Left ventricular hypertrophy and left atrial size are associated with ischemic strokes among non-vitamin K antagonist oral anticoagulant users.

BACKGROUND: Ischemic strokes (IS) occurring in patients taking non-vitamin K antagonist oral anticoagulants (NOACs) are becoming increasingly more frequent. We aimed to determine the clinical, echocardiographic, and neuroimaging markers associated with developing IS in patients taking NOACs for atrial fibrillation. METHODS: From a quaternary care center, clinical/radiologic data were collected from consecutive NOAC users with IS and age-matched controls without IS. Brain MRIs were reviewed for markers of cerebral small vessel disease. Variables with significant differences between groups were entered into a multivariable regression model to determine predictors of IS. Among IS patients, a Cox regression analysis was constructed to determine predictors of IS recurrence during follow-up. RESULTS: 112 patients with IS and 94 controls were included in the study. Variables significantly different between groups included apixaban use, dabigatran use, prior cerebrovascular events, hemoglobin A1c (HbA1c), left ventricular hypertrophy, left atrial volume index, and severe white matter hyperintensities. After multivariable adjustment, prior cerebrovascular events (aOR 23.86, 95% CI [6.02-94.48]), HbA1c levels (aOR 2.36, 95% CI [1.39-3.99]), left ventricular hypertrophy (aOR 2.73, 95% CI [1.11-6.71]) and left atrial volume index (aOR 1.05, 95% CI [1.01-1.08]) increased the risk of stroke, whereas apixaban use appeared to decrease the risk (aOR 0.38, 95% CI [0.16-0.92]). Malignancy was associated with IS recurrence (aHR 4.90, 95% CI [1.35-18.42]) after adjustment for age and chronic renal failure. CONCLUSIONS: Prior cerebrovascular events, diabetes, left ventricular hypertrophy, and increased left atrial size are risk factors for developing an IS among NOAC users.

Symmetric collateral pattern on CTA predicts favorable outcomes after endovascular thrombectomy for large vessel occlusion stroke.

Endovascular thrombectomy (EVT) has revolutionized large vessel occlusion (LVO) stroke management, but often requires advanced imaging. The collateral pattern on CT angiograms may be an alternative because a symmetric collateral pattern correlates with a slowly growing, small ischemic core. We tested the hypothesis that such patients will have favorable outcomes after EVT. Consecutive patients (n = 74) with anterior LVOs who underwent EVT were retrospectively analyzed. Inclusion criteria were available CTA and 90-day modified Rankin Scale (mRS). CTA collateral patterns were symmetric in 36%, malignant in 24%, or other in 39%. Median NIHSS was 11 for symmetric, 18 for malignant, and 19 for other (p = 0.02). Ninety-day mRS ≤2, indicating independent living, was achieved in 67% of symmetric, 17% of malignant, and 38% of other patterns (p = 0.003). A symmetric collateral pattern was a significant determinant of 90-day mRS ≤2 (aOR = 6.62, 95%CI = 2.24,19.53; p = 0.001) in a multivariable model that included age, NIHSS, baseline mRS, thrombolysis, LVO location, and successful reperfusion. We conclude that a symmetric collateral pattern predicts favorable outcomes after EVT for LVO stroke. Because the pattern also marks slow ischemic core growth, patients with symmetric collaterals may be suitable for transfer for thrombectomy. A malignant collateral pattern is associated with poor clinical outcomes.

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.

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.

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.

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.

Regional differences in ischemic stroke in India (north vs. south).

