Neurological Symptoms in the Sickle Cell Population

A 7-year-old female with sickle cell disease type SS comes to your office with a new complaint of acute onset headache.

Neurological symptoms in the sickle cell patient population have always been difficult to assess. As a hematology fellow, I often hear about these patients after they present to their pediatrician or the emergency department. Tremendous strides have been made over the past several decades to mitigate the risk of stroke in children with sickle cell disease, but the risk of neurologic complications has not been fully eradicated, and so we must remain astute in looking for these complications.

Strokes in the sickle cell population occur most frequently in patients with a hemoglobin-SS genotype and can be either ischemic or hemorrhagic. Ischemic strokes tend to occur in younger children, between 2 and 9 years old. In contrast, hemorrhagic stroke is seen more commonly in our adolescents and young adults, with a peak around age 20. Signs and symptoms can be subtle, but vary based on the location of the stroke.

Even more common than strokes, we often find our sickle cell patients have had silent infarcts (SI), including one-third of SS patients. SI occurs when we find changes on an MRI without overt neurological deficit. However, often the SI manifests as globally impaired processing skills, such as difficulty keeping up in school. Thus, these SIs are not truly silent, and they are linked to increased risk of stroke and developing further SIs, as well as decreased IQ by an average of 5 points.

Headaches pose a particularly difficult clinical scenario in SCD and are a common complaint. Thankfully, CNS pathology is usually rare, but up to 7 percent of patients with acute onset severe headaches have been reported to have an acute neurologic emergency. This was associated with older age, history of stroke, transient ischemic attack or seizure, neurologic symptoms, and focal neurologic exam findings. Hemorrhagic stroke is more common than ischemic stroke in this scenario. Interestingly, sickle cell patients also have a higher incidence of sinus venous thrombosis, especially in adolescents, and this should remain on the differential. We have also seen vaso-occlusive crisis of the skull bones with subsequent epidural hematoma in several patients with acute headaches. Chronic headaches have generally not been found to be associated with acute neurologic complications in SCD, so a thorough history is important in deciphering which patients merit an immediate neurologic consult.

Treatment of acute neurologic complications has shifted in recent years to primary prevention, through the use of screening with transcranial doppler ultrasound and brain MRI/A. The mainstay of secondary treatment ranges from hydroxyurea therapy to chronic transfusions or apheresis, depending on the particular patient. Curative therapy for sickle cell disease is currently limited to bone marrow transplant, but gene therapy is also on the horizon. CHOP is one of the few pediatric centers that offers bone marrow transplantation for sickle cell patients, and we anticipate gene therapy trials will be starting later this year.

Our young patient in the vignette would need a thorough history to determine if this headache was acute and new, gather information about her sickle cell history and current treatment, as well requiring a thorough neurologic exam. She would likely merit a referral to the emergency room for a full evaluation by the CHOP stroke team.

References and suggested readings

DeBaun MR, Kirkham FJ. Central nervous system complications and management in sickle cell disease. Blood. 2016;127:7.

Hines PC, McKnight TP, Seto W, Kwiatkowski JL. Central nervous system events in children with sickle cell disease presenting acutely with headache. J Pediatr. 2011;159(3):472-478.

Lawrence C, Webb J. Sickle cell disease and stroke: diagnosis and management. Curr Neurol Neurosci Rep. 2016;16:27.

Contributed by: Jessica Foster, MD