Worth 2nd opinion at Mayo? High likelihood of ALS

[powerpadman]

Hi everybody,

I posted this at /ALS at Reddit but also wanted to be part of this community.

My brother, who is under 40-years-old, has been given a provisional ALS diagnoses to get started on medication (Riluzole, Radicava, and Relyvrio). The neurologist has told him "it's looking like ALS" but he's not 100% sure yet and will need to see more progression over the next couple months.

My brother has all the hallmarks of ALS: positive EMG tests (upper and lower), many ALS symptoms, and a family history (just one blood aunt who passed from ALS). He has also done a lot of testing (blood work, CT, MRI, etc.) to rule out mimics.

Given this, and the fact that three independent neurologists have told him it is "likely ALS," would it make sense to get potential further testing? We just want to know, if there are any other possibilities besides ALS, and if so, how do we figure this out?

I was told if this could be ANYTHING else, the one place that may be able to figure it out is Mayo Clinic. However, it would be an additional commitment of financial, time, and emotional energy given it would be out of state and nearly 2,000 miles away. But the additional commitment would be worth it if we could uncover additional information.

It's worth noting that I've read some posts in /ALS that also talk about a 2nd opinion at Mayo that didn't lead to additional answers...

Thank you so much for your insight.

 

[lgelb]

My first question would be, at which centers were these three opinions rendered.

My second is, who said "likely" or what did they really say? Definite, probable, and the like are the typical delineations. If you can post the chart notes where these statements are made, we could be more helpful. Also, feel free to post the de-identified EMG(s).

I don't consider Mayo the closest option to get a sterling 4th opinion, nor necessarily the best. But that presumes that a 4th opinion has possible utility, as you say.

Since you can't inherit ALS from an aunt, I presume the parent that is related to the aunt is well?

 

[powerpadman]

Thank you so much for the follow up.

The three centers are all in the same city on the West Coast. One center in particular is an ALS Association Center and the neurologist is a leading doctor in ALS. So we don't doubt his opinion.

We did hear back yesterday from this doctor who clarified his opinion as "emerging ALS." So I guess that clears up our confusion. I think we will just proceed as it's ALS.

Your question about the inherited part of this, yes, our mother is sisters with the aunt who passed from ALS. It's a pretty big family and tracing back three generation, no other member had ALS, so it's surprising that this could be familiar ALS, because when our aunt was diagnosed (about 15 years ago), it was diagnosed as sporadic. Of course, we now know much more than we did.

My brother has done a DNS test which resulted in no match for about 34 genes associated with ALS. He is trying to get into a study to test for an additional 15 genes.

Thank you so much for jumping in to help answer our questions. As you likely know first hand, this is an extremely difficult time for our family.

 

[lgelb]

An ALSA center means nothing except that money has changed hands. If you don't want to name the centers, that's fine, but please note that neither an ALSA or MDA designation is any kind of 100% validation of either dx or treatment.

"Emerging ALS" is a rather vague clinical classification. The Gold Coast criteria, which are the most recent consensus worldwide, specify that there is ALS or not, with requirements for diagnosis as follows:

1. Progressive motor impairment documented by history or repeated clinical assessment, preceded by normal motor function,

AND

1. The presence of upper * and lower † motor neurone dysfunction in at least ONE body region‡, with:
   • upper and lower motor neurone dysfunction noted in the same body region if only one region is involved,
   • or lower motor neurone dysfunction in at least TWO body regions,

AND

1. Investigations§ excluding other disease processes.

*Upper motor neurone dysfunction implies at least one of the following:

• Increased deep tendon reflexes, including the presence of a reflex in a clinically weak and wasted muscle, or spread to adjacent muscles.
• Presence of pathological reflexes, including Hoffman sign, Babinski sign, crossed adductor reflex, or snout reflex.
• Increase in velocity-dependent tone (spasticity).
• Slowed, poorly coordinated voluntary movement, not attributable to weakness of lower motor neurone origin or Parkinsonian features.

