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HSV Encephalitis Jack Kuritzky, PGY-2 UNC Internal Medicine August 31, 2009 HSV Encephalitis: General Encephalitis: 20,000 cases/year HSV accounts for 10-20% HSV-1 causes encephalitis in adults HSV-1 or HSV-2 in neonates HSV-1 and 2 associated w/Mollaret’s meningitis Preferentially affects temporal lobe Benign recurrent lymphocytic meningitis Can rarely cause recurrent brainstem encephalitis HSV-2 tends to cause global encephalitis 1/3 cases <20yrs and 1/2 cases >50 yrs HSV Encephalitis: Pathogenesis Infiltrates CNS via 3 routes 1. Trigeminal nerve or olfactory tract 2. CNS invasion after recurrent infection Viral reactivation w/subsequent spread 3. CNS infection w/o primary or recurrent HSV-1 Typically after primary infection <18yrs old Latent HSV in situ within CNS Invades and replicates in neurons and glia Causes necrotizing encephalitis Widespread hemorrhagic necrosis throughout parenchyma HSV Encephalitis: Pathogenesis Necrosis of temporal lobe HSV Encephalitis: Pathogenesis Necrosis of temporal lobe Immune mediated Not more common in immunosuppressed Small studies suggest HSV viral load does not correlate with degree of temporal lobe damage HSV Encephalitis: Presentation Fever Altered mental status Altered level of consciousness Focal cranial nerve deficits Hemiparesis Dysphasia/aphasia Ataxia Focal seizures HSV Encephalitis: Presentation Fever Altered mental status Altered level of consciousness Focal cranial nerve deficits Hemiparesis Dysphasia/aphasia Ataxia Focal seizures HSV Encephalitis: Presentation More on AMS – consequences of temporal lobe damage Hypomania - elevated mood, excessive animation, decreased need for sleep, inflated self-esteem, and hypersexuality Kluver-Bucy syndrome (KBS) Initially seen in Rhesus monkeys Loss of normal anger and fear responses Increased sexual activity Amnesia HSV Encephalitis: Diagnosis CSF Lymphocytic pleocytosis Erythrocytosis (84% of patients) Elevated protein Low glucose uncommon CSF PCR now diagnostic test of choice Quickest, sensitive, and specific HSV culture out of favor Brain biopsies previously performed HSV Encephalitis: Diagnosis Imaging Temporal lobe injury HSV Encephalitis: Diagnosis Imaging – Temporal lobe injury Usually unilateral May have mass effect MRI much more sensitive/specific EEG – focal findings in >80% cases High amplitude slow waves (delta and theta slowing) Continuous periodic lateralized epileptiform discharges in the affected region HSV Encephalitis: Treatment EARLY TREATMENT IMPERATIVE! Acyclovir 10 mg/kg IV Q 8h (infuse slowly to prevent crystalluria/renal failure) Before loss of consciousness Within 24 hours of the onset of symptoms Glasgow Coma Scale score of 9 to 15 Mortality 19-28% vs. 50-58% w/vidarabine 6 month functional status significantly better w/acyclovir Treat 14-21 days Future treatment steroids? (non-randomized, retrospective study) HSV Encephalitis: Prognosis Untreated, mortality 70% Survivors with severe neurologic damage With treatment—mortality ~20%! Severe disability in 20% Simplified Acute Physiology Score II >/=27 Delay >2 days b/w admission and acyclovir GCS <6 Age>30 62% of survivors have neurologic sequelae REFERENCES Kimberline, DW. Management of HSV Encephalitis in Adults and Neonates: Diagnosis, Prognosis, and treatment. Herpes. (14)1. 2007. Klein, R. “Clinical manifestations and diagnosis of herpes simplex virus type 1 infection”. UpToDate, version 17.2. Jan 2009. Klein, R. “Herpes Simplex Type 1 Encephalitis”. UpToDate, version 17.2. Feb 2009. Shandera, WX and H Koo. “Infectious Diseases: Viral & Rickettsial”. 2007 Current Medical Diagnosis & Treatment. 46th ed. The McGraw Hill Companies: USA. 2007. THE END