Viral encephalitis medical therapy

Template:Encephalitis Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Priyamvada Singh, MBBS [2]; João André Alves Silva, M.D. [3]

Overview

Encephalitis is an acute inflammation of the brain, commonly caused by a viral infection. Sometimes, encephalitis can result from a bacterial infection, such as bacterial meningitis, or it may be a complication of other infectious diseases like rabies (viral) or syphilis (bacterial). Certain parasitic or protozoal infestations, such as toxoplasmosis, malaria, or primary amoebic meningoencephalitis, can also cause encephalitis in people with compromised immune systems. Treatment with acyclovir with or without steroids and antibiotics should be initiated as soon as possible. Antiviral agent like acyclovir has been useful in treatment of encephalitis due to herpes simplex virus and varicella zoster. Treatment for other causative agents of encephalitis is mostly supportive.

Medical Therapy

General Considerations

• Reliably tested specific antiviral agents are available only for a few viral agents (e.g. acyclovir or ganciclovir for herpes simplex virus and varicella-zoster encephalitis). Administer the first dose of acyclovir as soon as possible (in the emergency department itself). Acyclovir can be initiated with or without antibiotics or steroids.The advantages of an early antiviral drug administration are:
  • Decreases disease duration
  • Decreases development of latency
  • Decreases development of complications
  • Decreases recurrence
  • Decreases transmission from infected person
• Treatment for Toxoplasma gondii and cytomegalovirus encephalitis are available but are used with limited success
• Treatment is usually symptomatic. In patients who are very sick, supportive treatment, such as mechanical ventilation, is equally important.
• Systemic complications like hypotension, shock, hypoxemia, electrolyte imbalances (hyponatremia, SIADH should be treated promptly.
• Neuroimaging with MRI or CT scan should be done before lumbar puncture especially if raised intracranial pressure is suspected.
• Lab tests like blood samples should be taken before initiation of therapy.
• Bed rest, plenty of fluids and anti-inflammatory drugs to relieve headache and fever should be used.

Empirical Treatment Regimen

• Adult & Pediatrics - Acyclovir, 10 mg/kg body weight, 8hourly, intravenous, for 2-3 weeks.
• Neonatal HSV - Acyclovir 10-15 mg/kg 8hourly, intravenous, for neonatal HSV
• HIV Positive - Foscarnet is generally the treatment of choice given the high incidence of acyclovir resistance in these group of patients.

Treatment for Increased Intracranial Pressure

General

• Elevation of head end of the bed
• Hyperventilation may be used to decrease intra-cranial pressure on emergency basis
• Constant monitoring of neurological status
• Avoid increase in intra cranial pressure i.e. control of straining and coughing
• Antipyretics and analgesic for fever and pain.
• Monitoring and preventing seizures and hypotension.

Drug Therapy

• Furosemide 20 mg iv and mannitol 1 gm/kg intravenously for diuresis (blood pressure and CVP should be monitored while administrating these drugs)
• Dexamethasone 10mg intravenously 6 hourly to decrease cerebral edema.

Encephalitis Drug Summary

Acyclovir

• It is effective for HSV1, HSV2 and varicella zoster.
• It is selectively taken up by the body cells infected with HSV and varicella zoster
• Prompt treatment with acyclovir is useful in decreasing complications, latency and communicability
• Side effects may include nausea, vomiting, diarrhea, loss of appetite, and muscle or joint pain. Rarely, serious adverse effects may include renal and liver functions abnormalities or suppression of bone marrow activity.

Foscarnet

• It is effective against HSV 1, HSV 2 and CMV
• It is useful in patients who have developed resistance or are non-responders against acyclovir for e.g. HIV positive patients
• Drug dosage depends on the renal function of the patient as Foscarnet is excreted through kidneys.

Dexamethasone

• It is used in post-infectious and disseminated encephalitis.
• It may be used as an adjunct with the antiviral agents

Furosemide

• It is used to in encephalitis associated with increased intracranial pressure. The mechanism of action is;
  • It decreases the production of CSF by inhibiting carbonic anhydrase enzymes.
  • Decreases cerebral sodium uptake
  • Inhibits cellular membrane chloride pumps.
• The dose should be individualized for patients

Mannitol

• Used only on short term basis.
• The doses should be individualized based on renal function

Lorazepam

• It is used for treatment of seizures associated with encephalitis.

Empiric Therapy

▸ Click on the following categories to expand treatment regimens.

