David,

Glad you finally got some relief from the constant pain. Benzodiazepines like Diazapam aren't routinely prescribed for myotonia because they work on neurons in the brain, not the muscle.

Another main reason they aren't prescribed is because they are geared more toward short-term use. They are extremely addictive and patients develop a tolerance very quickly so that the dose has to be raised periodically to be effective. A doctor once put me on Librium to relax muscles before we knew that I had MC. I seem to recall that it did help a bit with the myotonia, but I had a car accident within the first few days because of the sedating and reflex-altering effect. He never even warned me about the potential side effects - in fact I didn't even know what I was taking. (I was on a 10mg dose).

Hopefully you will be able to stay at a low dose for a long period with no adverse effects. It is interesting that the GABA receptors which are targeted by benzodiazepines affect chloride ion channel function in the brain.

I think the researchers need to revisit this and see if there is some way to target the skeletal chloride ion channels in a similar way. I'll paste in some information about it below. The amino acid Taurine seems to have a similar effect. It activates GABA receptors in the brain, and it has now been proven to help with myotonia.

Thanks for sharing - it would be wonderful to get your life back!

Jan


Mechanism of action

Schematic diagram of the (α1)2(β2)2(γ2) GABAA receptor complex that depicts the five-protein subunits that form the receptor, the chloride (Cl-) ion channel pore at the center, the two GABA active binding sites at the α1 and β2 interfaces and the benzodiazepine (BZD) allosteric binding site at the α1 and γ2 interface.

Benzodiazepines work by increasing the efficiency of a natural brain chemical, GABA, to decrease the excitability of neurons. This reduces the communication between neurons and, therefore, has a calming effect on many of the functions of the brain.

GABA controls the excitability of neurons by binding to the GABAA receptor.[112] The GABAA receptor is a protein complex located in the synapses of neurons. All GABAA receptors contain an ion channel that conducts chloride ions across neuronal cell membranes and two binding sites for the neurotransmitter gamma-aminobutyric acid (GABA), while a subset of GABAA receptor complexes also contain a single binding site for benzodiazepines. Binding of benzodiazepines to this receptor complex promotes binding of GABA, which in turn increases the conduction of chloride ions across the neuronal cell membrane. This increased chloride ion conductance hyperpolarizes the neuron's membrane potential. As a result, the difference between resting potential and threshold potential is increased and firing is less likely.

Different GABAA receptor subtypes have varying distributions within different regions of the brain and, therefore, control distinct neuronal circuits. Hence, activation of different GABAA receptor subtypes by benzodiazepines may result in distinct pharmacological actions.[120] In terms of the mechanism of action of benzodiazepines, their similarities are too great to separate them into individual categories such as anxiolytic or hypnotic. For example, a hypnotic administered in low doses will produce anxiety-relieving effects, whereas a benzodiazepine marketed as an anti-anxiety drug will at higher doses induce sleep.[121]

Type of Myotonia: Thomsen's

Country: USA

David:

I'm glad you've found something that worked, but as Jan said, diazepam can be incredibly addictive, and I've seen lives ruined from it and other downers.

If my doctors had wanted to do such a thorough cardiac workup before giving me Mexiletine I might have actually have given it a try. But they didn't. One of my doctors said "It has a high mortality rate but I'll write the prescription if you want." And the other said "Mexilewhat?" And I said "Nevermind".

A few questions:
Were your muscles cramping up spontaneously or was it always initiated by movement or an attempt to move on your part?

Did you have pain all the time or just with the myotonia or any other muscle cramps?

Did you try things for non-myotonic muscle cramps, like potassium or magnesium? I think sometimes regular cramps can "piggy back" on top of the myotonia. This happens in one of my back muscles. It's very painful and potassium seems to help.

