Managing patients on oral anticoagulant therapy (OAC) who present with traumatic intracranial hemorrhage (ICH) poses a critical challenge in balancing the prevention of thromboembolic events and the risk of progression or recurrent ICH. The objective of this systematic review was to determine the optimal timing for resuming OAC in patients with traumatic ICH, and to assess the risk of hemorrhagic and thromboembolic events, and mortality in patients for whom anticoagulation was resumed. With a medical librarian, 4 databases and gray literature were searched without language or date restrictions. Eligible studies included patients with traumatic ICH undergoing OAC resumption and reporting on timing, ICH progression or recurrence, thromboembolic events, and/or mortality. Of 3384 identified studies, 12 cohort studies met inclusion criteria, involving 13,528 patients with varying severities of traumatic brain injury. Most patients were treated with vitamin K antagonists; only 3 studies included patients on direct oral anticoagulants. The median time to resume OAC ranged from 8 to 67 days. In studies limited to traumatic ICH, OAC resumption was not associated with increased recurrent ICH risk with reported RR 0.70 (95% CI, 0.52-0.95) and HR 0.45 (95% CI, 0.26-0.76). All but one study reported reduced thromboembolic events with OAC resumption. The studies also suggested that complete resolution of the initial ICH allowed for safe resumption of OAC. This systematic review suggests that resumption of OAC after traumatic ICH may be considered in selected patients, without a clear evidence of increase in the risk of recurrent ICH and with a potential reduction in thromboembolic events. However, we were unable to define a safe timeframe, and further studies are needed to establish recommendations to guide clinical practice. Level III, Systematic Review and Meta-Analysis.

Background: Mobile stroke units (MSUs) improve outcomes in thrombolytic-eligible ischemic stroke patients. Outcomes of MSU management in patients with intracranial hemorrhage (ICH) have not been reported. Methods: We conducted a retrospective review of ICH patients enrolled in the Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST-MSU), a prospective multicenter controlled trial comparing MSU with standard EMS management (SM). The primary outcome was utility weighted modified Rankin Scale (uw-mRS) at 90 days; secondary outcomes were hematoma expansion, length of inpatient stay, favorable discharge disposition or 90-day mRS, and mortality. Groups were compared using Chi-square or Fisher’s exact tests for categorical variables, and two sample t-test or Wilcoxon rank sum test for continuous variables. Adjusted analysis was performed to evaluate the relationship between the intervention group and uw-mRS at 90 days. Kaplan-Meier curves and log-rank test were used to compare the survival by 90 days between groups. Results: 201 ICH patients were identified; 102 in the MSU and 99 in the SM groups. MSU patients had more antiplatelet/antithrombotic (AP/AT) use (30.4% vs 15.2%, p=0.016); edema was more frequent in the SM group (72.7% vs 52.0%, p = 0.004). Initial ICH volume was similar between MSU and SM groups (11.50 mL [5.0, 22.0] vs. 9.0 mL [5.0, 20.0], p = 0.62). Anti-hypertensives were given earlier on the MSU (39.0 min [31.00, 45.00] vs 61.0 min [46.50, 75.25], p<0.001), and resulted in shorter time to systolic blood pressure (SBP) < 150mmHg (52 min vs. 121 min, p<0.001). The mean uw-mRS at 90 days was 0.364 ± 0.361 in the MSU and 0.465 ± 0.360 in the SM group (p=0.50, adjusted for AP/AT and edema). There was no difference in hematoma expansion, length of stay, discharge disposition or 90-day mRS. Higher mortality was noted after 5 days post-ictus in the MSU group (26.5% vs. 14.1%, p = 0.04). Conclusion: In ICH patients, MSU management resulted in faster treatment and time to target SBP with similar clinical outcomes except higher late mortality. Further study of the impact of prehospital ICH management including BP reduction and AT/AP reversal are required.

