Ghiasian Masoud, Bawand Rashed, Jabarzadeh Sulmaz, Moradi Abbas
Department of Neuroimmunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of General Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Heliyon. 2024 Feb 17;10(4):e26658. doi: 10.1016/j.heliyon.2024.e26658. eCollection 2024 Feb 29.
Our objective was to uncover the predictive factors that can help anticipate the malignant progression of individuals with Relapsing-Remitting Multiple Sclerosis (RRMS). Additionally, we sought to analyze and compare the response to treatment between patients with benign and malignant forms of RRMS.
This cohort study included RRMS patients categorized as benign (≥10 years since disease onset, Expanded Disability Status Scale (EDSS) ≤ 1) or malignant (≤5 years since disease onset, EDSS ≥6). Patients' data, including demographics, medical history, treatment, and MRI (Magnetic Resonance Imaging) scans, were collected and statistically analyzed.
Among the 254 patients diagnosed with RRMS, 174 were found to have benign RRMS, while the remaining 80 were diagnosed with malignant RRMS. Notably, patients with malignant RRMS exhibited a significantly higher mean age of onset (32.00 ± 7.96 vs. 25.70 ± 17.19; < 0.001) and a greater prevalence of males (40% vs. 18.4%; = 0.014. Additionally, within the initial five years of diagnosis, patients with malignant RRMS experienced a higher number of relapses (median: 4 vs. 2; < 0.001) and hospitalizations (median: 2 vs. 1; = 0.006) compared to those with benign RRMS. Clinical presentations of malignant RRMS were predominantly characterized by multifocal attacks, whereas unifocal attacks were more prevalent in patients with benign RRMS. MRI scans revealed that malignant RRMS patients displayed a higher burden of plaques in the infratentorial and cord regions, as well as a greater number of black hole lesions. Conversely, benign RRMS patients exhibited a higher number of Gadolinium-enhanced lesions. Utilizing Disease-Modifying Therapies (DMTs) with an escalating approach has shown effectiveness in managing benign RRMS. However, it has proven insufficient in addressing malignant RRMS, resulting in frequent transitions to higher-line DMTs. As a result, it places a considerable burden on patients with malignant RRMS, consuming valuable time and resources, and ultimately yielding subpar outcomes.
Our study identifies prognostic factors for malignant progression in RRMS, including older age of onset, male gender, increased relapses and hospitalizations, multifocal attacks, higher plaque load, and black hole lesions. The current escalation strategy for DMTs is insufficient for managing malignant RRMS, requiring alternative approaches for improved outcomes. In other words, MS is a spectrum rather than a single disease, and some patients progress to a malignant phenotype of MS that is not effectively treated by the current approach.
我们的目标是找出有助于预测复发缓解型多发性硬化症（RRMS）患者恶性进展的预测因素。此外，我们试图分析和比较良性和恶性RRMS患者对治疗的反应。
这项队列研究纳入了被分类为良性（疾病发作≥10年，扩展残疾状态量表（EDSS）≤1）或恶性（疾病发作≤5年，EDSS≥6）的RRMS患者。收集了患者的数据，包括人口统计学、病史、治疗情况和磁共振成像（MRI）扫描结果，并进行了统计分析。
在254例被诊断为RRMS的患者中，发现174例为良性RRMS，其余80例被诊断为恶性RRMS。值得注意的是，恶性RRMS患者的平均发病年龄显著更高（32.00±7.96岁 vs. 25.70±17.19岁；P<0.001），男性患病率更高（40% vs. 18.4%；P=0.014）。此外，在诊断后的最初五年内，恶性RRMS患者的复发次数更多（中位数：4次 vs. 2次；P<0.001），住院次数也更多（中位数：2次 vs. 1次；P=0.006），而良性RRMS患者则不然。恶性RRMS的临床表现主要以多灶性发作特征，而单灶性发作在良性RRMS患者中更为普遍。MRI扫描显示，恶性RRMS患者在幕下和脊髓区域的斑块负担更高，黑洞病变数量也更多。相反，良性RRMS患者的钆增强病变数量更多。采用逐步升级的方法使用疾病修饰疗法（DMTs）已显示出对良性RRMS的管理有效。然而，事实证明，这种方法在治疗恶性RRMS方面并不充分，导致频繁转向更高线的DMTs。因此，这给恶性RRMS患者带来了相当大的负担，消耗了宝贵的时间和资源，最终产生的结果也不尽人意。
我们的研究确定了RRMS恶性进展的预后因素，包括发病年龄较大、男性、复发和住院次数增加、多灶性发作、斑块负荷较高和黑洞病变。目前DMTs的逐步升级策略不足以管理恶性RRMS，需要采用替代方法以改善结果。换句话说，MS是一个谱系而非单一疾病，一些患者会进展为MS的恶性表型，而目前的方法无法有效治疗。
