Postural Muscle Tone depends on Norepinephrine

[User172840302]

https://doi.org/10.1016/j.neubiorev.2021.11.012


ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications

if Adhd and hypotonia run in your family, a mitochondrial disease may be investigated, or another neurometabolic disease.
Do you have muscle delayed relaxation after contraction or percussion?

Thanks so much for this. I guess it’s very plausible that some kind of metabolic disease is present given the FH. Finding that is the issue I guess (I’m 22 so kind of a newbie). I don’t think I have delayed muscle relaxation from a quick Google. As for mitochondrial disease - is this something that’s passed down through the mother’s mitochondria (because my mother has normal muscle tone) or can also be influenced by faulty genes? I ran my 23andMe results through Promethease and nothing of the sort came up, however that’s not exactly reliable I guess. Lots of autoimmune markers though. What’s interesting is we were literally all born with this and it hasn’t changed, might have slightly improved, with age and it’s just so puzzling how responsive it is to methylphenidate (I have taken mirtazapine before which increases noradrenaline I think, different mechanism, but it had no effect). Both of my parents have symptoms of ADHD and my father has symptoms of dyspraxia (DCD) and dyslexia too. Myself and my siblings all have ADHD and DCD, and my youngest sister also meets some criteria for high-functioning ASD (basically she can’t read facial expressions or tone of voice well). We don’t have EDS. I wonder what the next steps should be here, does anyone have any pointers? Much appreciated, thanks so much for the replies!

 

[User172840302]

First place to start is to make sure the basics are covered. If you avoid eggs and milk/yogurt/kefir due to allergies/intolerance or some other reason, these are the major source of iodine in most people's diets. So if you dont eat those daily in regular quantities or use iodized salt, then that is enough reason to trial some potassium iodide in physiological doses (around the RDA of 150mcg) to see if it will help. They have supplements with these kind of doses on amazon. NaturesPlus has a good potassium iodide supplement. Each egg has 25 mcg and each cup of milk/yogurt/kefir has 80 mcg. Allergies and intolerances can also run in the family. I have no idea how you eat but this a possibility. Are you and your family allergic to eggs and/or intolerant to dairy?

Also you may have hypothyroidism even if your iodine intake is normal. So if you have never done a thyroid panel to determine that, know that will also lead to low muscle tone. So that is the first kind of testing I would do if you never tested your thyroid.

Rarely there can also be a dopamine beta hydroxylase deficiency which is genetically related (or also low noradrenaline due to copper deficiency). Serum copper and ceruloplasmin can be tested for that. But there are many genetic disorders that have hypotonia as a symptom. You would need a specialist to really narrow this down. But its good to see MPH actually helped you. This means enhancing noradrenaline treats it which is good.

Muscle tone is the constant partial contraction of muscles. It is due to acetylcholine telling the muscles to contract as is the case in normal contractions due to resistance (like lifting a dumbbell) but muscle tone is a constant partial contraction that is being signalled from the brain when you are awake regardless of resistance from the environment.

Glutamate sends the signal from the brain to the muscles to contract. Noradrenaline (and also Adrenaline, but its only more active during exercise) amplifies the signalling from glutamate. So if noradrenaline is low it will be a weaker signal basically. Acetylcholine cannot make maintain the partial contraction (muscle tone) if there is no signal from glutamate, noradrenaline to release acetylcholine which can then bind to muscle cell to trigger the contraction process.

So something interfering or weakening a signal in this pathway can lead to low muscle tone. In this case, because noradrenaline enhancement helped you, the simple answer is there probably a problem there, which could be due to hypothyroidism like I explained above. Hopefully this helps you understand muscle tone better. Let me know if you don't understand something. I tried to make it as plain english as possible.

Thank you so much for this detailed reply, it was extremely helpful.

So I eat eggs daily, I don’t eat dairy or wheat due to ME/CFS.

I do use iodised salt and have done so for a couple of years and my family used to used is everything now and again growing up.

I’ve had my TSH tested and it is usually around 1.1-1.3 however after covid vaccines it went up to 3.0. Doctor says no need for concern and that this has been happening with lots of people, and I’ve seen 5 doctors who’ve refused to test me for T3 and T4 because of my TSH readings. I live in a country with public healthcare.

As for genetic disorders we don’t look syndromic and barely ever saw doctors or went to hospital (like for spider bites or minor injuries maybe) as children, and were cleared at childbirth.

Someone told me that the noradrenaline could be masking another issue and that low noradrenaline may not be the real reason it’s improving my muscle tone, however I know other people with normal muscle tone who took higher doses of methylphenidate than I did and it had no effect on their muscle tone whatsoever. I also know hypotonic people who took it and it didn’t change their hypotonia whatsoever. So bizarre.

