Abstract & Commentary
By Norm Latov, MD Professor of Neurology and Neuroscience and Director of the Peripheral Neuropathy Center at Weill Medical College at Cornell University. Dr. Latov is a consultant for Quest Diagnostics and Talecris Inc., is a stockholder of Therapath LLC, and has royalties in Athena Diagnostics.
Synopsis: The availability of sensitive and reproducible measures of autonomic function has improved physicians’ ability to diagnose these disorders.
Source: Freeman R. Autonomic Peripheral Neuropathy. Lancet. 2005;365:1259-1270.
This article summarizes our current understanding of the autonomic neuropathies, their manifestations, causes, mechanisms, and treatments. As these disorders can primarily affect the autonomic nerves, with few other signs of neuropathy, it behooves us to recognize the associated symptoms, so as to consider the diagnosis. Cardiovascular symptoms consist of orthostatic dizziness, headache, or tachycardia. Gastrointestinal manifestations result from gastropareis, with postprandial bloating, nausea or vomiting, or from decreased intestinal motility, with constipation or diarrhea. Genitourinary symptoms can include urinary retention with overflow incontinence, sexual dysfunction resulting from erectile or ejaculatory failure, or reduced vaginal lubrication. Reproducible measures of autonomic function, such as the tilt table test, heart rate variability response, or sudomotor-axon-relex test, are now available, and can be used to confirm the clinical diagnosis and follow progression or response to therapy.
The list of causes for autonomic neuropathy is extensive, and includes diabetes, primary or hereditary amyloidosis, certain genetic defects, autoimmune or paraneoplastic mechanisms, particular infections, including botulism or HIV-1, and some toxins. Freeman and colleagues recommend that testing for causes of autonomic neuropathy be tailored to the individual patient, and depend on the clinical presentation, history, and examination.
Therapy, as in other types of neuropathy, is directed at both the underlying cause and at ameliorating the symptoms. Orthostatic hypotension can respond to volume repletion, with the addition of the mineralocorticoid 9-alpha-fluorohudrocortisone, or of Midodrine, a sympathomimetic agent. Gastroparesis can be treated with frequent small meals and prokinetic agents such as metoclopramide or domperidone. Bowel hypomotility can be improved by increased dietary fiber with fluid, stool softener, and an osmotic laxative. Erectile dysfunction is now commonly treated with phosphodiesterase 5 inhibitors, including sildenafil, tadalafil, or vardenafil, which inhibit breakdown of cAMP and increase smooth muscle relaxation and blood flow. Vaginal lubrication can be helped by the use of vaginal lubricants and oestrogen creams. Intermittent self cathetierization is recommended for therapy of impaired or absent detrusor muscle activity or urinary retention. Most patients can be helped by judicious diagnosis and treatment.
The article provides an excellent overview of the autonomic neuropathies, with specific recommendations for diagnosis and treatment. A potential criticism is that the review is not evidence based or based on blinded controlled trials, but relies instead on non-blinded or controlled trials, case series or reports, chapters, review articles, and the author’s own experience and expert opinion. However, it represents the best currently available evidence and, as such, is an informative guide to the management of these patients.