Original subtitles

okay so I think we'll get started

so my name is Lauren Stiles

I am the president and founder

of Dysautonomia International

we're a patient advocacy organization

that assists and advocates

for people with a whole bunch of different autonomic

nervous system disorders

and we're very

very happy to be joined by Dr

David Goldstein

who is a preeminent expert in the field

he is the chief of the Autonomic Medicine Section

at the National Institutes of health

in the National Institutes of Neurologic Disorders

in stroke and he's really

really an expert in all things autonomics

and we're really happy to have him talk on this topic

because he has actually published

probably one of the few articles even discussing it

and I know that a lot of the patients

from the ETS surgical complications support groups

were really excited

to hear that he was going to present

so with that

I will turn it over to Dr Goldstein

you can type questions into

the Q and a

it says host disabled participant screen share

well that's not good hold on one second

let's see if you can try that again

that's better okay

okay so hi everybody I'm Dave Goldstein

and if you can see my screen then we'll

we'll get started here

Lauren can you see the screen

we can see your all your slides

so just pick the one right into presentation mode

great there you go

all right so this is this

this is the the list of topics for

for this talk

like everybody else in this business

I talk about what I know about and then

and that's not necessarily what people

want to know about

or I can know about

but eventually we'll deal with these nitty

gritty questions that I think are on people's minds so

why are dysautonomia is hard

what is the autonomic nervous system

how is it organized

what are the chemical messengers

this is important for post ETS kind of issue

what are the chemical messengers

of the autonomic nervous system

where does hyperhydrosis fit in the

dysautonomias universe as I call it

what are the treatments for hyperhydrosis

what are the complications of those treatments

in particular of endoscopic thoracic sympathectomy

that's ETS

what are what treatments are there

for the complications of ETS

and what research is being done for post ETS

kinds of problems

so that's a lot of stuff to go over

and in this short period of time

I'm only going to be just touching on some aspects

why are dysautonomias hard

first because they're multidisciplinary

if you go to a cardiologist

they look for a heart rhythm and rate problem

if you go to a neurologist

they look for seizures or parkinson's disease

and so forth and so on

there's no institution that I'm aware of that

including ours

that the focuses

on dysautonomias which are in generally multi system

multi disciplinary disorders of regulation

another reason that this

autonomies are hard is because they're complex

see if I can get this out of the way here

there we go

this is what happens when you

somebody stands up all sorts of arrows and

and abbreviations

another reason that dysautonomies are complex

is because there's a zillion autonomic tests

and only some of them are really relevant

to the problem

but it's a

and different institutions do different types of tests

and there's a many many abbreviations and

and tough tough to pronounce

words like dysautonomias or as we'll be getting into

catecholamines

which are key chemical messengers of the

autonomic nervous system

another reason that dyautonomias are hard

is because they're mind body disorders

it's not a matter of

this is a psychogenic problem

this is a problem

you know outside the brain

the the autonomic nervous system operates exactly

at the border of the the the

the mind and body

and another reason that dysautonomia is hard is that

the supply of clinicians

nation and worldwide

is puny compared to the patient demand

because there's so little

training in autonomic medicine

so what is the

what is the autonomic nervous system

well here's a

here's a diagram of the autonomic nervous system

and I think anybody who looks at this diagram

would pretty much conclude the same thing

which is that if this is impossibly complex

so we'll try to start

from something that people generally do know about

and build up from there

and I use the analogy of a Tootsie Roll pop

a Tootsie Roll pop

is as it has this this

this thick crusty shell but the key to it

touch Tootsie Roll Pop is the chewy chocolate center

the central nervous system

is organized like a Tootsie Roll pop

the stick is a rope of nerves called

the spinal cord and

the crusty candy shell

well that's the cortex of the brain

but the key to

the key to the Tootsie Roll pop

is the chewy chocolate center

and that's the brain stem

so this is kind of an organization

roughly of the central nervous system

you've got the cerebral cortex the brain stem

and importantly

the thoracic and lumbar spinal cord

which is where sympathetic nerves

come from

this is a sympathetic chain from a human who

