+100%-

Surprises

Off all the cities I drove through on the Vegas to Florida to D.C. to Nashville to Birmingham to Tuscaloosa to St Louis, Kansas City and then on to Denver, Nashville was the biggest surprise.  It’s not a big city, but cranes are everywhere lifting new, often striking skyscrapers into the sky.  This city is booming!

Nashville is booming!

Nashville is booming!

The energized city wasn’t the reason for the location of the conference, though. Since 1873, Nashville has been home to Vanderbilt University – which contains perhaps the largest autonomic nervous system research center in the U.S.. Vanderbilt researchers were in abundance at the conference.

I have to give a shoutout to the Drury hotel chain.  We were planning to do more camping, but after Skye had a horrid reaction to insect bites, except for a stay at my brother’s in DC, we hotelled it from Miami to Nashville, down to Alabama, up to St Louis and then over to Colorado.

After a horrid night at a cheap chain motel (mold ?), we largely went Drury for the rest of the trip and never regretted it. They’re a bit pricey but are clean and comfortable, accept pets, offer a free dinner buffet at night (and there’s something different about their sheets). If you’re traveling in the Midwest and South (or in Denver and Phoenix), they’re a good bet.

The Conference

The biggest surprise for this frequent ME/CFS conference attender was the crowd. The large room was packed to the gills with patients, doctors and researchers. Not only was attendance substantially larger than at the IACFS/ME conferences (how did that happen?) but younger female, probably postural orthostatic intolerance (POTS) patients, dominated. My guess is that the average age of the conference was a good 15 to 20 years younger than at the ME/CFS conferences I’ve attended. Many people come down with POTS during puberty.

Dr. Blair Grubb

The first speaker, Blair Grubb, MD, was perfect to kick off the conference. A dynamic and at time hilarious speaker with years of experience under his belt – Grubb participated in the first tilt-table studies ever – Grubb was full of hoary stories about the bad old days.

Grubb is professor of Medicine and Pediatrics at the University of Toledo. He authored the interesting “Quest for an Underlying Cause of POTS“, found on Dysautonomia International’s website (which features a hilarious slide) – and showed that in addition to about ten other conditions (diabetes, joint hypermobility syndrome, chemotherapy, amyloidosis, sarcoidosis, Lyme disease, Parkinson’s, MCAS), mitochondrial problems, traumatic brain injury  and multiple sclerosis can all cause or be associated with POTS.

Grubb’s talk was full of interesting insights. Who knew that it takes about a third of the blood in the body to digest a full meal or that digesting a meal is “the most energy intensive thing anyone can do”. For me that was a reminder – not that one should have been needed after toddling off to bed so many times after a large meal –  to eat small meals.

It was interesting to learn that humans are the only truly two-legged animals on the earth.  Standing on two legs allows us to run longer than any other animal – so much longer that some hunting cultures actually made a practice of running animals to death – but it comes at a cost.  In order to run, you need to relax the arteries to get more blood to your leg muscles while avoiding dropping the blood from your upper body into your legs.

That’s accomplished in a variety of ways – by increasing the heart rate and squeezing the blood vessels in the lower body to keep blood from pooling in the lower body. Plus, humans have developed a unique feature – a blood muscle pump. Most people use the muscle pump only during exercise, but people with autonomic problems also use it while standing.

Grubb noted how extraordinarily interconnected the ANS system is: you can’t change anything, he said, without changing everything,

Small Nerve Fibers

The destruction of the small nerve fibers in the skin (small fiber neuropathy or SFN) is a big deal in POTS and fibromyalgia research right now (and with Drs. Kaufman and Systrom reporting similar findings in their ME/CFS cohorts – ME/CFS appears to be next). SFN can also be caused by a wide variety of factors, but the good news is that if you can stop the nerve damaging process, those nerves can quickly regrow. The bad news is that it’s not easy to stop that process.

small fiber neuropathy POTSThese small nerve fibers do a lot – they convey sensory sensations, regulate autonomic nervous system functions, and help us sweat. Damage to those nerves can cause a long list of symptoms and problems, including burning sensations, pain, itching, and temperature dysregulation, to restless leg syndrome, heat intolerance and bladder problems.

Some of the really unusual symptoms found in ME/CFS/FM – those weird, hard-to-describe symptoms – could conceivably be caused by small nerve problems. (One person felt like he was sweating constantly, but was actually very poor at sweating. Gabapentin removed that sensation completely.)

