Headache as a Neurologic Manifestation of Systemic Disease

PURPOSE OF REVIEW: This is an update of headache attributed to systemic disease and current therapeutic strategies. Clinical scenarios are discussed. RECENT FINDINGS: The diagnosis of headache attributed to metabolic or systemic disorder appears in the Appendix of International Classification of Headache Disorders, Third Edition, and requires further evaluation and validation. However, recent studies characterizing headache appear in the literature. Specific treatment includes addressing underlying systemic disorders, managing concurrent primary headache, and treating comorbidities that may exacerbate headache. Evidence for specific treatment trials for headache as a symptom is lacking, including headaches post-COVID19 infection. Calcitonin gene-related peptide receptor antagonists and 5-HT(1F) receptor agonists are attractive options for migraine with vascular comorbidities, but long-term studies are needed. SUMMARY: Headache is commonly encountered as a manifestation or complication of systemic disease. Further research is needed to validate headache associated with systemic disorders and to determine optimal treatment strategies.