Perfusion Imaging Predicts Favorable Outcomes after Basilar Artery Thrombectomy.

OBJECTIVE: Perfusion imaging identifies anterior circulation stroke patients who respond favorably to endovascular thrombectomy (ET), but its role in basilar artery occlusion (BAO) is unknown. We hypothesized that BAO patients with limited regions of severe hypoperfusion (time to reach maximum concentration in seconds [Tmax] > 10) would have a favorable response to ET compared to patients with more extensive regions involved. METHODS: We performed a multicenter retrospective cohort study of BAO patients with perfusion imaging prior to ET. We prespecified a Critical Area Perfusion Score (CAPS; 0-6 points), which quantified severe hypoperfusion (Tmax > 10) in cerebellum (1 point/hemisphere), pons (2 points), and midbrain and/or thalamus (2 points). Patients were dichotomized into favorable (CAPS ≤ 3) and unfavorable (CAPS > 3) groups. The primary outcome was a favorable functional outcome 90 days after ET (modified Rankin Scale = 0-3). RESULTS: One hundred three patients were included. CAPS ≤ 3 patients (87%) had a lower median National Institutes of Health Stroke Scale score (NIHSS; 12.5, interquartile range [IQR] = 7-22) compared to CAPS > 3 patients (13%; 23, IQR = 19-36; p = 0.01). Reperfusion was achieved in 84% of all patients, with no difference between CAPS groups (p = 0.42). Sixty-four percent of reperfused CAPS ≤ 3 patients had a favorable outcome compared to 8% of nonreperfused CAPS ≤ 3 patients (odds ratio [OR] = 21.0, 95% confidence interval [CI] = 2.6-170; p < 0.001). No CAPS > 3 patients had a favorable outcome, regardless of reperfusion. In a multivariate regression analysis, CAPS ≤ 3 was a robust independent predictor of favorable outcome after adjustment for reperfusion, age, and pre-ET NIHSS (OR = 39.25, 95% CI = 1.34->999, p = 0.04). INTERPRETATION: BAO patients with limited regions of severe hypoperfusion had a favorable response to reperfusion following ET. However, patients with more extensive regions of hypoperfusion in critical brain regions did not benefit from endovascular reperfusion. ANN NEUROL 2022;91:23-32.

Neurological Complications Associated with Hereditary Bleeding Disorders.

PURPOSE OF REVIEW: Hereditary bleeding disorders may have a wide variety of clinical presentations ranging from mild mucosal and joint bleeding to severe central nervous system (CNS) bleeding, of which intracranial hemorrhage (ICH) is the most dreaded complication. In this review, we will discuss the pathophysiology of specific hereditary bleeding disorders, namely, hemophilia A, hemophilia B, and von Willebrand disease (vWD); their clinical manifestations with a particular emphasis on neurological complications; a brief overview of management strategies pertaining to neurological complications; and a review of literature guiding treatment strategies. RECENT FINDINGS: ICH is the most significant cause of morbidity and mortality in patients with hemophilia. Adequate control of bleeding with the administration of specific factors or blood products, identification of risk factors for bleeding, and maintaining optimal coagulant activity are essential for appropriately managing CNS bleeding complications in these patients. The administration of specific recombinant factors is tailored to a patient's pharmacokinetics and steady-state levels. During acute bleeding episodes, initial factor activity should be maintained between 80 and 100%. Availability of monoclonal antibody Emicizumab has revolutionized prophylactic therapies in patients with hemophilia. Management of ICH in patients with vWD involves using plasma-derived factor concentrates, recombinant von Willebrand factor, and supportive antifibrinolytic agents individualized to the type and severity of vWD. Hemophilia and vWD are the most common hereditary bleeding disorders that can predispose patients to life-threatening CNS complications-intracranial bleeds, intraspinal bleeding, and peripheral nerve syndromes. Early care coordination with a hematologist can help develop an effective prophylactic regimen to avoid life-threatening bleeding complications in these patients. Further research is needed to evaluate using emicizumab as an on-demand treatment option for acute bleeding episodes in patients with hemophilia.

Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke.