Empiric Therapy   ▸  Suspected encephalitis   ▸  Antimicrobials based on epidemiology/clinic   ▸  Rickettsial/ Ehrlichial infection   ▸  Acute Disseminated Encephalomyelitis

Suspected encephalitis Preferred Regimen ▸ Acyclovir 10 mg/kg IV q8h for 14-21 days, in children and adults with normal renal function ▸ Acyclovir 20 mg/kg IV q8h for 21 days, in neonates Antimicrobials based on epidemiology/clinic Preferred Regimen ▸ Please refer to Pathogen-based therapy according to epidemiology and clinical evaluation Rickettsial/ Ehrlichial infection Preferred Regimen ▸ Acyclovir 10 mg/kg IV q8h in children and adults with normal renal function ▸ Acyclovir 20 mg/kg IV q8h in neonates PLUS ▸ Doxycycline 200 mg/d in two divided doses Alternative Regimen ▸ Tetracycline 25-50 mg/kg per day Oral, in four divided doses Acute Disseminated Encephalomyelitis Preferred Regimen ▸ Acyclovir 10 mg/kg IV q8h in children and adults with normal renal function ▸ Acyclovir 20 mg/kg IV q8h in neonates PLUS ▸ Corticosteroids (dexamethasone) 10 mg IV q6h

Pathogen-Based Therapy — Viruses

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Viruses   ▸  Herpes simplex   ▸  Varicella-zoster virus   ▸  Cytomegalovirus   ▸  Epstein-Barr virus   ▸  Human herpesvirus 6   ▸  B virus   ▸  Influenza virus   ▸  Measles virus   ▸  Nipah virus   ▸  West Nile virus   ▸  Japanese encephalitis virus   ▸  St. Louis encephalitis virus   ▸  HIV   ▸  JC virus

Herpes simplex Preferred Regimen ▸ Acyclovir 10 mg/kg IV q8h for 14-21 days, in children and adults with normal renal function ▸ Acyclovir 20 mg/kg IV q8h for 21 days, in neonates Varicella-zoster virus Preferred Regimen ▸ Acyclovir 10-15 mg/kg IV q8h for 10-14 days, in children and adults with normal renal function ▸ Acyclovir 20 mg/kg IV q8h in neonates PLUS ▸ Corticosteroids (dexamethasone) 10 mg IV q6h Alternative Regimen ▸ Ganciclovir 5 mg/kg IV q12h for 14-21 days PLUS ▸ Corticosteroids (dexamethasone) 10 mg IV q6h Cytomegalovirus Preferred Regimen ▸ Ganciclovir 5 mg/kg IV q12h for 14-21 days, then valganciclovir 900 mg PO q24h PLUS ▸ Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h for 14-21 days; then 90-120 mg/kg IV q24h. Epstein-Barr virus Preferred Regimen ▸ Corticosteroids (dexamethasone) 10 mg IV q6h† † May be beneficial, however potential risks must be considered. Human herpesvirus 6 Preferred Regimen† ▸ Ganciclovir 5 mg/kg IV q12h for 14-21 days Alternative Regimen† ▸ Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h for 14-21 days; then 90-120 mg/kg IV q24h. † Used in immunocompromised patients; no good data on effectiveness in immunocompetent patients. B virus Postexposure prophylaxis ▸ Valacyclovir 1 gm PO q8h, for 14 days OR ▸ Acyclovir 800 mg PO 5x/day, for 14 days Treatment of disease (Absent CNS symptoms) ▸ Ganciclovir 5 mg/kg IV q12h OR ▸ Acyclovir 12.5-15 mg/kg IV q8h Treatment of disease (Presenting CNS symptoms) ▸ Ganciclovir 5 mg/kg IV q12h Influenza virus Preferred Regimen ▸ Oseltamivir 75 mg/day, for at least 10 days Measles virus Preferred Regimen† ▸ Ribavirin † Consider intrathecal ribavirin in patients with subacute sclerosing panencephalitis Nipah virus Preferred Regimen ▸ Ribavirin West Nile virus Preferred Regimen† ▸ † Ribavirin is not recommended Japanese encephalitis virus Preferred Regimen† ▸ † IFN-α is not recommended St. Louis encephalitis virus Preferred Regimen ▸ IFN-2α HIV Preferred Regimen ▸ HAART JC virus Preferred Regimen ▸ Reversal of immunosuppression OR ▸ HAART† † In HIV-infected patients

Pathogen-Based Therapy — Bacteria

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Bacteria   ▸  Bartonella bacilliformis   ▸  Bartonella henselae   ▸  Listeria monocytogenes   ▸  Mycoplasma pneumoniae   ▸  Tropheryma whipplei Mycobacteria   ▸  Mycobacterium tuberculosis Rickettsioses and ehrlichioses   ▸  Anaplasma phagocytophilum   ▸  Ehrlichia chaffeensis   ▸  Rickettsia rickettsii   ▸  Coxiella burnetii Spirochetes   ▸  Borrelia burgdorferi   ▸  Treponema pallidum