Factors associated with the initial intracranial hemorrhage occurrence in patients with cerebral venous thrombosis

Expansion of intracranial hemorrhage (ICH) is an important predictor of poor clinical outcomes. Various imaging markers on non-contrast computed tomography (NCCT) or computed tomographic angiography (CTA) have been reported as predictors of ICH expansion. We aimed to compare the associations between various CT imaging markers and ICH expansion. Patients with spontaneous ICH who underwent initial NCCT, CTA, and subsequent NCCT between January 2016 and December 2019 were retrospectively identified. ICH expansion was defined as a volume increase of > 33% or > 6 mL. We analyzed the presence of imaging markers such as the black hole sign, blend sign, island sign, or swirl sign on initial NCCT or spot sign on CTA. An alternative free-response receiver operating characteristic curve analysis was performed using a 4-point scoring system based on the consensus of the reviewers. The predictive value of each marker was assessed using univariate and multivariate logistic regression analyses. A total of 250 patients, including 60 (24.0%) with ICH expansion, qualified for the analysis. Among the patients with spontaneous ICH, 118 (47.2%) presented with a black hole sign, 52 (20.8%) with a blend sign, 93 (37.2%) with an island sign, 79 (31.6%) with a swirl sign, and 56 (22.4%) with a spot sign. In univariate logistic regression, the initial ICH volume (P = .038), initial intraventricular hemorrhage (IVH) presence (P < .001), swirl sign (P < .001), and spot sign (P < .001) were associated with ICH expansion. Multivariate analysis confirmed that the presence of initial IVH (odds ratio, 4.111; P = .002) and spot sign (odds ratio, 109.5; P < .001) were independent predictors of ICH expansion. Initial ICH volume, IVH, swirl sign, and spot sign are associated with ICH expansion. The presence of spot signs and IVH were independent predictors of ICH expansion.

In trauma patients using warfarin, current guidelines recommend computed tomography of the brain (CTH), 24-hour observation, and repeat CTH to monitor for stability. Despite growing evidence of uncommon delayed hemorrhage, this remains standard practice even in mild traumatic brain injury without intracranial hemorrhage (ICH). Our study sought to determine the incidence and outcomes of delayed ICH (DICH) in trauma patients on supra-therapeutic warfarin without initial ICH. A retrospective, single institutional study was performed of all adult trauma patients (>18years old) who presented on prehospital warfarin with an international normalized ratio (INR) >3 and initial CTH that did not demonstrate ICH. Each of these patients underwent subsequent CTH within 24hours and any DICH was identified. Those who demonstrated DICH were further examined to identify potential risk factors and outcomes such as need for further imaging or surgical intervention. Analyses were performed using Fisher's exact tests and Student's t-tests. 225 patients were identified from January 2015 to April 2021 that met inclusion criteria. Of those identified, only 3 (1.33%) were found to develop any DICH on routine repeat CTH. Identified characteristics did not reach statistical significance due to the low number of DICH. None of the patients with DICH went on to require intervention. In patients with identified traumatic injury on supra-therapeutic warfarin, an initial CTH without identified ICH alone is an adequate survey. DICH in these patients is uncommon and routine reimaging within 24hours is unlikely to change clinical management in patients with intact neurologic status.

