Atrial fibrillation is associated with anterior predominant white matter lesions in patients presenting with embolic stroke.

OBJECTIVE: High white matter hyperintensity (WMH) burden is commonly found on brain MRI among patients with atrial fibrillation (AF). However, whether the link between AF and WMH extends beyond a common vascular risk factor profile is uncertain. We sought to determine whether AF relates to a distinct WMH lesion pattern which may suggest specific underlying pathophysiological relationships. METHODS: We retrospectively analysed a cohort of consecutive patients presenting with embolic stroke at an academic hospital and tertiary referral centre between March 2010 and March 2014. In total, 234 patients (53% female, 74% anterior circulation infarction) fulfilled the inclusion criteria and were included in the analyses. WMH lesion distribution was classified according to previously defined categories. Multivariable logistic regression analysis was performed to determine variables associated with AF within 90 days of index hospital discharge. RESULTS: Among included patients, 114 had AF (49%). After adjustment for the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke/TIA (doubled), vascular disease, age 65-74 years, sex category (female)) score, WMH lesion burden as assessed on the Fazekas scale, embolic stroke pattern, infarct distribution and pertinent interaction terms, AF was significantly associated with presence of anterior subcortical WMH patches (OR 3.647, 95% CI 1.681 to 7.911, p=0.001). CONCLUSIONS: AF is associated with specific WMH lesion pattern among patients with embolic stroke aetiology. This suggests that the link between AF and brain injury extends beyond thromboembolic complications to include a cardiovasculopathy that affects the brain and can be detected and characterised by WMH.

Impact of Leukoaraiosis Burden on Hemispheric Lateralization of the National Institutes of Health Stroke Scale Deficit in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) awards higher deficit scores for infarcts in the dominant hemisphere when compared with otherwise similar infarcts in the nondominant hemisphere. This has been shown to adversely affect stroke recognition, therapeutic decisions, and outcome. However, factors modifying the association between infarct side and deficit severity are incompletely understood. Thus, we sought to determine whether age and age-related leukoaraiosis alter the relation between NIHSS deficit score and the side and volume of infarction. METHODS: We studied 238 patients with supratentorial, nonlacunar ischemic infarcts prospectively included in our stroke registry between January 2013 and January 2014. NIHSS deficit severity was assessed at the time of presentation. Infarct volumes were assessed by manual planimetry on diffusion-weighted imaging. Leukoaraiosis burden was graded on fluid-attenuated inversion recovery images according to the Fazekas scale and dichotomized to none-to-mild (0-2) versus severe (3-6). Multivariable linear regression with backward elimination was used to identify independent predictors of the admission NIHSS. RESULTS: Left-hemispheric infarction (P<0.001), severe leukoaraiosis (P=0.001), their interaction term (P=0.005), infarct volume (P<0.001), and sex (P=0.013) were independently associated with the NIHSS deficit. Analysis of the individual NIHSS components showed that severe leukoaraiosis was associated with an increase of the lateralizing components of the NIHSS in patients with right-hemispheric infarction (P<0.05). CONCLUSIONS: Severe leukoaraiosis substantially attenuates the classic hemispheric lateralization of the NIHSS deficit by relating to greater NIHSS scores of components that are typically assigned to left hemisphere function.

White Matter Hyperintensity-Adjusted Critical Infarct Thresholds to Predict a Favorable 90-Day Outcome.

BACKGROUND AND PURPOSE: There is increasing interest in defining stroke lesion volume thresholds to predict poststroke outcome. However, there is a paucity of data on factors that impact the association between critical infarct thresholds volume and outcome. We sought to determine whether lesion thresholds best predicting outcome depend on the degree of preexisting white matter hyperintensity (WMH) lesion burden. METHODS: Magnetic resonance imaging infarct volumes were quantified in 414 consecutive patients with anterior circulation ischemic strokes evaluated between January 2014 and December 2014. The WMH lesion volume was graded according to the Fazekas scale and dichotomized to absent to mild versus moderate to severe. Receiver operator characteristics curves were calculated to determine the infarct volume threshold best predicting the 90-day outcome. Multivariable logistic regression was used to determine whether the critical lesion thresholds independently predicted a favorable 90-day outcome after adjusting for pertinent confounders. RESULTS: The infarct volumes thresholds predicting the 90-day outcome for the entire cohort (standard thresholds) were ≤29.5 mL (modified Rankin scale [mRS] 0-1), ≤29.9 mL (mRS 0-2), and ≤34.1 mL (mRS 0-3). For patients with absent-to-mild WMH lesion burden, WMH-adjusted critical infarct thresholds were significantly greater than the standard infarct thresholds. In the fully adjusted multivariable regression models, the WMH-adjusted infarct thresholds correctly predicted the outcome to a similar degree as the standard thresholds. CONCLUSIONS: In this proof-of-concept study, the WMH lesion burden impacted the critical outcome-predicting infarct thresholds. If confirmed, using a WMH-adjusted infarct threshold could allow defining patients that have a favorable outcome despite having relatively large infarct volumes.

