Abstract & Commentary
Source: Klein CM, et al. The spectrum of autoimmune autonomic neuropathies. Ann Neurol. 2003;53:752-758.
In this report by Klein and colleagues, the clinical features of a series of 18 patients (13 female, 5 male, 61.4 years of age ± 12.0 years) evaluated at the Mayo Clinic for autonomic dysfunction are presented. Ten patients had subacute onset of symptoms (6 with an antecedent viral illness), and 8 patients had a chronic progressive course. Patients with other definable causes such as diabetes, amyloidosis, or multiple system atrophy were excluded.
Patients were identified first with neurogenic orthostatic hypotension, defined as a systolic blood pressure reduction of at least 30 mm Hg that occurred within 3 minutes of head tilt up. Of 121 patients meeting that diagnosis, 18 were found to have autoantibodies against autonomic ganglion acetylcholine receptor (ganglionic AchR Ab). Additional autonomic testing was performed to assess postganglionic sudomotor, cardiovagal, and adrenergic functions, and a composite autonomic severity score (CASS) was calculated from 0 (no deficit) to 10 (maximal deficit). The mean score for the 18 patients was 7.5, indicating severe generalized autonomic failure. The patients with more severe cholinergic autonomic failure had higher levels of ganglionic AchR antibodies.
The clinical profile of cholinergic neuropathy included a spectrum of parasympathetic/enteric symptoms: sicca (dry eyes and mouth), abnormal pupillary responses to light (Adies), upper gastrointestinal symptoms (early satiety, postprandial nausea, and vomiting), constipation, neurogenic bladder, erectile dysfunction, and reduced sweating.
The diagnosis of autonomic neuropathy is often delayed over years if not considered by the alert clinician. The causes are heterogeneous and the term idiopathic autonomic neuropathy, or "pure autonomic failure," customarily categorizes those cases without a definable underlying pathology. This report documents the existence of an autoimmune etiology for a subset of patients, whose clinical profile appears to have both a subacute onset or a progressive course, some of whom might be confused with neurodegenerative autonomic failure. The therapeutic implications of identifying an autoimmune autonomic neuropathy were not addressed in this report by Klein et al. For example, was any attempt at immune modulatory therapy attempted in these patients (corticosteroids, plasmapheresis, IVIG), and was any benefit achieved? It is hopeful that neurologists may soon reliably identify and treat a previously untreatable disorder. — Brian R. Apatoff, MD, PhD. Dr. Apatoff, Associate Professor of Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.