Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London, UK.
Acta Neurol Scand. 2019 May;139(5):422-427. doi: 10.1111/ane.13069. Epub 2019 Mar 5.
Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated that soluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the Cerebrospinal fluid (CSF) of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease-modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS.
We measured CSF sNCAM levels at baseline and after 12-24 months of DMT in 69 patients, 49 relapsing-remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in-house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone, and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured.
At baseline, the mean sNCAM level was 268.7 ng/mL (SD: 109 ng/mL) in MS patients compared with 340.6 ng/ml (SD: 139 ng/mL) in HC, and PMS had significantly lower sNCAM (239.2 ng/mL, SD: 123.0, P = 0.019) compared to RRMS (269.4, SD: 127.4, P = 0.043). After natalizumab and mitoxantrone treatments, we observed an increase in mean sNCAM. However, in the fingolimod-treated group, mean sNCAM decreased. There was no correlation found with EDSS or MSSS, or NfL levels as a whole.
Cerebrospinal fluid sNCAM levels were found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Following natalizumab and mitoxantrone treatments, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disability in the short-term or NfL levels.
多发性硬化症（MS）患者在复发之间的恢复原因知之甚少，尤其是在接受治疗后。过去，已经证明，在接受急性复发的 MS 患者的脑脊液（CSF）中，神经可塑性的假定生物标志物可溶性神经细胞黏附分子（sNCAM）在类固醇治疗后增加。更进一步，我们评估了各种 MS 亚型的疾病修饰治疗（DMT）对 CSF sNCAM 水平的影响。
我们使用内部 ELISA 在 69 名患者、49 名复发缓解型多发性硬化症（RRMS）、20 名进展型多发性硬化症（PMS）和 24 名健康对照者（HC）中测量了基线和 12-24 个月 DMT 后的 CSF sNCAM 水平。其中，31 名患者接受了那他珠单抗、17 名患者接受了米托蒽醌、21 名患者接受了芬戈莫德。使用 EDSS 测量残疾变化，使用 MSSS 测量疾病严重程度。同时，还测量了 CSF NfL 水平。
在基线时，MS 患者的平均 sNCAM 水平为 268.7ng/mL（SD：109ng/mL），而 HC 为 340.6ng/ml（SD：139ng/mL），PMS 的 sNCAM 明显低于 RRMS（239.2ng/mL，SD：123.0，P=0.019）。接受那他珠单抗和米托蒽醌治疗后，我们观察到平均 sNCAM 增加。然而，在芬戈莫德治疗组中，平均 sNCAM 下降。sNCAM 水平与 EDSS 或 MSSS 或整体 NfL 水平之间没有相关性。
MS 患者的 CSF sNCAM 水平低于 HC，PMS 患者的 sNCAM 水平最低。在接受那他珠单抗和米托蒽醌治疗后，我们观察到 sNCAM 水平升高，而在接受芬戈莫德治疗后则没有观察到这种升高。然而，这些变化似乎与短期残疾或 NfL 水平无关。