at death was plasticized and kind of immortalized

and you can see this sympathetic chain is obviously

outside the central nervous system

it's outside the spinal column

and you can get

you can identify the

this sympathetic chain by going along the spinal nerves

and and then looking for a chain that's

or a string of nerve tissue

that's going perpendicular to those nerves

so that's that's what the sympathetic chain looks like

and if you were to have a excision or or

cauterization

or clipping

of ganglion

then this would be

this is where it would be in the body

so I sort of idealized this

or make it simple

by thinking of the sympathetic chain as

like pearls on a necklace

on each side of the spinal column

so it's pretty clear that the sympathetic nerves

are not in the central nervous system

why are there ganglia

I use the analogy of how electricity gets to your house

you have these very thick

high voltage wires

that are coming from the distribution center

but then outside your house

at least if it's an old neighborhood like mine

you have a utility pole

and on that utility pole is transformer

and what actually goes to your house

are these thin wispy

wires the low voltage and so forth

and by analogy the ganglia

are like the transformers on the utility pole

they're coming out of the spinal cord

there are thick myelinated

rapidly conducting pre ganglionic neurons

but that's not what goes to the target organs

what goes to the target organs are wispy

thin slow conducting non myelinated fibers

these are called post ganglionic fibers

how in the body

is the autonomic nervous system organized it's

this is kind of complex

but it's not as complex as that first diagram

and what I want to focus on is

the sympathetic cholinergic outflow to sweat glands

which is here

so here's this here's the

here's the thoracolumber spinal cord

then you have this short myelinated

fiber then the ganglia

and then the thin slow conducting non myelinated fiber

and acetylcholine is the chemical messenger

that's released both in the ganglia

and also at the level of the target organs

such as the sweat glands

the autonomic nervous system has parts

it's not one thing

so when you say I have dysautonomia

that really doesn't have much meaning

the autonomic nervous system

is defined by Langley about a century ago

has 3 parts

the interic nervous system

that means nerves that are in the gut

the parasympathetic nervous system

which is a word they Langley invented

and the sympathetic nervous system

in the early 20th century

the American physiologist Walter Cannon

added a hormonal part to the autonomic nervous system

adrenaline or epinephrine

I call this the sympathetic adjoinergic system

and I think most relevant to the talk today

at about the same time Sir Henry Dale

introduced the idea of a sympathetic cholinergic system

sympathetic cholinergic system mediates sweating

thermo regulatory sweating

gustatory sweating

such as when you eat hot chili peppers

and you sweat on your forehead

and an emotional sweating

so there there are

there are at least 5 components

to the autonomic nervous system

and ositocoline is the chemical messenger

for the parasympathetic nervous system

and the sympathetic cholinergic system

so if we go back to this thing

here's the vagus nerve

which is the main parasympathetic nerve in the body

this is sympathetic neurogenergic system

this is sympathetic cholinergic system

and this is a special system

the system that goes to the adrenal Medulla

where epinephrine comes out

you'll notice

that there isn't any synapse in the ganglias

just a direct myelinated connection

it kind of fits teleologically

with the idea of fight or flight

you need something really rapid

all right well with that background

in terms of organization and the chemical messengers

we can begin to think about where hyperhydrosis fits

in the dysautonomias universe

there are numerous

numerous forms of autonomic dysfunction

I break it down in terms of pediatric

adult and geriatric

there are the ways of doing this

oops sorry and

in the pediatric age group

there's a lot of genetic load

and there's a lot of developmental problems

with the autonomic nervous system

in the adults

basically the apparatus is intact

but it's not being regulated right

and in the geriatric age group

the autonomic nervous system is degenerating

by and large

when we're talking about hyperhydrosis

I think we're talking about adults

this is a functional problem

functional not meaning that it's psychiatric

functional meaning that there's dysregulation

of the apparatus

that actually develop normally

so here here is where the hydrohydrosis comes in

what would cause that

and well you can see there are multiple places

where you could have an abdomality with

is an excessive delivery of acetylcholine

to its receptors

on sweat glands

and if I had a guess there's something that is

sorry there's something that's disregulated about