PURPOSE OF REVIEW: This review aims to provide an overview of neuroinflammation in ischemic and hemorrhagic stroke, including recent findings on the mechanisms and cellular players involved in the inflammatory response to brain injury. RECENT FINDINGS: Neuroinflammation is a crucial process following acute ischemic stroke (AIS) and hemorrhagic stroke (HS). In AIS, neuroinflammation is initiated within minutes of the ischemia onset and continues for several days. In HS, neuroinflammation is initiated by blood byproducts in the subarachnoid space and/or brain parenchyma. In both cases, neuroinflammation is characterized by the activation of resident immune cells, such as microglia and astrocytes, and infiltration of peripheral immune cells, leading to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. These inflammatory mediators contribute to blood-brain barrier disruption, neuronal damage, and cerebral edema, promoting neuronal apoptosis and impairing neuroplasticity, ultimately exacerbating the neurologic deficit. However, neuroinflammation can also have beneficial effects by clearing cellular debris and promoting tissue repair. The role of neuroinflammation in AIS and ICH is complex and multifaceted, and further research is necessary to develop effective therapies that target this process. Intracerebral hemorrhage (ICH) will be the HS subtype addressed in this review. Neuroinflammation is a significant contributor to brain tissue damage following AIS and HS. Understanding the mechanisms and cellular players involved in neuroinflammation is essential for developing effective therapies to reduce secondary injury and improve stroke outcomes. Recent findings have provided new insights into the pathophysiology of neuroinflammation, highlighting the potential for targeting specific cytokines, chemokines, and glial cells as therapeutic strategies.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

PURPOSE OF REVIEW: Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. RECENT FINDINGS: Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90 days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Cardiovascular Predictors of Intracerebral Hematoma Expansion.

BACKGROUND: There is limited evidence on the effect and relevance of cardiovascular parameters on the cerebrovascular system when an intracerebral hemorrhage (ICH) occurs. While recent studies evaluating this relationship are conflicting, one evaluating the effect of systolic cardiac function on clinical outcomes in ICH patients, found low cardiac ejection fractions to be associated with poor clinical outcomes. Our primary objective was to study such correlations and identify various cardiovascular disease states that may be associated with hematoma expansion. METHODS: This is an IRB-approved single-center retrospective study utilizing our institutional "Get with the Guidelines"-Stroke registry between 2013 and 2017. Patients included were older than 18 years of age, admitted with an acute ICH, and had an echocardiogram during their hospitalization. Univariate and multivariate logistical regression analyses were used to identify cardiovascular predictors of hematoma expansion. RESULTS: Two-hundred forty-nine patients were identified from our GWTG-S registry that met initial inclusion criteria. Of these patients, a history of peripheral arterial disease (PAD) (p = 0.015), presence of aortic stenosis (AS) on the echocardiogram (p = 0.025), and a positive spot sign on the CT-angiogram (CTA) of the head (p < 0.001) were found to be independently associated with ICH expansion. Both a history of hypertension and elevated blood pressure on presentation were not significant predictors. Additionally, patients with a history of congestive heart failure had decreased odds of hematoma expansion (p = 0.027). CONCLUSION: This exploratory study highlights potential novel cardiac predictors of hematoma expansion, including PAD and AS, which warrant further study. Larger prospective studies are needed to further investigate such associations to ultimately optimize cardio-cerebral health.

Collaborative Integration of Palliative Care in Critically Ill Stroke Patients in the Neurocritical Care Unit: A Single Center Pilot Study.

INTRODUCTION: Patients admitted to the Neurocritical Care Unit (NCCU) with moderate-to-severe acute strokes, along with their surrogate decision makers, have the potential for unrecognized or unmet emotional and psychological needs. Our primary objective was to determine if early integration of palliative care consultations within this cohort was feasible and would impact understanding, decision-making and emotional support to patients and their surrogate decision makers. Our secondary objective was to evaluate the long-term impact of early palliative care assessment on the development of post-traumatic stress disorder (PTSD). METHODS: This was a single center prospective pilot study. Patients with moderate-to-severe ischemic and hemorrhagic strokes were randomized into two arms. The control arm received standard intensive care and the intervention arm received an additional early palliative care consultation within 72 hours of hospitalization. Study assessments with the participants were obtained on day 1-3, and day 5-7 of care with comparisons of total scores on the Questionnaire on Communication (QOC), Decisional Conflict Scale (DCS), and Hospital Anxiety and Depression Scale (HADS). Furthermore, comparisons of HADS and PTSD DSM-5 (PCL- 5) scores were completed at 3 months. Linear mixed effects models were conducted to examine the association between intervention and participant's scores. RESULTS: A total of 22 participants were enrolled between February 2019 and April 2020. Statistically significant improvement in scores was seen in the total HADS score (p=0.043) and PCL5 score (p=0.033) at 3 months following intervention. CONCLUSION: Collaboration between the intensive care and palliative care team with early palliative assessment may be beneficial in lowering anxiety, depression and PTSD symptoms in critically ill stroke patients and their caregivers. Further research is needed to validate these findings.

Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke.

OBJECTIVE: Agonism of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculoprotection in experimental neuroinjury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurological injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients. METHODS: The NeuroNEXT trial, RHAPSODY, used a novel continual reassessment method to determine the MTD using tiers of 120, 240, 360, and 540 µg/kg of 3K3A-APC. After intravenous tissue plasminogen activator, intra-arterial mechanical thrombectomy, or both, patients were randomized to 1 of the 4 doses or placebo. Vasculoprotection was assessed as microbleed and intracranial hemorrhage (ICH) rates. RESULTS: Between January 2015 and July 2017, we treated 110 patients. Demographics resembled a typical stroke population. The MTD was the highest-dose 3K3A-APC tested, 540 µg/kg, with an estimated toxicity rate of 7%. There was no difference in prespecified ICH rates. In exploratory analyses, 3K3A-APC reduced ICH rates compared to placebo from 86.5% to 67.4% in the combined treatment arms (p = 0.046) and total hemorrhage volume from an average of 2.1 ± 5.8 ml in placebo to 0.8 ± 2.1 ml in the combined treatment arms (p = 0.066). INTERPRETATION: RHAPSODY is the first trial of a neuroprotectant for acute ischemic stroke in a trial design allowing thrombectomy, thrombolysis, or both. The MTD was 540 µg/kg for the PAR1 active cytoprotectant, 3K3A-APC. A trend toward lower hemorrhage rate in an exploratory analysis requires confirmation. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. ANN NEUROL 2019;85:125-136.

Role of Non-Perfusion Factors in Mildly Symptomatic Large Vessel Occlusion Stroke.

INTRODUCTION: Uncertainty regarding reperfusion of mildly-symptomatic (minor) large vessel occlusion (LVO)-strokes exists. Recently, benefits from reperfusion were suggested. However, there is still no strong data to support this. Furthermore, a proportion of those patients don't improve even after non-hemorrhagic reperfusion. Our study evaluated whether or not non-perfusion factors account for such persistent deconditioning. METHODS: Patients with identified minor LVO-strokes (NIHSS ≤ 8) from our stroke alert registry between January-2016 and May-2018 were included. Variables/ predictors of outcome were tested using univariate/multivariate logistic and linear regression analyses. Three month-modified ranking scale (mRS) was used to differentiate between favorable (mRS = 0-2) and unfavorable outcomes (mRS = 3-6). RESULTS: Eighty-one patients were included. Significant differences between the two outcome groups regarding admission-NIHSS and discharge-NIHSS existed (OR = 0.47, 0.49 / p = 0.0005, <0.0001 respectively).The two groups had matching perfusion measures. In the poor outcome group, discharge-NIHSS was unchanged from the admission-NIHSS while in the good outcome group, discharge-NIHSS significantly improved. CONCLUSION: Admission and discharge NIHSS are independent predictors of outcome in patients with minor-LVO strokes. Unchanged discharge-NIHSS predicts worse outcomes while improved discharge-NIHSS predicts good outcomes. Unchanged NIHSS in the poor outcome group was independent of the perfusion parameters. In literature, complement activation and pro-inflammatory responses to ischemia might account for the progression of stroke symptoms in major-strokes. Our study concludes similar phenomena might be present in minor-strokes. Therefore, discharge-NIHSS may be useful as a clinical marker for future therapies.

Clinician's Perception of Practice Changes for Stroke During the COVID-19 Pandemic.

