Brain Dev. 2025 Sep 26;47(5):104447. doi: 10.1016/j.braindev.2025.104447. Online ahead of print.
ABSTRACT
PURPOSE: Epileptic spasms are the predominant seizure type in infantile epileptic spasms syndrome (IESS). The pathophysiology of IESS, including blood-brain barrier (BBB) function involvement, remains unclear. To address this issue, we evaluated the serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in patients with IESS before and after initiating vigabatrin therapy.
METHODS: IESS was defined as epileptic spasms occurring within 2 years after birth. We prospectively assessed serum MMP-9 and TIMP-1 levels before and after initiating vigabatrin therapy in patients with IESS who attended Saitama Children’s Medical Center between February 2019 and December 2024 (n = 12; 5 boys) and compared them with those in age-matched controls (n = 14; 8 boys).
RESULTS: The median ages at epileptic spasm onset and vigabatrin therapy initiation were 3.5 (1-11) and 8 (3-13) months, respectively. Serum MMP-9 levels were higher in patients with IESS than in the controls (p < 0.001). Serum MMP-9 and MMP-9/TIMP-1 ratios decreased significantly after vigabatrin therapy (MMP-9: 308 [160-664] ng/mL vs. 220 [112-367] ng/mL, p < 0.01; MMP-9/TIMP-1 ratio: 1.48 [0.61-8.14] vs. 1.11 [0.31-1.92], p < 0.05). MMP-9 levels decreased in 9 of 11 patients whose epileptic spasms had disappeared by the time of the last measurement.
CONCLUSION: Decreased MMP-9 levels after the initiation of vigabatrin therapy suggested an improvement in BBB dysfunction. Our findings shed light on the role of the BBB in IESS and the role of vigabatrin in the recovery of this function.
PMID:41015830 | DOI:10.1016/j.braindev.2025.104447