If the small nerve fibers in the rest of the body (gut, blood vessels and more) are damaged – which Grubb and it seems everybody believes is happening in POTS, FM and ME/CFS – then watch out.  SFN issues could conceivably account for almost every symptom and problem – from fatigue to problems standing to poor energy production – found in these diseases.

Testing

Skin biopsies, which are easily and cheaply done, are the best test (stay away from Qsart), but even skin biopsies can be problematic at times. While nerve fiber density in Caucasians is well known, people of other races can have different nerve densities – and throw off the test.

Skin biopsies are good, but they’re not the be-all and end-all test. Grubb pointed out a 32 year old “mystery man” who, after a year of tests and treatments, still suffers from fatigue, muscle aches, palpitations, discoloration of his feet, etc. His nerve conduction, reflexes and skin biopsy are all normal, but he has reduced sweating in the lower part of his body and his feet are exquisitely sensitive. Something is going on but they don’t know what .. .there is still much to learn.

Causes

The cause of the small nerve damage in the skin is not clear but some clues are emerging. As in POTS, many diseases or conditions have been associated with SFN.

Diabetes – Grubb noted that people with pre-diabetes have nerve damage BEFORE they get diabetes, and that in diabetes, at least, exercise actually helped nerve fibers regrow.

Autoimmunity is the most likely cause of the SFN in Sjogren’s Syndrome (SS) and sarcoidosis, but treating SS and sarcoidosis with drugs does not, oddly enough, improve the nerve damage. That suggests that something other than the autoimmune processes is causing the nerve damage in these diseases. (Sjogren’s Syndrome is going to pop up again and again in the conference.)

Amyloidosis – the accumulation of amyloid guck in the blood can cause small nerve damage. In fact, lots of things, including hereditary neuropathies, too much or too little Vitamin B, alcohol, drugs (metronidazole, statins, nitrofurantoin, bortezimib) can smack these small nerves.

Disentangling what’s harming the small nerves in POTS, FM and ME/CFS is going to be fascinating. Interestingly, the small nerve fiber damage in fibromyalgia appears to be different from other diseases. Besides disappearing, the small nerves in FM that remain appear to be getting smaller. Thus far several studies, including immune studies, have failed to find the cause of the SFN damage in FM.

One animal study, though, suggested that central sensitization may be causing the small nerves to perish, possibly as a protective effect. Once pain levels get too high, the brain may somehow cull the pain-transmitting fibers in the skin as a kind of protective mechanism,

Treatments

The list of possible treatments is a long but not particularly encouraging one. Grubb always seemed, at least to me, more focused on side effects than positive effects. Still, it appears that small fiber neuropathy is not something the medical profession is particularly good at treating or has devoted that much effort to fixing.  Repurposed – not new drugs – appear to be the norm. I would be surprised if any drugs had been specifically developed to treat small nerve fiber problems.

Exercise (probably recumbent) can actually help regrow the nerves in some SFN patients. Intravenous immunoglobulin (IVIG) can be very helpful but is horribly expensive, hard to get covered by insurance, can cause headaches (already a problem in POTS) and comes from a lot of donors with all the worries (infections) that can entail. (Lauren Stiles announced that Dysautonomia International is sponsoring the first IVIG POTS trial.)

IVIG – Intravenous Gamma Globulin Therapy for Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia

Norepinephrine-based antidepressants can help, but can mess with blood pressure – not a good thing in a disease with orthostatic intolerance. SNRI’s increase blood pressure – which could help – but make some people worse. Anti-epileptics such as gapabentin and neurontin can cause weight gain and fatigue. Bear in mind that some of these obviously do help, but Grubb wasn’t exactly providing a lot of good news.

More POTS Than We Know (Or The Tests Pick Up)

The symptoms in POTS are very similar to those in chronic fatigue syndrome (ME/CFS). They manifest themselves more upon standing and include fatigue, exercise intolerance, cognitive problems, heart palpitations, chest pain or discomfort, lightheadedness, blurred vision, shortness of breath, headache, nausea, fatigue, and tremulousness. One different symptom is commonly present – the legs of about 50% of POTS patients turn red-blue (acrocyanosis) and feel cold to the touch upon standing.

