Abstract Some forms of peripheral autonomic dysfunction especially enteric neuropathy and subacute panautonomic failure occur as autoimmune phenomena either in isolation or in the context of cancer. Access to Document Link to publication in Scopus. Fingerprint Dive into the research topics of 'Antibody testing as a diagnostic tool in autonomic disorders. Together they form a unique fingerprint. View full fingerprint. Results: There was a total of panels sent on individuals.
Twenty percent individuals had more than one panel requested. Forty-seven overlapping evaluations were performed in 46 7.
Fifty-four 8. Ten repeat evaluations showed a change in antibody status, of which only two were clinically significant. There was a single case where clinical management was affected by repeat autoantibody evaluation. Repeat autoantibody testing is a commonplace practice yet yielded novel information in only a minority of cases. There is limited utility in these practice patterns.
Future efforts should be directed at the development and standardization of neurological autoimmune and paraneoplastic autoantibody testing practice standards. Autoimmune neurology is a rapidly evolving field of study, largely fueled by the discovery of autoantibodies targeting neuronal and glial proteins. Antibody-mediated neurological disorders typically present with severe, progressive neurological symptoms, and timely treatment with immunotherapy can result in dramatic improvement and favorable long-term outcomes 1.
Antibody testing for autoimmune and paraneoplastic neurological disorders is available through several commercial laboratories in the United States. Best practices for neurological antibody testing have not been defined, but it is generally advised that both serum and cerebrospinal fluid CSF samples be submitted for testing, as certain antibodies are more sensitive in CSF 2.
The growing options for antibody testing can create confusion amongst ordering clinicians, leading them to order multiple panels during a single encounter to ensure a comprehensive evaluation. Additionally, antibody testing is occasionally repeated in the same patient during a future patient encounter. Whether these practices increase detection of antibody-mediated neurological disorders has not been systematically examined.
In this study, we determined the frequency of overlapping and repeat antibody testing for autoimmune and paraneoplastic disorders in patients presenting to the University of Texas Southwestern Medical Center UTSW and investigated how these practices informed clinical decision making and management. The study was approved by the UTSW institutional review board.
These patients were cross matched with a list of requests for antibody testing submitted to the UTSW clinical laboratory from to Patients from with more than one antibody test requested during this period were included in the final analysis see Figure 1. A paired serum and CSF evaluation was defined as a request for serum and CSF panels obtained within 14 days of each other.
The day time period was chosen to demarcate overlapping and repeat testing as, in our experience, results from initial testing tend to return in this timeline. For those individuals with repeat autoantibody evaluations, the results of the panel testing were recorded. The number of results with a change in antibody status e. A single evaluation was considered positive if any of the individual panels returned with a positive result.
If a single individual had more than one repeat evaluation, the additional repeat evaluations were compared to the most recent evaluation for the purpose of determining change in antibody status. If an antibody status change was found, this was sorted into one of four categories based on comparison of identical or non-identical panels and positive to negative or negative to positive panel transition see Figure 1. The time between repeat evaluations was determined by the date of the last panel in the first evaluation to the date of the first panel in the second evaluation.
For individuals who had one or more repeat evaluations with a change in autoantibody status, medical records were reviewed for changes in clinical diagnosis and medical decision making based on repeat panel results. Clinical diagnoses were abstracted from neurology consultation notes and billing codes. There was a total of antibody panels submitted on individuals in The average age of this group was Ultimately 24 cases were due to autoimmune or paraneoplastic disorders.
One hundred and twenty six individuals There were an additional 45 panels ordered as repeat antibody evaluations from to on these individuals. In total, panels Six patients had both overlapping and repeat evaluations performed. There were 64 paired serum and CSF evaluations panels, Only One individual had two paired serum and CSF evaluations performed. Overlapping evaluations included 98 panels While the majority of overlapping evaluations consisted of two panels per evaluation, four individuals had overlapping evaluations with three panels ordered.
One individual additionally had two overlapping evaluations. The average time between repeat evaluations was days median days, range —1, days.
Identical panels were requested as a part of 41 Eight individuals underwent more than one repeat evaluation, with two individuals having three repeat evaluations. Ten repeat evaluations had a change in antibody status Figure 1.
Eight repeat evaluations One evaluation compared identical panels and seven compared non-identical panels. Two evaluations 2. The transition in antibody status changed clinical management in two cases. In the first case, ASMs were stopped in a patient with leucine-rich glioma-inactivated 1 LGI1 antibody associated seizures following panel transition from positive to negative. For the second case immunotherapy was started in an individual presenting with encephalopathy following a new positive glutamic acid decarboxylase 65 GAD antibody.
There were no cases in which new antibody panel results correlated to a change in clinical diagnosis or prompted a malignancy screening. Overlapping and repeat evaluations for suspected autoimmune and paraneoplastic disorders occurred frequently at our medical center, occurring in The results of these evaluations rarely differed from the initial evaluation and seldom influenced clinical management.
Our study suggests that, at our center, there is wide variability in practice habits surrounding autoantibody evaluations, reflecting the increasingly complex nature of autoantibody testing. Generally agreed upon practice standards include concurrent serum and CSF evaluations for suspected central nervous system autoimmune disorders—a practice that was only implemented a fraction of the time in this study.
The vast majority of unmatched panels There are numerous potential explanations for serum testing lacking a matched CSF sample. Lumbar punctures are invasive, time consuming procedures, which some patients may refuse in the outpatient setting. Additional medical factors, including body habitus, infection risk, and mental status, may limit the ability to perform a lumbar puncture.
J Neurosci — Vernino S, Kryzer T, Lennon V Autoantibodies in autoimmune autonomic neuropathies and neuromuscular hyperexcitability disorders. Clin Cancer Res — Vernino S, Lennon VA Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. J Neuroimmunol — N Engl J Med — Neurol Clin — Eur Neurol — Vincent A Unravelling the pathogenesis of myasthenia gravis. Nature Rev Immunol — Trends Neurosci — Trans Am Neurol Assoc — Download references.
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