2. Academic Validation
  3. Urine metabolomics signatures in reversible cerebral vasoconstriction syndrome

Urine metabolomics signatures in reversible cerebral vasoconstriction syndrome

  • Cephalalgia. 2020 Jun;40(7):735-747. doi: 10.1177/0333102419897621.
Wei-Hsiang Hsu 1,  Shuu-Jiun Wang 2 3 4 5,  Yen-Ming Chao 1,  Chao-Jung Chen 6,  Yen-Feng Wang 2 3 4,  Jong-Ling Fuh 2 3 4,  Shih-Pin Chen 2 3 4 7 8,  Yun-Lian Lin 1 9
Affiliations

Affiliations

  • 1 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung.
  • 2 Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei.
  • 3 Brain Research Center, National Yang-Ming University, Taipei.
  • 4 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei.
  • 5 Institute of Brain Science, National Yang-Ming University, Taipei.
  • 6 Graduate Institute of Integrated Medicine, China Medical University, Taichung.
  • 7 Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei.
  • 8 Institute of Clinical Medicine, National Yang-Ming University, Taipei.
  • 9 Department of Pharmacy, National Taiwan University, Taipei.
PMID: 31910660 DOI: 10.1177/0333102419897621
Abstract

Background: The pathophysiology of reversible cerebral vasoconstriction syndrome is unclear. An unbiased systems-based approach might help to illustrate the metabolite profiling and underlying pathophysiology.

Methods: Urine samples were collected from reversible cerebral vasoconstriction syndrome patients and matched controls recruited in Taipei Veterans General Hospital. 1H-Nuclear magnetic resonance was used to initially explore the metabolic profile, and liquid chromatography tandem mass spectrometry was then used to identify metabolic alterations in reversible cerebral vasoconstriction syndrome. Untargeted metabolite screening was randomly performed on 10 reversible cerebral vasoconstriction syndrome patients and 10 control subjects in the discovery phase. The selected untargeted metabolites were further validated on 47 reversible cerebral vasoconstriction syndrome patients during their ictal stage (with 40 of them having remission samples) and 47 controls in the replication phase.

Results and conclusion: Six metabolites-hippurate, citrate, 1,3,7-trimethyluric acid, ascorbic acid, D-glucurono-6,3-lactone, and D-threo-isocitric acid-with t-test derived p-value < 0.05 and VIP score >1, were identified as potential urine signatures that can well distinguish reversible cerebral vasoconstriction syndrome subjects at ictal stage from controls. Among them, citrate, hippurate, ascorbic acid, and D-glucurono-6,3-lactone were significantly lower, and 1,3,7-trimethyluric acid and D-threo-isocitric acid were higher in reversible cerebral vasoconstriction syndrome patients. Of these, four selected metabolites, citrate, D-glucurono-6,3-lactone, ascorbic acid, and 1,3,7-trimethyluric acid, returned to normal levels in remission. These metabolites are related to pathways associated with free radical scavenging, with the hub molecules being associated with endothelial dysfunction or sympathetic overactivity. Whether these metabolites and their implicated networks play a role in the pathogenesis of reversible cerebral vasoconstriction syndrome remains to be confirmed.

Keywords

1; 3; 7-trimethyluric acid; Reversible cerebral vasoconstriction syndrome (RCVS); ascorbic acid; thunderclap headaches; urine metabolomics.

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