Suresh Subramaniam

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study

BACKGROUND In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. METHODS PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. FINDINGS We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47–73) for the positive predictive value and 78% (71–84) for the negative predictive value, with 51% (39–63) sensitivity and 85% (78–90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). INTERPRETATION These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. FUNDING Canadian Stroke Consortium and NovoNordisk Canada.

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.

Incidence of radiocontrast nephropathy in patients undergoing acute stroke computed tomography angiography

Background and Purpose— Minimal research has evaluated the renal safety of emergent computed tomography angiography (CTA) procedures, consecutive contrast medium application, and the long-term outcome in acute stroke patients. We investigated the incidence of contrast-induced renal impairment in these populations. Methods— We retrospectively reviewed patients with acute stroke syndrome who received a CTA of the brain with or without the neck within 24 hours from onset of symptoms. All creatinine results and additional conventional angiography findings were recorded. With a positive history of renal disease, contrast administration was delayed until creatinine results were available. Radiocontrast nephropathy (RCN) was defined as a ≥25% increase in serum creatinine from the baseline value up to 5 days after CTA. Results— Four hundred eighty-one patients were reviewed, and 224 met the inclusion criteria. There were 7 of 224 (3%) who fulfilled the criteria for RCN. A number of patients underwent emergent CTA without knowledge of their creatinine value; 2 of 93 (2%) developed RCN. There were 36 patients who received an additional digital subtraction angiogram, and none of these developed subsequent RCN. No patients required dialysis, and 9 of 68 (13%) had a >25% increase in their creatinine levels at a late (>30 days) follow-up. Conclusions— Overall, these results illustrate that there is a low incidence of RCN in acute stroke patients undergoing emergency CTA.

Cerebral Microhemorrhages Predict New Disabling or Fatal Strokes in Patients With Acute Ischemic Stroke or Transient Ischemic Attack

Background and Purpose— Cerebral microhemorrhages (MHs) are common among patients presenting with acute ischemic stroke and may predict both subsequent ischemic and hemorrhagic strokes. Methods— We prospectively studied patients with and without MHs presenting within 12 hours of their ischemic stroke or transient ischemic attack (TIA). A magnetic resonance (MR) scan was performed within 24 hours of symptom(s) onset. The primary outcome was disabling or fatal stroke at 18 months. Results— An MR scan was done in 236 patients with acute ischemic stroke or TIA. Forty-five (19.1%) patients had an MH on a baseline MR scan. Patients with MHs were 2.8× (10.8% versus 4.0%; P=0.036) more likely to have a subsequent disabling or fatal stroke than patients without an MH. The risk of symptomatic intracerebral hemorrhage was not statistically significant among MH and non-MH patients (3.3% versus 0.8%; P=0.31). Conclusions— The presence of cerebral MH(s) in patients with acute ischemic stroke or TIA predicts recurrent disabling and fatal strokes. This risk is mainly assumed by recurrent ischemic strokes.

An improved scoring system for identifying patients at high early risk of stroke and functional impairment after an acute transient ischemic attack or minor stroke

Background Risk of a subsequent stroke following an acute transient ischemic attack (TIA) or minor stroke is high. The ABCD2 tool was proposed as a method to triage these patients using five clinical factors. Modern imaging of the brain was not included. The present study quantified the added value of magnetic resonance imaging (MRI) factors to the ABCD2 tool. Methods Patients with TIA or minor stroke were examined within 12 h and had a brain MRI within 24 h of symptom onset. Primary outcomes were recurrent stroke and functional impairment at 90 days. A new tool, ABCD2+ MRI, was created by adding diffusion-weighted imaging lesion and vessel occlusion status to the ABCD2 tool. The predictive accuracy of both tools was quantified by the area under the curve (AUC). Results One hundred and eighty patients were enrolled and 11·1% had a recurrent stroke within 90 days. The predictive accuracy of the ABCD2+MRI was significantly higher than ABCD2 (AUC of 0·88 vs. 0·78, P = 0·01). Those with a high score (7–9) had a 90-day recurrent stroke risk of 32·1%, moderate score (5–6) risk of 5·4%, and low score (0-4) risk of 0·0%. The ABCD2 tool did not predict risk of functional impairment at 90 days (P = 0·33), unlike the ABCD2+MRI (P = 0·02): high score (22·9%), moderate (7·5%), low (7·7%). Conclusions Risk of recurrent stroke and functional impairment after a TIA or minor stroke can be accurately predicted by a scoring system that utilizes both clinical and MRI information. The ABCD2+MRI score is simple and its components are commonly available during the time of admission.

Recurrent events in transient ischemic attack and minor stroke: what events are happening and to which patients?

