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    • VACCINE RECOMMENDATION:  DINET encourages all its members to receive the vaccinations and boosters for COVID-19, unless specifically advised against it by your medical provider.  To better understand the virus, the vaccine and the effects on people living with dysautonomia, please watch Dr. Svetlana Blitshteyn's video "COVID-19 and Dysautonomia"

Dysautonomia Research & Studies - December 2017


edriscoll

Research and Studies

Ongoing Study Information

Recruiting: Two new studies open for patients with MSA.  The NYU Dysautonomia Center has 2 new clinical trials to test new drugs that are being developed for the treatment of OH in patients with MSA.  Both compounds work by enhancing the body's levels of norepinephrine.  Both studies are also being carried out at the Autonomic Dysfunction Center at Vanderbilt University.  NYU Dysautonomia Center and Vanderbilt are long time collaborative partners in rare autonomic disorders.  Contact information and more information about the studies can be found in this article. https://dysautonomiacenter.com/2017/04/10/two-new-studies-open-for-patients-with-msa/

Recruiting:  Vagal Stimulation in POTS- The Autonomic Inflammatory Reflex (Pilot 3) The purpose of this study is to investigate how the electrical stimulation of a nerve in the skin of your ear lobe (transcutaneous vagal nerve stimulation) affects the way your autonomic nervous system controls your heart rhythm.   Participants must be females between the ages of 18 - 45 with POTS.  To learn more about this study or to participate, visit https://www.rarediseasesnetwork.org/cms/autonomic/6111

Recruiting:   Clinical Autonomic Disorders:  A Training Protocol is a study to learn more about dysautonomias for the specific purpose of developing training protocols to help new physicians understand the illness and to better diagnose patients.  To participate in the study or read more about it, visit our studies page or go directly to the clinical trials site.

Recruiting:  The Big POTS Survey  is still going on.  Vanderbilt University and Dysautonomia International sponsored survey.  The study's lead investigator is Dr. Satish Raj, MD MSCI, Adjunct Professor of Medicine at Vanderbilt University's Autonomic Dysfunction Center.  Dr. Raj says that the information collected as part of this survey "will help us learn more about the possible underlying causes and risk factors for developing POTS, treatments, and the economic, educational and social impact of POTS on patients and their families."  Dr Raj serves on the Medical Advisory Board for DINET and Dysautonomia International.  Go directly to the survey

News and Information

Deadly risks of taking kratom  This seemingly innocent natural product can be very harmful to your health.

Research_DNA.jpg.161f8d9dd5f6f4ef82d6b183eab3899e.jpgIMPORTANT INFORMATION:  POTS & Ehlers-Danlos Syndrome "Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype?" by Miglis MG, Schultz B, and Muppidi S, from the Departments of Neurology and Psychiatry at Stanford University Medical Center.

"It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS."  https://www.ncbi.nlm.nih.gov/pubmed/28986003

POTS Related Information

Estimation of Sleep Disorders using Wrist Actigraphy in Patients with POTS  https://ww2.mc.vanderbilt.edu/adc/43572   

  • Investigators conducted a questionnaire study to assess sleep disturbances and quality of life in patients with POTS and healthy subjects.  Patients with POTS and healthy volunteers were given several surveys to assess their sleep (Epworth Sleepiness Index & Medical Outcomes Study [MOS] Sleep Survey), level of fatigue (a visual analogue scale) and health related quality of life (RAND36 and EQ5D).

  • Patients with POTS reported more sleep problems, daytime sleepiness and fatigue, and worse health related quality of life than the healthy volunteers.

  • Patients with POTS had a markedly diminished quality of life in both physical health and mental/social health domains compared to the healthy volunteers.  The scores were comparable to previously published scores for patients with kidney failure requiring hemodialysis.  The Vanderbilt data were similar to a prior publication from the Mayo Clinic {PMID: 12059122} that also found diminished quality of life in patients with POTS.

  • There was a strong correlation between sleep problems and physical and mental health related quality of life. In fact, 60% of the variability in score for each of the physical health domain and the mental health domains could be accounted for by the Sleep Problems Index (a summary score from the MOS Sleep Survey).

Orthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter (NET) Deficiency  https://www.ncbi.nlm.nih.gov/pubmed/10684912

Lack of function of the norepinephrine-transporter can cause POTS*

Some years ago, a patient with POTS was found to be heterozygous (had one copy of the mutant allele) for a mutation in the norepinephrine transporter gene that caused a single amino acid (protein building block) change in the protein (A457P). The mutation was “dominant negative” and resulted in an almost complete “loss of function” of the norepinephrine transporter compared to the normal gene. Since the transporter is involved in clearance of norepinephrine from the sympathetic nerve synapse (area between nerve terminals), this mutation likely led to an increase in norepinephrine in the synapse, and in excessive sympathetic activation. This likely resulted in the excessive heart rate seen in this patient, which was worse on standing (when there would be more sympathetic nervous system activation). Other members of this patient’s family that had this genetic mutation also had a greater increase in heart rate with standing and elevated plasma norepinephrine compared to those without this genetic mutation. This demonstrates that orthostatic intolerance and tachycardia are associated with norepinephrine transporter deficiency.

Do Other Non-Related Patients Have This Mutation?
For several years, we looked for this mutation in other POTS patients.  We have not found any other non-related patients to have this same loss of function mutation.

Decreased NET Protein Expression in Some POTS Patients
We had just about lost hope in NET deficiency as an important contributor to POTS in many patients. More recently, colleagues from Melbourne Australia published a very nice paper in which they performed forearm vein biopsy in a handful of POTS patients and healthy volunteers.  They then assessed the amount of NET protein in the vein tissue.  They found that several patients, but not all, had low levels of NET protein expression compared to the healthy volunteers,  These data suggest that even though most POTS patients do not have a genetic mutation causing dysfunctional NET protein, it may be more common to have decreased protein expression.  Further work from their group has suggested that the relevant DNA may not “uncoil” properly in some POTS patients.  This would be required to make it available for transcription to RNA to then make the protein.  In another very elegant paper from the Czech Republic, the authors performed MIBG heart scans in 20 POTS patients.  MIBG is a radiotracer that is taken up by sympathetic nerves via NET.  They found that 20% of the patients had markedly diminished heart uptake of MIBG.  They concluded that these hearts were denervated.  An alternative explanation could be that these patients had decreased NET expression (as shown in the Melbourne studies) and could not take up the MIBG tracer.

*Summary information above from the Vanderbilt Autonomic Dysfunction Center

 

Return to Newsletter Table of Contents - December 2017

Edited by edriscoll




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