Recurrent Intracranial Hemorrhage Research Articles

Unveiling the mystery: Infective endocarditis as an etiological cause of recurrent intracranial hemorrhage

Intracerebral hemorrhage (ICH) in the context of infective endocarditis (IE) is an uncommon and complex phenomenon involving diverse underlying mechanisms. We present a compelling case of a 48-year-old patient with recurrent ICH, ultimately leading to the diagnosis of IE with vegetation on the anterior leaflet of the mitral valve. The patient underwent a successful mitral valve replacement followed by a gradual improvement in neurological symptoms. This case report delves into the intricate diagnostic journey, highlighting the significance of suspecting IE in patients presenting with ICH. A multidisciplinary and comprehensive management approach played a pivotal role in achieving positive outcomes.

Symptomatic carotid artery intraluminal thrombus: risk of medical management failure and distal embolization

BackgroundCarotid artery intraluminal thrombus (ILT), or free-floating thrombus, is an uncommon cerebrovascular entity with considerable equipoise regarding its clinical management. Likewise, in patients treated with medical management (MM), distal embolization...

Abstract 14464: Meta-Analysis Comparing Early vs Delayed Anticoagulation After Stroke in Patients With Atrial Fibrillation

Introduction: Secondary prevention with anticoagulants is recommended for patients with acute ischemic stroke and atrial fibrillation (AF), but the timing of initiation of anticoagulation is debated. We performed a meta-analysis of the available studies. Methods: Studies comparing early (≤ 7 days) vs delayed (> 7 days) start of anticoagulation after acute stroke in patients with AF were searched from online databases. The primary endpoints of interest were recurrent ischemic stroke, intracranial haemorrhage (ICH), and mortality at the longest available follow up. Random-effects model was used to estimate risk ratios (RR) with 95% confidence intervals (CI). Results: Four studies (2 randomized trials and 2 observational studies), with a total of 5,606 patients - 2,918 in the early group and 2,688 in the delayed group were included. The mean age was 79 years and 55% of patients were men. The follow up duration varied from 30 days to 6 months. No significant differences were found between the early and delayed anticoagulation groups with regards to risk of recurrent ischemic stroke (RR 0.80, 95% CI 0.51-1.27, p = 0.35) (Figure 1), ICH (RR 0.62, 95% CI 0.17-2.24, p = 0.47) or mortality (RR 0.88, 95% CI 0.64-1.22, p = 0.45) (Figure 2). Conclusions: In patients with acute ischemic stroke and AF, early initiation of anticoagulation has similar risk of recurrent stroke, ICH, and mortality, when compared with delayed initiation.

Abstract 117: Digitally Subtracted Angiogram & 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.

Dual antiplatelet therapy is associated with favorable outcome in acute minor stroke with an onset-to-door time beyond 24 h

In patients with noncardioembolic acute minor ischemic stroke (AMIS), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 24h after stroke onset was more effective than aspirin alone. This study investigated the efficacy and safety of DAPT in AMIS patients with an onset-to-door time (OTDT) of more than 24h. This was a retrospective analysis of a prospective stroke registry from 2015 to 2021. Patients with AMIS and an OTDT within seven days were classified into the Early (≤24h) and Late groups (>24h) according to the time of antiplatelet administration after stroke onset. In total, 691 patients were identified. Of these, 446 (64.5%) and 245 (35.5%) patients were classified into the Early and Late groups, respectively. The rates of recurrent infarction and symptomatic intracranial hemorrhage at 90 days were similar between the single antiplatelet therapy (SAPT) and DAPT subgroups in both the Early and Late groups. More patients in the DAPT subgroup had a favorable outcome (modified Rankin scale of 0-1) at 90 days in both Early (84.2% versus 75.0%, p=0.016) and Late (88.2% versus 76.9%, p=0.040) groups. DAPT was independently associated with a favorable outcome in both the Early (odds ratio, 1.95; 95% CI, 1.15-3.32; p=0.013) and Late (odds ratio, 2.72; 95% CI, 1.14-6.48; p=0.024) groups. In patients with AMIS and an OTDT of more than 24h, DAPT was associated with a favorable outcome at 90 days.

