Peter L. Salgo, MD: Let’s talk about clinical sense right now. Let’s go over something like the diagnostic work-up for SMA [spinal muscular atrophy], all right? What does that include?
John Brandsema, MD: For the patient who is presenting with symptoms that are concerning for the disorder, it’s quite straightforward. You would do genetic testing. Usually, it’s through quantitative PCR [polymerase chain reaction] or some other method looking for that double deletion of the SMN1 gene. If you didn’t find it, but you were very convinced the patient fit that phenotype, you would then have to sequence the SMN1 gene to look for a mutation if you didn’t find the double deletion. That will establish your diagnosis in the patient.
The challenge is that in the most severe form, there are many symptoms that start to make the clinician be suspicious of SMA that come relatively quickly in infantile onset, such as tongue fasciculations and changes in the breathing pattern. But in the milder forms, it can be much more slowly progressive and simulate a lot of other disorders, so you may just have a limb-girdle distribution of weakness that looks a lot like a muscular dystrophy or something else in terms of the way that the patient is presenting. Then, you might need tests such as electromyography [EMG] and other things to be able to get into the neurogenic category.
Peter L. Salgo, MD: When do you pull the trigger on an EMG? An EMG is not very expensive, right?
John Brandsema, MD: It is not, unless you also have to sedate the patient as part of the procedure, which is common in the pediatricsbecause of the procedural support as well. It’s tough to go through for a child to do an EMG test, so I try to be judicious about when I use that. But nowadays—I mean, in our center [Children’s Hospital of Philadelphia]—we do the double-deletion test in-house, so we can have an answer within 3 days when we send it off, whether the patient is affected. Because we’re now again in the realm of having disease-modifying therapies that need to be instigated as soon as possible, I think for doing a genetic test early on in today’s world, if you have a suspicion for a disorder like this, it is important because you need to identify the patients who could benefit from treatment as soon as possible.
Peter L. Salgo, MD: You’ve got a scale, right? The Hammersmith Functional Motor Scale?
John Brandsema, MD: That’s 1 outcome measure. The challenge in SMA is that there’s such a huge spectrum of involvement that you can’t have 1 scale that’s going to measure every patient with SMA accurately. We start off in the very youngest ones with a scale called CHOP INTEND [Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders], which was developed to measure type 1 SMA patients, as well as the Hammersmith Infant Neurological Exam. The scale you mentioned, the Hammersmith Functional Motor Scale—there’s now an expanded form—is more appropriate in the slightly older patients with a lot of upper-limb function, so classically a type 2 or type 3 natural history patient would be measured with that scale. Then if someone is ambulatory with SMA, they may actually be maxed out on that Hammersmith scale. For them, it may be better to use something like a 6-minute walk test to measure their function. You’re really trying to find the right test that’s going to measure the patient’s function in the moment and also how they’re changing—which, in the natural history, would be loss over time on these scales of points or function. But with these new disease-modifying therapies, it may in fact be improvement.
Peter L. Salgo, MD: What is this MFM-20 [Motor Function Measure 20] that we need to know about?
John Brandsema, MD: That would be another functional scale that’s meant to follow patients with SMA. There’s a bit of a continental difference. People in Europe tend to prefer the MFM compared with people in the United States using other outcome measures. But they’re all applicable in measuring SMA function in the appropriate context.