Computed Tomography--Verified Leukoaraiosis Is a Risk Factor for Post-thrombolytic Hemorrhage.
BACKGROUND
Is computed tomography (CT)-verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage?


METHODS
(1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (tPA)-treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were excluded. (2) Pooled analysis with 1312 tPA-treated patients from literature.


RESULTS
In all, 311 tPA-treated patients were included between April 2009 and July 2012. LA was present in 113 (36%). Twenty-three (7%) showed hemorrhagic transformation. LA positive patients had significantly higher hemorrhagic transformation frequency (11.5%, P = .04). LA doubled hemorrhagic transformation risk (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-5.8). Only 4 patients developed symptomatic intracerebral hemorrhage, 3 with LA. LA was not an independent risk factor for hemorrhagic transformation (P = .2). Pooled analysis of 1623 patients in total, hereof 479 LA positive patients, showed significantly higher symptomatic intracerebral hemorrhage frequency in 35 (7.3%) LA positive than that in 44 (3.8%) LA negative patients, (P = .005) and doubled symptomatic intracerebral hemorrhage risk in LA positives (OR, 1.97; 95% CI 1.22-3.19).


CONCLUSIONS
LA doubles the risk of post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage; this finding does not support withholding thrombolysis from patients with LA.
Department of Neurology, Copenhagen University Hospital, Bispebjerg, Denmark.
Lasse
L
Willer
Department of Radiology, Copenhagen University Hospital, Bispebjerg, Denmark. Electronic address: seestein@gmail.com.
Inger
I
Havsteen
Department of Neurology, Copenhagen University Hospital, Bispebjerg, Denmark.
Christian
C
Ovesen
Department of Radiology, Copenhagen University Hospital, Bispebjerg, Denmark.
Anders F
AF
Christensen
Department of Neurology, Copenhagen University Hospital, Bispebjerg, Denmark.
Hanne
H
Christensen
D000368:Aged; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D020300:Intracranial Hemorrhages / Q000209:etiology*; D049292:Leukoaraiosis / Q000150:complications / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
Leukoaraiosis; brain hemorrhage; computed tomography; thrombolytic therapy