Leukoaraiosis as a Promising Biomarker of Stroke Recurrence among Stroke Survivors: A Systematic Review.

Stroke is the leading cause of functional disability worldwide, with increasing prevalence in adults. Given the considerable negative impact on patients' quality of life and the financial burden on their families and society, it is essential to provide stroke survivors with a timely and reliable prognosis of stroke recurrence. Leukoaraiosis (LA) is a common neuroimaging feature of cerebral small-vessel disease. By researching the literature of two different databases (MEDLINE and Scopus), the present study aims to review all relevant studies from the last decade, dealing with the clinical utility of pre-existing LA as a prognostic factor for stroke recurrence in stroke survivors. Nineteen full-text articles published in English were identified and included in the present review, with data collected from a total of 34,546 stroke patients. A higher rate of extended LA was strongly associated with stroke recurrence in all stroke subtypes, even after adjustment for clinical risk factors. In particular, patients with ischemic stroke or transient ischemic attack with advanced LA had a significantly higher risk of future ischemic stroke, whereas patients with previous intracerebral hemorrhage and severe LA had a more than 2.5-fold increased risk of recurrent ischemic stroke and a more than 30-fold increased risk of hemorrhagic stroke. Finally, in patients receiving anticoagulant treatment for AF, the presence of LA was associated with an increased risk of recurrent ischemic stroke and intracranial hemorrhage. Because of this valuable predictive information, evaluating LA could significantly expand our knowledge of stroke patients and thereby improve overall stroke care.

Early Versus Delayed Oral Anticoagulation in Patients With Acute Ischemic Stroke Due to Atrial Fibrillation: A Meta-Analysis.

The aim of this study was to compare the safety and efficacy of early oral anticoagulation with delayed anticoagulant therapy in patients who have had a recent stroke and have atrial fibrillation (AF). This meta-analysis was conducted following the Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) statement. The literature search was independently performed by two authors. We searched PubMed and Scopus using search strings that included the following terms: "stroke," "atrial fibrillation," "oral anticoagulants," "recurrent stroke," and "intracerebral hemorrhage." Our search spanned from the inception of databases to May 25, 2023. The primary outcome assessed in this study was the composite efficacy outcome (as defined by individual studies). Recurrent ischemic stroke (IS), intracranial hemorrhage (ICH), and death from any cause were assessed as secondary outcomes. For safety analysis, bleeding events were compared between the two study groups. We included five articles in this meta-analysis, comprising a total of 7958 patients (including 3793 in the early treatment group and 4165 in the delayed treatment group). Pooled analysis showed that the risk of composite efficacy outcome (RR: 0.69, 95% CI: 0.51-0.93, p-value: 0.01) and recurrent ischemic stroke (RR: 0.71, 95% CI: 0.53-0.94, p-value: 0.02) were lower in the early treatment group. However, no significant differences were observed between the two groups in terms of all-cause mortality, intracranial hemorrhage, or bleeding events. In light of the findings, healthcare professionals should carefully evaluate the risks and benefits of early versus delayed DOAC treatment in individual patients, considering factors such as stroke severity, bleeding risk, and patient preferences.

Intracranial hemorrhage (ICH) in acute leukemia (AL): A single-center study from a general hospital with two cases managed with middle meningeal artery (MMA) embolization.

