Guideline offers roadmap for spinal and bulbar muscular atrophy care

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is a rare, progressive neuromuscular disorder that is often misdiagnosed and diagnosed late. A new CMAJ guideline offers Canadian-specific recommendations for its recognition and management.

On this episode we hear from Richard Paul, a former bus driver from Saskatoon, who recalls how his symptoms began suddenly with an inability to bite into a sandwich and, over the years, progressed so gradually he barely noticed the loss of strength. His experience captures both the slow, inexorable progression of SBMA and the uncertainty of living without a diagnosis for decades.

Mr. Paul was finally diagnosed by Dr. Kerri Schellenberg, a neuromuscular neurologist at the University of Saskatchewan and lead author of the guideline. She explains the clinical hallmarks of SBMA, its overlap with conditions such as ALS, and the non-motor manifestations that require attention. She also discusses the higher prevalence among Indigenous populations in Canada and how her team worked with a community Guiding Circle to ensure the recommendations reflect culturally appropriate care.

For physicians, the guideline provides practical direction to support earlier recognition, timely referral, and multidisciplinary management. While there is no cure, coordinated care can significantly improve quality of life for people living with SBMA.

For more information from our sponsor, go to md.ca/md-difference

Join us as we explore medical solutions that address the urgent need to change healthcare. Reach out to us about this or any episode you hear. Or tell us about something you'd like to hear on the leading Canadian medical podcast.

You can find Blair and Mojola on X @BlairBigham and @Drmojolaomole

X (in English): @CMAJ
X (en français): @JAMC
Facebook
Instagram: @CMAJ.ca

The CMAJ Podcast is produced by PodCraft Productions

Transcript

Dr. Blair Bigham:

I'm Blair Bigham.

Dr. Mojola Omole:

I'm Mojola Omole. This is the CMAJ Podcast.

Dr. Blair Bigham

So, Jola, today we're talking about a rare disease. Should we set this up as a mystery? It is X-linked.

It is a neuromuscular disease. It presents with progressive muscle weakness. It is…

Dr. Mojola Omole

You know that, like, most of us don't, like, this isn’t jeopardy. We won't get this. 

Dr. Blair Bigham

Well, let's just cut to the chase.  We're going to talk about spinal and bulbar muscular atrophy, or SBMA.

Dr. Mojola Omole

And it's such a fascinating, like, this practice article that's in the new CMAJ was just fascinating to go through because it looked at the latest evidence and offered Canadian-specific recommendations for the management and diagnosis of SBMA.

Dr. Blair Bigham

And it's particularly interesting to me because, as I've learned, SBMA is usually diagnosed relatively late. People don't pick up on it right away. And so that can lead to, you know, worse quality of life, delayed symptom management.

And so I think this article is really interesting. There's another aspect to it, though, that I think listeners will be interested in, and that's an equity piece. This disease tends to be found more often in people who are Indigenous.

Dr. Mojola Omole

Yeah. And part of why this article is so important is that it addresses those knowledge gaps that international guidelines don't fully cover, especially when we're talking about what is culturally appropriate care for Indigenous populations who are disproportionately, as you said, affected by SBMA.

Dr. Blair Bigham

So we're going to speak to a Canadian expert, Dr. Kerri Schellenberg, about these Canadian guidelines. She is a neuromuscular disease expert from the University of Saskatchewan. But first, we're going to hear from one of her patients, Richard Paul, who has SBMA.

Richard Paul

My first time, I had a symptom that blew my mind. I had no idea why it happened.

Dr. Blair Bigham

About 30 years ago, Richard Paul was sitting in a Subway restaurant eating his favourite, a foot-long meatball sub.

Richard Paul

When I went to take another bite, and my mouth would not work to bite through the bread, meat, anything. I couldn't bite it at all. I had to set the sub down and have a drink.

And then I told my wife that this is really weird. I couldn't bite.

Dr. Blair Bigham

After a few minutes, he tried again, and this time he had no problems biting into the sub. Richard didn't think much of it at the time, just something odd that happened and then went away. About a month later, though, it happened again, and again a month after that.