BACKGROUND: India is a large country with geographically diverse populations and varying risk factors. Identification of regional differences can improve healthcare policy decisions. AIM: To study regional differences in stroke between North and South India. METHODS: We analyzed data from the Indo-US Collaborative Stroke Project, a National Institute of Health-funded multicentre prospective study conducted in five academic centers in India with a US-based coordinating center. Risk factors, severity, mechanisms, management, complications, and outcomes among ischemic stroke patients were compared between North and South Indian centers. RESULTS: Of the 2066 patients enrolled from North (n = 1060) and South India (n = 1006), North Indian patients were significantly older with fewer men and had lower rates of diabetes (32.8% vs. 38.7%, p < 0.01), dyslipidemia (3.5% vs. 25.7%, p < 0.01), tobacco use (27% vs. 38%, p < 0.001), and alcohol use (30.1% vs. 38.6%, p < 0.01). North Indian patients had higher median National Institute of Health stroke scale scores (10 vs. 9, p < 0.01), more frequent large-artery atherosclerosis mechanism (34% vs. 25.6%, p < 0.001), intravenous thrombolysis (14.0% vs. 6.1%, p < 0.001), and lower rates of pneumonia (10.5% vs. 15.1%, p = 0.02). The three-month outcome (modified Rankin Scale score 0-2, 45.8% vs. 50.3%, p = 0.08) did not differ; however, North Indian patients had higher 90-day mortality (23.5% vs. 13.5%, p < 0.0001). CONCLUSIONS: The substantial regional differences in stroke risk factors and mechanisms may be partly explained by factors such as differing dietary habits and lifestyle, which can be addressed at a national level. Differences in acute and inpatient stroke care suggest a need for better adoption of national stroke management guidelines.

Performance of a Hospital Pathway for Patients With a New Single Brain Mass.

PURPOSE:: To reduce care variation and improve the management of patients with newly identified single brain masses and no history of cancer, we implemented a dedicated admission protocol. METHODS:: We reviewed records of 206 patients who presented to our emergency department between January 2010 and May 2016 with a new single brain mass but no history of cancer. Patients admitted before the protocol implementation were designated the pre-implementation group (PRE), and those admitted after implementation were designated the post-implementation group (POST). RESULTS:: Ninety-six patients were in the PRE group and 110 in the POST group. Length of stay for POST patients was significantly shorter than for PRE patients (6 v 7 days, respectively; P = .042), and this effect was more robust after excluding the 66 patients who were discharged to rehabilitation, skilled nursing, or hospice facilities (5 v 7 days, respectively; P = .001). Additional comparison of POST with PRE patients showed that time to surgery was significantly reduced (2.7 v 3.5 days, respectively; P = .006) and that computed tomography scans of the chest, abdomen, and pelvis were reduced (12% v 47%, respectively; P < .001). No difference was found in the 30-day readmission rates. For patients with GBM, there also was no significant difference in time to initiation of chemoradiation or in median overall survival. CONCLUSION:: Implementation of a specialized admission pathway for patients with a new single brain mass decreased average length of hospital stay and time to surgery and reduced unnecessary diagnostic imaging tests in patients with primary brain tumors.

RCVS2 score and diagnostic approach for reversible cerebral vasoconstriction syndrome.

OBJECTIVE: To develop a method to distinguish reversible cerebral vasoconstriction syndrome (RCVS) from other large/medium-vessel intracranial arteriopathies. METHODS: We identified consecutive patients from our institutional databases admitted in 2013-2017 with newly diagnosed RCVS (n = 30) or non-RCVS arteriopathy (n = 80). Admission clinical and imaging features were compared. Multivariate logistic regression modeling was used to develop a discriminatory score. Score validity was tested in a separate cohort of patients with RCVS and its closest mimic, primary angiitis of the CNS (PACNS). In addition, key variables were used to develop a bedside approach to distinguish RCVS from non-RCVS arteriopathies. RESULTS: The RCVS group had significantly more women, vasoconstrictive triggers, thunderclap headaches, normal brain imaging results, and better outcomes. Beta coefficients from the multivariate regression model yielding the best c-statistic (0.989) were used to develop the RCVS2 score (range -2 to +10; recurrent/single thunderclap headache; carotid artery involvement; vasoconstrictive trigger; sex; subarachnoid hemorrhage). Score ≥5 had 99% specificity and 90% sensitivity for diagnosing RCVS, and score ≤2 had 100% specificity and 85% sensitivity for excluding RCVS. Scores 3-4 had 86% specificity and 10% sensitivity for diagnosing RCVS. The score showed similar performance to distinguish RCVS from PACNS in the validation cohort. A clinical approach based on recurrent thunderclap headaches, trigger and normal brain scans, or convexity subarachnoid hemorrhage correctly diagnosed 25 of 37 patients with RCVS2 scores 3-4 across the derivation and validation cohorts. CONCLUSION: RCVS can be accurately distinguished from other intracranial arteriopathies upon admission, using widely available clinical and imaging features. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the RCVS2 score accurately distinguishes patients with RCVS from those with other intracranial arteriopathies.