e19033 Background: ICH is a devastating and potentially fatal complication in patients with AL. Contributing factors for ICH include thrombocytopenia, hyperleukocytosis, and coagulopathy. Acute promyelocytic leukemia (APL) has a higher risk of disseminated intravascular coagulation (DIC) and fatal ICH, contributing to early deaths from the disease. At our institution, we have incorporated MMA embolization into traditional methods of observation and surgery for the management of ICH in AL patients. Methods: We performed a single-center retrospective study of adult AL patients with ICH at Memorial Hermann Hospital Texas Medical Center from January 1, 2013, to December 31, 2022. Data collected included: age at diagnosis, type of AL, white blood cell count (WBC), platelet count, coagulation profile, Glasgow Coma Scale score at presentation, response to platelet transfusion, need for surgical, minimally invasive intervention, and mortality rates at 72 hours and 30 days. Descriptive statistics were used to analyze the data. Results: Among 160 consecutive AL patients, we identified 22 (13.75%) with ICH at presentation (APL = 11, AML = 6, B-ALL = 3, Burkitt leukemia = 1, myeloid sarcoma = 1). All were newly diagnosed except for one (an intracranial relapse of AML). Median age was 54 (range, 20–82) years; 60% were women. Subject races included white (n = 10), Asian (n = 5), Hispanic (n = 2), African American (n = 2), and others (n = 3). Median WBC count at admission was 23 (range, 0.2–400) × 109/L. Thrombocytopenia (platelet levels < 50,000/μL) was present in 16 patients (72%), and 3 had platelet counts < 10,000/μL. Twelve patients (54%) had evidence of DIC. Sites of ICH included intraparenchymal (n = 8), subarachnoid (n = 3), subdural (n = 10), cerebellum (n = 1). In 3 patients, ICH extended into the ventricles. Three patients had ≥2 types of ICH. Three patients had middle cerebral artery ischemic stroke in addition to ICH. One patient with myelofibrosis and myeloid sarcoma had bilateral subdural hematomas (SDHs) on admission and developed a fatal basal ganglia ICH during induction chemotherapy. All APL patients were promptly started on all-trans retinoic acid. Two patients had refractory thrombocytopenia. Five patients required craniotomy, with 2 deaths from recurrent ICH. Two patients with SDH underwent MMA embolization with favorable outcomes. Four patients (18%) died within 72 hours of admission (APL = 3, AML = 1). The 30-day mortality rate among patients presenting with ICH was 31% (n = 7). Conclusions: ICH in AL continues to be a major cause of mortality and morbidity. Early diagnosis, transfusion support, correction of coagulopathy, and neurosurgical expertise are critical in improving outcomes in AL-associated ICH. MMA embolization is a new, minimally invasive strategy for the management of SDH in these critically ill patients.

Management of oral anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation.

Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.

Biological and physical mechanisms of cerebral aneurysms formation, growth and rupture

According to various researchers, the prevalence of unruptured cerebral aneurysms (CAs) in the general population varies from 2 to 5 %. In the vast majority of cases, CAs do not have clinical and neurological manifestations and are discovered incidentally during routine neuroimaging studies. CAs can cause intracranial hemorrhage. As a rule, hemorrhages of this type occur in patients aged 40–60 years. It has been established that about 10–15 % of patients die from an aneurysmal hemorrhage before they receive specialized medical care. Recurrent aneurysmal intracranial hemorrhage is the main cause of high mortality and disability in this group of patients. The search for literature sources in the scientific databases PubMed/Medline, EMBASE, Cochrane Library and eLibrary demonstrated the existence of numerous studies devoted to the study of molecular biology and biophysical mechanisms of formation, growth and rupture of CAs. Combining the results of these studies was the motivation for writing this literature review. The paper reflects in detail the role of inflammation and molecular genetic factors in the growth and rupture of the CAs, and presents the biophysical factors of the rupture of the CAs. The authors pay special attention to the shape, size and coefficient of the CAs as the most important geometric risk factors for the formation and rupture of the CAs. This review presents current data on mathematical modeling of various types of CAs with an assessment of the risk of rupture of the latter, which has found its application in wide clinical practice. The authors also attempted to describe the hemodynamic features in various types of CAs. In turn, the type of blood flow in the CAs cavity largely depends on the size and shape of the latter and the geometry of the carrier artery, which is the basis for preoperative planning and the choice of tactics for surgical treatment of patients with unruptured CAs.

