Case Presentation: A 48 year-old woman with a past medical history of prediabetes presented with a one-week history of confusion, cough, and fever. She was lethargic with slurred speech on admission and intubated for airway protection in the Emergency Department. A few hours after admission to the intensive care unit (ICU), her respiratory PCR returned positive for COVID-19, and a lumbar puncture was also performed given the severity of encephalopathy. Her cerebrospinal fluid (CSF) was notable for 106 nucleated cells x 106/L with 12% neutrophils, 76% lymphocytes, 11% monocytes, glucose 94 mg/dL, and total protein 40 mg/dL.On hospital day 2, her CSF HSV-1 PCR returned positive, and her antimicrobial coverage was narrowed to acyclovir.On hospital day 3, the patient was extubated and transferred to a medicine wards service. The patient remained encephalopathic despite treatment with acyclovir, and an MRI brain was obtained on hospital day 5 which showed abnormal signal in bilateral frontal and temporal lobes felt to be consistent with HSV encephalitis. Over the next 3 weeks, her hospital course was complicated by seizures, an aspiration event, and a urinary tract infection. Given minimal improvement in her encephalopathy, a repeat lumbar puncture was performed on hospital day 25. The CSF was notable for 179 nucleated cells x 106/L with 94% lymphocytes, 6% monocytes, glucose 101mg/dL, and total protein 103 mg/dL. Since her CSF profile was worse than the one on admission, the medical teams were concerned for a secondary autoimmune process and empiric high dose steroids and intravenous immunoglobulin (IVIG) were administered. 10 days after the second lumbar puncture, her CSF returned positive for anti-NMDA receptor antibody confirming the diagnosis of post-herpetic anti-NMDA receptor encephalitis. The patient showed gradual signs of improvement and was discharged to a skilled nursing facility on hospital day 37.
Discussion: While this patient had a prolonged admission with unexpected complications, this case highlights resiliency in the healthcare system. The patient’s initial clinical presentation did not fit with one unifying diagnosis, and her clinical team diagnosed her with COVID-19 and HSV-1 encephalitis within the first 24 hours of admission. The mortality of untreated HSV encephalitis is roughly 70% (1). Despite a timely and accurate diagnosis on admission, when she failed to improve with appropriate treatment, the medical team avoided premature closure and ultimately diagnosed her with secondary autoimmune encephalitis. Total time from HSV encephalitis diagnosis to autoimmune encephalitis diagnosis was 33 days in this patient, and studies show that the median time to diagnosis is 43 days for patients over the age of 4 (2).
Conclusions: This review was part of a national collaborative–Achieving Diagnostic Excellence through Prevention and Teamwork (ADEPT). The safety-II approach to reviewing this case recognizes the complexities of the diagnostic process and places value on the expertise of the clinicians. Ready access to EEGs, MRIs, fluoroscopy assisted lumbar punctures, laboratory testing, and the collaboration between multiple teams contributed to the diagnostic success of this case.