Soon, every few weeks, he would have these episodes where his jaw was suddenly too weak to chew.

Richard Paul

It wasn't consistent, but it was my jaws that were my first sign of real weakness.

Dr. Blair Bigham

About seven years after the meatball sub incident, Richard experienced a new symptom while at work as a Saskatoon City bus driver. The bus had three small steps, something Richard climbed every day without trouble.

Richard Paul

One year I went out, I went to step up my steps, and I tripped. My toe tripped on a step and knocked me down.

Dr. Blair Bigham

A few mornings later, it happened again. He tripped on the steps getting into his bus.

Richard Paul

And it was my first sign of my legs giving out on me.

Dr. Blair Bigham

The weakness in Richard's legs progressed slowly, but inexorably forward. Eventually, in 2010, about ten years after that first trip up the stairs, Richard retired from the bus service. It had now been 17 years since his first problems began with that meatball sub.

The difficulties came so slowly, Richard had trouble noticing them.

Richard Paul

It was almost hard to tell something was going on until you tried to do something you hadn't done in a while and you couldn't do it as easily as you once could.

Dr. Blair Bigham

In 2015, Richard finally went to see his family doctor about his symptoms. He was sent for an MRI with contrast, blood tests, and a nerve conduction study. He was then referred to a neurologist at the University of Saskatchewan.

Richard Paul

And we were in the examining room and he was standing across the room looking at me and asked me, Have you ever been diagnosed with Bell's palsy?

Dr. Blair Bigham

The physician asked about Bell's palsy because he noticed that Richard's face was drooping.

Richard Paul

Well, I said, No, I've never heard of Bell's palsy, ever.

Dr. Blair Bigham

It wasn't impossible that as a child Richard did have Bell's palsy and didn't know about it. He grew up on a family farm. They were, as he says, poor as church mice.

They didn't go to the doctor unless there was an urgent problem. It was around this time that Richard learned his brother was also suffering from many of the same symptoms. He had been diagnosed with SBMA, spinal and bulbar muscular atrophy, also known as Kennedy's disease.

Richard saw another neurologist before he was eventually referred to Dr. Kerri Schellenberg. She ran a genetic test confirming a diagnosis of SBMA. Richard's symptoms continued to progress.

He now uses a scooter and eating, drinking and speaking are increasingly difficult. It's all forcing him to confront what this might mean for his future.

Richard Paul

Every now and then, every day, it makes you wonder, if things get worse, what do I do? So I'm playing with this idea and death is near.

Dr. Mojola Omole

You heard Richard say the last neurologist he saw, the one that finally diagnosed him, was Dr. Kerri Schellenberg. She's the first author of the new guideline, “Best practice recommendations for the clinical care of spinal and bulbar muscular atrophy,” published in the CMAJ. She's a neuromuscular neurologist at the University of Saskatchewan, where she's also associate professor and medical director of the ALS and Motor Neuron Disease Clinic.

She's also the medical director of electromyography at Royal University Hospital. Kerri, thank you so much for joining us today.

Dr. Kerri Schellenberg

My pleasure. Thank you so much for having me.

Dr. Blair Bigham

Kerri, Richard Paul was one of your patients. What goes through your mind as you listen to him?

Dr. Kerri Schellenberg

I think Richard's story really illustrates the diagnostic odyssey that people go through to find out what's going on. One of the difficulties is that this disease is so slowly progressive and involves multiple body areas. It's very difficult for physicians to sort out the problem immediately.

It's also a very rare disease. And because of that, many physicians aren't familiar and patients may be diagnosed with other conditions before they're actually eventually diagnosed with SBMA. So I think this also really highlights the need for increased awareness and advocacy.

Dr. Blair Bigham

I'm going to stick with the acronym here, SBMA. It is very rare, and I have heard of it ostensibly. I don't know much about it. And I'm wondering if our listeners might be in the same boat.

Can you walk us through SBMA? What is it?

Dr. Kerri Schellenberg

Yeah, absolutely. So SBMA, otherwise known as Kennedy's disease, is a motor neuron disease. It's hereditary.