Multidisciplinary approach to Patent Foramen Ovale (PFO) closure for Cryptogenic Stroke: Brain-Heart Board Experience (P11-5.024)

<h3>Objective:</h3> Our study evaluates the predictors of closure recommendation by multidisciplinary board for PFO closure and its impact on outcomes. <h3>Background:</h3> PFO closure in carefully selected patients is an effective secondary preventive strategy in young cryptogenic stroke patients which requires close collaborative approach. <h3>Design/Methods:</h3> Brain-Heart Board is comprised of vascular neurology and cardiology subspecialities. Adult patients referred to the board for consideration of PFO closure between October 2017 to March 2021 were included in this analysis. Demographics, comorbid conditions, infarct location, Risk of Paradoxical Embolism (RoPE) Score, event frequencies (recurrent TIA or stroke, intracranial hemorrhage (ICH), post-PFO closure cardiac arrythmias) and modified Rankin Scale (mRS at 1 year) were compared between the groups (PFO closure vs. medical management). Multivariable logistic regression was used to identify predictors of closure and chi-square tests to test differences in outcomes for patients according to management. <h3>Results:</h3> 270 patients (229 stroke; 41 TIA) were included in the analysis. 119 (44%) patients were recommended for PFO closure of which 117 (98%) had infarct on neuroimaging. Age and RoPE score were similar in closure and medical management cohorts (age; 50±12 vs. 52±13, p&gt;0.05 RoPE 4±3 vs. 6±2 p&gt;0.05). In multivariable analysis, absence of infarct on neuroimaging was an independent predictor of medical management recommendation by the board (OR 0.05 95% CI 0.01–0.19 p&lt;0.05). Event frequency was low in both cohorts (5.9% vs. 4.8% p&gt;0.05) and were comprised primarily of cardiac arrhythmias (6 atrial fibrillation and 1 ICH in Closure group; 1 TIA and 1 recurrent stroke in medical management group). Excellent functional outcome (mRS 0–1) was similar in both cohorts (66% vs. 71% p&gt;0.05) at 1 year. <h3>Conclusions:</h3> Multidisciplinary approach towards PFO closure results in low frequency of complications (recurrent ischemic stroke, ICH and post-PFO closure cardiac arrythmias) and good outcomes. Infarct on neuroimaging predicts closure recommendation by the multidisciplinary board. <b>Disclosure:</b> The institution of Dr. Khan has received research support from NINDS. The institution of Dr. Khan has received research support from Genentech. The institution of Dr. Khan has received research support from Spectrum Health-MSU alliance. Dr. Khan has received research support from NIH. Dr. McCarthy has nothing to disclose. Dr. Haggerty has nothing to disclose. Dr. Min has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott . Dr. Min has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic . Dr. Miller has nothing to disclose. Dr. Tsai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerenovus. Dr. Merhi has nothing to disclose. Dr. Berkompas has received personal compensation in the range of $10,000-$49,999 for serving as a Proctor and consultant with Medtronic. Dr. Wees has nothing to disclose. Dr. Khan has nothing to disclose. Dr. Ahrar has nothing to disclose. Mrs. Evans has nothing to disclose. Dr. Dahu has nothing to disclose. Dr. Gauri has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic . Dr. Gauri has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Atricure . Mrs. Moelker has nothing to disclose. Dr. Chalfoun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Chalfoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atricure. Dr. Chalfoun has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Atricure.

Efficacy and safety of anticoagulation in atrial fibrillation patients with intracranial hemorrhage: A systematic review and meta-analysis.

