Autoimmune autonomic ganglionopathy with late-onset encephalopathy

A 47-year old female presented with a 4 month history of early satiety, constipation, light sensitivity, orthostatic intolerance, siccca, and anhydrosis. Her examination revealed dilated, unreactive pupils with dry eyes and mouth but normal strength, phasic reflexes, and sensation. After 3 min of quiet standing her systolic pressure dropped 70 mmHg with a fixed heart rate of 74 bpm. Her α3 ganglionic AChR level was 2060 pmol/L (normal ≤ 50). Orthostatic symptoms significantly improved within 10 days of completing 2.0 g/kg IVIg. Her supine norepinephrine (NE) level improved over baseline but remained low (i.e., 0.36 à 0.61 nmol/L). Persisting gut inertia prompted a trial of plasma exchange (PLEx) which restored her supine NE level (2.18 nmol/L), bowel patterns, and pupillary reactivity. Five months later, while her AAG was well controlled, she developed gait unsteadiness, confusion, horizontal and vertical nystagmus, bladder retention, and long tract motor signs. A contrast MRI head was normal. Further serum testing demonstrated binding avidity for neuronal α4 and α7 nAChRs. She responded to high-dose steroid and immunomodulation. This is the first case report of AAG presenting with antibodies directed against both peripheral and central nAChRs. It is tempting to speculate that CNS α4 or α7 antibodies may have precipitated the treatment-responsive encephalopathy.