the central autonomic network

that's supposed to be regulating core temperature

unlike unlike dogs

let's say that pant for

for regulation

of their temperature

unlike rats that use their tails for Thermal regulation

human beings are basically naked apes

and the way they regulate their core temperature

is by way of evaporative heat loss from the skin

for evaporative heat loss from the skin you need

you need sweat

and you need to deliver blood to the skin's surface

so the sweating by and large

is mediated by the sympathetic cholinergic system and

the regulation of blood flow to the skin is

by and large by the sympathetic neurodegenergic system

and together there can be tremendously effective

in terms of maintaining core temperature

by evaporative heat loss

this is why people can survive in a sauna

let's say that's just so hot that you could you could

you could fry an egg

so

nobody knows what causes hyperhydrosis

my guess is that there's some sort of discombobulation

in the parts of the brain that control

sympathetic neurogenergic

and sympathetic cholinergic alphlose

but that's just the guess

well what do you do about hyperhydrosis

well if it's

if it's mediated by acetylcholine

at muscarinic receptors you could

you could treat the hyperhydrosis with

locally with an anticholinergic cream

and this can be very effective

there's a there's a

a anti cholinergic that's been around for a long time

called glycopyrrolate and

we've tried that in a person who had

not only a problem with excessive sweating

but the sweating hurt

it was painful sweating

which is almost a unique situation

glycopyrrolate

applied locally not only alleviated the sweating

but also alleviated the pain

it was really interesting

for glycopyrrolate to work though

it takes several many hours

and so if you're going to apply it

it's not like applying like

a steroid cream for poison Ivy or something like that

it's you would have to apply it and kind of have

some sort of plastic glove

and and have have

and wait several hours for the glycopyrrolate to to work

or you could be traded with a systemic

systemic anti cholinergic

but then there are quite a few side effects that are

that can be kind of nasty

you could be treated I suppose with with Botox

which would eliminate the release of acetylcholine

at the level of the at the level of the sweat glands

or

you could try

surgical sympathectomy

now we go back a little bit here

if you were to cut ganglia here

he would say there is alleviation of the sweating

but you're also interfering with sympathetic

neurogenergic neurogenergic function as well

the 2 go together

so

what are the principles of management of hyperhydrosis

as for all forms of autonomic dysfunction

the most important treatment is education

you have to know what you're dealing with

what you're not dealing with

what the syndrome would look like

if there were multiple

components of the autonomic nervous system involved

or multiple transmitters etc

you want to learn what to avoid

what would make things better

which drugs would work

would cause problems

and which drugs would not cause problems and so forth

after that there's non drug treatments

then drugs are a week 3rd

and in the case of hyperhydrosis

the last resort would be neurosurgery

cut the ganglia or clip

or clip the sympathetic chain

and eliminate the

or cut down on the release of acetylcholine

at the sweat glands

well what's the problem with endoscopic thoracic

sympathectomy

a lot depends on who you ask

because neurosurgeons don't like to think about

complications of what they do

especially complications that take time to develop

and

and nobody knows what the denominator is

that is to say

of people who have ETS

what proportion of people have complications

we know that there are complications

and the people who have the complications are

not happy with them

but what's the denominator

what about the people who sail through the surgery

and they're cured and that's the end of the story

I think one of the more common complications is

called compensatory or ectopic hyperhydrosis

and I'm going to guess that there are people on this

zoom call who have this or had it

and it's not a lot of fun

the sweaty palms might be improved

or sweaty scalp might be improved

but now there's increased sweating

in parts of the body that weren't involved

this is below the level of the

the sympathectomy

the the the back the abdomen the the crotch

the feet and toes

this is a screenshot that I took of a patient who had

compensatory hyperhydrosis

after ETS for Palmer's sweating, well

Woody another

I think important but grossly under recognized

a complication of the thoracic sympathectome is

since you're also disrupting sympathetic

neurogenergic nerves that are supplying the heart

there can be a decrease

in the amount of sympathetic nerves in the heart

this is what was found with the bio group

in terms of sympathetic innovation of the heart

and this is with the unilateral sympathectomy