Background: The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a history of intracranial hemorrhage (ICH) remain controversial. We performed a systematic review and meta-analysis to compare the safety and efficacy of starting oral anticoagulation (OAC) and non-oral anticoagulation in these patients. Methods: PubMed, Cochrane Library, and Embase were searched from inception to 01 May 2022 for randomized controlled trials and cohort studies, reporting effectiveness and safety outcomes for anticoagulation therapy in atrial fibrillation patients with intracranial hemorrhage. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration tool were used to evaluate bias risks for all randomized controlled trials (RCTs) and cohort studies. An effects model was applied to calculate adjusted hazard ratios (aHRs) for randomized controlled trials and cohort studies. Results: We analyzed data from two randomized controlled trials (304 patients) and seven Cohort studies (17,477 patients). Compared to non-oral anticoagulation, starting oral anticoagulation therapy reduced the risk of Ischemic Stroke/Systemic Embolism (SE) (aHR: 0.64, 95% CI: 0.55-0.57) and all-cause death (aHR: 0.53, 95% CI: 0.35-0.80) in atrial fibrillation patients and a prior history intracranial hemorrhage. Starting oral anticoagulation therapy did not increase the risk of recurrent intracranial hemorrhage (aHR: 1.07, 95% CI: 0.66-1.74), but increased the risk of major bleeding (aHR: 1.38, 95% CI: 1.00-1.91) than no oral anticoagulation therapy. The DOACs had a lower risk of Ischemic Stroke/SE (aHR: 0.84, 95% CI: 0.70-1.00), recurrent intracranial hemorrhage (aHR: 0.63, 95% CI: 0.49-0.82), and all-cause death (aHR: 0.65, 95% CI: 0.48-0.88) compared to warfarin. According to subgroup analyses, starting oral anticoagulation therapy have a higher risk of recurrent intracranial hemorrhage than non-oral anticoagulation therapy (aHR: 1.57, 95% CI: 1.36-1.81) for Asians. Conclusion: After intracranial hemorrhage in atrial fibrillation patients, restarting or initiating oral anticoagulation therapy decreased the risk of Ischemic Stroke/SE and all-cause death but did not increase the risk for recurrent intracranial hemorrhage. Direct oral anticoagulations have better efficacy and safety than warfarin if oral anticoagulation therapy is started. However, starting oral anticoagulation increases the risk for recurrent intracranial hemorrhage in the Asian region.

Intracranial hemorrhage in a patient with depressive anxiety disorder about a case

IntroductionWe present the case of a 69-year-old patient who went to the emergency department due to an episode of aggressiveness and behavioral alteration, presenting irritability and nervousness, of about 2 days of evolution according to her family member. Given that the patient had previously presented chronic behavioral disorders and had previously been followed up in psychiatric consultations, psychiatry was notified after an initial evaluation by the emergency physician.ObjectivesSomatic personal history: NAMC. HTA. Not DM, not DL. Former smoker of 20 cigarettes/day. Recurrent intracranial hemorrhage secondary to amyloid angiopathy and suspected amyloid vasculitis. Last admission to the neurology service in June 2022, also presenting symptomatic epileptic seizures and secondary behavioral alterations. Mastocytosis. Post-traumatic vertebral fracture. Non-anticoagulated paroxysmal atrial fibrillation. Surgical: Left ear surgery. appendectomy. Hysterectomy + oophorectomy.Personal psychiatric history: In follow-up since May 2021 referred from neurology for emotional lability, episodes of anger and fear. Diagnosed with anxiety-depressive disorder secondary to a medical illness.Current psychiatric treatment: Oxcarbazepine 800mg 0-0-1, trazodone 100mg 0-0-1, aripiprazole 10mg 1-0-0.MethodsCurrent illness: The patient goes to the emergency room brought by her husband. During the interview she minimizes her aggressive behaviors or even does not remember them. She is disoriented in time, with very striking memory failures. Her husband comments verbal aggressiveness if he contradicts her in something, sometimes even presenting physical aggressiveness with her relatives. They report that in the last psychiatric consultation a little over 1 month ago, aripiprazole was withdrawn due to an increased risk of cardiovascular events.After the examination of the patient, she was referred back to the emergency department for a new assessment and to rule out the organicity of the current condition, given that the patient had cardiovascular risk factors, due to the suspicion of a new episode of intracranial hemorrhage.Resultssychopathological examination: Vigil, conscious, disoriented in time, partially in space. Collaborative, calm during the interview. Coherent, structured speech, with obvious memory failures. Labile, irritable mood. Verbal and physical heteroaggressiveness at home, not during the interview. No structured or planned autolytic ideation at this time. Appetite and sleep preserved.ConclusionsAn urgent head CT was requested, with the result of a small intraparenchymal bleeding in the left frontal location, and she was admitted to the neurology department, with a diagnosis at discharge of: small left frontal haematoma, suspected amyloid vasculitis, and secondary behavioral alteration (vascular dementia).Disclosure of InterestNone Declared

