Glutamate in cerebrospinal fluid as a diagnostic marker for acute encephalopathy in childhood

Abstract

Backgrounds

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most frequent form of acute encephalopathy in early childhood in Japan. Magnetic resonance imaging provides useful hallmarks of diagnosing AESD. However, metabolomic profiles for AESD remain elusive. This study investigates whether measurement of amino acids in the cerebrospinal fluid (CSF) is useful for the diagnosis of AESD before onset.

Methods

In the first study, CSF samples were collected from patients (11 AESD and 17 controls) admitted to Kyushu University Hospital during 2011–2016. Amino acids in the CSF were analyzed using mass spectrometry. Cytometric bead arrays were used to measure cytokine and chemokine levels in the CSF. The second study was performed by recruiting patients (8 AESD patients and 10 controls) admitted during 2011–2024. CSF samples were stored at −20 °C for 1 month to 12 years.

Results

In the first study, glutamate levels in the CSF from AESD patients were higher than in controls and correlated with methionine, threonine, and tyrosine levels. A correlation map of cytokines and amino acids revealed that glutamate formed a cluster with IL-1β, IL-10, and IL-12 p70. In the second study, no difference in glutamate levels was observed between AESD and control groups.

Conclusions

CSF glutamate potentially serves as a useful marker for diagnosing AESD. The long-term storage of CSF samples was likely to cause a decay of glutamate in the CSF. Prospective studies using fresh CSF samples are necessary to validate the results in this study.