Autonomic Nerve Disorders

Relationship between P-wave axis and heart rate in individual patients with postural tachycardia syndrome (POTS) and in controls.

Relationship between P-wave axis and heart rate in individual patients with postural tachycardia syndrome (POTS) and in controls.

Autonomic nerve disorders (dysautonomia) refer to disorders of autonomic nervous system (ANS) function. Dysautonomia is a general term used to describe a breakdown or abnormal function of the ANS. The autonomic nervous system controls much of your involuntary functions. Symptoms are wide-ranging and can include problems with the regulation of heart rate, blood pressure, body temperature, perspiration, and bowel and bladder functions. Other symptoms include fatigue, lightheadedness, feeling faint or passing out (syncope), weakness, and cognitive impairment.

Orthostatic intolerance refers to impairment in the body's ability to handle gravity. When a person stands, blood pools in the abdomen and legs. Normally, the autonomic nervous system will compensate by constricting blood vessels and pushing the blood to the brain. When autonomic pathways are damaged, these reflexes, termed baroreflexes, do not function adequately. As a result, the person becomes dizzy, light-headed, and may faint.

In addition, digestion is controlled by the autonomic nervous system. When the ANS malfunctions, the "victim" commonly develops gastrointestinal problems. Symptoms include nausea, bloating, vomiting, severe constipation, and abdominal pain.

Autonomic dysfunction can occur as a secondary condition of another disease process, like diabetes, or as a primary disorder where the autonomic nervous system is the only system impacted. These conditions are often misdiagnosed.

Over one million Americans are impacted by a primary autonomic system disorder. The more common forms of these conditions include:

  • Orthostatic hypotension (OH)
  • Orthostatic intolerance (OI)
  • Postural orthostatic tachycardia syndrome, also known as postural tachycardia syndrome (POTS)
  • Syncope
  • Neurogenic bowel (gastroparesis, intestinal dysmotility, constipation)
  • Erectile dysfunction and neurogenic bladder

Ongoing research

Phillip Low, M.D., heads an autonomic disorders program project. This program is focused on studies of the pathophysiology of orthostatic intolerance and its amelioration. Major areas of research are autonomic pathophysiology of the synucleinopathies, especially multiple system atrophy; the autonomic neuropathies, especially autoimmune autonomic ganglionopathy; diabetic neuropathy; and the postural tachycardia syndrome. Dr. Low's laboratory is equipped to use non-invasive measures such as beat-to-beat blood pressure to evaluate baroreflex sensitivity, both vagal and adrenergic, as well as sudorometric and laser Doppler methods of measuring sudomotor and vasomotor activity. The lab is also equipped to obtain direct measurements of muscle sympathetic activity using microneurography of peripheral nerve.

Dr. Low also heads an experimental laboratory on peripheral nerve microenvironment with particular focus on the basic mechanisms underlying the pathogenesis of diabetic and ischemic neuropathies. He is specifically investigating the hypothesis that diabetic neuropathy is mediated by oxidative injury. A related focus is on the pathophysiology of ischemic neuropathies and mechanisms of neuroprotection. His laboratory techniques include immunohistochemical, molecular, microelectrode, and autoradiographic methods of studying nerve tissues.

Eduardo Benarroch, M.D., D.Sc., heads a research program devoted to defining the neurochemical and structural brainstem lesions that underlie major dysautonomic manifestations in the synucleinopathies including multiple system atrophy (MSA) and other parkinsonian syndromes, including Parkinson's disease and Lewy body dementia. Dr. Benarroch maintains a particular focus on neurochemical organization of autonomic control regions of the medulla and brain stem to the hypothalamus. He additionally undertakes some clinical studies in living patients that extend this clinico-pathological correlation.

Paola Sandroni, M.D., focuses on pure autonomic failure (PAF), autoimmune autonomic neuropathies (AAN), postural tachycardia syndrome (POTS), and multiple system atrophy (MSA). Dr. Sandroni's main effort has been to study the interaction of adrenergic dysfunction and pain, characterize and describe the natural history of these disorders, assess their quality of life, identify predictors of good versus poor outcome, and conduct therapeutic trials to control their most disabling symptoms.

Robert Fealey, M.D., heads the Thermoregulatory Laboratory and has a particular interest in disorders of sweating and thermoregulation. Dr. Fealey collaborates closely with the Autonomic Center on the role of thermoregulatory failure in the diagnosis and progression of the dysautonomias.

All these studies have been conducted in the Center for Translational Science Activities (CTSA) in collaboration with the group led by Michael Camilleri, M.D., and Adil Bharucha, M.B.B.S., M.D. (Department of Gastroenterology), Michael Joyner, M.D. (Department of Anesthesiology), and the personnel of the CTSA. Close collaboration exists between the programs of Drs. Camilleri and Bharucha, with their focus on gastrointestinal dysmotility and the Neurology Autonomic Group. Dr. Joyner collaborates closely with his expertise in exercise physiology. The Autonomic Center collaborates with other neurologic investigators, in particular with Eric Ahlskog, M.D., Ph.D., and Jim Maraganore, M.D., in Rochester, William Cheshire, M.D., in Jacksonville, and Brent Goodman, M.D., in Scottsdale.

Research advances

Dr. Phillip Low invented the quantitative sudomotor axon reflex test (QSART), which evaluates postganglionic sudomotor function. He also developed the autonomic reflex screen, the nation's standard in the evaluation of sudomotor, cardiovagal, and adrenergic functions. The composite autonomic severity score (CASS) utilizes these studies to generate a score that corrects for the confounding effects of age and gender.

Together with Guillermo Suarez, M.D., Dr. Low developed and standardized the autonomic symptom profile (ASP), which evaluates 10 domains of autonomic symptoms. The composite autonomic symptom score (COMPASS) provides a score of deficits.

Mayo Clinic autonomic investigators are responsible for describing a number of novel entities including POTS, chronic idiopathic anhidrosis, and autoimmune autonomic ganglionopathy.

Dr. Low led the national study that demonstrated the efficacy of midodrine in the treatment of orthostatic hypotension (OH). This is the only approved drug for the treatment of neurogenic OH.

Paola Sandroni, M.D., Ph.D., Wolfgang Singer, M.D., and Dr. Low initiated a smart drug approach in the treatment of OH. They demonstrated, in a double-blind study, that pyridostigmine will improve orthostatic hypotension, without worsening supine hypertension.

Drs. Low, Schondorf, Sandroni, Fealey, and collaborators have demonstrated that a significant subset of POTS is a limited autonomic neuropathy.

Dr. Benarroch has defined the nuclear groups in human brain stem and hypothalamus that are responsible for specific aspects of autonomic failure and contribute to respiratory manifestations of MSA.