As an active adult and business owner, there were few things Roger loved more than being busy. Of course, his wife of over 41 years, Judy, and their two children topped the list; but as a land surveyor for three decades, Roger worked outside each day and often spent his evenings golfing, hiking, running or snowshoeing. He also loved playing his acoustic guitar, mandolin and bass guitar. He enjoyed pursuing his hobbies until they slowly became more difficult to do.
Roger first started experiencing subtle changes in 2001, shortly after he went to a baseball game with his family and the scoreboard appeared blurry. Roger’s blurred vision was the beginning of his symptoms that eventually evolved into complete loss of vision in one eye. His eye doctor referred him to a neurologist, who conducted an MRI that revealed two lesions on his brain potentially suggestive of MS.
It took Roger several months to get most of his vision back, while seeing a new neurologist specializing in MS who continued to monitor his brain with routine MRI scans. After two years of additional monitoring, Roger’s brain lesions remained unchanged, and his doctor let him know he didn’t need to continue the MRIs unless a symptom arose. Roger kept pursuing his passions, including getting a black belt in martial arts, completing a triathlon and hiking mountains—and his favorite, playing music.
Multiple years went by without further vision issues, so when Roger started to notice other changes, including needing to use the bathroom more frequently and longer bouts of fatigue, he didn’t naturally connect this with his brain inflammation, but rather as a result of aging.
When he was 59, Roger’s foot stopped functioning properly during a long walk with his wife. He decided to visit an MS center near his home in Colorado, where he received the official diagnosis of secondary progressive MS (SPMS), a type of MS where people typically have stopped experiencing relapses but continue to have disability accumulation with symptoms including motor impairment, fatigue, brain fog, depression, incontinence or sexual dysfunction. “Being diagnosed with SPMS is still a shock, but at least we know what we’re fighting,” said Roger. After that diagnosis, his symptoms continued to worsen. He experienced trouble moving his left side and difficulty walking in general. Because of this, Roger was forced to slowly give up hiking, then his music, and finally his career.
MS is a complex neurological condition that impacts approximately 1 million people in the U.S. alone.1 Accumulation of irreversible disability in MS may result from two different clinical phenomenon: relapse-associated worsening (RAW), which is the worsening of symptoms following a clinical relapse, caused by focal acute inflammation, and progression independent of relapse activity (PIRA), which refers to the gradual and sustained worsening of MS symptoms unrelated to any relapse.2 While PIRA is a commonly used term, this concept of progression has more recently been characterized as smoldering-associated worsening (SAW). SAW includes PIRA events, and typically manifests as an accumulation of motor disability and disability progression in other areas, including cognitive function, fatigue, pain and sexual dysfunction. As MS progresses, there often is a gradual shift in the main driver of increased disability from RAW to SAW, which is driven by a combination of persistent chronic inflammatory processes and neurodegenerative mechanisms that start very early in the disease course, much before symptoms appear, and can continue even when MRI scans show no activity.2 This is very similar to Roger’s experience of his symptoms worsening over the years while his MRIs reflected no major changes.
“In MS, the immune system mistakenly targets the protective sheath around the nerves, leading to inflammatory attacks that cause acute symptoms. In addition to focal inflammatory activity, which can easily be detected on MRIs, more complex smoldering pathological mechanisms, including chronic inflammation and neurodegenerative processes, drive a subtle accumulation of cognitive and physical symptoms, which are difficult to detect, and they are not accompanied by any change on standard MRI. This smoldering-associated worsening, leading to the gradual decline in neurological function, remains an important unmet therapeutic need,” explains Antonio Scalfari, MD, PhD, Consultant Neurologist, Imperial College Healthcare Trust & Northwest London Healthcare Trust. “With MS, physical disabilities, like trouble walking, often grab our attention, but additional subtle symptoms affecting, for instance, cognition or fatigue, are often missed or mistaken as ‘related to aging,’ and they may not be detected with our current monitoring tools.”
The Science Behind Smoldering-Associated Worsening Symptoms
Dr. Scalfari highlights the importance of recognizing the symptoms linked to smoldering-associated worsening early on. “Many people living with MS like Roger may not realize the importance of staying on top of symptoms. Any change can be a sign of ongoing SAW and can better inform discussions with healthcare providers on next steps,” he notes.
SAW symptoms include the decline of cognitive abilities, like memory, learning and processing speed, as well as physical abilities, like functional loss in upper and lower extremities, strength, walking, vision and speech. “It’s not just about managing relapses when we treat people living with MS,” Dr. Scalfari emphasizes. “We must also address the underlying smoldering pathological processes early-on and across the spectrum of the disease to potentially slow down the progression of disability.”
The Path Forward: Taking Action Through Advocacy and Awareness
Roger encourages people living with MS to educate themselves as much as possible and find support with others in the community who have shared experiences.
For people living with MS and their care partners, tracking symptoms closely can be the first step in understanding progression on a deeper level. Using these insights to encourage actionable dialogue with healthcare providers may be a useful tool to help mitigate long-term effects.
As MS research continues to evolve, understanding both processes of progression—RAW and SAW—is essential for patients, families and healthcare providers.2 Through shared experiences and expert insights, the MS community can better navigate this challenging journey and seek pathways to improve care.
If you or someone you know is living with MS, talk to your healthcare provider about developing symptoms. Also, visit https://www.rediscoverms.com/ to learn more.
Roger Kelley and Antonio Scalfari, MD, PhD were compensated for their participation in this article.
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References:
1. https://www.nationalmssociety.org/about-the-society/who-we-are/research-we-fund/ms-prevalence