which is not really something that's done commonly

for hyperhydrosis

because it's usually bilateral problem

this is bilateral

and you can see this kind of

an obvious decrease in the signal here in the heart

and this is what you see in pure autonomic failure

which is a rare form of autonomic failure

where it's known that there's a substantial loss

of norepinephrine or neurogenergic nerves in the heart

so it's not a complete denervation

it's partial

and and this is because

when you do the

the ganglion clipping or ganglionectomy

you're you're not necessarily eliminating all the

the sympathetic supply to the heart

what would the consequence be of

this partial cardiac denervation

well I think one of the main things would be

shortness or breath with exercise

you can't tolerate exercise

your heart rate might go up as much as it's supposed to

the brain depends on input from the heart

and other parts of the periphery

for deciding whether you're emotional

and if this is

if there's a car if there's a cardiac denervation

then you can get like a weird sort of blunted affect

the sympathetic

the sympathetic nerves also supply

the pineal gland

and so sleep can be disrupted

these are these are complications

that no one would think about

if you're focusing on the effect of the delete the

the sympathectomy on the sweat glands in the skin

what one of the things that was tried early on

for for the

this compensatory hyperhydrosis is

well let's just extend

let's just extend the sympathectomy further down

and then and then

that'll take care of the compensatory hyperhydrosis

and that's what was done in this particular patient

and it's kind of obvious

you can see that

the person developed orthostatic hypotension

which was quite severe

interestingly

the heart rate increased just fine

so this is an example of

where one part of the autonomic nervous system

the sympathetic neurogenergic system

is screwed up

but the parasympathetic nervous system

which is to a large extent what determines

the increase in hard rate with standing is fine

there are other examples where

sympathetic failure produces orthostatic hypotension

but if you depend on the heart rate response

to determine whether

the orthostatic hypotension is neurogenic

you'll miss that

that this really is sympathetic failure

and it's neurogenic orthostatic hypotension because the

the vagal part is intact

that's above the level of where the sympathectomy was

what treatments are there for complications of ETS

well we just went through one of them

extend the sympathectomy

but I think those days are over

if you've if you've had ganglionectomies

that's tough

there have been attempts to kind of re

rewire or or transplant nervous tissue

and there if you look at the literature

of course only they're mainly going to become

going to be

reports of success

and again you don't know what the denominator is

if you've had surgical clipping

well the clips could be removed

but you have to remember that

when you put on those clips

you are causing degeneration

of sympathetic nerves distal to those clips

and even if you remove those clips

those nerves those post ganglionic

non myelinated slow conducting nerves

they may not regenerate

or if they do it may take a long time

finally what research is being done for post ETS and

this is kind of humiliating and embarrassing because

I don't think there's much of

any research being done on post ETS

certainly not in the

in the autonomics world

just the fact

so I have you know some anecdotal

results to talk about but

except for the finding of the partial

cardiac innervation

there's really a dearth of literature

based on research for post ETS

so that that's

that's the end of my my talk

I'm gonna stop sharing

and and hopefully there's some questions

yeah there's

there are some questions

and then also up

let me turn my video on

there's some questions

and then also

I thought we could have sort of a discussion

and encourage our audience members to use

the Q and a feature

to sort of engage in the discussion because

I actually have some questions for these patients

your last slide

saying we don't have any ETS

sort of complications research going on

I actually think that's something that

Dysautonomia International could help facilitate

in the simpler sense

you know we're not running big autonomic labs but as Dr

Goldstein knows

we've done survey based research on pots

where we just try to capture the patient experience

we ask people

how long have you been living with this

what are your symptoms

what treatments have you tried

and I really think

it's actually not too hard to do that kind of research

and I think the best way to do it is actually to ask

the ETS surgical complication patient community

what are things that are important to you

that you would want to ask

a large group of patients about

in a survey

so that kind of research doesn't get us

the rate of people that have this after the surgery

