A ketogenic diet normalizes interictal cortical but not subcortical responsivity in migraineurs

BMC Neurol. 2019 Jun 22;19(1):136. doi: 10.1186/s12883-019-1351-1.


Background: A short ketogenic diet (KD) treatment can prevent migraine attacks and correct excessive cortical response. Here, we aim to prove if the KD-related changes of cortical excitability are primarily due to cerebral cortex activity or are modulated by the brainstem.

Methods: Through the stimulation of the right supraorbital division of the trigeminal nerve, we concurrently interictally recorded the nociceptive blink reflex (nBR) and the pain-related evoked potentials (PREP) in 18 migraineurs patients without aura before and after 1-month on KD, while in metabolic ketosis. nBR and PREP reflect distinct brain structures activation: the brainstem and the cerebral cortex respectively. We estimated nBR R2 component area-under-the-curve as well as PREP amplitude habituation as the slope pof the linear regression between the 1st and the 2nd block of 5 averaged responses.

Results: Following 1-month on KD, the mean number of attacks and headache duration reduced significantly. Moreover, KD significantly normalized the interictal PREP habituation (pre: + 1.8, post: - 9.1, p = 0.012), while nBR deficit of habituation did not change.

Conclusions: The positive clinical effects we observed in a population of migraineurs by a 1-month KD treatment coexists with a normalization at the cortical level, not in the brainstem, of the typical interictal deficit of habituation. These findings suggest that the cerebral cortex may be the primary site of KD-related modulation.

Trial registration: ClinicalTrials.gov NCT03775252 (retrospectively registered, December 09, 2018).

Keywords: Habituation; Ketogenesis; Ketogenic diet; Migraine; Nociceptive blink reflex; Pain-related evoked potentials.

MeSH terms

  • Adult
  • Blinking / physiology
  • Brain Stem / physiopathology*
  • Case-Control Studies
  • Cerebral Cortex / physiopathology*
  • Diet, Ketogenic*
  • Evoked Potentials / physiology
  • Female
  • Habituation, Psychophysiologic / physiology*
  • Humans
  • Male
  • Migraine Disorders / physiopathology*
  • Migraine Disorders / prevention & control*
  • Pain / physiopathology
  • Retrospective Studies
  • Trigeminal Nerve

Associated data

  • ClinicalTrials.gov/NCT03775252