Atrial Fibrillation Is Associated With a Worse 90-Day Outcome Than Other Cardioembolic Stroke Subtypes.

BACKGROUND AND PURPOSE: Patients with a cardioembolic stroke (CES) have worse outcomes than stroke patients with other causes of stroke. Among patients with CES, atrial fibrillation (AF) is a common comorbidity. Mounting data indicate that AF may be related to stroke pathogenesis beyond acute cerebral thromboembolism. We sought to determine whether AF represents an independent risk factor for stroke severity and outcome among patients with CES. METHODS: We retrospectively analyzed patients with acute hemispheric CES included in an academic medical center's stroke registry. CES was determined using the Causative Classification System of ischemic stroke. Multivariable logistic regression was used to determine whether AF was associated with 90-day outcome functional status. RESULTS: Our cohort included 140 patients. Of these, 52 had prevalent AF and 28 had incident AF diagnosed during their index hospitalization or within 90 days of hospital discharge. After adjustment for potential confounders or mediators, any AF (odds ratio, 2.51; 95% confidence interval, 1.03-6.33; P=0.049), infarct volume (odds ratio, 1.03; 95% confidence interval, 1.01-1.06; P=0.005), preadmission modified Rankin Scale score (odds ratio, 2.58; 95% confidence interval, 1.66-4.01; P<0.001), and admission National Institutes of Health Stroke Scale score (odds ratio, 1.17; 95% confidence interval, 1.08-1.28; P<0.001) remained associated with an unfavorable 90-day outcome (modified Rankin Scale score, 2-6). CONCLUSIONS: AF is associated with an unfavorable 90-day outcome among patients with a CES independent of established risk factors and initial stroke severity. This suggests that AF-specific mechanisms affect CES severity and functional status after CES. If confirmed in future studies, further investigation into the underlying pathophysiological mechanisms may provide novel avenues to AF detection and treatment.

Time to Presentation Is Associated with Clinical Outcome in Hemispheric Stroke Patients Deemed Ineligible for Recanalization Therapy.

BACKGROUND: Delayed thrombolysis adversely impacts functional outcome after stroke. Therefore, great efforts are undertaken to reduce delay in patient presentation and initiate treatment as quickly as possible. However, little is known regarding the impact of time to presentation (TTP) on outcome in patients who are ineligible for acute stroke therapy. Thus, we sought to determine whether the TTP is associated with the 90-day outcome irrespective of eligibility for acute recanalization therapy. METHODS: We retrospectively analyzed 258 consecutive acute ischemic stroke patients evaluated between January 2013 and February 2014. Multivariable logistic regression was used to determine whether a greater TTP is independently associated with a poor 90-day outcome defined as a modified Rankin scale (mRS) score of 3-6. RESULTS: In the unadjusted analyses, the TTP was inversely correlated with transfer from an acute facility (r = -.126, P = .043), cardioembolic stroke etiology (r = -.146, P = .019), and acute recanalization therapy (r = .-412, P < .001). Conversely, a longer TTP was correlated with a worse 90-day mRS score (r = .127, P = .045). After adjustment, the TTP (P = .019), age (P < .001), female sex (P = .001), National Institutes of Health Stroke Scale score (P < .001), preadmission mRS score (P = .001), atrial fibrillation (P < .001), and infarct volume (P < .001) were independently associated with a poor 90-day outcome. Importantly, a longer TTP (odds ratio 1.016, 95% confidence interval 1.001-1.032, P = .036) remained independently associated with the 90-day outcome when we restricted the analyses to patients ineligible for acute intravenous and endovascular recanalization therapies. CONCLUSIONS: Each hour delay in the TTP decreased chances for good outcome by approximately 2% independent of patient eligibility for acute recanalization therapies.

Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) provides a reliable, quantitative measure of ischemic stroke severity and is predicted by the infarct size. We sought to determine whether leukoaraiosis severity affects the association between infarct size and NIHSS. METHODS: NIHSS and diffusion-weighted imaging-defined infarct volumes from 312 prospectively enrolled patients with supratentorial, ischemic strokes were analyzed. Leukoaraiosis severity was graded according to the Fazekas scale and conceptually defined as absent (0; n=44), mild (1-2; n=106), moderate (3-4; n=105), and severe (5-6; n=57). ANCOVA was used to describe the effect of leukoaraiosis on the association between infarct volume and NIHSS. Multivariable linear regression models were constructed to assess whether the association of leukoaraiosis and infarct volume on NIHSS was independent of other clinically relevant covariates. RESULTS: Overall, there was a significant correlation between the infarct volume and NIHSS (r=0.591; P<0.001). This correlation significantly attenuated with increasing leukoaraiosis severity from r=0.786 (P<0.001; absent leukoaraiosis) to r=0.498 (P<0.001; severe leukoaraiosis) and as shown by ANCOVA (P<0.001). Leukoaraiosis (coefficient, 0.107; 95% confidence interval, 0.036-0.179; P=0.016) and infarct volume (coefficient, 0.360; 95% confidence interval, 0.305-0.416; P<0.001) were independently associated with a greater NIHSS deficit in the fully adjusted multivariable model. CONCLUSIONS: Leukoaraiosis significantly modulates the association between infarct volume and NIHSS. The clinical implications of these findings need further exploration in prospective studies but may be relevant to mitigate outcome differences in patients with stroke by aiding treatment decisions that rely on the NIHSS.

Extensive leukoaraiosis is associated with high early risk of recurrence after ischemic stroke.

BACKGROUND AND PURPOSE: The integrity of white matter tracts connecting different parts of the brain is important for rapid compensation for the lost function from ischemic stroke. Impaired white matter reserve capacity secondary to leukoaraiosis may facilitate detection of new symptomatic ischemic events that would otherwise remain inconspicuous after an initial ischemic stroke. We sought to identify whether the extent of leukoaraiosis was a predictor of risk of early stroke recurrence. METHODS: We used Cox regression analysis in consecutive patients with ischemic stroke to determine the relationship between leukoaraiosis burden and symptomatic stroke recurrence within 90 days. We graded total leukoaraiosis, periventricular leukoaraiosis, and subcortical leukoaraiosis using the Fazekas scale as mild (<2) and extensive (≥2) on fluid-attenuated inversion recovery images obtained within 72 hours of stroke onset in the hemisphere contralateral to acute stroke. RESULTS: There were 106 recurrent events in 2378 patients. The cumulative incidence of recurrence was 5.9% at 90 days. Kaplan-Meier estimate of recurrence-free survival rate was lower in patients with extensive leukoaraiosis (P=0.04) and extensive periventricular leukoaraiosis (P=0.02) but not in extensive subcortical leukoaraiosis (P=0.09). Multivariable Cox regression analysis revealed a hazard ratio of 1.50 (95% confidence interval, 1.00-2.25) for extensive leukoaraiosis, 1.67 (95% confidence interval, 1.11-2.51) for extensive periventricular leukoaraiosis, and 1.42 (95% confidence interval, 0.94-2.12) for extensive subcortical leukoaraiosis. CONCLUSIONS: The extent of leukoaraiosis independently predicts 90-day recurrent stroke risk after ischemic stroke. This suggests that leukoaraiosis may be used for risk stratification in ischemic stroke.

Concurrent acute brain infarcts in patients with monocular visual loss.

