Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.

Stroke-Related Visceral Alterations: A Voxel-Based Neuroanatomic Localization Study.

OBJECTIVE: Functional and morphologic changes in extracranial organs can occur after acute brain injury. The neuroanatomic correlates of such changes are not fully known. Herein, we tested the hypothesis that brain infarcts are associated with cardiac and systemic abnormalities (CSAs) in a regionally specific manner. METHODS: We generated voxelwise p value maps of brain infarcts for poststroke plasma cardiac troponin T (cTnT) elevation, QTc prolongation, in-hospital infection, and acute stress hyperglycemia (ASH) in 1,208 acute ischemic stroke patients prospectively recruited into the Heart-Brain Interactions Study. We examined the relationship between infarct location and CSAs using a permutation-based approach and identified clusters of contiguous voxels associated with p < 0.05. RESULTS: cTnT elevation not attributable to a known cardiac reason was detected in 5.5%, QTc prolongation in the absence of a known provoker in 21.2%, ASH in 33.9%, and poststroke infection in 13.6%. We identified significant, spatially segregated voxel clusters for each CSA. The clusters for troponin elevation and QTc prolongation mapped to the right hemisphere. There were 3 clusters for ASH, the largest of which was in the left hemisphere. We found 2 clusters for poststroke infection, one associated with pneumonia in the left and one with urinary tract infection in the right hemisphere. The relationship between infarct location and CSAs persisted after adjusting for infarct volume. INTERPRETATION: Our results show that there are discrete regions of brain infarcts associated with CSAs. This information could be used to bootstrap toward new markers for better differentiation between neurogenic and non-neurogenic mechanisms of poststroke CSAs. ANN NEUROL 2023;94:1155-1163.

Percent Insular Ribbon Infarction for Predicting Infarct Growth Rate and 90-Day Outcomes in Large-Vessel Occlusive Stroke: Secondary Analysis of Prospective Clinical Trial Data.

BACKGROUND. Insight into the natural history of infarct growth could help identify patients with slowly progressing stroke who may benefit from delayed endovascular thrombectomy (EVT). OBJECTIVE. The purpose of this article is to evaluate associations of percent insular ribbon infarction (PIRI) with infarct growth rate (IGR) and 90-day outcomes in patients with large-vessel occlusive stroke. METHODS. This retrospective study was a secondary analysis of a prior clinical trial that enrolled patients with acute stroke not treated with reperfusion therapies from January 2007 to June 2009. The present analysis evaluated 31 trial patients (median age, 71 years; 12 women, 19 men) with anterior-circulation large-vessel occlusion who underwent serial MRI examinations. Two neuroradiologists independently scored PIRI on presentation MRI examinations on the basis of the ratio of the length of the portion of the insula showing restricted diffusion to the insula's total length using a previously described 0-4 scale; scores were categorized (mild [0-1], moderate [2], or severe [3-4]), and discrepancies were resolved by consensus. The 90-day modified Rankin Scale (mRS) was obtained. As part of earlier clinical trial analyses, collateral pattern on CTA was classified as symmetric, malignant, or other, and infarct volumes were measured on DWI during the initial 48 hours after presentation and on FLAIR at 90 days. RESULTS. Interrater agreement for PIRI category was strong (κ = 0.89). PIRI was mild in 10, moderate in four, and severe in 17 patients. For mild, moderate, and severe PIRI, median IGR from onset to presentation was 1.6 cm3/h, 8.5 cm3/h, and 17.5 cm3/h (p < .001); median IGR from presentation to 48 hours was 0.3 cm3/h, 0.2 cm3/h, and 1.2 cm3/h (p = .005); median 90-day infarct volume was 9.4 cm3, 39.8 cm3, and 108.6 cm3 (p = .01); and 90-day mRS of 2 or less occurred in 78%, 67%, and 6% of patients (p = .001). In multivariable models controlling for age, internal carotid artery occlusion, and collateral pattern, PIRI category independently predicted onset-to-presentation IGR (ß = 1.5), presentation-to-48-hour IGR (ß = 1.3), and 90-day mRS of 2 or less (OR = 0.2). For predicting 90-day mRS of 2 or less, mild-to-moderate PIRI had sensitivity of 90.0% and specificity of 84.2%; symmetric collateral pattern had sensitivity of 70.0% and specificity of 73.7%. CONCLUSION. PIRI was independently associated with IGR and 90-day outcome. CLINICAL IMPACT. PIRI may help identify patients who could benefit from late-window EVT when requiring transfer to EVT-capable centers.

