Abstract Details

Title Investigating Glymphatic Dysfunction in Migraine: A Role in Headache Pain and Migraine Chronification?

Topic Headache

Presentation(s) P4 - Poster Session 4 (5:00 PM-6:00 PM)

Poster/Presentation
Number 12-002

Objective To investigate the role of glymphatic dysfunction in the acute headache phase of migraine and in mechanisms of chronification and medication overuse (MO).

Background The glymphatic system facilitates fluid exchange and waste removal in the brain. What is the involvement of glymphatic dysfunction in migraine is still unclear.

Design/Methods One hundred twenty migraine patients and 52 controls underwent diffusion tensor (DTI) and susceptibility weighted (SWI) magnetic resonance imaging (MRI). Using DTI and SWI, we computed the Diffusion Along Perivascular Space (DTI-ALPS) index, reflecting diffusivity in the perivascular space near the left lateral ventricle. Based on previous evidence linking glymphatic function to changes in intra/extracellular compartments, we also used neurite orientation dispersion and density imaging to evaluate voxel-wise maps of white matter extracellular (EVF) and intracellular (IVF) volume fraction. Age- and sex-adjusted between-group comparisons were run using R and FSL software.

Results Compared to controls, migraine patients were older and had a higher proportion of female subjects. Among patients, 95 were headache-free (MwoH), 25 experienced headache during the MRI (MwH), 93 had episodic migraine (EM), 24 had chronic migraine (CM) with MO, and three CM without MO. We found no significant differences between patients and controls, neither concerning the DTI-ALPS index nor regarding EVF and IVF. No differences in the DTI-ALPS index were observed between subgroups of patients. Compared to MwoH and controls, MwH patients had decreased EVF and increased IVF. Likewise, compared to controls, CM patients with MO showed decreased EVF and increased IVF.

Conclusions Despite no significant differences in the DTI-ALPS index, our results of reduced EVF and concomitant expansion of IVF suggest impaired glymphatic clearance in CM patients with MO and in MwH patients. These findings suggest potential involvement of glymphatic dysfunction in the acute pain phase of migraine and the mechanisms underlying chronification and MO.

Authors/Disclosures
Roberta Messina, MD, PhD (San Raffaele Hospital) PRESENTER	Dr. Messina has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Messina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizer. Dr. Messina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck. Dr. Messina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Dr. Messina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Organon. Dr. Messina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Messina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly.
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
Francesca Genovese (IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University)	No disclosure on file
Ilaria Cetta, MD (Ospedale San Raffaele)	Dr. Cetta has nothing to disclose.
Laura Zanandrea, MD	Dr. Zanandrea has nothing to disclose.
Bruno Colombo	Bruno Colombo has nothing to disclose.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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