†Lower motor neurone dysfunction in a given muscle requires either :

• Clinical examination evidence of muscle weakness and muscle wasting, or
• EMG abnormalities that must include both:
  • Evidence of chronic neurogenic change, defined by large motor unit potentials of increased duration and/or increased amplitude (with polyphasia), and motor unit instability regarded as supportive but not obligatory evidence, and
  • Evidence of ongoing denervation, including fibrillation potentials or positive sharp waves, or fasciculation potentials.

‡Body regions are defined as bulbar, cervical, thoracic and lumbosacral. To be classified as an involved region with respect to lower motor neurone involvement, there must be abnormalities in TWO limb muscles innervated by different roots and nerves, or ONE bulbar muscle, or ONE thoracic muscle, either by clinical examination or by electromyography (EMG).

§The appropriate investigations depend on the clinical presentation, and may include nerve conduction studies and needle EMG, MR or other imaging, biofluid studies, or other modalities as clinically indicated.

 

[powerpadman]

Thank you for the detailed response.

The center is Swedish Neuroscience and ALS Center in Seattle. He has also been seen at University of WA and Virginia Mason, also both in Seattle.

I believe he has all of the above "ANDs" and just needing to see more progression of muscle deterioration/weakness over time. He has upper/lower in his left leg right now with symptoms (fasciculations, reflexes) in other body areas.

The neurologist already has my brother visiting the ALS Center (with all of their resources) and will give a clearer answer over the next couple of months.

Seems like almost a 100% diagnosis, but not there yet I suppose...

 

[rmt]

Did any of the neuromuscular specialists think it might be something other than ALS? Did they suggest any other testing? Or do they feel like they have ruled out everything else?

We went to UW and saw Dr. Weiss. I thought he was very knowledgeable.

I understand wanting to rule everything else out, but I'm glad your brother is starting on the three R's right away.

 

[lgelb]

We have at least one member who is quite dissatisfied with Swedish in Seattle, for good reason, and I had years of experience with the current Swedish program director when he was at VM.

Like rmt, I would suggest UW for care, if you have the option. Their staff is far more storied as regards ALS, and involved in more trials. That they are "certified" [sic] by the MDA (as are Seattle Children's and 150 other pretty good centers) instead of the ALSA matters not.

 

[powerpadman]

Interesting about UW. They initially told us that they would get my brother into additional DNA testing through a Columbia University study, but after several messages and phone calls, we haven't yet heard back...and it's been about a month. Good info on Dr. Weiss. I believe my brother met with Dr. Wang.

@rmt Many tests were ordered to rule out mimics. This included what seemed like dozens of blood tests, a CT, and MRI. None of the three independent neurologists could name anything else they think it could be.

I posted this same info on the /ALS subReddit and somebody replied that "when you have been diagnosed with ALS, only 10% of the time will have been a misdiagnosis and you have something else." I'm not doubting that number, but I also couldn't verify it anywhere else.

I appreciate all the helpful responses here. Any and all information is helpful!

 

[lgelb]

I don't believe 10%, in modern litigious times, and the abstract that provides this figure does not present convincing references for it, all older/predating the Gold Coast criteria. I'd take 2-3% at US tertiary care centers. Your brother's been to three.

This excerpt from a leading ALS primer (Hardiman et.al.) may be helpful:

Several conditions have similar initial clinical features as ALS and should be considered in the differential diagnosis, including cervical myelopathy, multifocal motor neuropathy, myasthenia gravis, Lambert Eaton myasthenic syndrome and inclusion body myositis.

Features that should alert the clinician to a possible mimic syndrome include presentation of symmetrical findings; prominent extensor plantar responses (which should raise suspicion of a cervical myelopathy) and the presence of sensory findings.

Although sensory symptoms are common in ALS, clinical evidence of sensory loss is atypical and should trigger further investigations. In addition, the presence of substantial weakness in the absence of wasting [which is common in multifocal motor neuropathy and myasthenia gravis] and the presence of disproportionate involvement of quadriceps [which is common in inclusion body myositis] may indicate the presence of an ALS mimic syndrome.

As ALS is a progressive disease, failure of the condition to progress over months should also trigger a re-investigation.

-----
Not defending lack of communication, of course, but Columbia may be the holdup. UW should certainly keep you informed. I would use the MyChart portal rather than the phone.

 

[powerpadman]

Thank you so much for the information. This has been very helpful.