ArticleJournal of neurology2026
Alternative diagnoses in patients referred to neuroimmunology for autoimmune encephalitis evaluation.
Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo evaluate alternative diagnoses in patients referred to neuroimmunology for evaluation of autoimmune encephalitis (AE) and/or positive neural antibodies.
backgroundWith increased awareness of AE, AE misdiagnosis has increased-often from improper suspicion of AE or misinterpretation of clinically irrelevant neural antibodies.
methodsWe retrospectively evaluated all cases referred to our center for AE evaluation and/or a positive neural antibody. We evaluated the frequency and characteristics of patients eventually diagnosed with an alternative diagnosis.
resultsA total of 119 patients were referred between 2017 and 2024. Twenty-two were referred for a positive neural antibody, and seven for possible antibody-negative AE after testing negative before referral. Eighty-one patients1 were tested by our center after inpatient admission or outpatient referral. Our center deemed antibody testing unnecessary in 9 patients. Overall, 74 patients were antibody-positive (62%). An alternative diagnosis was found in 60 patients (50.4%), including 32 with positive neural antibodies, and 28 antibody-negative patients. Of patients with alternative diagnoses, 22 had low-clinical-relevance antibodies: low-titer GAD65 (12), AchG (6), VGCC (5), and double-seronegative VGKC (4). Conversely, 10 had antibodies classically considered highly clinically relevant: high-titer GAD65 (4), GABA-BR (2), NMDAR (1), LGI-1 (1), CASPR2 (1), and GFAP (1). Of these, two had concurrent low-titer GAD65. The most common alternative diagnoses included other immune-mediated disorders (28.3%), somatic symptom disorder (23.3%), primary psychiatric disorders (11.7%), metabolic encephalopathy/myoclonus (5%), neurodegenerative disorders (5%), and at 3.3% each, Down syndrome regression disorder, genetic disorders, neuromuscular disorders, and posterior reversible encephalopathy syndrome.
conclusionAlternative diagnoses are common in patients referred for AE evaluation and include mostly psychiatric and other autoimmune conditions. Alternative diagnoses are not restricted to patients with low-clinical-relevance neural antibodies-they are also seen in patients with high-clinical-relevance antibodies and antibody-negative patients.
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