BackgroundMany patients treated with endovascular thrombectomy (EVT) in clinical practice would not have qualified for inclusion in the initial clinical trials demonstrating benefit for EVT, yet likely will benefit from reperfusion. One such subset for which data are sparse is patients with emergent large‐vessel occlusion and concomitant intracranial hemorrhage (ICH). The objective of this report is to document patients who underwent thrombectomy for large‐vessel occlusion in the presence of concomitant ICH and evaluate their clinical characteristics and outcomes.MethodsWe retrospectively reviewed prospectively collected patient records at 4 comprehensive stroke centers from 2012 to 2019. Patients were identified who had pre‐EVT ICH. Data collected included baseline patient demographics and laboratory values, stroke characteristics, ICH radiographic variables, antiplatelet/anticoagulant/thrombolytic medication use, and procedural factors. The primary safety outcome was any worsening of ICH on neuroimaging obtained 24 hours after EVT.ResultsEight patients were identified who underwent thrombectomy with concomitant ICH. The mean age was 71.9 years (range, 37–90). Median National Institutes of Health Stroke Scale score was 25 (interquartile range, 16.5–28.8), and 5 (63%) received tissue plasminogen activator. All patients underwent EVT and had mTICI2B or greater reperfusion. In 7 patients (88%), the initial ICH remained stable on postprocedure imaging. In 1 patient who received intravenous antiplatelet agents during thrombectomy, the hemorrhagic transformation was radiographically increased but without clinical correlate or mass effect.ConclusionsIn a multi‐institution evaluation of 8 patients with ICH at the time of thrombectomy, 1 patient had radiographic worsening of hemorrhage, and no patient experienced clinical worsening related to hemorrhage progression. These findings suggest that thrombectomy may be safe in this population.

BackgroundAlthough the association between periventricular target collateral anastomosis and recurrent ipsilateral hemorrhage has been evaluated in adult patients with moyamoya disease (MMD), no studies have investigated the relationship between target anastomotic territory and recurrent ipsilateral hemorrhage. The goal of this study was to assess this association.MethodsConsecutive adult MMD patients who had experienced initial intracranial hemorrhage and undergone conservative treatment were included. Two readers assessed angiographic results to identify the target anastomotic territory (medial medullary artery, lateral medullary artery, multiple medullary arteries, or nonmedullary artery) responsible for the hemorrhage. Cox proportional hazard regression models were used to estimate the risk of recurrent hemorrhage.ResultsIn the 36 hemispheres with initial hemorrhage, the target anastomotic territory was in the anastomotic territory of the medial medullary artery in 10 (27.8%), lateral medullary artery in 15 (41.7%), multiple medullary arteries in 2 (5.6%), and a nonmedullary artery in 9 (25.0%) hemispheres. During 45.1 ± 40.0 months of follow-up, recurrent ipsilateral hemorrhage occurred in 44.4% (16/36) of hemispheres. The target anastomotic territories responsible for the recurrent event were in the anastomotic territory of the medial medullary artery in 9 (56.3%) hemispheres, lateral medullary artery in 6 (37.5%) hemispheres, and multiple medullary arteries in 1 (6.3%) hemisphere. The anastomotic territory of the medial medullary artery was associated with recurrent hemorrhage before (HR = 2.94; 95% CI, 1.07–8.08; p = 0.037) and after (HR = 6.65; 95% CI, 1.32–33.60; p = 0.022) adjustments were made for confounding factors.ConclusionsThe incidence of recurrent ipsilateral hemorrhage varies with the target anastomotic territory in adult patients with MMD. Medial target medullary artery anastomosis is a significant risk factor for recurrent ipsilateral hemorrhage.

Recurrent Intracranial Hemorrhage and Venous Thromboembolism Following Initial Intracranial Hemorrhage in Patients with Brain Tumors on Anticoagulation

Outcome on Reinstitution of Anticoagulation Following Intracranial Hemorrhage: A Single Institutional Analysis

Timing of vitamin K antagonist re-initiation following intracranial hemorrhage in mechanical heart valves: Systematic review and meta-analysis

