Abstract Introduction Calcineurin inhibitors can precipitate posterior reversible encephalopathy syndrome (PRES), while transplant-related immunosuppression confers risk for severe West Nile virus (WNV) neuroinvasive disease. Overlapping presentations such as encephalopathy or seizures can obscure dual pathology and delay targeted management. Case Description A 44-year-old woman with type 1 diabetes mellitus and end-stage renal disease underwent pancreas-kidney transplant in 2014 and a second renal transplant in 2024. Due to graft failure, she was on tacrolimus immunosuppression, which had been increased recently from 8mg to 10mg daily. She presented 8 months after second renal transplant with fever, profuse diarrhea, and progressive altered mental status. Initial CT brain was unrevealing; stool testing suggested C. difficile infection, which was treated with fidaxomicin. On hospital day 2 she developed nuchal rigidity and worsening encephalopathy for which empirical bacterial meningitis coverage was started. Brain MRI demonstrated bilateral parieto-occipital FLAIR hyperintensities consistent with PRES. Tacrolimus was discontinued, and sirolimus plus prednisone were continued for maintenance immunosuppression. CSF revealed lymphocytic pleocytosis with negative early viral studies. On day 7 she had a generalized seizure and was started on levetiracetam. She continued to deteriorate, was intubated and later underwent tracheostomy due to persistent depressed consciousness and respiratory failure. An extensive CSF panel returned positive for WNV IgM, confirming neuroinvasive WNV. Supportive treatment for WNV was continued. Clinical course was further complicated by central fever, upper-extremity DVT and norovirus enteritis. Over the next four weeks, she showed improvement in encephalopathy, as well as motor and sensory function in all extremities. She was transferred to LTACH for further rehabilitation and ventilator weaning. Discussion This case underscores co-existing etiologies of encephalopathy in transplant recipients, tacrolimus-associated PRES and WNV meningoencephalitis. Early MRI expedited PRES recognition and safe withdrawal of tacrolimus with BP control, while repeated CSF testing enabled WNV diagnosis after initial negative assays, an expected pitfall in immunosuppressed hosts. This case highlights the importance of maintaining high suspicion for WNV in late summer even with early negative serology, prompt imaging and adjustment of calcineurin inhibitors in unexplained encephalopathy or seizures and anticipating prolonged recovery. Awareness of this dual-pathology pattern may reduce morbidity via earlier recognition and management of infection and drug neurotoxicity. This abstract is funded by: None
Khan et al. (Fri,) studied this question.