BACKGROUND: Approach to acute cerebrovascular disease management has evolved in the past few months to accommodate the rising needs of the 2019 novel coronavirus (COVID-19) pandemic. In this study, we investigated the changes in practices and policies related to stroke care through an online survey. METHODS: A 12 question, cross-sectional survey targeting practitioners involved in acute stroke care in the US was distributed electronically through national society surveys, social media and personal communication. RESULTS: Respondants from 39 states completed 206 surveys with the majority (82.5%) from comprehensive stroke centers. Approximately half stated some change in transport practices with 14 (7%) reporting significant reduction in transfers. Common strategies to limit healthcare provider exposure included using personal protective equipment (PPE) for all patients (127; 63.5%) as well as limiting the number of practitioners in the room (129; 64.5%). Most respondents (81%) noted an overall decrease in stroke volume. Many (34%) felt that the outcome or care of acute stroke patients had been impacted by COVID-19. This was associated with a change in hospital transport guidelines (OR 1.325, P = 0.047, 95% CI: 1.004-1.748), change in eligibility criteria for IV-tPA or mechanical thrombectomy (MT) (OR 3.146, P = 0.052, 95% CI: 0.988-10.017), and modified admission practices for post IV-tPA or MT patients (OR 2.141, P = 0.023, 95% CI: 1.110-4.132). CONCLUSION: Our study highlights a change in practices and polices related to acute stroke management in response to COVID-19 which are variable among institutions. There is also a reported reduction in stroke volume across hospitals. Amongst these changes, updates in hospital transport guidelines and practices related to IV-tPA and MT may affect the perceived care and outcome of acute stroke patients.

Herniation despite Decompressive Hemicraniectomy in Large Hemispherical Ischemic Strokes.

BACKGROUND: Despite decompressive hemicraniectomy (DHC), progressive herniation resulting in death has been reported following middle cerebral artery (MCA) strokes. We aimed to determine the surgical parameters measured on brain computed tomography (CT) scan that are associated with progressive herniation despite DHC in large MCA strokes. METHODS: Retrospective chart review of medical records of patients with malignant hemispheric infarction who underwent DHC for cerebral edema was performed. Infarct volume was calculated on CT scans obtained within 24 hours of ictus. Radiological parameters of craniectomy bone flap size, brain volume protruding out of the skull, adequate centering of the craniectomy over the stroke bed, and the infarct volume outside the craniectomy bed (volume not centered [VNC]) were measured on the postoperative brain CT. RESULTS: Of 41 patients who underwent DHC, 7 had progressive herniation leading to death. Radiographic parameters significantly associated with progressive herniation included insufficient centering of craniectomy bed on the stroke bed (P = .03), VNC (P = .011), additional anterior cerebral artery infarction (P = .047), and smaller craniectomy length (P = .05). Multivariate logistic regression analysis for progressive herniation using craniectomy length and VNC as independent variables demonstrated that a higher VNC was significantly associated with progressive herniation despite surgery (P = .029). CONCLUSIONS: In large MCA strokes, identification of large infarct volume outside the craniectomy bed was associated with progressive herniation despite surgery. These results will need to be verified in larger prospective studies.

Predictors of poor outcome in patients with posterior reversible encephalopathy syndrome.

PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome that, although characteristically reversible, can be fatal or result in long-term disability in a subset of patients. Our aim was to identify factors associated with poor discharge outcome in PRES patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical and radiological records of all patients with PRES admitted at our tertiary care medical center from 2007 to 2014. They were divided based their modified Rankin Score at discharge and compared for their baseline variables, clinical, laboratory and imaging features. Poor outcome was defined by a modified Rankin scale 2-6 and was subdivided based on the primary mechanism that led to poor outcome. RESULTS: Out of 100 PRES subjects, 36% had poor discharge outcomes. Factors associated with poor outcomes on univariate analysis were history of diabetes mellitus, coma, high Charlson comorbidity index, post-transplantation, autoimmune condition, lack of systolic or diastolic hypertension, elevated blood urea nitrogen and involvement of the corpus callosum. On multivariate analysis, only prior diabetes mellitus odd ratio (OR) = 6.8 (95% CI 1.1-42.1, p = 0.04), corpus callosum involvement (OR = 11.7; 95% CI 2.4-57.4, p = 0.00) were associated with poor outcome. Poor outcome also correlated with increased length of hospital stay (OR = 7.9; 95% CI 1.3-49.7, p = 0.03). CONCLUSION: Large prospective studies incorporating serial blood glucose values and advanced imaging studies are required to validate these findings.

