Autoimmune autonomic ganglionopathy with reversible cognitive impairment

Abstract

Background: Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of antibody-mediated impaired transmission across the autonomic ganglia resulting in severe autonomic failure. Some patients with AAG report cognitive impairment of unclear etiology despite treatment of autonomic symptoms.

Objective: To investigate the relationship between orthostatic hypotension, antibody titers, and cognitive impairment in patients with AAG.

Design: Prospective cohort.

Setting: Academic medical center.

Participants: Three patients with AAG underwent neuropsychological testing before and after cycles of plasma exchange in both the seated and standing positions.

Main outcome measures: Patients' responses to neuropsychological tests were measured by percentage change from baseline in the seated and standing positions before and after plasma exchange to determine the effects of orthostatic hypotension and antibody titers on cognition.

Results: Orthostatic hypotension and elevated antibody titer were associated independently with neuropsychological impairment (P < .05), particularly in domains of executive function, sustained attention, and working memory. Cognitive dysfunction improved, even in the seated normotensive position, after plasmapheresis and consequent reduction in antibody levels.

Conclusion: Reversible cognitive impairment is independently associated with both orthostatic hypotension and elevated nicotinic acetylcholine receptor autoantibodies, thereby expanding the clinical spectrum of autonomic ganglionopathy and, in so doing, providing an additional treatable cause of cognitive impairment.

Figures

Figure 1. Changes in cognitive performance by position, before and after plasma exchange

The results are shown for the individual cognitive tests (mean ± standard deviation of 10 cycles of testing across the 3 patients). Pre-pheresis data is shown with black bars, post-pheresis data is shown with grey bars. Note the direction of improvement is test specific. There were differences between the seated and standing tests pre-pheresis (i.e., associated with orthostatic hypotension) with all 3 trail making tests and the controlled oral word association. There were differences between seated tests pre- and post-pheresis (i.e., associated with changes in antibody titer) with all tests except the digit span backward test (*denotes P

Figure 2. Changes in cognitive performance due to orthostatic hypotension and antibody removal

The figure expresses the change in the cognitive test result, expressed as a percentage, related to the seated, pre-plasma exchange baseline. A negative percentage change denotes worsening of the test result and a positive percentage change denotes improvement. The dotted line represents performance prior to plasma exchange in the seated position (baseline condition, no orthostatic hypotension). The black circles represent performance prior to treatment while in the standing position (change due to orthostatic hypotension). Tests of executive function (Trail making tests and controlled oral word association) worsened due to orthostatic hypotension (* denotes P