Posted on July 17, 2022
Mayo Clin Proc 1989;64:617C628
Mayo Clin Proc 1989;64:617C628. seronegative putative autoimmune autonomic ganglionopathy. Plasma exchange or combined therapy with immunosuppressive agents should be considered in patients who do not benefit from IV immunoglobulin alone. GLOSSARY AAG = autoimmune autonomic ganglionopathy; AB = ganglionic 3 acetylcholine receptor Bay 59-3074 antibody; AChR = acetylcholine receptor; AE = antecedent event; ASP = autonomic symptom profile; Aza = azathioprine; BP = blood pressure; CASS = Composite Autonomic Severity Score; CCS = COMPASS Change Score; COMPASS = Composite Autonomic Symptom Score; GI = gastrointestinal; HR_db = heart rate response to deep breathing; IVIg = IV immunoglobulin; LGI = lower gastrointestinal tract symptoms; Myc = mycophenolate mofetil; OI = orthostatic intolerance; OH = orthostatic hypotension; NA = not applicable; NCS = nerve conduction studies; PE = plasma exchange; QSART = quantitative sudomotor axon reflex test; TST = thermoregulatory sweat test; UGI = upper gastrointestinal tract symptoms; VR = Valsalva ratio. Autoimmune autonomic ganglionopathy (AAG) is characterized by prominent and selective involvement of the peripheral autonomic nervous system due to an autoimmune process.1 Patients typically develop generalized autonomic failure including orthostatic hypotension, Rabbit Polyclonal to Desmin anhidrosis, and parasympathetic dysfunction. The onset can be acute, subacute, or gradual.1C3 The course is variable, with spontaneous improvement occurring in about one-third of patients,1 but recovery is typically incomplete. In about 50% of patients with AAG, ganglionic (3-type) acetylcholine receptor (AChR) autoantibodies are detected in high titers.4 Antibody levels correlate with the severity of dysautonomia.2,3 This underlying immune-mediated pathogenesis in AAG has led to individual case reports showing clinical improvement with the use of immunotherapy including plasma exchange (PE), corticosteroids, and IV immunoglobulin (IVIg).5C11 The clinical presentation, disease progression, and autonomic function tests do not distinguish between seropositive and seronegative putative AAG patients,3 and some individual seronegative putative AAG patients respond to immunotherapy as well (P.A.L., unpublished observations). This observation suggests that the clinical phenotype of AAG, persistent severe autonomic failure, unassociated with ganglionic AChR antibodies could have another underlying autoimmune etiology and may respond to immunotherapy. The aim of our study is to evaluate the efficacy of IVIg, PE, and immunosuppressants alone or in combination therapy in both seropositive and seronegative putative AAG patients. METHODS Patients. We studied six patients with a clinical diagnosis of AAG. Patients with dysfunction of the sympathetic, parasympathetic, and enteric nervous systems with a ganglionic AChR autoantibody titer of 0.05 Bay 59-3074 nmol/L prior to treatment were defined as Bay 59-3074 having antibody-positive AAG.2 In the absence of a confirmatory ganglionic antibody titer, patients with idiopathic pandysautonomia were required to have the following characteristics to be considered seronegative putative AAG: 1) orthostatic hypotension, defined as a systolic blood pressure reduction of 30 mm Hg or mean blood pressure reduction of 20 mm Hg occurring within 3 minutes of head-up tilt2; 2) significant gastrointestinal symptoms with predominant upper gastrointestinal dysmotility; and 3) severe autonomic dysfunction on standardized autonomic testing (Composite Autonomic Severity Score 7; see the corresponding section under Methods for details). Additional criteria suggestive of seronegative putative AAG include pupillary involvement, prior antecedent event (i.e., viral illness), evidence of tissue inflammation (i.e., nerve, sweat gland), and subacute onset. Onset was defined as the time to peak autonomic dysfunction (subacute 3 months, gradual 3 months). Comprehensive clinical, hematologic, biochemical, and serologic assessments of all patients were performed at baseline. Patients with known causes of autonomic failure including multiple system atrophy, diabetes, amyloidosis, rheumatologic disorders, and known malignancies were excluded. All the patients but one (case 4, table 1) were free of any other neuronal autoantibody on standard paraneoplastic antibody panels (Mayo Clinic, Rochester, MN). Table 1.