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Home All Specialties Neurology

Autoimmune encephalitis misdiagnosis in adults can lead to harm

byZoya GomesandYuchen Dai
December 4, 2022
in Neurology
Reading Time: 3 mins read
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1. In this retrospective multicenter study, among a total of 107 outpatients misdiagnosed with autoimmune encephalitis, correct diagnoses included functional neurologic disorder, neurodegenerative disease, primary psychiatric disease, and cognitive deficits from comorbidities and cerebral neoplasms.

2. Overinterpretation of positive serum antibodies and misinterpretation of functional/psychiatric or nonspecific cognitive dysfunction as encephalopathy were found to be major contributors to the misdiagnosis of autoimmune encephalitis.

Evidence Rating Level: 2 (Good)

Study Rundown: In patients presenting with any combination of subacute onset memory loss, altered mental status, and psychiatric symptoms, autoimmune encephalitis is frequently a diagnostic consideration. However, diagnostic mimics of autoimmune encephalitis, including functional neurological disorders, toxic metabolic encephalopathies, and primary psychiatric disease, are far more prevalent than the actual condition itself. While the discovery of novel autoantibodies has improved diagnostic sensitivity for autoimmune encephalitis, there is potential for false-positive, which can contribute to misdiagnosis. As such, the objective of this study was to determine the diseases misdiagnosed as autoimmune encephalitis and the reasons behind misdiagnosis. This retrospective study took place between January 2014 to December 2020. The main outcomes included clinical features, investigations, alternative diagnoses, and potential contributors to the misdiagnosis of autoimmune encephalitis. A total of 107 patients misdiagnosed with autoimmune encephalitis were included in this study, with a median age of 48 years. Correct diagnoses of those misdiagnosed with autoimmune encephalitis included functional neurologic disorder, neurodegenerative disease, primary psychiatric disease, cognitive deficits from comorbidities, and cerebral neoplasm. Potential contributors to the misdiagnosis of autoimmune encephalitis were the overinterpretation of positive serum antibodies and the misinterpretation of functional/psychiatric or nonspecific cognitive dysfunction as encephalopathy. This study emphasized that when evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered to avoid the repercussions of a misdiagnosis.  A limitation of this study was its selection bias in analyzing autoimmune encephalitis misdiagnosed at subspecialty autoimmune neurology clinics, which could have led to an underestimation of the rate of autoimmune encephalitis misdiagnosis.

Click to read the study in JAMA Neurology

Click to read an accompanying editorial in JAMA Neurology

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In-Depth [retrospective cohort]: This study investigated the diseases misdiagnosed as autoimmune encephalitis and the reasons behind the condition’s misdiagnosis. A total of 107 patients misdiagnosed with autoimmune encephalitis were included in this study. The mean (IQR) age was 48 (35.5-60.5) years, and 65 (61%) were female. Data was collected between January 2014 and December 2020 on the following measures: clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions. Among those misdiagnosed with autoimmune encephalitis, correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). The onset was either acute or subacute in 56 (52%) or insidious (>3 months) in 51 (48%). In terms of diagnostic imaging, magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%), and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). When evaluating antibody testing, thyroid peroxidase antibodies were found to be positive in 24 of 62 participants (39%), and neural autoantibodies were identified more often in serum (48 of 105 [46%]) than CSF (7 of 91 [8%]). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). This study found that potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]) and misinterpretation of functional/psychiatric or nonspecific cognitive dysfunction as encephalopathy (41 [38%]).

Image: PD

©2022 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

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