2026 年 43 巻 3 号 p. 378-381
Multiple sclerosis (MS) is a disease that progresses without disease modifying therapy. With the advent of high–efficacy therapies (HET) in recent years, it has become possible to robustly suppress relapses. This has clarified that disability progression in MS includes not only relapse–associated worsening but also progression that occurs relatively early and independently of relapses, leading to the proposal of the concept progression independent of relapse activity (PIRA). Smouldering inflammation represents the key pathological driver, and both its mechanisms and clinical implications in smouldering progression have been studied. Two main pathological processes are considered to contribute to smouldering progression. One proposed mechanism is that activated microglia surrounding demyelinated lesions drive lesion expansion and disease progression. Another posits that MS–related pathology is already present in normal–appearing white and gray matter, where damage to myelin and axons can occur even in the absence of overt demyelinating lesions, ultimately leading to neurodegeneration and progression. With advances in understanding the underlying pathophysiology, it has become possible in clinical practice to detect smouldering–associated worsening (SAW) at an early stage through clinical assessment and imaging. As clinical outcome measures, it is necessary to assess not only EDSS or EDSS–plus, but also cognitive function, fatigue, and other relevant domains. As for biomarkers, there are still no serum or CSF markers that can be reliably used in routine clinical practice. However, MRI–based measures such as slowly expanding lesions (SELs), cortical lesions (CLs), and paramagnetic rim lesions (PRLs) are increasingly considered potential biomarkers of SAW. In particular, PRLs are considered a highly promising candidate biomarker for monitoring SAW. To date, few effective treatments specifically target MS progression. Further research into SAW is expected to contribute to the development of therapies capable of slowing or preventing disease progression.