OBJECTIVE: Embolism from a proximal source to the retinal circulation could be a sign of embolism from the same source to the hemispheric circulation. We sought to determine the frequency of acute brain infarcts on diffusion-weighted imaging (DWI) in patients with monocular visual loss of presumed ischemic origin (MVL). METHODS: We retrospectively studied 129 consecutive patients with MVL secondary to retinal ischemia. All patients underwent DWI, comprehensive ophthalmologic and neurologic examination, and diagnostic evaluations for the underlying etiology. Statistical analyses explored univariate and multivariate predictors of DWI evidence of acute brain infarcts. RESULTS: DWI revealed concurrent acute brain infarct(s) in 31 of the 129 patients (24%). The probability of positive DWI was higher in embolic versus nonembolic MVL (28 vs 8%, p = 0.04), in MVL characterized by permanent visual loss versus transient symptoms (33 vs 18%, p = 0.04), and in MVL associated with concurrent hemispheric symptoms versus isolated MVL (53 vs 20%, p < 0.01). Patients with positive DWI were more likely to harbor a major underlying etiology as compared to those with normal DWI (odds ratio, 3.7; 95% confidence interval, 1.5-9.4). INTERPRETATION: This study demonstrates that MVL does not always represent an isolated disease of the retina; approximately 1 of every 4 patients with MVL demonstrates acute brain infarcts on DWI. Because patients with concurrent brain infarcts are more likely to exhibit a cardiac or vascular source of embolism, imaging evidence of brain injury in patients with MVL may be a useful marker to guide the timing and extent of diagnostic examinations.

Left atrial cross-sectional area is a novel measure of atrial shape associated with cardioembolic strokes.

OBJECTIVE: Cardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes. METHODS: A cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA. RESULTS: A total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p<0.001), independent of age, gender, atrial fibrillation, left ventricular ejection fraction and CHA2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119). CONCLUSIONS: LA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

Ischaemic stroke patients with heterozygous factor V Leiden present with multiple brain infarctions and widespread atherothrombotic disease.

Factor V Leiden (FVL) mutation is a risk factor for venous and, to a degree, arterial thrombosis. It is unknown whether and how FVL affects the manifestations of ischaemic stroke (IS). We assessed the clinical, laboratory, radiological, and prognostic characteristics in an observational study with adult IS patients having FVL. We tested 860 patients with first-ever IS for FVL and found 48 FVL positive patients. Detailed clinical, laboratory, and radiological evaluation were compared with that of 144 (1:3) gender and age matched IS patients without FVL. All patients underwent a prognostic evaluation at an average of five years follow-up. Despite the relatively young age (mean 48.5 years, range 44-54 years) of the FVL positive IS patients, peripheral arterial occlusive disease (PAOD), coronary artery disease (CAD), and previous transient cerebrovascular event occurred more frequently compared with controls. Family history of cardiovascular disease (CVD) and multiple silent brain infarctions were revealed in half of the FVL positive patients, whereas these were seldom encountered among controls. Stroke severity, long-term recovery, and recurrence rates seemed similar irrespective of FVL status. Our findings indicate that the clinical profile of IS patients with FVL associated with wider manifestation of atherothrombosis, positive family history of arterial thrombosis, and presence of multiple silent infarctions on brain images.

The effect of severe carotid occlusive disease and its surgical treatment on cognitive functions of the brain.

Surgery of a high-grade carotid stenosis is evidence-based stroke prevention. Also cognitive effects are reported after carotid endarterectomy (CEA): both deterioration and improvement, the former attributed to perioperative complications and the latter often to learning effect. By imaging, brain perfusion and diffusion changes were shown in subjects with a high-grade stenosis undergoing CEA. We wanted to find out if the cognition of patients undergoing CEA display postoperative worsening or true improvement in association with findings in serial MR imaging. The patients had a poorer overall cognition than healthy matched controls. The cerebral hemisphere ipsilateral to the stenosis had higher diffusion and more sluggish perfusion leading to perfusion deficits. These asymmetries were abolished by CEA. Postoperatively, the patients showed a trend for cognitive worsening, most often attentional, but over months, the group performance improved similarly to the controls. Still, lower baseline perfusion was associated with a greater cognitive improvement, most clearly in executive functions. Consequently, despite the risk for transient decline, true cognitive benefit by CEA seems possible.

Acid-suppressive medications and risk of pneumonia in acute stroke patients: A systematic review and meta-analysis.

