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Invited Article: Autonomic ganglia

Target and novel therapeutic tool

From the Department of Neurology (S.V.), UT Southwestern Medical Center, Dallas, TX; and Department of Neurology (P.S., W.S., P.A.L.), Mayo Clinic, Rochester, MN.

Address correspondence and reprint requests to Dr. Phillip A. Low, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 low{at}mayo.edu

Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The muscle AChR mediates transmission at the neuromuscular junction; antibodies against the muscle AChR are the cause of myasthenia gravis. The ganglionic (3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic, and enteric autonomic ganglia. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Pharmacologic enhancement of ganglionic synaptic transmission may be a novel way to improve autonomic function. Ganglionic AChR antibodies are found in patients with autoimmune autonomic ganglionopathy (AAG). Patients with AAG typically present with rapid onset of severe autonomic failure. Major clinical features include orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction, and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia, AAG is an antibody-mediated neurologic disorder. The disease can be reproduced in experimental animals by active immunization or passive antibody transfer. The patient may improve with plasma exchange treatment or other immunomodulatory treatment. Antibodies from patients with AAG inhibit ganglionic AChR currents. Other phenotypes of AAG are now recognized based on the results of antibody testing. These other presentations are generally associated with lower levels of ganglionic AChR antibodies. A chronic progressive form of AAG may resemble pure autonomic failure. Milder forms of dysautonomia, such as postural tachycardia syndrome, are associated with ganglionic AChR in 10–15% of cases. Since ganglionic synaptic transmission is a common pathway for all autonomic traffic, enhancement of autonomic function through inhibition of acetylcholinesterase is a potential specific therapeutic strategy for autonomic disorders. Increasing the strength of ganglionic transmission can ameliorate neurogenic orthostatic hypotension without aggravating supine hypertension. Recent evidence also suggests a potential role for acetylcholinesterase inhibitors in the treatment of postural tachycardia syndrome.

Abbreviations: AAG = autonomic ganglionopathy; AChR = acetylcholine receptors; BP = blood pressure; EAAG = experimental AAG; OH = orthostatic hypotension; POTS = postural tachycardia syndrome; Py = pyridostigmine.

Supported by K08NS02247, R01NS48077, NS32352, NS 39722, NS 44233, and NS 43364 from the NIH, Bethesda, MD; grant MO1 RR00585 from the Mayo General Clinical Research Center, Rochester, MN; Mayo Funds; and UT Southwestern Medical Center.

Disclosure: The authors report no disclosures.

Presented in part at the 59th annual meeting of the American Academy of Neurology, Boston, 2007.

Received August 9, 2007. Accepted in final form January 24, 2008.