Francesca M. Chappell

Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis

BACKGROUND Accurate carotid imaging is important for effective secondary stroke prevention. Non-invasive imaging, now widely available, is replacing intra-arterial angiography for carotid stenosis, but the accuracy remains uncertain despite an extensive literature. We systematically reviewed the accuracy of non-invasive imaging compared with intra-arterial angiography for diagnosing carotid stenosis in patients with carotid territory ischaemic symptoms. METHODS We searched for articles published between 1980 and April 2004; included studies comparing non-invasive imaging with intra-arterial angiography that met Standards for Reporting of Diagnostic Accuracy (STARD) criteria; extracted data to calculate sensitivity and specificity of non-invasive imaging, to test for heterogeneity and to perform sensitivity analyses; and categorised percent stenosis by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. RESULTS In 41 included studies (2541 patients, 4876 arteries), contrast-enhanced MR angiography was more sensitive (0.94, 95% CI 0.88-0.97) and specific (0.93, 95% CI 0.89-0.96) for 70-99% stenosis than Doppler ultrasound, MR angiography, and CT angiography (sensitivities 0.89, 0.88, 0.76; specificities 0.84, 0.84, 0.94, respectively). Data for 50-69% stenoses and combinations of non-invasive tests were sparse and unreliable. There was heterogeneity between studies and evidence of publication bias. INTERPRETATION Non-invasive tests, used cautiously, could replace intra-arterial carotid angiography for 70-99% stenosis. However, more data are required to determine their accuracy, especially at 50-69% stenoses where the balance of risk and benefit for carotid endarterectomy is particularly narrow, and to explore and overcome heterogeneity. Methodology for evaluating imaging tests should be improved; blinded, prospective studies in clinically relevant patients are essential basic characteristics.

Lacunar stroke is associated with diffuse blood–brain barrier dysfunction†

Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood–brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke.

Comparison of 10 Different Magnetic Resonance Perfusion Imaging Processing Methods in Acute Ischemic Stroke Effect on Lesion Size, Proportion of Patients With Diffusion/Perfusion Mismatch, Clinical Scores, and Radiologic Outcomes

Background and Purpose— Several methods are available to assess the magnetic resonance perfusion lesion in acute ischemic stroke. We tested 10 of these to compare perfusion lesion sizes and to assess the relation to clinical scores and final infarct extent. Methods— We recruited patients with acute ischemic stroke, performed diffusion- and perfusion-weighted imaging, and recorded stroke severity at baseline, final infarct size on T2-weighted imaging at ≥1 month, and Rankin Scale score at 3 months. We calculated 10 perfusion parameters (6 of mean transit time, MTT; 3 of cerebral blood flow; 1 of cerebral blood volume; 7 relative and 3 quantitative), measured the perfusion-weighted imaging lesion and diffusion/perfusion mismatch volumes, and compared each with clinical and radiologic outcomes. Results— Among 32 patients, the median perfusion lesion volume varied from 0 to 14 882 voxels (P<0.0001); the proportion of patients with mismatch varied from 9% to 72% (P<0.05), depending on the perfusion parameter. Five measures of relative MTT were associated with baseline National Institutes of Health Stroke Scale score; 1 (arrival time fitted) was also associated with clinical outcome. Final infarct size was most strongly associated with MTT measures, including arrival time fitted. There was no advantage of quantitative perfusion measures and no relation between mismatch presence/absence and infarct expansion with any of the 10 perfusion measures. Conclusions— Perfusion lesion size differs markedly depending on the parameter calculated. Relative perfusion parameters performed as well as quantitative ones. Some parameters (mainly representing MTT measures) were correlated with clinical scores; others were correlated with final infarct size; and arrival time fitted was correlated with both. These findings should be validated in other datasets. A consensus is required on which perfusion measurement and processing methods should be used.

Computed tomography and magnetic resonance perfusion imaging in ischemic stroke: Definitions and thresholds†

Cerebral perfusion imaging with computed tomography (CT) or magnetic resonance (MR) is widely available. The optimum perfusion values to identify tissue at risk of infarction in acute stroke are unclear. We systematically reviewed CT and MR perfusion imaging in acute ischemic stroke.