POTS often starts with an acute stress such as an infection, during pregnancy, after surgery, etc., and like ME/CFS and FM, mostly affects women.  People tend to get POTS earlier in life than ME/CFS.

Grubb, being the smart researcher that he is, believes the criteria for POTS are too rigid. Not meeting the criteria doesn’t mean you don’t have “POTS” – it just means the criteria need work. He has patients with all the symptoms of POTS who don’t meet the criteria.

Indeed the test results are quite mutable depending on how the test is done.  As Dr. Peter Rowe has pointed out, a tilt table test taken earlier in the day can have quite different results from one taken later in the day. A longer tilt table test pushes many more people into POTS. Plus, a small study performed by Dr. Baraniuk found that a bout of exercise temporarily induced POTS in almost half his ME/CFS patients.  There’s still a lot to learn about just what POTS is…

The Big News: Larger Autoimmunity Study Succeeds

The big news in POTS has been the discovery of autoantibodies that are whacking a receptor (adrenergic-1 receptor) in the legs that causes the veins in our legs to narrow or vasconstrict as we stand. The knock on the past autoantibody POTS studies has been their size, but Grubb reported that a much larger antibody study (75 patients) found that no less that 92% of POTS patients had autoantibodies which were attacking that receptor, and other autoantibodies were elevated as well. There will be more on this study and its implications in the second blog.

autoimmunity POT

POTS is looking more and more like an autoimmune disorder.

Grubb said he’d suspected autoimmunity in POTS all along but the testing used to be too expensive.  It’s still expensive, but a lot less than it used to be.

The autoimmune finding looks like it’s going to redefine at least a very large subset of POTS patients and possibly the disease itself. Not only that, but it’s affecting other fields as well. Taking a clue from the POTS findings,  Dr. Scheibenbogen found evidence of autoimmunity in about 40% of ME/CFS patients.  Reports from the ME/CFS Montreal Conference suggest that a follow-up study from another lab is getting similar results.

POTS Treatment

The big question is treatment. The next generation of drugs will probably be biologics that affect the autoimmune processes in POTS. These definitely work better and many more are expected to come on the market over time. Their downside is expense and the potential for significant side effects.

The treatment picture for POTS is mixed indeed. Treatment effectiveness has been spotty – no surprise in such a heterogeneous field. Several reviews mention the long trial-and-error period often needed to find a drug that works – if that happens at all.  Many of the treatments produce side effects which render them intolerable as well.

Standard Treatments for Neurogenic POTS

  • Hydration, salt loading, reconditioning
  • Blood volume expanders – (fludrocortisone, DVAP)
  • Vasoconstriction – midodrine, droxidopa
  • Heart rate – beta blockers, ivrabadine
  • Nerve activity enhancement – pyridostigmine bromide.

Hyperadrenergic POTS

  • Alpha/beta blockers
  • Clonidine
  • Methyldopa
  • Biofeedback – Grubb expects more use of this therapy.

No drug has yet been FDA approved for POTS, but an old drug is helping and a new drug to the U.S. is making quite a splash.

The Old/New Hope – Pyridostigmine Bromide (Mestinon)

Pyridostigmine bromide (Mestinon) has been around for a long time but it’s often not mentioned as a drug for POTS. Several studies, though, have found that it reduced heart rate. One large study (203 POTS patients) found that about 60% experienced significant improvements in fatigue and heart rates.  Mestinon has been a favorite drug of Dr. Systrom’s in both POTS and ME/CFS for quite some time. If I remember correctly, a study assessing its effectiveness either is or will be underway. Check out how Mestinon dramatically helped one long term ME/CFS patient.

A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise

The New, New Hope – Ivabradine

While Grubb hasn’t been particularly happy about the treatments available, he’s very high on Ivabradine (Corlanor in the U.S., Procoralan (worldwide), Coralan (in Hong Kong, Singapore, Australia and some other countries), Corlentor (in Armenia, Spain, Italy and Romania), Lancora (in Canada) and Coraxan (in Russia and Serbia).

Grubb said Ivabradine has a 75% success rate: that’s unheard of in this complex condition.

Ivabradine appears to be unique in its ability to affect heart rates without affecting other aspects of cardiovascular functioning such as blood pressure. It’s been available as a heart failure medication in Europe for years. Amgen apparently bought up rights to it in the U.S., got it approved for heart failure in 2015, and then jacked up the price significantly to $4,500 for a year’s supply.  Grubb said many of his patients are getting it from Canada.