Abstract TP186: Multidisciplinary Approach To Patent Foramen Ovale (pfo) Closure For Cryptogenic Stroke: Brain-heart Board Experience

Background: The prevalence of PFO is up to 40% in patients with cryptogenic stroke and TIA suggesting paradoxical embolism. PFO closure in carefully selected patients is an effective secondary preventive strategy in these patients. We report predictors of closure recommendation by multidisciplinary board for PFO closure and its impact on outcomes. Methods: Brain-Heart Board is comprised of vascular neurology, cardiology subspecialities (structural, electrophysiology and cardiac imaging). Adult patients referred to the board for consideration of PFO closure between October 2017 to March 2021 were included in this analysis. Demographics, comorbid conditions, infarct location, Risk of Paradoxical Embolism (RoPE) Score, event frequencies (recurrent TIA or stroke, intracranial hemorrhage (ICH), post-PFO closure cardiac arrythmias) and modified Rankin Scale (mRS at 1 year) were compared between the groups (PFO closure vs. medical management). Multivariable logistic regression was used to identify predictors of closure and chi-square tests to test differences in outcomes for patients according to management. Results: The board discussed 270 patients (229 stroke; 41 TIA). 119 (44%) patients were recommended for PFO closure of which 117 (98%) had infarct on neuroimaging. Age and RoPE score were similar in closure and medical management cohorts (age; 50±12 vs. 52±13, p&gt;0.05 RoPE 4±3 vs. 6±2 p&gt;0.05). In multivariable analysis, absence of infarct on neuroimaging was an independent predictor of medical management recommendation by the board (OR 0.05 95% CI 0.01-0.19 p&lt;0.05). Event frequency was low in both cohorts (5.9% vs. 4.8% p&gt;0.05) and were comprised primarily of cardiac arrhythmias (6 atrial fibrillation and 1 ICH in Closure group; 1 TIA and 1 recurrent stroke in medical management group). Excellent functional outcome (mRS 0-1) was similar in both cohorts (66% vs. 71% p&gt;0.05) at 1 year. Conclusion: Multidisciplinary approach for selecting patients for PFO closure results in low frequency of complications (recurrent ischemic stroke, ICH and post-PFO closure cardiac arrythmias) and good outcomes. Presence of infarct on neuroimaging predicts closure recommendation by the multidisciplinary brain-heart board.

Abstract TMP83: Optimal Timing For Resumption Of Anticoagulation After Intracranial Hemorrhage In Patients With Mechanical Heartvalves

