Early Career Award: Alterations in Functional Connectivity during Different Phases of the Triggered Migraine Attack

Nazia Karsan, MRCP PhD

AHSAM 2020 - Oral session
Published on July 17, 2020


5 minute read

Key messages

  • Understanding the possible changes in brain function during the different phases of the migraine attack is essential to developing disease biomarkers and advancing therapeutics.
  • The subcortical regions such as the hypothalamus, thalmus and basal ganglia are involved during the early phases of migraine.
  • Functional reorganization of the brain networks occurs between the subcortical and cortical areas which fluctuate during different phases of a migraine attack and lead to corresponding symptoms.
  • This knowledge could lead to the development of disease and treatment biomarkers in the future to improving patient outcomes and prognosis.

Key messages

  • Understanding the possible changes in brain function during the different phases of the migraine attack is essential to developing disease biomarkers and advancing therapeutics.
  • The subcortical regions such as the hypothalamus, thalmus and basal ganglia are involved during the early phases of migraine.
  • Functional reorganization of the brain networks occurs between the subcortical and cortical areas which fluctuate during different phases of a migraine attack and lead to corresponding symptoms.
  • This knowledge could lead to the development of disease and treatment biomarkers in the future to improving patient outcomes and prognosis.

Background

What do we already know about this topic?

  • Migraine is a symptomatically heterogeneous disorder.
  • Non-painful symptoms can be present up to several days before the onset of pain and can persist after headache resolution.
  • Understanding the possible changes in brain function during the different phases of the migraine attack is essential to developing disease biomarkers and advancing therapeutics.
  • Nitroglycerin has previously been shown to be a potent migraine trigger and can be used alongside resting-state fMRI to study the changes in functional connectivity between brain areas of potential importance in migraine during different phases of the attack.1

How was this study conducted?

  • A randomised, double-blind, placebo-controlled study of 53 adult patients, with a history of migraine who were recruited from across the UK and randomised to receive either a 0.5 mcg/kg/min nitroglycerin infusion or placebo over a 20-minute period. All patients were exposed to a nitroglycerin infusion at the screening visit.
  • Twenty-one patients consented to participate in imaging visits, structural T1, T2 and FLAIR sequences, and resting state blood oxygen level dependant contrast (rsBOLD) time series were conducted at baseline, and rsBOLD during premonitory symptoms and migraine headache on a 3T General Electric MR750 MRI scanner. For the placebo visit, the imaging was conducted at the same time following infusion in the absence of symptoms.

Findings

What does this study add?

  • Significant positive functional coupling was found between the thalami bilaterally and the right precuneus and cuneus regions during the nitroglycerin-triggered premonitory phase (T=3.23, peak connectivity change at [-6, -68, 40] for left thalamus, P=0.012 and [-4, -68, 40] for right thalamus, P=0.019).
  • The nitroglycerin-triggered premonitory phase was associated with a change in the direction of connectivity from positive to negative between the pons and the limbic lobe (T=3.47, peak connectivity change at [2, 8, 50], P< 0.001).
  • The headache phase of the nitroglycerin-triggered migraine attack was associated with ongoing negative functional coupling between the pons and the cingulate and frontal cortices, and positive functional coupling between the pons and  the spinal trigeminal nucleus (T=3.47, peak connectivity change at [-8, -52, -58], P=0.007).

Figure: Functional reorganisation of brain networks during different phases of a migraine attack.2

Perspectives

How does this study impact clinical practice?

  • The subcortical regions such as the hypothalamus, thalmus and basal ganglia are involved during the early phases of migraine.
  • Functional reorganisation of the brain networks occurs between the subcortical and cortical areas which fluctuate during different phases of a migraine attack and lead to corresponding symptoms.
  • The study furthers our understanding of the abnormal sensory processing and integration that occurs during a migraine, and the functional correlation with clinical symptoms displayed during each phase.
  • This knowledge could lead to the development of disease and treatment biomarkers in the future to improving patient outcomes and prognosis.

This is a highlights summary of an oral session given at the AHSAM 2020 Virtual Annual Scientific Meeting and presented by:

Nazia Karsan, MRCP PhD
Neurology Resident
King's College London
London, England, United Kingdom

The content is produced by Infomedica, the official reporting partner of ASHAM 2020 Virtual Annual Scientific Meeting. The summary text was drafted by Goldcrest Medical Writing, reviewed by Marco Vercellino, MD, an independent external expert, and approved by Jessica Ailani, MD, FAHS and Mark J. Burish, MD, PhD, the scientific editors of the program.

The presenting authors of the original session had no part in the creation of this conference highlights summary.

1. Karsan N, Bose PR, Thompson C, et al. Headache and non-headache symptoms provoked by nitroglycerin in migraineurs: A human pharmacological triggering study [published online ahead of print, 2020 Mar 12]. Cephalalgia. 2020;333102420910114.

2. Kros L, Angueyra Aristizábal CA, Khodakhah K. Cerebellar involvement in migraine. Cephalalgia. 2018;38:1782-1791.



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