Headache in Sickle Cell Disease: A Scoping Review

Objectives: Headaches are thought to be common neurological manifestations of sickle cell disease (SCD). We reviewed headaches in SCD to determine their prevalence, characteristics, and knowledge gaps and to identify new directions in clinical research. Methods: We carried out a scoping review and followed guidance from the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR). Our team evaluated 1414 articles based on a formal search process conducted across the MEDLINE (PubMed), Cochrane Library (Wiley), Embase (Elsevier) and Scopus (Elsevier) databases. We selected information on the prevalence and associated features of headaches in SCD, excluding secondary causes of headaches and studies dealing with treatments for SCD. Abstract review was managed using the Rayyan system. Results: 30 articles were included for final review. They generally employed small sample sizes, disparate methods, and retrospective analyses. The overall prevalence of headaches was 34% though a few larger studies showed prevalence of headaches in SCD ranging from 47% to 60%. Headache severity varied and could have features of migraine headaches, however, information on headache characteristics was limited. Discussion: There are gaps in our knowledge about the prevalence, characteristics, and underlying mechanisms of headaches in SCD. Since headaches in SCD are common and sometimes severe in intensity, clinicians must distinguish between those that are primary, and those secondary to a serious underlying cause. Knowledge gaps in characterizing headaches in SCD need to be bridged. Clinical trials in SCD provide an opportunity to study pre- and post-intervention prevalence, characteristics, and mechanism(s) of the headache. Well-designed large observational studies provide similar opportunities to better define headaches in SCD.