Citation: Sharma, R.; Spradley, T.; Campbell, M.; Biyani, S.; Singhal, P.; Elkhider, H.; Nalleballe, K.; Gokden, M.; Kumar, M.; Kapoor, N. CD8 Encephalitis: A Diagnostic Dilemma. Diagnostics 2022, 12, 2687. https://doi.org/10.3390/ diagnostics12112687 Academic Editor: Sang Kun Lee Received: 12 October 2022 Accepted: 3 November 2022 Published: 4 November 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). diagnostics Case Report CD8 Encephalitis: A Diagnostic Dilemma Rohan Sharma 1, * , Thomas Spradley 2 , Morgan Campbell 3 , Shubham Biyani 4 , Pulkit Singhal 5 , Hisham Elkhider 4 , Krishna Nalleballe 4 , Murat Gokden 6 , Manoj Kumar 7 and Nidhi Kapoor 8 1 Department of Neurocritical Care, Mayo Clinic in Florida, Jacksonville, FL 32224, USA 2 Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 3 College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 4 Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 5 College of Osteopathic Medicine, California Health Sciences University, Clovis, CA 93612, USA 6 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 7 Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA 8 Department of Neurology, Baptist Medical Center, Jacksonville, FL 32207, USA * Correspondence: sharma.rohan@mayo.edu Abstract: CD8+ encephalitis is a subacute encephalopathy associated with HIV infection. Patho- physiology is thought to be auto-reactive CD8+ cells attacking on HIV infected CD4+ cells and ‘viral escape’ phenomena (replication of CD8+ cells in CSF). We present a case of a 45-year-old man with well controlled HIV who developed CD8 encephalitis following Herpes simplex encephalitis. He had persistent encephalopathy for several weeks with status epilepticus and agitated delirium, and diagnosis remained elusive until a brain biopsy confirmed the diagnosis. Keywords: CD8 encephalitis; HIV; HSV; encephalitis 1. Case 1.1. Admission 1 A 45-year-old man with well-controlled HIV (CD4 count one year prior of 575/μL (40%) and viral load <20 copies/mL) on bictegravir, emtricitabine, and tenofovir alafe- namide; hepatitis C (previously treated); liver cirrhosis; prior polysubstance abuse (includ- ing methamphetamine, cannabis, cocaine and ETOH); presented with new-onset seizure and confusion. Given the patient’s confusion, history was obtained from the patient’s husband. Patient reportedly had nausea and vomiting after an episode of binge drinking for three days followed by new-onset seizures. He had daily seizures for three days which caused him to seek medical attention. There was no history of similar events. Patient reportedly had a tick bite a few weeks prior to presentation. He did not report any fever, chills, rash, headaches, vision changes, cough, diarrhea, or abdominal pain. On presentation he was found to be febrile at 102.9 F (39.3 C) and tachycardic at 115/min, with a normal blood pressure of 119/52 mmHg and respiratory rate of 18/min. His cardiorespiratory and abdominal exams were unremarkable. He was drowsy, arousable with minimal stimuli, and confused, but he followed simple commands without any cranial nerve or sensory-motor deficits or neck rigidity. His labs were significant for a neutrophil-predominant leukocytosis of 12,000/mm 3 , hyponatremia of 133 mg/dL, and an elevated creatinine of 1.25 mg/dL. His chest radiograph was unremarkable, and a CT head without contrast was also unremarkable. His CSF studies showed a lymphocyte- predominant pleocytosis: 162 (97% monocytes), with a protein of 45 mg/dL, and a glucose of 77 mg/dL. He was given supplemental oxygen by nasal cannula; IV acyclovir, ceftriaxone, and vancomycin for presumed meningitis/encephalitis; doxycycline for possible tick-bone illness; and levetiracetam for seizures. He was also given thiamine for possible Wernicke’s encephalitis secondary to alcohol use. Electroencephalogram (EEG) showed left focal temporal slowing. Diagnostics 2022, 12, 2687. https://doi.org/10.3390/diagnostics12112687 https://www.mdpi.com/journal/diagnostics