Objective:

To evaluate alternative diagnoses in patients referred to neuroimmunology for evaluation of autoimmune encephalitis and/or positive neuronal antibodies.  

Background:

With the increased awareness of autoimmune encephalitis, there has been an increase in misdiagnosis of this condition. This usually results from misinterpretation of clinically irrelevant neural antibodies or improper suspicion of antibody-negative autoimmune encephalitis.  

Design/Methods:

We retrospectively evaluated all cases referred to our center for evaluation of autoimmune encephalitis and/or a positive neural antibody. We calculated the frequency and characteristics of patients who were eventually diagnosed with an alternative diagnosis.  

Results:

The dataset included 125 patients referred in the period from 2017 to 2024. Of the total, 70 patients (56%) were referred for a positive neural antibody and 55 patients (44%) were referred for evaluation of a possible antibody-negative autoimmune encephalitis. An alternative diagnosis was found in 40 patients (32%) including 21 patients (52% of the total patients with an alternative diagnosis) with clinically-irrelevant neural antibodies, and 19 patients (48%) who were referred for evaluation of antibody-negative disease.  The most common clinically irrelevant antibodies included one or more of the following antibodies: GAD65 (10 including 2 with high titer), VGCC (4), VGKC (3), AchG (2), GABA-BR (2), NMDAR (1), LGI1 (1), and GFAP (1). The most common alternative diagnoses in the whole cohort included somatic symptom disorder (30%), primary psychiatric disorder (schizophrenia or bipolar- 17.5%), other immune-mediated disorders (15%), metabolic encephalopathy/myoclonus (7.5%), genetic disorders (7.5%), neurodegenerative disorders (7.5%), and miscellaneous causes(12.5%).  

Conclusions:

Alternative diagnoses are common in patients referred for autoimmune encephalitis evaluation and include mostly psychiatric, metabolic, neurodegenerative, or other autoimmune conditions. Alternative diagnoses are not restricted to patients with low clinical relevance neural antibodies as they are also seen in patients with antibodies of high clinical relevance and in antibody-negative patients.