right because you're only asking the people

who have the problem

you're not asking all the healthy people that

had a surgery and had no big deal

but Dr david goldstein

I don't know if we can recruit you

and I don't want to do it on a webinar

but we can recruit you to be part of that

because I think

you know it's simple

just capturing the patient experience and publishing it

can maybe encourage

other researchers to do more substantive research

you know so

where'd you go

there you are

so let's go through a few of the questions here

I'm at a hotel

oh the Wi Fi is problem problematic you're back

okay here's one of the questions

um what oh well here's

let's see I'm not sure if we have an answer on this

but I'll ask you

someone wants to know what would it take

for sympathectomies to be banned in the US

just as ETS was banned in Sweden

I don't know the politics at all

yeah I think it's

I mean it's pretty unlikely that

the surgery would be banned

because there are it doesn't feel like it

when you're hanging out in the ETS support groups

but there are lots of people who get the surgery

and benefit from it

so it would seem unlikely

if you were going to pursue this

you would have to find out what the denominator is

it turns out that 99% of the people are fine

and 1% have a complication

you're not going to ban the procedure yeah

and there are other reasons sympathectomies are used

besides hyperhydrosis

there have been people

proposing it for some other medical conditions

so even if there was any kind of regulation on it

it would have to be probably very tailored right

I focused entirely on the hyperhydrosis thing but

there's quite

I think convincing

experience with at least left Stelly ganglionectomy

to treat particular types of heart rhythm problems

and can be very effective

so I think this is this is

it's not going to happen in the United States

I'd be surprised

so here's a question

do people automatically have dysautonomia

if they have had ETS surgery

yes by definition

this is an iatrogenic form of autonomic failure

so just explain what iatrogenic means for people

it's caused by doctors

yeah

so what are here's the second question

what are your thoughts on reversal

given the many success stories coming out of Taiwan

I

when I when I looked at the

when I looked at the the studies they were

there were some

there were some positive and there were some

some negative

I'm guessing that if you

if you have an unclipping kind of procedure

that's more hopeful

no then some graft of

sural nerve or something like that

I can't figure out how that would work

you're only put together once

and it's tough to think that some neurosurgeon

is going to just take a piece of nerve tissue

so ram it in there

and somehow all these wispy

non myelinated fibers that developed over the course of

your fetal development and early postnatal life

somehow they're all going to just magically work

I would maybe

I'd be kind of skeptical

yeah I look a lot

sort of with just fascination

with research on spinal cord injury

which has a lot more funding than dysautonomia research

and sympathectomy

research to look at what are the different techniques

researchers are using to

make severed spinal cords work better

so you know

and there's a lot of advancements happening there

and my hope is that very interesting topic really is

I don't know how well that applies

for the post ganglionic or sympathetic

sympathetic nerves

you're right

there's some

it takes a long time

but there can be some surprising

beneficial effects of spinal cord stimulation

below the level of the

of the lesion

at least then

people who are quadriplegic

from high spinal cord injury

I was at a meeting a few months ago in Louisville

and there were patients there who

showed videos of themselves going through this

very difficult

complex and long physical therapy

with the spinal cord stimulator

being adjusted this way and that way but

at least some of them could start to walk

amazing so right now it's not being studied

and sort of thinking about the ganglia

but I feel like the concepts that they've Learned

that they're learning from that maybe someday

that applies to other parts of the nervous system

that we need to regenerate or reconnect or get possible

it's a major research question

how does this happen

you can see it does

how does it happen

the spinal cord is cut

it's

I think that's what was most fascinating about

about attending this symposium

people are kind of scratch on their heads

and coming up with very fancy

speculations about how it might

might happen

and it's not just

it's not just a matter of locomotion

there are autonomic problems after all

cut you know

the sympathetic chain is not chain

but the the

the spinal cord descending pathways they're

they're cut

and yet with this spinal cord stimulation thing

and the intensive physical therapy that is

over the course of several months

somehow when these people are tilted