Analysis of youtube as a source of information for peripheral neuropathy.

INTRODUCTION: YouTube is an important resource for patients. No study has evaluated the information on peripheral neuropathy disseminated by YouTube videos. In this study, our aim was to perform a systematic review of information on YouTube regarding peripheral neuropathy. METHODS: The Web site (www.youtube.com) was searched between September 19 and 21, 2014, for the terms "neuropathy," "peripheral neuropathy," "diabetic neuropathy," "neuropathy causes," and "neuropathy treatment." RESULTS: Two hundred videos met the inclusion criteria. Healthcare professionals accounted for almost half of the treatment videos (41 of 92; 44.6%), and most came from chiropractors (18 of 41; 43.9%). Alternative medicine was cited most frequently among the treatment discussions (54 of 145, 37.2%), followed by devices (38 of 145, 26.2%), and pharmacological treatments (23 of 145, 15.9%). CONCLUSIONS: Approximately half of the treatment options discussed in the videos were not evidence-based. Caution should be exercised when YouTube videos are used as a patient resource.

Predictors of seizures in patients with posterior reversible encephalopathy syndrome.

PURPOSE: Although seizures are common in patients with posterior reversible encephalopathy syndrome (PRES), epilepsy is rare. Our objective was to identify predictors and impact of seizures in patients with PRES. METHODS: A retrospective review of the clinical and radiological parameters of all patients diagnosed with PRES from 2007 to 2014 was performed. Patients were divided into two groups based on the occurrence of PRES-related seizures at presentation or during their hospital course. Univariate and multivariate analyses were performed to determine factors associated with the occurrence of PRES-related seizures. RESULTS: Of 100 patients, 70% experienced at least one seizure from PRES. On univariate analysis, the factors associated with seizures were the following: high Charlson comorbidity index (4.16±2.89 vs. 2.87±2.20, p=0.03), systemic malignancy (41.4% vs. 16.7%, p=0.02), occipital lobe involvement (97.1% vs. 83.3%, p=0.02), more lobes involved (4.6±1.48 vs. 3.9±1.32, p=0.03) but less likely in patients with visual disturbances (15.7% vs. 46.7%, p=0.005), and facial droop (12.9% vs. 16.7%, p=0.002). On multivariate analysis, only occipital lobe involvement was significantly (odds ratio: 9.63, 95% CI: 1.45-64.10, p=0.02) associated with the occurrence of PRES-related seizures. Despite the occurrence of seizures, they were less likely to require a nursing home placement upon hospital discharge (odds ratio: 0.17, 95% CI: 0.03-0.91, p=0.04). CONCLUSION: We conclude that seizures are common in patients with occipital lobe involvement from PRES.

Predictors of major improvement after intravenous thrombolysis in acute ischemic stroke.

BACKGROUND: Intravenous thrombolysis improves outcomes of stroke patients. The immediate response to thrombolysis is variable and few studies attempted to identify predictors of major neurological improvement (MNI) 24 h following thrombolysis. Our objective is to determine predictors of MNI 24 h following thrombolysis. METHODS: We reviewed the prospective database of patients treated through our telestroke network and at our institution between November 2008 and June 2012. We included all patients who received IV t-PA and had a 24-h NIHSS score available. Similar to previous studies, we defined MNI as a reduction in NIHSS score by ≥8 points, or a score of 0 or 1 at 24 h. Demographics, risk factors, time to treatment, and clinical and laboratory data, were compared between MNI present or absent. Baseline predictors were compared using t- and Fisher's exact tests, and outcomes using multivariate logistic regression analysis. RESULTS: Out of 316 patients, 306 had 24-h NIHSS scores and 38% of them experienced MNI. Patients with MNI were less likely to be older than 80 years (16% vs. 29%, p = 0.008) and to have atrial fibrillation (9% vs. 24%, p = 0.001) compared to those without; we found no other predictors of MNI. After adjusting for baseline demographics and risk factors, age less than 80 years (OR = 1.9, 95% CI 1.1-3.6) and absence of atrial fibrillation (OR = 3.0, 95% CI: 1.4-6.2) predicted MNI. CONCLUSION: Major neurological improvement within 24 h after thrombolysis is more likely in younger patients and those without atrial fibrillation.

