Mark E. Hudon

Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging.

Background and objectives: Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. Methods: Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. Results: bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p<0.001). The level of interrater agreement ranged from good to excellent across all modalities and time periods. Bland–Altman plots showed more variability between bCT and bDWI than at 24 hours. The difference between bCT and bDWI was ⩽2 ASPECTS points. Of bCT scans with ASPECTS 8–10, 81% had DWI ASPECTS 8–10. Patients with bCT ASPECTS of 8–10 were 1.9 times more likely to have a favourable outcome at 90 days than those with a score of 0–7 (95% CI 1.1 to 3.1, p = 0.002). The relative likelihood of favourable outcome with a bDWI ASPECTS 8–10 was 1.4 (95% CI 1.0 to 1.9, p = 0.10). Of patients receiving tPA 45% had contraindications to urgent MRI. Conclusion: The differences between CT and DWI in visualising early infarction are small when using ASPECTS. CT is faster and more accessible than MRI, and therefore is the better neuroimaging modality for the treatment of acute stroke.

Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score.

Background In ischemic stroke, functional outcomes vary depending on site of intracranial occlusion. We tested the prognostic value of a semiquantitative computed tomography angiography-based clot burden score. Methods Clot burden score allots major anterior circulation arteries 10 points for presence of contrast opacification on computed tomography angiography. Two points each are subtracted for thrombus preventing contrast opacification in the proximal M1, distal M1 or supraclinoid internal carotid artery and one point each for M2 branches, A1 and infraclinoid internal carotid artery. We retrospectively studied patients with disabling neurological deficits (National Institute of Health Stroke Scale score ≥ 5) and computed tomography angiography within 24-hours from symptom onset. We analyzed percentages independent functional outcome (modified Rankin Scale score ≤ 2), final infarct Alberta Stroke Program Early Computed Tomography Score and parenchymal hematoma rates across categorized clot burden score groups and performed multivariable analysis. Results We identified 263 patients (median age 73-years, National Institute of Health Stroke Scale score 10, onset-to-computed tomography angiography time 165 min). Clot burden score < 10 was associated with reduced odds of independent functional outcome (odds ratio 0.09 for clot burden score ≤5; odds ratio 0.22 for clot burden score 6–7; odds ratio 0.48 for clot burden score 8–9; all versus clot burden score 10; P <0.02 for all). Lower clot burden scores were associated with lower follow-up Alberta Stroke Program Early CT Scores (P <0.001) and higher parenchymal hematoma rates (P = 0.008). Inter-rater reliability for clot burden score was 0.87 (lower 95% confidence interval 0.71) and intra-rater reliability 0.96 (lower 95% confidence interval 0.92). Conclusion The quantification of intracranial thrombus extent with the clot burden score predicts functional outcome, final infarct size and parenchymal hematoma risk acutely. The score needs external validation and could be useful for patient stratification in stroke trials.

ASPECTS on CTA Source Images Versus Unenhanced CT Added Value in Predicting Final Infarct Extent and Clinical Outcome

Background and Purpose— The Alberta Stroke Program Early CT Score (ASPECTS) is a grading system to assess ischemic changes on CT in acute ischemic stroke. CT angiography–source images (CTA-SI) predict final infarct volume. We examined whether the final infarct ASPECTS and clinical outcome were more related to acute CTA-SI ASPECTS than to the acute noncontrast CT (NCCT) ASPECTS. Methods— ASPECTS was assigned by 2 raters on the acute NCCT, CTA-SI, and follow-up imaging. The mean baseline ASPECTS of acute NCCT and CTA-SI was compared with the follow-up ASPECTS. Rate ratios (RRs) were used to quantify the relationship between the dichotomized baseline ASPECTS (categorized as 0 to 7 versus 8 to 10) and favorable patient outcome. Results— Thirty-nine patients were recruited. Proximal occlusion (internal carotid artery or middle cerebral artery) was seen in 62%, M2 occlusion in 18%, and no occlusion was seen in 20% of patients. The median time between symptom onset and imaging was 1.9 (1.2 to 2.5) hours. There was a significantly larger difference of 1.4 between the mean baseline NCCT and CTA-SI ASPECTS in patients who had more ischemic changes (follow-up ASPECTS=0 to 3) than a difference of 0.6 in patients who had near-to-normal CT scans (follow-up ASPECTS=8 to 10). The rate of favorable outcome for acute NCCT ASPECTS of 8 to 10 was 51.8% versus 25.0% for 0 to 7 (RR, 2.1, 95% CI: 0.7 to 5.9, P=0.12). For acute CTA-SI ASPECTS of 8 to 10, the rate of favorable outcome was 58.8% versus 31.8% for 0 to 7 (RR, 1.8, 95% CI: 0.9 to 3.8, P=0.09). Conclusions— CTA-SI ASPECTS provides added information in the prediction of final infarct size.

