Dysautonomia International Conference 2020- Day 4 Notes

First, I would like to thank Dysautonomia International for the excellent conference. I learned a lot and I hope these notes helpful to you all as well. Let me know if you have any questions.

The POTS/OI Workup- Dr. Brent Goodman

• It is important to get a full autonomic workup to distinguish if there is any autonomic neuropathy. This is what they do at the Mayo clinic with the sweat test.
• It is important to rule out systemic conditions that look like POTS such as: Sjogren’s Syndrome, Antiphospholipid Antibody Syndrome, Lupus (rare), and toxicity from things like chemotherapy (rare).
• Once POTS criteria is established, it is important to rule out mimickers such as: severe anemia, adrenal insufficiency, mastocytosis, thyroid disease, paraganglioma and pheochromocytoma.
• Sjogren’s Syndrome and Antiphospholipid Antibody Syndrome can be secondary causes of POTS.
• At least half of patients with Sjogren’s have autonomic symptoms. Sjogren’s is one of the most common autoimmune diseases that Dysautonomia patients have. Other symptoms include dry mouth, dry eyes, and itchy skin/hives. Sjogren’s is tested for using SSA and a minor salivary gland biopsy.
• Dr. Goodman recommends the following laboratory studies: CBC, B12, folate, Vitamin D, celiac testing, ANA, SSA, complement total, C3, C4, IgA, IgM, IgG, tryptase, thyroid function, cortisol, metanephrines, urine 11 beta prostaglandin F2, n-methylhistamine, leukotriene E4.
• He also would consider: lupus anticoagulant, beta 2 glycoprotein, antiphospholipid antibodies, paraneoplastic autoimmune panel, EKG, echo, motility testing if symptoms warrant, supine vs. standing catecholamines, salivary gland biopsies (if suspect Sjogren’s), and skin biopsy if suspect small fiber neuropathy.
• Dr. Goodman recommends the following tests to be repeated annually for Dysautonomia patients: CBC, thyroid function, B12, vitamin D, ANA, SSA, and possibly C4.
• POTS is a “heterogenous disorder with multiple risk factors that result in a final common pathway of recognizable symptoms and signs”.
• POTS subtypes (what we identify so far): neuropathic POTS (autonomic nerves affected which will become apparent during the sweat test), hyperadrenergic POTS (impairment of breaks on sympathetic nervous system activity which is sometimes demonstrated by an increase in blood pressure upon upright position in tilt test).
• Sometimes a patient can begin looking like a neuropathic POTS patient, but after a year present more as a hyperadrenergic POTS patient. They do not know why this is.
• 30% of POTS patients have MCAS which may be more common in hyperadrenergic POTS. Clinical clues of this include: hives, itchy skin, flushing, diarrhea, bloating, bladder symptoms (feels like UTI, but doesn’t have one), recurrent anaphylaxis, bone pain, and hair loss.
• Dr. Goodman says treating the MCAS is important to treating the POTS.
• Some patients present with CSF leaks. EDS is a risk factor of this. The headache involved is postural.

Autoimmunity in POTS- Dr. Artur Federowksi

• POTS symptoms are similar to autoimmune symptoms.
• Several studies found autoantibodies associated with POTS.
• Autoimmunity is very common among POTS patients.
• G protein coupled receptors are believed to be targeted by POTS patient’s autoantibodies. Some studies show elevated autoantibodies and some show similar levels between POTS patients and controls. So, the research is unclear.
• Most likely, it is not as simple as there being a high presence of these autoantibodies. Researchers like Dr. Federowski believe there is a nuanced way these autoantibodies act in POTS patients that is distinct from healthy controls, but this hasn’t been proven yet.
• If POTS is proven to be an autoimmune disease, it would be treated as many others are today: IVIg, drugs like rituximab, or plasmaphoresis/immunoadsorption. It is possible that there could one day be a peptide treatment that targets these autoantibodies.
• Dr. Federowski believes hyperadrenergic POTS is likely an overstimulation of adrenergic receptors and is probably affected by an autoimmune attack on adrenergic receptors.
• In response to someone’s question about “why do I have venous pooling but cold feet”, Dr. Federowski explained that there is a dysregulation of normal reflexes, so there is vasoconstriction on the arterial side and vasodilation on the venous side. It’s random, but I have wondered why this seemingly contradictory thing occurred as well.

Non-Pharmacological Treatment of POTS- Dr. Tae Chung

• The pump failure in venous return leads to the sympathetic overcompensation in POTS.
• To target the pump failure, Dr. Chung recommends aggressive volume expansion (oral hydration of 4 liters of water and 4-5 g sodium daily and physical exercise).
• To target the sympathetic overcompensation, Dr. Chung recommends things like meditation and mindfulness.
• Dr. Chung says that beginning an exercise program is usually more successful if the patient can begin with the fluid expansion methods (water and salt) first.
• Cardio exercise is key.
• Dr. Chung described the anxiety seen in POTS is more of a physical anxiety vs. emotional anxiety.

