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Withdrawal from acute medication normalises short-term cortical synaptic potentiation in medication overuse headache

  • Francesca CorteseEmail author
  • Francesco Pierelli
  • Flavia Pauri
  • Cherubino Di Lorenzo
  • Chiara Lepre
  • Giulia Malavolta
  • Chiara Merluzzo
  • Vincenzo Parisi
  • Anna Ambrosini
  • Mariano Serrao
  • Gianluca Coppola
Original Article

Abstract

Objectives

To study the effects of a standard acute medication withdrawal program on short-term cortical plasticity mechanisms in patients with medication overuse headache (MOH).

Methods

Thirteen patients with MOH and 16 healthy volunteers underwent repetitive transcranial magnetic stimulation (rTMS) over the left motor cortex; in patients with MOH, recordings were performed before and after a 3-week medication withdrawal program. Ten trains of 10 stimuli each (120% resting motor threshold) were delivered at 1 Hz or 5 Hz in two separate sessions in a randomised order. Motor evoked potential (MEP) amplitudes were measured from the right first dorsal interosseous muscle and the slope of the linear regression line from the first to the tenth stimuli was calculated for each participant.

Results

All subjects exhibited MEP amplitude inhibition in response to 1 Hz rTMS. Alternatively, the 5-Hz trains of rTMS inhibited rather than potentiated MEP amplitudes in patients with MOH. The physiological potentiating effect of 5 Hz rTMS on MEP amplitudes was restored after drug withdrawal and in proportion with the percentage reduction in monthly headache days in patients with MOH.

Conclusions

The results suggest that acute medication withdrawal normalises brain responses in patients with MOH. Clinical improvements after medication withdrawal may reflect the reversal of neurophysiological dysfunction. Accordingly, medication withdrawal should be offered to patients with MOH as early as possible in order to prevent the development of more pronounced alterations in brain plasticity.

Keywords

Chronic migraine Repetitive transcranial magnetic stimulation Short-term depression Short-term potentiation Synaptic plasticity 

Notes

Funding information

The contribution of the G.B. Bietti Foundation to this article was supported by the Italian Ministry of Health and Fondazione Roma.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • Francesca Cortese
    • 1
    Email author
  • Francesco Pierelli
    • 1
    • 2
  • Flavia Pauri
    • 3
  • Cherubino Di Lorenzo
    • 4
  • Chiara Lepre
    • 3
  • Giulia Malavolta
    • 3
  • Chiara Merluzzo
    • 3
  • Vincenzo Parisi
    • 5
  • Anna Ambrosini
    • 2
  • Mariano Serrao
    • 1
  • Gianluca Coppola
    • 1
  1. 1.Department of Medico-Surgical Sciences and Biotechnologies“Sapienza” University of Rome Polo PontinoLatinaItaly
  2. 2.IRCCS NeuromedPozzilliItaly
  3. 3.Department of Medico-Surgical Sciences and Biotechnologies, Neurology Section“Sapienza” University of RomeRomeItaly
  4. 4.IRCCS - Fondazione Don Carlo GnocchiMilanItaly
  5. 5.Research Unit of Neurophysiology of Vision and NeurophthalmologyIRCCS - Fondazione BiettiRomeItaly

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