Autoimmune Autonomic Ganglionopathy Classification
No, autoimmune autonomic ganglionopathy (AAG) is not a central autonomic network disorder—it is a peripheral autoimmune disorder affecting autonomic ganglia, not the central nervous system. 1, 2
Anatomic Localization of AAG
AAG is definitively a peripheral autonomic disorder where antibodies target the ganglionic nicotinic acetylcholine receptors (α3gAChR) located in sympathetic, parasympathetic, and enteric ganglia 2, 3, 4. The pathophysiology involves:
- Direct antibody-mediated disruption of synaptic transmission at the level of autonomic ganglia, which are peripheral structures located outside the central nervous system 3, 4
- Antibodies specifically inhibit ganglionic acetylcholine receptors, causing autonomic failure through peripheral mechanisms rather than central pathology 3
- The disorder affects sympathetic, parasympathetic, and enteric ganglia—all peripheral autonomic structures 4
Distinction from Central Autonomic Disorders
The classification framework clearly separates peripheral from central autonomic dysfunction 1:
- Primary central autonomic disorders include Multiple System Atrophy (MSA), Parkinson's Disease, and Lewy Body Dementia, where the central nervous system autonomic pathways are the primary target 1
- Peripheral autoimmune autonomic disorders include AAG, paraneoplastic autonomic neuropathy, and acute autonomic and sensory neuropathy 2
- AAG manifests with generalized or selective autonomic failure due to peripheral ganglionic dysfunction, not central network pathology 2, 4
Synuclein Status
AAG is correctly classified as a non-synuclein disorder because:
- It is an antibody-mediated autoimmune condition, not a neurodegenerative synucleinopathy 2, 3
- Unlike Parkinson's Disease, MSA, or Lewy Body Dementia (which are synucleinopathies affecting central structures), AAG involves immune-mediated peripheral ganglionic dysfunction 1, 2
Clinical Implications
The peripheral nature of AAG has critical treatment implications 5, 3:
- AAG responds to immunomodulatory therapy (plasmapheresis, IVIG, corticosteroids, immunosuppression) because it is antibody-mediated 5, 3, 6
- Combined immunotherapy with prednisone, mycophenolate mofetil, and plasmapheresis produces substantial clinical improvement 5
- Central autonomic disorders like MSA do not respond to immunotherapy and have fundamentally different management approaches 1
The correct classification is: AAG is a peripheral, non-synuclein, autoimmune autonomic disorder—not a central autonomic network disorder.