor score of 5 or less on POD 5 from decompressive craniectomy for TBI is predictive of need for tracheostomy.

Andexanet alfa therapy showed No increased rate of thromboembolic events in spontaneous intracranial hemorrhage patients: A multicenter electronic health record study

•Intracranial hemorrhage accounts for two out of every three major intracranial hemorrhages.•Systemic anticoagulation is routinely prescribed for prevention of cerebrovascular accidents.•The FDA approved Andexanet alfa to treat life-threatening bleeding.•Andexanet alfa relationship to outcomes requires further investigation.

Mirror Image of Spontaneous Intracranial Hemorrhage.

In this paper, we reported the first case of mirrored spontaneous intracranial hemorrhage with almost identical hematoma morphological characteristics. This patient's first symptom was loss of consciousness, without any local neurological symptoms. This clinical presentation fits well with the atypical computed tomography (CT) image showing bilateral hematomas, and indicates that the distribution of hypertensive vascular damage may be symmetric and that the degree of the bilateral lesions may be similar.

Spontaneous Intracranial Hemorrhages in a Community of Asian Americans: Case Series and Literature Review.

Background and objectives Several Asian populations abroad are reported to have a higher prevalence of spontaneous intracranial hemorrhages (sICH) and a greater proportion of all stroke types attributed to ICH compared to non-Asians. However, the causes are unknown, and few studies have examined the issue among Asian Americans. This report aims to highlight some less common, but not rare, clinical features that could bear on several pathophysiological factors, by presenting a selected case series of 13 Asian American patients admitted to a Boston-based healthcare system and hospital. Methods The selected cases were classified into six categories based on presumed sICH mechanisms including vasculopathy, hypertensive crises, moyamoya disease/syndrome, venous sinus thrombosis, brainstem hemorrhages, and arterial malformation/aneurysm. We also examined 5 years of medical records at our institution, a single healthcare system among several in a large urban area having itsmain hospital embedded in an Asian community, to arrive at stroke-type proportions, comparing our Asian to non-Asian population. ICH cases excluded trauma, coagulopathy, and hemorrhagic transformation. ICH patient counts were compared to acute ischemic stroke and subarachnoid hemorrhage across various ethnicities. Results Pathophysiology-biomarker correlations within each ICH stroke category were reviewed,some possibly having specificity for Asian populations. We found some evidence to support an increased proportion of sICH among all stroke types in our Asian American patients, relative to other ethnic groups. A higher apparent estimate of sICH incidence in Asian Americans vs. Caucasians was also uncovered. However, these did not reach statistical significance and so no conclusion on risk could be made from this preliminary study. Conclusions We review the extensive literature on epidemiology and genetic markers and affirm that an awareness of the potential increased risk of sICH in this expanding population is clinically prudent. An expanded epidemiologic study to refine ICH risk estimates in Asian Americans is planned.

Minimally invasive surgical approaches for spontaneous intracranial hemorrhage in neonates aged 0–3 months

Objective The aim of this study is to assess the clinical efficacy of minimally invasive surgical interventions in addressing spontaneous intracranial hemorrhage among neonates aged 0–3 months. Methods A retrospective analysis was conducted on a cohort of 30 neonates diagnosed with spontaneous intracranial hemorrhage, who underwent minimally invasive cranial trepanation and drainage procedures at our department between 2011 and 2015. Results A comprehensive follow-up, spanning a duration of 1–5 years, was conducted for all 30 neonates, revealing a 100% survival rate among the pediatric cohort. Conclusion The findings suggest that minimally invasive cranial trepanation and drainage exhibit efficacy in neonates aged 0–3 months experiencing spontaneous intracranial hemorrhage, leading to a reduction in both mortality and disability rates. It is recommended that surgery be promptly performed upon definitive diagnosis and identification of operation indications to prevent severe brain damage resulting from prolonged intracranial hypertension and potential fatal outcomes in neonates. Furthermore, the surgical procedure is characterized by its simplicity, involving minimal trauma.

Effect of heparin for the prevention of venous thromboembolism in patients with spontaneous intracranial cerebral hemorrhage: a meta-analysis.

