Clinical laboratory evaluation of autoimmune autonomic ganglionopathy: Preliminary observations

Abstract

Several forms of chronic autonomic failure manifest as neurogenic orthostatic hypotension, including autoimmune autonomic ganglionopathy (AAG) and pure autonomic failure (PAF). AAG and PAF are thought to differ in pathogenesis, AAG reflecting decreased ganglionic neurotransmission due to circulating antibodies to the neuronal nicotinic receptor and PAF being a Lewy body disease with prominent loss of sympathetic noradrenergic nerves. AAG therefore would be expected to differ from PAF in terms of clinical laboratory findings indicating post-ganglionic noradrenergic denervation. Both diseases are rare. Here we report preliminary observations about clinical physiologic, neuropharmacologic, neurochemical, and neuroimaging data that seem to fit with the hypothesized pathogenetic difference between AAG and PAF. Patients with either condition have evidence of baroreflex-sympathoneural and baroreflex-cardiovagal failure. Both disorders feature low plasma levels of catecholamines during supine rest, but plasma levels of the other endogenous catechols, dihydroxyphenylalanine (DOPA), dihydroxyphenylacetic acid (DOPAC), and dihydroxyphenylglycol (DHPG), seem to be lower in PAF than in AAG, probably reflecting decreased norepinephrine synthesis and turnover in PAF, due to diffuse sympathetic noradrenergic denervation. PAF entails cardiac sympathetic denervation, whereas cardiac sympathetic neuroimaging by thoracic 6-[(18)F]fluorodopamine scanning indicates intact myocardial sympathetic innervation in AAG.

Fig. 1

Mean (±SEM) values for sweat production in the quantitative sudomotor axon reflex test in patients with autoimmune autonomic ganglionopathy (AAG), pure autonomic failure (PAF), multiple system atrophy (MSA), or Parkinson disease with neurogenic orthostatic hypotension (PD+NOH).

Fig. 2

Mean (±SEM) values for 6-[¹⁸F]flurodopamine-derived radioactivity in the interventricular septum in patients with autoimmune autonomic ganglionopathy (AAG), pure autonomic failure (PAF), multiple system atrophy (MSA), or Parkinson disease with neurogenic orthostatic hypotension (PD+NOH). Horizontal dashed line shows normal mean value.

Fig. 3

Mean (±SEM) values for plasma levels of catecholamines (norepinephrine, NE; epinephrine, EPI; dopamine, DA) in patients with autoimmune autonomic ganglionopathy (AAG), pure autonomic failure (PAF), multiple system atrophy (MSA), or Parkinson disease with neurogenic orthostatic hypotension (PD+NOH).

Fig. 4

Mean (±SEM) values for plasma levels of non-catecholamine catechols (L-3,4-dihydroxyphenylalanine, DOPA; dihydroxyphenylacetic acid, DOPAC; dihydroxyphenylglycol, DHPG) in patients with autoimmune autonomic ganglionopathy (AAG), pure autonomic failure (PAF), multiple system atrophy (MSA), or Parkinson disease with neurogenic orthostatic hypotension (PD+NOH).