Headache in Children with Sickle Cell Disease

Children with sickle cell disease (SCD) commonly experience headaches, both acutely and chronically. Although migraine and tension headache are common causes, headaches may also be related to their underlying SCD and associated with acute central nervous system events. The purpose of this study was to determine the frequency, severity, and associated characteristics of headaches in children with SCD.

This retrospective study was approved by the Johns Hopkins Institutional Review Board. Subjects were children < 18 years old with SCD identified using Hopkins' clinic rosters and medical records. Patient medical records were searched to determine reports of headaches in inpatient or outpatient encounters. Data were extracted from subjects' charts including, SCD history, headache history, stroke and silent cerebral infarction (SCI) history with additional review of imaging by neurologist (EIL) and radiologist if needed to confirm diagnosis, medications, laboratory values, neurology referrals, and neuroimaging results. Based on patient-reported headache details in the medical record, we determined headache type using the International Classification of Headache Disorders criteria. Headaches were further characterized by frequency and severity. We used descriptive statistics to describe the SCD population with and without headaches. We then compared demographic and clinical characteristics of patients with headaches to those without headaches using parametric and nonparametric statistical tests when appropriate.

We included 276 subjects in our data analysis. Fifty three percent of patients had a history of headache. Characteristics of subjects with (N=147) and without (N=129) headache are in Table 1. Sixty-six of the headache subjects were seen by a neurologist/neurodevelopmental physician. The primary reason for referral for 10 subjects was headache, SCI for seven subjects, ADHD for 11 subjects, learning difficulties for 25 subjects, and other for 19 subjects. Compared to those without headaches, subjects with headaches were significantly older at time of chart review (10.52 vs. 6.67, p < 0.0001), had more severe disease (62.2% sickle cell anemia vs. 37.4% compound heterozygous, p<0.001), had more neurological complications (7% stroke & 12% SCI - headache group vs. 3% stroke and 1% SCI - no headache group, p <0.003), had higher median reticulocyte count (8.0% vs. 4.3%, p < 0.003), and lower median hemoglobin F (7.95% vs. 11.7%, p <0.003).

In terms of headache characteristics, nine patients reported headaches less than one day per month on average; 13 subjects reported one to 14 days of headache per month on average for more than three months; and four subjects reported greater than 15 days of headache per month on average for more than three months. Five subjects also reported avoidance of their routine due to headaches. Twelve subjects were hospitalized for headache and 30 reported an emergency department visit for headache. Only 10 subjects had enough details about their headache features to determine their headache type (Table 2). Nine of the subjects' headache types were consistent with criteria for migraine headaches and one subject had tension type headache.

Headaches are common in children with SCD. Our findings suggest that children with SCD and history of headache are more likely to have SCD-related and neurological complications. Additionally, children with SCD and headache are more likely to have a higher median reticulocyte count which is associated with more severe disease. More studies are needed to classify and understand headaches in children with SCD, which may help guide management and treatment in this patient population.

Pecker:GBT: Research Funding; Novo Nordisk: Consultancy; Global Blood Therapeutics: Consultancy. Lance:Novatis: Membership on an entity's Board of Directors or advisory committees.