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Early Phase Increase in Serum TIMP-1 in Patients with Acute Encephalopathy with Biphasic Seizures and Late Reduced
Ayaka Kasai1,2, Jun Kobayashi2,3, Makoto Nishioka1,3,4
1Department of Medical Genetics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Insights
Tissue inhibitor matrix metalloproteinase-1 (TIMP-1) levels increase in the early phase of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), suggesting a role in its pathophysiology.
Area of Science:
- Pediatric Neurology
- Neuroinflammation
- Biomarker Discovery
Background:
- Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common neurological disorder in Japanese children.
- Exanthem subitum is the primary cause of AESD.
- Understanding AESD pathophysiology and early diagnostic markers is crucial.
Purpose of the Study:
- To investigate the role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) in AESD.
- To identify potential biomarkers for early AESD diagnosis.
Main Methods:
- Retrospective analysis of serum and cerebrospinal fluid (CSF) from 17 AESD patients and 8 with prolonged febrile seizure (FS).
- Measurement of MMP-9, TIMP-1, and seven cytokines using ELISA and cytometric bead arrays.
- Comparison of biomarker concentrations between AESD seizure phases and FS.
Main Results:
- Serum TIMP-1 concentrations were significantly elevated in the first seizure phase of AESD compared to the second.
- No significant differences in serum MMP-9 or MMP-9/TIMP-1 ratio were found between groups.
- Cytokine levels were also analyzed but not detailed in the abstract.
Conclusions:
- An MMP-9-independent rise in circulating TIMP-1 may be linked to AESD pathophysiology during the initial seizure phase.
- TIMP-1 shows potential as an early biomarker for AESD.
Background:
Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most frequent subtype of acute encephalopathy syndrome among Japanese children. Exanthem subitum is the most common causative infectious disease of AESD. We herein retrospectively analyzed serum and cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor matrix metalloproteinase-1 (TIMP-1), and seven cytokines in patients with AESD or prolonged febrile seizure (FS) to assess the pathophysiology of AESD and detect biomarkers for diagnosing AESD in the early phase.
Methods:
Serum and CSF samples were obtained from 17 patients with AESD (1st seizure phase group, n = 7; 2nd seizure phase group, n = 10) and 8 with FS. The concentrations of MMP-9, TIMP-1, and seven cytokines were measured by enzyme-linked immunosorbent assays or cytometric bead arrays.
Results:
Serum concentrations of TIMP-1 were significantly higher in the 1st seizure phase group than in the 2nd seizure phase group. No significant differences were observed in serum concentrations of MMP-9 or the MMP-9/TIMP-1 ratio.
Conclusions:
The MMP-9-independent increase in circulating TIMP-1 concentrations observed in the present study may be associated with the pathophysiology of AESD in the 1st seizure phase.
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