Hyperdense Sylvian Fissure MCA “Dot” Sign A CT Marker of Acute Ischemia

Background and Purpose— The hyperdense appearance of the main middle cerebral artery (HMCA) is now a familiar early warning of large cerebral infarction, brain edema, and poor prognosis. This article describes the hyperdensity associated with embolic occlusion of branches of the middle cerebral artery in the sylvian fissure (MCA “dot” sign). We define it and determine its incidence, diagnostic value, and reliability. Methods— CT scans performed on patients with acute ischemic stroke within 3 hours of symptom onset were analyzed for signs of thromboembolic stroke and evidence of early CT ischemia. Two neuroradiologists and 2 stroke neurologists initially blinded to all clinical information and then with knowledge of the affected hemisphere evaluated scans for the presence of the MCA dot sign, the HMCA sign, and early MCA territory ischemic changes. Results— Of 100 consecutive patients who presented within 3 hours of symptom onset, 91 were considered at symptom onset to have anterior circulation stroke syndromes. Early CT ischemia was seen in 74% of these baseline CT scans. The HMCA sign was seen in 5% of CT scans, whereas the MCA dot sign was seen in 16%. All patients then received intravenous tissue plasminogen activator. All 5 patients with an HMCA sign, including 2 with an associated MCA dot sign, were either dead or dependent at 3 months. The 14 patients with an MCA dot sign alone were independent at 3 months in 64% of cases, compared with 50% without the sign (Fisher’s exact test P =0.79). Balanced &kgr; statistics for both the HMCA and the MCA dot sign were in the moderate to good range when the stroke symptom side was given. Conclusions— The MCA dot sign is an early marker of thromboembolic occlusion of the distal MCA branches seen in the sylvian fissure and is associated with better outcome than the HMCA sign.

Reliability of Assessing Percentage of Diffusion-Perfusion Mismatch

Background and Purpose— Emergent neurovascular imaging holds promise in identifying new and optimum target populations for thrombolysis in stroke. Recent research has focused on patients with diffusion-weighted MRI (DWI)-perfusion-weighted MRI (PWI) mismatch as a marker of tissue at risk of infarction and a means to select the most suitable candidates for thrombolysis. The present study sought to estimate the reliability of assessing the percentage of DWI-PWI mismatch. Methods— Thirteen patients with acute strokes had DWI and PWI within 7 hours of symptom onset. Six raters independently created relative mean transit time (rMTT) maps and then compared them with DWI images to assess the percentage of mismatch (PWI>DWI) in 10% increments. The MR scans were reassessed by 4 raters, tracing around the lesions to calculate the volume percentage of mismatch. Results— Visual assessment had an interrater reliability of 0.68 (95% CI, 0.52 to 1.0; SEM=21.6%) and an intrarater reliability of 0.80 (95% CI, 0.47 to 1.0; SEM=16.9%). Hand-drawn assessment had an interrater reliability of 0.66 (95% CI, 0.45 to 1.0; SEM=26.2%) and an intrarater reliability of 0.94 (95% CI, 0.81 to 1.0; SEM=10.9%). Conclusions— Results from the present study suggest that quantifying mismatch by the human eye is reproducible but not reliable among observers. This raises doubts about using mismatch for clinical decision making and clinical trial enrollment.

MR angiography compared to conventional selective angiography in acute stroke.

BACKGROUND AND PURPOSE Accuracy of intracranial magnetic resonance angiography (MRA) and reliability of interpretation are not well established compared to conventional selective catheter angiography. The purpose of this study was to determine the accuracy of MRA in evaluation of intracranial vessels in acute stroke and transient ischemic attack (TIA) patients METHODS Twenty-nine patients (seven females, 22 males; median age 53) with acute stroke or TIA were enrolled into the study. All patients underwent both MRA using a 3 T clinical magnet and conventional angiography within 48 hours. Median time between MRA and angiography was 263 minutes. Conventional angiography preceded MRA in 15 cases. Fourteen patients received thrombolysis during MRA or angiography. National Institutes of Health Stroke Scale scores were obtained prior to the MR exam. One neuroradiologist rated all conventional angiograms, which were used as gold standard. Five observers, blinded to conventional angiography results and all clinical information except symptom side, rated the MR angiograms. Kappa statistics were used to assess reliability; contingency tables were used to assess accuracy of non-enhanced and enhanced MRA. RESULTS Two hundred and fifty two intracranial vessels were assessed. Agreement between raters was good for both non-enhanced (kappa = 0.50) and gadolinium-enhanced (kappa = 0.46) images. There were a total of 26 vessels occluded by DSA. Overall, the non-enhanced MRA showed sensitivity of 84.2% (95% CI 60.4-96.6) and specificity of 84.6% (95% CI 78.6-89.4). The enhanced MRA showed sensitivity of 69.2 (95% CI 38.6-90.9) and specificity of 73.6 (95% CI 65.5-80.7). CONCLUSIONS Magnetic resonance angiography is a good non-invasive screening tool for assessing intracranial vessel status in acute ischemic stroke. Angiography remains the gold standard for definitive assessment of the intracranial circulation.

