Persistent Fever After Treatment of HSV Encephalitis – Is This Expected?

Published:February 21, 2022DOI:
      A previously well 69-year-old woman presented with 2 days of fever, headache, vomiting, Broca aphasia, and upper respiratory tract symptoms. She was empirically treated for meningoencephalitis with intravenous (IV) ceftriaxone, vancomycin, ampicillin, and acyclovir after lumbar puncture was performed. Cerebrospinal fluid analysis showed lymphocytic pleocytosis and positive herpes simplex virus polymerase chain reaction (PCR) (Table). Initial computed tomography of the brain was normal. Magnetic resonance imaging (MRI) of the brain findings are demonstrated in the Figure. The patient became increasingly confused and developed status epilepticus, and was intubated and transferred to the intensive care unit. Her aphasia improved and she remained seizure free. However, she continued to have low-grade temperature despite 21 days of IV acyclovir; hence, a repeat lumbar puncture was performed, which showed persistent pleocytosis but negative herpes simplex virus PCR. Since day 38, she developed receptive aphasia, auditory and visual hallucinations, and emotional lability. MRI of the brain was repeated (Figure). A third cerebrospinal fluid analysis showed persistent pleocytosis (Table) and positive anti-N-methyl-d-aspartate (NMDA) receptor. She was treated for autoimmune encephalitis with IV methylprednisolone, followed by IV immunoglobulin and a tapering dose of oral prednisolone, with clinical and radiological improvement.
      TableSerial Cerebrospinal Fluid Analyses
      Day 1 Day 25 Day 42
      White blood cells (WBC) (/uL)

      n: 0-4 × 109/L
      138 123 35
      Lymphocytes (%) 38 75 89
      Red blood cells (RBC) (/uL) 15 83 84
      Protein (g/L)

      n: 0.15-0.45
      0.53 1.73 1.53
      Herpes simplex virus PCR +
      NMDA receptor antibodies Not tested Not tested 1:100
      NMDA = anti-N-methyl-d-aspartate; PCR = polymerase chain reaction.
      Figure(A, B, C) MRI of the brain on day 4 of admission, demonstrating swelling with T2 FLAIR hyperintensity of the left (A) anterior and (B) medial temporal lobe and (C) left insula, and mild left basitemporal and insular leptomeningeal enhancement (not shown); (D, E, F) Repeat MRI of the brain on day 41 demonstrating increased T2 FLAIR hyperintensity of the left (D) anterior and (E) medial temporal lobe and (F) insula and new T2 FLAIR hyperintensity in the (F) left dorsomedial thalamus, with increased leptomeningeal enhancement of these areas (not shown). FLAIR = fluid-attenuated inversion recovery; MRI = magnetic resonance imaging.
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