Fatal Rapidly Progressive Encephalopathy Mimicking Depression: A Diagnostic Dilemma of Suspected Seronegative Autoimmune Encephalitis

The diagnosis of "seronegative" autoimmune encephalitis (AE) is challenging, particularly when patients present with psychiatric symptoms but lack definitive neurological signs or specific autoantibodies. A fatal case of suspected seronegative AE in a male patient in his 50s with no documented history of psychiatric illness was reported. The patient initially presented with depressive mood and apathy, leading to a diagnosis of major depressive disorder. Despite antidepressant treatment, he rapidly exhibited confusion, agitation, and catatonic features. Conventional diagnostic procedures, including head magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cell counts, yielded no remarkable findings. However, he exhibited paroxysmal autonomic instability (tachycardia and fever) and diffuse slowing on electroencephalography. CSF analysis revealed positive oligoclonal bands (OCBs), while neuronal surface antibody panels were negative. A clinical diagnosis of suspected seronegative AE was made based on the subacute progression and inflammatory markers, despite the absence of classic focal neurological signs or MRI abnormalities. Aggressive immunotherapy, encompassing high-dose corticosteroids, intravenous immunoglobulin, and plasma exchange, did not demonstrate any improvement. He succumbed to respiratory failure on Day 100. This case underscores the difficulty in distinguishing seronegative AE from other rapidly progressive encephalopathies or primary psychiatric disorders. While OCBs may indicate inflammation, relying solely on non-specific markers in the absence of stringent diagnostic criteria can result in diagnostic uncertainty. In treatment-refractory cases, clinicians must maintain a broad differential diagnosis, including neurodegenerative and neoplastic conditions.