Discussion Author: James G. Smirniotopoulos, M.D.
The herpes virus family, including herpes simplex virus (HSV) is a group of eight double-stranded DNA viruses that can establish latency and lie dormant within living human cells (e.g. neurons). HSV 1 establishes latency in the trigeminal (semilunar) ganglia; while HSV 2 usually resides in the sacral ganglia. PMID: 18657720 HSV 1 may also reside in the geniculate ganglia of the facial nerve, and may cause recurrent Bell's palsy (facial paralysis). Proposed causes of re-activation of latent virus include stress, trauma (including surgery), and relative immune suppression. PMID: 17572889
The incidence HSE (herpes simplex encephalitis) is estimated at roughly one case per million per year. Herpes labialis (HSV1) is the most common cause of viral encephalitis - representing 90% of herpes simplex encephalitis; and, most of these patients are immunocompetent adults. HSV 2 - herpes genitalis - accounts for most of the remaining 10% of HSE; and, it is most often a neonatal infection, acquired from the mother during vaginal delivery. Immunocompromised patients may also develop HSV 2 encephalitis. PMID: 18657720 PMID: 14978145
» Presentation:
Confusion, Fever, Headache, Seizures, olfactory or gustatory hallucinations, aphasia, hemiparesis, obtundation
» Prognosis: without Tx ~70% mortality, with acyclovir or Valacyclovir, 20-50% mortality
» Diagnosis:
Clinical suspicion!
» Lumbar Puncture: CSF is usually abnormal (95%) PMID: 14978145
CSFglucose is usually normal
Pleocytosis w/Lymphocytes - 10-200/ml
Protein - 60 - 200 mg/dl
PCR is 98% sensitive and > 94% specific PMID: 18657720
NOTE: CSF PCR is false negative early in disease (24-48 hrs); and, also can be false-negative 10 days to weeks after onset; and, PCR negative or inaccurate with a bloody tap. PMID: 14978145 PMID: 18657720
EEG is abnormal, slowing in temporal and frontal regions
» Imaging with MR is more sensitive than CT. Early gray-matter lesions (bright on FLAIR, T2W, dark on CT T1W, abnormal gyral enhancement) in the temporal, cingulate, subfrontal regions. The cortex may appear thickened. Imaging cannot rule-out HSV encephalitis Depending on the stage and course of the disease, even MR imaging can be "normal" in up to 1/3 of patients with HSE. PMID: 15918625 PMID:15885053
In patients with abnormal CT and MR imaging, temporal lobe involvement is most common (more than 50%). However, extra-temporal lesions are also seen in about 1/2 of cases; and, up to 1/4 of patients may have only extra-temporal disease. PMID: 15918625 PMID:15885053
Abnormally decreased ADC values (bright DWI/Dark ADC map) indicate active desctruction of cells; and, may be as senstive as Gd contrast enhancement for HSE. PMID: 18983763
In more than 1/2 of neonates with HSV2, there may be involvement of the deep gray matter and brainstem PMID: 18246335. The WM and and basal ganglia are less commonly affected in adults with HSV1 -while brainstem lesons are not atypical. PMID:15885053
» Differential Diagnosis:
• MELAS
• HHV-6
• Limbic encephalitis (paraneoplastic) (more gradual)
• Listeriosis
• Voltage-gated potassium channel antibody syndrome [slower (weeks) onset tempo , hyponatremia, serology for the Ab]
» Treatment: early institution of IV acylovir, TID, 10 mg/kg for 2-3 weeks. Some sources suggest 20 mg/kg in very young children.
NOTE: Any delay in Tx is associated with worse outcome. Acyclovir may be started while PCR is pending. Acyclovir is a specific for HSV infected cells, tolerated well and high safety margin. PMID: 14978145
Corticosteroids may improve prognosis.
Relapse is possible.
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