GOAL: We performed a systematic review and meta-analysis aiming to clarify the relationship between acid-suppressive medication (ASM) and the risk of pneumonia in acute stroke. METHODS: The included studies examined patients with an acute ischemic and/or hemorrhagic stroke, assessed the relationship of one or both groups of ASM, histamine-2 receptor antagonist (H2RA) and proton-pump inhibitor (PPI), as a variable of interest, and used the occurrence of hospital-acquired pneumonia (HAP) as an outcome measure. The search was conducted in MEDLINE, Cochrane, Embase, and Google Scholar. Random-effects meta-analyses were used to obtain pooled estimates of the effect. RESULTS: 5 retrospective cohort-studies fulfilled study criteria. The results revealed a higher risk of pneumonia for both, patients receiving PPI (adjusted relative risk [RR] 2.37, 95% confidence interval [CI] 1.36-4.17, I2 0%) and H2RAs (adjusted RR 1.73, 95% CI 0.74-4.25, I2 68.3%), although the latter did not reach statistical significance. A comparison of the overall acid versus non-acid groups using unadjusted values yielded likewise an increased risk for pneumonia for patients receiving ASM (unadjusted RR 4.65, 95% CI 1.64-13.16, I2 93.3%). CONCLUSION: Results of this meta-analysis show an increased risk for HAP in acute stroke patients who receive ASM, particularly those exposed to PPIs. Larger, well-controlled studies in acute stroke populations are needed to establish a clearer association between ASM and HAP. These results, however, urge caution when prescribing ASM - especially to stroke patients considered to be at high risk for pneumonia.

Progression of White Matter Injury After Intracerebral Hemorrhage: A Magnetic Resonance Imaging Study.

BACKGROUND: White matter injury (WMI) has been observed after experimental intracerebral hemorrhage (ICH). The supporting clinical data have been sparse. We assessed the presence, extent, and progression of WMI in patients with ICH. METHODS: We performed a retrospective review of data from 65 consecutive patients with spontaneous supratentorial ICH who had undergone baseline brain magnetic resonance imaging (MRI) within 7 days of ICH onset and repeat MRI afterward. We used the Fazekas scale (FZKS) to grade the severity of WMI. The clinical and imaging characteristics of the patients with and without WMI progression (WMIP) were compared using uni- and multivariate logistic regression analyses. RESULTS: We observed WMIP in 23 patients (35.4%). WMIP was noted in both hemispheres but more commonly ipsilateral to the ICH (33% vs. 21%). The mean total FZKS score had increased from 3 (interquartile range [IQR], 1-4) at baseline to 4 (IQR, 2-5) on repeat MRI (P < 0.0001). Patients with lobar ICH had a greater median FZKS score than those with deep ICH (median, 3; IQR, 2-4; vs. 1.5, IQR, 1-3.25; P = 0.027). The baseline parenchymal ICH volume (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.018-1.119; P = 0.007) and ventricular volume on baseline MRI (OR, 1.073; 95% CI, 1.019-1.130; P = 0.007) were predictors of WMIP after adjustment. Multivariate analyses showed an independent association between WMIP and unfavorable 3-month outcomes (OR, 5.196; 95% CI, 1.059-25.483; P = 0.042). CONCLUSIONS: WMI will progress over time in patients with ICH, and WMIP has been associated with worse outcomes. This novel finding could represent a potential therapeutic target. Future prospective larger studies are needed to confirm our findings.

Cerebral small vessel disease burden and functional and radiographic outcomes in intracerebral hemorrhage.

OBJECTIVE: To examine the effect of individual cerebral small vessel disease (CSVD) markers and cumulative CSVD burden on functional independence, ambulation and hematoma expansion in spontaneous intracerebral hemorrhage (ICH). METHODS: Retrospective analysis of prospectively collected data from an observational study of consecutive patients with spontaneous ICH, brain MRI within 1 month from ictus, premorbid modified Rankin Scale (mRS) score ≤ 2, available imaging data and 90-day functional status in a tertiary academic center. Functional outcomes included 90-day functional independence (mRS ≤ 2) and independent ambulation; radiographic outcome was hematoma expansion (> 12.5 ml absolute or > 33% relative increase in ICH volume). We identified the presence and burden of individual CSVD markers (cerebral microbleeds (CMBs), enlarged perivascular spaces, lacunes, white matter hyperintensities) and composite CSVD burden score and explored their association with outcomes of interest in multivariable models adjusting for well-established confounders. RESULTS: 111 patients were included, 65% lobar ICH, with a median volume 20.8 ml. 43 (38.7%) achieved functional independence and 71 (64%) independent ambulation. In multivariable adjusted models, there was higher total CSVD burden (OR 0.61, 95% CI 0.37-0.96, p = 0.03) and CMBs presence (OR 0.32, 95% CI 0.1-0.88, p = 0.04) remained independently inversely associated with functional independence. Individual CSVD markers or total CSVD score had no significant relation with ambulation and ICH expansion. Larger ICH volume and deep ICH location were the major determinants of lack of independent ambulation. CONCLUSIONS: Our findings suggest that in ICH patients without previous functional dependence, total CSVD burden and particularly presence of CMBs significantly affect functional recovery. The latter is a novel finding and merits further exploration.