Venous thromboembolism (VTE) has a serious impact on the prognosis of patients with spontaneous intracranial hemorrhage (sICH). However, the use of prophylactic heparin remains controversial. This study investigated the safety and timing of prophylactic heparin for VTE in patients with sICH. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Two authors systematically searched Web of Science, Cochrane Library, Embase, and PubMed to find all published research before June 2023. The incidence of deep venous thrombosis (DVT) and mortality were set as primary endpoints. This meta-analysis included seven randomized controlled trials (RCTs) and five observational studies involving a total of 4419 sICH patients in the heparin (n = 2808) and control (n = 1183) groups. Among these patients, 205 received early heparin administration, while 223 received late heparin administration. The results suggested that, compared to the control group, patients in the heparin group had a lower incidence of VTE [odds ratio (OR), 0.47; 95% CI, 0.31-0.71; p < 0.001], DVT (OR, 0.53; 95% CI, 0.33-0.85; p = 0.009), pulmonary embolism (OR, 0.31 95% CI, 0.15-0.65; p = 0.002), and mortality (OR, 0.70; 95% CI, 0.54-0.90; p = 0.006), but there were no statistical differences in hematoma enlargement, extracranial hematoma, and major disability (p > 0.05). There was no statistically significant difference in DVT, mortality, hematoma enlargement, and extracranial hemorrhage between the early heparin group (<24-48 h) and the late heparin group (p > 0.05). In patients with sICH, prophylactic use of heparin may be beneficial because it reduces the incidence of VTE and mortality without increasing the risk of additional bleeding. In addition, early prophylactic use of heparin appears to be safe. However, large-scale RCTs are lacking to support this evidence.

Evaluation of the last 2 decades in the characteristics of presentation, management and prognosis of serious spontaneous intracerebral hemorrhage in a third level hospital

ObjectiveTo analyze the change in the characteristics of presentation, evolution and treatment in the ICU, as well as the functional evolution at 12 months of spontaneous intracranial hemorrhages (ICHs) treated in an ICU reference center. Patient and methodsDescriptive, retrospective study in a Neurocritical Reference Hospital. All admissions of patients with HICE during three periods are studied: 1999–2001 (I), 2015–2016 (II) and 2020–2021 (III). Evolution in the three periods of demographic variables, baseline characteristics of the patients, clinical variables and characteristics of bleeding, evolutionary data in the ICU are studied. At one year we assessed the GOS scale (Glasgow Outcome Score) according to whether they had a poor (GOS 1−3) or good (GOS 4−5) prognosis. Results300 admitted patients, distributed in periods: I: 28.7%, II: 36.3% and III: 35%. 56.7% were males aged 66 (55.5–74) years; ICH score 2 (1−3). The ICU stay was 5 (2–14) days with a mortality of 36.8%. GOS 1−3 a year in 67.3% and GOS 4−5 in 32.7%. Comparing the three periods, we observed a higher prevalence in women, and the presence of cardiovascular factors; no changes in etiology; in relation to the location, it increases cerebellar hemorrhage and in the brainstem. Although the severity was greater, the stay in the ICU, the use of invasive mechanical ventilation and tracheostomy were lower. Open surgery has decreased its use by 50%. Mortality continues to be high, stagnating in the ICU at 35% and entails a high degree of disability one year after assessment. ConclusionsSevere ICH is a complex pathology that has changed some characteristics in the last two decades, with more severe patients, with more cardiovascular history and a greater predominance of brainstem and cerebellar hemorrhage. Despite the increase in severity, better parameters during the ICU stay, with open surgery used 50% less. Mortality remains stagnant at 35% with high disability per year.

Pediatric Spontaneous Intracranial Hemorrhage (SICH) with unknown etiology in rural area

Background: Spontaneous intracranial haemorrhage (SICH) on paediatrics is a rare condition which usually doesn’t present specific sign and symptoms. Therefore, quick diagnosis followed by appropriate initial treatment is necessary to reduce morbidity and mortality rate. Case Presentation: An 11-year-old boy was admitted to the ER (emergency room) with sudden altered mental status 2 hours prior to admission. According to his parents, he complains headache after playing with friends previously. No history of trauma was found. Non contras CT scan shows intracerebral haemorrhage in the left and right lateral periventricular of the posterior horn (Vol 0.77 cc) and intraventricular haemorrhage in all the ventricles. EVD (External Ventricular Drain) placement surgery was performed. After two weeks of hospitalization, he was allowed to go home without any neurological deficits, and continued follow up in outpatient unit. Summary: Spontaneous intracranial bleeding in children have high mortality and morbidity rates, but children do not always have specific signs and symptoms. Therefore, a quick diagnosis accompanied by appropriate initial treatment is very necessary to reduce morbidity and mortality rate, such as those to reduce intracranial pressure.

