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Published on: June 18, 2021
Trimethylamine N-oxide (TMAO) in patients with subarachnoid hemorrhage: a prospective observational study
Julian Josef Emonds1,2, Felix Arlt1, Alexander Gaudl2
1Department of Neurosurgery, University of Leipzig Medical Center, Leipzig, Germany.
Background:
It is suspected that microbiome-derived trimethylamine N-oxide (TMAO) may enhance platelet responsiveness and accordingly be thrombophilic. The purpose of this prospective observational study is to evaluate TMAO in patients with subarachnoid hemorrhage (SAH) and compare it with a control group. A secondary aim was to investigate TMAO in the cerebrospinal fluid (CSF) from SAH patients. This should provide a better understanding of the role of TMAO in the pathogenesis of SAH and its thrombotic complications.
Methods:
The study included patients with diagnosed spontaneous SAH recruited after initial treatment on admission and patients with nerve, nerve root, or plexus disorders serving as controls. Blood samples were gathered from all patients at recruitment. Additionally, sampling of SAH patients in the intensive care unit continued daily for 14 days. The CSF was collected out of existing external ventricular drains whenever possible.
Results:
Thirty-four patients diagnosed with SAH, and 108 control patients participated in this study. Plasma TMAO levels at baseline were significantly lower in the SAH group (1.7 μmol/L) compared to the control group (2.9 μmol/L). TMAO was detectable in the CSF (0.4 μmol/L) and significantly lower than in plasma samples of the SAH group at baseline. Plasma and CSF TMAO levels correlated positively. The TMAO levels did not differ significantly during the observation period of 15 days.
Conclusions:
Although we assumed that patients with higher TMAO levels were at higher risk for SAH a priori, plasma TMAO levels were lower in patients with SAH compared with control subjects with nerve, nerve root, or plexus disorders on admission to the hospital. A characteristic pattern of plasma TMAO levels in patients with SAH was not found.
Insights
Trimethylamine N-oxide (TMAO) levels were lower in subarachnoid hemorrhage (SAH) patients compared to controls. Cerebrospinal fluid (CSF) TMAO was also lower in SAH patients, contrary to the hypothesis that TMAO is thrombophilic.
Area of Science:
- Neurology
- Biochemistry
- Cardiovascular Science
Background:
- Microbiome-derived trimethylamine N-oxide (TMAO) is suspected to promote thrombosis by enhancing platelet responsiveness.
- The role of TMAO in subarachnoid hemorrhage (SAH) pathogenesis and thrombotic complications remains unclear.
Purpose of the Study:
- To prospectively evaluate TMAO levels in patients with SAH.
- To compare TMAO levels between SAH patients and a control group.
- To investigate TMAO presence in cerebrospinal fluid (CSF) of SAH patients.
Main Methods:
- Prospective observational study including 34 SAH patients and 108 controls.
- Blood samples collected at baseline and daily for 14 days in SAH patients.
- CSF samples collected from SAH patients via external ventricular drains.
Main Results:
- Baseline plasma TMAO levels were significantly lower in SAH patients (1.7 μmol/L) than in controls (2.9 μmol/L).
- TMAO was detectable in CSF (0.4 μmol/L), and levels were lower than in SAH patient plasma.
- Plasma and CSF TMAO levels showed a positive correlation in SAH patients.
Conclusions:
- Contrary to the hypothesis, plasma TMAO levels were lower in SAH patients upon hospital admission.
- No characteristic pattern of plasma TMAO levels was observed during the 15-day observation period in SAH patients.

