Current Series: Advances in the Treatment of Spinal Muscular Atrophy

Crystal Proud, MD: We've reviewed the fact that patients with spinal muscular atrophy [SMA] demonstrate different degrees of strength, and may demonstrate different degrees of strength at different ages. Julie, I was hoping that you could take us through some of the various assessments that we use to assess our patients and in clinic. 
Julie Parsons, MD: I think that it's a great question and actually a huge discussion because I think that we look at following 2 different groups of patients. We have patients who have not benefited from some of the new treatments that we have available and that really is our prevalent population. Then we have patients who have been involved in some of the new trials and some of the new commercially available treatments that we have for children.  
It may be that our assessments are a little bit different in that population of patients. Three of us are child neurologists, and so we are lucky to work at centers where we have wonderful evaluators who can apply standardized motor evaluation tools to patients. For providers who might not have this benefit, it's a little bit more difficult, I think, to run through all of the vernacular of the various tests that we have available.  
Certainly, as we read about the clinical trials and some of the clinical trial results, we all hear the words about CHOP INTEND [Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders]. What is the CHOP INTEND for? That's for a very specific group of patients who are the younger infants who are quite weak, maybe more related to the type I patients that Nancy was describing a little bit earlier. This test was specifically designed for babies who are very weak to try to detect various changes. 
We also have the Hammersmith test, and that is a motor function test for a variety of different functions and giving points on a scale to those functions to be able to evaluate how patients are doing over time with regard to either natural history, or if they’re treated, can we follow those metrics. We have the Bayley, which is also a motor test more for toddlers, infants, and younger children. 
Then as we get into older populations who are seated patients, then we start looking at upper limb function and looking at the RULM [Revised Upper Limb Module], for instance, to look at how their motor function is faring in terms of upper limb strength. I think in terms of the testing that we are able to do with the valuations are some of the tests that we would be able to look at and categorize and score. I think that those are extremely important tests to be able to do to follow long-term history for patients with SMA. 
Then we have the group of patients who have been treated pre-symptomatically who have done well. For those patients maybe hopefully in the future we move into just looking at what are normal milestones? What are normal motor milestones and can we use those? Can we use the WHO [World Health Organization] milestones of development to see how those babies are faring over time? That really is my ultimate hope, that we won't have to have separate motor scales.  
I also think it's really important to understand that although we can give points and scores using these validated standard scores, we really need to ask patients and families about their motor development and their motor ability as well because we really aren't able to capture some of the improvements that patients have demonstrated after treatment on some of our standardized testing. For instance, inpatients early on who were given nusinersen, being able to have increased core strength and drop an object, bend over and pick it up as a seated patient was something that was amazing to them. Or patients who were actually able to lift their own plates or to feed themselves when they hadn't been able to do that previously. 
Patients whose parents would say, “My gosh, now I can hear their voice. I can hear them cry. I’m not as worried about walking out of the room because I can actually hear them cry. I can hear their words when they’re trying to speak with me.” Those are all things that I think we aren’t able to actually capture in some of our motor testing. I think for patients and families that those assessments are really important to be able to try to understand as well. We also know that patients fatigue easily who have SMA, and we’re not great about understanding and measuring the fatigue factor. 
We sometimes equate that a little bit to strength, and so I think that there are some things that we have to tease out that will be a little bit more nuanced in the future as we go forward with treatments for patients with SMA. 
Crystal Proud, MD: You're right, there are certainly areas that we could use some improvements on with regard to how to measure dysfunction but also gains in function, or even maintenance of function. One area that I know we've all been talking a lot about has been bulbar function as well, and how do we go about measuring that? How do we go about monitoring that in a way that it's going to be reproducible and reliable? Any comments on that from the panel? 
Julie Parsons, MD: I think for bulbar function, there are a couple of things. Certainly, watching kids feed and eat, hearing them speak, having them sing, hearing them cough, to me all of those things are helpful in terms of functional testing. Certainly, we have swallow studies and all that we can do as well, but I think looking at functional abilities, even during physical examinations, is very important. John and Nancy, do you have other ways that you assess that in the clinic? 
Nancy L. Kuntz, MD: With the very young babies, obviously, the weight gain, because of the effectiveness of swallowing and the safety of that. Obviously, if they are having problems and they're being supplemented with tube feedings, you lose that as something to follow. Certainly in the very young infants and we're hoping the treated infants, seeing them grow at a normal rate is very good reassurance that they have a good swallow. 
John Brandsema, MD: I think also following the respiratory function is linked with this, that often those 2 things go together, the trouble with the breathing and the trouble with the bulbar in swallowing. In the older patients, you can get much more objective with pulmonary function tests and sleep studies in terms of trying to evaluate this. But in the younger babies, again, it's all tied to thriving and to the pattern of respiratory effort that you're seeing in the infant.