Platelet dysfunction has been attributed to progression of initial intracranial hemorrhage (ICH) on repeat head computed tomographic (RHCT) scans in patients on prehospital antiplatelet therapy. However, there is little emphasis on the effect of platelet count and progression of ICH in patients with traumatic brain injury. The aim of this study was to determine the platelet count cutoff for progression on RHCT and neurosurgical intervention in patients on antiplatelet therapy. We performed a prospective cohort analysis of all traumatic brain injury patients with an ICH on prehospital antiplatelet therapy. Antiplatelet therapy was defined as aspirin, clopidogrel, or a combination of both. Admission platelet count was recorded and used for analysis. Receiver operating characteristic curves were plotted to identify the optimal platelet count for progression on RHCT scan and neurosurgical intervention in patients on antiplatelet therapy. A total of 264 patients were enrolled. Platelet count of 135,000/µL or less (area under the curve, 0.80) and platelet count of 95,000/µL or less (area under the curve, 0.92) were the optimal threshold points for progression on RHCT scan and neurosurgical intervention, respectively. Patients with platelet count of 135,000/µL or less were 12.4 times (95% confidence interval, 7.1-18.4) more likely to have progression on RHCT scan and patients with platelet count 95,000/µL or less were 31.5 times (95% confidence interval, 19.7-96.2) more likely to require neurosurgical intervention. A platelet count of less than 135,000/µL in patients on antiplatelet therapy is predictive of both radiographic and clinical worsening. This is a clinically relevant target intended to help tailor and improve management in patients on antiplatelet therapy. Therapeutic study, level III.

Clinical outcomes in patients on preinjury ibuprofen with traumatic brain injury

To compare the safety and efficacy of the remodeling technique with that of conventional coil embolization in a large multicenter series involving the endovascular treatment of ruptured intracranial aneurysms, the CLARITY study (Clinical and Anatomic Results in the Treatment of Ruptured Intracranial Aneurysms). The institutional review board approved the CLARITY study, and written informed consent was obtained from all patients. A total of 768 patients (age range, 19-80 years; mean age ± standard deviation, 51.0 years ± 11.1) with 768 ruptured aneurysms were treated with either conventional coil embolization (608 patients, 79.2%) or the remodeling technique (160 patients, 20.8%). Patient and aneurysm characteristics, the rate of adverse events related to the treatment or initial intracranial hemorrhage, and patient outcome were compared between treatment groups by using the χ(2), Fisher exact, or Student t test. The overall rate of treatment-related complications, with or without clinical manifestations, was 17.4% (106 of 608 patients) with coil embolization and 16.9% (27 of 160 patients) with remodeling (P = .999). The difference in the rates of thromboembolic events, intraoperative rupture, and early repeat bleeding between the treatment groups was not statistically significant. The cumulative morbidity and mortality rate related to the treatment in the remodeling group (3.8%, six of 160 patients) was similar to that in the coil embolization group (5.1%, 31 of 608 patients) (P = .678). Likewise, the global cumulative morbidity and mortality rates related to both the treatment and the initial hemorrhage did not differ significantly between groups (16.2% [26 of 160 patients] with remodeling and 19.6% [119 of 608 patients] with coil embolization, P = .366). The rate of adequate aneurysm occlusion, however, was significantly higher in the remodeling group (94.9%, 150 of 158 aneurysms) than in the coil embolization group (88.7%, 534 of 602 aneurysms) (P = .017). In our large series of patients treated for ruptured aneurysms, the remodeling technique-despite being performed in aneurysms with unfavorable characteristics-was as safe as conventional coil embolization and more efficacious in terms of the rate of adequate postoperative occlusion. These results indicate that the remodeling technique can be routinely used in the treatment of ruptured aneurysms.

We analyzed the effect of superficial temporal to middle cerebral artery (STA-MCA) bypass to prevent future strokes based on the data of the clinical course and the course of the collateral circulation. Thirty-five patients with hemorrhagic type moyamoya disease were examined during the follow-up period with a mean of 6.3 years after the initial intracranial hemorrhage. Eighteen patients were conservatively managed, 12 patients underwent STA-MCA bypass, and the last 5 patients underwent encephaloduroarteriosynangiosis (EDAS). The ophthalmic artery flow was examined as the collateral circulation using the color Doppler flow imaging (CDFI). During the follow-up period, 13 patients (43%, 5.86%/patient/year) experienced a cerebral event such as ischemia or rebleeding. The incidence of a future stroke event in the patients treated with STA-MCA bypass (ppp Clinical symptoms and ophthalmic artery CDFI findings confirmed that STA-MCA bypass in patients with hemorrhagic type moyamoya disease prevents future strokes.

