Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN Score

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Francis Wood
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1 Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN Score Daniel Strbian, MD, PhD Department of Neurology, Helsinki University Hospital Helsinki, Finland Atte Meretoja Satu Mustanoja Tiina Sairanen Nina Forss Markku Kaste Turgut Tatlisumak Basel, Switzerland Stefan Engelter Frank J Ahlhelm Philippe Lyrer Lausanne, Switzerland Patrik Michel Maria Cordier Geneva, Switzerland Lucka Sekoranja Igor Kuzmanovic

2 Outline of the presentation Background information Developing the score The score in the validation cohort Internal cross-validation External validation Comparison with other scores Summary and Implications

3 tpa for ischemic stroke tpa license: 1996 (USA), 1999 (Canada), 2002 (EU): but only a few percent of acute ischemic stroke patients are treated ~ 17% in Helsinki (Kaste M, Stroke 2007) logistic problem: time window fear of the most serious complication: symptomatic intracranial hemorrhage (sich) How many patients will have sich? Number Needed to Harm: 36.5 (fatal outcome) / 29.7 to 40.1 (any worsening, mrs) Saver JL, Stroke 2007 But which patients? prediction scores

4 Developing the score Based on easily assessable variables Applicable on / shortly after admission, prior to administration of iv tpa Helsinki University Central Hospital 1104 consecutive ischemic stroke patients treated with iv tpa ( ) excluded: patients with basilar artery occlusion (n=119): very different protocol the score was tested separately in this cohort excluded: patients that underwent endovascular treatment (n=11): beyond the focus final cohort: 974 patients

5 Developing the score Imaging & Criteria Baseline CT head scan: all patients Follow-up imaging routinely at 24 hours post tpa whenever hemorrhage was suspected CT: 940 / MRI: 20 / both: 14 Neuroradiologist: radiological ICH subtypes (HI-1, HI-2, PH-1, PH-2) Stroke neurologist (without knowledge of patients 3-month outcome) classified sich according to the ECASS-II criteria: any hemorrhage (HI-1, HI-2, PH-1, PH-2) clinical deterioration causing an increase in the NIHSS score of 4 points time window: 7 days the hemorrhage was likely to be the cause of the clinical deterioration in case of doubt regarding whether edema or hemorrhage was the leading pathology, an association of the hemorrhage with the deterioration was assumed

6 Developing the score Statistics Univariate comparison of patients with and without sich the Mann-Whitney Rank Sum test or the Pearson χ2 test Variables were entered into the logistic regression model based on univariate associations (p<0.10) Backward logistic regression with a stepwise removal of p<0.10 Various combinations of cut-off values of continuous baseline parameters improvement of the model? (area under ROC curve) Calibration of the model: the Hosmer-Lemeshow test

7 Developing the score Univariate results Univariate associations age (p<0.01) baseline NIH Stroke scale score (p<0.001) hyperdense cerebral artery sign and early infarct signs on admission head CT scan (p<0.001) baseline glucose level (p<0.01) No univariate associations gender, onset-to-treatment time, blood pressure prior to tpa, platelet count medical history of hypertension, DM, A. fib, hyperlipidemia, CHF, previous stroke prior medication: antihypertensive, OAC, any antithrombotic

8 Blood pressure prior to thrombolysis Sare GM et al. Stroke 2009 Meretoja A et al. Stroke 2010 Kellert L et al. Stroke 2011

9 Blood pressure following thrombolysis Yong M & Kaste M. Stroke 2008 unsignificant unsignificant significant Δ 0-24t significant Δ 0-24t, Δ 0-7d Ahmed N et al. Stroke 2009

10 Developing the score Final model Characteristic Category Points Regression coefficient (95% CI) Sugar (glucose) level on admission Early infarct signs on admission CT head scan (hyper)dense cerebral artery sign on admission CT 8 mmol/l ( 144 mg/dl) mmol/L ( mg/dl) > 12 mmol/l (>216 mg/dl) 0 Reference p-value < <0.001 no 0 Reference yes no 0 Reference yes <0.01 Age 75 years 0 Reference > 75 years NIHSS score on admission 0-9 points 0 Reference 10- points

11 SEDAN in the derivation cohort Helsinki, n=974; sich: 7.0% ( %) Likelihood ratios 0: 0.19 ( ) 1: 0.40 ( ) 2: 1.23 ( ) 3: 1.85 ( ) 4: 3.68 ( ) 5: 5.66 ( ) The Hosmer-Lemeshow test: 2 =1.7, df=7, p=0.98 SEDAN in patients with BA occlusion (n=119)

12 Internal cross-validation Accuracy of the final regression model (not of the score) 1000 bootstrap replicates (R-project ) 93.1% ( )

13 SEDAN in the validation cohort Basel, Lausanne, Geneva, n=828 sich: 6.5% ( %) Helsinki vs. Switzerland very heterogeneous cohorts Similar likelihood ratios c-statistics=0.77 ( )

14 Comparison with other scores HAT score_original % sich, n=302, c=0.68 HAT score_validation % sich, n=965, c=0.59 HAT: Lou et al. Neurology 2008 Validation (HAT&MSS): Cucchiara et al. Int J Stroke Glucose or DM 0 / 1 (>11.1 mmol/l) Early infarct signs 0 / 1 / 2 (No; <1/3 MCA>) NIHSS 0 / 1 / 2 (<15-20>) MSS score_original % sich n=481, c= MSS score_validation % sich n=965, c= MSS: Cucchiara et al. J Stroke Cerebrovasc Dis 2008 Glucose 0 / 1 (>8.3 mmol/l) Age 0 / 1 (>60 y) NIHSS 0 / 1 (>10 p) Platelet count 0 / 1 (<150000/mm 3 ) SEDAN_Helsinki % sich, n=972, c= SEDAN_validation % sich, n=828, c= SEDAN: Strbian et al. Ann Neurol 2012 (in press) Sugar 0 / 1 / 2 (<8-12 mmol/l>) Early infarct signs 0 / 1 Dense artery sign 0 / 1 Age 0 / 1 (>75 y) NIHSS 0 / 1 ( 10 p)

15 Limitations of the study Additional baseline parameters may have impact on sich leukoaraiosis? detailed information on the status of vessel occlusion, infarct core, and salvageable tissue based on CT imaging only ( Time is brain ; door-to-needle-time in Helsinki: median 22 minutes) Interpretation of early infarct signs requires radiological expertise stroke physician + radiologist in Helsinki telemedicine consultation systems

16 Summary and Implications The SEDAN score is simple, fast to perform, and reliably assesses risk for sich The score is based on 5 easily accessible baseline variables Internal cross-validation showed high accuracy of the final model The score was validated externally with similar results, AUC=0.77 Heterogeneity between the derivation and validation cohorts supports generalization No single cut-off above which tpa should be withheld The score scrutinizes the sich risk to create a single number helps in decisionmaking process High-risk patients intensive post-tpa blood pressure & hyperglycemia monitoring and management recruitment into RCTs: add-on trials studying reduction of tpa-related hemorrhage to be used together with scores predicting the final functional outcome after iv tpa informed consent? candidates for endovascular procedures? The SEDAN score must be evaluated prospectively

EMS Management of Stroke. Deaver Shattuck, M.D. Brian Wiseman, M.D. Keith Woodward, M.D.

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