I’m concerned about the increased noradrenergic activity as I can’t really handle the anxiety it gives me (I think from the POTS) so haven’t been able to take it much. I was taking 10 mg but had to drop to 5 mg, now I’m too scared to take it again due to physical panic attacks if I sit or stand up.

As for copper, I’ll have to find a way to test that. My serum zinc is fine but not sure how reliable that test is. Do you know where I could find a specialist? I’m worried that I’ll be brushed away as it’s “borderline” but it really affects my quality of life.

 

[User172840302]

Yes, these meds (Strattera/droxidopa) could aggravate the norepinephrine surge that comes with sitting or standing in hyperadrenergic POTS: https://forums.phoenixrising.me/threads/addressing-blood-pooling.88152/#post-2405716.

Methylphenidate also increases dopamine and norepinephrine in both peripheral and central synapses, but I believe it is more centrally acting (CNS). I think our dysautonomia's can lead to deficiencies of a neurotransmitter in some areas and excess in others, so perhaps you have lowered norepinephrine signaling in some regions of the brain and excess peripherally....

@redsun did a nice job of summarizing the proposed role of noradrenaline in muscle tone, and, indeed, in the article from @pattismith the way they increased the muscle tone in the rats was by injecting norepinephrine into the CNS (in this case where the trigeminal nerve leaves the brain stem). They they were able to observe that this amplified the glutamate signaling, and then ultimately the acetylcholine signaling at the neuromuscular junction of a muscle in the jaw. This ties in with methylphenidate acting more centrally and its potential tie to symptom relief.

Obviously, acetylcholine is also critical for muscle tone. The medication pyridostigmine is used for POTS and muscle weakness and may be worth considering as well if you haven't already.

Thank you so much for this response. Blood pooling is currently the bane of my existence along with B-vitamin responsive issues despite “no deficiencies”. Then the B vitamins tank my potassium, I just can’t win lol. Really interesting. I should mention the methylphenidate also removes all of my DCD-related coordination issues, it’s like magic, however I’ve spoken to others with DCD and it has had no impact on their symptoms. The lowered CNS noradrenaline and increased peripheral noradrenaline activity kind of makes sense. It must have been present since we were born though as the hypotonia was. Will look into pyridostigmine, thank you!

 

[pattismith]

Thanks so much for this. I guess it’s very plausible that some kind of metabolic disease is present given the FH. Finding that is the issue I guess (I’m 22 so kind of a newbie). I don’t think I have delayed muscle relaxation from a quick Google. As for mitochondrial disease - is this something that’s passed down through the mother’s mitochondria (because my mother has normal muscle tone) or can also be influenced by faulty genes? I ran my 23andMe results through Promethease and nothing of the sort came up, however that’s not exactly reliable I guess. Lots of autoimmune markers though. What’s interesting is we were literally all born with this and it hasn’t changed, might have slightly improved, with age and it’s just so puzzling how responsive it is to methylphenidate (I have taken mirtazapine before which increases noradrenaline I think, different mechanism, but it had no effect). We don’t have EDS. I wonder what the next steps should be here, does anyone have any pointers? Much appreciated, thanks so much for the replies!

-23andme only gives you a small sample of your genes;
-mitochondrial diseases can be either inherited from mitochondrial DNA or nuclear DNA.
-Some mitochondrial disease are nuclear and dominant so that an affected father can have affected children.

unfortunatly medecine is good at finding neurometabolic diseases affecting babies, it's not yet the same for later onset and lighter forms..

Do you have eyelids ptosis in your family?

 

[User172840302]

Do you have eyelids ptosis in your family?

I have minor ptosis in one eyebrow and maybe eyelid (not sure if it’s just the drooping eyebrow creating such an effect) that seems to go away with methylphenidate, strange. I was literally born with it. On my mother’s side there is slight unilateral drooping of the eyelid in some people but only really noticeable in photos. None on father’s side, my other siblings don’t have it.

 

[redsun]

I have minor ptosis in one eyebrow and maybe eyelid (not sure if it’s just the drooping eyebrow creating such an effect) that seems to go away with methylphenidate, strange. I was literally born with it. On my mother’s side there is slight unilateral drooping of the eyelid in some people but only really noticeable in photos. None on father’s side, my other siblings don’t have it.

Ptosis is seen in those with mutations in DBH gene causing norepinephrine deficiencies.

You can check this link and see if you match some of the other clinical findings associated with this.

https://www.ncbi.nlm.nih.gov/books/NBK1474/

 

[User172840302]

Ptosis is seen in those with mutations in DBH gene causing norepinephrine deficiencies.

