Paraneoplastic autonomic neuropathies and GI dysmotility.

A number of the well-recognized autoimmune and paraneoplastic neurologic syndromes commonly involve the autonomic nervous system. In some cases, the autonomic nerves or ganglia are primary targets of neurologic autoimmunity, as in immune-mediated autonomic ganglionopathies. In other disorders such as encephalitis, autonomic centers in the brain may be affected. The presence of autonomic dysfunction (especially gastrointestinal dysmotility) is sometimes overlooked even though this may contribute significantly to the symptom burden in these paraneoplastic disorders. Additionally, recognition of autonomic features as part of the clinical syndrome can help point the diagnostic evaluation toward autoimmune and paraneoplastic etiologies. As with other paraneoplastic disorders, the clinical syndrome and the presence and type of neurologic autoantibodies help to secure the diagnosis and direct the most appropriate investigation for malignancy. Optimal management for these conditions typically includes aggressive treatment of the neoplasm, immunomodulatory therapy, and symptomatic treatments for orthostatic hypotension and gastrointestinal dysmotility.

Responsiveness of UMSARS and other clinical measures in a longitudinal structured care clinic for multiple system atrophy.

PURPOSE: As understanding of multiple system atrophy (MSA) pathophysiology improves, clinical trials of disease-modifying therapies are starting. Outcome measures responsive to disease progression will be critical, but the United MSA Rating Scale (UMSARS) has limitations. The MSA multidisciplinary clinic at the University of Texas Southwestern is a longitudinal clinic with structured assessments performed at fixed time intervals. The objective of this study was to evaluate the performance of clinical measures in assessing MSA progression over time. METHODS: Data from 73 subjects with clinically diagnosed MSA were analyzed using repeated measures correlation models. Observations were made every 4 months, with up to 3 years of data included for each patient. RESULTS: UMSARS-I and UMSARS-II correlated positively with the MSA Quality of Life (QOL) scale. The rate of change was 3.12 points per year (ppy) for UMSARS-I and 5.55 ppy for UMSARS-II. Some individual UMSARS questions contributed more significantly than others to overall UMSARS rate of change. Based on this finding, and using repeated measures correlations between question combinations and QOL, an optimization of UMSARS parts I and II was curated. The amended UMSARS-I included 8 of the 12 subquestions, and the amended UMSARS-II included 10 of the 14 subquestions. CONCLUSIONS: Data from a longitudinal MSA clinic allows better characterization of the performance of UMSARS as a clinical outcome measure. A curated set of UMSARS questions appears more responsive to change and accounts for correlation with QOL, and could be the starting point for an improved MSA outcome measure.

Symptomatic use of carbidopa in autonomic disorders.

Carbidopa is being explored as a novel therapy for hyperadrenergic symptoms of autonomic disorders, due to its potential to decrease peripheral catecholamine levels. This study retrospectively characterized patients in our autonomic clinic who were prescribed carbidopa for open label treatment of autonomic symptoms. 23 patients were included; approximately half had postural orthostatic tachycardia syndrome. Those with documented plasma catecholamines had elevated standing norepinephrine. Patients typically had multiple comorbidities and multiple failed therapies. 19 took carbidopa (typically 25 mg three times daily); 12 continued it for longer than 3 months. 11 patients reported better symptom control with carbidopa, most commonly tremor and gastrointestinal dysfunction. 4 patients reported side effects. In this small retrospective study, carbidopa was well tolerated in patients with dysautonomia, and half reported symptomatic benefit. Larger, placebo-controlled trials are warranted for further investigation of this therapy.

Autoimmune autonomic neuropathies and ganglionopathies: epidemiology, pathophysiology, and therapeutic advances.

Autonomic disorders can be the result of autoimmunity. The classic, well-characterized example is autoimmune autonomic ganglionopathy (AAG), in which antibodies against the ganglionic nicotinic acetylcholine receptor impair autonomic transmission, causing autonomic failure, which responds to immunotherapy. However, a number of other autoimmune disorders cause autonomic failure through a variety of mechanisms. In this article, we review autoimmune disorders causing impairment of the peripheral autonomic nervous system (ganglia and nerves), including AAG, other autoimmune autonomic neuropathies, paraneoplastic autonomic neuropathies, and neuromuscular and rheumatologic diseases with autonomic symptomatology. Awareness of primary autoimmune autonomic disorders and the autonomic manifestations of other autoimmune diseases promotes timely diagnosis and appropriate management, including supportive care for unpleasant or dangerous autonomic dysfunction, a search for underlying malignancy when indicated, and the use of immunotherapy when appropriate. A better understanding of the underlying pathophysiology aids in the judicious use and selection of immunotherapy.

Seronegative autoimmune autonomic neuropathy: a distinct clinical entity.

PURPOSE: Autoimmune autonomic ganglionopathy (AAG) is associated with ganglionic acetylcholine receptor (gAChR) antibodies. We describe a similar but distinct series of patients with autoimmune autonomic failure lacking this antibody. METHODS: Retrospective chart review. RESULTS: Six patients presented with subacute autonomic failure, seronegative for gAChR antibodies. Orthostatic hypotension and gastrointestinal complaints were common. Autonomic testing revealed predominant sympathetic failure and no premature pupillary redilation. All patients had sensory symptoms and/or pain, which was severe in three. Immunotherapy with plasma exchange, intravenous immunoglobulin, and rituximab was ineffective. Three patients responded to intravenous steroids. CONCLUSION: In these cases of autoimmune autonomic failure, key differences from seropositive AAG emerge. Testing showed prominent sympathetic (rather than cholinergic) failure, specific pupillary findings of AAG were absent, and sensory symptoms were prominent. AAG responds to antibody-targeted immunotherapy, while these patients responded best to steroids. This seronegative autoimmune autonomic neuropathy is a distinct clinical entity requiring a different treatment approach from AAG.