Enlarged perivascular spaces and cerebral small vessel disease

Background and aims Enlarged perivascular spaces (also known as Virchow-Robin spaces) on T2-weighted brain magnetic resonance imaging are common, but their etiology, and specificity to small vessel as opposed to general cerebrovascular disease or ageing, is unclear. We tested the association between enlarged perivascular spaces and ischemic stroke subtype, other markers of small vessel disease, and common vascular risk factors. Methods We prospectively recruited patients with acute stroke, diagnosed and subtyped by a stroke physician using clinical features and brain magnetic resonance imaging. A neuroradiologist rated basal ganglia and centrum semiovale enlarged perivascular spaces on a five-point scale, white matter lesions, recent and old infarcts, and cerebral atrophy. We assessed associations between basal ganglia-, centrum semiovale- and total (combined basal ganglia and centrum semiovale) enlarged perivascular spaces, stroke subtype, white matter lesions, atrophy, and vascular risk factors. Results Among 298 patients (mean age 68 years), after adjusting for vascular risk factors and white matter lesions, basal ganglia-enlarged perivascular spaces were associated with increasing age (P = 0·001), centrum semiovale-enlarged perivascular spaces (P < 0·001), cerebral atrophy (P = 0·03), and lacunar stroke subtype (P = 0·04). Centrum semiovale- enlarged perivascular spaces were associated mainly with basal ganglia-enlarged perivascular spaces. Total enlarged perivascular spaces were associated with increasing age (P = 0·01), deep white matter lesions (P = 0·005), and previous stroke (P = 0·006). Conclusions Enlarged perivascular spaces are associated with age, lacunar stroke subtype and white matter lesions and should be considered as another magnetic resonance imaging marker of cerebral small vessel disease. Further evaluation of enlarged perivascular spaces in studies of ageing, stroke, and dementia is needed to determine their pathophysiological importance.

Counting Cavitating Lacunes Underestimates the Burden of Lacunar Infarction

Background and Purpose— On brain imaging, lacunes, or cerebrospinal fluid–containing cavities, are common and are often counted in epidemiological studies as old lacunar infarcts. The proportion of symptomatic lacunar infarcts that progress to lacunes is unknown. Noncavitating lacunar infarcts may continue to resemble white matter lesions. Methods— We identified patients with acute lacunar stroke, with or without an acute lacunar infarct on computed tomography or MRI, who had follow-up imaging. A neuroradiologist classified lacunar infarcts progressing to definite or possible cavities on follow-up imaging. We tested associations between cavitation and patient-related, stroke-related, and imaging-related features, including other features of small vessel disease. Results— Among 90 patients (mean age 67 years), any cavitation was present on follow-up imaging in 25 (28%), and definite cavitation in 18 (20%). Definite cavitation was associated with increasing time to follow-up imaging (median 228 days, range 54 to 1722, versus no cavitation 72 days, range 6 to 1440; P=0.0003) and deep cerebral atrophy (P=0.03) but not with age, stroke severity, larger initial infarct size, or other features of small vessel disease. Hypertension and diabetes were negatively associated with cavitation (P=0.01 and 0.02, respectively). Conclusions— Definite cavitation occurs in one fifth of symptomatic lacunar ischemic strokes, implying that most continue to resemble white matter lesions. Epidemiology and pathophysiology studies of lacunar stroke, which have only counted lacunes as lacunar infarcts, may have substantially underestimated by as much as 5 times the true burden of lacunar stroke disease.

Blood–Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

Background and Purpose— Increased blood–brain barrier (BBB) permeability occurs in cerebral small vessel disease. It is not known if BBB changes predate progression of small vessel disease. Methods— We followed-up patients with nondisabling lacunar or cortical stroke and BBB permeability magnetic resonance imaging after their original stroke. Approximately 3 years later, we assessed functional outcome (Oxford Handicap Score, poor outcome defined as 3–6), recurrent neurological events, and white matter hyperintensity (WMH) progression on magnetic resonance imaging. Results— Among 70 patients with mean age of 68 (SD±11) years, median time to clinical follow-up was 39 months (interquartile range, 30–45) and median Oxford Handicap Score was 2 (interquartile range, 1–3); poor functional outcome was associated with higher baseline WMH score (P<0.001) and increased basal ganglia BBB permeability (P=0.046). Among 48 patients with follow-up magnetic resonance imaging, WMH progression at follow-up was associated with baseline WMH (ANCOVA P<0.0001) and age (ANCOVA P=0.032). Conclusions— Further long-term studies to evaluate the role of BBB dysfunction in progression of small vessel disease are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age.