Prognosis and safety of anticoagulation in intracranial artery dissections in adults.

BACKGROUND AND PURPOSE: To characterize different forms of intracranial artery dissections (IADs), and to test the assumption that IADs are frequently associated with subarachnoid hemorrhage (SAH) and poor outcome, and that anticoagulant therapy is contraindicated in these patients. METHODS: We studied 81 consecutive non-SAH IAD patients and 22 IAD patients with SAH, diagnosed between 1994 and 2004 and 1998 and 2004, respectively, and treated the former patients immediately with heparin, followed with at least 3 months of warfarin. Outcomes were recorded at 3 months. RESULTS: Approximately one-third of all cervicocephalic artery dissections were identifiably either completely located intracranially or extended into the intracranial space. At 3 months, 64 of the 81 non-SAH patients (79%) had a favorable outcome (modified Rankin Scale, 0 to 2); 1 patient died of brain infarction in the acute stage. Only 1 aneurysm developed during follow-up in the non-SAH group, and no intracranial bleeding was observed during anticoagulant treatment. Those presenting with SAH formed approximately 25% of all IADs, and 21 cases out of 22 (95%) were associated with ruptured fusiform dissecting aneurysm. This latter group displayed significantly worse outcomes: 7 died, and only 7 had modified Rankin Scale 0 to 2 at 3 months. CONCLUSIONS: Our results provide important information for clinical practice. IADs appear to polarize into 2 groups: (1) nonaneurysmatic IADs presenting without SAH that are associated with favorable outcomes and safe anticoagulant therapy; and (2) aneurysmatic IADs, characterized by SAH and poorer prognosis. Literature on IADs may have been biased toward group 2.

Assessment of the Predictive Validity of Etiologic Stroke Classification.

Importance: The ability of present-day etiologic stroke classification systems to generate subtypes with discrete stroke characteristics is not known. Objective: To test the hypothesis that etiologic stroke subtyping identifies different disease processes that can be recognized through their different clinical courses. Design, Setting, and Participants: We performed a head-to-head evaluation of the ability of the Causative Classification of Stroke (CCS), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and ASCO (A for atherosclerosis, S for small-vessel disease, C for cardiac source, and O for other cause) classification systems to generate etiologic subtypes with different clinical, imaging, and prognostic characteristics in 1816 patients with ischemic stroke. This study included 2 cohorts recruited at separate periods; the first cohort was recruited between April 2003 and June 2006 and the second between June 2009 and December 2011. Data analysis was performed between June 2014 and May 2016. Main Outcomes and Measures: Separate teams of stroke-trained neurologists performed CCS, TOAST, and ASCO classifications based on information available at the time of hospital discharge. We assessed the association between etiologic subtypes and stroke characteristics by computing receiver operating characteristic curves for binary variables (90-day stroke recurrence and 90-day mortality) and by calculating the ratio of between-category to within-category variability from the analysis of variance for continuous variables (admission National Institutes of Health Stroke Scale score and acute infarct volume). Results: Among the 1816 patients included, the median age was 70 years (interquartile range, 58-80 years) (830 women [46%]). The classification systems differed in their ability to assign stroke etiologies into known subtypes; the size of the undetermined category was 33% by CCS, 53% by TOAST, and 42% by ASCO (P < .001 for all binary comparisons). All systems provided significant discrimination for the validation variables tested. For the primary validation variable (90-day recurrence), the area under the receiver operating characteristic curve was 0.71 (95% CI, 0.66-0.75) for CCS, 0.61 (95% CI, 0.56-0.67) for TOAST, and 0.66 (95% CI, 0.60-0.71) for ASCO (P = .01 for CCS vs ASCO; P < .001 for CCS vs TOAST; P = .13 for ASCO vs TOAST). The classification systems exhibited similar discrimination for 90-day mortality. For admission National Institutes of Health Stroke Scale score and acute infarct volume, CCS generated more distinct subtypes with higher between-category to within-category variability than TOAST and ASCO. Conclusions and Relevance: Our findings suggest that the major etiologic stroke subtypes are distinct categories with different stroke characteristics irrespective of the classification system used to identify them. We further show that CCS generates discrete etiologic categories with more diverse clinical, imaging, and prognostic characteristics than either TOAST or ASCO.

