2 of 63 patients with muscle pain/fibro had Myotonic Dystrophy type 2

[pattismith]

(I think I finally found my disease...after a long an lonely journey)

Myotonic Dystrophy Type 2 Found in Two of Sixty-Three Persons Diagnosed as Having Fibromyalgia


Satu Auvinen, MD,1 Tiina Suominen, MSc,2 Pekka Hannonen, MD, PhD,1 Linda L. Bachinski, PhD,3 Ralf Krahe, PhD,3 and Bjarne Udd, MD, PhD4
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The publisher's final edited version of this article is available free at Arthritis Rheum
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Abstract
Because of its high prevalence, fibromyalgia (FM) is a major general health issue. Myotonic dystrophy type 2 (DM2) is a recently described autosomal-dominant multisystem disorder. Besides variable proximal muscle weakness, myotonia, and precocious cataracts, muscle pain and stiffness are prominent presenting features of DM2. After noting that several of our mutation-positive DM2 patients had a previous diagnosis of FM, suggesting that DM2 may be misdiagnosed as FM, we invited 90 randomly selected patients diagnosed as having FM to undergo genetic testing for DM2. Of the 63 patients who agreed to participate, 2 (3.2%) tested positive for the DM2 mutation. Their cases are described herein. DM2 was not found in any of 200 asymptomatic controls. We therefore suggest that the presence of DM2 should be investigated in a large sample of subjects diagnosed as having FM, and clinicians should be aware of overlap in the clinical presentation of these 2 distinct disorders.

"Muscle pain in DM2 can be very disabling, especially in individuals who perform physically demanding work."

In MD2, the muscle or some area have a delayed relaxation after contraction, which lead to lactate building, pain, and exercice intolerance.

Some reflex test can be performed to screen for this disease, and DM2 is corelated to delayed relaxation of the trapezius.

It can be seen in this video:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721102/bin/supp_80_24_e251__index.html

(Myodystrophies can produce scoliosis, so It may be that my neck scoliosis is the result of this disease.)

 

[Wilma]

I had also a lot of muscle pain and stiffness.
What helped me was eating a lot of vegetables and fruit. And what really helped for the pain was vitamin c, fish and olive oil. I think it,s because of the vitamin a and e in it. But just fish oil didn't help me. I think that all these vitamins and minerals need each other to get it to the cells.

 

[pattismith]

@Wilma

You should be screened for myotonic dystrophy. MD is a multisystemic disease and everyone here with widespread pain should be screened.

In the link I allready posted, you can see the video with the delayed relaxation of the trapezius after contraction. It's an easy test that anyone can perform.

Here the comment of the video by the author:

Video 1 Title: Proximal percussion myotonia of the Trapezius in patients with Myotonic Dystrophy type 2

Three patients with genetically confirmed DM2 are shown in sequential videos.

-Percussion of the trapezius disclosed several seconds of muscle myotonia (patients 1-3).

-Percussion of the thenar eminence and forearm extensors elicits minimal myotonia (patients 1 and 3).

-Minimal grip myotonia is shown in patients 1 and 3.

 

[Wilma]

Thank you for your concern. But i don 't have pain anymore. As long as i keep eating healthy. I think that in my case it's a lack of antioxidants

 

[Gingergrrl]

(I think I finally found my disease...after a long an lonely journey)

Wow, Patti, how did you figure out that you had Myotonic Dystrophy?! Were you tested for it or did you figure it out b/c your symptoms matched the research that you were finding?

 

[pattismith]

Wow, Patti, how did you figure out that you had Myotonic Dystrophy?! Were you tested for it or did you figure it out b/c your symptoms matched the research that you were finding?

ginger, it was a long journey, yes.
After my neck MRI in september, I discovered that I had a slight neck scoliosis. Scoliosis is known to occur when there are muscle diseases (it can come also from brain disease, or neuromuscular disease).

So I started to look for scoliosis associated muscle diseases.