It’s a drug that’s begging for a good randomized trial.  Thus far two prospective open-label trials, three retrospective cohort studies, and eight case reports have examined its efficacy in POTS.  All have been successful but none are large or rigorous enough for prime time.

A June 2018 review concluded that Ivabradine lowered HR and provided symptomatic relief of POTS without affecting blood pressure.  A 2018 retrospective analysis found Ivabradine (0.1 mg/kg twice daily) improved symptoms in almost 70% of adolescents.

A 2015 study on just eight patients found Ivabradine (7.5 mg) significantly slowed their heart rates both at rest and during tilt without producing significant adverse effects. That study noted that beta-blockers (propanolol, atenolol) can slow the heart rate in POTS as well, but often at the cost of increased fatigue, sleep disorders, and impotence. Those side-effects are apparently not a problem with Ivabradine.

A 2010 case series found the drug reduced symptoms in 55% and fatigue in 70% of POTS patients. The study found a low dose formulation (2.5 mg od) the most effective for most patients. The study suggested that Ivabradine may be more effective in some people when taken in conjunction with midodrine or fludrocortisone.

A small POTS Ivabradine trial (n=20) that’s underway at the University of San Diego should be finishing up about now.

The Struggles of Chronic Illness

Do not be daunted by the enormity of the world’s grief. Love now, Do justly now. Love, mercy, now. You are not obligated to complete the work, but neither are you free to abandon it. The Talmud

Grubb ended on a kind of transformative note. He’s had his own struggles with serious illness – his wife’s death and his struggle with cancer.  He was irritable, angry and mean during these struggles – so altered emotionally that he saw a counsellor (you would never think this guy would see a counsellor… :)) and the counsellor really helped.

It can take a long time to reframe your life if you have a chronic illness – to accept that your life for the foreseeable future is going to be very different. Grubb emphasized that, no matter what our condition is, every one of us makes a difference. It was a lovely and unexpected ending to an excellent talk.

The Mayo Perspective – Paola Sandroni

Then came the drill sergeant – Dr. Paola Sandroni from the Mayo Clinic. She was in the big room and I came late to her talk. Looking rather severe and talking in a clipped manner, she was the picture – at least to me – of a Mayo Clinic researcher.

She seemed to be on top of her game when it came to POTS, but when it came to ME/CFS she was wanting – and in the worst way.

Quite a few questions dealt with the Mayo’s “POTS Clinic” which features, she admitted, a “tough love” approach. The goal of the clinic is to increase functionality and reduce isolation. It was originally intended for use in pain patients but will apparently take on just about any condition that is severe enough to disable a patient. It’s now being used in POTS, ME/CFS, fibromyalgia and other conditions.

Thankfully, she didn’t call the clinic a cure but she did, without saying what the clinic considers a “success”, state that the clinic’s success rate is about 70% in POTS and about 50% in chronic pain.

The 8 hours a day, 3 week program can work in the right person. One of the most astounding treatment successes I’ve ever seen involved a young woman with a devastating case of chronic regional pain syndrome (CRPS) in her leg. She was unable to walk or even to put pressure on her deformed foot when she started the program. She left the program much improved and eventually resumed a normal life.

One young POTS patient, whose story was chronicled on Health Rising, used the program to help him fully recover as well. Prior to entering the clinic, he was greatly aided by the iron infusions he took which allowed him to finally exercise, but the program helped him return to full functioning.

Sandroni simply touted the biopsychosocial party line when it came to ME/CFS. People with ME/CFS have PEM, stop exercising, become deconditioned and exercise intolerant. Orthostatic intolerance (OI) is the next logical step.

Among many others, Peter Rowe would have a fit at this. At the Montreal Conference, Rowe agreed that deconditioning can, of course, lead to OI, but cited a soon-to-be-published study showing that the OI is NOT related to deconditioning in ME/CFS.  People who are deconditioned with ME/CFS have OI and so do people who are not deconditioned. He hoped that study would put the deconditioning saga in ME/CFS to rest. Let’s hope that Sandroni reads it.

Sandroni was very focused on stress and the stress response in these diseases. She believes that an overly active stress response increases the excitability of neurons which results in central sensitization; i.e. lots of pain, stimuli problems and fatigue.

