Recurrent Intracranial Hemorrhage Research Articles

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 They report that in the last psychiatric consultation a little over 1 month ago, aripiprazole was withdrawn due to an increased risk of cardiovascular events.After the examination of the patient, she was referred back to the emergency department for a new assessment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>0.05 RoPE 4±3 vs. 6±2 p>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<0.05). Event frequency was low in both cohorts (5.9% vs. 4.8% p>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>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>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.

Short-term intermittent prophylaxis post-intracranial hemorrhage in children with hemophilia

Background Intracranial hemorrhage (ICH) is one of the major bleeding events causing mortality and long-term morbidity in children with hemophilia, especially those who receive on-demand therapy.&#x0D; Objective To evaluate the outcome of children with hemophilia after ICH receiving short-term intermittent prophylactic treatment.&#x0D; Methods This retrospective study was conducted in the Department of Child Health, Dr. Cipto Mangunkusumo Hospital, Jakarta. Children £18 years of age with hemophilia presenting with ICH between 2015-2020 were included. We recorded patients’ demographics, type and severity of hemophilia, the presence of factor VIII (FVIII) inhibitor, brain CT scan, treatment, and outcomes of these patients. Patients who received short-term intermittent prophylaxis using clotting factor concentrate (CFC) post-ICH episodes were observed for ICH recurrence.&#x0D; Results There were 19 episodes of ICH experienced by 18 patients, consisting of 16 patients with hemophilia A and 2 with hemophilia B. Patients’ median age was 4 years (range 0-16 years). Hemophilia was classified as severe in 13 patients, moderate in 4 patients, and mild in 1 patient. Thirteen episodes were preceded by head trauma. The most common clinical manifestation was seizures (13.2%). The most common type of ICH was subdural hematoma. Two patients died and 2 patients had neurological sequelae during hospitalization. The median dose of short-term intermittent prophylaxis using CFC (n=16) was 20 IU/kg of FVIII twice a week and 30 IU/kg of FIX twice a week, for a median duration of 8 weeks (range 5-12 weeks). One patient who did not adhere to the prophylaxis regimen had recurrent ICH at a similar location 6 months after the first episode. &#x0D; Conclusion Our findings suggest that short-term intermittent prophylaxis is important to prevent the recurrence of ICH in children with hemophilia.

Long‐Term Blood Pressure Variability and Major Adverse Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage

BackgroundSurvivors of intracranial hemorrhage (ICH) are at increased risk for major adverse cardiovascular and cerebrovascular events (MACCE), in the form of recurrent stroke and myocardial Infarction. We investigated whether long‐term blood pressure (BP) variability represents a risk factor for MACCE after ICH, independent of average BP.Methods and ResultsWe analyzed data from prospective ICH cohort studies at Massachusetts General Hospital and the University of Hong Kong. We captured long‐term (ie, visit‐to‐visit) BP variability, quantified as individual participants’ variation coefficient. We explored determinants of systolic and diastolic BP variability and generated survival analyses models to explore their association with MACCE. Among 1828 survivors of ICH followed for a median of 46.2 months we identified 166 with recurrent ICH, 68 with ischemic strokes, and 69 with myocardial infarction. Black (coefficient +3.8, SE 1.3) and Asian (coefficient +2.2, SE 0.4) participants displayed higher BP variability. Long‐term systolic BP variability was independently associated with recurrent ICH (subhazard ratio [SHR], 1.82; 95% CI, 1.19–2.79), ischemic stroke (SHR, 1.62; 95% CI, 1.06–2.47), and myocardial infarction (SHR, 1.54; 95% CI, 1.05–2.24). Average BP during follow‐up did not modify the association between long‐term systolic BP variability and MACCE.ConclusionsLong‐term BP variability is a potent risk factor for recurrent hemorrhage, ischemic stroke, and myocardial infarction after ICH, even among survivors with well‐controlled hypertension. Our findings support the hypothesis that combined control of average BP and its variability after ICH is required to minimize incidence of MACCE.

COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.

Variants of COL4A1/COL4A2 genes have been reported in fetal intracranial hemorrhage (ICH) cases but their prevalence and characteristics have not been established in a large series of fetuses. Fetal neonatal alloimmune thrombocytopenia is a major acquired ICH factor but the prevalence and characteristics of inherited platelet disorder (IPD) gene variants leading to thrombocytopenia are unknown. Herein, we screened COL4A1/COL4A2 and IPD genes in a large series of ICH fetuses. A cohort of 194 consecutive ICH fetuses were first screened for COL4A1/COL4A2 variants. We manually curated a list of 64 genes involved in IPD and investigated them in COL4A1/COL4A2 negative fetuses, using exome sequencing data from 101 of these fetuses. Pathogenic variants of COL4A1/COL4A2 genes were identified in 36 fetuses (19%). They occurred de novo in 70% of the 32 fetuses for whom parental DNA was available. Pathogenic variants in two megakaryopoiesis genes (MPL and MECOM genes) were identified in two families with recurrent and severe fetal ICH, with variable extraneurological pathological features. Our study emphasizes the genetic heterogeneity of fetal ICH and the need to screen both COL4A1/COL4A2 and IPD genes in the etiological investigation of fetal ICH to allow proper genetic counseling.