Abnormal intravoxel cerebral blood flow heterogeneity in human ischemic stroke determined by dynamic susceptibility contrast magnetic resonance imaging.

BACKGROUND AND PURPOSE: The determination of cerebral blood flow heterogeneity (FH) by dynamic susceptibility contrast (DSC) magnetic resonance imaging has recently been proposed as a tool to predict final infarct size in acute stroke. In this study, we describe the evolution of FH during the first week as well as its correlation to the patients' clinical status. METHODS: Ten patients with ischemic stroke were studied with DSC MRI and diffusion-weighted imaging in hyperacute (<6 hours) phase, at 24 hours, and 1 week after symptom onset. In addition to intravoxel FH, cerebral blood volume (CBV), cerebral blood flow (CBF), and contrast agent mean transit time (MTT) were determined from DSC MRI. All patients were evaluated neurologically with National Institute of Health Stroke Scale concurrently with the imaging sessions. RESULTS: All patients showed infarct growth, judged by diffusion-weighted imaging, during the week with simultaneous decrease in the sizes of FH, CBV, CBF, and MTT abnormalities. The FH abnormality was shown to be larger than CBV and CBF abnormalities at the hyperacute phase and 24 hours, but smaller than MTT abnormality in all 3 imaging sessions. The sizes of hyperacute FH, CBV, CBF, and MTT abnormalities correlated well with infarct size at 24 hours and at 1 week. Additionally, FH was the only perfusion parameter that correlated with the clinical score. CONCLUSIONS: FH predicts infarct size equally well with the other perfusion parameters but is superior in correlation with the clinical score. FH can easily be incorporated to hyperacute stroke imaging without additional efforts.

Sensitivity to acute cerebral ischemic injury in migraineurs: A retrospective case-control study.

OBJECTIVE: Migraine, particularly with aura, is a risk factor for ischemic stroke. Recent data in migraine mutant mice suggest that cerebral hyperexcitability associated with migraine accelerates recruitment of ischemic penumbra into the core, resulting in faster infarct growth compared with wild type. We hypothesized that individuals with a history of migraine are more likely to exhibit increased recruitment of ischemic tissue into the infarct in acute stroke. METHODS: In this retrospective case-control study, we identified participants with reliably documented migraine history, measured lesion volumes on diffusion-weighted and perfusion-weighted MRI obtained within 72 hours of symptom onset, calculated the proportion of ischemic tissue on perfusion-weighted imaging (PWI) hyperintense on diffusion-weighted imaging (DWI), and compared the proportion of patients with no-mismatch pattern defined as DWI lesion >83% of PWI lesion. RESULTS: Migraineurs (n = 45) were younger, more often female, less likely to have vascular risk factors, and more often had cervical artery dissection, but otherwise did not differ from controls (n = 27). A significantly larger proportion of migraineurs had no-mismatch pattern, indicating that the entire perfusion defect was recruited into the infarct by the time of MRI (22% vs 4% of migraineurs and controls, respectively; p = 0.044). The difference was even more prominent in migraineurs with aura (36% vs 4%, p = 0.019). The association between migraine and no-mismatch pattern persisted after adjustment for time to MRI (p = 0.041). CONCLUSIONS: This case-control study supports the hypothesis that a history of migraine, particularly with aura, is associated with a no-mismatch pattern during acute ischemic stroke, consistent with data obtained in migraine mutant mice.