Introduction: Neurologic complications are a major cause of morbidity in sickle cell disease (SCD). The cumulative cerebral risk for neurological complications in sickle cell anemia has been estimated around 50% by age 14 (Bernaudin et. al, 2011;Blood 4:1130-40). Silent cerebral infarcts (SCI), is the most commonly recognized cause of neurological injury, associated with cognitive difficulties (King et al, Am J Hematol 2014;89:162-7) found in 20-40% of children with SCD, more common in genotype SS or Sβ0 thalassemia. The prevalence of SCI has not been well studied in adults. The prevalence of intracranial saccular aneurysms by radiographic and autopsy series is estimated to be 3.2% in a population without comorbidity, a mean age of 50 years, and a 1:1 gender ratio. (Valk et al, Lancet Neurol 2011; 10: 626–36) while other investigators found a 1.8% prevalence and no increased incidence with age (Vernooij et al NEJM 2007;357:1821-8). The goal of this study was to assess the prevalence of neurologic morbidity, including SCI, overt stroke, and cerebral aneurysm, in a large cohort of adults with SCD. We hypothesized the SCI would be more prevalent in adults compared to children with SCD.
Methods: Due to the high prevalence of cerebral infarcts in children with SCD, we elected to obtain as part of routine clinical practice, a MRI and magnetic resonance angiography (MRA) of the brain in adults
with SCD in our Hematology clinic. As standard care if SCIs are seen, neurocognitive testing is recommended, and based on this testing and MRI results, appropriate patients are referred for vocational rehabilitation service. All MRIs and MRAs were reviewed by 2 board certified neuroradiologists and consensus findings were recorded including presence of cerebral infarcts, intracerebral hemorrhage, aneurysms and cerebralvasculopathy. All adults with SCD were followed by a single hematologist and were asked about neurological symptoms. Medical records were reviewed to see if stroke like symptoms had been reported. If no symptoms were reported and no abnormalities were documented on neurological examination, then infarcts were judged to be silent.
Results: The study population included 94 adults with SCD (80% HbSS or Hb Sβ0 thalassemia; 11% HbSC, and 9% other), 51% males, median age 26 years, interquartile range (22-36 years) who had MRI of the brain and 88 had MRA of the brain. Of these, 91 MRIs were of sufficient quality to assess for the presence or absence of infarcts. Infarcts were present in 58% (53 individuals) with multiple infarcts in 40% (37 patients); infarcts were overt/symptomatic in 13% (12) and silent in 45% (41). Hemorrhages were present in 8 patients (9%) and of these, 7 of 8 also had infarcts present on MRI. MRI and MRA of the brain were felt of adequate quality to assess for vascular disease or aneurysm in 79 patients. Of these 7.5% (6 of 79 patients) had moyamoya vasculopathy and 7.5% (6 of 79 patients) had saccular aneurysms with no overlap between groups. All of the adults with moyamoya vasculopathy had overt strokes. The aneurysms were incidental findings and all were <5mm in size. Patients were referred to Neurosurgery for evaluation of aneurysmal lesions. Amongst the 12 adults with a history of overt stroke, 67% were on therapy (50% on hydroxyurea therapy; 17% on chronic blood transfusion therapy), 42% (5 of 12) received aspirin for stroke and 1 patient was already on warfarin for history of systemic thrombosis at the time of stroke.
Conclusions: Silent cerebral infarctions are common in adults with SCD. Silent cerebral infarcts were present in 45% and over strokes had occurred in 13% of adults with SCD. Our aneurysm prevalence of 7.5% in a younger cohort (median age 26 years) suggests that adults with SCD may have a higher prevalence of cerebral aneurysms than the general population. Further study is warranted to assess whether SCD should be considered a comorbidity that confers a higher risk of cerebral aneurysm in adults. The optimal strategies for primary and secondary stroke prevention and to mitigate against the progressive cerebral vasculopathy in adults with SCD are still being debated.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.