Leveraging molecular biomarkers to make the common diagnosis in the uncommon patient

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.

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.

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.

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.