Case Presentation: A 31 year old woman with sickle cell disease (SCD), homozygous SS variant, reported infrequent bony vaso-occlusive crises, necessitating the use of ibuprofen at times, when she presented for a routine clinic visit. Her review of systems was significant for mild unilateral, non-radiating, sharp headaches lasting a few minutes at a time and occurring 1-2 times per week for the past 10 years. She denied recent changes in the character of her headaches and had no other associated neurological symptoms. Examination was significant for pale and icteric mucous membranes, and a normal neurologic exam. MRI brain revealed multiple frontal lacunar infarcts with areas of stenosis involving the right middle cerebral artery, right internal carotid artery and left anterior carotid artery, consistent with a “moyamoya” pattern. This led to a diagnosis of silent cerebral infarction (SCI). Secondary stroke prevention with blood transfusion was started but aborted after the first treatment as she developed severe delayed hemolytic transfusion reaction that required an ICU admission. She declined second line therapy with hydroxyurea. She continues to be followed closely in the sickle cell and neurologic clinics.
Discussion: Headaches are quite common and range in severity. More importantly, headaches can also herald a more serious underlying condition and in certain groups, such as sickle cell patients, require a thorough evaluation. Neurologic complications, often manifesting as overt stroke or SCI, are seen in up to 30% of patients with SCD, particularly the homozygous (SS) variant. SCI describes an abnormal MRI brain finding in the setting of a normal neurologic examination and may be a precursor to overt stroke or other long term neurologic sequelae which underscores the need for early recognition and treatment. SCI is common in children but is poorly defined in adult patients. Headaches in adult SCD patients should raise suspicion for cerebral infarction. The underlying pathophysiology of SCI is smooth muscle hyperplasia and intraluminal thrombus formation accompanied by extensive lenticulostriate collaterals. The data available for SCI in adults with SCD, including the natural history, is limited which presents a challenge in clinical practice. Studies have shown that blood transfusion and less effectively so, hydroxyurea can reduce the recurrence of cerebral infarction in children. However, these practices are of uncertain effectiveness in the secondary prevention of stroke in adult patients and may actually present increased treatment risks.
Conclusions: While recommendations such as aspirin and statin therapies along with blood pressure control have been found to be significant in the secondary prevention of stroke in adults, these recommendations have not proven useful in the secondary prevention of stroke in SCD patients as atherosclerosis is not integral in the development of stroke in this patient population. There is clear need for more research on the issue of secondary stroke prevention in SCD patients with SCI as it affects a third of adult SCD patients.