A case of a heterozygous ABCC6 mutation showing recurrent ischemic strokes and intracranial hemorrhages

AbstractMutations in the ATP‐binding cassette subfamily C member 6 (ABCC6) gene are responsible for pseudoxanthoma elasticum (PXE). PXE is a rare genetic metabolic disease with autosomal recessive inheritance that shows ectopic mineralization in skin, eyes, and blood vessels and causes cerebrovascular disease. There are few reports of intracranial hemorrhages in patients with the ABCC6 mutation. We report the first Japanese case with a heterozygous ABCC6 mutation displaying recurrent ischemic strokes and intracranial hemorrhages. We propose that the ABCC6 mutation may be one cause of neurovascular diseases with a family history.

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation.

ObjectiveTo investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years.MethodsIndividual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all‐cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.ResultsIn total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient‐years follow‐up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%‐CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%‐CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient‐years for ICH‐weights 1.5 to 3.1).InterpretationThe favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78–88

Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial

Oral anticoagulation reduces the rate of systemic embolism for patients with atrial fibrillation by two-thirds, but its benefits for patients with previous intracranial haemorrhage are uncertain. In the Start or STop Anticoagulants Randomised Trial (SoSTART), we aimed to establish whether starting is non-inferior to avoiding oral anticoagulation for survivors of intracranial haemorrhage who have atrial fibrillation. SoSTART was a prospective, randomised, open-label, assessor-masked, parallel-group, pilot phase trial done at 67 hospitals in the UK. We recruited adults (aged ≥18 years) who had survived at least 24 h after symptomatic spontaneous intracranial haemorrhage, had atrial fibrillation, and had a CHA2DS2-VASc score of at least 2. Web-based computerised randomisation incorporating a minimisation algorithm allocated participants (1:1) to start or avoid long-term (≥1 year) full treatment dose open-label oral anticoagulation. The participants assigned to start oral anticoagulation received either a direct oral anticoagulant or vitamin K antagonist, and the group assigned to avoid oral anticoagulation received standard clinical practice (antiplatelet agent or no antithrombotic agent). The primary outcome was recurrent symptomatic spontaneous intracranial haemorrhage, and was adjudicated by an individual masked to treatment allocation. All outcomes were ascertained for at least 1 year after randomisation and assessed in the intention-to-treat population of all randomly assigned participants, using Cox proportional hazards regression adjusted for minimisation covariates. We planned a sample size of 190 participants (one-sided p=0·025, power 90%, allowing for non-adherence) based on a non-inferiority margin of 12% (or adjusted hazard ratio [HR] of 3·2). This trial is registered with ClinicalTrials.gov (NCT03153150) and is complete. Between March 29, 2018, and Feb 27, 2020, consent was obtained at 61 sites for 218 participants, of whom 203 were randomly assigned at a median of 115 days (IQR 49-265) after intracranial haemorrhage onset. 101 were assigned to start and 102 to avoid oral anticoagulation. Participants were followed up for median of 1·2 years (IQR 0·97-1·95; completeness 97·2%). Starting oral anticoagulation was not non-inferior to avoiding oral anticoagulation: eight (8%) of 101 in the start group versus four (4%) of 102 in the avoid group had intracranial haemorrhage recurrences (adjusted HR 2·42 [95% CI 0·72-8·09]; p=0·152). Serious adverse events occurred in 17 (17%) participants in the start group and 15 (15%) in the avoid group. 22 (22%) patients in the start group and 11 (11%) patients in the avoid group died during the study. Whether starting oral anticoagulation was non-inferior to avoiding it for people with atrial fibrillation after intracranial haemorrhage was inconclusive, although rates of recurrent intracranial haemorrhage were lower than expected. In view of weak evidence from analyses of three composite secondary outcomes, the possibility that oral anticoagulation might be superior for preventing symptomatic major vascular events should be investigated in adequately powered randomised trials. British Heart Foundation, Medical Research Council, Chest Heart & Stroke Scotland.

Resuming anticoagulation in patients with atrial fibrillation experiencing intracranial hemorrhage.