Diffusion-weighted imaging and diagnosis of transient ischemic attack.

Magnetic resonance (MR) diffusion‐weighted imaging (DWI) is sensitive to small acute ischemic lesions and might help diagnose transient ischemic attack (TIA). Reclassification of patients with TIA and a DWI lesion as “stroke” is under consideration. We assessed DWI positivity in TIA and implications for reclassification as stroke.

Changes in NAA and lactate following ischemic stroke A serial MR spectroscopic imaging study

Objective: Although much tissue damage may occur within the first few hours of ischemic stroke, the duration of tissue injury is not well defined. We assessed the temporal pattern of neuronal loss and ischemia after ischemic stroke using magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). Methods: We measured N-acetylaspartate (NAA) and lactate in 51 patients with acute ischemic stroke at five time points, from admission to 3 months, in voxels classified as normal, possibly or definitely abnormal (ischemic) according to the appearance of the stroke lesion on the admission DWI. We compared changes in NAA and lactate in different voxel classes using linear mixed models. Results: NAA was significantly reduced from admission in definitely and possibly abnormal (p < 0.01) compared to contralateral normal voxels, reaching a nadir by 2 weeks and remaining reduced at 3 months. Lactate was significantly increased in definitely and possibly abnormal voxels (p < 0.01) during the first 5 days, falling to normal at 2 weeks, rising again later in these voxels. Conclusion: The progressive fall in N-acetylaspartate suggests that some additional neuronal death may continue beyond the first few hours for up to 2 weeks or longer. The mechanism is unclear but, if correct, then it is possible that interventions to limit this ongoing subacute tissue damage might add to the benefit of hyperacute treatment, making further improvements in outcome possible. DT-MRI = diffusion tensor MRI; DWI = diffusion-weighted imaging; [DWI] = directionally averaged DWI; FOV = field of view; MRSI = magnetic resonance spectroscopic imaging; MS = multiple sclerosis; NAA = N-acetylaspartate; NIHSS = NIH Stroke Scale; PRESS = point resolved spectroscopy; TE = echo time; VOI = volume of interest.

Changes in Background Blood–Brain Barrier Integrity Between Lacunar and Cortical Ischemic Stroke Subtypes

Background and Purpose— Lacunar stroke is associated with endothelial dysfunction and histologically with intrinsic cerebral microvascular disease of unknown cause. Endothelial dysfunction could impair blood–brain barrier integrity. We assessed background blood–brain barrier leakage in patients with lacunar ischemic stroke compared with cortical stroke controls. Methods— We recruited patients with lacunar or mild cortical ischemic stroke and assessed generalized cerebral blood–brain barrier leak with MRI and intravenous gadolinium at least 1 month after stroke. We used detailed image processing to compare signal change before and for 30 minutes postcontrast throughout gray matter, white matter, and cerebrospinal fluid with summary analyses and general linear modeling. Results— Among 48 patients (29 lacunar, 19 cortical), postcontrast enhancement was significantly higher in cerebrospinal fluid (P=0.04, Mann-Whitney U), and nonsignificantly higher in white matter, in lacunar than in cortical strokes, with no difference in gray matter. General linear modeling confirmed significantly greater postcontrast enhancement in cerebrospinal fluid in lacunar patients than in cortical controls (t=3.37, P<0.0008). Conclusion— These preliminary data suggest that the blood–brain barrier may be dysfunctional throughout subcortical white matter (white matter drains via interstitial spaces to cerebrospinal fluid) in patients with lacunar stroke. Further studies are required to confirm these findings and determine whether abnormal blood–brain barrier might predate development of lacunar disease. Blood–brain barrier dysfunction may be an important mechanism for brain damage in cerebral microvascular disease.