And so it's due to a trinucleotide repeat on the androgen receptor gene. And so women are carriers and make it symptoms to a lesser degree. But it's the men who exhibit full symptoms.

Dr. Mojola Omole

How common is it in the general population?

Dr. Kerri Schellenberg

Not common at all. It's very rare. And most people haven't heard of it.

And even many neuromuscular specialists only see a few cases in their career. It's generally reported to be 1 to 2 per 100,000. And we've recently published that in Saskatchewan, we expect that their prevalence is 14 per 100,000.

And that's probably an underestimation.

Dr. Mojola Omole

If this is something rare, why did you think it was important to publish these guidelines regarding best practices for it?

Dr. Kerri Schellenberg

So that's an excellent question. So maybe I'll take a step back and let you know that while this is quite rare, I'm not the first person to notice an association between SBMA and people with Indigenous heritage. But this is not well understood nationally or globally.

And in fact, there are some publications that suggest that it hasn't been reported in Indigenous populations. And so in my training and practice, I've been in the prairie provinces and I've seen this association, but I was never struck by the high prevalence so much as when I came back to Saskatchewan to practice eight years ago. And I would be picking up spinal bulbar muscular atrophy and people who had been admitted for strokes or people who were in the rehab department and not improving.

And I would get a question, what's going on? Do they have another neuromuscular disease? And indeed they did.

They had SBMA. And so I was so struck by this high prevalence and the lack of any literature surrounding this association between SBMA and the Indigenous population that we started to explore it in more detail.

Dr. Blair Bigham

So walk us through what it looks like. Like, what's the natural history? How do how do patients feel when they have this disease?

Dr. Kerri Schellenberg

Right. So symptom onset is probably in the 20s or 30s when men develop postural tremor and begin having cramps and fasciculations. One of the hallmarks is perioral fasciculations.

And then over time, men develop weakness of arms and legs and then bulbar dysfunction. So difficulty with speech and swallow. And then eventually in latter stages, they develop respiratory weakness.

And so the phenotype looks quite similar to ALS. But how it presents is very different in younger individuals with these additional symptoms that progress very slowly over decades.

Dr. Blair Bigham

And do women have any symptoms at all, or is it all men who would present to a physician?

Dr. Kerri Schellenberg

Women do get symptoms, but to a lesser degree. And this is not well studied. And so this is one of our active areas of research because it's not well understood.

And so women typically develop symptoms in latter years after middle age, and they tend to have the symptoms that men have very early in disease. So cramps, fasciculations, perhaps a little bit of weakness. Bulbar dysfunction is very rare.

Respiratory function has not been recorded. And so it's to a much lesser extent.

Dr. Blair Bigham

What about non neurologic symptoms? Are there other things to be looking out for?

Dr. Kerri Schellenberg

Absolutely. This is another area that has not been well studied, but has important implications. So, for example, cardiac arrhythmias have been reported and sometimes potentially fatal arrhythmias such as Brugada syndrome. And so part of our multidisciplinary care now has been to include referral to cardiologists for each and every patient.

There are multiple endocrine abnormalities that can occur, including issues with osteoporosis and bone health, diabetes, impaired fasting glucose, fatty liver disease, hyperlipidemia. So there are a number of things to look out for that may certainly impact health that are not well recognized and understood even amongst neuromuscular physicians. One of the things that makes our guidelines unique is that we focus on some of these non-motor manifestations, including sensory dysfunction.

There's only one set of guidelines in the past, and these are French guidelines that don't address carrier status and they don't address the high prevalence in Indigenous populations. So this really makes our guideline unique.

Dr. Mojola Omole

You said there were sensory, like what kind of sensory changes would someone notice?

Dr. Kerri Schellenberg

The numbness in the feet would be the biggest issue, and this can translate into gait imbalance, and so falls can happen because of the numbness.

Dr. Mojola Omole

Wow. And is this like a later manifestation or this is even like in their 20s?

