Kirsten Shuler

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.

A Systematic Review of Dynamic Cerebral and Peripheral Endothelial Function in Lacunar Stroke Versus Controls

Background and Purpose— The etiology of cerebral small vessel disease is unknown. An association with endothelial dysfunction has been suggested. We systematically assessed all relevant studies of dynamic endothelial function in patients with lacunar stroke as a marker of small vessel disease. Methods— We searched for studies of cerebral or peripheral vascular reactivity in patients with lacunar or cortical (ie, large artery atheromatous) ischemic stroke or nonstroke control subjects. We calculated standardized mean difference (SMD) in vascular reactivity±95% CIs between small vessel disease and control groups. Results— Sixteen publications (974 patients) were included. In lacunar stroke, cerebrovascular reactivity (n=534) was reduced compared with age-matched normal (SMD −0.94, 95% CI −1.17 to −0.70), but not age+risk factor-matched control subjects (SMD 0.08, 95% CI −0.36 to 0.53) or cortical strokes (SMD −0.29, 95% CI −0.69 to 0.11); forearm flow-mediated dilatation (n=401) was reduced compared with age-matched normal control subjects (SMD −1.04, 95% CI −1.33 to −0.75) and age+risk factor-matched control subjects (SMD −0.94, 95% CI −1.26 to −0.61), but not cortical strokes (SMD −0.23, 95% CI −0.55 to 0.08). Conclusions— Endothelial dysfunction is present in patients with lacunar stroke but may simply reflect exposure to vascular risk factors and having a stroke, because a similar degree of dysfunction is found in cortical (large artery atheromatous) stroke. Current data do not confirm that endothelial dysfunction is specific to small vessel stroke. Future studies should include control subjects with nonlacunar stroke.

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.

ABCD2 score and secondary stroke prevention Meta-analysis and effect per 1,000 patients triaged

Objective: Patients with TIA have high risk of recurrent stroke and require rapid assessment and treatment. The ABCD2 clinical risk prediction score is recommended for patient triage by stroke risk, but its ability to stratify by known risk factors and effect on clinic workload are unknown. Methods: We performed a systematic review and meta-analysis of all studies published between January 2005 and September 2014 that reported proportions of true TIA/minor stroke or mimics, risk factors, and recurrent stroke rates, dichotomized to ABCD2 score </≥4. We calculated the effect per 1,000 patients triaged on stroke prevention services. Results: Twenty-nine studies, 13,766 TIA patients (range 69–1,679), were relevant: 48% calculated the ABCD2 score retrospectively; few reported on the ABCD2 scores ability to identify TIA mimics or use by nonspecialists. Meta-analysis showed that ABCD2 ≥4 was sensitive (86.7%, 95% confidence interval [CI] 81.4%–90.7%) but not specific (35.4%, 95% CI 33.3%–37.6%) for recurrent stroke within 7 days. Additionally, 20% of patients with ABCD2 <4 had >50% carotid stenosis or atrial fibrillation (AF); 35%–41% of TIA mimics, and 66% of true TIAs, had ABCD2 score ≥4. Among 1,000 patients attending stroke prevention services, including the 45% with mimics, 52% of patients would have an ABCD2 score ≥4. Conclusion: The ABCD2 score does not reliably discriminate those at low and high risk of early recurrent stroke, identify patients with carotid stenosis or AF needing urgent intervention, or streamline clinic workload. Stroke prevention services need adequate capacity for prompt specialist clinical assessment of all suspected TIA patients for correct patient management.

Systematic Review of Perfusion Imaging With Computed Tomography and Magnetic Resonance in Acute Ischemic Stroke: Heterogeneity of Acquisition and Postprocessing Parameters A Translational Medicine Research Collaboration Multicentre Acute Stroke Imaging Study

Background and Purpose— Heterogeneity of acquisition and postprocessing parameters for magnetic resonance– and computed tomography–based perfusion imaging in acute stroke may limit comparisons between studies, but the current degree of heterogeneity in the literature has not been precisely defined. Methods— We examined articles published before August 30, 2009 that reported perfusion thresholds, average lesion perfusion values, or correlations of perfusion deficit volumes from acute stroke patients <24 hours postictus. We compared acquisition parameters from published studies with guidance from the Acute Stroke Imaging Research Roadmap1. In addition, we assessed the consistency of postprocessing parameters. Results— Twenty computed tomography perfusion and 49 perfusion-weighted imaging studies were included from 7152 articles. Although certain parameters were reported frequently, consistently, and in line with the Roadmap proposals, we found substantial heterogeneity in other parameters, and there was considerable variation and underreporting of postprocessing methodology. Conclusions— There is substantial scope to increase homogeneity in future studies, eg, through reporting standards.

