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神经丝轻链、胶质纤维酸性蛋白和 tau 在区域性癫痫队列中的研究:血浆中高水平较为罕见,但与癫痫发作相关。

Neurofilament light, glial fibrillary acidic protein, and tau in a regional epilepsy cohort: High plasma levels are rare but related to seizures.

机构信息

Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Wallenberg Center of Molecular and Translational Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

Epilepsia. 2023 Oct;64(10):2690-2700. doi: 10.1111/epi.17713. Epub 2023 Jul 19.

DOI:10.1111/epi.17713
PMID:37469165
Abstract

OBJECTIVE

Higher levels of biochemical blood markers of brain injury have been described immediately after tonic-clonic seizures and in drug-resistant epilepsy, but the levels of such markers in epilepsy in general have not been well characterized. We analyzed neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau in a regional hospital-based epilepsy cohort and investigated what proportion of patients have levels suggesting brain injury, and whether certain epilepsy features are associated with high levels.

METHODS

Biomarker levels were measured in 204 patients with an epilepsy diagnosis participating in a prospective regional biobank study, with age and sex distribution correlating closely to that of all patients seen for epilepsy in the health care region. Absolute biomarker levels were assessed between two patient groups: patients reporting seizures within the 2 months preceding inclusion and patients who did not have seizures for more than 1 year. We also assessed the proportion of patients with above-normal levels of NfL.

RESULTS

NfL and GFAP, but not tau, increased with age. Twenty-seven patients had abnormally high levels of NfL. Factors associated with such levels were recent seizures (p = .010) and epileptogenic lesion on radiology (p = .001). Levels of NfL (p = .006) and GFAP (p = .032) were significantly higher in young patients (<65 years) with seizures ≤2 months before inclusion compared to those who reported no seizures for >1 year. NfL and GFAP correlated weakly with the number of days since last seizure (NfL: r  = -.228, p = .007; GFAP: r  = -.167, p = .048) in young patients. NfL also correlated weakly with seizure frequency in the last 2 months (r  = .162, p = .047).

SIGNIFICANCE

Most patients with epilepsy do not have biochemical evidence of brain injury. The association with seizures merits further study; future studies should aim for longitudinal sampling and examine whether individual variations in NfL or GFAP levels could reflect seizure activity.

摘要

目的

在强直阵挛性发作后和耐药性癫痫中,已经描述了更高水平的生化血液脑损伤标志物,但一般癫痫中的此类标志物水平尚未得到很好的描述。我们分析了区域性医院癫痫队列中的神经丝轻链(NfL)、胶质纤维酸性蛋白(GFAP)和 tau,并调查了有多少患者的水平提示脑损伤,以及某些癫痫特征是否与高水平相关。

方法

在参加前瞻性区域性生物库研究的 204 名癫痫诊断患者中测量了生物标志物水平,其年龄和性别分布与该医疗保健区域所有癫痫患者的分布密切相关。在两组患者之间评估了绝对生物标志物水平:在纳入前 2 个月内报告发作的患者和 1 年以上无发作的患者。我们还评估了具有高于正常水平 NfL 的患者比例。

结果

NfL 和 GFAP,但不是 tau,随年龄增长而增加。27 名患者的 NfL 水平异常升高。与这些水平相关的因素是近期发作(p = .010)和放射影像学上的致痫病变(p = .001)。与那些报告无 1 年以上发作的患者相比,在纳入前 2 个月内有≤2 次发作的年轻患者(<65 岁)中,NfL(p = .006)和 GFAP(p = .032)水平明显更高。在年轻患者中,NfL 和 GFAP 与上次发作后天数呈弱相关(NfL:r  = -.228,p = .007;GFAP:r  = -.167,p = .048)。NfL 也与最近 2 个月内的发作频率呈弱相关(r  = .162,p = .047)。

意义

大多数癫痫患者没有生化证据表明存在脑损伤。与发作的关联值得进一步研究;未来的研究应旨在进行纵向采样,并检查 NfL 或 GFAP 水平的个体差异是否可以反映发作活动。

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