在亚急性和慢性创伤性脑损伤中，NfL、tau、GFAP 和 UCH-L1 的时间进程和诊断效用。
Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI.
机构信息
From the NIH (P.S., A.P., S.M.L., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); Center for Neuroscience and Regenerative Medicine (P.S., A.v.d.M., B.M., V.E., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); The Henry M. Jackson Foundation for the Advancement of Military Medicine (P.S., A.v.d.M., B.M., V.E., D.L.B.), Bethesda, MD; Department of Psychiatry and Neurochemistry (P.S., H.Z., K.B.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; National Intrepid Center of Excellence (S.M.L.) and Defense and Veterans Brain Injury Center (S.M.L.), Walter Reed National Military Medical Center, Bethesda, MD; Department of Neurology (R.D.-A.), University of Pennsylvania, Philadelphia; UK Dementia Research Institute at UCL (H.Z.); Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London, UK; and Uniformed Services University of the Health Sciences (D.L.B.), Bethesda, MD.
出版信息
Neurology. 2020 Aug 11;95(6):e623-e636. doi: 10.1212/WNL.0000000000009985. Epub 2020 Jul 8.
OBJECTIVE
To determine whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI.
METHODS
Patients with TBI (n = 162) and controls (n = 68) were prospectively enrolled between 2011 and 2019. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n = 30), 90 (n = 48), and 180 (n = 59) days, and 1 (n = 84), 2 (n = 57), 3 (n = 46), 4 (n = 38), and 5 (n = 29) years after injury.
RESULTS
At enrollment, patients with TBI had increased serum NfL compared to controls ( 0.0001). Serum NfL decreased over the course of 5 years but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with an area under the receiver-operating characteristic curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrollment, serum GFAP was elevated in patients with TBI compared to controls ( 0.001). GFAP showed a biphasic release in serum, with levels decreasing during the first 6 months of injury but increasing over the subsequent study visits. The highest AUROC for GFAP was measured at 30 days, distinguishing patients with moderate and severe TBI from controls (both 0.89). Serum tau and UCH-L1 showed weak associations with TBI severity and neuroimaging measures. Longitudinally, serum NfL was the only biomarker that was associated with the likely rate of MRI brain atrophy and DTI measures of progression of TAI.
CONCLUSIONS
Serum NfL shows greater diagnostic and prognostic utility than GFAP, tau, and UCH-L1 for subacute and chronic TBI.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.
目的
确定神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）、tau 和泛素羧基末端水解酶-L1（UCH-L1）在血清中的测量值是否与创伤性脑损伤（TBI）的诊断、损伤严重程度、脑容量以及创伤性轴索损伤（TAI）的扩散张量成像（DTI）测量值有关。
方法
2011 年至 2019 年间，前瞻性纳入 162 例 TBI 患者和 68 例对照者。TBI 患者还在伤后 30（n=30）、90（n=48）和 180（n=59）天，以及伤后 1（n=84）、2（n=57）、3（n=46）、4（n=38）和 5（n=29）年时进行血清、功能结局和影像学评估。
结果
在入组时，TBI 患者的血清 NfL 水平高于对照组（ 0.0001）。在 5 年的过程中，血清 NfL 下降，但与对照组相比仍显著升高。30 天的血清 NfL 可将轻度、中度和重度 TBI 患者与对照组区分开来，其受试者工作特征曲线（ROC）下面积（AUROC）分别为 0.84、0.92 和 0.92。在入组时，TBI 患者的血清 GFAP 水平高于对照组（ 0.001）。GFAP 在血清中呈双相释放，在伤后 6 个月内水平下降，但随后的研究随访中升高。GFAP 的最高 AUROC 在 30 天测量，可将中度和重度 TBI 患者与对照组区分开来（均为 0.89）。血清 tau 和 UCH-L1 与 TBI 严重程度和神经影像学测量值呈弱相关。纵向来看，血清 NfL 是唯一与 MRI 脑萎缩和 TAI 进展的 DTI 测量值相关的生物标志物。
结论
与 GFAP、tau 和 UCH-L1 相比，血清 NfL 在亚急性和慢性 TBI 中具有更大的诊断和预后效用。
证据分类
本研究提供 III 级证据，表明血清 NfL 可将轻度 TBI 患者与健康对照者区分开来。
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