they were able to release norepinephrine

and the autonomic problems which can be very severe

also get better amazing

so I'm going to hop on to another question here

are there any medical tests that you recommend

people who have ETS complications get

any types of autonomic testing or anything like that

that might be helpful to figure out

a good treatment plan for them

I I'm not sure I mean the

that pet scanning of the heart is kind of cool

but that's a very fancy technology that's only

it's only available at the NIH

and I'm not doing it anymore for

for this problem for reasons that I want to get into so

what would be the purpose of the testing

well this person

was just asking if there was any medical tests

but I added to their question

that might help them get an optimized treatment

I mean so let's say you have the surgery

you have all kinds of awful

worse dysautonomia stuff happening now

you know what

it's not just a compensatory hyperhydrosis

you know it's

there's other autonomic stuff that these folks have

so you know

with standard autonomic type

it's probably very dependent on your individual case

right like well if you

let's just say you really do have a partial

sympathectomy

of the heart and

and you do have symptoms

where you have exercise and tolerance

shortness or breath

and your pulse rate doesn't go up like it should

the receptors for norepinephrine are there

on the myocardial cells

they're just fine

it's possible that

treatment with a drug that acts on those receptors

might increase the force and rate of the heartbeat

enough that there's actually an effect

in terms of exercise tolerance

let's just say

just a guess

from the point of view of the sleep

I think melatonin can be very effective

and people who have

this have insomnia

as a complication of the ETS

melatonin would be pretty simple to try yeah

do you think that people who have sort of complex

autonomic presentations after this surgery

do you think that they benefit from

trying to see someone who's an autonomic specialist

which there aren't many of in the world

do you think but like

that type of doctor is most likely to understand

the lesion is causing a problem

and here's some things we might be able to do to help

maybe if you if

I'm not going to go back to it

but if you look at that dysautonomias universe

as many circles as there are

hyperhydrosis and post ETS are not there

so I think even in autonomic centers

they'd be

pretty ignorant of what you would actually do

well hopefully not as dismissive

I think a lot of these patients

just like other dysautonomia patients

if they go to their primary care doctor

they often kind of get poo pooed and you know this is

no yeah absolutely

you know when you have

when you have a like a blunted affect or

nothing really affects your

affects how you feel one way or the other

you can't feel joy or

or or rage or or grief or what have you

who studies that and what what would you do about that

I think unfortunately what I said about

dysautonomia is being mind body conditions

I think this is

this could be an example

if the brain is not getting the input from the heart

about a situation

that should be evoking an emotional feeling

they the brain may say well I don't feel anything

so here's a

it's more of a statement and a suggestion

but it's pretty cool so I'm gonna read the whole thing

Dr Goldstein

will you please check EMG

including repetitive STIM and jitter

on sympathectomized limb muscles

in rodent studies

muscle autonomic neuropathy

leads to atrophy

and instability of the neuromuscular junction

post sympathetic patients are perfect to study

autonomic muscle neuropathy

this could explain autoimmune sarcopenia syndromes

as well as motor power

trace instabilities in general

and generated

instabilities in generated power

and possibly muscle irritability

thanks from Bree

so I think it's a cool comment

I'm not sure if you have a

that's interesting

but it's neat

you're removing not only the sympathetic cholinergic

innervation of sweat glands

you're removing sympathetic neurogenergic innervation

which goes to a whole variety of types

of cells and it's

yeah there could be consequence there

that could be objectively

evaluated I don't think anybody's thought about that

yeah that's a neat idea

so here's a question

is the compensatory hyperhydrosis

that occurs after ETS surgery so typically present as

like an immediate onset like it

like a spinal shock type like a

like a spinal severing type of problem

or is it more of an onset gradual post surgery onset

you know do you

do you know what the breakdown

I have a feeling it was pretty quick but progressive

but my guess is that

if you canvassed the attendees at the zoom call

you'd be getting a better answer

than me I'm gonna guess that compensatory hyperhydrosis

is is a factor in half of these attendees

and they can tell you yes

when it came on yes

I'm a true believer that patients

are really the experts

