Long-COVID postural tachycardia syndrome: an American Autonomic Society statement

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

     

Response to: Human papillomavirus (HPV) vaccine safety concerning POTS,CRPS and related conditions

Clinical Autonomic Research -     

Prominent dysautonomia in a patient with POEMS syndrome

POEMS syndrome is a rare, multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and/or skin changes. Here we present an unusual case of a patient with POEMS syndrome who exhibited a prominent autonomic neuropathy.     

A comparison of stroke risk factors in patients enrolled in stroke prevention trials

The high prevalence of stroke risk factors may explain, in part, the high incidence of stroke in African Americans. To further investigate the role of stroke risk factors, we compared stroke risk factor profiles of patients in the African-American Antiplatelet Stroke Prevention Study (AAASPS) with those in other stroke prevention studies in which the enrollees were predominately white. The baseline characteristics of the AAASPS enrollees obtained from an interim AAASPS database of 1,087 patients from 65 centers in the U.S. between December 1995 and June 1999 was compared to the baseline characteristics of 53,293 predominantly non-African American patients enrolled in 23 other stroke prevention studies (pNAA). Percentages were reported for qualitative characteristics, and means and standard deviations (SDs) for quantitative characteristics. For selected qualitative characteristics, 95% confidence intervals were given for population percentages in each study. The comparison of baseline characteristics showed that hypertension was more prevalent in AAASPS (84% [95% CI 82.2, 86.61) compared to pNAA trial patients (range of 27% to 67%). Diabetes mellitus was more common in AAASPS (39.1%) compared to pNAA trial patients (17.1%). Cardiac disease, however, was less common in AAASPS than in pNAA trials. The frequency of baseline characteristics of AAASPS patients is different from those of pNAA studies. Risk factor profiles are important as they may help to predict stroke subtype and outcome. Furthermore, the differences in baseline characteristics may portend differences in response to treatment and incidence of adverse events.     

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS

Introduction: Of the nearly 38 million people in the USA who receive statin therapy, 0.1‐0.5% experience severe or life‐threatening myopathic side effects. Methods: We performed a genome‐wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin‐tolerant group to identify genetic susceptibility loci. Results: Replication studies in independent groups of severe statin myopathy (n = 190) and statin‐tolerant controls (n = 130) resulted in the identification of three single‐nucleotide polymorphisms (SNPs), rs9342288, rs1337512, and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (P = 0.0003–0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. Conclusion: Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle. Muscle Nerve, 2011     

Rapid gastric emptying is more common than gastroparesis in patients with autonomic dysfunction

OBJECTIVES: Autonomic dysfunction is associated with a wide variety of gastrointestinal symptoms. It is unclear how many patients with autonomic dysfunction have slow or rapid gastric emptying. The aim of this study was to determine the prevalence of rapid and delayed solid phase gastric emptying in patients with autonomic dysfunction referred for evaluation of gastrointestinal symptoms and the association of emptying rate with clinical symptoms. METHODS: Retrospective review of all patients with autonomic dysfunction who had a gastric emptying test from January, 1996 to March, 2005. Demographic data, clinical symptoms, composite autonomic scoring scale (CASS) score, and gastric emptying parameters were analyzed. RESULTS: Sixty-one subjects (women 49, age 42 [16-74] yr) with autonomic dysfunction were reviewed. Patients had mild-to-moderate (mean CASS score 3) autonomic dysfunction. Twenty-seven, 17, and 17 patients had rapid, normal, and delayed gastric emptying t(1/2), respectively. In addition, 10 patients had initially rapid emptying in phase 1, with subsequent slowing in phase 2 to produce an overall normal or delayed t(1/2). There was no difference in demographic data or CASS score among the three groups. More patients with initial or overall rapid emptying had diarrhea (70%) compared to patients with normal (33%) or delayed (33%) emptying (P= 0.018). CONCLUSIONS: Unexpectedly, more patients with autonomic dysfunction have rapid rather than delayed gastric emptying. The presence of diarrhea in patients with autonomic symptoms should prompt consideration for the presence of rapid gastric emptying. Conversely, the finding of rapid gastric emptying in patients with gastrointestinal symptoms should prompt consideration for the presence of underlying autonomic dysfunction.     

Genetic risk factors associated with lipid-lowering drug-induced myopathies

Lipid-lowering drugs produce myopathic side effects in up to 7% of treated patients, with severe rhabdomyolysis occurring in as many as 0.5%. Underlying metabolic muscle diseases have not been evaluated extensively. In a cross-sectional study of 136 patients with drug-induced myopathies, we report a higher prevalence of underlying metabolic muscle diseases than expected in the general population. Control groups included 116 patients on therapy with no myopathic symptoms, 100 asymptomatic individuals from the general population never exposed to statins, and 106 patients with non-statin-induced myopathies. Of 110 patients who underwent mutation testing, 10% were heterozygous or homozygous for mutations causing three metabolic myopathies, compared to 3% testing positive among asymptomatic patients on therapy (P = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (P < 0.0001) due to an increased presence of mutation homozygotes. The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease was increased 13- and 20-fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25-fold with no increase in carrier status. In 52% of muscle biopsies from patients, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. Variable persistent symptoms occurred in 68% of patients despite cessation of therapy. The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for myopathic outcomes in certain high-risk groups.