Department of Neurology, Regional Hospital in Legnica, Iwaszkiewicza 5, 59-220 Legnica, Poland.
Clinical Department of Neurology, University Centre of Neurology and Neurosurgery, Faculty of Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2024 Aug 11;25(16):8751. doi: 10.3390/ijms25168751.
Primary progressive multiple sclerosis (PPMS), the least frequent type of multiple sclerosis (MS), is characterized by a specific course and clinical symptoms, and it is associated with a poor prognosis. It requires extensive differential diagnosis and often a long-term follow-up before its correct recognition. Despite recent progress in research into and treatment for progressive MS, the diagnosis and management of this type of disease still poses a challenge. Considering the modern concept of progression "smoldering" throughout all the stages of disease, a thorough exploration of PPMS may provide a better insight into mechanisms of progression in MS, with potential clinical implications. The goal of this study was to review the current evidence from investigations of PPMS, including its background, clinical characteristics, potential biomarkers and therapeutic opportunities. Processes underlying CNS damage in PPMS are discussed, including chronic immune-mediated inflammation, neurodegeneration, and remyelination failure. A review of potential clinical, biochemical and radiological biomarkers is presented, which is useful in monitoring and predicting the progression of PPMS. Therapeutic options for PPMS are summarized, with approved therapies, ongoing clinical trials and future directions of investigations. The clinical implications of findings from PPMS research would be associated with reliable assessments of disease outcomes, improvements in individualized therapeutic approaches and, hopefully, novel therapeutic targets, relevant for the management of progression.
原发性进展型多发性硬化症（PPMS）是多发性硬化症（MS）中最不常见的类型，其具有特定的病程和临床症状，且预后较差。它需要广泛的鉴别诊断，通常在正确识别之前需要长期随访。尽管目前在进展型 MS 的研究和治疗方面取得了进展，但这种疾病的诊断和管理仍然具有挑战性。鉴于疾病所有阶段都存在“潜伏”进展的现代概念，对 PPMS 的深入研究可能会更好地了解 MS 进展的机制，并具有潜在的临床意义。本研究的目的是回顾 PPMS 的现有研究证据，包括其背景、临床特征、潜在的生物标志物和治疗机会。讨论了 PPMS 中中枢神经系统损伤的潜在机制，包括慢性免疫介导的炎症、神经退行性变和髓鞘再生失败。对潜在的临床、生化和影像学生物标志物进行了综述，这对于监测和预测 PPMS 的进展很有用。总结了 PPMS 的治疗选择，包括已批准的治疗方法、正在进行的临床试验以及未来的研究方向。PPMS 研究的临床意义将与可靠的疾病结局评估、个体化治疗方法的改进以及希望的新型治疗靶点相关，这些靶点与进展的管理相关。