Quality of care for ischemic stroke in China vs India: Findings from national clinical registries.

OBJECTIVE: To understand stroke risk factors, status of stroke care, and opportunities for improvement as China and India develop national strategies to address their disproportionate and growing burden of stroke. METHODS: We compared stroke risk factors, acute management, adherence to quality performance measures, and clinical outcomes among hospitalized ischemic stroke patients using data from the Indo-US Collaborative Stroke Project (IUCSP) and China National Stroke Registry-II (CNSR-II). The IUCSP included 5 academic stroke centers from different geographic regions (n = 2,066). For comparison, the CNSR-II dataset was restricted to 31 academic hospitals among 219 participating sites from 31 provinces (n = 1,973). RESULTS: Indian patients were significantly younger, had health insurance less often, and had significantly different risk factors (more often diabetes mellitus, dyslipidemia, and coronary heart disease; less often prior stroke, hypertension, atrial fibrillation, and smoking). Hospitalized Indian patients had greater stroke severity (median NIH Stroke Scale score 10 vs 4), higher rates of IV thrombolysis within 3 hours (7.5% vs 2.4%), greater in-hospital mortality (7.9% vs 1.2%), and worse outcome (3-month modified Rankin Scale score 0-2, 49.3% vs 78.1%) (all p < 0.001). The poorer clinical outcomes were attributable mainly to greater stroke severity in IUCSP patients. Chinese patients more often received antithrombotics, stroke education, and dysphagia screening during hospitalization. CONCLUSION: These data provide insights into the status of ischemic stroke care in academic urban centers within 2 large Asian countries. Further research is needed to determine whether these patterns are representative of care across the countries, to explain differences in observed severity, and to drive improvements.

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.

Recrudescence of Deficits After Stroke: Clinical and Imaging Phenotype, Triggers, and Risk Factors.

Importance: Reemergence of previous stroke-related deficits (or poststroke recrudescence [PSR]) is an underrecognized and inadequately characterized phenomenon. Objective: To investigate the clinical features, triggers, and risk factors for PSR. Design, Setting, and Participants: This retrospective study incorporated a crossover cohort study to identify triggers and a case-control study to identify risk factors. The study used the Massachusetts General Hospital Research Patient Data Repository to identify patients for the period January 1, 2000, to November 30, 2015, who had a primary or secondary diagnosis of cerebrovascular disease, who underwent magnetic resonance imaging of the brain at least once, and whose inpatient or outpatient clinician note or discharge summary stated the term recrudescence. In all, 153 patients met the preliminary diagnostic criteria for PSR: transient worsening of residual poststroke focal neurologic deficits or transient recurrence of prior stroke-related focal deficits, admission magnetic resonance imaging showing a chronic stroke but no acute infarct or hemorrhage, no evidence of transient ischemic attack or seizure, no acute lesion on diffusion-weighted imaging, and no clinical or electroencephalographic evidence of seizure around the time of the event. Main Outcomes and Measures: Clinical and imaging features of PSR; triggers (identified by comparing PSR admissions with adjacent admissions without PSR); and risk factors (identified by comparing PSR cases with control cases from the Massachusetts General Hospital Stroke Registry). Results: Of the 153 patients, 145 had prior infarct, 8 had hypertensive brain hemorrhage, and 164 admissions for PSR were identified. The patients' mean (SD) age was 67 (16) years, and 92 (60%) were women. Recrudescence occurred a mean (SD) of 3.9 (0.6) years after the stroke, lasted 18.4 (20.4) hours, and was resolved on day 1 for 91 of the 131 episodes with documented resolution time (69%). Deficits were typically abrupt and mild and affected motor-sensory or language function. No patient had isolated gaze paresis, hemianopia, or neglect. During PSR, the National Institutes of Health Stroke Scale (NIHSS) score worsened by a mean (SD) 2.5 (1.9) points, and deficits were limited to a single NIHSS item in 62 episodes (38%). The underlying chronic strokes were variably sized, predominantly affected white matter tracts, and involved the middle cerebral artery territory for 112 patients (73%). Infection, hypotension, hyponatremia, insomnia or stress, and benzodiazepine use were higher during PSR admissions. Compared with the control group (patients who did not experience recrudescence), the PSR group (patients who were hospitalized for recrudescence) had more women, African American individuals, and those who self-identified as being from "other" race. The PSR group also had more diabetes, dyslipidemia, smoking, infarcts from small-vessel disease, and "other definite" causes and worse onset NIHSS scores. Six patients (4%) received intravenous tissue plasminogen activator without complications. Conclusions and Relevance: The PSR features identified in the study should enable prompt diagnosis and distinguish recrudescence from mimics, such as transient ischemic attacks, migraine, Todd paralysis, and Uhthoff phenomenon. Prospective studies are required to validate the proposed diagnostic criteria and to decipher underlying mechanisms.

