Cerebral Ischemia in Adults with Sickle Cell Disease after First Stroke

Introduction

People with sickle cell disease (SCD) have a greatly increased risk of silent cerebral infarct (SCI) and ischemic and hemorrhagic stroke compared with the general population. A prospective cohort study of pediatric patients with SCD after first stroke demonstrated recurrent brain injury (SCI and stroke) in 45% of the participants (median follow-up of 5.5 years) despite regular transfusions to maintain a hemoglobin S concentration less than 30%. The rate of recurrent brain injury in adults with SCD with a history of stroke has not been described.

Methods

This retrospective cohort study identified patients with SCD treated at Johns Hopkins Hospital who were at least 15 years old with a history of ischemic or hemorrhagic stroke and at least 2 MRIs of the brain available for interpretation. Two neuroradiologists interpreted and completed a data extraction form for each MRI and, when available, MR angiography. The form included the type of lesion, the number of lesions, the progression of the lesion from previous MRIs, and the presence or absence of cerebral vasculopathy by vessel. Clinical and demographic data were extracted from paper and electronic medical records. All data were entered into Microsoft Access and verified for accuracy. We used Stata Intercooled 12^®to calculate descriptive statistics and rates and 95% confidence intervals by exact methods.

Results

We identified 24 patients (50% male) with a median age of 20 years (IQR 13, 24) at the baseline imaging and 23 (IQR 21, 30) at the time of the most recent imaging. Twenty had sickle cell anemia (HbSS) and 4 had hemoglobin SC disease. At baseline, 23 (96%) had evidence of cerebral ischemic lesions with a median of 8 (IQR 4, 10) lesions and 4 (16%) had global atrophy. Two participants had acute intraparenchymal hemorrhage and one prior hemorrhage with hemosiderin deposition in the brain parenchyma. Of the 20 with interpretable MR angiography, 15 (75%) had cerebral vasculopathy. Median follow-up was 3.3 years (IQR 1.9, 8.7) with a median of 2.5 MRIs obtained during follow-up (IQR 1.5, 4). We identified recurrent ischemic brain injury in 13 (54%) of participants with 17 new SCIs (3 also had enlargement of existing lesions) and 5 overt strokes. The rate of recurrent brain injury was 18 per hundred person-years (95% CI 12, 28). The rate was lower (15 per 100 person-years) in those with cerebral vasculopathy compared with those without cerebral vasculopathy (40 per 100 person-years), but this difference was not statistically significant (p=0.12). The rate of new SCI was 14 (95% CI 8.3, 23) and the rate of recurrent ischemic stroke was 4.2 per 100 person-years (95% CI 1.4, 9.8). No participants had new hemorrhagic strokes.

Discussion

People with SCD and a history of stroke have high rates of recurrent brain ischemia as adolescents and adults. The proportion in this study with recurrent ischemic events was similar to that seen in children and adolescents despite a substantially shorter period of follow-up. This may be secondary to differences in the treatment of adults with SCD and stroke (perhaps lower rates of chronic transfusion therapy), ascertainment bias (adolescents and adults with concerning symptoms for recurrent stroke may be more likely to have follow-up MRIs of the brain), or a continued high rate of recurrent ischemia in this population. Given the high rate of ischemia, regular screening for brain injury should be considered in adults with SCD and a history of stroke.