You can check this link and see if you match some of the other clinical findings associated with this.

https://www.ncbi.nlm.nih.gov/books/NBK1474/

Thanks, I just checked it out. I seem to match no other defining symptoms. My BP has always been normal/high and I definitely have an overactive sympathetic nervous system. I get orthostatic hypertension with my POTS, not hypotension. Is the ptosis in this condition uni or bilateral? Mine is unilateral and I’m the only one with it. I just checked and it seems to just affect my eyebrow. I’ve definitely got an excess of adrenaline.

 

[redsun]

Thanks, I just checked it out. I seem to match no other defining symptoms. My BP has always been normal/high and I definitely have an overactive sympathetic nervous system. I get orthostatic hypertension with my POTS, not hypotension. Is the ptosis in this condition uni or bilateral? Mine is unilateral and I’m the only one with it. I just checked and it seems to just affect my eyebrow. I’ve definitely got an excess of adrenaline.

Yeh ptosis does not have to be present in both eyes. Yeh so if you still have adrenergic like symptoms such as POTS and BP is normal, then likely you dont have a genetic DBH deficiency. And probably are not copper deficient since the symptoms would be quite similar. Its still a possibility but unlikely.

Thank you so much for this detailed reply, it was extremely helpful.

So I eat eggs daily, I don’t eat dairy or wheat due to ME/CFS.

I do use iodised salt and have done so for a couple of years and my family used to used is everything now and again growing up.

I’ve had my TSH tested and it is usually around 1.1-1.3 however after covid vaccines it went up to 3.0. Doctor says no need for concern and that this has been happening with lots of people, and I’ve seen 5 doctors who’ve refused to test me for T3 and T4 because of my TSH readings. I live in a country with public healthcare.

As for genetic disorders we don’t look syndromic and barely ever saw doctors or went to hospital (like for spider bites or minor injuries maybe) as children, and were cleared at childbirth (except sister for her tongue but it ended up not being an issue as she grew up and she could always keep it inside her mouth, sometimes as a baby and almost always after 8 months). She’s also tiny (like 150 cm tall) but they put that down to the smoking and short maternal grandmother.

Someone told me that the noradrenaline could be masking another issue and that low noradrenaline may not be the real reason it’s improving my muscle tone, however I know other people with normal muscle tone who took higher doses of methylphenidate than I did and it had no effect on their muscle tone whatsoever. I also know hypotonic people who took it and it didn’t change their hypotonia whatsoever. So bizarre.

I’m concerned about the increased noradrenergic activity as I can’t really handle the anxiety it gives me (I think from the POTS) so haven’t been able to take it much. I was taking 10 mg but had to drop to 5 mg, now I’m too scared to take it again due to physical panic attacks if I sit or stand up.

As for copper, I’ll have to find a way to test that. My serum zinc is fine but not sure how reliable that test is. Do you know where I could find a specialist? I’m worried that I’ll be brushed away as it’s “borderline” but it really affects my quality of life.

The body has autoreceptors to deal with excess neurotransmitters so people who have normal muscle tone don't get hypertonia. But those with hypotonia who do not respond to norepinephrine may have lower motor neuron lesions or something else that is making them not respond.

Because you don't eat dairy I assume you supplement with calcium? If so how much? Even though calcium itself has no direct role in the signalling to the muscle, it is necessary for the actual muscle contraction and thus it is also necessary for the partial muscle contraction (muscle tone). I even noticed this in myself if I do not get calcium for even a few days I can feel the fullness and density of my muscles is reduced. Its possible, especially in chronic low calcium intakes, the intracellular calcium available to the muscles is reduced and both contractions and muscles are weaker. Low calcium intake also can cause or contribute to anxiety and adrenaline related symptoms, and higher BP. Calcium supplements have been shown to lower BP and may improve some of your symptoms if you have not been supplementing calcium to compensate lack of dairy.

Its worse too if you, like many, supplement with magnesium which is a common thing in health communities. Magnesium directly competes with calcium for the binding sites in the muscle fibers. Mg is actually bad for flaccid muscles while calcium will improve flaccid muscles. So if you happen to take Mg I would lay off that.

If you have public healthcare, you would need to get referred by a doctor to a neurologist. Thats what they specialize in. Otherwise I am not aware of any other way.

 

[pattismith]

I have minor ptosis in one eyebrow and maybe eyelid (not sure if it’s just the drooping eyebrow creating such an effect) that seems to go away with methylphenidate, strange. I was literally born with it. On my mother’s side there is slight unilateral drooping of the eyelid in some people but only really noticeable in photos. None on father’s side, my other siblings don’t have it.