The probability of middle cerebral artery MRA flow signal abnormality with quantified CT ischaemic change: targets for future therapeutic studies

Objectives: In this study we define the probability of vascular abnormality in the middle cerebral artery (MCA) territory according to the extent of ischaemic change seen using computed tomography (CT). We assessed the sensitivity and specificity of the hyperdense middle cerebral artery (HMCA) and the “dot” sign using magnetic resonance angiography (MRA). Methods: Patients presenting with ischaemic stroke had a CT scan (<6 h) prior to MRI (<7 h). A quantitative CT scoring system (ASPECTS) was applied to CT and diffusion weighted images (DWI) at baseline and follow up (24 h) by five independent observers. The presence of HMCA and the MCA “dot” sign was also evaluated. An expert reader assessed the 3D time of flight (TOF) MRA in the anterior circulation for areas of decreased vascular signal in the MCA territory, with an absent signal taken to represent severely reduced or absent flow. Results: A total of 100 consecutive patients had baseline CT and MR scans. The median NIHSS was 9. The median CT ASPECTS was 8 and equalled the median DWI ASPECTS. There were a total of 10 HMCA and 19 MCA “dot” signs, with four patients having both HMCA and “dot” signs. A total of 47 MRA flow signal abnormalities were observed in the anterior circulation. Conclusions: In the absence of accessible neurovascular imaging, the extent of CT ischaemia (ASPECTS) is a strong predictor of vascular occlusion. The CT hyperdense artery signs have a high positive predictive value but low negative predictive value.

Thunderclap headache and reversible segmental cerebral vasoconstriction associated with use of oxymetazoline nasal spray

OXYMETAZOLINE IS A SYMPATHOMIMETIC amine found in over-the-counter nasal decongestants. We report a case of chronic use of nasal oxymetazoline associated with thunderclap headache due to reversible segmental intracranial vasoconstriction.

Mild Neurological Symptoms Despite Middle Cerebral Artery Occlusion

Background and Purpose— Only a small percentage of stroke patients are treated with thrombolytic therapy. We sought to determine whether vessel occlusion in mild strokes represented a new target population for interventional therapy. Methods— We imaged 106 acute stroke patients with MRI. Patients were identified with evidence of middle cerebral artery (MCA) occlusion and mild or no stroke signs (National Institutes of Health Stroke Scale [NIHSS] ≤3). They were compared with patients with signs of stroke, NIHSS >3, and MCA occlusion. Results— We identified 5 patients with absent flow on MRA in the MCA and mild or no stroke signs (NIHSS ≤3). All 5 were functionally independent at 3 months. Conclusions— Caution should be exercised in considering thrombolytic therapy in these patients. Quantification of perfusion imaging is required to identify “at risk” mild stroke populations.

Combined full‐dose IV and endovascular thrombolysis in acute ischaemic stroke

Background There is an increasing trend to treating proximal vessel occlusions with intravenous–inter-arterial (IV-IA) thrombolysis. The best dose of IV tissue plasminogen activator (tPA) remains undetermined. We compared the combination of full-dose IV recombinant tissue plasminogen activator (rtPA) and IA thrombolytic therapy to IA therapy. Methods Between 2002 and 2009, we reviewed our computed tomographic angiography database for patients who received full-dose intravenous rtPA and endovascular therapy or endovascular therapy alone for acute ischaemic stroke treatment. Details of demographics, risk factors, endovascular procedure, and symptomatic intracranial haemorrhage were noted. Modified Rankin Scale ≤2 at three-months was used as good outcome. Recanalization was defined as Thrombolysis in Myocardial Ischaemia 2–3 flow on angiography. Results Among 157 patients, 104 patients received IV-IA treatment and 53 patients underwent direct IA therapy. There was a higher recanalization rate with IV-IA therapy compared with IA alone (71% vs. 60%, P < 0·21) which was driven by early recanalization after IV rtPA. Mortality and independent outcome were comparable between the two groups. Symptomatic intracranial haemorrhage occurred in 8% of patients (12% in the IA group, 7% in the IV-IA group) but was more frequent as the intensity of intervention increased from device alone to thrombolytic drug alone to device plus thrombolytic drug(s). Recanalization was a strong predictor of reduced mortality risk ratio (RR) 0·48 confidence interval95 0·27–0·84) and favourable outcome (RR 2·14 confidence interval95 1·3–3·5). Conclusions Combined IV-IA therapy with full-dose intravenous rtPA was safe and results in good recanalization rates without excess symptomatic intracranial haemorrhage. Testing of full-dose IV tPA followed by endovascular treatment in the IMS3 trial is justified.