Dr. Kerri Schellenberg

So numbness tends to progress a little bit later, but again, this is not well studied. We don't have good natural history data, and so that's one of the reasons that we're studying this further. So when we first noticed this association, I reached out to a neurogeneticist in Calgary.

His name is Gerald Pfeffer, and also we partnered with Dr. Alexandra King and Dr. Malcolm King, who have Indigenous heritage and lead Indigenous research programs here at the University of Saskatchewan. And so they formed a community guiding circle of men with lived experience, as well as a knowledge holder and elder. And so this group meets regularly with Dr. Pfeffer and I and regularly informs us as to what the research priorities are. And we work back and forth to present the research that we have and determine what's acceptable and appropriate in context. And they keep saying over and over that awareness is so important. They want more advocacy.

They want more awareness of the disease. They'll often present to health care professionals, and the health care professionals don't know much about SBMA and they don't know how to treat it. And this is an ongoing concern for our population.

This was really the impetus for why we decided to work on the guidelines.

Dr. Mojola Omole

So once you have the suspicion of it, are there a range of tests or assessments that you need to order?

Dr. Kerri Schellenberg

The most important thing is sending the person to a neuromuscular specialist who can look at their presentation and context. They will likely do an EMG and genetic testing to confirm the diagnosis.

Dr. Blair Bigham

How do you sort of split that between... So I feel like I'm on the lookout for ALS. Like it sounds more common.

I know how it can be caught early on, at least. How should a clinician frame this and maybe what they're more comfortable with when it comes to being on the lookout for ALS?

Dr. Kerri Schellenberg

That's a great question. And these two diseases are often confused. I have been referred patients for ALS who end up to have SBMA because it is difficult to discern the difference.

Some of the clues can be younger onset and more protracted disease. Perioral fasciculations are a hallmark of SBMA and a distinguishing factor. And then additionally, these non-motor manifestations should point you in the direction of SBMA.

So if there's associated tremor, if there are the metabolic involvements. So some of those additional features will help to determine.

Dr. Blair Bigham

So my trigger may be to say, oh, I need to find a neuromuscular specialist are younger age, the perioral fasciculations. And so are there any other red flags or any other early stage signs where I should be like, oh, neuromuscular specialist?

Dr. Kerri Schellenberg

Yeah. So the first symptoms are tremor and cramps and fasciculations. And this progresses to the limb weakness followed by bulbar dysfunction.

And so any of those early signs would be a good trigger. You may also see an elevation in CK level.

Dr. Mojola Omole

Oh. So do most of your patients present to ER with certain symptoms or is it kind of like they're going to their family doctor and it seems vague what's going on with them?

Dr. Kerri Schellenberg

They present in multiple ways. So I do get some from the hospital system when people are admitted for other reasons and it's suspected that they may have a neuromuscular condition. Sometimes it's as late stage as difficulty with respiration and need for BiPAP.

Sometimes it's so early that they're referred to me for facial twitches. So it's a whole range. And I think that's part of the problem, that the symptoms are so nonspecific early in disease course that often these people are missed.

And so having awareness of the prevalence may be really helpful in terms of ensuring that these patients get the care and the multidisciplinary supports that they need.

Dr. Mojola Omole

So your work shows that the prevalence is in Cree and Soto populations. Do we know why it's concentrated in those indigenous groups?

Dr. Kerri Schellenberg

When we first looked at this, we did genetic testing. And so Dr. Pfeffer's lab took DNA samples and they did haplotype analysis and they were able to see that there is a founder effect, at least one founder effect, probably around 200 years ago. It's interesting because the highest prevalence we think is in Saskatchewan, followed by Manitoba and Alberta and portions of Western Ontario.

In our study, we found that the highest incidence was in those of Cree and Soto heritage and also Métis. If you superimpose the traditional homeland of the Cree, that maps almost exactly to where we're finding the highest prevalence in Canada.

Dr. Mojola Omole

And how about internationally, like any other indigenous populations that this has been noted in?