Globally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were <20 years old, who were not using OACs 6 months prior to ICH, or who had a CHA2DS2-VASc score of ≤1. We also excluded patients who died during admission for ICH, with follow-up for <6 weeks after discharge, or who started OAC >6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20–0.76) and IS/SE (HR = 0.12, 95% CI = 0.03–0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34–0.93) and IS/SE (HR = 0.26, 95% CI = 0.09–0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.

Association of intracranial vessel wall enhancement and cerebral hemorrhage in moyamoya disease: a high-resolution magnetic resonance imaging study.

This study aimed to investigate the enhancement characteristics of vessel wall in patients with moyamoya disease (MMD) using 3D high-resolution magnetic resonance (MR) imaging and their relationship with initial and recurrent intracranial hemorrhage. Consecutive patients with MMD were retrospectively analyzed and classified as intracranial hemorrhagic and non-hemorrhagic groups according to the CT or MR images. The clinical features and vessel wall characteristics were compared between the two groups. Logistic regression was performed to relate the vessel wall characteristics to the initial hemorrhage in MMD patients. Patients in hemorrhagic group were followed up after surgery to evaluate the relationship between vessel wall characteristics and recurrent hemorrhage. A total of 507 MMD patients including 79 hemorrhagic and 428 non-hemorrhagic MMD patients were recruited in the study. We found that hemorrhagic group had more patients with vessel wall enhancements (40.5% vs. 25.7%, p = 0.009) and more eccentric enhanced lesions (17.7% vs. 6.5%, p = 0.001) compared to those in non-hemorrhage group and vessel wall enhancements were independently associated with ipsilateral initial hemorrhage after adjusted for clinical factors (OR = 1.99, CI 1.20-3.28, p = 0.007). Furthermore, three recurrent intracranial hemorrhagic episodes in the present study were all observed in MMD patients with vessel wall enhancement during the long-term follow-up after surgery. Wall enhancement of intracranial vessels was significantly associated with intracranial hemorrhage in MMD patients. Our findings suggest that vessel wall enhancement may serve as a marker of intracranial hemorrhage.

Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study

Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic...

Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence.

Black and Hispanic survivors of intracerebral hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic cerebral small vessel disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk. We analyzed data from the Massachusetts General Hospital ICH study (n = 593) and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study (n = 329). Using CSVD markers derived from MRIs obtained within 90 days of index ICH, we classified ICH cases as cerebral amyloid angiopathy (CAA)-related, hypertensive arteriopathy (HTNA)-related, and mixed etiology. We quantified CSVD burden using validated global, CAA-specific, and HTNA-specific scores. We compared CSVD subtype and severity among White, Black, and Hispanic ICH survivors and investigated its association with ICH recurrence risk. We analyzed data for 922 ICH survivors (655 White, 130 Black, 137 Hispanic). Minority ICH survivors had greater global CSVD (p = 0.011) and HTNA burden (p = 0.021) on MRI. Furthermore, minority survivors of HTNA-related and mixed-etiology ICH demonstrated higher HTNA burden, resulting in increased ICH recurrence risk (all p < 0.05). We uncovered significant differences in CSVD subtypes and severity among White and minority survivors of primary ICH, with direct implication for known disparities in ICH recurrence risk. Future studies of racial/ethnic disparities in ICH outcomes will benefit from including detailed MRI-based assessment of CSVD subtypes and severity and investigating social determinants of health.

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. British Heart Foundation and Stroke Association.

Early MRI imaging and follow-up study in cerebral amyloid angiopathy.

AimTo study the imaging features of leukoaraiosis (LA) and hemorrhage in cerebral amyloid angiopathy (CAA) patients.MethodsThe earliest MRI images of probable CAA patients and non-CAA patients were collected. The characteristics of LA in the two groups were analyzed. Cerebral micro bleeding (CMB), superficial siderosis (SS), and intracranial hemorrhage (ICH) were recorded in the follow-up study. The space relationship between CMB or SS and ICH was assessed.ResultsWe found that 10/21 (47.6%) patients had occipital prominent LA and 14/21 (66.7%) patients had subcortical punctate LA before the ICH, which was higher than that of the ones in the control group (p = 0.015 and 0.038, respectively). The recurrence rate of ICH was 100% (3/3) in patients with diffuse SS and 36.4% (4/11) in patients without. The recurrence rate of ICH was 60% (3/5) in patients with multiple-lobe CMBs and 44.4% (4/9) in those without. The location of the ICH and CMB was inconsistent. ICH occurred in the ipsilateral cerebral hemisphere of SS in three patients with diffuse SS.ConclusionLA, diffuse SS, and multiple-lobe CMBs are important imaging characteristics of CAA, which may help make early diagnosis and predict the recurrence of ICH.