Symmetric CTA Collaterals Identify Patients with Slow-progressing Stroke Likely to Benefit from Late Thrombectomy.

Background Understanding ischemic core growth rate (IGR) is key in identifying patients with slow-progressing large vessel occlusion (LVO) stroke who may benefit from delayed endovascular thrombectomy (EVT). Purpose To evaluate whether symmetric collateral pattern at CT angiography (CTA) can help to identify patients with low IGR and small 24-hour diffusion-weighted MRI ischemic core volume in patients with LVO not treated with reperfusion therapies. Materials and Methods In this secondary analysis of clinical trial data from before EVT became standard of care from January 2007 to June 2009, patients with anterior proximal LVO not treated with reperfusion therapies were evaluated. All patients underwent admission CTA and at least three MRI examinations at four time points over 48 hours. Arterial phase CTA collaterals at presentation were categorized as symmetric, malignant, or other. Diffusion-weighted MRI ischemic core volume and IGR at multiple time points were determined. The IGR at presentation was defined as follows: (ischemic core volume in cubic centimeters)/(time since stroke symptom onset in hours). Multivariable analyses and receiver operator characteristic analyses were used. Results This study evaluated 31 patients (median age, 71 years; interquartile range, 61-81 years; 19 men) with median National Institutes of Health Stroke Scale (NIHSS) score of 13. Collaterals were symmetric (45%; 14 of 31), malignant (13%; four of 31), or other (42%; 13 of 31). Median ischemic core volume was different between collateral patterns at all time points. Presentation was as follows: symmetric, 16 cm3; other, 69 cm3; and malignant, 104 cm3 (P < .001). At 24 hours, median ischemic core volumes were as follows: symmetric, 28 cm3; other, 156 cm3; and malignant, 176 cm3 (P < .001). Median IGR was also different, and most pronounced at presentation: symmetric, 4 cm3 per hour; other, 17 cm3 per hour; and malignant, 20 cm3 per hour (P < .001). After multivariable adjustment, independent determinants of higher presentation IGR included only higher NIHSS (parameter estimate [ß = 0.20; 95% CI: 0.05, 0.36; P = .008) and worse collaterals (ß = -2.90; 95% CI: -4.31, -1.50; P < .001). The only independent determinant of 24-hour IGR was worse collaterals (ß = -2.03; 95% CI: -3.28, -0.78; P = .001). Symmetric collaterals had sensitivity of 87% (13 of 15) and specificity of 94% (15 of 16) for 24-hour ischemic core volume less than 50 cm3 (area under the receiver operating characteristic curve, 0.92; 95% CI: 0.81, 1.00; P < .001). Conclusion In patients with large vessel occlusion not treated with reperfusion therapies, symmetric collateral pattern at CT angiography was common and highly specific for low ischemic core growth rate and small 24-hour ischemic core volume as assessed at diffusion-weighted MRI. After further outcome studies, collateral status at presentation may prove useful in triage for endovascular thrombectomy, especially when MRI and CT perfusion are unavailable. Clinical trial registration no. NCT00414726. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Messina in this issue.

Use of Prolonged Cardiac Rhythm Monitoring to Identify Atrial Fibrillation After Cryptogenic Stroke.