Race/ethnicity is associated with overall incidence of intracranial hemorrhage (ICH), but its impact in patients with brain arteriovenous malformation is unknown. We evaluated whether race/ethnicity was a risk factor for ICH in the natural course in a large, multiethnic cohort of patients with brain arteriovenous malformation followed longitudinally. Data were collected prospectively for patients with brain arteriovenous malformation evaluated at the University of California, San Francisco (n=436) and retrospectively through databases and chart review in the 20 hospitals of the Kaiser Permanente Medical Care Program (n=1028). Multivariate Cox regression was performed to assess the influence of race/ethnicity on subsequent ICH, adjusting for risk factors. Cases were censored at first treatment, loss to follow-up, or death. Average follow up was 4.7+/-8.0 years for Kaiser Permanente Medical Care Program patients and 2.8+/-7.3 years for University of California, San Francisco patients with no difference in time to ICH between cohorts (log rank P=0.57). The annualized 5-year ICH rate was 2.1% (3.7% for ruptured at presentation; 1.4% for unruptured). Initial ICH presentation (hazard ratio: 3.0, 95% CI: 1.9 to 4.9, P<0.001) and Hispanic race/ethnicity (hazard ratio: 1.9, 95% CI: 1.1 to 3.3, P=0.02) were independent predictors of ICH, adjusting for age, gender, cohort, and a cohort-age interaction. The ICH risk for Hispanics versus whites increased to 3.1 (95% CI: 1.3 to 7.4, P=0.013) after further adjusting for arteriovenous malformation size and deep venous drainage in a subset of cases with complete data. Similar trends were observed for blacks (hazard ratio: 2.1, 95% CI: 0.9 to 4.8, P=0.09) and Asians (hazard ratio: 2.4, 95% CI: 0.8 to 7.1, P=0.11), although nonsignificant. This study reports the first description of race/ethnic differences in brain arteriovenous malformation, with Hispanics at an increased risk of subsequent ICH compared with whites.

Accurate estimates for risk and rates of intracranial hemorrhage (ICH) in the natural course of patients harboring brain arteriovenous malformation (BAVM) are needed to provide a quantitative basis for planning clinical trials to evaluate interventional strategies and to help guide practice management. We identified patients with BAVM at the Kaiser Permanente Northern California health maintenance organization and documented their clinical course. The influences of age at diagnosis, gender, race-ethnicity, ICH at presentation, venous draining pattern, and BAVM size on ICH subsequent to presentation were studied using the multivariate Cox proportional hazards model and Kaplan-Meier curves. We identified 790 patients with BAVM (51% female; 63% white; mean age+/-SD at diagnosis: 38+/-19 years) between 1961 and 2001. Patients who presented with ICH experienced a higher rate of subsequent ICH than those who presented without ICH under multivariate analysis (hazard ratio, 3.6; 95% CI, 1.1 to 11.9; P<0.032). The effect was similar across race-ethnicity and gender. This difference in ICH rates was greatest in the first year (7% versus 3% per year) and converged over time. The effect of subsequent ICH on functional status was similar to that of the initial ICH. Presentation with ICH was the most important predictor of future ICH, confirming previous studies. Future ICH had similar impact on functional outcome as incident ICH. Intervention to prevent ICH would be of potentially greater benefit to patients presenting with ICH, although the advantage decreases over time.

