Why Does My MS Feel Worse If I Don’t Have Any New Lesions?

People with multiple sclerosis may develop ‘silent progression,’ in which worsening symptoms sneak up slowly and evade common neurological testing.

My neurologist smiles as she reviews my latest MRI scans. No new lesions, no active demyelination showing a relapse of my multiple sclerosis (MS).

She runs me through my biannual exam and notes that I’m even showing functional improvement in some areas since my last exam.

“The meds are working,” she says. “Just keep doing what you’re doing.”

It’s good news, I know. But confusing news.

If everything is so great, why do I feel worse?

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A ‘silent disease’

Those of us with relapsing-remitting multiple sclerosis (RRMS) are familiar with relapses — when a new or worsening symptom appears suddenly and remains for at least 24 hours. When the symptom subsides or disappears entirely, we’re in remission.

But MS is sometimes called a “silent disease” because the disease advances even during remission. This process is referred to as “silent progression” or PIRA (progression independent of relapse activity) and is an infrequently discussed reason for feeling worse.

What we know, though, is that despite a stable MRI, a clinical change is taking place during PIRA.

Sometimes, the change is so slow-moving that people with MS are unaware of the development. Sometimes doctors miss it during a standard neurological exam.

Eventually, of course, the new symptom becomes more apparent, and the person is left to wonder when the progression took place.

Silence can be maddening.

So what happened?

According to a 2022 study, PIRA may be the result of accelerated brain atrophy resulting from chronic inflammation.

So, no, you’re not “crazy.” There’s a real reason you feel worse.

And it’s an extremely common reason, too. According to a 2023 study, PIRA is the most common form of disability accumulation among all types of MS. Yes, that includes the traditional and oft-discussed relapses.

Data suggests that the proportion of PIRA-associated progressions (versus relapse-associated progressions) increases with age, longer disease duration, and use of highly effective disease-modifying therapies (DMTs), which may suppress actual relapses.

Clearly, silent progression is real, common, and (unfortunately) isn’t going away.

How PIRA can be detected

Most frequently, neurologists turn to the Expanded Disability Status Scale (EDSS) to uncover progression in their MS patients.

The EDSS assesses function in eight areas:

• visual: visual impairment; blurred vision; loss of visual field
• motor: impaired mobility; stiffness; limb weakness
• cerebellar: problems with balance or tremors
• brainstem: double vision; problems with speech or swallowing
• sensory: abnormal skin sensations like tingling, numbness, or pain
• bowel and bladder: increased or decreased frequency; urgency; incontinence; an inability to empty the bladder completely
• cerebral: problems with thinking or memory
• ambulation: difficulty with walking

Silent progression, however, may not be immediately apparent through the EDSS. Thus, when a person’s EDSS score is unchanged and their MRI is stable, the healthcare team may initially assume there has been no progression.

Other, more sensitive tests may detect PIRA:

• The Timed 25-Foot Walk Test, where you walk a specified distance and a doctor measures the time that was needed.
• The 9-Hole Peg Test involves taking pegs from a bowl with your left hand, then your right hand, and inserting them into nine holes while a doctor measures the time needed to complete the task.
• The Symbol Digit Modalities Test is a timed test of assigning numbers to characters which is used to evaluate cognitive function.

These tests, in combination with the EDSS, may uncover silent progression in real-time.

Speak up!

While MRIs and your neurologist’s standard examination are effective in exposing many of the signs of MS progression, they are not perfect. PIRA can be a normal part of the MS disease process and something we all may face despite our best efforts.

If you find yourself “silently progressing,” don’t assume that your DMT is not working. It may very well be doing exactly what you want it to do: reducing the number of relapses you experience, which remains a highly significant factor in slowing disability in MS.

No drug is perfect, and, as always, your doctor is your best partner for setting (and changing) your treatment protocol.

But do remain a vigilant participant in your care and communicate any and all new MS symptoms to your neurologist. If the numbness in your fingers is now creeping into your toes, mention it. If your daily pain is a 7 out of 10, when it used to be a 5, call the office.

MS throws a lot our way. Be sure to update your doctor during each appointment about every new symptom and contact them immediately if you experience a major shift in how you feel.

It is only by speaking up that we can give voice to the silence.