Low LDL-C/HDL-C Ratio is Associated with Poor Clinical Outcome After Intracerebral Hemorrhage: A Retrospective Analysis of Multicenter, Prospective Cohort Data in China.

The association between low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and the clinical outcomes of acute intracranial hemorrhage (ICH) remains unclear. In this study, we attempt to investigate whether low LDL-C/HDL-C ratio is associated with poor clinical outcomes in patients with ICH. The database was collected from a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. A total of 1,964 patients with ICH were initially screened in our database. Next, we selected patients with admission serum lipid information for retrospective analysis. Patients were categorized into four groups based on LDL-C/HDL-C ratio quartiles. The main outcomes were 30-day and 90-day poor functional outcome, which is defined as modified Rankin Scale score of 3 to 6, and 90-day all-cause death. Logistic regression was used to assess the association between LDL-C/HDL-C ratio and 30-day or 90-day poor functional outcome. Kaplan-Meier survival analysis and Cox regression were used to assess the association between LDL-C/HDL-C ratio and 90-day all-cause death. Restricted cubic splines were used to explore the nonlinear association between LDL-C/HDL-C ratio and the outcome of patients with ICH. A total of 491 patients with spontaneous ICH were finally enrolled in our study. The mean age was 57.6years old, and 72.1% (357/491) were men. After adjustment for confounders, patients in the lowest LDL-C/HDL-C quartile (< 1.74) had a significantly higher risk of 30-day and 90-day poor functional outcome compared with those in the highest quartile (> 3.16; 30-day: adjusted odds ratio 3.61, 95% confidence interval 1.68-7.72; 90-day: adjusted odds ratio 2.82, 95% confidence interval 1.33-5.95). Restricted cubic splines depicted a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcomes, indicating LDL-C/HDL-C ratio of 3.1-3.5 was correlated with better 90-day functional outcome. However, no significant correlation was found between low LDL-C/HDL-C ratio and 90-day all-cause death. Lower LDL-C/HDL-C ratio (< 1.74) is independently associated with an increased risk of poor functional outcome in patients with ICH. In the population of patients whom we studied, there is a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcome, and patients with an LDL-C/HDL-C ratio of 3.1 to 3.5 tend to have the lowest risk of 90-day poor functional outcome.

When Atrial Fibrillation Meets Cerebral Amyloid Angiopathy: Current Evidence and Strategies.

Non-valvular atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) are two common diseases in elderly populations. Despite the effectiveness of oral anticoagulant therapy in cardioembolic stroke prevention, intracranial hemorrhage represents the most serious complication of these therapies. Cerebral amyloid angiopathy is one of the main risk factors for spontaneous intracranial bleeding, and this risk is highly increased by age and concomitant antithrombotic therapies. Cerebral amyloid angiopathy can be silent for years and then manifest with clinical features simulating TIA (TIA-mimics) or stroke in AF patients, pushing clinicians to rapidly start VKAs or DOACs, thus increasing the risk of intracranial bleeding if the diagnosis of CAA was unknown. Because the cerebral amyloid angiopathy is easily diagnosed with non-contrast MRI, suspecting the disease can avoid catastrophic complications. In this review, we will provide physicians managing anticoagulant therapies with key tips to familiarize themselves with cerebral amyloid angiopathy, with a focus on the possible clinical presentations and on the diagnostic criteria.

