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

Cherubino Di Lorenzo, Gianluca Coppola, Martina Bracaglia, Davide Di Lenola, Giulio Sirianni, Paolo Rossi, Giorgio Di Lorenzo, Vincenzo Parisi, Mariano Serrao, MacKenzie C. Cervenka, Francesco Pierelli

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number136
JournalBMC Neurology
Issue number1
Publication statusPublished - Jun 22 2019


  • Habituation
  • Ketogenesis
  • Ketogenic diet
  • Migraine
  • Nociceptive blink reflex
  • Pain-related evoked potentials

ASJC Scopus subject areas

  • Clinical Neurology


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