Little Association between Intracranial Arterial Stenosis and Lacunar Stroke

Atheromatous middle cerebral artery (MCA) stenosis could cause lacunar stroke by occluding lenticulostriate artery origins, but atheroma is common, and previous studies lacked suitable controls. We aimed to determine if intracranial atheroma was more common in lacunar than in cortical ischaemic stroke. We recruited patients with lacunar stroke and controls with mild cortical stroke, confirmed the stroke subtype with magnetic resonance imaging and used transcranial Doppler ultrasound imaging to record flow velocity and focal stenoses in the basal intracranial arteries 1 month after stroke. We compared ipsi- and contralateral MCA mean flow velocities between stroke subtypes and tested for associations using linear mixed models. Amongst 67 lacunar and 67 mild cortical strokes, mean age 64 and 67 years, respectively, we found no difference in MCA mean flow velocity between cortical and lacunar patients. Increasing age and white matter lesion scores were independently associated with lower MCA flow velocities (0.2 cms–1 fall in velocity per year increase in age, p = 0.045; 3.75 cms–1 fall in flow velocity per point increase in white matter lesion score, p = 0.004). We found no intracranial arterial stenoses. MCA atheromatous stenosis is unlikely to be a common cause of lacunar stroke in white populations. Falling velocities with increasing white matter lesion scores may reflect progressive brain tissue loss leaving less tissue to supply.

Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood–brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3–90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities (P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age (P < 0.001), all biomarkers varied with white matter hyperintensities burden (P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension (P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood–brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood–brain barrier leakage mediates small vessel disease-related brain damage.

Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke

Cerebral small vessel disease (SVD) is common in ageing and patients with dementia and stroke. Its manifestations on magnetic resonance imaging (MRI) include white matter hyperintensities, lacunes, microbleeds, perivascular spaces, small subcortical infarcts, and brain atrophy. Many studies focus only on one of these manifestations. A protocol for the differential assessment of all these features is, therefore, needed.

Acute symptomatic hypoglycaemia mimicking ischaemic stroke on imaging: a systemic review

BackgroundAcute symptomatic hypoglycaemia is a differential diagnosis in patients presenting with stroke-like neurological impairment, but few textbooks describe the full brain imaging appearances. We systematically reviewed the literature to identify how often hypoglycaemia may mimic ischaemic stroke on imaging, common patterns and relationships with hypoglycaemia severity, duration, clinical outcome and add two new cases.MethodsWe searched EMBASE and Medline databases for papers reporting imaging in adults with symptomatic hypoglycaemia. We analysed the clinical presentation, outcome, brain imaging findings, duration and severity of hypoglycaemia, time course of lesion appearance, including two new cases.ResultsWe found 42 papers describing computed tomography or magnetic resonance imaging in 65 patients, plus our two cases with symptomatic hypoglycaemia. Imaging abnormalities on computed tomography and magnetic resonance were uni or bilateral, cortical or sub-cortical. Thirteen (20%) mimicked cortical or lacunar stroke. Acute lesions had restricted diffusion on magnetic resonance or low attenuation on computed tomography, plus swelling; older lesions showed focal atrophy or disappeared, as with ischaemic stroke. The association between the depth or duration of hypoglycaemia, the severity or extent of neurological deficit, and the imaging abnormalities, was weak.ConclusionImaging abnormalities in patients with hypoglycaemia are uncommon but very variable, weakly associated with neurological deficit, and about a fifth mimic acute ischaemic stroke. Blood glucose testing should be routine in all patients with acute neurological impairment and hypoglycaemia should be included in the differential diagnosis of imaging appearances in patients presenting with acute stroke.