Background and Purpose— The risk of a recurrent stroke after transient ischemic attack (TIA) or minor stroke is high. Clinical trials are needed to assess acute treatment options in these patients. We sought to evaluate the type of recurrent events and to identify which subsets of patients are at risk for recurrent events. Methods— One hundred and eighty patients with TIA or minor stroke were examined within 12 hours and underwent brain MRI within 24 hours. Any neurological deterioration was recorded, and a combination of clinical and MRI factors were used to create a combined event classification. Subgroups of patients analyzed included classical TIA, patients with NIHSS=0, and patients with NIHSS >0 in ED. Results— Overall there were 38 events in 36 patients (20% event rate); 20 were symptomatic and 18 were silent (only evident because of the follow up MRI). 18/20 (90%) symptomatic events were associated with progression of presenting symptoms, compared to 2/20 (10%) with a clear recurrent stroke distinct from the original event. We found a low risk of recurrent stroke among classical definition TIA patients (1.1%). Patients with an NIHSS=0 in the ED, had an intermediate event rate (6.6%) between TIA (classical – 1.1%) and NIHSS >0 (14.4%; &khgr;2 test for trend, P=0.02). All clinical categories of patient (TIA, stroke, NIHSS=0) accumulated silent lesions on MRI. Conclusions— Most events were classified as stroke progression or infarct growth rather than a recurrent stroke. A low risk of recurrence was found in patients with classical TIA and those with no neurological deficits on initial assessment.

Acute ischemic lesions of varying ages predict risk of ischemic events in stroke/TIA patients

Background: Multiple ischemic lesions identified by diffusion-weighted imaging (DWI) have been shown to predict high risk of future ischemic events. However, the importance of lesion age has not been factored into this risk. Our goal was to evaluate whether the presence of ischemic lesions of varying ages identified by DWI and apparent diffusion coefficient (ADC) suggests a higher risk of future ischemic events. Methods: Patients with acute stroke and TIA presenting within 12 hours of symptom onset who had a baseline and 1-month follow-up MRI were enrolled in the study. Acute ischemic lesions were divided into DWI positive with ADC low lesions and DWI positive with ADC normalized lesions. The baseline MRI and the presence of new lesions on the follow-up MRI were analyzed. Results: A total of 360 patients were prospectively enrolled, and all had appropriate imaging. Two hundred twenty-three were excluded as there were no DWI lesions, they received recombinant tissue plasminogen activator, or they did not have the 30-day follow-up MRI. One hundred seventeen patients had DWI lesions of one age (DWI positive with either ADC low lesions or ADC normalized lesions alone) and 20 had lesions of varying ages (DWI positive lesions with reduced and normalized ADC) on the baseline MRI. Patients with multiple DWI lesions of varying ages were at more risk of having new lesions on the 30-day MRI compared with those having lesions of the same age (relative risk = 3.6; 95% CI 1.9 to 6.8). Multiple DWI lesions of varying ages (odds ratio [OR] 6.6; 95% CI 2.3 to 19.1) and cardioembolic stroke subtype (OR 3.2; 95% CI 1.1 to 8.7) were independently associated with new lesion recurrence by multiple logistic regression analysis. Conclusion: The presence of multiple diffusion-weighted imaging lesions of varying ages suggests very active early recurrence over time and portends a higher early risk of future ischemic events.

Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion

Background and Purpose— Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK–tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. Methods— TNK–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK–tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ⩽5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0–1). Results— Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01–20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0–1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0–1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09–2.5; P=0.026). Conclusions— Administration of TNK–tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654445.

Diffusion-weighted imaging-negative patients with transient ischemic attack are at risk of recurrent transient events.

Background and Purpose— Among patients presenting with a transient ischemic attack (TIA), some clinical features predispose to recurrent TIA, whereas others predispose to subsequent strokes. We assessed the implication of negative diffusion-weighted imaging on a baseline MRI in predicting subsequent TIA. Methods— We prospectively studied patients presenting in the emergency department within 12 hours of a TIA (motor or speech). All patients had a MRI within 24 hours of the index event. The primary outcome was TIA within 1 year of study entry. The 1-year risk of stroke was also evaluated. Results— A total of 85 patients had a MRI, among which 35 patients (41.2%) had a diffusion-weighted imaging lesion. The mean time from symptom onset to MRI was 12.1 hours. Patients without a diffusion-weighted imaging lesion on baseline MRI were 4.6 times (27.4% versus 5.9%; P<0.05) more likely to have a subsequent TIA at 1 year than patients with a diffusion-weighted imaging lesion, but 4.3 times (2.1% versus 9.1%; P=0.19) less likely to have a subsequent stroke. Conclusions— The absence of a diffusion-weighted imaging lesion on the baseline scan predicts recurrent transient events rather than stroke.

Cerebral microhemorrhages in a patient with mycotic aneurysm: relevance of T2-GRE imaging in SBE.

A 43-year-old man presented with sudden onset left hemicranial headache and right superior quadrantanopia after 5 weeks of treatment with antibiotics for subacute bacterial endocarditis (SBE). Head CT (figure, A) showed left occipital …