Cerebrovascular fibromuscular dysplasia: The MGH cohort and literature review.

BACKGROUND: Fibromuscular dysplasia (FMD) is a rare noninflammatory, nonatherosclerotic arteriopathy of medium-sized arteries affecting up to 7% of the population. The disease can affect any artery but commonly affects renal, extracranial carotid, and vertebral arteries. The epidemiology and natural course of cerebrovascular FMD is unknown and requires further investigation. METHODS: We present demographic and outcomes data on a case series of 81 patients with cerebrovascular FMD from Massachusetts General Hospital presenting between 2011 and 2015 followed by a review of the peer-reviewed literature. RESULTS: Patients were a median age of 53 years (±12 SD) and the majority were women. Approximately 50% had a history of tobacco use and more than two-thirds had hypertension. Most patients were on monoplatelet therapy with aspirin; during follow-up, 7 of 67 had progressive disease or additional symptoms. One of 67 patients had a cerebrovascular event: TIA. There were 5 of 67 who had noncerebrovascular events or disease progression and 1 death of unclear cause. CONCLUSIONS: Cerebrovascular FMD may present with myriad symptoms. Our data support that patients with FMD with symptomatic disease have a low rate of recurrent symptoms or disease progression and can be managed conservatively with stroke risk modification, antiplatelet agents, surveillance imaging, and counseling.

Hemorrhagic primary CNS angiitis and vasoconstrictive drug exposure.

BACKGROUND: Primary angiitis of the CNS (PACNS) typically manifests with accumulating neurologic deficits from ischemic strokes. Intracerebral hemorrhage (ICH) is an uncommon complication. There is limited knowledge about the risk factors and features of hemorrhagic PACNS. METHODS: We identified 49 patients (20 biopsy-proven) with PACNS diagnosed at our hospital from 1993 to 2015. We compared the features of hemorrhagic and nonhemorrhagic PACNS and analyzed the hemorrhagic PACNS cases in detail. RESULTS: The mean age was 51 ± 15 years; 13 patients were men. Five patients had ICH (mean age 52 ± 14 years; 4 men) including 4 where ICH was the first manifestation of PACNS. All ICH patients reported recent exposure to sympathomimetic drugs (e.g., diet pills, nasal decongestants). Patients with ICH had higher rates of headache (100% vs 43%, p = 0.022), especially thunderclap headache (60% vs 0%, p = 0.001), and eosinophilic vascular infiltrates on brain biopsy (50% vs 9%, p = 0.084). In all ICH patients, brain MRI showed lobar hemorrhages with concurrent punctate diffusion-restricted lesions, suggesting an acute inflammatory process. Four received a short course of immunosuppressive therapy. All patients showed complete clinical resolution or significant improvement within weeks. CONCLUSIONS: In this study, hemorrhagic PACNS was exclusively associated with sympathomimetic drug exposure. The high rate of thunderclap headache, lobar hemorrhages, and the self-limited clinical course suggests a shared mechanism between hemorrhagic PACNS and the reversible cerebral vasoconstriction syndrome (RCVS), a PACNS mimic. This RCVS-PACNS overlap syndrome may result from sympathomimetic drug-induced prolonged distal vasoconstriction, culminating in inflammation.

