Atrophy of Brain Lesions Predicts Disability in MS, 10-year Study Finds

Atrophy of Brain Lesions Predicts Disability in MS, 10-year Study Finds

Atrophy (shrinkage) of brain lesions correlates with physical disability in patients with multiple sclerosis (MS), new research reports.

The study, “Atrophied Brain Lesion Volume: A New Imaging Biomarker in Multiple Sclerosis,” was published in the Journal of Neuroimaging.

Magnetic resonance imaging (MRI) scans are used routinely on MS patients to track new lesions and the growth of existing ones, which have long been regarded as indicators of disease progression. Approval of a new medication typically depends on its ability to reduce the number of brain lesions over 24 months.

However, researchers now suggest that the disappearance of lesions may indicate pathological change, such as atrophy, as well as beneficial alterations, including resolution or repair of myelin (the protective layer of nerve fibers which is typically damaged in MS patients).

Focusing on pathological changes in brain lesions, the scientists examined lesions observed in prior scans, but later replaced by cerebrospinal fluid (the liquid filling the brain and spinal cord). This opposed the traditional approach of examining new lesions, they noted.

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“The big news here is that we did the opposite of what has been done in the last 40 years,” Michael G. Dwyer, PhD, first author of the five-year study, said in a press release. “Instead of looking at new brain lesions, we looked at the phenomenon of brain lesions disappearing into the cerebrospinal fluid.”

Specifically, investigators compared the rate of lesion loss due to atrophy to the appearance or enlargement of lesions both at the start of the study and at five or 10 years of follow-up.

Conducted at the University at Buffalo (UB) in New York, the five-year study included 192 patients with either the most common form of MS, relapsing-remitting MS (126 patients), progressive MS (48), or clinically isolated syndrome — the first episode of inflammation and loss of myelin, but not yet meeting the criteria for MS.

The team found that unlike new or enlarged lesions, the amount of atrophied lesion volume correlated with clinical disability as assessed by the Expanded Disability Status Scale (EDSS), a widely used method to quantify disability in MS.

Similar results were found in a 10-year study of 176 patients conducted in a collaboration between UB researchers and scientists at Charles University, in the Czech Republic. This 10-year research was presented at the annual meeting of the American Academy of Neurology (AAN) in Los Angeles, California, in April.

“We didn’t find a correlation between people who developed more or larger lesions and developed increased disability,” Dwyer said, “but we did find that atrophy of lesion volume predicted the development of more physical disability.”

When dividing the analysis by MS types, the scientists found that patients with relapsing-remitting MS had the highest number of new lesions, while those with progressive MS (the most severe subtype of the disease) had the most pronounced atrophy of brain lesions.

“Atrophied lesion volume is a unique and clinically relevant imaging marker in MS, with particular promise in progressive MS,” the researchers wrote.

“Paradoxically, we see that lesion volume goes up in the initial phases of the disease and then plateaus in the later stages,” said Robert Zivadinov, MD, PhD. Zivadinov is senior author of the five-year study and first author of the 10-year research. “When the lesions decrease over time, it’s not because the patients’  lesions are healing but because many of these lesions are disappearing, turning into cerebrospinal fluid.”

Also of importance, Zivadinov noted, was the finding that atrophied brain lesions were a better predictor of disability progression than whole brain shrinkage, which is the most accepted biomarker of neurodegeneration in MS.

“Our data suggest that atrophied lesions are not a small, secondary phenomenon in MS, and instead indicate that they may play an increasingly important role in predicting who will develop a more severe and progressive disease,” Zivadinov concluded.

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has studied Biochemistry also at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario, in London, Ontario. His work ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has studied Biochemistry also at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario, in London, Ontario. His work ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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20 comments

  1. Yael Gottlieb says:

    So does this mean that there is no such thing as healing lesions in MS? But rather their shrinkage or disappearance is a sign of worsening MS condition/symptoms in the long run due to lesions that turn into spinal fluid?