Pharmacological Treatment of POTS- Dr. Satish Raj

• Medications to increase blood volume: Florinef, octreotide (not used very often, is injected and refrigerated), DDAVP, and saline.
• Florinef is the most commonly used drug for this effect.
• Saline helps a lot acutely, but there are concerns with its use long-term. The concerns aren’t about the saline itself, but about how you get it in. The risks include infections and clots.
• DDAVP promotes free water retention in the kidney (more of a direct mechanism than Florinef, for example). The risk is that when given to patients that are water loading (like POTS patients), they can become hyponatremic (low sodium). So, patients that use this medication must be monitored.
• Studies on POTS patients using DDAVP plus drinking significant water showed a robust decrease in heart rate for a few hours. Dr. Raj doesn’t prescribe this medication a lot, but when he does he uses it as a “special event drug”.
• Dr. Raj just briefly mentioned Clonidine and Methyldopa. They work at the brain/brainstem level to lower sympathetic tone, but can be difficult to handle.
• Studies show that less is more with dosage of propranolol. You have to balance lowering the heart rate without lowering the stroke volume too much. It’s about blunting the heart rate, not fixing it.
• Mestinon decreases heart rate in studies, but propranolol does it better. So, he usually tries propranolol first.
• Ivabradine can be a good option for POTS patients. 38/49 in a study experienced improvement. More studies will be coming soon including a trial of ivabradine vs. placebo vs. propranolol. That will be an interesting comparison.
• There is not a lot of data on IVIg yet. In a 2018 study, IVIg demonstrated a decrease in autonomic symptoms and improved functionality for patients. Dr. Vernino is working on more studies along with other researchers.
• Dr. Raj cautions against the use of norepinephrine transport blockers like: Cymbalta, Effexor, Concerta, Adderall, Strattera, and Pristiq. They increase sympathetic tone and can be bad for hyperadrenergic POTS patients. In a study, atomoxetine (Strattera) increased heart rate and worsened symptoms.
• SSRI’s like Zoloft and Lexapro are usually safe for POTS patients. Studies demonstrated that there were no acute heart rate effects with these drugs.

Research Updates- Long-Term Outcomes in POTS Patients and Vagus Nerve Stimulation- Dr. Raffaelo Furlan and Dr. Franca Dipaola

• This study assessed the symptom burden over time in POTS patients.
• There was “progressive global clinical improvement” in POTS patients at the two year mark.
• It is important to note that the symptoms burden was still significant although it was improved.
• This study was small. Long-term studies typically struggle to retain their subjects.
• The vagus nerve stimulation study was done using a transcutaneous device (non-invasive- attached to the external ear). POTS is associated with low vagal tone and a hyperadrenergic state, so the hypothesis is that vagus nerve stimulation (VNS) may cause improvement. VNS works by reducing sympathetic activity and causes a shift in cardiac autonomic function toward parasympathetic predominance.
• The benefits to a transcutaneous device is that it is noninvasive, it bears minimal side effects (local irritation), it is easy to use, and it is inexpensive.
• The study observed 11 hyperadrenergic POTS patients. They received 4 hours of VNS for 2 weeks. The effect on the heart rate during tilt had minimal change. However, measures of heart rate variability (which is a good way to observe vagal tone) and plasma norepinephrine improved significantly. Patients also reported an improvement in the sensation of rapid heartbeat. The conclusion of the study is that VNS may be considered an adjunct therapy in POTS. Like most preliminary studies, this has a small sample size. Larger studies will be needed for this to gain more traction. And, to do larger studies, this kind of research needs more money.

• They stimulate the vagus nerve on the right side because the right vagus nerve branch acts the most on the sinus node to decrease heart rate.
• Dr. Furlan feels EDS patients respond especially well to VNS.
• GI motility improves with increase vagal activity.
• Dr. Furlan said you can buy or rent these devices in Europe. It seems it is more tricky in the US. There are a few FDA approved devices for things like IBS or migraines. However, we can’t access these yet for Dysautonomia.

Research Update- Zack Orban

• He is observing human leukocyte antigen (HLA) genes in POTS patients. The HLA system distinguishes self from non-self and this system is linked with autoimmunity.
• HLA associations alone do not prove immune dysfunction, but this may contribute to the overall understanding of POTS.
• There seem to be a few risk alleles for POTS and some of these overlap with conditions like Sjogren’s.

Advocacy Update- Lauren Stiles JD

• Wow, Lauren and Dysautonomia International work their butts off. They bring data to congress to convince them to increase funding for research in the field of Dysautonomia.
• They also petition for the approval or retention of important Dysautonomia medications.
• The group also works on getting Dysautonomia properly recognized and described by the NIH and other organizations (which also helps with funding).
• DI got a specific ICD code for POTS that will soon be implemented. This will improve the ability to do epidemiological research.
• I seriously cannot express how much good work DI does for the Dysautonomia community.

Q&A- Future of Research with Dr. Steven Vernino, Dr. Laura Pace, and Dr. Mitch Miglis

• Some of the top future big picture things this group would like to see worked on is: phenotyping POTS, discovering better biomarkers, understanding autoimmunity, reframing autonomic nervous system disorder genetics to understand the underlying pathophysiology, educating future and current doctors, and physicians working in consortium on Dysautonomia.
• They would like to see whole genome sequencing in multiple affected family members with Dysautonomia to help identify responsible genes.
• There are educational deficits in medical schools on autonomic disorders. Most do not learn about it at all. Some have one lecture on the topic. Clearly, that is not enough as it takes an average of 5 years for a patient to be diagnosed with Dysautonomia.

Did anyone else attend the conference? What did you learn?

Disclaimer: I am not a medical professional. Statements on this site are not meant to be taken as medical advice. These statements reflect my personal experiences having mild-ish post-viral POTS and ME. Due to the wide spectrum of these diseases, comorbidities, and everyone being different, your experiences may be very different than mine.

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