Primary headaches

Handb Clin Neurol. 2017:146:267-284. doi: 10.1016/B978-0-12-804279-3.00016-2.


Headache disorders, characterized by recurrent headache, are among the most common disorders of the nervous system. Primary headache disorders are by definition not the result of any other underlying disease or process. In this chapter the current status of cerebrospinal fluid (CSF) research and applications for clinical practice for the three main primary headaches - migraine, cluster headache, and tension-type headache - will be described. Primary headaches are clinically diagnosed disorders, with typically normal routine CSF measurements. Research in these headaches has been focused on identifying pathophysiologic pathways with a wide array of measured molecules. CSF research in the headache field is still in the discovery phase, with most studies performed in migraine and with unreplicated findings for most of the identified molecules. From a clinical standpoint it would be of great value if CSF biomarkers could be used as disorder-specific biomarkers for difficult primary headache cases, or to predict treatment responsiveness or risk for headache chronification. These applications are currently not yet feasible. For future research into CSF biomarkers for primary headache disorders, two different strategies should be employed: hypothesis-driven and nonhypothesis-driven biochemical research, to show new avenues for treatment strategies and develop prediction models for clinical use.

Keywords: biomarkers; cluster headache; discovery phase; hypothesis-driven; migraine; non-hypothesis-driven; pathophysiological pathways; tension-type headache.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / cerebrospinal fluid
  • Headache Disorders, Primary / cerebrospinal fluid*
  • Headache Disorders, Primary / diagnosis*
  • Headache Disorders, Primary / therapy
  • Humans
  • Inflammation Mediators / cerebrospinal fluid*
  • Recurrence


  • Biomarkers
  • Inflammation Mediators