Updated review on the link between cortical spreading depression and headache disorders.

Vuralli D., Karatas H., Yemisci M., Bolay H.

Expert review of neurotherapeutics, vol.21, pp.1069-1084, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 21
  • Publication Date: 2021
  • Doi Number: 10.1080/14737175.2021.1947797
  • Journal Name: Expert review of neurotherapeutics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Psycinfo
  • Page Numbers: pp.1069-1084
  • Keywords: Cortical spreading depression, migraine, aura, headache, thalamocortical dysfunction, brain networks, treatment targets, calcitonin gene-related peptide, transcranial magnetic stimulation, vagal nerve stimulation, GENE-RELATED PEPTIDE, TRANSCRANIAL MAGNETIC STIMULATION, VAGUS NERVE-STIMULATION, SOMATOSENSORY TEMPORAL DISCRIMINATION, CEREBRAL-BLOOD-FLOW, LATENCY AFFERENT INHIBITION, GYRENCEPHALIC FELINE BRAIN, MIGRAINE AURA, DOUBLE-BLIND, NMDA RECEPTOR
  • Hacettepe University Affiliated: Yes


Introduction: Experimental animal studies have revealed mechanisms that link cortical spreading depression (CSD) to the trigeminal activation mediating lateralized headache. However, conventional CSD as seen in lissencephalic brain is insufficient to explain some clinical features of aura and migraine headache. Areas covered: The importance of CSD in headache development including dysfunction of the thalamocortical network, neuroinflammation, calcitonin gene-related peptide, transgenic models, and the role of CSD in migraine triggers, treatment options, neuromodulation, and future directions are reviewed. Expert opinion: The conventional understanding of CSD marching across the hemisphere is invalid in gyrencephalic brains. Thalamocortical dysfunction and interruption of functional cortical network systems by CSD may provide alternative explanations for clinical manifestations of migraine phases including aura. Not all drugs showing CSD blocking properties in lissencephalic brains have efficacy in migraine headache and monoclonal antibodies against CGRP ligand/receptors which are effective in migraine treatment, have no impact on aura in humans or CSD properties in rodents. Functional networks and molecular mechanisms mediating and amplifying the effects of limited CSD in migraine brain remain to be investigated to define new targets.