Association of White Matter Hyperintensities With Short-Term Outcomes in Patients With Minor Cerebrovascular Events.

BACKGROUND AND PURPOSE: White matter lesions (WML) are associated with cognitive decline, increased stroke risk, and disability in old age. We hypothesized that superimposed acute cerebrovascular occlusion on chronic preexisting injury (leukoaraiosis) leads to worse outcome after minor cerebrovascular event, both using quantitative (volumetric) and qualitative (Fazekas scale) assessment, as well as relative total brain volume. METHODS: WML volume assessment was performed in 425 patients with high-risk transient ischemic attack (TIA; motor/speech deficits >5 minutes) or minor strokes from the CATCH study (CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Complete baseline characteristics and outcome assessment were available in 412 patients. Primary outcome was disability at 90 days, defined as modified Rankin Scale score of >1. Secondary outcomes were stroke progression, TIA recurrence, and stroke recurrence. Analysis was performed using descriptive statistics and regression models including interaction terms. RESULTS: Median age was 69 years, 39.8% were female. Sixty-two patients (15%) had unfavorable outcome with disability at 90 days (modified Rankin Scale score >1). Higher Fazekas scores were strongly correlated with higher WML volume (r=0.79). Both higher Fazekas score and higher WMH volume were associated with disability at 90 days in univariate regression (odds ratio 1.22; 95% confidence interval, 1.04-1.43 and odds ratio, 1.25 per milliliter increase; 95% confidence interval, 1.02-1.54, respectively) but not with stroke progression, TIA recurrence, or stroke recurrence. In multivariable-adjusted analyses, additive interaction terms were associated with unfavorable outcome (adjusted odds ratio 3.99, 95% confidence interval, 1.87-8.49). CONCLUSIONS: Our data suggest that quantitative and qualitative WML assessments are highly correlated and comparable in TIA/minor stroke patients. WML burden is associated with short-term outcome of patients with good prestroke function in the presence of intracranial stenosis/occlusion.

Nocturnal Hypoxemia Is Associated with White Matter Hyperintensities in Patients with a Minor Stroke or Transient Ischemic Attack.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a risk factor for stroke, which is modulated by accompanying nocturnal hypoxemia. White matter hyperintensities (WMH) share many of the same risk factors as stroke. The purpose of this study was to investigate whether OSA and nocturnal hypoxemia are associated with white matter disease in patients with minor stroke and transient ischemic attack. METHODS: Patients with minor stroke or TIA were recruited. Level 3 diagnostic sleep testing was used to diagnose OSA and quantify nocturnal hypoxemia. Significant OSA was defined as respiratory disturbance index ≥ 15, and nocturnal hypoxemia was defined as oxyhemoglobin saturation < 90% for ≥ 12% of total monitoring time. WMH were assessed and quantified on FLAIR MRI. The volume of WMH was compared between those with and without significant OSA and between those with and without nocturnal hypoxemia. RESULTS: One hundred nine patients were included. Thirty-four (31%) had OSA and 37 (34%) had nocturnal hypoxemia. Total WMH volume was significantly greater in the OSA than in the non-OSA groups (p = 0.04). WMH volume was also significantly higher in the hypoxic than the non-hypoxic groups (p = 0.001). Mutivariable analysis with adjustment for age, hypertension, and diabetes showed that nocturnal hypoxemia was independently associated with WMH volume (p = 0.03) but OSA was not (p = 0.29). CONCLUSIONS: We conclude that nocturnal hypoxemia, predominantly related to OSA, is independently associated with WMH in patients who present with minor ischemic stroke and TIA and may contribute to its pathogenesis.

Refinement of Imaging Predictors of Recurrent Events following Transient Ischemic Attack and Minor Stroke.

BACKGROUND: TIA and minor stroke have a high risk of recurrent stroke. Abnormalities on CT/CTA and MRI predict recurrent events in TIA and minor stroke. However there are many other imaging abnormalities that could potentially predict outcome that have not been assessed in this population. Also the definition of recurrent events used includes deterioration due to stroke progression or recurrent stroke and whether imaging is either of these is not known. AIMS: To improve upon the clinical, CT/CTA and MRI parameters that predict recurrent events after TIA and minor stroke by assessing further imaging parameters. Secondary aim was to explore predictors of stroke progression versus recurrent stroke. METHODS: 510 consecutive TIA and minor stroke patients had CT/CTA and most had MRI. Primary outcome was recurrent events (stroke progression or recurrent stroke) within 90 days. Further imaging parameters were assessed for prediction of recurrent events (combined outcome of stroke progression and recurrent stroke). We also explored predictors of symptom progression versus recurrence individually. RESULTS: 36 recurrent events (36/510, 7.1% (95% CI: 5.0-9.6)) including 19 progression and 17 recurrent strokes. On CT/CTA: white matter disease, prior stroke, aortic arch focal plaque≥4 mm, or intraluminal thrombus did not predict recurrent events (progression or recurrent stroke). On MRI: white matter disease, prior stroke, and microbleeds did not predict recurrent events. Parameters predicting the individual outcome of symptom progression included: ongoing symptoms at initial assessment, symptom fluctuation, intracranial occlusion, intracranial occlusion or stenosis, and the CT/CTA metric. No parameter was strongly predictive of a distinct recurrent stroke. CONCLUSIONS: There was no imaging parameter that could improve upon our original CT/CTA or MRI metrics to predict the combined outcome of stroke progression or a recurrent stroke after TIA and minor stroke. We are better at using imaging to predict stroke progression rather than recurrent stroke.

High rate of magnetic resonance imaging stroke recurrence in cryptogenic transient ischemic attack and minor stroke patients.

