HSV EncephalitisHSV EncephalitisJack Kuritzky, PGY-2Jack Kuritzky, PGY-2

UNC Internal MedicineUNC Internal Medicine

August 31, 2009August 31, 2009

HSV Encephalitis: HSV Encephalitis: GeneralGeneral

Encephalitis: 20,000 cases/yearEncephalitis: 20,000 cases/year HSV accounts for 10-20%HSV accounts for 10-20%

HSV-1 causes encephalitis in adultsHSV-1 causes encephalitis in adults HSV-1 or HSV-2 in neonatesHSV-1 or HSV-2 in neonates HSV-1 and 2 associated w/Mollaret’s meningitisHSV-1 and 2 associated w/Mollaret’s meningitis

Benign recurrent lymphocytic meningitisBenign recurrent lymphocytic meningitis

Preferentially affects temporal lobePreferentially affects temporal lobe Can rarely cause recurrent brainstem Can rarely cause recurrent brainstem

encephalitisencephalitis HSV-2 tends to cause global encephalitisHSV-2 tends to cause global encephalitis

1/3 cases <20yrs and 1/2 cases >50 yrs1/3 cases <20yrs and 1/2 cases >50 yrs

HSV Encephalitis: HSV Encephalitis: PathogenesisPathogenesis

Infiltrates CNS via 3 routesInfiltrates CNS via 3 routes 1. Trigeminal nerve or olfactory tract1. Trigeminal nerve or olfactory tract

Typically after primary infectionTypically after primary infection <18yrs old<18yrs old

2. CNS invasion after recurrent infection2. CNS invasion after recurrent infection Viral reactivation w/subsequent spreadViral reactivation w/subsequent spread

3. CNS infection w/o primary or recurrent HSV-13. CNS infection w/o primary or recurrent HSV-1 Latent HSV in situ within CNSLatent HSV in situ within CNS

Invades and replicates in neurons and gliaInvades and replicates in neurons and glia Causes necrotizing encephalitisCauses necrotizing encephalitis Widespread hemorrhagic necrosis throughout Widespread hemorrhagic necrosis throughout

parenchymaparenchyma

HSV Encephalitis: HSV Encephalitis: PathogenesisPathogenesis

Necrosis of temporal lobeNecrosis of temporal lobe

HSV Encephalitis: HSV Encephalitis: PathogenesisPathogenesis

Necrosis of temporal lobeNecrosis of temporal lobe Immune mediatedImmune mediated

Not more common in immunosuppressedNot more common in immunosuppressed Small studies suggest HSV viral load does Small studies suggest HSV viral load does

not correlate with degree of temporal lobe not correlate with degree of temporal lobe damagedamage

HSV Encephalitis: HSV Encephalitis: PresentationPresentation

FeverFever Altered mental status Altered mental status Altered level of consciousnessAltered level of consciousness Focal cranial nerve deficitsFocal cranial nerve deficits HemiparesisHemiparesis Dysphasia/aphasiaDysphasia/aphasia AtaxiaAtaxia Focal seizures Focal seizures

HSV Encephalitis: HSV Encephalitis: PresentationPresentation

FeverFever Altered mental statusAltered mental status Altered level of consciousnessAltered level of consciousness Focal cranial nerve deficitsFocal cranial nerve deficits HemiparesisHemiparesis Dysphasia/aphasiaDysphasia/aphasia AtaxiaAtaxia Focal seizuresFocal seizures

HSV Encephalitis: HSV Encephalitis: PresentationPresentation

More on AMS – consequences of More on AMS – consequences of temporal lobe damagetemporal lobe damage Hypomania - elevated mood, excessive Hypomania - elevated mood, excessive

animation, decreased need for sleep, animation, decreased need for sleep, inflated self-esteem, and hypersexuality inflated self-esteem, and hypersexuality

Kluver-Bucy syndrome (KBS)Kluver-Bucy syndrome (KBS) Initially seen in Rhesus monkeysInitially seen in Rhesus monkeys Loss of normal anger and fear responses Loss of normal anger and fear responses Increased sexual activityIncreased sexual activity AmnesiaAmnesia

