title: Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis.
abstract: Objective To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures. Results Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased β-endorphin (β-EP) in both chronic (four studies, SMD: -1.37, 95% CI: -1.80, -0.94) and interictal episodic migraine patients (three studies, SMD: -1.12, 95% CI: -1.65, -0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and β-EP (chronic, interictal and ictal) was decreased. Conclusions Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.
authors.affiliation: 1 Department of Neurology, Leiden University Medical Centre, the Netherlands.
authors.forename: Robin M
authors.initials: RM
authors.lastname: van Dongen
authors.affiliation: 1 Department of Neurology, Leiden University Medical Centre, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Zielman
authors.affiliation: 2 Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, the Netherlands.
authors.forename: Marek
authors.initials: M
authors.lastname: Noga
authors.affiliation: 3 Department of Clinical Epidemiology, Leiden University Medical Centre, the Netherlands.|4 Department of Clinical Epidemiology, Aarhus University Hospital, Denmark.
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.affiliation: 2 Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, the Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.affiliation: 1 Department of Neurology, Leiden University Medical Centre, the Netherlands.|5 Department of Human Genetics, Leiden University Medical Centre, the Netherlands.
authors.forename: Arn Mjm
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.affiliation: 1 Department of Neurology, Leiden University Medical Centre, the Netherlands.
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Terwindt
authors.affiliation: 1 Department of Neurology, Leiden University Medical Centre, the Netherlands.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D018592:Cross-Over Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D008881:Migraine Disorders / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D009479:Neuropeptides / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides
keywords: Migraine; biomarkers; cerebrospinal fluid; meta-analysis