Introduction: Anticoagulation in patients with acute intracranial hemorrhage (ICH) and mechanical heart valves (MHV) is often held to mitigate the risk of ICH expansion or recurrence; however there exists a competing risk of acute ischemic stroke (AIS). Optimal timing to resume anticoagulation after ICH remains uncertain. Methods: We retrospectively studied ICH patients with MHV at two academic hospitals from April, 2000-August, 2018. The primary outcome was a composite endpoint of symptomatic hematoma expansion or new ICH, AIS, and intracardiac thrombus up to 30 days post-ICH. The exposure was timing of re-initiation of anticoagulation classified as early if therapeutic anticoagulation was resumed up to 7 days after ICH; late if ≥7 and up to 30 days after ICH; and never if not resumed or resumed after 30-days post-ICH. Cox proportional hazard models were built adjusted for age, sex, and covariates significantly different in univariate analysis at a pre-specified p-value threshold of 0.05. Results: We identified 184 patients with ICH and MHV (65 anticoagulated early, 100 resumed late, 19 not resumed by day 30 post-ICH). We observed 12 AIS, 16 new ICH, and 6 intracardiac thromboses. The mean time from ICH to anticoagulation in the cohort was 12.7 days. Patients resumed early versus late were more likely to have atrial fibrillation (62% versus 42%), and less likely to be reversed (75% versus 94%), to undergo hematoma evacuation (23% versus 43%), have midline shift (27% versus 52.9%), and to have intracerebral involvement (26% versus 49%). There was no significant difference in the hazard of AIS, new or symptomatic ICH expansion, or the composite outcome among those resumed early versus late. Patients not resumed within 30 days post-ICH had a significantly higher risk of AIS compared to those resumed within 30 days (HR 15.9; 95% C.I.1.9-129.7, p=0.0098). Discussion: In this study of ICH patients with MHV, there was no difference in the 30-day thrombotic and hemorrhagic brain-related outcomes in patients anticoagulated within 7 days versus 7-30 days. Withholding anticoagulation within the first 30 days was associated with a significantly higher risk of AIS. Our findings provide a discrete time window to guide resumption of anticoagulation in MHV patients with ICH.

The first reported case of factor X deficiency in a Filipino child – case study

Abstract Factor X (FX) deficiency is an extremely rare inherited bleeding disorder affecting one in 1,000,000 people. According to the most recent published census of the World Hemophilia Federation, to date there is no reported case of FX deficiency in the Philippines. Rare disorders like FX deficiency often go unrecognised or misdiagnosed. Here, we report the first case of FX deficiency in a Filipino child. A two-month-old male child with consanguinity was referred to our hospital due to bleeding episodes. On the third day of life, he had haematomas to the cervical area and upper extremities, and spontaneous bleeding of the umbilical cord was noted. Initial workup showed prolonged PT and aPTT. Factor deficiencies including FVIII and FIX were considered, however assays were normal. At six weeks of age, the child developed convulsions and deteriorating neurologic status. CT scan showed subarachnoid haemorrhage. The child was referred for further workup. Additional assay of clotting factors showed decreased FX activity at less than 1% and he was diagnosed with severe congenital FX deficiency. Following recurrent intracranial bleeding, the child has been observed to have permanent neurological deficit. This case highlights the importance of timely and accurate diagnosis to prevent life-threatening complications and the risk of permanent disability. Despite being an extremely rare disorder, the incidence of FX deficiency is estimated to be higher in populations where consanguineous marriages are common. Awareness of this rare condition must be emphasised. Families may benefit from screening through coagulation studies as well as genetic counselling, especially when planning future pregnancies. The rarity of this condition has not allowed for the establishment of evidence-based management guidelines, with treatment based on limited literature. Despite development of FX-specific clotting factor products, the high cost and limited availability impact their use in low-resource settings.

A case of recurrent intracranial hemorrhage in CADASIL caused by NOTCH3 c.1759C&gt;T heterozygous mutation

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebrovascular disease that is closely related to the NOTCH3 gene. Recurrent ischemic stroke, progressive cognitive dysfunction, and mental symptoms are the main clinical manifestations, whereas symptomatic intracranial hemorrhage is rare. We detected a heterozygous mutation of c.1759C>T in exon 11 of the NOTCH3 gene that caused recurrent intracranial hemorrhage in CADASIL. Second-generation sequencing of a sample of the patient's genome revealed a heterozygous mutation of c.1759C>T in exon 11 of NOTCH3, which resulted in amino acid changes (p.R587C). This variation may be rated as a CADASIL clinical variation. The discovery of this mutation site provides an important theoretical basis for a gene-based diagnosis and treatment of recurrent intracranial hemorrhage.

Effect of Statin Therapy on Mortality and Recurrence of Intracerebral Hemorrhage in Patients With Spontaneous Intracerebral Hemorrhage.