  2. Jack McDee says:

    I’m kind of speechless – I’ve read this article over and over again for the last 2 hours, and then searched the web and dug out all of the verbatim study details I can find. And their conclusion seems to be that the disappearance of MS lesions creates an expectation of MORE severe progression.

    And the headlines of the various articles I’ve been able to find interpret the results the same way and suggest the same conclusion. A point of view that is the total opposite of what every person with progressive Multiple Sclerosis has been led to believe for the last three decades. Completely contrary to the solitary belief that PPMS and SPMS patients cling to — hoping that maybe, just maybe, there is some medical discovery to be found out there. Be it a drug, a vascular procedure, a diet, a treasure trove of homeopathic And natural supplements & a specific exercise regimen, a bleeding edge stem cell transplant, something – anything – that might actually make their lives better: if lesions start to disappear, because your cerebrospinal fluid seems to be spontaneously healing your myelin sheath: it’s a really bad sign.

    So what now?

    • b says:

      I think your final conclusion isn’t quite right. Lesions are disappearing because those neurons are dying and leaving a void, nothing is there anymore and it is instead filling with CSF. If myelin is being repaired and the neurons are being restored to a “healthy” state, then there is no concomitant sign of increased CSF in that region.

    • Carol says:

      I agree, spending all those years, money etc, for what???? Blah blah blah, approve stem cell therpy, make it affordable & access able to MS suffers !!!

  3. I find myself wanting to have all of my past MRI’s looked at again and reassessed. Could be a ploy to get all MS patients to do the same, thereby, causing a huge flux of cash flow into the hospitals. Can you imagine???? Planned or unplanned, the hospitals win again and we continue to remain at their mercy.

    • The way I interpret the findings revealed in this study is that lesions which disappeared and were replaced with cerebrospinal fluid were indicative of a loss of nerve cell tissue.
      A lesion that disappears without a loss of tissue was not was not what was being discussed in theses findings. That would presumably correlate with no loss of function measured by EDSS, or “healing” at the lesion site.

  4. Debbie says:

    Most people with primary progressive MS, tend to have MRIs that do not change much, yet we get worse over time. This might not hold true for all of us, but for many.

  5. Christina says:

    I have been diagnosed with ppms but have been told I fall in the 5% that has no spinal cord lesions and spinal fluid shows no signs. I have brain lesions that are very typical of ppms.

  6. Tyler Schortgen says:

    I just got home from my neurologist appointment in Indy at IU Health today! My doctor said my new MRI of my brain showed lesions in my previous MRI’s had actually shrunk! I decided to look and see what this actually meant! Guess what this is saying it isn’t good news after all!!!

  7. Marlene Mallett says:

    Just how often do MS patients get MRI’s. My husband has PPMS and hasn’t had an MRI in over two years. Is that normal?

    • Pam says:

      My MS doc will go 2-3 years before I have to have an MRI if my previous MRI has no change and looks ok. Hope this helps. FYI…….I have RRMS.

    • Špela Bukovec says:

      I have MRI once a year, sometimes twice. I had till now only one relapse and my desiase is not very progressive. But I think we should have it at least once a year because MRI picture can change fast. (Sorry for my bad english)

  8. Bandy Singh says:

    My initial understanding was that with age the brain does lose volume (hence shrinkage) and that this also seen in Parkinson’s. If an old lesion is replaced by CSF then the argument has relevancy. But what if shrinkage is in total brain volume and not at an old lesion site. For this reason, I believe the study outcome is misleading. Shrinkage of lesions is a good thing and not necessarily a marker of disability. Keep in mind these studies are suggestive but not in stone. Wait for another study to counteract the results and further confuse all of us c

  9. Karla Schmidt says:

    My question would be does the spinal fluid look like myelin tissue? What exactly made them decide its being replaced with the spinal fluid. If the lesions were being replaced with spinal fluid, i believe the tissue would have died and i wouldnt have regained mobility. So obviously there has been some type of healing of myelin. I have relapsing remitting MS. Diagnosed 14yrs ago. I couldnt walk, but I can now. No new lesions, the 13 I had upon diagnoses in 2005 shrunk in size. I have not had a recent MRI. But really wld like to get one now…

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