PURPOSE OF REVIEW: Prolonged cardiac monitoring (PCM) improves detection of atrial fibrillation (AF) after cryptogenic stroke. We summarize current research supporting the use of PCM as part of the cryptogenic stroke evaluation, while highlighting areas that require more investigation. RECENT FINDINGS: Despite increased AF detection with longer durations of PCM, more definitive research is needed to demonstrate how PCM improves clinical outcomes. The optimal type, timing, and length of cardiac monitoring after cryptogenic stoke remains unknown. Clinical calculators will be important to risk stratify which cryptogenic stroke patients are most likely to benefit from PCM. Currently, AF detection after cryptogenic stroke should prompt consideration of anticoagulation, but it is unclear if all durations and timing of AF after stroke should be treated the same. PCM remains an important part of the cryptogenic stroke work up, and detection of AF allows for anticoagulation initiation. Additional research is needed to further refine our application of PCM to cryptogenic stroke.

Prognostication in Acute Neurological Emergencies.

BACKGROUND: For patients with acute, serious neurological conditions presenting to the emergency department (ED), prognostication is typically based on clinical experience, scoring systems and patient co-morbidities. Because estimating a poor prognosis influences caregiver decisions to withdraw life-sustaining therapy, we investigated the consistency of prognostication across a spectrum of neurology physicians. METHODS: Five acute neurological presentations (2 with large hemispheric infarction; 1 with brainstem infarction, 1 with lobar hemorrhage, and 1 with hypoxic-ischemic encephalopathy) were selected for a department-wide prognostication simulation exercise. All had presented to our tertiary care hospital's ED, where a poor outcome was predicted by the ED neurology team within 24 hours of onset. Relevant clinical, laboratory and imaging data available before ED prognostication were presented on a web-based platform to 120 providers blinded to the actual outcome. The provider was requested to rank-order, from most to least likely, the predicted 90-day modified Rankin Scale (mRS) score. To determine the accuracy of individual outcome predictions we compared the patient's the actual 90-day mRS score to highest ranked predicted mRS score. Additionally, the group's "weighted" outcomes, accounting for the entire spectrum of mRS scores ranked by all respondents, were compared to the actual outcome for each case. Consistency was compared between pre-specified provider roles: neurology trainees versus faculty; non-vascular versus vascular faculty. RESULTS: Responses ranged from 106-110 per case. Individual predictions were highly variable, with predictions matching the actual mRS scores in as low as 2% of respondents in one case and 95% in another case. However, as a group, the weighted outcome matched the actual mRS score in 3 of 5 cases (60%). There was no significant difference between subgroups based on expertise (stroke/neurocritical care versus other) or experience (faculty versus trainee) in 4 of 5 cases. CONCLUSION: Acute neuro-prognostication is highly variable and often inaccurate among neurology providers. Significant differences are not attributable to experience or subspecialty expertise. The mean outcome prediction from group of providers ("the wisdom of the crowd") may be superior to that of individual providers.

Outcomes among patients with primary angiitis of the CNS: A Nationwide United States analysis.

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a relapsing-remitting disease with a heterogeneous course. Case series have delineated the long-term disease course but not acute outcomes or their determinants. The national United States hospital burden of PACNS has not been quantified. METHODS: Analysis of the United States Nationwide Readmissions Database (2016-2018) to characterize the frequency of PACNS hospitalizations, demographic features, inpatient mortality, and discharge outcomes. RESULTS: During the 3-year study period, unweighted 1843 (weighted 3409) patients with PACNS were admitted to the 1078 Healthcare Cost and Utilization Project HCUP participating hospitals; with weighting, this value indicates that 1136 patients were admitted each year to US hospitals, representing yearly 0.01 cases per 100 000 national hospitalizations. The majority of patients were hospitalized in metropolitan teaching hospitals (81.6%). The median age at admission was 54.9 (IQR: 44.0-66.5) years and 59.4% were women. Neurologic manifestations included ischemic stroke in 38.2%, transient ischemic attack in 20.2%, seizure disorder in 22.8%, and intracranial hemorrhage in 13.0%. Overall, 60.0% of patients were discharged home, 35.0% discharged to a rehabilitation facility or nursing home and 5.0% died before discharge. Patient features independently associated with the discharge to another facility or death included older age (odds ratio [OR], 1.03 [95% CI, [1.03-1.04]]), male sex (OR, 1.22 [1.04-1.43]), intraparenchymal hemorrhage (OR, 1.41 [1.08-1.84]), ischemic stroke (OR, 2.79 [2.38-3.28]), and seizure disorder (OR, 1.57 [1.31-1.89]). CONCLUSION: Our study showed PACNS is still a rare inflammatory disorder of the blood vessels of the central nervous system suggesting an annual hospitalization of 5.1 cases per 1,000,000 person-years in the more diverse and contemporary US population. Overall, 4 in 10 had unfavorable discharge outcome, being unable to be discharged home, and 1 in 20 died before discharge.

