eMedicine Specialties > Neurology > Neurological Infections
Viral Encephalitis: Treatment & Medication
Updated: Oct 4, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Medical care should be devoted to appropriate management of the airway; bladder function; fluid and electrolyte balance; nutrition; and prevention of bedsores, secondary pulmonary infection, and hyperpyrexia.
- Increased intracranial pressure should be managed in the ICU setting with head elevation, gentle diuresis, mannitol, and hyperventilation.
- Seizures
- Encephalitis causes a wide range of behavioral manifestations with limbic and frontal syndromes that can be difficult to distinguish from partial seizures.
- Seizure activity can be closely observed using EEG monitoring, and the threshold for administering temporary anticonvulsant therapy should be low.
- Phenytoin and valproic acid can be administered intravenously. Phenytoin and carbamazepine can be administered when oral or intragastric drug administration is possible. Benzodiazepines are also important when used to abort status epilepticus.
Surgical Care
Brain biopsy can yield definitive diagnosis. A biopsy may be considered when a lumbar puncture is precluded or when the diagnosis is uncertain (eg, to rule out other conditions such as vasculitis). Caution should be exercised before requesting a brain biopsy. PCR for HSV has significantly decreased the need for brain biopsy in herpesvirus encephalitis. Despite the lack of controlled studies, patients with life-threatening cerebral edema may benefit from craniectomy or other approaches to lower the increased intracranial pressure in neurocritical care units.6
Consultations
Encephalitis is a neurological emergency. Consultation with a neurologist is recommended. Consultation with a neurosurgeon is helpful if a brain biopsy is considered.
- Consultation with an infectious disease specialist is also appropriate.
- Given the high likelihood of long-term need for cognitive rehabilitation and physical rehabilitation, especially in moderately severe and severe forms of encephalitis, establishing a multidisciplinary approach early in the disease course is appropriate. A multidisciplinary approach includes consultations with physical, occupational, and speech therapists, as well as consultation with a dietitian.
Diet
No dietary restrictions are necessary. The infectious process, especially with the presence of fever, increases nutritional requirements. Early assessment by a speech therapist and a dietitian helps prevent further body wasting and detects early behavioral manifestations that prevent adequate nutritional intake such as placidity, apraxia, dysphagia, or agitation.
Medication
No specific treatment is available for the arbovirus encephalitides. Ribavirin seems to be effective for Lassa fever. The efficacy of ribavirin in other viral infections is being evaluated.
Pharmacotherapy for herpesvirus encephalitis consists of acyclovir and vidarabine. Outcome is improved with either agent, but acyclovir is more effective and less toxic. Even if the final diagnosis of HSV encephalitis has not been established, IV acyclovir should be initiated immediately.
After promising results were demonstrated by a small series, recombinant interferon alpha is currently being assessed in a trial for Japanese B encephalitis.
At some centers, antibacterial treatment of bacterial meningitis is administered until the diagnosis of bacterial meningitis is excluded.
Antiviral agents
These agents shorten the clinical course, prevent complications, prevent development of latency and subsequent recurrences, decrease transmission, and eliminate established latency.
Acyclovir (Zovirax)
Has demonstrated inhibitory activity against both HSV-1 and HSV-2 and is taken up selectively by infected cells. Rate of mortality from herpes simplex encephalitis before use of acyclovir was 60-70%; since acyclovir, approximately 30%.
Adult
10 mg/kg/dose IV or 500 mg/m2/dose IV q8h
Pediatric
Administer as in adults
Probenecid or zidovudine prolongs half-life and increases toxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Use caution in patients with renal failure or receiving other nephrotoxic drugs concurrently
Ribavirin (Virazole)
Synthetic guanosine analogue (1-beta-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) that inhibits viral replication by inhibiting DNA and RNA synthesis. Phosphorylated in vivo, and active form may interfere with viral genomic synthesis.
Clinical experience in treatment of arenavirus infections is primarily with Lassa fever, but anecdotal experience in South American arenaviruses also exists. Clinically used in combination with interferon for hepatitis C, as aerosol for RSV, and as potential prophylaxis and/or treatment of Congo-Crimean hemorrhagic fever, hantavirus infections, and arenavirus hemorrhagic fevers. In vitro evidence exists for activity against West Nile virus. IV form not readily available and manufacturer should be contacted if need arises.
Adult
Lassa fever (with hepatitis and/or hemorrhagic manifestations): 2 g (30 mg/kg) IV initial; 1 g (15 mg/kg) IV q6h for 4 d; then 500 mg (7.5 mg/kg) IV q8h for 6 d
Suggested prophylactic dose: 600 mg PO qid for 10 d
Pediatric
Prophylaxis
<10 years: 400 mg/dose
>10 years: Administer as in adults
Decreases zidovudine effects
Documented hypersensitivity; women who may become pregnant
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor patients with chronic obstructive pulmonary disease and/or asthma closely for deterioration of respiratory function; systemic use causes dose-related anemia and hyperbilirubinemia related to extravascular hemolysis, and at higher doses, bone marrow suppression of erythroid elements; caution when administered by aerosol for RSV; teratogenic, mutagenic, and, possibly, gonadotoxic
Ganciclovir (Cytovene, Vitrasert)
Synthetic guanine derivative active in CMV. Acyclic nucleoside analogue of 2'-deoxyguanosine that inhibits viral replication in vitro and in vivo by competing with deoxyguanosine triphosphate for viral DNA polymerase, inhibiting DNA synthesis. Ganciclovir triphosphate levels are up to 100-fold greater in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation in infected cells.
