“We often think of spinal muscular atrophy (SMA) as a disease of the peripheral nervous system, but there’s evidence that the SMN protein is expressed in the central nervous system,” says Emilie Groulx-Boivin, MD, pediatric neurology resident, Montreal Children’s Hospital.

Neurology Learning Network spoke with lead author Dr Groulx-Boivin on-site at the 52nd Child Neurology Society Annual Meeting to learn more about the findings from her recent study “Structural brain abnormalities detected by Magnetic Resonance Imaging in Spinal Muscular Atrophy,” presented via poster at the conference.

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Editor’s note: This interview has been edited for length and clarity.

Brionna Mendoza, Associate Digital Editor, Neurology Learning Network: What led you and your colleagues to investigate structural brain abnormalities in children and adults with SMA?

Emilie Groulx-Boivin, MD: So I think we often think of spinal muscular atrophy as the disease of the peripheral nervous system, but there's been evidence that the protein itself, the SMN protein is expressed everywhere, in the central nervous system, in the brain. Some animal studies and case reports have pointed to central nervous system involvement, and with the advent of disease modifying therapies now, despite how much the developmental outcomes of these children have improved, and these adults, they are still left with significant motor impairments. So there's a role for potentially some adjunct therapies. We were thinking, "Could the central nervous system be a target for some of these adjunct therapies to try to further improve those outcomes?"

Mendoza, NLN: Could you walk us through your study methods and most significant findings?

Dr Groulx-Boivin: So it's a cross-sectional case control study of individuals between 5 and 45 years old who have a genetic diagnosis of SMA and 2 to 4 SMN2 copies. We also had the same number of healthy peers matched by age and sex. All of our 21 SMA patients and 21 controls underwent a brain MRI with a 3T MRI scanner, producing T1, T2, and fluid-attenuated inversion recovery (FLAIR) images. Then, all of these scans were reviewed by a single pediatric neuroradiologist who's highly specialized in this field. She reported all the abnormalities, and then we compiled them and analyzed not only the difference between the patients and the controls, but also trying to see if they correlated with any other measures, like the severity of their motor scores or the number of SMN copies that they have.

As per our most significant findings: In SMA patients, 9 of 21, or 43%, had structural brain abnormalities compared to 2 out of 21, or 10%, of controls. This gives an odds ratio of 7.1, which is quite a significant difference. In terms of what abnormalities we were seeing, the most common ones in SMA patients were widening of the arachnoid spaces and supratentorial ventriculomegaly. Of the 9 SMA patients who have abnormalities 2, or one-third, had both abnormalities, and of all of these patients, these 3 had only 2 SMN copies and the most severe phenotype of SMA.

So it seems like maybe the patients who are more severely affected tend to have those abnormalities.

Mendoza, NLN: Were there any outcomes different than what you expected to find?

Dr Groulx-Boivin: I don't think we had a very clear idea of what we were going to find. For my part, I think I was a little bit surprised that the majority of the patients with SMA actually had completely normal structural imaging. Although there's a difference, I think I expected the difference to be even bigger. As per the types of abnormalities that we found, it's a bit unclear to me whether they're specific to SMA, or general to neuromuscular or even just chronic diseases as a whole, because some of these findings are also seen in other neuromuscular disorders. So, I think a lot more studies are going to be needed to try to look into that.

Mendoza, NLN:  What would you say are the practical applications of your findings for clinicians who are treating SMA?

Dr Groulx-Boivin: I think it's a little bit early to directly translate this study into something clinical, but starting to look at the changes at the structural, at the functional MRI, at the white matter tracks in the brain just in general, is potentially going to be a target for some therapies. It would be an exciting adjunct therapy to add to the disease modifying therapies that we already have to further improve the outcomes.

Mendoza, NLN: What future areas of inquiry do your findings point towards?

Dr Groulx-Boivin: This is 1 of 3 elements that we're going to be looking at. So all of our patients were scanned with the MRIs, and one of my colleagues is already working on the white matter tracks. My next project is going to be on the functional MRI. So there's a lot more to come, and we're very excited to be looking at this data and trying to improve the outcomes in these patients.

Mendoza, NLN: Are there any other takeaways surrounding this research that you would like to leave our audience with?

Dr Groulx-Boivin: It goes along with what I was saying already, but this is kind of a brand new perspective on this disease, and now because of the disease modifying therapies, we see these children living longer, having a much improved quality of life. So, I think it's a very interesting field, and I encourage other researchers to get involved in trying to help us find out more about what's going on at the central nervous system level to try to see if that's a potential target.

Emilie Groulx-Boivin, MD, is a first-year pediatric neurology resident at the Montreal Children’s Hospital in Montreal, Quebec. She completed her undergraduate studies in physiology and medical school at McGill University. Under the mentorship of Dr. Maryam Oskoui, she has been investigating the involvement of the central nervous system in spinal muscular atrophy with the goal of ultimately optimizing patient outcomes