Dr. Kerri Schellenberg

No, there are pockets of higher prevalence in Finland and Italy, probably Japan as well. Our rate is far, far higher than in any of those populations that I've listed. And I suspect that what we're seeing is actually an underestimation because of some additional social determinants of health.

We don't see all the people that I know have SBMA because our patients will talk about their cousins and their uncles and their brothers who have symptoms, but don't get seen for a variety of reasons.

Dr. Mojola Omole

Which part of the social determinants of health is influencing them for us not to see the prevalence in indigenous communities? And I'm assuming that will also affect their outcomes.

Dr. Kerri Schellenberg

Yeah, I think part of the reason we don't see people is some appropriate distrust of the medical system. And so I know, for example, some of the people that I have seen, their symptoms have been misattributed to other issues. So, for example, there was an article in CBC a few years ago about somebody who was evicted from a furniture store because they thought he was drunk when, in fact, he was not.

And he had dysarthria because of his SBMA. And so as I talk to more people, I hear more and more of these horrible stories of how people's symptoms have been misattributed to other issues. And this really, again, is one of the reasons why our population is so insistent that we need more education and advocacy and awareness.

Dr. Mojola Omole

You said that they've been misattributed to other things. Are there like other medical things that sometimes practitioners might think it is?

Dr. Kerri Schellenberg

Yeah, some of my patients have been previously diagnosed with Bell's palsy, for example, because there's facial weakness and it can be asymmetric. Many of my patients have been misdiagnosed as stroke because of the limb weakness that's involved and the dysarthria. ALS is another common misdiagnosis.

And there can be other myopathies that people may be diagnosed with erroneously. And part of the reason is because it is rare and it is challenging. And there are many phenotypic correlates with other possible diseases.

Dr. Mojola Omole

And how does this, like the delay to care, influence outcomes for patients?

Dr. Kerri Schellenberg

We don't have good...

Dr. Mojola Omole

Sorry, delay to diagnosis and then care. Sorry.

Dr. Kerri Schellenberg

Yeah, yeah. We don't have good data on this. And this is an area that we want to study more.

We know from extrapolating from the ALS population that patients who go to a multidisciplinary clinic have better outcomes, both quality of life and quantity of life. We don't have that same data for SBMA simply because it hasn't been studied.

Dr. Blair Bigham

Once you have diagnosed it, Kerri, what treatment options are available?

Dr. Kerri Schellenberg

At this time, there is no disease modifying agent or cure. And treatment is symptomatic. But we do know that appropriate symptomatic care provides multiple benefits.

So, for example, if there's dysphagia, then modifying food, safe swallow strategies and sometimes feeding tube are important to try to reduce aspiration pneumonia. Respiratory support is also important. There can be obstructive sleep apnea as well as reduced respiratory function that can create need for BiPAP.

And then the symptomatic management is so important. People need equipment and aids and supports in order to have maximum independence with the functional difficulty that they do have.

Dr. Mojola Omole

I know this sounds really weird to say, like, I think as I'm a surgeon, you're a neurologist. This seems like awful to have.

Dr. Blair Bigham

Seems horrible.

Dr. Mojola Omole

It's like chronic, debilitating, slow disease that with no changes in your lifespan.

Dr. Kerri Schellenberg

It is very hard. And so one of the things that we're realizing is how emotionally difficult this is and how there's needs for additional supports. And so we've been partnering with other organizations such as the Kennedy's Disease Association, Muscular Dystrophy Canada, in order to help provide not only physical supports, but also emotional supports.

And community supports and sharing circles. The Pewaseskwan group at the University of Saskatchewan has been so wonderful. This is an indigenous research group that has created these community guiding circles and sharing circles so that people can tell their story.

And we're actively looking at qualitative research, such as PhotoVoice, in order to capture these stories and these experiences from a patient perspective. 

Dr. Mojola Omole

Sorry what's PhotoVoice? 

People take pictures of their environment and situation, not people, but things, in order to help tell a story from their own perspective.

The idea is that a picture is worth a thousand words. And so we're actively engaged in this research project and should have results available soon that we can share.