Then I found that muscular dystrophies could match, among them you can find:

-Cervical myotonia (the head is usually tilted but it was my first idea)
-Myotonic Dystrophy (a multisystem disease, so it matches better with my multisystem symptoms)

Then I found very easy testing to screen for DM at home, with no help.

-DM1 can be screened by hand check test, toes test, tongue test (I will send videos so anyone will be able to test oneself)

-DM2 can be screened by trapezius percussion test and thumb base percussion: you can see the contraction and delayed relaxation of the muscle. (the video is at the end of my first post)

So I did all these tests and I fit with DM2.
When I did the trapezius test, I also did it on all people around me (all negatives)... and when I realized I was like the people in the video, it was like I was not on my own any more, like if I had found my family back.
I can't say how deep was my emotion.

I have already contacted a doc here in my country (a hospital neurosurgeon working on these diseases) that should be able to confirm, and maybe will do some genetic testing if available over there.

DM2 is usually considered milder than DM1, but my symptoms began early so I suppose I have a more severe form than many.

DM can have very similar symptoms to ME/CFS + fibro.

It also induces autonomic dysfunction with activated sympathetic nervous system and reduced parasympathetic, but no POTS nor OI (well I don't think so).

The tests are so easy to do, that I will do my best to advocate for a screening of patients like me.

 

[Gingergrrl]

ginger, it was a long journey, yes. After my neck MRI in september, I discovered that I had a slight neck scoliosis. Scoliosis is known to occur when there are muscle diseases (it can come also from brain disease, or neuromuscular disease).

I can relate to the long journey of searching for answers when you don't quite match with any illness. I am so glad that you kept searching and did not give up.

-DM2 can be screened by trapezius percussion test and thumb base percussion: you can see the contraction and delayed relaxation of the muscle. (the video is at the end of my first post)

I remember you posting about the thumb test a few months ago, and I cannot remember the details, but do remember that it did not match in my case.

and when I realized I was like the people in the video, it was like I was not on my own any more, like if I had found my family back. I can't say how deep was my emotion.

This brought tears to my eyes re: the moment that you found your family and were not alone. In my case, when we discovered that I had the calcium channel autoantibody, it was a game-changer in my treatment except I did not realize that until much later and was initially very confused what it meant or if it was significant.

I have already contacted a doc here in my country (a hospital neurosurgeon working on these diseases) that should be able to confirm, and maybe will do some genetic testing if available over there.

I am so happy that you found a specialist in your country! Do you know what the treatment will be in your case? Is it purely a genetic disease or is it autoimmune (or something else)? Please keep us posted.

 

[pattismith]

I am so happy that you found a specialist in your country! Do you know what the treatment will be in your case? Is it purely a genetic disease or is it autoimmune (or something else)? Please keep us posted.

thank you for answering Ginger,

I have investigated a lot mito diseases and ion channel diseases, because I thought it could match with my symptoms. In fact DM affects nuclear DNA transcription and down the road affects mitochondria and ion channel functions, so I was not too much wrong.

All the reported DM cases I can see on internet are genetic in origin, and all the scientific research (treatment as well) focuses on DM1 because it can affect children.
DM2 (my DM type) was identified later in 1994, and I am not sure if treatments investigated for DM1 may have any effect on DM2. DM2 is considered much more benign and starting later in life, but some cases that show up earlier in the twenty are more severe (like I am).

By the way there is not dedicaced drug for DM1.
I selected Metformin and AICAR as drug that may be useful for DM1, so I'd like to try it as they have a good safety profile.

 

[Nine lives]

Have you seen this on thiamine - though only tested in DM1 might still be useful.

Neural Regen Res. 2016 Sep; 11(9): 1487–1491.
doi: 10.4103/1673-5374.191225
PMCID: PMC5090854
PMID: 27857755
Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?
Antonio Costantini, M.D.,1,2,* Erika Trevi,1 Maria Immacolata Pala,1 and Roberto Fancellu3
Author information Article notes Copyright and License information Disclaimer

Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients’ activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2–4 in the distal muscles (the MRC score before the treatment was 3–4 and 1–3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

 

[pattismith]

@Nine lives
thank you for reminding me Constantin's trials with Thiamine.

