Hemorrhagic Risk of Recent Silent Cerebral Infarct on Prethrombolysis MR Imaging in Acute Stroke

Clinical Data and Study Design

We performed a retrospective analysis of prospectively collected data in all patients with acute IS treated with intravenous or intra-arterial rtPA between January 2007 and December 2008 in our academic stroke center. Patients with a pretreatment cranial CT only or pretreatment MR imaging with the absence of 1 of the required sequences were excluded. A total of 93 patients were treated with rtPA during the study period. Of these, 7 (8%) were excluded because pretreatment imaging was a CT scan (n = 6) or an incomplete MR imaging (n = 1), thus limiting the study to 86 patients. We systematically recorded and retrieved the following data: age, sex, NIHSS score on admission, blood test results on admission (including platelet count <100 × 10³/mm³, blood glucose level of >200 mg/dL, partial thromboplastin time, prothrombin time, and blood creatinine level), symptom-to-needle time, blood pressure at presentation (systolic and diastolic), and intravenous or intra-arterial rtPA administration and a history of high blood pressure, smoking, diabetes mellitus, left cardiac dysfunction, coronaropathy, atrial fibrillation, previous stroke, and thrombophilia status. We also assessed the history of minor IS or TIA in the 3 months preceding the acute IS.

Thrombolysis Procedure

Patients with IS were considered for thrombolysis according to local protocol derived from current guidelines and recent evidence-based data. Intravenous thrombolysis with rtPA (full dose, 0.9 mg/kg) was considered for patients within 4.5 hours of symptom onset; intra-arterial thrombolysis with rtPA (dose ranging from 20 to 50 mg), whether associated with intra-arterial mechanical thrombectomy or not, was considered between 4.5 and 6 hours postonset or when intravenous rtPA was contraindicated for anterior circulation stroke with large-vessel occlusion and within 24 hours of symptom onset in patients with posterior circulation stroke with basilar artery occlusion. A CT scan was performed 1 day after thrombolysis (<36 hours after rtPA administration) in all patients, with ≥1 further CT or MR imaging, including T2*-weighted imaging, performed during the hospital stay when required to assess HT.

Imaging Protocol and Interpretation

During the study period, multimodal MR imaging was performed in all patients with acute stroke unless contraindicated. MR imaging was the routine imaging technique and was performed on an Intera 1.5T machine (Philips Healthcare, Best, the Netherlands) and included DWI (SE EPI, TR/TE = 4221/81 ms, b=0–1000 s/mm², voxel = 1.8/2.99/5 mm with no gap) with ADC (FLAIR TSE, TR/TE/TI = 6000/120/2000 ms, voxel = 0.9/1.15/5 mm with gap 1 mm), T2WI imaging (TSE, TSE factor = 23, TR/TE = 5600/110 ms, voxel = 0.9/1.14/5 mm), T2*WI imaging (FFE, TR/TE = 653/23 ms, flip angle = 18°, voxel = 1.8/1.8/5 mm), 3D time-of-flight (FFE T1 inflow, TR/TE = 23/2.5 ms, voxel = 0.94/1.05/1.4 mm) with maximum-intensity-projection reconstructions, first-pass gadolinium PWI (3D gradient echo EPI, Preston, Philips Healthcare, TR/TE = 17/25 ms, voxel = 3.59/4.51/5 mm), and pre- and postgadolinium T1WI imaging (SE, TR/TE = 582/15, voxel = 0.94/0.94/5 mm).

Pretreatment MR imaging and follow up CT scans as well as any additional cerebral imaging performed before patient discharge were reviewed by a stroke neurologist (N.G.) and a neuroradiologist (C.S.) independently, blinded to clinical data. RSCI on MR imaging was defined when fulfilling the following criteria: 1) a parenchymal area markedly hyperintense on FLAIR relative to the surrounding tissue and different from the hyperacute infarct, and 2) mildly-to-markedly hyperintense on DWI with high b=1000 relative to surrounding tissue, or 3) enhanced on postgadolinium T1WI. Three RSCI patterns on MR imaging were thus distinguishable, as illustrated by Fig 1. To distinguish RSCI and hyperacute IS, which may appear slightly hyperintense on FLAIR, we only considered RSCI if it was clearly separable from the acute infarct area and more hyperintense on FLAIR, reflecting an older lesion.¹⁴ Small chronic infarcts were distinguished from RSCI and identified as hypointense lesions with a surrounding hyperintense margin on FLAIR,¹⁵ neither enhanced nor appearing brightly hyperintense on DWI. There were no discrepant cases between the 2 readers. ADC maps were reviewed but were not included as a criterion of the RSCI definition, being either decreased in the RSCI within a few days after ischemic injury or normal in RSCI within a few weeks after ischemia, thus providing redundant data compared with DWI b=1000 analysis.

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Fig 1.

Three different patterns of RSCIs defined on MR imaging. A, “Gad+/DWI+” indicates area enhanced on postgadolinium T1WI imaging and in hypersignal intensity on DWI. B, “Gad+/DWI−” is the area enhanced on postgadolinium T1WI imaging but not in hypersignal on DWI. C, “Gad−/DWI+” is the area unenhanced on postgadolinium T1WI but in hypersignal intensity on DWI. GAD indicates gadolinium.

We defined an HT as a hemorrhage occurring within the area of the hyperacute infarct or within an RSCI on any follow-up CT or MR imaging scan before patient discharge. HT was classified according to ECASS imaging criteria as HI-1, HI-2, PH-1, and PH-2.⁴ We defined an EIH as a hemorrhage occurring in a region remote from the visible infarct on pretreatment MR imaging. We defined an SICH, according to ECASS II criteria, as any neurologic deterioration defined as ≥4 points worsening of the NIHSS score or death, associated with HT or EIH on imaging during inpatient follow-up.

Stroke etiology was assigned according to TOAST criteria¹⁶: Patients with middle cerebral artery occlusion and definite ipsilateral carotid atherosclerotic stenosis or occlusion (“tandem occlusion”) only were assigned to large-vessel disease. Basilar artery occlusion was, as well, considered as large-vessel disease when atherosclerotic stenosis was identified on cervical or intracranial vertebral or basilar arteries without another source of embolism.

Statistical Analysis

Data were expressed either as frequency and percentages or as a median and IQR. Comparative analysis was performed by using the 2-sided Fisher exact test or Wilcoxon-Mann-Whitney test. J.P.B. performed statistical analysis with SAS, Version 8.1 (SAS Institute, Cary, North Carolina) with the α level set at 5%.