Dr. Mojola Omole

Sorry, that's really beautiful. So your paper emphasizes a lot about culturally appropriate care. So these are things that you've been talking about, or is there other aspects of when we try to put that into practice that primary practitioners, specialists can do to make sure that there's culturally appropriate care?

Dr. Kerri Schellenberg

That's a really good question. And I think that having some cultural sensitivity training is very important and most institutions do offer that. Additionally, we want to work with home communities and the resources that are available in people's communities and work with the elders and knowledge holders.

So we're actively doing that in Saskatchewan. And part of what we hope to do as we roll out the guidelines is to have engagement with various neuromuscular clinics across Canada. So that we can help to work with our community guiding circle to put forth ideas that are culturally appropriate and that our community feels are necessary and helpful.

Dr. Blair Bigham

Fantastic. 

Dr. Mojola Omole

Great. Thank you.

Dr. Blair Bigham

Kerri, thank you so much for joining us today. That was really great.

Dr. Kerri Schellenberg

Thank you. It was my pleasure.

Dr. Mojola Omole

Dr. Kerri Schellenberg is a neuromuscular neurologist and the lead author of the new guideline, “Best practice recommendations for the clinical care of spinal and bulbar muscular atrophy”. She's an associate professor at the University of Saskatchewan. This was really hard for me to process.

And this is maybe a little bit beyond the practice guidelines, but just how devastating of a diagnosis this is to patients and the fact that there's a delay in diagnosis. I found that having, you know, this practice guideline could be life changing for those who have this disorder.

Dr. Blair Bigham

Absolutely. You know, in the ICU, I see a lot of patients who have ALS, which is not the same, but a similar, you know, progressive neurologic disease. And the impact that this has on people.

I mean, it is a devastating diagnosis to have a progressive neurologic disorder.

Dr. Mojola Omole

But the difference, though, between ALS and this is that there is no shortening of your lifespan. And so that is a longer window. And I think that that was something impactful that Richard said is that you're just waiting for the end to come.

And so I do think that being able to have guidelines that  lead to genetic testing. And so people are aware of that. This is something that is in their genetics is so important.

And being able to create multidisciplinary care around it to support people, and the community and the family, everybody is so important.

Dr. Blair Bigham

Yeah, it's not just about nailing that diagnosis, I mean, which is hard enough. It's about that longitudinal support to keep people, I don't know, to keep people motivated, to give them hope, not at recovery, but that life isn't going to be too miserable. I took care of this woman recently who has ALS, and she just was so fixated on the fact that it was going to get worse that I found it challenging to kind of focus on not the worst of it, but what's going well, what can we focus on?

And when we finally got there, we had a lovely conversation. And it really did. I don't know, it just does set people up for less misery.

And you realize how resilient people can be and how much joy you can still get out of life, even when you have a terrible diagnosis like this.

Dr. Mojola Omole

And so for me, I'm just in awe of our colleagues in neurology and other specialties who deal with these, you know, chronic illnesses and being able to create something like these guidelines that give a roadmap to clinicians, like family practitioners and family and primary care practitioners, to be able to help support their patients is so important.

Dr. Blair Bigham

It's so great to have a guideline that even though you can't cure a disease, you can still really make an impact. And for me, this guideline gives clinicians a little bit of, a little bit of hope and a little bit of a pathway to feeling like they do good. So many neurologic diseases, you know, you can't make them turn around, you can't make them better, but you can at least make life a little bit better.

And I think that's what these guidelines are going to help clinicians do. 

Dr. Mojola Omole

For sure. 

Dr. Blair Bigham

That's it for this episode of the CMAJ Podcast.

The link to the guidelines is in the show notes. Please have a look. Also, go online and subscribe wherever you get your podcasts.

Rate, share, like, and review our podcast. It really does go a long way to helping us bump up on the charts. Our podcast is produced for CMAJ by Neil Morrison at PodCraft Production.

Catherine Varner is deputy editor of the CMAJ and senior editor of the podcast. I'm Blair Bigham. 

Dr. Mojola Omole

I'm Mojola Omole. Until next time, be well.