Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
Fluids Barriers CNS. 2023 Jan 11;20(1):3. doi: 10.1186/s12987-022-00403-2.
Impaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients.
NfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry.
CSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = - 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort.
The observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.
脑脊液（CSF）稳态的损害是特发性颅内高压（IIH）发病机制的核心，尽管涉及的确切机制仍不完全清楚。本研究的目的是评估神经丝轻链水平的 CSF/血清比值（QNfL）作为 IIH 患者功能性 CSF 流出阻塞的潜在指标。
通过单分子阵列测量了 87 例 IIH 患者和三个对照组（包括 52 例急性复发的多发性硬化症（MS）患者、21 例轴索性多神经病（PNP）患者和 41 名神经健康对照组（HC））的 CSF 和血清样本中的 NfL 水平。QNfL 计算为 CSF 和血清 NfL 水平的比值。同样，我们还评估了神经胶质纤维酸性蛋白（QGFAP）水平的 CSF/血清比值，以验证 QNfL 数据。所有组均测定常规 CSF 参数，包括 CSF/血清白蛋白比值（QAlb）。通过压力计测量 IIH 患者的腰椎穿刺开口压力。
CSF-NfL 水平（r=0.29，p=0.008）和 QNfL（0.40，p=0.0009）与 IIH 患者的腰椎穿刺开口压力相关，但 CSF 中 NfL 水平（S-NfL）与 IIH 患者的腰椎穿刺开口压力无关。IIH 患者、MS 患者和 PNP 患者的 CSF-NfL 水平升高，而 IIH 患者的 S-NfL 水平正常，但 MS 和 PNP 患者的 S-NfL 水平升高。值得注意的是，仅在 IIH 患者中，QNfL（p<0.0001）和 QGFAP（p<0.01）升高。在 HC 中，QNfL 与 CSF-NfL 水平呈正相关（r=0.51，p=0.0012），与 S-NfL 水平呈负相关（r=-0.51，p=0.0012），而在 IIH 患者中，QNfL 仅与 CSF-NfL 水平呈正相关（r=0.71，p<0.0001）。任何队列中，血脑屏障通透性的增加（用 QAlb 评估）都不会导致 QNfL 下降。
在 IIH 患者中观察到的 QNfL 升高与腰椎穿刺开口压力相关，表明 NfL 从 CSF 向血清区室的转移减少。这支持 CSF 流出阻塞与压力相关的假说，这是 IIH 发病机制中的关键因素。