I have no doubt that central sensitization is part of ME/CFS and FM. Nor do I mind the idea of watching out for negative thoughts that increase one’s pain and fatigue – it’s only natural that those would occur in a chronic illness. But to boil an illness down to those and other basic problems (poor sleep hygiene), as it seemed to me she was doing, was shocking.

It was disappointing to see Mayo show up like this again. I just heard of a patient who, after getting a lot of testing done at Mayo, was told they had chronic fatigue syndrome (ME/CFS) but there was nothing they could do for them.  That’s obviously not a great result, but it’s not such a bad result either. The Mayo doc apparently did not pooh-pooh ME/CFS, and he apparently acknowledged that it was real and serious – he just didn’t know what to do with it. That’s a step forward but we obviously have a long way to go.

A Kaufman Interlude

Dr. David Kaufman was one of two ME/CFS practitioners (Theresa McDowell was the second) that I saw at the conference. (Jaime Selzer and Beth Mazur of ME Action, and Fred Friedberg of the IACFS/ME also attended.)

During a break, Dr. Kaufman said that antibody results and the multisystem effects in ME/CFS were causing him to lean towards an autoimmune cause.  He was the first to approach Dr. Kem after Kem’s autoantibody talk on POTS. Kaufman said he was having good results with Rituximab in patients targeted using Dr. Scheibenbogen’s CellTrend antibody screen (which is different from the Mayo screen some doctors are using).

His major new interest of the last couple of years, though, is mast cell activation syndrome (MCAS) – which, in his experience, is common in ME/CFS. Dr. Kaufman is also finding a very high incidence of small fiber neuropathy (@80%) in his ME/CFS patients. (He tests all of his ME/CFS patients for SFN.) Recently Dr. Systrom reported that 50% or more of his ME/CFS patients are testing positive for it as well. It’s taken awhile but small fiber neuropathy is coming to ME/CFS…

Kaufman’s ascent into ME/CFS was fortuitous – he was an immunologically-based HIV doc who left New York to start a practice, and just happened upon the Open Medicine Institute (which he has since left) where he learned about ME/CFS.  He loves his practice and knows of several ex-HIV docs who enjoy the complexity of treating ME/CFS patients.

Kaufman has been practicing a long time but looks to be in great shape and said he loves his work and has no intention of retiring. Here he was – several thousand miles away from his Mountain View practice – learning more about dysautonomia and ME/CFS.

Dr. Maitland from Icahn School of Medicine on MCAS and Dysautonomia

I found the talk much like the field – complex and a bit confusing. This is a field that is still finding itself but it’s clearly full of promise.  Mass cell activation syndrome (MCAS) cropped up frequently in the conference presentations. It’s becoming a big deal in dysautonomia/POTS, etc. The big room was packed and afterwards Dr. Maitland was swarmed by patients asking for more.

Maitland was a ball of fire. She has sterling credentials – an MD AND PhD – and is Board Certified in allergy and immunology. An immunologist in a field that knows almost nothing about MCAS, it was clear that she was rather disgusted with the hidebound nature of the field.  She said the average time to get diagnosed with immune- mediated disorder was 12 years. Of the 77 training programs on allergy and immunology in the U.S., only a handful inform our future immunologists on MCAS. Clearly at ease, she punctuated her talk with numerous humorous asides.

Mast cells produce allergic responses, but MCAS is a very different kind of immune reaction. Despite the fact that mast cells were the first immune cells discovered, MCAS – mast cell activation which does not involve allergy – is only now just getting traction in the medical field.  Mast cells are now in the process of being rediscovered. That seems very odd given how powerful and versatile these cells are.

One of the immune system’s first responders, mast cells are filled with nasty pro-inflammatory granules they’re just waiting to unload when a virus, parasite, toxin, allergen, etc. comes along. Carrying an enormous quiver of immune factors (tryptase, histamine, serotonin, heparin, eicosanoids, lysosomal enzymes, prostaglandins, cytokines, TNF-a, chemokines, etc.), they are armed for battle indeed. A complex process determines which factors a mast cell will release.  Occurring across the body, in the gut and the brain they have the potential to produce many different symptoms.

