Migraine in Multiple Sclerosis Patients Affects Functional Connectivity of the Brain Circuitry Involved in Pain Processing.

Emanuele Pravatà,Gianna C Riccitelli,Carlo Sestieri,Alessandro Cianfoni,Rosaria Sacco,Chiara Zecca,Claudio Gobbi

doi:10.3389/fneur.2021.690300

Abstract

Migraine is particularly common in patients with multiple sclerosis (MS) and has been linked to the dysfunction of the brain circuitry modulating the peripheral nociceptive stimuli. Using MRI, we explored whether changes in the resting state-functional connectivity (RS-FC) may characterize the occurrence of migraine in patients with MS. The RS-FC characteristics in concerned brain regions were explored in 20 MS patients with migraine (MS+M) during the interictal phase, and compared with 19 MS patients without migraine (MS-M), which served as a control group. Functional differences were correlated to the frequency and severity of previous migraine attacks, and with the resulting impact on daily activities. In MS+M, the loss of periaqueductal gray matter (PAG) positive connectivity with the default mode network and the left posterior cranial pons was associated with an increase of migraine attacks frequency. In contrast, the loss of PAG negative connectivity with sensorimotor and visual network was linked to migraine symptom severity and related daily activities impact. Finally, a PAG negative connection was established with the prefrontal executive control network. Migraine in MS+M patients and its impact on daily activities, underlies RS-FC rearrangements between brain regions involved in pain perception and modulation.

Highlights

Migraine affects up to 43% of patients with multiple sclerosis (MS), with a significantly higher prevalence than in the general population [1]
A series of studies conducted in stroke patients (reviewed in [34]) have indicated that the behavioral deficits following stroke are associated with both reduced inter-hemispheric functional connectivity and reduced anti-correlation between the fronto-parietal and the default mode networks
The MS patients with migraine (MS+M) patients experienced a substantial decrease in the positive RSFC from the periaqueductal gray matter (PAG) compared to MS patients without migraine (MS-M) patients, the residual default mode network (DMN) and Left Posterior caudal pons (L-PoCP) connectivity strength was directly correlated to a higher monthly migraine days (MMD)

Summary

Introduction

Migraine affects up to 43% of patients with multiple sclerosis (MS), with a significantly higher prevalence than in the general population [1]. In MS-unrelated migraine, clinical and electrophysiology studies have shown that the development of attacks is linked to the dysfunctions in the interaction between areas of the brain network deputed to pain stimuli palliation and Migraine Pathways in Multiple Sclerosis processing [2, 3]. In this circuit, the periaqueductal gray matter (PAG) has a pivotal role in the modulation of peripheral hyperexcitability developing along the trigemino-vascular system [2, 3]. The PAG exhibited either positive or negative connectivity with other brain regions [11, 12], respectively indicating functional integration or segregation [13, 14]

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