when we have a total unknown that really

no one's studying

the first place to ask is the patients

and then try to evolve it into more detailed research

from from after

after you understand the patient experience

so I see patients are tremendous scientific resource

because they tell you what's wrong

it's up to the researcher to try to figure out

how that happens

but they tell you what's wrong

yeah I see some people raising their hands

so if you have a question

just please type it into the Q and a toolbar

and I'm trying to get to as many as we can

we can probably do a few more before the 8 o'clock

Eastern time hour

there are physicians

this person is just saying

there are physicians that do specialize in dysautonomia

so if you want to try to see someone who has

autonomic expertise

you can go to Dysautonomia international's website

dysautonomiainternational.org

slash doctors

and we also welcome

I put in the chat earlier

we welcome people with any type of dysautonomia

in our online support groups on Facebook

we have support groups in all 50 US states

most Canadian provinces and 60 other countries

we also have some

international sized groups that are everyone

and if you go on those groups

you can ask the local patients like

who are the good autonomic specialists in this area

and they will tell you

even more so than what's on our website

and then also

I put a link to there's an

ETS focus support group

it's not run by Dysautonomia International

but the people who run it are very friendly

and knowledgeable

and there's quite a few of you

probably came from that group

but if you haven't found it yet

check out in the chat

if you have an ETS surgical complication

I think getting the patient community

that has this organized in one place

so you can network with each other

and almost certainly if you get enough people in a room

somebody there is a statistician

and somebody has a contact in the media

and somebody's uncle is a doctor or something like that

so organize your patient community

so that you can do a little more advocacy

so here's a question

is mestinon useful in these post ETS patients

Mestinon, Mestinon is a

that's kind of an interesting one

Mestinon is

a a blocker of acetylcholinesterase

most of the acetylcholine that gets released

is rapidly metabolized so

if you have an acetylcholinester ace inhibitor on board

then for a given amount of acetylcholine release

you'll deliver more acetylcholine to its receptors

acetylcholine

if you remember my organization slide is also

also mediates the ganglionic transmission

that's kind of an interesting question

I don't understand why

compensatory hyperhydrosis happens

I'm going to guess that there's some sort of a

discombobuulation and a hypothalamus

that caused the hyperhydrosis in the first place

and then if the brain can't uh

can't have the

the amount of sweating that it wants

because of the sympathectomy

then it figures out a way around it

so you have compensatory hyper

hyper hydrosis

it if that were the case then

Mestinon could make the deck topic

or compensatory hyperhydrosis worse

so I just want to jump in because you mentioned

you know some people

might who have hyperhydrosis

that leads to them getting these surgeries

it might have been primed

for a broader autonomic problem

so we've talked about this with Dr

Brock at Johns Hopkins

who runs the hyperhydrosis clinic at Johns Hopkins

and he's not a bad guy

he's not promoting these surgeries at everyone

I know a lot of the ETS surgical patients

that have had complications

think that you know like

every doctor who does these surgeries is awful but Dr

Brock actually

very aggressively tries not to do the surgery

and really really

really only saves it for

people who are just in super dire straits

and nothing else

he actually does great research

trying to find alternative ways to deal with it

but one of the things he's studying right now

that it's actually a study

that Dysautonomia International is funded

looking at families of his hyperhydrosis patients

and it turns out a lot of them

have relatives with other types of dysautonomia

they have orthostatic intolerance

they have pots

they have really significant gastroparesis

which is sort of like dysautonomia

of the GI tract sometimes

so he started doing genetic research

on his hyperhydrosis patients and their families

to try to find it

is there some kind of genetic thing that

makes you more prone to

this autonomic problem

and so he's got some preliminary findings

from our study

that we gave him 100 grand

so it wasn't a huge study

seems like a lot of money

but in terms of biomedical research

$100,000 is kind of like not much

so we gave them the seed funding

to get the prelimary data

and he found enough genetic evidence

to then apply to the National Institutes of health

and he got a large grant to study more

do bigger study

on the genetic markers

and hyperhydrosis

and sort of multi generational dysautonomias

I know that doesn't help people