Symptoms

A huge question is what role MCAS plays in POTS, ME/CFS and FM. Does it cause those diseases or is it simply associated with them? White’s 2015 overview “A Tale of Two Syndromes – POTS and MCAS”, published on Dysautonomia International’s website, indicates we still have much to learn about all these disorders. He calls the POTS/MCAS connection “an extremely complicated intersection of two poorly understood illnesses”.

The symptom presentations in MCAS, POTS and ME/CFS appear to be similar but also somewhat different. In his 2013 overview, Afrin describes a truly enormous number of possible symptoms, but White highlighted specific symptoms (recurrent abdominal pain, diarrhea, flushing, itching, nasal congestion, coughing, chest tightness, wheezing, lightheadness), some of which commonly occur in ME/CFS and some of which do not.

A 2010 review reported the following symptoms can be present: anaphylaxis, fainting, fatigue, flushing, rashes, itching, hives, chest pain, rapid heart rate, wheezing,  pain, nausea, vomiting, cramping, bloating, diarrhea, GERD, cognitive problems, dizziness, migraine, tingling sensations, and peripheral neuropathy.

Some of the symptoms commonly found in MCAS (flushing, hives, asthma, anaphylaxis and diarrhea) are not particularly common in ME/CFS or POTS. Exercise intolerance – a key feature of ME/CFS – is not mentioned.

Odd sensitivities are an intriguing part of MCAS. If you’re experiencing a sensitivity to something which is obviously not allergy-based; i.e. does not respond to antihistamines, Dr. Maitland believes MCAS might be the cause.

Hypersensitivity Disease

Like so many other hypotheses concerning these diseases, Maitland believes a hypersensitivity plays a role. Instead of a microglial cell hypersensitivity and/or a central nervous hypersensitivity, she believes that trigger-happy mast cells that are over-reacting to all sorts of stimuli are the main problem in MCAS.

Testing

Testing, unfortunately, is suboptimal at best. Maitland said that tryptase is the best current marker but one tryptase test is not enough. In fact, Maitland said, she doesn’t know what a “normal” tryptase test looks like, and three tests are needed, including a baseline test done during symptom exacerbation. (I understand why getting a marker during symptom exacerbation can help, but what I don’t understand is why a key marker isn’t elevated even when I’m in my “normal shitty baseline” (NSB – thank you Trina Berne). My NSB is pretty darn bad…)

A POTS review suggested that a methylhistamine test done within four hours of a flushing episode can diagnose MCAS/MCAD.  White recommended measuring histamine, prostaglandins and leukotrienes in a 24 hour urine sample.

mast cells and chronic fatigue syndrome and fibromyalgia

Dr. Maitland believes the mast cells in MCAS are on a hair trigger.

A 2017 retrospective study of 117 POTS patients found evidence of increased prostaglandins in 50%, increased methyl-histamine in 16%, but no evidence at all of increased tryptase. It also found that symptoms didn’t differ between POTS patients with MCAD and those without it. The authors believed that 20% of their cohort probably had MCAS.

Interestingly, if you’ve had a colonoscopy done, you can have it restained to see if mast cells are present. Mailand mentioned one woman who’d never recovered from food poisoning whose colon turned out to be packed with mast cells….

Treatment

Treatment depends on “what’s tickling your mast cells”.  That means testing for various triggers.  Besides the limited mast cell tests available, Maitland does limited allergy testing, rheumatology panel, EDS screen, neuropathy screens, celiac panel, colonoscopy, pathogen screens, and testing for a primary immune deficiency disorder. She mentioned using prophylactic antibiotics and gamma globulin, but oddly enough I don’t remember hearing about quercetin.

A treatment slide on MCAS and Dysautonomia mentioned medications that are rarely used in ME/CFS (fexofenadine, diphenhydramine, cromolyn, pepcid/Zantac, aspirin, omalizumab).

You don’t need a pollen allergy to have an IgE (histamine based) reaction; you can have a histamine reaction to foods, drugs or other allergens. If antihistamines work for you, they may apply to those factors.  Because of the many sensitivities Maitland comes across, about ten percent of her patients leave her office with script for compounded meds due to problems with the fillers in prescriptions.

Interestingly, Maitland mentioned low dose doxepin elixir (Sinequan), an old favorite of Dr. Cheney’s. Generally used as a tricyclic antidepressant, Cheney instead used low doses of doxepin for its anti-histamine and immunomodulator properties. Cheney called the histamine receptors the “grand maestro” of the central nervous system and believed that doxepin could calm the over-active nervous systems in ME/CFS/FM and allow healing to take place.

