Seronegative autoimmune autonomic neuropathy: a distinct clinical entity

Abstract

In these cases of autoimmune autonomic failure, key differences from seropositive AAG emerge. Testing showed prominent sympathetic (rather than cholinergic) failure, specific pupillary findings of AAG were absent, and sensory symptoms were prominent. AAG responds to antibody-targeted immunotherapy, while these patients responded best to steroids. This seronegative autoimmune autonomic neuropathy is a distinct clinical entity requiring a different treatment approach from AAG.

Supine plasma NE predicts the pressor response to droxidopa in neurogenic orthostatic hypotension

“…Inclusion criteria were (1) patients with nOH 9 diagnosed with standardized autonomic function testing 10 ; (2) nOH caused by neurodegenerative synucleinopathies (PD, MSA, and PAF) according to current clinical diagnostic criteria 7,11,12 ; or (3) nOH caused by autoimmune autonomic ganglionopathies (AAGs)/ autoimmune autonomic neuropathies (AANs), including AAG seropositive for antibodies against the acetylcholine ganglionic (nicotinic) receptor, 13 seronegative AAG defined as acute-onset nOH in combination with other signs of widespread sympathetic and parasympathetic failure such as neurogenic bladder, pupillary involvement, and gastroparesis but no identifiable serum antibodies, 14,15 and patients with acute autonomic and sensory neuropathy. 16 Patients with non-nOH, diabetes mellitus, lupus, congestive heart failure, vasovagal syncope, infectious diseases, or amyloidosis were excluded.…”

Autoimmune autonomic neuropathies: time to look beyond autoimmune autonomic ganglionopathy

“…These patients also have characteristic hyperintensities in the dorsal columns on spinal magnetic resonance (MR) imaging as well as very low plasma norepinephrine levels [4]. Although the patients of this series reported by Golden, Bryarly, and Vernino seem to have a predominantly subacute course with no changes on spinal MR imaging, their clinical phenotypes are remarkably similar to those of patients with AASN [5]. Do these seronegative patients have more in common with AASN than with AAG, and does that provide clues to the underlying pathophysiology?…”

“…Golden, Bryarly, and Vernino present their experience in these patients with antibody-negative, albeit severe, autoimmune autonomic neuropathy [5]. This case series offers many novel useful insights into patients with seronegative autoimmune autonomic neuropathy.…”

Acute Sensory and Autonomic Neuronopathy: A Devastating Disorder Affecting Sensory and Autonomic Ganglia

“…45,46 Among disorders that cause acute-onset autonomic failure, the differential diagnosis includes autoimmune autonomic ganglionopathy, which is associated with antibodies against the ganglionic nicotinic acetylcholine receptor in 50% of the cases, and which manifests as an acute or subacute onset of autonomic failure with no sensory deficits. 47,48 Some drugs (e.g., pyridoxine intoxication, cisplatinum) or infections (herpes zoster) can also result in a combination of symptoms resembling ASANN. 11,20,[49][50][51][52][53][54]…”