Thrombolysis in ischemic stroke without arterial occlusion at presentation.

BACKGROUND AND PURPOSE: None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. METHODS: We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). RESULTS: A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01). CONCLUSIONS: This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis.

Hematoma expansion in spontaneous intracerebral hemorrhage: predictors and outcome.

BACKGROUND: Hematoma growth is an independent determinant of outcome in patients with intracerebral hemorrhage (ICH). Predictors of hematoma expansion are poorly defined. Our aim is to determine predictors of hematoma expansion in patients with ICH. METHODS: We reviewed our prospective database of patients with ICH between January 2009 and June 2012. Patients were divided into two groups based on the presence or absence of hematoma expansion. Hematoma volume was calculated by thin volumetric cuts using special software. Expansion was defined as 33% increase in hematoma volume over 24 hours. We compared risk factors, laboratory parameters, medications and CT findings between the two groups using Fisher's exact test. A multivariate regression analysis was performed to identify predictors of expansion. RESULTS: We identified 200 patients with ICH. On univariate analysis, patients with hematoma expansion were more likely to have Warfarin use (37% vs. 11% p = 0.001), low admission GCS (9 ± 4, 11 ± 4, p = 0.003), intraventricular hemorrhage (IVH) (79% vs. 45% p = 0.002) and hydrocephalus (43% vs. 22% p = 0.032). On multivariate regression analysis, prior Warfarin use (OR = 3.6, 95% CI: 1.3,10.3; p = 0.016) and IVH (OR = 5.7, 95% CI: 1.5,20.9; p = 0.009) were significant predictors of hematoma expansion. The ICU length of stay (8 ± 8 vs. 4 ± 6, p = 0.004), intubation rate (82% vs. 32%, p = 0.034), and hospital mortality (68% vs. 20%, p = < 0.001) were significantly higher among patients with hematoma expansion. CONCLUSION: Patient with prior Warfarin use and IVHs are at risk of hematoma expansion. Aggressive measures to prevent hematoma growth are important in these patients.

ASPECTS is a predictor of favorable CT perfusion in acute ischemic stroke.

BACKGROUND AND PURPOSE: Computed tomography perfusion (CTP) is used by some stroke centers to stratify stroke patients who may potentially benefit from endovascular treatment. Our aim is to identify predictors of a favorable CTP in acute ischemic stroke patients evaluated within 8h from symptoms onset for possible endovascular treatment. MATERIALS AND METHODS: We reviewed records of patients who had CTP studies between August 2010 and September 2012. We included all patients with anterior circulation strokes with evidence of large vessel disease. All patients had CT head and CT angiography head and neck as part of our protocol. Favorable CTP was defined as core infarct size less than one third the middle cerebral artery distribution and penumbra>20% of infarct size. The patients were divided into two groups based on favorable CTP or not. Baseline characteristics, time parameters, laboratory data and radiological data were compared between both groups. For statistical analysis, we used independent and Fisher's exact tests and a multivariate logistic regression model. RESULTS: During this period, 60 patients met the inclusion criteria. Patients with favorable CTP were likely to be ≥ 80 years (33% vs 9%, P = 0.026), have Alberta Stroke Program early CT score (ASPECTS) > 7 (81% v. 21%, P ≤ 0.001) and lower mean time from symptom onset to CTP (234 ± 91 vs 305 ± 122, P = 0.015). On regression analysis, ASPECTS was the only independent predictor of a favorable CTP (OR = 16.2, CI: 4.3-62.2, P < 0.001). CONCLUSION: ASPECT score may be used as a tool to predict a favorable CTP. Larger studies are needed to confirm our findings.

Clinical Factors Associated With Mode of Death Following Cardiac Arrest.

