Division of Neurology, Saitama Children's Medical Center, 1-2, Shintoshin, Chuo-ku, Saitama, Japan; Department of Pediatrics, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan.
Division of Neurology, Saitama Children's Medical Center, 1-2, Shintoshin, Chuo-ku, Saitama, Japan.
Epilepsy Res. 2024 Nov;207:107454. doi: 10.1016/j.eplepsyres.2024.107454. Epub 2024 Sep 27.
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 + 0.195x + 195.15, R² = 0.77, p < 0.001). Using MMP >188 ng/mL as the cutoff level, the sensitivity for diagnosing IESS was 95.5 %, the specificity was 75.0 %, the positive likelihood ratio was 3.82 (95 % confidence interval (CI) 1.43-10.22), and the relative risk was 8.75 (95 % CI 1.36-56.5).
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.
癫痫性痉挛是婴儿癫痫性痉挛综合征（IESS）的主要症状；然而，其对血脑屏障（BBB）功能的直接影响尚不清楚。基质金属蛋白酶-9（MMP-9）降解 IV 型胶原，这是血脑屏障的关键成分，而基质金属蛋白酶抑制剂-1（TIMP-1）抑制其活性，保护 BBB 的完整性。本研究旨在评估病因不明的 IESS 患者的血清 MMP-9 和 TIMP-1 水平。
我们前瞻性评估了 2012 年 2 月至 2023 年 12 月期间在埼玉儿童医疗中心接受病因不明的 IESS 治疗的患者在使用氨己烯酸或促肾上腺皮质激素治疗前的血清 MMP-9 和 TIMP-1 水平。我们比较了这些生物标志物在癫痫性痉挛患者和年龄匹配的对照组之间的差异，并进行了生物标志物与癫痫性痉挛频率之间的曲线回归分析。此外，我们评估了 MMP-9 和 TIMP-1 水平是否是 IESS 的诊断预测指标。
这项研究包括 22 名患有 IESS（11 名男性）的患者和 12 名对照组。IESS 患者的血清 MMP-9 和 MMP-9/TIMP-1 比值高于对照组（p < 0.001 和 p = 0.002）。癫痫性痉挛的高频率也导致了更高的血清 MMP-9 水平（y = 0.0871x + 0.195x + 195.15，R² = 0.77，p < 0.001）。使用 MMP > 188ng/mL 作为截断值，诊断 IESS 的敏感性为 95.5%，特异性为 75.0%，阳性似然比为 3.82（95%置信区间（CI）1.43-10.22），相对危险度为 8.75（95%CI 1.36-56.5）。
患有 IESS 的患者血清 MMP-9 水平升高，提示癫痫性痉挛与血脑屏障功能障碍之间存在关联。MMP-9 水平的测量可能对诊断疑似患者有用。
