@article{0440149d36d5495cb4224ba187b5a300,
title = "Leveraging molecular biomarkers to make the common diagnosis in the uncommon patient",
abstract = "Background and purpose: The factors that predispose to relapse in patients recovering with autoimmune encephalitis (AE) are largely unknown, complicating efforts to distinguish patients with resurgent symptoms who may benefit from additional immune-modulating therapies from those with other causes of impairment. Methods: We report a patient with AE with leucine-rich glioma-inactivated 1 autoantibodies with a typical presentation, but atypical course complicated by treatment-refractory psychoses and progressive cognitive decline. We leveraged emergent molecular biomarkers, including [18F]florbetapir (amyloid) and [18F]flortaucipir AV45 (tau) PET neuroimaging, to evaluate for common neurodegenerative causes of impairment. The patient was followed until death and a brain autopsy performed. Results: No evidence of active inflammation was observed on neuroimaging or cerebrospinal fluid analyses in our patient with resurgent, treatment-refractory cognitive decline. [18F]Florbetapir and [18F]flortaucipir retention were increased in cerebral cortices in a pattern consistent with symptomatic Alzheimer's disease. Immunomodulatory therapies were stopped, and appropriate counseling provided to the patient and family. The patient died 2.4 months following [18F]flortaucipir PET neuroimaging. Brain autopsy confirmed changes typical of Alzheimer's disease without evidence of active inflammation or sequelae of AE, establishing Alzheimer's disease as the likely cause of resurgent symptoms in this patient. Conclusions: Symptoms of age-related neurodegenerative illnesses may emerge following AE, particularly in older patients in whom neurodegenerative dementing illnesses are more common. Molecular biomarkers may aid in the evaluation of treatment-refractory patients with resurgent symptoms and signs, influencing management.",
keywords = "Alzheimer's disease, Amyloid, Autoimmune encephalitis, Flortaucipir, LGI1, PET imaging, Tau",
author = "Day, {Gregory S.} and Gordon, {Brian A.} and Bucelli, {Robert C.} and Perrin, {Richard J.} and Lopez-Chiriboga, {A. Sebastian} and Ances, {Beau M.}",
note = "Funding Information: This study was supported by grants from the National Institutes of Health (K23 AG064029, GSD), the Paula and Roger O. Riney Fund (BMA), the Daniel J Brennan Fund (BMA) and patient-directed donations (GSD). [ 18 F]Flortaucipir precursor and technology were supported by AVID Radiopharmaceuticals (a wholly-owned subsidiary of Eli Lilly and Company; Indianapolis, IN, USA) . Funding Information: This study was supported by grants from the National Institutes of Health (K23 AG064029, GSD), the Paula and Roger O. Riney Fund (BMA), the Daniel J Brennan Fund (BMA) and patient-directed donations (GSD). [18F]Flortaucipir precursor and technology were supported by AVID Radiopharmaceuticals (a wholly-owned subsidiary of Eli Lilly and Company; Indianapolis, IN, USA).GS Day is supported by a career development grant from the NIH (K23AG064029). He owns stock (>$10,000) in ANI Pharmaceuticals (a generic pharmaceutical company). He serves as a topic editor for DynaMed (EBSCO), overseeing development of evidence-based educational content, and as the Clinical Director of the Anti-NMDA Receptor Encephalitis Foundation (Inc, Canada; uncompensated). BA Gordon takes part in clinical trials sponsored by Roche and Eli Lilly (via DIAN-TU) outside of the reported work. RC Bucelli has served on an advisory board for MT Pharma, has a consulting role with Biogen, has Equity in Neuroquestions.LLC and receives a recurring annual gift from a patient's family for research on neuralgic amyotrophy. RJ Perrin takes part in clinical trials sponsored by Roche and Eli Lilly (via DIAN-TU) outside of the reported work. AS Lopez-Chiriboga reports no disclosures. BM Ances reports no disclosures. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",
year = "2021",
month = mar,
day = "15",
doi = "10.1016/j.jneuroim.2021.577474",
language = "English",
volume = "352",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
}