Regional Changes in Patterns of Stroke Presentation During the COVID-19 Pandemic.

[Figure: see text].

Cerebral Microembolism in Intracerebral Hemorrhage: A Prospective Case-Control Study.

BACKGROUND: Small and remote acute ischemic lesions may occur in up to one-third of patients with spontaneous intracerebral hemorrhage (ICH). Possible mechanisms include cerebral embolism, small vessel disease, blood pressure variability and others. The embolic mechanism has not been adequately studied. Using transcranial Doppler (TCD), we assessed the incidence of spontaneous microembolic signals (MESs) in patients with acute ICH. METHODS: Twenty acute ICH patients were prospectively evaluated within 48 h of hospital admission. Clinical and imaging data were collected. Continuous TCD monitoring was performed in both middle cerebral arteries for a one-hour period on days 1, 3 and 7 of hospital admission. Monitoring was performed in the emergency room, ICU or ward, according to patient location. We compared the frequency and risk factors for MES in patients with ICH and in 20 age- and gender-matched controls without history of ischemic or hemorrhagic stroke. RESULTS: The mean age was 57.5 ± 14.1 years, and 60% were male. MESs were detected in 7 patients with ICH and in one control patient without ICH (35% vs 5%, p = 0.048). The frequency of MES on day 1 was 15% (3 of 20 patients), on day 3, 26% (5 of 19 patients) and on day 7, 37.5% (3 of 8 patients). Among patients with ICH, those with MES had a tendency to higher frequencies of dyslipidemia (83% vs 33%, p = 0.13) and lobar location of hemorrhages (71% vs 30%, p = 0.15). Two out of 6 patients with ICH who also underwent MRI had remote DWI lesions, of whom one showed MES on TCD. CONCLUSION: Micro-embolic signals occur in over one-third of patients with ICH. Further research is needed to identify the sources of cerebral microembolism and their relationship with small acute infarcts in ICH.

Mechanical Thrombectomy in Stroke from Infective Endocarditis: Case Report and Review.

OBJECTIVE: To characterize outcomes after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) from infective endocarditis. METHODS: Case report and review of published cases. RESULTS: We report the case of a 59-year-old woman with fungal endocarditis who developed AIS from a proximal middle cerebral artery (MCA) embolus. She underwent MT, with good outcome. An additional 25 similar cases were identified from 14 publications. Among the 26 cases analyzed (mean [SD] age, 55 [18.7] years, 42% women), the MCA was the most common site of arterial occlusion. Four patients received intravenous tissue plasminogen activator treatment before MT. The median admission NIH Stroke Scale score (NIHSSS) was 15.5 [interquartile range 9.75-19.25] and the median post-procedure NIHSSS was 2 [interquartile range .75-6]. No patient developed symptomatic intracerebral hemorrhage. CONCLUSIONS: MT appears to be a safe and effective therapeutic option in infective endocarditis-related AIS with proximal-artery occlusion.

Subdural Hematoma: Predictors of Outcome and a Score to Guide Surgical Decision-Making.