Adult
Initial dose: 5 mg/kg IV bid for 14 d
Maintenance: 5 mg/kg IV qd for 5-7 d/wk; alternative, 500 mg PO q4h or 1 g PO tid for life
Pediatric
<3 months: Not established
>3 months: Administer as in adults (IV regimen)
Cytotoxic drugs, such as dapsone, pentamidine, flucytosine, vincristine, vinblastine, doxorubicin, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogues, may have additive toxicity in rapidly dividing cell populations (eg, bone marrow, spermatogonia, germinal layers of skin, GI mucosa); consider concomitant use of these drugs only if potential benefits outweigh risks; imipenem-cilastatin may cause generalized seizures, use only when potential benefits outweigh risks; cyclosporine or amphotericin B may increase serum creatinine; probenecid reduces renal clearance; increases bioavailability of didanosine if administered either 2 h prior to or simultaneously with ganciclovir, whereas steady-state bioavailability of ganciclovir may decrease if didanosine administered 2 h prior to ganciclovir administration but not when the 2 drugs administered simultaneously; zidovudine may decrease bioavailability of ganciclovir, but ganciclovir increases bioavailability of zidovudine; sinceboth drugs can cause granulocytopenia and anemia, combination therapy at full dosing may not be possible
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Adverse effects include granulocytopenia, anemia, and thrombocytopenia; since PO ganciclovir is associated with higher rate of CMV retinitis progression than IV formulation, use PO only when benefits outweigh risks, as in advanced HIV disease; use caution in renal failure because of increased half-life and drug levels; dosages > 6 mg/kg IV may be more toxic than lower doses; rapid infusions also result in increased toxicity; initially, reconstituted IV solutions have high pH (11) and may cause phlebitis or pain at infusion site despite further dilution; adequate hydration important during infusion; photosensitization (photoallergy or phototoxicity) warrants limitation of exposure to UV light
Foscarnet (Foscavir)
Organic analogue of inorganic pyrophosphate, inhibits viral replication in vitro. Exerts antiviral activity by selective inhibition at pyrophosphate-binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases, inhibiting DNA synthesis.
Viral resistance should be considered in patients with poor clinical response or persistent viral excretion. Patients who show excellent tolerance of foscarnet may benefit from initiation of maintenance dosage (ie, 120 mg/kg/d) earlier in their treatment. Individualize dosing according to patient's renal function status.
Adult
Induction: 60 mg/kg/dose IV q8h or 100 mg/kg q12h for 14-21 d; in acyclovir-resistant HSV infections: 40 mg/kg/dose IV q8-12h for 14-21 d
Maintenance: 90-120 mg/kg/d as single IV infusion for life
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Because of nephrotoxicity, avoid combination with other potentially nephrotoxic drugs, such as aminoglycosides, amphotericin B, and pentamidine, unless benefits outweigh risks; IV pentamidine may cause hypocalcemia
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Usually causes decline in renal function; 24-h urine CrCl should be determined at baseline and periodically thereafter to ensure correct dosing; discontinue foscarnet if CrCl drops to <0.4 mL/min/kg; hydration may reduce nephrotoxicity; because of propensity to chelate divalent metal ions and alter serum electrolytes, including calcium and magnesium, closely monitor patients for such changes; serum electrolytes should be determined immediately when patients develop perioral numbness, paresthesias, or seizures; infuse only into veins with adequate blood flow to permit rapid dilution and to avoid local irritation; do not administer by rapid or bolus IV injection, which may increase plasma levels and, thus, toxicity; granulocytopenia (17%) and anemia (33%) are common adverse effects, regularly monitor CBCs
More on Viral Encephalitis |
| Overview: Viral Encephalitis |
| Differential Diagnoses & Workup: Viral Encephalitis |
 Treatment & Medication: Viral Encephalitis |
| Follow-up: Viral Encephalitis |
| References |
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Further Reading
Keywords
encephalitides, herpes simplex virus, HSV, herpesvirus, arbovirus, St Louis encephalitis, eastern equine encephalitis, Japanese B encephalitis, rabies, La Crosse encephalitis, western equine encephalitis, mumps meningoencephalitis, mumps encephalitis, insect vector, mosquito, tick, influenza virus, West Nile virus, dengue fever, enteroviral encephalitis, encephalomyelitis, von Economo encephalitis, encephalitis lethargica, enterovirus 71, rhombencephalitis, Nipah virus, varicella-zoster virus, VZV, lymphocytic choriomeningitis virus, Lassa fever, Venezuelan encephalitis, Far East tick-borne encephalitis, Central European tick-borne encephalitis, Powassan encephalitis, Colorado tick fever, Murray Valley encephalitis, California encephalitis, Jamestown Canyon encephalitis, cytomegalovirus ventriculoencephalitis, CMV
