Stanford Autonomic Disorders Program Research

Research

Diagnostic Modalities
Our group optimized certain techniques of autonomic assessment which have become now among the standards of testing. For instance, we have demonstrated the importance of changing time measurements and the configuration and topography of sweat responses as a tool to differentiate various types of small fiber neuropathies.  We have also incorporated and individualized various interactive and dynamic maneuvers during our autonomic testing to individualize and gain further insight into the patient’s disorder.

Gastrointestinal (GI) motility disorders
In the field of GI dysfunction, our group was the first to show the role that autonomic dysfunction plays in the etiology of gastroesophageal reflux.  We also showed that, contrary to a widely held belief, patients with dysautonomia and gastric fullness exhibit rapid gastric emptying as often as slow emptying.  This altered the way we manage these patients, and the differences could have clues to the underlying etiology of their disorder. Our group found that autonomic impairment accounts for a significant amount of the GI manifestations in patients with inflammatory bowel disease.  We were also the leaders in studying the pattern of autonomic nervous system function in adult patients with cyclic vomiting syndrome, and our findings currently have significant implications pertaining to the management.  We are evaluating the imbalance between the vagus nerve and the sympathetic nervous system as the origin of various gastrointestinal disorders.

POTS (Postural Orthostatic Tachycardia Syndrome)
POTS is an autonomic syndrome commonly triggered by an infection or a surgical stress. Our clinic has a major POTS clinic in California with a large number of referrals. Since the coronavirus disease 2019 (COVID-19) has been found to cause various neurological complications in survivors, our group have launched a study to investigate clinical characteristics of post-COVID POTS cases.

Neurogenic Orthostatic hypotension and alpha-Synucleinopathies
Our center has participated in pharmacological trials for neurogenic orthostatic hypotension and alpha-synucleinopathies, particularly multiple system atrophy (MSA). We are also studying natural history of synucleinopathies by participating an international registry.

Sleep disorders and autonomic dysfunction
Our group evaluated the association between sleep disorders and autonomic dysfunction.  We have studied autonomic impairment and findings of peripheral degeneration from skin biopsy and quantitative sudomotor test in idiopathic REM sleep behavior disorders (RBD) and neurodegenerative conditions following RBD.  We also found a strong association between sympathetic dysfunction and obstructive sleep apnea.  The association became even stronger when we considered those with obstructive sleep apnea and hypertension, leading to increased cardiovascular morbidity.

Autoimmune Autonomic Disorders
The possible role of autoimmune dysregulation in causing autonomic dysfunction has come to the forefront since 2000 after the description of autoantibodies to ganglionic acetylcholine receptors.  Since then, we and other investigators have expanded the role of other autoimmune conditions, with or without antibodies leading to autonomic dysfunction.  Some of these conditions involve the central autonomic nervous system, while others involve the peripheral autonomic nervous system. The latter also includes an increasing number of autonomic and small fiber neuropathies will that are immune mediated.

Other topics
Our group has a long history of evaluating and managing complex diabetic neuropathies and polyradiculopathies with autonomic manifestations.  Patients with mild diabetic autonomic neuropathies have a higher incidence of neuropathy, while those with more advanced autonomic neuropathy have orthostatic intolerance, and gastrointestinal motility dysfunction. Those patients are particularly at a higher risk of arrhythmia and silent myocardial infarction (painless heart attack).

Our group is part of the Stanford Amyloidosis Center.  We work closely with Cardiology, Hematology, Nephrology, and Genetics to evaluate these patients. This is a condition that involves the excessive generation and deposition of insoluble fibrillary proteins in various organ systems, and has acquired and hereditary forms. We actively diagnose these patients and participate in treating them with newly approved, state-of-the-art pharmacologic therapies.

Another condition we studied is that of rhinitis, a condition that affects 33 million U.S. residents. Approximately one half of those affected non-allergic rhinitis. Symptoms of vasomotor rhinitis include intermittent nasal obstruction, rhinorrhea, and headaches that often occur in response to physical stimuli such as cold air, tobacco smoke, sudden temperature changes, wet extremities, and emotional stimuli.  The autonomic nervous system regulates the vascular tone, secretory function, and inflammatory status of the nasal cavity.  We found that an imbalance in parasympathetic and sympathetic input to the sinuses, nasal cavity and the upper or lower respiratory tract is associated with vasomotor nasal symptoms and chronic respiratory tract inflammation.

Orthostatic dizziness and imbalance is a growing medical and social health issue. We work with Otolaryngology and our Stanford balance center to evaluate these patients. While a significant percentage of these patients have orthostatic intolerance from either orthostatic hypotension or tachycardia, our group have found a small but substantial group who have vestibular (inner ear) disorders leading to the autonomic dysfunction, leading to significant implications and their management and rehabilitation. We are further characterizing these patterns in various age groups.