Charlotte Zerna, MD, MSc
Cerebral small vessel disease has been shown to lead to worse clinical outcomes in both ischemic and hemorrhagic stroke, affect post stroke neuroplasticity, and thus impair cerebral network reorganization that is needed after neuronal injury. Several imaging features of cerebral small vessel disease exist and can be measured on both magnetic resonance imaging and computed tomography. In this study, the authors aimed to investigate the association of two of these imaging factors (leukoaraiosis measured as reduced area of x-ray attenuation on CT and brain atrophy measured as volume loss not related to a specific macroscopic focal injury such as trauma or infarction) with functional outcome at 90 days and a recovery trajectory marker (difference between modified Rankin Scale score at discharge and day 90).
Retrospective analysis of prospectively collected data of 3000 patients enrolled in multiple centers across the United States within the ERICH (Ethnic and Racial Variations in Intracerebral Hemorrhage) study was undertaken. Trained and blinded investigators used visual rating scales to assess the extent of leukoaraiosis and brain atrophy with good intra-class correlation coefficients on available baseline CT scans. Severe intracerebral hemorrhage patients with prominent hydrocephalus, large midline shift or primary intraventricular hemorrhage were excluded from the analysis so the results do not pertain to these patients. Clinical characteristics, demographics, and discharge modified Rankin Scale score were gathered through medical record review and were available for 2344 patients. Patients were attempted to be contacted for assessment of their 90-day modified Rankin Scale scores to calculate the recovery trajectory marker, which the authors were able to obtain for 1778 patients. There was a trend of association for both increasing leukoaraiosis and global atrophy scores with poor functional outcome at discharge (modified Rankin Scale score 3-5) and poor recovery trajectory in unadjusted and adjusted analysis of intracerebral hemorrhage survivors, respectively.
The novel use of the recovery trajectory marker was used as an attempt to disentangle the severity of the intracerebral hemorrhage and how it predicts poor functional outcome and mortality in itself from the subacute phase from hospital discharge to day 90 that is potentially modified by cerebral small vessel disease. The authors acknowledge that the recovery trajectory marker is a crude measurement, as well as that it does not take into account that patients can show improvement beyond day 90 and thus slower but satisfying recovery might be missed. Hospital discharge is not a defined time point, and thus the recovery trajectory marker encompasses heterogeneous time periods across patients. Furthermore, the 376 missing modified Rankin Scale scores at day 90 are possibly not missing at random, and a sensitivity analysis assuming both best and worst outcome for those patients could have added to the authors’ results and potentially influenced their conclusions. It is unclear whether the amount of correlation between leukoaraiosis and age was assessed since the input of variables highly correlated with one another (known as multicollinearity) lessens the precision with which each predictor of the regression model can be calculated.
The authors themselves mention that spontaneous intracerebral hemorrhage can be the result of the rupture of blood vessels with diminished microvascular integrity when affected by cerebral small vessel disease. Thus, cerebral small vessel disease and intracerebral hemorrhage could rather be viewed as phenotypes of a common pathophysiological pathway instead of independent disease entities. The article rightly concludes that it is unclear if cerebral small vessel disease impairs recovery from intracerebral hemorrhage or the occurrence of the intracerebral hemorrhage has led to the decompensation of a brain that had so far functioned albeit presence of cerebral small vessel disease. Future studies are needed to gain further understanding of this interaction.