OBJECTIVE: There is little evidence to guide patient selection for subdural hemorrhage (SDH) evacuation. This study was designed to assess the benefit of surgical evacuation of SDH, identify predictors of functional outcome, and create a bedside score to guide the clinical management of SDH. METHODS: A cohort of 331 patients presenting to a single center from 2010 to 2014 with a principal diagnosis of subdural hemorrhage was identified. Clinical and radiographic information were extracted from the medical record. Outcomes of interest were (1) the occurrence of surgical evacuation of SDH, and (2) an unfavorable 90-day functional status represented by a modified Rankin score (mRS) ≥ 3. Propensity score matching and adjustment techniques were employed to assess the benefit of surgery accounting for confounding by indication. Multivariable logistic regression models predicting follow-up functional outcome were generated and bootstrapped separately among those with acute SDH and those with either subacute or chronic SDH. Clinical scores were created using model coefficients. RESULTS: In this cohort [65% male, mean age 67 years], 47% underwent surgery. Age, focal neurologic deficit, SDH thickness > 10 mm, midline shift > 5mm, and SDH acuity predicted undergoing surgery. Propensity score matching analysis demonstrated that operated patients overall were less likely to have unfavorable 90-day mRS outcome (OR 0.35, 95% C.I. 0.15-0.82). Among patients with acute SDH, age, female sex, pre-admission mRS, focal neurologic deficit, and neuropsychiatric symptoms predicted 90-day functional outcome (c-statistic 0.89, optimism-corrected c-statistic 0.87) and were incorporated into an acute SDH score (range 1-10). Patients with SDH score > 4 were significantly more likely to have an unfavorable outcome if treated medically versus surgically; there was no difference in 90-day functional status by treatment strategy among patients with SDH score ≤ 4. No difference in outcome was seen by surgical status across the spectrum of chronic SDH scores. CONCLUSIONS: Surgical evacuation of subdural hematomas overall is associated with favorable outcome. Patient selection for evacuation is enhanced by the application of the acute SDH score. Future studies are necessary to validate the SDH score in an external cohort.

Cerebral Small Vessel Diseases and Sleep Related Strokes.

BACKGROUND AND PURPOSE: Sleep related Stroke (SRS) is common and has been associated with cerebral small vessel diseases (SVD) in ischemic strokes (ISs). We tested the hypothesis that SRS is associated with SVD in both ischemic and hemorrhagic stroke. METHODS: Prospectively collected data from patients consecutively enrolled after intracerebral hemorrhage (ICH) related to SVD or after IS were analyzed. Symptom onset was recorded as SRS versus awake. Each ICH was grouped according to lobar and deep locations. The IS cohort was etiologically characterized based on the Causative Classification of Stroke system. Frequencies of SRS within and between ICH and IS cohorts as well as its associations (etiology, risk factors) were analyzed. RESULTS: We analyzed 1812 IS (mean age 67.9 years ± 15.9 years, 46.4% female) and 1038 ICH patients (mean age 72.5 years ± 13.0 years, 45.4% female). SRS was significantly more common among SVD-related ICH patients (n = 276, 26.6%) when compared to all IS (n = 363, 20.0%, P < .001) and in both, small artery occlusion (SAO) related IS and lobar ICH within the respective IS and ICH cohorts (16.3% SRS versus 9.1% awake for SAO within all IS, P < .001; and 57.1% SRS versus 47.7% awake for lobar bleeds within all ICH, P = .008). These associations remained significant after controlling for age, sex and risk factors. CONCLUSIONS: SRS was associated with SVD. The SAO etiology and cerebral amyloid angiopathy related lobar ICH suggest that the presence of SVD can interact with sleep or arousal related hemodynamic changes to cause ischemic and hemorrhagic stroke.

Reduced Ischemic Lesion Growth with Heparin in Acute Ischemic Stroke.

