Headache as a Neurologic Manifestation of Systemic Disease

Alexandra N. Cocores, Teshamae S. Monteith

Research output: Contribution to journalReview articlepeer-review


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-HT1F 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.

Original languageEnglish (US)
Pages (from-to)17-40
Number of pages24
JournalCurrent Treatment Options in Neurology
Issue number1
StatePublished - Jan 2022


  • COVID-19
  • Migraine comorbidity
  • Neurologic manifestation
  • Secondary headache
  • Systemic disease

ASJC Scopus subject areas

  • Clinical Neurology


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