Spontaneous Intracranial Haemorrhage as Part of the Initial Manifestation of Childhood Systemic Lupus Erythematosus: An Unusual Clinical Presentation

Childhood-onset systemic lupus erythematosus is a systemic autoimmune disorder with a variety of clinical manifestations. Most children and adolescents experience the gradual onset of prolonged fever, weight loss, fatigue, and arthralgia over weeks or months. Nonetheless, isolated haematological abnormalities are unusual as an initial clinical manifestation. We report a case of spontaneous intracranial haemorrhage due to severe thrombocytopenia as part of the initial manifestation of SLE in childhood. A high index of suspicion is necessary to diagnose systemic lupus erythematosus in children who present with unexplained spontaneous intracranial haemorrhage and isolated thrombocytopenia as an initial presentation.

Fetal Maternal Hemorrhage As a Trigger for Fetal/Neonatal Alloimmune Thrombocytopenia: Evidence from a Murine Model

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a severe bleeding disorder caused by maternal alloantibodies targeting fetal platelet alloantigens. Among the 37 human platelet alloantigens (HPAs) identified, the HPA-1a/HPA-1b polymorphism, involving a Leu33Pro amino acid substitution in the integrin β3 subunit, is the most common cause of severe FNAIT, particularly in Caucasians. Leu33 serves as a key target for alloantibody binding, leading to fetal and neonatal thrombocytopenia and, in severe cases, spontaneous or trauma-induced intracranial hemorrhage. FNAIT shares a pathophysiologic basis with Hemolytic Disease of the Fetus and Newborn (HDFN), which stem from maternal immunization to alloantigens on fetal platelets and red blood cells (RBCs), respectively. While alloimmunization against RBC alloantigens typically occurs in response to fetal maternal hemorrhage (FMH), a clear link between FMH and maternal alloimmunization against HPA-1a on circulating fetal platelets has remained elusive. To assess whether FMH can induce platelet alloimmunization and lead to the development of FNAIT during pregnancy, we utilized recently developed transgenic mice expressing the HPA-1a allogeneic epitope on a murine GPIIIa backbone. To simulate varying degrees of FMH, we transfused different doses of HPA-1a platelets into wild-type (WT), non-pregnant female mice. We found that transfusing as few as 1x10 7 HPA-1a-positive platelets (equivalent to a FMH of approximately 30 ml in humans) resulted in production of high-titer HPA-1a-specific alloantibodies. Since &amp;gt;25% of the cases of FNAIT in humans are thought to occur in what are experienced as first pregnancies, we further investigated whether exposure to HPA-1a in pregnant female mice could still induce FNAIT. We found that when WT female mice pregnant with HPA-1a-positive fetuses were transfused with HPA-1a-positive platelets, they consistently developed HPA-1a-specific antibodies with similar titers as observed in non-pregnant females and delivered thrombocytopenic pups with FNAIT. Taken together, these findings demonstrate that exposure to HPA-1a-positive platelets in the maternal circulation during pregnancy is sufficient to trigger FNAIT, and that maternal tolerance, normally increased during pregnancy, does not play a significantly immunosuppressive role to prevent alloimmunization to the HPA-1a epitope. These findings support the notion that FMH may be a possible cause of alloimmunization in humans, even during a first pregnancy. Finally, the result of this study further validates the usefulness of this HPA-1a alloantigen-specific humanized transgenic mouse model to explore the etiology and pathophysiology of FNAIT. Further studies should significantly advance preventative and therapeutic strategies for this life-threatening immunologic disorder.

Non-Traumatic Epidural Hematoma in Sickle Cell Disease

Non-traumatic epidural hematoma is an extremely rare finding in patients with sickle cell disease. Spontaneous intracranial epidural hemorrhage has been associated with coagulopathy, malignancy, and infection, but few cases secondary to sickle cell disease have been reported in the literature. The mechanism of hemorrhage in these patients is often unclear, although previous cases have suggested associations with vaso-occlusive pain crises, bone infarction, and/or vascular malformations. We report a 9 year old male with sickle cell disease type SS who presented with right shoulder pain, headaches, emesis, and no neurological deficits. CT head revealed large mixed density left frontoparietal epidural hematoma leading to complete left lateral ventricle effacement and 0.5 cm left to right midline shift. He subsequently underwent a left parietal craniotomy for evacuation of epidural hematoma from which he recovered well. The prevalence and proposed pathologic process behind this rare complication will be discussed.

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.