Because Maitland is dealing with a hypersensitive, trigger-happy mast cell system, stress reduction is on the list as well.

MCAS and POTS

There was little on MCAS and POTS in Maitland’s presentation, but MCAS is clearly a subject of great interest to the field and numerous presenters mentioned it.

In his recent POTS review, Raj, a speaker at the conference, stated that a subgroup of POTS patients with episodic flushing have a mast cell activation disorder. Biaggioni also recommended testing for MCAS in POTS if flushing is present and suggested that hyperadrenergic POTS is more common in MCAS-POTS patients.

The flushing can be produced by a wide variety of triggers (exercise, standing, sexual activity, eating, menstrual activity) and can be accompanied by many other symptoms (lightheadedness, dizziness, shortness of breath, excessive diuresis, nausea, diarrhea, vomiting, and headache).

Several presenters simply recommended that practitioners not rely on testing for MCAS and treat for it if they believe it’s present and see what happens.

It’ll be interesting to see over the next five to ten years how all these disorders – MCAS, ME/CFS, EDS, IBS, POTS, FM – come together. Will they merge or split apart?

Non-invasive Vagus Nerve Stimulation Helps POTS (Somewhat)

We know that implanted vagus nerve stimulators can do wonders for people with epilepsy, and can help in depression and heart failure and even in fibromyalgia. Benjamin Natelson’s small fibromyalgia study produced some scorchingly good results, even in some really severely ill patients. Natelson, who’s been in this business for decades, said he’d never seen anything like it.

“Reborn” – Reversing Fibromyalgia with Vagus Nerve Stimulation

Stimulating the vagus nerve – the largest nerve in our body – suppresses overactive sympathetic nervous system activity and boosts parasympathetic nervous system activity. This results in enhanced anti-inflammatory activity.

Dietrich got interested in vagus nerve stimulation (VNS) after a young girl and a woman with epilepsy found that turning their stimulator on allowed them to endure a tilt table test without getting ill.   Given the reduced vagus nerve activity found in POTS (low heart rate variability (HRV), high heart rates (HR’s)), it made perfect sense to try out non-invasive VNS.

Dietrich’s goal was to increase POTS patients’ HRV (low HRV = decreased vagus nerve activity) and to reduce their heart rate. He took 20 patients, put them on the tilt table, and then turned on the stimulator!

Unfortunately, several of his FM patients had high HRV’s (another subset?) instead of the low HRV’s he expected.

A non-invasive vagus nerve POTS trial produced mixed results.

He wasn’t able to normalize his POTS patients’ tilt table readings, but he was able to increase the time they tolerated the tilt table test by five minutes and increase the HRV (in those with low HRV). Some symptoms including brain fog and tremulousness improved, and lightheadedness improved significantly, but HR was not reduced and in the end the results were mixed.

This certainly isn’t the end of VNS studies in these diseases. Natelson is now, or should soon be, beginning a non-invasive vagus nerve stimulator study in fibromyalgia.

We’re a long way from knowing how to tweak the peripheral nervous system effectively. Thankfully, Francis Collins realized how many potential therapies we may be missing out on and began NIH’s 1/4 billion dollar SPARC initiative. This high-risk, high-gain initiative is an attempt to learn how to manipulate our peripheral nerves (those in our body, as opposed to our central nervous system) to reduce pain, relieve inflammation, heal heart problems, fix gut disorders and more.

Making Drugs Obsolete: The Electroceutical Revolution – A Fibromyalgia and ME/CFS Perspective

The first day of the conference was over. The only thing missing was a good rest area with couches or beds one could lie down on. (Montreal lacked a good rest room as well.) One day was enough – more than enough, actually, for my partner who, as she did in Montreal, had to skip the next day. I went back to the hotel and rested up.

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Health Rising's BIG (little) End of the Year Donation Drive

health rising donationsHealth Rising brings you the latest research and treatment findings on chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). Funded almost entirely by donors, Health Rising makes a big impact on a small budget.  Its 1,600 blogs, pages and resources were visited by over 600,000 people last year. Please keep the information flowing with your recurring (as low as $5/month) or one-time donation. Find out more here.
Health Rising's BIG (Little) Fundraising Drive is On!Find out more here

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