Authors :
Presenting Author: Jee Hyun Kim, MD, PhD – Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine
Inho Yoon, MD – Ewha Womans University Seoul Hospital
Dongyeop Kim, MD, PhD – Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine
Hyunjin Cho, MD, PhD – Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine
Rationale:
Despite advances in neuroimmunology and the discovery of numerous anti-neuronal antibodies, distinguishing true autoimmune encephalitis (AE) from AE mimics remains challenging. In routine clinical practice, patients referred for “possible AE” often lack confirmatory serologic or cerebrospinal fluid (CSF) markers, yet clinicians must decide whether to initiate immunotherapy based on the clinical symptoms. This uncertainty stems from heterogeneous clinical presentations, variable imaging findings, and inconsistent treatment responses. We therefore sought to characterize, in a real-world cohort, the clinical features of patients ultimately diagnosed with AE versus those found to have alternative (“mimic”) etiologies.
Methods:
We performed a retrospective review of adult patients (≥ 18 years) admitted to the Department of Neurology at Ewha Womans University Seoul Hospital between March 2020 and April 2025, for whom “possible AE” was recorded as a tentative diagnosis. Of 50 patients initially identified, three were excluded due to insufficient clinical history or unavailable CSF results. The remaining 47 patients underwent detailed chart review to capture demographics, presenting symptoms, imaging, and CSF findings, antibody status, final diagnoses, and treatments administered.,
Results:
A total of 47 patients were included in the analysis (57.4% female; mean age 60.6 ± 16.2 years). Among them, 14.8% (6 patients) were ultimately diagnosed with conditions mimicking autoimmune encephalitis (AE), including psychiatric disorder (n = 1), tumorous conditions (n = 2), metabolic encephalopathy (n = 1), sporadic Creutzfeldt–Jakob disease (n = 2), and normal pressure hydrocephalus (n = 1). AE was confirmed in seven patients: six with anti-LGI1 encephalitis (12.7%) and one with anti-NMDA receptor antibody positivity (2.1%). The remaining patients were considered seronegative AE without detectable antineuronal antibodies. The most common clinical presentation was confusion with status epilepticus or lateralizing cortical signs, observed in 48.9% (23/47). Other phenotypes included brainstem symptoms such as diplopia, dysarthria, and gait disturbance (n = 6), akinetic-abulic states (n = 3), and recurrent meningoencephalitis with fever mimicking viral or tuberculous meningitis (n=2). Approximately half of the patients received immunotherapy, including intravenous corticosteroids, IVIG, rituximab, and, in five cases, tocilizumab. Two patients with frequent seizures and subacute dementia showed seizure improvement with steroids, but their cognitive decline persisted. In these cases, further immunotherapy was not pursued due to diagnostic uncertainty.
Conclusions:
In real-world clinical practice, distinguishing AE from its mimics remains challenging. In the absence of confirmatory antineuronal antibodies, clinicians are often hesitant to escalate immunotherapy beyond initial treatments such as steroids or IVIG, particularly in patients presenting with dementia. Further research is needed to characterize the clinical spectrum of seronegative AE and to develop more reliable diagnostic criteria to guide therapeutic decisions.
Funding: NA