I already tried his protocol (although with lower dosage), and found muscle strength to improve. Unfortunately I had to stop because of increasing cramps/myoclonies.
It's a long time since I stopped, so I should try it again.

 

[pattismith]

Strong association between myotonic dystrophy type 2 and autoimmune diseases.
Tieleman AA1, den Broeder AA, van de Logt AE, van Engelen BG. 2009
Author information
1Neuromuscular Centre Nijmegen, Department of Neurology (935), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Abstract
BACKGROUND:
Myotonic dystrophy type 2 (DM2) is a dominantly inherited multisystem disorder, characterised by progressive proximal weakness, myotonia, cataracts and cardiac conduction abnormalities. Our clinical impression of an association between DM2 and autoimmune diseases or autoantibody formation has not been published previously.
OBJECTIVE:
The aim of the present study was to investigate the frequency of autoimmune diseases and serum autoantibodies in patients with DM2 compared with patients with adult onset myotonic dystrophy type 1 (DM1).
METHODS:
28 genetically proven Dutch DM2 patients participated in the study and were compared with 51 age and sex matched adult onset DM1 patients. As the primary outcome measure, the presence of an autoantibody or autoreactive T cell associated autoimmune disorder was assessed. As a secondary outcome measure, the presence of autoantibodies in serum (nuclear and non-nuclear antibodies) was assessed in all patients.
RESULTS:
The frequency of autoimmune diseases (21% vs 2%) and the frequency of autoantibodies (25% vs 2%) were both significantly (p<0.01) higher in DM2 patients compared with DM1 patients. Data on DM1 patients were comparable with the general population. Results were not confounded by smoking, medication use, familial clustering, age or sex.
CONCLUSION:
The results provide new insight into the clinical picture of DM2. In addition, possible explanations for the association between DM2 and autoimmune diseases are proposed.

 

[Gingergrrl]

The frequency of autoimmune diseases (21% vs 2%) and the frequency of autoantibodies (25% vs 2%) were both significantly (p<0.01) higher in DM2 patients compared with DM1 patients.

That is really interesting, Patti, and I am now wondering if you think your case could be autoimmune since you have DM2 vs. DM1? Have they identified a specific autoantibody or are they looking at general autoimmunity like a positive ANA titer?

 

[pattismith]

That is really interesting, Patti, and I am now wondering if you think your case could be autoimmune since you have DM2 vs. DM1? Have they identified a specific autoantibody or are they looking at general autoimmunity like a positive ANA titer?

No antibody was positive up to date for me, only anti thyroid ones. (I am currently hyperthyroid but this doesn't explain my percussion myotonic symptoms , only hypothyroidism can produce similar symptoms to myotonia).

Nonetheless the journey in front of me is long before I find a doc to diagnose my myotonia and willing to discover the disease that is actually causing it.

DM2 seems a reasonable hypothesis, but some other genetic or auto-immune disease are possible as well.

Anyway, I found it interesting that some people with DM2 can have additional complications to their disease with some autoantibodies.

 

[Nine lives]

Couldn't access full test but useful link to dysautonomia and peripheral neuropathy.