BACKGROUND AND PURPOSE: Cryptogenic stroke is common in patients with transient ischemic attack (TIA) and minor stroke. It is likely that the imaging recurrence risk is higher than the clinical recurrence rate. We sought to determine the rate of clinical and radiographic stroke recurrence in a population of cryptogenic TIA and minor stroke. METHODS: Patients with TIA/minor stroke (National Institutes of Health Stroke Scale score≤3) were prospectively enrolled and imaged within 24 hours of symptom onset as part of 2 cohorts. Patients were assessed at 3 months to document any clinical recurrence and underwent repeat magnetic resonance imaging (MRI) at either 30 or 90 days. Stroke mechanism was categorized as cryptogenic after standard etiologic work-up was completed and was negative. Follow-up MRI was assessed for any new lesions in comparison with baseline imaging. RESULTS: Three hundred thirty-three of 693 (48%) patients had cryptogenic stroke. Of these cryptogenic patients, 207 (62%) had follow-up imaging. At 30-day MRI follow-up, 6.6% (5/76) had new lesions (3 in a remote arterial territory). At 90-day MRI follow-up, 14.5% (19/131) had new lesions (9 in a remote arterial territory). Clinical recurrent stroke was seen in 1.2% (4/333) of patients within 90 days. CONCLUSIONS: Cryptogenic etiology is common in a TIA/minor stroke population. This population shows a high rate of silent radiographic recurrence, suggesting active disease. Use of MRI as a surrogate marker of disease activity is 1 potential way of assessing efficacy of new treatments in this population with reduced sample size.

What causes disability after transient ischemic attack and minor stroke?: Results from the CT and MRI in the Triage of TIA and minor Cerebrovascular Events to Identify High Risk Patients (CATCH) Study.

BACKGROUND AND PURPOSE: Minor stroke and transient ischemic attack portend a significant risk of disability. Three possible mechanisms for this include disability not captured by the National Institutes of Health Stroke Scale, symptom progression, or recurrent stroke. We sought to assess the relative impact of these mechanisms on disability in a population of patients with transient ischemic attack and minor stroke. METHODS: Five hundred ten consecutive minor stroke (National Institutes of Health Stroke Scale<4) or patients with transient ischemic attack who were previously not disabled and had a CT/CT angiography completed within 24 hours of symptom onset were prospectively enrolled. Disability was assessed at 90 days using the modified Rankin Scale. Predictors of disability (modified Rankin Scale≥2) and the relative impact of the initial event versus recurrent events were assessed. RESULTS: Seventy-four of 499 (15%; 95% CI, 12%-18%) patients had a disabled outcome. Baseline factors predicting disability were: age≥60 years, diabetes mellitus, premorbid modified Rankin Scale 1, ongoing symptoms, baseline National Institutes of Health Stroke Scale, CT/CT angiography-positive metric, and diffusion-weighted imaging positivity. In the multivariable analysis ongoing symptoms (OR, 2.4; 95% CI, 1.3-4.4; P=0.004), diabetes mellitus (OR, 2.3; 95% CI, 1.2-4.3; P=0.009), female sex (OR, 1.8; 95% CI, 1.1-3; P=0.025), and CT/CT angiography-positive metric (OR, 2.4; 95% CI, 1.4-4; P=0.001) predicted disability. Of the 463 patients who did not have a recurrent event, 55 were disabled (12%). By contrast 19 of 36 (53%) patients were disabled after a recurrent event (risk ratio, 4.4; 95% CI, 3-6.6; P<0.0001). CONCLUSIONS: We found that a substantial proportion of patients with transient ischemic attack and minor stroke become disabled. In terms of absolute numbers, most patients have disability as a result of their presenting event; however, recurrent events have the largest relative impact on outcome.

CT/CT angiography and MRI findings predict recurrent stroke after transient ischemic attack and minor stroke: results of the prospective CATCH study.

BACKGROUND AND PURPOSE: Transient ischemic attack and minor stroke portend a substantial risk of recurrent stroke. MRI can identify patients at high risk for a recurrent stroke. However, MRI is not commonly available as an emergency. If similarly clinically predictive, a CT/CT angiographic (CTA) imaging strategy would be more widely applicable. METHODS: Five hundred ten patients with consecutive transient ischemic attack and minor stroke underwent CT/CTA and subsequent MRI. We assessed the risk of recurrent stroke within 90 days using standard clinical variables and predefined abnormalities on the CT/CTA (acute ischemia on CT and/or intracranial or extracranial occlusion or stenosis ≥50%) and MRI (diffusion-weighted imaging-positive). RESULTS: There were 36 recurrent strokes (7.1%; 95% CI, 5.0-9.6). Median time to the event was 1 day (interquartile range, 7.5). Median time from onset to CTA was 5.5 hours (interquartile range, 6.4 hours) and to MRI was 17.5 hours (interquartile range, 12 hours). Symptoms ongoing at first assessment (hazard ratio, 2.2; 95% CI, 1.02-4.9), CT/CTA abnormalities (hazard ratio, 4.0; 95% CI, 2.0-8.5), and diffusion-weighted imaging positivity (hazard ratio, 2.2; 95% CI, 1.05-4.7) predicted recurrent stroke. In the multivariable analysis, only CT/CTA abnormalities predicted recurrent stroke. In a secondary analysis, CT/CTA and MRI were not significantly different in their discriminative value in predicting recurrent stroke (0.67; (95% CI, 0.59-0.76 versus 0.59; 95% CI, 0.52-0.67; P=0.09). CONCLUSIONS: Early assessment of the intracranial and extracranial vasculature using CT/CTA predicts recurrent stroke and clinical outcome in patients with transient ischemic attack and minor stroke. In many institutions, CTA is more readily available than MRI and physicians should access whichever technique is more quickly available at their institution.