Autoimmune autonomic neuropathies: time to look beyond autoimmune autonomic ganglionopathy

Excerpt

Autoimmune autonomic neuropathies are rare disorders with an acute or subacute onset of autonomic failure which are potentially responsive to immunotherapy. Among these diseases, autoimmune autonomic ganglionopathy (AAG) is the most well-known syndrome. AAG is caused by antibodies against the ganglionic nicotinic acetylcholine receptor (AChR) that disrupt cholinergic transmission at the sympathetic and parasympathetic ganglia. Ganglionic AChR antibodies are known to have a pathogenic role in AAG [1], and antibody levels correlate with disease severity [2]. In addition, AAG has many unique features, including severe autonomic failure, pupillary fatigue, and responsiveness to known therapies for antibody-mediated diseases such as plasma exchange, intravenous immunoglobulins (IVIG), or other types of immunotherapy. Autonomic clinicians and neurologists are aware of AAG and usually have a fairly low threshold for requesting ganglionic AChR antibody titers in acute- or subacute-onset focal or generalized autonomic syndromes, since they are relatively easy to obtain [3]. However, not all patients with autoimmune autonomic neuropathies have a positive titer of ganglionic AChR antibodies. If the degree and nature of the autonomic neuropathy is severe (e.g., with associated severe orthostatic hypotension), and all signs point to an underlying autoimmune etiology, these seronegative patients are typically treated with immunotherapy too. In clinical practice, the treatment response and long-term outcomes of patients with acute-onset autonomic failure and negative ganglionic AChR antibodies are unknown. …