yeah I know that doesn't help people

who have already had the surgery

and have bad complications

but maybe this is the kind of thing that

when we understand this better

we can guide

those patients who have a sort of

genetically driven thing

maybe those are the patients

that really shouldn't be getting the surgery

because it might

make a different part of their autonomic nervous system

maybe even worse

I wonder about the people who get

sympathectomy for other reasons

do they have hyperhydrosis

I'm gonna guess you know compensator I'm gonna guess no

the people with hyperhydrosis

some is they're coming

they have something wrong upstairs that's causing that

that hyperhydrosis and

and if you don't have that problem

I'm gonna guess that you don't get

compensatory hyperhydrosis

but I don't know

so I just want to clarify for the patients

because I know what you mean when you said that

but I don't want people to misinterpret it

when you said they have something wrong upstairs

you're not suggesting it's mental health

they're all crazy

they're just sweating because they're nervous

that's not what you mean

like there's actual

they're parts of the central autonomic network that

that are that are that

keep your core temperature where it's supposed to be

and somehow

I'm gonna guess the

not hypothalamus

but I really don't know

somehow the set point for sweating

is that a temperature that's wrong

but yeah I'm sorry to be

I don't mean to insult anybody

I just clarified

because I didn't want to tell Mrs Upstairs

so you know

it's funny too

because a lot of dysautonomia patients

you know people are sometimes dismissive of them

by telling them it's all in your head right

I'm like yeah

a neurological disease usually does involve the brain

right like so even if you have neuropathy in your toes

it's somehow affecting how your brain works

so it's not really an insult

it's probably true

but it's not

obviously it's insulting when

the way people are trying to use it sometimes

to be dismissive of things

but the patient's complain of

in my experience

is god's truth

and just because you can't figure out an explanation

that doesn't justify

dismissing the

the validity of what the person is complaining about

Hmm so here's the last question

since it's 8 o'clock and I gotta let you go home to Mrs

Goldstein at some point

oh you said you're out at a hotel

so maybe we keep you

I'm actually

I'm faculty for a course on

on autonomics for medical residents and

this is a very intensive course

and I'm missing the case discussions

now this thing is from 7 a m

until 09:30 PM

okay here's the last question then

do you ever see people using clonidine

for hyperhydrosis

and maybe explain to people what clonidine is

well clonidine is a type of drug called an ibidazolene

but it traditionally

is is viewed as a stimulator of alpha 2 receptors

alpha 2 receptors in general

act as breaks on sympathetic neurogenergic outflow

what this means is that clonidine decreases

release of norepinephrine from sympathetic nerves

I'm gonna guess that

the problem with hyperhydrosis is a sympathetic choline

urgent problem

the clonidine

I believe can have anti cholinergic sorts of

of side effects

I I don't see a strong rationale for quantity

okay well I think that you know

a lot of doctors will pretend they have the answer

and kind of make something up to make you

you know feel good that you got an answer but Dr

goldstein is honest

he'll tell us when he doesn't know

or when there's just no research

and I think really

I want this session to be sort of an impetus for us

to help organize this patient community

because even though

you know really

honestly Dysautonomia International doesn't have

we don't have anything on our website about this

but we connected with these patients

and realized they need a

they need an organization

whether it's the ETS community itself

creating their own nonprofit or something

but for now

we're happy to sort of

you know let you um

kind of hang out amongst our beefs and

and try to get you guys

organized as a patient community

because you need to do that

to get the research

and to get doctors specializing in this and

and you know hopefully

protect other people from getting this in the future

in addition to finding some more effective treatments

for all of you that already have it

so I am on the Facebook support group that another

group of folks run

and I would any of you who are science minded people

and want to kind of help design

like a patient survey

feel free to reach out

I'll probably post on that group tonight

and see if anyone else is interested

I have a lot on my plate right now

but I'm sure amongst the

several hundred people in that group

someone has a science or research background

that could maybe help lead it

so anyways thank you so much for your time

Dr Goldstein

Alright see you around

and have a good night

thanks everybody

for tuning in

see you guys bye

recording stop