I'm not a doctor so can't tell you what you may have or may not, but this is an article from italian neurologists

Acquired isolated unilateral or bilateral blepharoptosis has many aetiologies. When the pupils are normal, a myasthenic syndrome or myopathy has to be ruled out.
If the tests for myasthenia gravis are negative, the next step is to perform a muscle biopsy to establish a diagnosis.
Muscle examination may show a mitochondrial disorder, non‐specific abnormalities or be quite normal. ....

Eyelid ptosis from sympathetic nerve dysfunction mistaken as myopathy: a simple test to identify this condition - PMC (nih.gov)

 

[User172840302]

Yeh ptosis does not have to be present in both eyes. Yeh so if you still have adrenergic like symptoms such as POTS and BP is normal, then likely you dont have a genetic DBH deficiency. And probably are not copper deficient since the symptoms would be quite similar. Its still a possibility but unlikely.



The body has autoreceptors to deal with excess neurotransmitters so people who have normal muscle tone don't get hypertonia. But those with hypotonia who do not respond to norepinephrine may have lower motor neuron lesions or something else that is making them not respond.

Because you don't eat dairy I assume you supplement with calcium? If so how much? Even though calcium itself has no direct role in the signalling to the muscle, it is necessary for the actual muscle contraction and thus it is also necessary for the partial muscle contraction (muscle tone). I even noticed this in myself if I do not get calcium for even a few days I can feel the fullness and density of my muscles is reduced. Its possible, especially in chronic low calcium intakes, the intracellular calcium available to the muscles is reduced and both contractions and muscles are weaker. Low calcium intake also can cause or contribute to anxiety and adrenaline related symptoms, and higher BP. Calcium supplements have been shown to lower BP and may improve some of your symptoms if you have not been supplementing calcium to compensate lack of dairy.

Its worse too if you, like many, supplement with magnesium which is a common thing in health communities. Magnesium directly competes with calcium for the binding sites in the muscle fibers. Mg is actually bad for flaccid muscles while calcium will improve flaccid muscles. So if you happen to take Mg I would lay off that.

If you have public healthcare, you would need to get referred by a doctor to a neurologist. Thats what they specialize in. Otherwise I am not aware of any other way.

My issue hasn’t changed regardless of calcium intake, I used to eat a lot of dairy and never noticed any difference. I now have fortified alternatives. Thanks, I think I’ll have to push to see a neurologist maybe for an EMG. Anyway thank you so much for this help!

 

[User172840302]

I'm not a doctor so can't tell you what you may have or may not, but this is an article from italian neurologists



Eyelid ptosis from sympathetic nerve dysfunction mistaken as myopathy: a simple test to identify this condition - PMC (nih.gov)

Thank you! Yes, definitely seems like something in that domain is not quite right. Have you had any success with anything other than duloxetine? Makes me wonder if we have the same condition, though it seems to be quite rare

 

[Methyl90]

I have to say I am still simultaneously slapping my forehead and rejoicing in this revelation.

I do have some GABA for my husband, I will try some of that. I also had ordered some tyrosine and royal jelly for the BH4 issue, which looks like it's upstream from norepinephrine. Let me see what else I can find.

Thank you so much for taking the time to write about this.

Several things about raising norepinephrine have come across my path in the past week, which seems like a blessed coincidence.

What would be the correlation between royal jelly and BH4? I'm asking because I've been trying pollen for a few days with slight benefits.

 

[Violeta]

What would be the correlation between royal jelly and BH4? I'm asking because I've been trying pollen for a few days with slight benefits.

Royal jelly contains tyrosine.

https://www.sciencedirect.com/scien...ain levels of,in queenless honey bee colonies

I learned a lot about BH4 from @Learner1's messages.

"I would look into BH4, tetrahydrobiopterin, deficiency. BH4 is necessary for adequate catecholamine production and has been associated with ME/CFS. There is current research going on. Kuvan can be prescribed if you have a problem with making or recycling BH4."

I went straight to the tyrosine. I found N-acetyl-l-tyrosine very helpful and I take it with Butcher's broom.

 

[Methyl90]

@Violeta Very kind of you, thanks. I had memories that royal jelly could inhibit xanthine oxidase so something related to circadian rhythms and uric acid.

 

[Violeta]

@Violeta Very kind of you, thanks. I had memories that royal jelly could inhibit xanthine oxidase so something related to circadian rhythms and uric acid.

That's very interesting, I didn't know that. I have had what seemed like uric acid problems in the past and definitely circadian rhythm problems intermittently.

Wow, look at this study. I have to run an errand but this is an eye opener. I should probably get some royal jelly.

https://journals.sagepub.com/doi/pdf/10.1177/1934578X20908080