Statins can play an essential role in the tertiary and primary prevention of cardiovascular events by reduction of cholesterol in a stroke patient. This meta-analysis aims to assess statin therapy's effect on mortality and recurrence of Intracranial Hemorrhage (ICH) in patients with spontaneous ICH. The current meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was performed using PubMed, EMBASE, and Cochrane Library to identify studies assessing the use of statins in patients with ICH. The primary outcome assessed in the current meta-analysis was a hemorrhagic stroke. The secondary outcomes included cardiac-related events and all-cause mortality. A total of 9 studies were included in the current meta-analysis enrolling 49027 patients, with 8094 patients on statin therapy and 40933 patients in the control group. The risk of recurrent ICH was significantly lower in patients receiving stains (RR: 0.81, 95% CI: 0.67-0.99, p-value: 0.02) compared to placebo. However, no significant differences were observed regarding all-cause mortality (RR: 0.80, 95% CI: 0.53-1.20, p-value: 0.27) and cardiovascular events (RR: 1.24, 95% CI: 0.88-1.74). In ICH patients, statins can reduce the risk of recurrent ICH in patients with a history of ICH. However, statins had no significant effect on all-cause mortality and cardiovascular events.

Effect of oral anticoagulation therapy in atrial fibrillation patients with a history of intracranial hemorrhage: a systematic review and meta-analysis.

Use of oral anticoagulants (OACs) among atrial fibrillation (AF) patients surviving intracranial hemorrhage (ICH) represents a challenge due to the difficult balance between thrombosis and hemorrhage. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of OACs resumption in AF patients with a history of ICH during long-term follow-up. The outcome measures were ischemic stroke (IS), IS or systemic embolism (SE), all-cause death, recurrent ICH and major bleeding. Meta-analyses of pooled odds ratios (ORs) were conducted with random-effects models. A total of 2 randomized controlled trials (RCTs) and 9 observational studies were included, covering 18,115 patients with AF and a history of ICH. The risk of IS was not statistically different between the group of patients receiving OAC therapy and the no-OAC group (OR: 0.41, 95% CI: 0.16 to 1.0, P=0.05). The rate of IS or SE (OR: 0.42, 95% CI: 0.27 to 0.70, P=0.0008), all-cause death (OR: 0.54, 95% CI: 0.41 to 0.70, I2=42%, P<0.00001) were significantly decreased in patients receiving OAC therapy compared to those with no-OAC therapy. The pooled OR estimates for ICH recurrence (OR: 1.46, 95% CI: 0.94 to 2.26, P=0.09) and major bleeding (OR: 1.35, 95% CI: 0.86 to 2.11, P=0.19) were not significantly increased in the OAC therapy group. There was heterogeneity between the results of observational studies and RCTs in terms of all-cause death (I2=83.4%). Considering the heterogeneity in results between observational studies and RCTs, as well as the limited number and small size of RCTs, high grade evidences are needed. Pooled analysis is required when more RCTs are completed in the future to resolve this therapeutic dilemma.

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Cerebral Venous Thrombosis: A Systematic Review and Meta-Analysis.

High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis. This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs). Out of 10 665 records identified, we screened 254 as potentially eligible. Nineteen studies (16 observational studies [n=1735] and 3 randomized controlled trials [n=215]) met the inclusion criteria. All 3 randomized controlled trials had some concerns, and all 16 observational studies had at least moderate risk of bias. When compared with vitamin K antagonist treatment, DOAC had comparable risks of recurrent venous thromboembolism (relative risk [RR], 0.85 [95% CI, 0.52-1.37], I2=0%), major hemorrhage (RR, 0.70 [95% CI, 0.40-1.21], I2=0%), intracranial hemorrhage (RR, 0.58 [95% CI, 0.30-1.12]; I2=0%), death (RR, 1.14 [95% CI, 0.54-2.43], I2=1%), and complete venous recanalization (RR, 0.98 [95% CI, 0.87-1.11]; I2=0%). This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.