Glutamate in cerebrospinal fluid as a diagnostic marker for acute encephalopathy in childhood
Kenta Kajiwara1, Daiki Setoyama2, Kanako Higashi3
1Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Insights
Cerebrospinal fluid (CSF) glutamate may help diagnose acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). However, sample storage duration impacts glutamate levels, necessitating fresh samples for future research on this childhood neurological condition.
Area of Science:
- Pediatric Neurology
- Neurochemistry
- Biomarker Discovery
Background:
- Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common childhood neurological disorder in Japan.
- While MRI is diagnostic, the metabolomic profile of AESD is not well understood.
- Investigating cerebrospinal fluid (CSF) amino acids may offer diagnostic insights.
Purpose of the Study:
- To determine if CSF amino acid levels, particularly glutamate, can aid in diagnosing AESD.
- To explore potential correlations between amino acids and cytokines in AESD patients.
- To assess the impact of CSF sample storage on glutamate levels.
Main Methods:
- Two studies analyzed CSF samples from AESD patients and controls using mass spectrometry.
- Cytokine and chemokine levels were measured using cytometric bead arrays.
- CSF samples in the second study were stored for varying durations (1 month to 12 years).
Main Results:
- The first study showed elevated CSF glutamate in AESD patients, correlating with methionine, threonine, and tyrosine.
- Glutamate clustered with specific cytokines (IL-1β, IL-10, IL-12 p70) in AESD patients.
- The second study found no significant difference in glutamate levels between AESD and control groups, likely due to sample storage.
Conclusions:
- CSF glutamate shows potential as a diagnostic biomarker for AESD.
- Long-term CSF sample storage may lead to glutamate degradation, affecting results.
- Further prospective studies with fresh CSF samples are required for validation.
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.
Related Concept Videos
01:18Viral Meningitis
01:19Encephalitis l: Introduction
01:26Encephalitis ll: Pathophysiology
01:29Hepatic Encephalopathy