Autoimmune Dysautonomia Evaluation
Published: February 2011
Hot Topic Q&A is an opportunity for viewers to submit questions to the Hot Topic presenter. The opportunity to submit questions for this topic is now closed.
The following questions were submitted by viewers and answered by the presenter, Andrew McKeon, MB, BCh, MD (N-AI), consultant in the Neuroimmunology Laboratory in the Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota. Questions are presented as submitted (unedited).
Are there patients that test positive for ANNA-1, CRMP5, and amphiphysin that do not have autoimmune dysautonomia? If so, what may be indicated by this seropositivity?
Patients with paraneoplastic neurological disorders in general are better characterized by the rapidity of onset and progression of an often multifocal neurological disorder, rather than one specific syndrome. Frequently 2 or more of the antibodies mentioned in the query can coexist in the same patient. However, some presentations are "classical," including, but by no means restricted to, sensory ganglionopathy (ANNA-1), basal ganglionitis (CRMP-5 IgG) and a stiff-man like presentation (amphiphysin).
Do you ever have false positives or negatives with dysautonomia and what do you do to rule out either?
False negatives are not uncommon; we can only test for what we know about, and the clinical presentation may be suspicious for an autoimmune disorder in the absence of an identified antibody marker. False positivity is more difficult to comment on since the context is crucial. I think it is unlikely to be an issue in patients with clinical findings consistent with an autoimmune dysautonomia (objective autonomic abnormalities, a subacute presentation and an immunotherapy response). These antibodies have rarely been identified in "healthy" controls.
In one of our patients who has a striated muscle antibody titer =1:40, the additional testing was normal. Is this someone who still has an autoimmune basis for their symptoms and should I investigate for an underlying thymoma or other neoplasm?
I think it depends on the context. Certainly a striational antibody detected in isolation may be a clue to autoimmunity, but is no more specific than that and is not a reliable marker of thymoma when detected in isolation. If the rest of the picture fits (a subacute onset and rapid progression, definite objective abnormalities without other clear reasons for the presentation and a history of other autoimmune disease and/or cancer), then I think that finding may be a further clue to bolster confidence that this is an autoimmune diagnosis.