OBJECTIVE: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. METHODS: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and showed a PWI-DWI lesion mismatch, and who underwent follow-up neuroimaging at least 4 days after admission. Lesion growth was assessed by (1) absolute lesion growth and (2) percentage mismatch lost (PML). Univariate and multivariate regression analysis, and propensity score matching, were used to determine the effects of heparin on ischemic lesion growth. RESULTS: Of the 113 patients meeting study criteria, 59 received heparin within 24 hours. Heparin use was associated with ∼5-fold reductions in PML (3.5% versus 19.2%, P = .002) and absolute lesion growth (4.7 versus 20.5 mL, P = .009). In multivariate regression models, heparin independently predicted reduced PML (P = .04) and absolute lesion growth (P = .04) in the entire cohort, and in multiple subgroups (patients with and without proximal artery occlusion; DWI volume greater than 5 mL; cardio-embolic mechanism; DEFUSE-3 target mismatch). In propensity score matching analysis where patients were matched by admission NIHSS, DWI volume and proximal artery occlusion, heparin remained an independent predictor of PML (P = .048) and tended to predict absolute lesion growth (P = .06). Heparin treatment did not predict functional outcome at discharge or 90 days. CONCLUSION: Early heparin treatment in acute ischemic stroke patients with PWI-DWI mismatch attenuates ischemic lesion growth. Clinical trials with careful patient selection are warranted to investigate the potential ischemic protective effects of heparin.

Different Effects of Normobaric Oxygen in Normotensive Versus Hypertensive Rats After Focal Cerebral Ischemia.

BACKGROUND AND PURPOSE: The efficacy of neuroprotective approaches in stroke may be influenced by existing comorbidities. Here, we compared the effects of normobaric hyperoxia (NBO) in normotensive versus hypertensive rats subjected to transient focal cerebral ischemia. METHODS: Male Sprague-Dawley and spontaneously hypertensive rats were subjected to transient focal ischemia via intraluminal filament occlusions of the middle cerebral artery. NBO was started 15 minutes after ischemic onset and stopped at the time of reperfusion. Acute neurological deficits and tetrazolium-stained infarct volumes were quantified at 24 hours. RESULTS: NBO reduced mean infarct volumes by ≈50% (P=0.0064) in normotensive Sprague-Dawley rats subjected to 100 minutes transient ischemia. No effects of NBO were observed in hypertensive spontaneously hypertensive rats subjected to either 100 minutes or 75 minutes of transient ischemia. No significant changes in neurological outcomes were detectable in any group. CONCLUSIONS: NBO reduced infarction in Sprague-Dawley but not in spontaneously hypertensive rats. These findings suggest that comorbidities may influence responses to potential treatments after stroke.

Ischemic Stroke Profile, Risk Factors, and Outcomes in India: The Indo-US Collaborative Stroke Project.

BACKGROUND AND PURPOSE: The Indo-US Collaborative Stroke Project was designed to characterize ischemic stroke across 5 high-volume academic tertiary hospitals in India. METHODS: From January 2012 to August 2014, research coordinators and physician coinvestigators prospectively collected data on 2066 patients with ischemic stroke admitted <2 weeks after onset. Investigator training and supervision and data monitoring were conducted by the US site (Massachusetts General Hospital, Boston). RESULTS: The mean age was 58.3±14.7 years, 67.2% men. The median admission National Institutes of Health Stroke Scale score was 10 (interquartile range, 5-15) and 24.5% had National Institutes of Health Stroke Scale ≥16. Hypertension (60.8%), diabetes mellitus (35.7%), and tobacco use (32.2%, including bidi/smokeless tobacco) were common risk factors. Only 4% had atrial fibrillation. All patients underwent computed tomography or magnetic resonance imaging; 81% had cerebrovascular imaging. Stroke etiologic subtypes were large artery (29.9%), cardiac (24.9%), small artery (14.2%), other definite (3.4%), and undetermined (27.6%, including 6.7% with incomplete evaluation). Intravenous or intra-arterial thrombolysis was administered in 13%. In-hospital mortality was 7.9%, and 48% achieved modified Rankin Scale score 0 to 2 at 90 days. On multivariate analysis, diabetes mellitus predicted poor 3-month outcome and younger age, lower admission National Institutes of Health Stroke Scale and small-artery etiology predicted excellent 3-month outcome. CONCLUSIONS: These comprehensive and novel clinical imaging data will prove useful in refining stroke guidelines and advancing stroke care in India.