Vécsei László
Szegedi Tudományegyetem, ÁOK, Neurológiai Klinika, Interdiszciplináris Kiválósági Centrum, MTA-SZTE Idegtudományi Kutatócsoport, Szeged.
Ideggyogy Sz. 2020 Jan 30;73(1-2):7-14. doi: 10.18071/isz.73.0007.
Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.
近期数据表明,复发缓解型多发性硬化症患者中病情长期恶化很常见,且很大程度上与复发或脑部磁共振成像(MRI)上新病灶形成无关。继发进展型多发性硬化症的当前定义是,在至少6个月的间隔期内,残疾状况恶化且与复发无关。早期局灶性炎症疾病活动和脊髓病变是复发型多发性硬化症超长期疾病预后的预测指标。正电子发射断层扫描(PET)成像在体内可视化多发性硬化症脑部隐匿性炎症的潜力,对于更好地理解疾病进展具有重要意义。因此,PET成像在检测复发缓解型多发性硬化症向继发进展型多发性硬化症的转变方面是一种很有前景的工具。此外,神经轴突损伤是包括多发性硬化症在内的不同神经系统疾病中永久性残疾的病理基础。在这种情况下,神经丝蛋白很有前景,因为它们的水平不仅在脑脊液中,而且在血液中,会随着神经轴突损伤而升高。基线时血清神经丝水平升高的患者,与其他临床和MRI变量无关,在2年和5年的随访中,脑和脊髓体积损失明显更多。犬尿氨酸途径异常可能与疾病从早期轻度阶段向衰弱性进展形式的转变有关。分析血清中的这些代谢物可能用作多发性硬化症疾病生物标志物。自由基作用被认为是该疾病的一个致病因素。在疾病活动期发现自由基产生增加以及清除分子的消耗增加。基于临床研究结果(EXPAND研究)和疾病发病机制,西尼莫德已获美国食品药品监督管理局批准,用于治疗复发缓解型多发性硬化症,包括伴有活动性疾病的继发进展型多发性硬化症、复发缓解型多发性硬化症和临床孤立综合征。