Persistance Makes a Diagnosis Perfect; A Case of HSV PCR Negative Herpes Simplex Encephalitis

Abstract

CASE PRESENTATION: A 68 year-old male with a past medical history of TIA presented from an outside hospital with fever,altered mental status and generalized tonic-clonic seizures.He was empirically started on steroids,antibiotics and anti-epileptics, and a lumbar puncture at that time showed a WBC count of 48 with 94% neutrophils. CSF cultures and HSV PCR were negative.The patient was subsequently transferred to our hospital as he continued to be in status epilepticus. The patient was started on a Propofol and based on clinical suspicion empirically on acyclovir. MRI showed hypo-attenuation of the temporal lobe in addition to hippocampus,medial frontal lobe and insula.An EEG was performed that showed periodic lateralized epileptic discharges.A repeat lumbar puncture was performed three days after admission which returned positive for HSV.Treatment was scheduled for 21 days with Acyclovir; unfortunately, after completing the course there was minimal neurological recovery. DISCUSSION: Herpes Simplex is the most common cause of acute sporadic focal encephalitis associated with a 70% mortality without prompt management. A rapid and accurate diagnostic test is essential for its treatment. HSV PCR is the diagnostic procedure of choice,with a reported sensitivity of 98% and specificity of 94-99%. Interpretation of the result is critically influenced by the timing of the test and its pretest probability.False negative results can result from:blood contaminant CSF,specimen obtained during the earliest phase of the disease, or a sample that contained < 10 leukocyte/mm3 with a polymorphonuclear cell predominance. Other supporting neurodiagnostic tests are recommended,including EEG and MRI. Temporal lobe involvement is seen on MRI; and on EEG lateralizing epileptiform discharges is seen in over 80% of patients with HSE. Conclusions: Despite being very sensitive,this case highlights the need for cautious interpretation of an initial negative HSV PCR result. A repeat lumbar puncture within the first 1-3 days of treatment is warranted when HSE remains the primary diagnosis with other supporting neurodiagnostic test results.