Dysautonomia as Onset Symptom of Myotonic Dystrophy Type 2

Rossi S.a · Romano A.a · Modoni A.a · Perna F.b · Rizzo V.c · Santoro M.d · Monforte M.a · Pieroni M.b,f · Luigetti M.a · Pomponi M.G.e · Silvestri G.a

Eur Neurol 2018;79:166–170

https://doi.org/10.1159/000487508


Abstract

Myotonic dystrophy type 2 (DM2) is an autosomal dominant muscular dystrophy caused by the expansion of an intronic tetranucleotide CCTG repeat in CNBP on chromosome 3. As DM1, DM2 is a multisystem disorder affecting, beside the skeletal muscle, various other tissues, including peripheral nerves. Indeed, a subclinical involvement of peripheral nervous system has been described in several cohorts of DM2 patients, whereas DM2 patients manifesting clinical signs and/or symptoms of neuropathy have been only rarely reported. Here, we describe 2 related DM2 patients both of whom displayed an atypical disease onset characterized by dysautonomic symptoms, possibly secondary to peripheral neuropathy.

 

[pattismith]

in this 2013 study about muscle calcium signaling in DM1 and DM2:

"Here, we have focused on proteins involved in Ca2+ metabolism, as calcium ion has a key role in cell signaling and muscle contraction, and defects in Ca2+-regulated pathways have been associated to DM1 previously [20, 41, 43].
As a novel finding, we present aberrant splicing of RYR1 and ATP2A1 in DM2.

More importantly, we observed abnormal expression of mRNA and protein of a larger range of molecules involved in muscle Ca2+ release and reuptake, Ca2+ storage, and Ca2+-dependent signaling. While similar in many ways, we have identified novel differences between DM1 and DM2. Interestingly, in most cases increases in mRNA transcript levels were not consistently reflected in increased protein levels.
...

The Ca2+ storage protein encoding genes CASQ1 and CASQ2, preferentially expressed in fast and slow fibres, respectively, both showed approximately 2-fold up-regulation in DM samples compared to controls.
In addition, the Ca2+ re-uptake channel encoding genes, ATP2A1 (SERCA1) and ATP2A2 (SERCA2) were both up-regulated, ATP2A2 showing more increased expression in DM1 compared to DM2.
...
However, it should be noted that RYR1 aberrant splicing was still significantly higher in DM2 samples, suggestive of more pronounced RYR1 aberrant splicing.
...
We previously reported proportionally more pronounced aberrant splicing of TNNT3 and LDB3 in DM2 [17], and here we show a similar trend for ATP2A1
...
. SERCA1 is almost exclusively expressed in fast fibres, and given that the fast type 2 fibres are more affected in DM2 than in DM1, our observation that aberrant SERCA1 splice variants occur more frequently in DM2, suggests that it may have a role in DM2 differential muscle pathogenesis.
...
On the contrary, ATP2A2 and JPH1 showed reduced total protein levels, even though mRNA was up-regulated. NFATC3, a downstream effector of calcineurin, also showed increased protein levels in DM2 vs. DM1 (p-value = 0,036), although without significant dysregulation at the mRNA level [17].
;;;
When assessed by immunohistochemistry, RYR1 levels in SR were reduced in both DM1 and DM2,...

A similar pattern of expression was seen with CASQ2, showing severely reduced immunolabeling in DM2, and less prominent reduction in DM1, but without significantly reduced amounts in DM2 or DM1 specimens compared to healthy controls on western blotting.
A slight reduction in JPH1 immunoreactivity was also observed in the severely affected DM1 muscles. Together with reduced DHPR levels in DM1, this is intriguing in the context of the more severe muscle phenotype in DM1. JPH1 facilitates the interaction of DHPR and RYR1, hence enhancing EC coupling [58]. In accordance with its function, JPH1 also was more intensely expressed in fast muscle fibres.

 

[pattismith]

Genotype-phenotype correlations and characterization of medication use in inherited myotonic disorders
Author InfoMeyer, Alayne

Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu155506792600104



Year and Degree
2019, Master of Science, Ohio State University, Genetic Counseling.

Abstract

Objective: The purpose of this study is to characterize the genetic and phenotypic profile of patients with myotonic disorders, compare symptom profiles for significant clinical differences and summarize use of antimyotonia agents.

