Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria
Abstract Objective We describe neurologic phenotype, clinical associations, and outcomes in autoimmune brainstem encephalitis. Methods Medical records of neural‐IgG positive autoimmune brainstem encephalitis patients diagnosed at Mayo Clinic (January 1, 2006–December 31, 2022) were reviewed. Results...
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Wiley
2025-01-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.52273 |
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| author | Michael Gilligan Smathorn Thakolwiboon Emma Orozco Samantha Banks Eoin P. Flanagan Sebastian Lopez‐Chiriboga Jan‐Mendelt Tillema John R. Mills Sean J. Pittock Cristina Valencia Sanchez Anastasia Zekeridou Divyanshu Dubey Andrew McKeon |
| author_facet | Michael Gilligan Smathorn Thakolwiboon Emma Orozco Samantha Banks Eoin P. Flanagan Sebastian Lopez‐Chiriboga Jan‐Mendelt Tillema John R. Mills Sean J. Pittock Cristina Valencia Sanchez Anastasia Zekeridou Divyanshu Dubey Andrew McKeon |
| author_sort | Michael Gilligan |
| collection | DOAJ |
| description | Abstract Objective We describe neurologic phenotype, clinical associations, and outcomes in autoimmune brainstem encephalitis. Methods Medical records of neural‐IgG positive autoimmune brainstem encephalitis patients diagnosed at Mayo Clinic (January 1, 2006–December 31, 2022) were reviewed. Results Ninety‐eight patients (57 male) were included. Median age of symptom onset was 51 years (range, 8 months‐85 years). Frequent presenting features were ≥1: diplopia (80%), ataxia (78%), dysarthria (68%), vestibulocochlear symptoms (67%), dysphagia (61%), nausea/vomiting (42%), and facial weakness (32%). Altered mental status (11%) was uncommon. Neural antibodies detected were as follows: KLHL‐11 (26 patients), GAD65 (high titer, 12), ANNA‐1 (anti‐Hu, 8), ANNA‐2 (anti‐Ri, 8), Ma2 (7), IgLON‐5 (6), AQP4 (6), MOG (4), glycine receptor (4), GQ1B (4), PCA‐1 (anti‐Yo, 4), DPPX (2), neurochondrin (2), neurofilament (2), NMDA‐R (2), AGNA‐1 (SOX‐1, 1), ANNA‐3 (DACH1, 1), amphiphysin (1), CRMP‐5 (1), ITPR‐1 (1), PCA‐Tr (DNER, 1), and PDE10A (1). Cancer was identified in 55 patients: germ cell (23 patients; 3 extra‐testicular), ductal breast adenocarcinoma (8), small cell carcinoma (6, lung 4), adenocarcinomas (6), neuroendocrine carcinoma (3), hematologic (2), squamous cell (2), and other (7). Median modified Ranking score (mRS) at last follow‐up was 3 (range, 0–6). Factors associated with poor outcome included abnormal brain MRI, bulbar symptoms, and elevated CSF IgG index. Kaplan–Meier analysis revealed faster progression to wheelchair in patients who were immunotherapy refractory and with elevated CSF IgG index. Diagnostic criteria for autoimmune brainstem encephalitis (definite and probable) are proposed. Interpretation Autoimmune brainstem encephalitis is a distinct clinical subphenotype of autoimmune encephalitis. Abnormal brain MRI, bulbar symptoms, and elevated CSF‐IgG index associate with poor outcome. |
| format | Article |
| id | doaj-art-5fd04b048a2141dcbad8b15fc9e99966 |
| institution | Kabale University |
| issn | 2328-9503 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-5fd04b048a2141dcbad8b15fc9e999662025-01-21T05:41:42ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-01-0112121322510.1002/acn3.52273Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteriaMichael Gilligan0Smathorn Thakolwiboon1Emma Orozco2Samantha Banks3Eoin P. Flanagan4Sebastian Lopez‐Chiriboga5Jan‐Mendelt Tillema6John R. Mills7Sean J. Pittock8Cristina Valencia Sanchez9Anastasia Zekeridou10Divyanshu Dubey11Andrew McKeon12Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USADepartment of Neurology Mayo Clinic Rochester Minnesota USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USADepartment of Neurology Mayo Clinic Rochester Minnesota USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USADepartment of Neurology Mayo Clinic Jacksonville Florida USADepartment of Neurology Mayo Clinic Rochester Minnesota USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USADepartment of Neurology Mayo Clinic Phoenix Arizona USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USAAbstract Objective We describe neurologic phenotype, clinical associations, and outcomes in autoimmune brainstem encephalitis. Methods Medical records of neural‐IgG positive autoimmune brainstem encephalitis patients diagnosed at Mayo Clinic (January 1, 2006–December 31, 2022) were reviewed. Results Ninety‐eight patients (57 male) were included. Median age of symptom onset was 51 years (range, 8 months‐85 years). Frequent presenting features were ≥1: diplopia (80%), ataxia (78%), dysarthria (68%), vestibulocochlear symptoms (67%), dysphagia (61%), nausea/vomiting (42%), and facial weakness (32%). Altered mental status (11%) was uncommon. Neural antibodies detected were as follows: KLHL‐11 (26 patients), GAD65 (high titer, 12), ANNA‐1 (anti‐Hu, 8), ANNA‐2 (anti‐Ri, 8), Ma2 (7), IgLON‐5 (6), AQP4 (6), MOG (4), glycine receptor (4), GQ1B (4), PCA‐1 (anti‐Yo, 4), DPPX (2), neurochondrin (2), neurofilament (2), NMDA‐R (2), AGNA‐1 (SOX‐1, 1), ANNA‐3 (DACH1, 1), amphiphysin (1), CRMP‐5 (1), ITPR‐1 (1), PCA‐Tr (DNER, 1), and PDE10A (1). Cancer was identified in 55 patients: germ cell (23 patients; 3 extra‐testicular), ductal breast adenocarcinoma (8), small cell carcinoma (6, lung 4), adenocarcinomas (6), neuroendocrine carcinoma (3), hematologic (2), squamous cell (2), and other (7). Median modified Ranking score (mRS) at last follow‐up was 3 (range, 0–6). Factors associated with poor outcome included abnormal brain MRI, bulbar symptoms, and elevated CSF IgG index. Kaplan–Meier analysis revealed faster progression to wheelchair in patients who were immunotherapy refractory and with elevated CSF IgG index. Diagnostic criteria for autoimmune brainstem encephalitis (definite and probable) are proposed. Interpretation Autoimmune brainstem encephalitis is a distinct clinical subphenotype of autoimmune encephalitis. Abnormal brain MRI, bulbar symptoms, and elevated CSF‐IgG index associate with poor outcome.https://doi.org/10.1002/acn3.52273 |
| spellingShingle | Michael Gilligan Smathorn Thakolwiboon Emma Orozco Samantha Banks Eoin P. Flanagan Sebastian Lopez‐Chiriboga Jan‐Mendelt Tillema John R. Mills Sean J. Pittock Cristina Valencia Sanchez Anastasia Zekeridou Divyanshu Dubey Andrew McKeon Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria Annals of Clinical and Translational Neurology |
| title | Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria |
| title_full | Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria |
| title_fullStr | Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria |
| title_full_unstemmed | Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria |
| title_short | Autoimmune brainstem encephalitis: Clinical associations, outcomes, and proposed diagnostic criteria |
| title_sort | autoimmune brainstem encephalitis clinical associations outcomes and proposed diagnostic criteria |
| url | https://doi.org/10.1002/acn3.52273 |
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