Member of family Herpesviridae HSV-1- tropism for oral mucosa 80% of adult population seropositive, though only 30%

report clinically significant outbreaks Only 10-20% of those with HSV-2 Abs report a hx of lesions Large, enveloped, double strandedDNA virus

 Most adults with HSV encephalitis have clinical or serologic evidence of mucocutaneous HSV-1 infection before the onset of the CNS symptoms. HSV DNA has been demonstrated in brain tissue from healthy adults. ( = reactivation) In about 25% of the patients, the HSV-1 strains from the oropharynx and brain tissue of the same patient differ; thus some cases may result from reinfection with another strain of HSV-1 that reaches the CNS

 In children and young adults, primary HSV infection may result in encephalitis; virus enters the central nervous system (CNS) by neurotropic spread from the periphery via the olfactory bulb Subtype 1 virus causes more than 95% of cases of HSV encephalitis The most commonly identified cause of acute, sporadic viral encephalitis; 10 to 20% of all cases

Necrotizing HSV Infection

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Clinical Features of HSE

HSE is an acute or subacute illness that causes both general and focal signs of cerebral dysfunction. Although the presence of fever, headache, behavioral changes, confusion, focal neurologic findings, and abnormal cerebrospinal fluid (CSF) findings are suggestive of HSE, no pathognomonic clinical findings reliably distinguish HSE from other neurologic disorders with similar presentations

CF
Prodrome of Fever , malaise , Headache ,Nausea-or sub acute Encephalopathy Lethargy Confusion and delirium Fever 90%, Headache 81%, Psy Sx 71% Seizures 67%, Vomiting 46% , Focal Weakness 33%, Memory Loss 24% In Neonates- develop 6-12 days post deliver Lethargy, poor feeding, irritability tremorss or seizures . Dissemenitaed Disease abnormal LFT. Neonates can have herpetci skin lesions.

Physical Findings
Altered Conscious Fever, Dysphagia, Ataxia, Seixures , Focal or Generalised Hemiparesis , Cranial Nerve Defects Visual Field Loss, Papilloedema HSV 1- Brain Stem Encephalitis , HSV2 Myelitis.

Atypical Presentation
Global aphasia can occur McGrath et all reported anterior Opercular Sysdrome paralysis of Masticatory, facial, pharyngeal and lingual muscles. In Children basal Ganlgia involvement demonstrating Extra pyramidal sx.

 Differential is broad

Diagnosis

Encephalitis from other viruses (West Nile, WEE, enteroviruses, adenovirus, flu, other herpesviruses, JC virus, etc.) Brain abscess or subdural empyema (bacteria, mycobacteria, rickettsiae, mycoplasma, protozoa) Neurosyphilis Brain tumors Subdural hematoma SLE Vasculitis Toxic encephalopathy Acute disseminated encephalomyelitis

Diagnosis
CSF WBC: 20-300 cells/mm3 (rare;y < 5) Protein: 30-2,500 , median 80 (normal<60) Glucose usually normal EEG: spike and slow wave activity from the temporal lobe. Sensitivity 85%. Specificity 33%.

HSE Diagnosis Radiological

CT: Edema in the temporal lobe ->>hemorrhagic necrosis ->> midline shift . Neuroimaging (temporal lobe abnormalities)
CT- hypodense lesions (medial temporal regions) MRI- increased T2 signal (orbitofrontal, temporal, insulae)

First 5 days: CT sensitivity 73%, specificity 89% >5 days: CT sensitivity 90%, specificity 92%

Herpes simplex Encephalitis: confirmation of etiology

Brain biopsy (complications 3%) Serologic analysis in serum and CSF: low sensitivity in the first 10 days.

CSF Cultures: negative

PCR in CSF: highly sensitive and specific. The diagnostic procedure of choice.

Treatment
High Index of suspicion Necessary , Start Rx early Acyclovir 10 mg/kg IV Q8hrs for 14-21 days Acyclovir is a nucleoside analog that is activated by the viral thymidine kinase, is incorporated into viral DNA resulting in chain termination Vidarabine is an alternative agent that has been used in past but is inferior to Acyclovir
Purine analog that inhibits viral DNA polymerase Has neurologic side effects, esp in pts with impaired renal or liver function If PCR negative and no other support for HSE, stop acyclovir

Managing associated Complications

Manage ABCs in ICU ICP Management with Head elevation to Fursoemide Mannitol , Intubation , Hyperventillation Management of Seizures If EEG is positive for Non convulsive seizures Benzodiazepines to abort seizures, Post IV treatment Oral valcyclovir for 3 months susggested to prevent relapse.

Prognosis
Untreated, ~70% of cases are fatal
Survivors have neuropsychiatric and behavioral issues. Only 2.5% of untreated survivors return to normal neurologic function

With treatment, mortality can still be as high as 20-30%

Delayed treatment >2 days poorer outcome

Even with early treatment, nearly 2/3 survivors have significant neurologic sequelae

Prognosis
Postencephalitic Syndrome
Behavioral abnormalities, ex. features of KluverBucy Syndrome Cognitive impairment (ex. dysnomia, impaired new learning for verbal and visual material) Seizures

Take Home Points

Acute onset fever, altered level of consciousness, neurologic deficits, seizuresconsider HSE. LP CSF PCR for HSV, elevated protein, lymphocytic pleocytosis, normal glucose Temporal lobe abnormalities on neuroimaging High mortality rate if not treated Early treatment with Acyclovir 10 mg/kg IV Q8hrs for 14-21 days Even with treatment, significant neurologic deficits can persist in survivors