Coexisting vascular lesions in reversible cerebral vasoconstriction syndrome.

Background The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) is not known. Published cases have documented coexisting cervical artery dissection and unruptured aneurysms, raising the possibility that ultrastructural vessel wall abnormalities underlie the development of vascular lesions as well as RCVS. Methods In this retrospective study we compared the frequency of neurovascular abnormalities in 158 consecutive RCVS patients, 44 patients with primary angiitis of the central nervous system (PACNS, positive controls), and 177 non-stroke patients with acute neurological symptoms (non-arteriopathy controls). Results Coexisting neurovascular abnormalities were significantly higher ( p < 0.001) in RCVS (23%) as compared to the PACNS (5%) or non-arteriopathy groups (8%). Cervical artery dissections were noted only in the RCVS group (8%, p < 0.001). The RCVS group had more unruptured aneurysms than PACNS (13% vs. 5%, p = 0.099) or non-arteriopathy controls (13% vs. 7%, p = 0.05). Seven RCVS patients also had other vascular malformations (venous anomaly, cavernous malformations, fibromuscular dysplasia). There was no significant association between coexisting vascular abnormalities and brain lesions or discharge clinical outcome in the RCVS group. Conclusion The high prevalence and heterogeneous anatomy of coexisting vascular lesions suggest that subtle ultrastructural arterial wall abnormalities may contribute to their development and also predispose to RCVS.

Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical, imaging, and angiographic comparison.

Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. However, prompt and accurate diagnosis remains challenging. Here we compared the features of 159 RCVS to 47 PACNS patients and developed criteria for prompt bedside diagnosis. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. In patients without TCH and positive angiography, neuroimaging can discriminate RCVS (no lesion) from PACNS (deep/brainstem infarcts). Ann Neurol 2016;79:882-894.

Brain edema predicts outcome after nonlacunar ischemic stroke.

BACKGROUND AND PURPOSE: In malignant infarction, brain edema leads to secondary neurological deterioration and poor outcome. We sought to determine whether swelling is associated with outcome in smaller volume strokes. METHODS: Two research cohorts of acute stroke subjects with serial brain MRI were analyzed. The categorical presence of swelling and infarct growth was assessed on diffusion-weighted imaging (DWI) by comparing baseline and follow-up scans. The increase in stroke volume (ΔDWI) was then subdivided into swelling and infarct growth volumes using region-of-interest analysis. The relationship of these imaging markers with outcome was evaluated in univariable and multivariable regression. RESULTS: The presence of swelling independently predicted worse outcome after adjustment for age, National Institutes of Health Stroke Scale, admission glucose, and baseline DWI volume (odds ratio, 4.55; 95% confidence interval, 1.21-18.9; P<0.02). Volumetric analysis confirmed that ΔDWI was associated with outcome (odds ratio, 4.29; 95% confidence interval, 2.00-11.5; P<0.001). After partitioning ΔDWI into swelling and infarct growth volumetrically, swelling remained an independent predictor of poor outcome (odds ratio, 1.09; 95% confidence interval, 1.03-1.17; P<0.005). Larger infarct growth was also associated with poor outcome (odds ratio, 7.05; 95% confidence interval, 1.04-143; P<0.045), although small infarct growth was not. The severity of cytotoxic injury measured on apparent diffusion coefficient maps was associated with swelling, whereas the perfusion deficit volume was associated with infarct growth. CONCLUSIONS: Swelling and infarct growth each contribute to total stroke lesion growth in the days after stroke. Swelling is an independent predictor of poor outcome, with a brain swelling volume of ≥11 mL identified as the threshold with greatest sensitivity and specificity for predicting poor outcome.