HSV Encephalitis: HSV Encephalitis: DiagnosisDiagnosis

CSFCSF Lymphocytic pleocytosisLymphocytic pleocytosis Erythrocytosis (84% of patients)Erythrocytosis (84% of patients) Elevated proteinElevated protein

Low glucose uncommonLow glucose uncommon CSF PCR now diagnostic test of CSF PCR now diagnostic test of

choicechoice Quickest, sensitive, and specificQuickest, sensitive, and specific HSV culture out of favorHSV culture out of favor Brain biopsies previously performedBrain biopsies previously performed

HSV Encephalitis: HSV Encephalitis: DiagnosisDiagnosis

Imaging Imaging Temporal lobe Temporal lobe

injuryinjury

HSV Encephalitis: HSV Encephalitis: DiagnosisDiagnosis

Imaging – Temporal lobe injuryImaging – Temporal lobe injury Usually unilateralUsually unilateral May have mass effectMay have mass effect MRI much more sensitive/specificMRI much more sensitive/specific

EEG – focal findings in >80% casesEEG – focal findings in >80% cases High amplitude slow waves (delta and theta High amplitude slow waves (delta and theta

slowing)slowing) Continuous periodic lateralized Continuous periodic lateralized

epileptiform discharges in the affected epileptiform discharges in the affected region region

HSV Encephalitis: HSV Encephalitis: TreatmentTreatment

EARLY TREATMENT IMPERATIVE!EARLY TREATMENT IMPERATIVE! Before loss of consciousness Before loss of consciousness Within 24 hours of the onset of symptoms Within 24 hours of the onset of symptoms Glasgow Coma Scale score of 9 to 15Glasgow Coma Scale score of 9 to 15

Acyclovir 10 mg/kg IV Q 8h (infuse slowly Acyclovir 10 mg/kg IV Q 8h (infuse slowly to prevent crystalluria/renal failure)to prevent crystalluria/renal failure) Mortality 19-28% vs. 50-58% w/vidarabineMortality 19-28% vs. 50-58% w/vidarabine 6 month functional status significantly better 6 month functional status significantly better

w/acyclovirw/acyclovir Treat 14-21 daysTreat 14-21 days

Future treatment Future treatment steroids? (non- steroids? (non-randomized, retrospective study)randomized, retrospective study)

HSV Encephalitis: HSV Encephalitis: PrognosisPrognosis

Untreated, mortality 70%Untreated, mortality 70% Survivors with severe neurologic damageSurvivors with severe neurologic damage

With treatment—mortality ~20%!With treatment—mortality ~20%! Severe disability in 20%Severe disability in 20%

Simplified Acute Physiology Score II >/=27Simplified Acute Physiology Score II >/=27 Delay >2 days b/w admission and acyclovirDelay >2 days b/w admission and acyclovir GCS <6GCS <6 Age>30Age>30

62% of survivors have neurologic sequelae62% of survivors have neurologic sequelae

REFERENCESREFERENCES

Kimberline, DW. Management of HSV Encephalitis in Adults Kimberline, DW. Management of HSV Encephalitis in Adults and Neonates: Diagnosis, Prognosis, and treatment. and Neonates: Diagnosis, Prognosis, and treatment. Herpes. (14)1. 2007.Herpes. (14)1. 2007.

Klein, R. “Clinical manifestations and diagnosis of herpes Klein, R. “Clinical manifestations and diagnosis of herpes simplex virus type 1 infection”. UpToDate, version 17.2. simplex virus type 1 infection”. UpToDate, version 17.2. Jan 2009.Jan 2009.

Klein, R. “Herpes Simplex Type 1 Encephalitis”. UpToDate, Klein, R. “Herpes Simplex Type 1 Encephalitis”. UpToDate, version 17.2. Feb 2009.version 17.2. Feb 2009.

Shandera, WX and H Koo. “Infectious Diseases: Viral & Shandera, WX and H Koo. “Infectious Diseases: Viral & Rickettsial”. Rickettsial”. 2007 Current Medical Diagnosis & Treatment2007 Current Medical Diagnosis & Treatment. . 4646thth ed. The McGraw Hill Companies: USA. 2007. ed. The McGraw Hill Companies: USA. 2007.

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