Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Department of Neurosciences, Civil Hospital of Baggiovara, AOU Modena, Modena, Italy.
J Neurochem. 2018 Oct;147(2):275-284. doi: 10.1111/jnc.14550. Epub 2018 Aug 30.
Neurosteroids such as allopregnanolone may play a role in epilepsy as positive modulators of inhibitory currents mediated by γ-aminobutyric acid type A (GABA ) receptor. Indeed, these molecules have been consistently shown to be anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated neurosteroids in the cerebrospinal fluid (CSF) of patients with status epilepticus (SE) by liquid chromatography tandem-mass spectrometry. Patients were retrospectively identified within subjects who received a lumbar puncture in the 2007-2017 period. Seventy-three patients (median age 65, ranging from 13 to 94 years; 67% women) with SE were evaluated. Controls (n = 52, median age 53, ranging from 16 to 93 years; 65% women) were patients presenting with symptoms for which a lumbar puncture was required by clinical guidelines, and who were negative at the end of the diagnostic work-up. Progesterone was 64% lower in patients with SE (p < 0.001). With respect to progesterone, upstream pregnenolone sulfate and pregnenolone did not change. Instead, downstream 5α-dihydroprogesterone, pregnanolone and allopregnanolone were, respectively, 49% (p < 0.001), 21% (p < 0.01) and 37% (p < 0.001) lower than in controls. Duration or type of SE, age and sex did not consistently affect CSF neurosteroid levels in the SE cohort. Instead, pregnenolone sulfate (Spearman's ρ = 0.4335, p < 0.01), allopregnanolone (ρ = 0.4121, p < 0.05) and pregnanolone (ρ = 0.592, p < 0.001) levels significantly increased by aging in controls. We conclude that neurosteroidogenesis is defective in patients with SE.
神经甾体，如别孕烯醇酮，可能作为 γ-氨基丁酸 A 型 (GABA A ) 受体介导的抑制性电流的正调节剂在癫痫中发挥作用。事实上，这些分子在动物模型中一直被证明具有抗惊厥作用，但它们在患者中的作用仍不清楚。出于这个原因，我们通过液相色谱串联质谱法研究了癫痫持续状态 (SE) 患者脑脊液中的神经甾体。通过回顾性分析，我们确定了在 2007 年至 2017 年期间接受腰椎穿刺的患者。共评估了 73 名 SE 患者（中位年龄 65 岁，范围 13-94 岁；67%为女性）。对照组（n=52，中位年龄 53 岁，范围 16-93 岁；65%为女性）为根据临床指南需要进行腰椎穿刺且诊断性检查结束时为阴性的患者。SE 患者的孕酮水平降低了 64%（p<0.001）。与孕酮相比，上游孕烯醇酮硫酸盐和孕烯醇酮没有变化。相反，下游 5α-二氢孕酮、孕烷醇酮和别孕烯醇酮分别降低了 49%（p<0.001）、21%（p<0.01）和 37%（p<0.001）。SE 队列中，SE 的持续时间或类型、年龄和性别并未一致影响 CSF 神经甾体水平。相反，孕烯醇酮硫酸盐（Spearman ρ=0.4335，p<0.01）、别孕烯醇酮（ρ=0.4121，p<0.05）和孕烷醇酮（ρ=0.592，p<0.001）水平在对照组中随年龄增长而显著增加。我们的结论是，SE 患者的神经甾体生成存在缺陷。
