When the Mind Fails: A Mysterious Case of Concurrent Neurosyphilis, Herpes Simplex Virus Encephalitis, and Suspected Autoimmune Encephalitis

Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic viral encephalitis and is associated with significant morbidity and mortality if not promptly recognized and treated. Neurosyphilis is now rare due to the widespread use of antibiotics. This case report discusses a 65-year-old man with no notable past medical history who presented to the emergency department with acute shortness of breath, choking, and altered mental status, following six months of cognitive and behavioral decline. Initial evaluations revealed fever and hypoxia, necessitating urgent intubation. While most laboratory tests were unremarkable, cerebrospinal fluid (CSF) analysis demonstrated positivity for the venereal disease research laboratory (VDRL) test, HSV-1, and N-methyl-D-aspartate (NMDA) receptor antibodies, indicating the presence of neurosyphilis, HSV encephalitis, and questionable autoimmune encephalitis. Imaging studies showed chronic microvascular disease without significant lesions. The interplay of infectious and autoimmune processes complicated the clinical picture, emphasizing the need for thorough diagnostic evaluation. Prompt treatment with acyclovir for HSV encephalitis and penicillin for neurosyphilis was critical. This case underscores the necessity of considering multiple etiologies in patients with rapid cognitive decline, highlighting the importance of timely recognition and appropriate management in complex clinical scenarios.