Effect of Asymptomatic Intracerebral Hemorrhage on Utility Weighted Modified Rankin Scale in Patients Undergoing Mechanical Thrombectomy

Adnan I. Qureshi MD, Department of Neurology, University of Missouri, Columbia, MO

Approximately 30-40% of the acute ischemic stroke patients who undergo mechanical thrombectomy develop asymptomatic intracerebral hemorrhages (ICH) including petechial hemorrhages.1 The odds of any ICH was significantly higher among patients treated with intravenous thrombolysis and mechanical thrombectomy in randomized clinical trials 2-5 and study by Hassan et al. 6 which may negatively affect quality of life among survivors 7, an important outcome for patients and families 8. The lower Utility-Weighted Modified Rankin Scale (UW-mRS) at 90 days associated with ICH was confirmed in an analysis of IMS-3 trial.
There continues to be ambiguity whether asymptomatic ICHs increase the rate of disability as measured by UW-mRS and whether there are certain patient subgroups which are at higher risk for increase in disability associated with asymptomatic ICHs.

Patient population
We propose to analyze the data come from the Virtual International Stroke Trials Archive—Endovascular database (VISTA-Endovascular, URL: www.virtualtrialsarchives.org): anonymized data of approximately 1,788 patients with acute ischemic stroke enrolled in randomized controlled trials focused on mechanical thrombectomy. We request anonymized data from the archive based on the availability of pre-specified variables of interest for the current analysis. A template of table with variables requested for analysis is provided at the end of the document.

Variable of interest:
We will identify all patients who have any ICH. The ICHs will be further characterized (wherever possible) as HI- petechial infarction without space-occupying effect, HI1- small petechiae HI2- more confluent petechiae, PH- hemorrhage (coagulum) with mass effect, PH1- 30% of the infarcted area with mild space-occupying effect, PH2- 30% of the infarcted area with significant space-occupying effect. Asymptomatic ICH will be defined9 based on absence of a local or remote Type 2 parenchymal hemorrhage on imaging 22 to 36 hours after treatment or earlier and/or a neurological deterioration of ≥4 NIH Stroke Scale/Score (NIHSS) points from baseline or from the lowest NIHSS score between baseline and 24 hours or leading to death within 24 hours. A grading of Type 2 parenchymal hemorrhage for ICH was based on hematoma exceeding 30% of the infarct with substantial space occupation.

Clinical and imaging endpoints
For this analysis, the site of arterial occlusion will be categorized into four groups; internal carotid artery (ICA) only; internal carotid artery with involvement of M1 segment of the middle cerebral artery (MCA) or M1 segment only or M1 along with several M2 segments afflicted; single M2 segment only; and other proximal vessel occlusions i.e., proximal occlusion of the anterior cerebral artery (ACA) or M3 segment. Successful recanalization will be defined as the Thrombolysis in Cerebral Infarction (TICI) grade 2B or 3 on angiography 24-hour post-treatment. Successful reperfusion will be defined as modified Thrombolysis in Cerebral Infarction (mTICI) grade 2B or 3 on 24-hour follow-up scan.
The primary end point will be the mean score for disability on the UW-mRS at 90 days. UW-mRS weights the mRS against a health utility scale that reflects the spectrum between perfect health (a score of 1) and outcomes worse than death (where death is a score of 0 and negative values indicate an outcome worse than death) 10,11. The main outcome of interest will be derived from the modified Rankin Scale (mRS; an ordered nominal score ranging from 0 to 6 with 0 indicating no symptoms and 6 indicating death) assessed 90 days post-stroke on an ordinal scale and good outcome defined as a binary variable (mRS ≤/> 2). To determine the utility-weighted score, the score on the UW-mRS is weighted according to average values calculated from patient-centered and clinician-centered studies 12-14. The following weights are assigned to scores 0 (best function) through 6 (worst function) on the mRS: 10.0, 9.1, 7.6, 6.5, 3.3, 0, and 0, respectively. Thus, the UW-mRS ranges from 0 (death) to 10 (no symptoms or disability) and indicates the value to patients, families, and health providers of the long-term disability outcome, across a broad range from fully normal, through varying degrees of disability, to death.

Statistical analyses
For all two-group univariate analyses (patients who did and did not experience asymptomatic ICH) will be performed. Categorical and continuous data will be presented as mean with standard deviation (SD) and percentages with 95% confidence interval (CI) and compared with Chi-square tests or Fisher’s exact test, and one-way analysis of variance, respectively, with Bonferroni correction for multiple comparisons. Ordinal logistic regression analysis and non-parametric Kruskal-Wallis tests will be used to identify any differences in the distribution of mRS grades between patients who did and did not experience asymptomatic ICH.
We will perform regression analyses for all pre-defined outcome measures and reported unadjusted and adjusted odds ratios (OR) for asymptomatic ICH. Prespecified variables to be included in the model are age (7, last known well-puncture time: early time window (≤6 hours) and extended time window (>6 hours), site of angiographic occlusion (ICA only; ICA with involvement of M1 segment of the MCA or M1 segment only or M1 along with several M2 segments afflicted; single M2 segment only; and other proximal vessel occlusions i.e., proximal occlusion of the ACA or M3 segment, and the baseline NIHSS score (<10, 10-19 and ≥20). Additional variables that will be included are those that were significantly different between the two groups in the univariate analysis.
Significance will be set at P<0.05, and all P will be 2-sided. Statistical analyses will be performed using SPSS 27 software (IBM Armonk, NY) and University Edition of SAS statistical software (SAS Institute, Inc).

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