Serum matrix metallopeptidase-9 levels in infantile epileptic spasms syndrome of unknown etiology.

Epileptic spasms are the primary symptom of infantile epileptic spasms syndrome (IESS); however, their direct impact on blood-brain barrier (BBB) function is unknown. Matrix metallopeptidase-9 (MMP-9), degrades type IV collagen, a key component of the blood-brain barrier, while tissue inhibitor of metalloproteinase-1 (TIMP-1) suppresses its activity, protecting BBB integrity. This study aimed to assess serum MMP-9 and TIMP-1 levels in patients with IESS of unknown etiology. We prospectively assessed serum MMP-9 and TIMP-1 levels prior to administering vigabatrin or adrenocorticotropic hormone therapy in patients with IESS of unknown etiology at Saitama Children's Medical Center between February 2012 and December 2023. We compared these biomarkers between patients with epileptic spasms and age-matched controls and performed a curve regression analysis between the biomarkers and the frequency of epileptic spasms. Additionally, we assessed whether MMP-9 and TIMP-1 levels were diagnostic predictors of IESS. This study included 22 patients with IESS (11 males) and 12 controls. Serum MMP-9 and MMP-9/TIMP-1 ratios were higher in patients with IESS than in controls (p < 0.001 and p = 0.002, respectively). A high frequency of epileptic spasms also led to higher serum MMP-9 levels (y = 0.0871x Patients with IESS had elevated serum MMP-9 levels, suggesting an association between epileptic spasms and blood-brain barrier dysfunction. MMP-9 level measurement may be useful for diagnosing suspected patients.

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Declaration of Competing Interest Shin-ichiro Hamano received funding from Daiichi Sankyo Co. Ltd., UCB Japan Co. Ltd., and Eisai Co. Ltd. Kenjiro Kikuchi received research funding from Syneos Health Clinical Co. Ltd. and Janssen Pharmaceutical K.K. The other authors declare no conflicts of interest.