Background: Myotonic disorders are characterized by hyperexcitability and delayed relaxation of muscle. Variants in CLCN1 and SCN4A cause non-dystrophic myotonia while pathogenic expansions in DMPK and CNBP cause dystrophic myotonia, clinically distinguished by presence of progressive muscle deterioration.

Symptoms may include stiffness, weakness, cramping and pain and can be exacerbated by a variety of environmental factors. Combination of clinical examination, laboratory workup, electromyography (EMG) results and genetic testing aid in diagnosis of these patients.

Methods: A total of 142 patients at The Ohio State University were identified to have a myotonia diagnostic code assigned to their medical record and a variant or expansion in CLCN1, SCN4A, DMPK or CNBP in themselves or a family member. Data collected from the electronic medical record included demographics, symptom history, clinical examination, family history, lab work, EMG results, genetic testing results and medication history. Descriptive statistics and Fisher’s exact tests were utilized in data analysis.

Results:

The final cohort consisted of 27 individuals with CLCN1-related myotonia (23 dominantly inherited, 4 recessively inherited), 15 with SCN4A-related myotonia, 89 with myotonic dystrophy I and 11 with myotonic dystrophy 2.

Patient reported weakness was found in the majority of our non-dystrophic (ND) cohort (65.2% CLCN1, 69.2% SCN4A), while clinically identified weakness was only found in 20%.

Pain was reported by the majority of our overall cohort (69% CLCN1, 53% SCN4A, 59.5% DMPK, 100% CNBP (DM2)).

Frequency of patient reported-weakness, clinical myotonia, percussion myotonia and clinical weakness were found in significantly more individuals in our dystrophic (D) cohort compared to our ND cohort while cold exacerbation was found in significantly more individuals in the ND cohort.

The only significant difference between our CLCN1 and SCN4A cohorts were the proportion of individuals reporting stiffness (100% CLCN1, 78.6% SCN4A).

Only 50% of our overall cohort had trialed an antimyotonia agent and only 28% were currently taking one. Our ND cohort was more likely to have trialed and be currently utilizing an antimyotonia agent than our D cohort (73% ND, 39% D).

Conclusions: The results of this study suggest that weakness may be a more significant symptom in ND myotonias than previously identified and may not be detectable via standard manual muscle testing. Additionally, pain may be a more prevalent symptom in all myotonia disorders than previously identified, particularly in CLCN1. Differentiation between ND patients by phenotype may not be feasible due to significant phenotypic overlap. Most individuals with myotonic disorders are not currently taking an antimyotonia agent despite the presence of symptoms that may be aided by these medications, but ND patients were more likely to do so than D patients

 

[Gingergrrl]

Only 50% of our overall cohort had trialed an antimyotonia agent

I was curious what meds or treatments they were referring to by "antimyotonia agent" and the only thing I could find on Google was "Mexiletine" which is a sodium channel blocker. Does this make sense in your case @pattismith?

 

[pattismith]

I was curious what meds or treatments they were referring to by "antimyotonia agent" and the only thing I could find on Google was "Mexiletine" which is a sodium channel blocker. Does this make sense in your case @pattismith?

yes, mexiletine seems number one, taurine may be useful as well.
But as usual with ion channel dysfunction, hormonal balance also plays its role...

 

[pattismith]

@Nine lives

I had an EMG done and nerve velocity, and nothing showed up.
I know that some DM2 cases don't show up in EMG, but I have some doubt about my percussion myotonia to be a DM2 case: it may be something else... Possibly a kind of myotonia that is not even known yet.

This makes my quest more difficult!

I share here my trapezius percussion test (video), in case someone will find the same as I do:

https://files.fm/u/kw6q5uwu

...

 

[Nine lives]

Sorry, that the quest goes on. But, did they agree to the genetic blood test for DM2 to absolutely rule that out?

As you know, my trapezius percussion myotonia also looks like yours. Maybe, this is related to a channelopathy. In my case, no channelopathy SNPs stand out on GENOS, so perhaps related to an antibody?

I would be interested if others could test this, as this may relate to a subset.