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Updated: Sep 10, 2025
Hippocampal Neuronal Cultures to Detect and Study New Pathogenic Antibodies Involved in Autoimmune Encephalitis
Published on: June 2, 2022
Indications and Diagnostic Yield of Paraneoplastic and Autoimmune Encephalitis Antibody Testing: A Retrospective
Hannah Ford1, Nabil Seery1,2, Tracie Tan1,2
1Department of MS and Neuroimmunology, Alfred Hospital, Melbourne, Victoria, Australia.
Background:
Autoimmune encephalitis (AE) and paraneoplastic syndromes (PNS) are rare disorders with distinct phenotypes. They are increasingly considered in patients with diverse neurologic symptoms, but the clinical context remains critical for diagnosis. Commercial diagnostic assays for AE and PNS are embedded as available tests, however the diagnostic yield and clinical impact of autoantibody testing remain uncertain.
Methods:
This single-center study analyzed all cerebrospinal fluid (CSF) and serum neuronal cell-surface antigen antibody (NCSAA) and intracellular neuronal antigen antibody (INAA) tests requested as part of routine care between 2019 and 2022. Data was collected retrospectively on clinical indications, supportive investigations, diagnosis, and management.
Results:
2161 antibody tests (1371 serum, 790 CSF) from 491 patients were reviewed. The most frequent testing indications were cognitive (26.5%, 130) and psychiatric (20.6%, 101) syndromes, 56.9% (74) and 18.8% (19) of which had associated focal neurology/seizures, respectively. Other common indications included neuropathy, seizures, movement disorders, ataxia, visual symptoms, myelitis, and motor neuron syndromes. Only 1.6% (34) of all autoantibody tests were positive, 38.2% of which were true positives (seven NCSAA, six INAA) and 61.8% (21) were false positives (one NCSAA, twenty INAA). Most false positives (95.2%, 20) were tested in serum only. 0.8% (4) of patients were diagnosed with seropositive AE (LGI1, NMDAR) and 0.8% (4) with INAA-associated syndromes (CRMP5, Yo, GAD65). All had focal neurology/seizures or supportive paraclinical investigations. 98.4% (2127) of antibody tests were negative, 99.1% (2107) of which were true negatives and 0.9% (20) were false negatives (19 seronegative AE, one seronegative PNS). 24% (118) of patients received immunosuppression, 93.2% (110) of whom were antibody negative.
Conclusions:
Our findings demonstrate that indications for autoantibody testing are heterogenous, with a low true positive yield and frequent INAA false positives. This underscores the importance of clinical phenotyping and supportive investigations to prevent inappropriate widespread autoantibody testing.