BACKGROUND: Death after resuscitation from cardiac arrest is common. Although associated factors have been identified, knowledge about their relationship with specific modes of death is limited. OBJECTIVE: To identify clinical factors associated with specific modes of death following cardiac arrest. METHODS: This study involved a retrospective medical record review of patients admitted to a single health care center from January 2015 to March 2020 after resuscitation from cardiac arrest who died during their index hospitalization. Mode of death was categorized as either brain death, withdrawal of life-sustaining therapies due to neurologic causes, death due to medical causes, or withdrawal of life-sustaining therapies due to patient preference. Clinical characteristics across modes of death were compared. RESULTS: The analysis included 731 patients. Death due to medical causes was the most common mode of death. Compared with the other groups of patients, those with brain death were younger, had fewer comorbidities, were more likely to have experienced unwitnessed and longer cardiac arrest, and had more severe acidosis and hyperglycemia on presentation. Patients who died owing to medical causes or withdrawal of life-sustaining therapies due to patient preference were older and had more comorbidities, fewer unfavorable cardiac arrest characteristics, and fewer days between cardiac arrest and death. CONCLUSIONS: Significant associations were found between several clinical characteristics and specific mode of death following cardiac arrest. Decision-making regarding withdrawal of care after resuscitation from cardiac arrest should be based on a multimodal approach that takes account of a variety of personal and clinical factors.

Analysis of brain edema in RHAPSODY.

BACKGROUND: Cerebral edema is a secondary complication of acute ischemic stroke, but its time course and imaging markers are not fully understood. Recently, net water uptake (NWU) has been proposed as a novel marker of edema. AIMS: Studying the RHAPSODY trial cohort, we sought to characterize the time course of edema and test the hypothesis that NWU provides distinct information when added to traditional markers of cerebral edema after stroke by examining its association with other markers. METHODS: A total of 65 patients had measurable supratentorial ischemic lesions. Patients underwent head computed tomography (CT), brain magnetic resonance imaging (MRI) scans, or both at the baseline visit and after 2, 7, 30, and 90 days following enrollment. CT and MRI scans were used to measure four imaging markers of edema: midline shift (MLS), hemisphere volume ratio (HVR), cerebrospinal fluid (CSF) volume, and NWU using semi-quantitative threshold analysis. Trajectories of the markers were summarized, as available. Correlations of the markers of edema were computed and the markers compared by clinical outcome. Regression models were used to examine the effect of 3K3A-activated protein C (APC) treatment. RESULTS: Two measures of mass effect, MLS and HVR, could be measured on all imaging modalities, and had values available across all time points. Accordingly, mass effect reached a maximum level by day 7, normalized by day 30, and then reversed by day 90 for both measures. In the first 2 days after stroke, the change in CSF volume was associated with MLS (ρ = -0.57, p = 0.0001) and HVR (ρ = -0.66, p < 0.0001). In contrast, the change in NWU was not associated with the other imaging markers (all p ⩾ 0.49). While being directionally consistent, we did not observe a difference in the edema markers by clinical outcome. In addition, baseline stroke volume was associated with all markers (MLS (p < 0.001), HVR (p < 0.001), change in CSF volume (p = 0.003)) with the exception of NWU (p = 0.5). Exploratory analysis did not reveal a difference in cerebral edema markers by treatment arm. CONCLUSIONS: Existing cerebral edema imaging markers potentially describe two distinct processes, including lesional water concentration (i.e. NWU) and mass effect (MLS, HVR, and CSF volume). These two types of imaging markers may represent distinct aspects of cerebral edema, which could be useful for future trials targeting this process.

Primary antiphospholipid syndrome manifesting as partial status epilepticus.

Primary antiphospholipid syndrome (APS) is an autoimmune disease defined by vascular thrombosis, pregnancy complications, and persistent antiphospholipid antibodies. Neurological manifestations include stroke, seizures, and chorea among others. Seizures are often precipitated by an acute ischemic event, but occasionally, structural abnormalities are absent. We present a 61-year-old man who developed partial seizures that progressed into partial status epilepticus. His seizures were intractable and required aggressive treatment with multiple anti-epileptic medications. He was diagnosed with primary APS and treated with anticoagulation. Head imaging did not reveal any acute ischemic events. This case demonstrates that primary APS may present as a refractory status epilepticus unrelated to acute cerebral ischemia.