Type of Myotonia: Becker

Country: USA

Thank you both Jan and Jenna. Jenna, I had pain with movement in certain positions. Slight rotation of my upper body would do it. I also had muscle episodes with or without movement.
Jan, I'm always impressed with your knowledge as well and I was made aware of the possible addictive nature. I am on the lowest dose and it's helping. I, like many, are searching for a natural product that does the same. Questions; why would so many doctors try muscle relaxers, including some involved in M.D.A.? How much Potassium is safe to use? I'm going to look into your recommendation. I realize that all these drugs are harmful in some way but, for whatever the reason, this relaxer is doing what I've been praying for for years...to stop the pain and multiple episodes. I take the 2mg tab before bed as mentioned but plan to cut it in half starting next monday to see if even a lower maintenance dose will work. I don't take it during the day so my ability to do the things I want are not impaired. As promised from the beginning, I'll keep you posted on any improvements or findings.
Still looking and with a prayer, Dave

Type of Myotonia: Becker

Country: USA

My guess is they use the muscle relaxers because they can be an easy fix and people usually don't complain about them.

As for the potassium, I usually just eat a thing of yogurt, which has about 340-450mg of potassium. I've recently discovered those juice boxes of Minute Made fruit punch have about the same amount and it usually seems to help.

I haven't tried the supplements because they can be hard on the stomach.

Type of Myotonia: Becker

Country: USA

Hi all, just checking in with an update. Sometime around the first week of June, I reported that I was having amazing results with Diazepan. It's August ninth and I have only had 2 mild episodes of Myotonia. I also stopped the med for 2 days to see if it was all in my desperate head. The severe pain and attacks jumped right in. I'm taking 2mg/day sometimes 1mg/day and I'm free again. Now, I am not jumping to conclusions and no one can figure out why it's working on me. I'm staying on this dose that I can't even tell I'm taking for the next 6 months before I make any attempts to return to employment. I need to make sure that I don't have to keep increasing my dose every so many months. I feel like I'm about 30 and I'm going to be 56. I'm walking a lot, losing weight and smiling again. God is good!

Type of Myotonia: Becker

Country: U.S.A.

David:

I'm glad the medication has continued to work. I don't know much about pharmacology so I can't really say much on how it works either. Various sources say it suppresses the nervous system. I think I was given diazapam once when I couldn't reply with the request to relax my muscles during an outpatient procedure. It did relax my muscles but it also slurred my speech. In MC, when the chloride channels fail to let sufficient amounts of chloride into the cell to cease muscle contraction, it results in repetitive discharges which sustain the contraction.

This is pure speculation and I could be completely wrong...I don't know much about pharmacology or how diazapam works in the body, but maybe it's attenuating the signal at the origin, either in amplitude, or just preventing the excitation of so many muscle cells by inhibiting the part of the brain that activates them.

In addition, it might be reducing the amount of stress hormones in your body.

As I said though, pure speculation :-)

Just out of curiosity, do you happen to know what mutation you have? I used to have pretty bad hyperexcitability. I'm betting that is what was causing your pain. Maybe you would go to move and a few of your muscle cells would contract so hard that they nearly blew up, or actually did cause a rupture. It still happens in my calves when I try to stretch them in bed and I always realize the error of my ways too late when the only thing I can do is try to lay completely still and try my best brace myself without tensing my muscle, for the impending pain. Each time I think "This is it, I'm going to tear it!" but 10 seconds later it's fine.

Type of Myotonia: Becker

Country: USA

Thanks Jenna, I have a mutation in the clcn1 and one or more DNA variants of unknown significance

Type of Myotonia: Becker

Country: U.S.A.

Dave:

Did you post the exact mutations a few years ago? If you're the right Dave, then I think you have two of the same mutations I have. F413C, and then, the one of unknown significance, a C to T transition at nucleotide position 1392.

I can't help but wonder if that mutation of unknown significance is responsible for our atypical symptoms.

There was a study a while back which documented someone with the other disease causing mutation I have, and this same C to T transition, who was symptomatic even though the disease causing mutation was thought to be recessive.

One theory put forth to explain those with single recessive mutations who still have clinical symptoms is something called "copy number variation". Essentially the section of the gene with the mutation is copied and integrated into the chromosome, so you have the same mutation on the same chromosome twice.

Maybe this unknown mutation is a marker for it. We should see if someone wants to do a study on it :-)

Type of Myotonia: Becker

Wow Jenna, what a memory! It is me. I don't have time right now to write about my past 5 year journey but, I will get back in a few to compare notes.

Type of Myotonia: Becker

Country: U.S.A.