TY - JOUR
T1 - Cerebrospinal Fluid and Plasma Amine Profiles in Interictal Migraine
AU - Onderwater, Gerrit L. J.
AU - van Dongen, Robin M.
AU - Harms, Amy C.
AU - Zielman, Ronald
AU - van Oosterhout, Willebrordus P. J.
AU - van Klinken, Jan B.
AU - Goeman, Jelle J.
AU - Terwindt, Gisela M.
AU - van den Maagdenberg, Arn M. J. M.
AU - Hankemeier, Thomas
AU - Ferrari, Michel D.
N1 - Funding Information:
This work was supported by the Netherlands Organization for Scientific Research (VICI grant 918.56.601 and Spinoza 2009 to M.D.F.), the Netherlands Organization for Health Research and Development (Clinical Fellowship grant 90700217 and Vidi grant 917‐11‐31 to G.M.T.), and European Community‐funded FP7‐EUROHEADPAIN (grant 602633 to M.D.F. and A.M.J.M.v.d.M.).
Funding Information:
This work was supported by the Netherlands Organization for Scientific Research (VICI grant 918.56.601 and Spinoza 2009 to M.D.F.), the Netherlands Organization for Health Research and Development (Clinical Fellowship grant 90700217 and Vidi grant 917-11-31 to G.M.T.), and European Community-funded FP7-EUROHEADPAIN (grant 602633 to M.D.F. and A.M.J.M.v.d.M.). We greatly acknowledge all study participants; the medical students who assisted with recruitment of participants; Drs F. Bakels, N. Pelzer, L. Wilbrink, and A. van der Plas for sample collection; and E. van Zwet and S. Koval for their advice on the applied statistics.
Publisher Copyright:
© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2023/4
Y1 - 2023/4
N2 - Objective: Impaired amine metabolism has been associated with the etiology of migraine, that is, why patients continue to get migraine attacks. However, evidence from cerebrospinal fluid (CSF) is lacking. Here, we evaluated individual amine levels, global amine profiles, and amine pathways in CSF and plasma of interictal migraine patients and healthy controls. Methods: CSF and plasma were sampled between 8:30 am and 1:00 pm, randomly and interchangeably over the time span to avoid any diurnal and seasonal influences, from healthy volunteers and interictal migraine patients, matched for age, sex, and sampling time. The study was approved by the local medical ethics committee. Individual amines (n = 31), global amine profiles, and specific amine pathways were analyzed using a validated ultraperformance liquid chromatography mass spectrometry platform. Results: We analyzed n = 99 participants with migraine with aura, n = 98 with migraine without aura, and n = 96 healthy volunteers. Univariate analysis with Bonferroni correction indicated that CSF L-arginine was reduced in migraine with aura (10.4%, p < 0.001) and without aura (5.0%, p = 0.03). False discovery rate-corrected CSF L-phenylalanine was also lower in migraine with aura (6.9%, p = 0.011) and without aura (8.1%, p = 0.001), p = 0.088 after Bonferroni correction. Multivariate analysis revealed that CSF global amine profiles were similar for both types of migraine (p = 0.64), but distinct from controls (p = 0.009). Global profile analyses were similar in plasma. The strongest associated pathways with migraine were related to L-arginine metabolism. Interpretation: L-Arginine was decreased in the CSF (but not in plasma) of interictal patients with migraine with or without aura, and associated pathways were altered. This suggests that dysfunction of nitric oxide signaling is involved in susceptibility to getting migraine attacks. ANN NEUROL 2023;93:715–728.
AB - Objective: Impaired amine metabolism has been associated with the etiology of migraine, that is, why patients continue to get migraine attacks. However, evidence from cerebrospinal fluid (CSF) is lacking. Here, we evaluated individual amine levels, global amine profiles, and amine pathways in CSF and plasma of interictal migraine patients and healthy controls. Methods: CSF and plasma were sampled between 8:30 am and 1:00 pm, randomly and interchangeably over the time span to avoid any diurnal and seasonal influences, from healthy volunteers and interictal migraine patients, matched for age, sex, and sampling time. The study was approved by the local medical ethics committee. Individual amines (n = 31), global amine profiles, and specific amine pathways were analyzed using a validated ultraperformance liquid chromatography mass spectrometry platform. Results: We analyzed n = 99 participants with migraine with aura, n = 98 with migraine without aura, and n = 96 healthy volunteers. Univariate analysis with Bonferroni correction indicated that CSF L-arginine was reduced in migraine with aura (10.4%, p < 0.001) and without aura (5.0%, p = 0.03). False discovery rate-corrected CSF L-phenylalanine was also lower in migraine with aura (6.9%, p = 0.011) and without aura (8.1%, p = 0.001), p = 0.088 after Bonferroni correction. Multivariate analysis revealed that CSF global amine profiles were similar for both types of migraine (p = 0.64), but distinct from controls (p = 0.009). Global profile analyses were similar in plasma. The strongest associated pathways with migraine were related to L-arginine metabolism. Interpretation: L-Arginine was decreased in the CSF (but not in plasma) of interictal patients with migraine with or without aura, and associated pathways were altered. This suggests that dysfunction of nitric oxide signaling is involved in susceptibility to getting migraine attacks. ANN NEUROL 2023;93:715–728.
UR - https://www.scopus.com/pages/publications/85147375035
U2 - 10.1002/ana.26576
DO - 10.1002/ana.26576
M3 - Article
C2 - 36511835
SN - 0364-5134
VL - 93
SP - 715
EP - 728
JO - Annals of neurology
JF - Annals of neurology
IS - 4
ER -