Revascularization surgery for moyamoya patients is believed to prevent cerebral ischemic attacks by improving cerebral blood flow. However, measures preventing the occurrence of hemorrhagic moyamoya in patients have not yet been established in the literature due to the low rate of hemorrhage onset as well as the originally limited numbers of patients with moyamoya disease, poor understanding of the clinical course of rebleeding, correct surgical management, and long-term outcome. We present here the results of an overall survey of patients with hemorrhagic moyamoya disease in a district of Miyagi Prefecture in Japan and examine their clinical course, efficacy of revascularization surgery, and long-term outcome. This study included 28 moyamoya patients with episodes of intracranial hemorrhage between 1976 and 1988. The mean follow-up period was 14.2 years. There were 4 males and 24 females, aged 7 to 69 years (mean 39.2 years). Cerebral angiography and CT scans were performed for all patients. Surgical treatment was performed in 19 patients (67. 9%), and 10 patients (35.7%) underwent revascularization surgery. We observed the clinical course of all 28 patients. We also studied the relationship between the efficacy of surgical treatment and long-term outcome. Five of the 28 patients (17.9%) died of the initial intracranial hemorrhage, and 2 patients died of other causes. Rebleeding occurred in 6 of the remaining 21 patients (28. 6%). The interval to rebleeding ranged from 2 to 20 years (mean 7.3 years). Of these 6 patients, 4 died of rebleeding. Rebleeding was observed in 1 of 8 patients who underwent bypass surgery and in 5 of 13 patients who did not, which suggested that rebleeding was less likely to occur in patients who had undergone bypass surgery. However, there was no significant difference in rebleeding ratio or mortality between patients with and those without revascularization surgery (P>0.05). In this study, we compiled the results of meticulous follow-up conducted over the past 10 years for patients with hemorrhagic moyamoya disease. Because hemorrhagic moyamoya disease is known for its high rate of mortality at the time of rebleeding and often causes rebleeding long after the initial episode (as much as 20 years later), implementation of long-term preventive measures for rebleeding is necessary. This suggests that a long-term prospective study of a large number of patients with hemorrhagic moyamoya disease is required to determine whether bypass surgery prevents rebleeding of hemorrhagic moyamoya disease.

Thirty-six infants who had an intracranial hemorrhage (diagnosed by cranial ultrasound) within four days after delivery (mean age 2.4 +/- 0.9 (SD) days), were reexamined at three- to seven-day intervals for extension of their intracranial hemorrhage. Seventeen infants had a patent ductus arteriosus and were treated with indomethacin after the initial intracranial hemorrhage was diagnosed. The age for starting indomethacin was 3.8 +/- 1.1 days. Nineteen infants did not have a patent ductus arteriosus and did not receive indomethacin. Both the indomethacin-treated and nontreated groups were similar in birth weight, gestational age, Apgar scores, gender, incidence of respiratory distress, as well as the location and the degree of hemorrhage in the initial scans. Only one of 17 (6%) infants who received indomethacin v tow of 19 (11%) infants who did not receive it, had extension of their initial intracranial hemorrhage. Although indomethacin may alter platelet function, it does not appear to cause extension of a preexisting intracranial hemorrhage.

Because indomethacin interferes with normal platelet aggregation, its use has been contraindicated in infants with an intra-cranial hemorrhage (ICH). From 1/81 to 8/83 we examined 1) all infants less than 1250g and 2) infants between 1250-1500g who had respiratory distress for the presence of an ICH by ultrasonography within the first 4 days after birth. There were 33 infants who had an ICH diagnosed within the first 4 days (mean age 2.6 ± 1.0 days, ± SD). They were reexamined by ultrasound at 3-7 day intervals for extension of their ICH. An ICH was considered to have extended if the ICH had either: 1) increased in size within the germinal matrix, 2) appeared in a new parenchymal site, or 3) extended into the ventricle. 16 infants had a PDA and were treated with indomethacin (0.4 mg/kg over 36 hr) after the initial ICH was diagnosed. The age for starting indomethacin was 4.1 ± 0.9 days. 17 infants did not have a PDA and did not receive indomethacin. Both the indomethacin-treated and non-treated groups were similar in birthweight, gestational age, gender, Apgar scores, incidence of IRDS, timing of the initial ultrasound scan, number of followup scans (5.4 ± 2.6), as well as the location (germinal matrix alone = 13, GM or parenchymal plus IVH = 20) and the degree of hemorrhage in the initial scans. Only one of 16 (6.3%) who received indomethacin versus 2 of 17 (11%) who did not receive it, had extension of their initial ICH. Although indomethacin may alter platelet function it does not appear to cause extension of a preexisting ICH.