Clinical laboratory evaluation of autoimmune autonomic ganglionopathy: Preliminary observations.

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.

Other autonomic neuropathies associated with ganglionic antibody.

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer. This review describes the autonomic neuropathies most frequently encountered in clinical practice in which an autoimmune etiology is suspected. They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. In each of these conditions, occasional positivity to the G-AchR antibody has been found, but the pathogenetic significance of such finding is still uncertain. Other antigens and antibodies yet to be identified are more likely to be responsible in these disorders.

Ubiquitin-positive inclusions in different types of multiple system atrophy: distribution and specificity.

Multiple system atrophy (MSA) is a neurodegenerative disorder that encompasses different clinicopathological syndromes, either occurring alone or with a variable degree of overlap. Oligodendroglial, intracytoplasmic argyrophilic and ubiquitin-reactive inclusions are regarded as a histologic hallmark. We examined the distribution and specificity of these ubiquitin-reactive inclusions (UBRI) in 20 cases of MSA (7 cases of sporadic adult olivoponto-cerebellar atrophy [OPCA], 1 case of hereditary adult OPCA, 4 cases of infantile OPCA, 2 cases of Shy-Drager-Syndrome [SDS], 4 cases of striatonigral degeneration [SND] and 2 cases of non-classified atrophy of multiple systems) and 93 control cases with various disorders. Antibodies were used against ubiquitin, PGP 9.5, TAU-protein, glutathion-S-transferase (GST) and metallothionein (MT). Oligodendroglial UBRI were detected in all but 2 cases of sporadic adult MSA and 3 controls, whereas they were absent in hereditary and infantile OPCA. They could also be recognized with Gallyas stain and anti-TAU. Immunopositivity was also seen with GST (11 cases), PGP 9.5 (4 cases) and MT (1 case). Distribution of oligodendroglial UBRI, although not showing topographical linkage to neuronal degeneration in all cases, does not seem to occur in a haphazard pattern.