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Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody
Jeroen Kerstens1, Marco W J Schreurs1, Juna M de Vries1
1From the Department of Neurology (J.K., J.M.V., R.F.N., J.B., Y.C., R.W.v.S., M.A.A.M.d.B., M.H.v.C.-H., A.E.M.B., M.V., S.C.F., M.M.P.N., M.P., P.A.E.S.S., M.J.T.); Department of Immunology (M.S., S.B., S.V.), Laboratory Medical Immunology, Erasmus University Medical Center, Rotterdam; Department of Neurology (M.A.A.M.D.B.), Elisabeth-TweeSteden Hospital, Tilburg; Department of Neurology (A.v.S.), Haaglanden Medical Center, The Hague; Central Diagnostic Laboratory (J.D.), Maastricht University Medical Center; Central Diagnostic Laboratory (H.G.O.); Department of Neurology (C.J.M.F.), Utrecht University Medical Center; Department of Medical Microbiology and Immunology (B.M.), Saint Antonius Hospital, Nieuwegein; Laboratory of Medical Microbiology and Immunology (A.C.M.P.), Elisabeth-TweeSteden Hospital, Tilburg; Department of Neurology (A.M., C.C.D.); Clinical Laboratory (M.A.C.B.), Máxima Medical Center, Veldhoven; Departments of Neurology and Human Genetics (M.M.V.), Radboud University Medical Center, Nijmegen; and Department of Neurology (E.I.H.), Zuyderland Medical Center, Heerlen, The Netherlands.
Autoimmune encephalitis and paraneoplastic neurologic syndromes are increasing. While antibody tests show high specificity, positive predictive values can be low, especially for intracellular antigen tests in serum. Further research is needed.
Area of Science:
- Neurology
- Immunology
- Epidemiology
Background:
- Autoimmune encephalitis (AIE) and paraneoplastic neurologic syndromes (PNSs) are antibody-associated disorders with increasing diagnostic tests.
- There is a need for population-based data on the epidemiology and real-world performance of these antibody tests.
Purpose of the Study:
- To assess the epidemiology and incidence of AIE/PNS in the Netherlands.
- To evaluate the real-world performance of commercial antibody tests for AIE/PNS.
Main Methods:
- Nationwide retrospective cohort study of serum and CSF samples tested for various intracellular and extracellular antibodies from 2016-2021.
- Calculated sensitivity, specificity, PPV, and NPV for antibody tests.
- Assigned AIE/PNS diagnoses and calculated incidence rates.
Main Results:
- Over 30,000 samples were analyzed, with 9.5% testing positive.
- Most antibody tests demonstrated high sensitivity and specificity (>95%).
- Positive predictive values were moderate to poor for some tests, particularly serum tests for intracellular antibodies (25%-80%).
- The incidence of AIE/PNS increased from 4.70 to 5.76 per million person-years between 2016 and 2021.
- Anti-NMDAR, anti-LGI1, anti-Hu, and anti-GAD65 were the most common diagnoses.
Conclusions:
- Commercial antibody tests generally perform well, but limitations exist, especially regarding positive predictive values in rare diseases.
- Increasing incidence trends for antibody-associated AIE/PNS were observed.
- Careful interpretation of test results is crucial, considering specificity and PPV.
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