A54-24 Lost in the Fog: The Hidden Layer of Encephalitis in Post-Arrest Encephalopathy

Altered mental status in the elderly often represents overlapping metabolic, infectious, autoimmune, or hypoxic processes. When neuroimaging is unrevealing, the distinction between reversible and irreversible encephalopathy becomes particularly challenging. This case of subacute encephalopathy with GPEDs and inflammatory cerebrospinal fluid findings after cardiac arrest highlights the difficulty of differentiating autoimmune or infectious encephalitis from post-anoxic injury. A 75-year-old man with hypertension, type 2 diabetes, and urothelial carcinoma of the bladder presented with three days of generalized weakness & fluctuating mentation. His family reported gradual cognitive decline over the prior year, which had rapidly accelerated in the preceding month to full functional dependence. On admission, he was afebrile, hemodynamically stable, but disoriented. Laboratory evaluation was unremarkable. Urinalysis suggested infection and empiric antibiotics were started. However, the degree of encephalopathy was disproportionate to an infection alone. EEG demonstrated GPEDs with triphasic morphology, findings classically associated with toxic-metabolic encephalopathy. Given his subacute decline, neurology raised concern for an autoimmune or infectious encephalitis. During hospitalization, he experienced asystolic cardiac arrest with return of spontaneous circulation after ten minutes of CPR. He was intubated and transferred to the ICU for post-cardiac arrest care. Although hypoxic-ischemic brain injury (HIBI) was suspected, the pre-arrest decline and EEG findings prompted further evaluation. Lumbar puncture showed inflammatory cerebrospinal fluid (27 WBC/μL, 91% lymphocytes; 266 RBC/μL; protein 300 mg/dL; normal glucose), inconsistent with isolated HIBI and suggestive of underlying encephalitis. Repeat EEG findings were unchanged. A multidisciplinary team initiated empiric therapy with acyclovir, ceftriaxone, doxycycline, and high-dose IV methylprednisolone (1 g daily ×5). Comprehensive infectious (West Nile, arbovirus, Lyme) and autoimmune (anti-NMDA, Hu, LGI1, GABA, AMPA) panels were negative. Despite aggressive management, he failed to recover meaningful neurologic function and required tracheostomy and PEG for long-term care. This case underscores the diagnostic and prognostic complexity of encephalopathy after cardiac arrest. Persistent GPEDs with inflammatory CSF findings created a diagnostic crossroads between possible Lyme-associated neuroinfection, autoimmune encephalitis, and post-anoxic injury. Graus et al. propose that possible autoimmune encephalitis may be diagnosed when subacute cognitive decline in less than 3 months coexists with CSF pleocytosis or new focal findings once alternative causes are excluded. Thus, even after cardiac arrest, clinicians should not attribute encephalopathy solely to hypoxia when CSF inflammation is present. Early CSF analysis, integration of EEG findings, and a parallel empiric “treat-while-testing” approach are essential in evaluating ambiguous encephalopathy, as timely recognition of reversible etiologies may alter prognosis.