Bartonella bacilliformis Preferred Regimen ▸ Chloramphenicol50 mg/kg/day IV q6h. Resistant strains might require up to 100 mg/kg/day Alternative Regimen ▸ Ciprofloxacin 500 mg PO q12h OR ▸ Doxycycline 100 mg/day PO q12h OR ▸ Ampicillin 250-500 mg/day PO q6h OR ▸ Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h Bartonella henselae Preferred Regimen† ▸ Azithromycin Adults: 500 mg PO, 1x, then 250 mg/day PO for 4 days; Children: 10 mg/kg 1x, then 5 mg/kg/day PO for 4 days Alternative Regimen ▸ Doxycycline 100 mg PO 2x/day for 8 weeks † With or without Rifampin 300 mg PO 2x/day. Listeria monocytogenes Preferred Regimen ▸ Ampicillin 250-500 mg PO q6h or 1-2 g IV/IM q4-6h PLUS ▸ Gentamicin 1-2.5 mg/kg/dose IV/IM q8-12h Alternative Regimen† ▸ Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h † In the penicillin-allergic patient Mycoplasma pnumoniae Preferred Regimen ▸ Azithromycin 500 mg PO once, then 250 mg 1x/day, for 4 days Alternative Regimen ▸ Doxycycline 200 mg/day BID PO or IV 1x/day, then 100-200 mg/day qDay or divided q12h PO/IV OR ▸ Fluoroquinolone 500 mg PO/IV 1x/day, for 7-14 days or 750 mg PO/IV 1x/day, for 5 days Tropheryma whipplei Preferred Regimen ▸ Ceftriaxone 1-2 g/day IV/IM 1x/day or divided q12h, for 4-14 days PLUS ▸ Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h OR ▸ Cefixime 400 mg/day PO 1x/day or divided q12h Mycobacterium tuberculosis Preferred Regimen ▸ Isoniazid 300 mgPO qDay, for 9 months PLUS ▸ Rifampin 10 mg/kg/day PO or 10 mg/kg PO 2x/week (do not exceed 600 mg/day) (DOT) PLUS ▸ Ethambutol 15 mg/kg PO qDay PLUS ▸ Pyrazinamide 15-30 mg/kg PO qDay; not exceeding 2 g/day or 50 mg/kg PO 2x/weekly, not exceeding 2 g/dose PLUS ▸ Dexamethasone 10mg IV q6h† † Add in patients with meningitis Anaplasma phagocytophilum Preferred Regimen ▸ Doxycycline 100 mg PO 2x/day for 30-60 days Ehrlichia chaffeensis Preferred Regimen ▸ Doxycycline 100 mg PO 2x/day for 30-60 days Rickettsia rickettsii Preferred Regimen ▸ Doxycycline 100 mg PO 2x/day for 30-60 days Alternative Regimen ▸ Chloramphenicol 50 mg/kg/day IV divided q6hr† † In certain clinical scenarios (pregnancy) Coxiella burnetii Preferred Regimen ▸ Doxycycline 100 mg PO 2x/day for 30-60 days PLUS ▸ Fluoroquinolone 500 mg PO q12h or 400 mg IV q12h for 10 days PLUS ▸ Rifampin 600 mg q12hr for 2 days Borrelia burgdorferi Preferred Regimen ▸ Ceftriaxone 1-2 g/day IV/IM 1x/day or divided q12h, for 4-14 days OR ▸ Cefotaxime 2 g IV q4h, up to 12 g/day OR ▸ Penicillin G 4.4 million units/4mL syringe x1 Treponema pallidum Preferred Regimen ▸ Penicillin G 4.4 million units/4mL syringe x1 Alternative Regimen ▸ Ceftriaxone 1-2 g/day IV/IM 1x/day or divided q12h, for 4-14 days

Pathogen-Based Therapy — Fungi, Protozoa and Helminths

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Fungi   ▸  Coccidioides species   ▸  Cryptococcus neoformans   ▸  Histoplasma capsulatum Protozoa   ▸  Acanthamoeba   ▸  Balamuthia mandrillaris   ▸  Naegleria fowleri   ▸  Plasmodium falciparum   ▸  Toxoplasma gondii   ▸  Trypanosoma brucei gambiense   ▸  Trypanosoma brucei rhodesiense Helminths   ▸  Baylisascaris procyonis   ▸  Gnathostoma species   ▸  Taenia solium

Coccidioides species Preferred Regimen ▸ Fluconazole Alternative Regimen ▸ Itraconazole OR ▸ Voriconazole OR ▸ Amphotericin B (IV or Intratechal) Cryptococcus neoformans Preferred Regimen ▸ Amphotericin B deoxycholate PLUS ▸ Flucytosine Alternative Regimen ▸ Lipid formulation of amphotericin B PLUS ▸ Flucytosine Histoplasma capsulatum Preferred Regimen ▸ Liposomal Amphotericin B PLUS ▸ Itraconazole Acanthamoeba Preferred Regimen ▸ Trimethoprim-Sulfametoxazole PLUS ▸ Rifampin PLUS ▸ Ketoconazole Alternative Regimen ▸ Fluconazole PLUS ▸ Sulfadiazine PLUS ▸ Pyrimethamine Balamuthia mandrillaris Preferred Regimen ▸ Pentamidine PLUS ▸ Macrolide (Azithromycin or Clarithromycin) PLUS ▸ Fluconazole PLUS ▸ Sulfadiazine PLUS ▸ Flucytosine PLUS ▸ Phenothiazine Naegleria fowleri Preferred Regimen ▸ Amphotericin B 1.5 mg/kg/day IV divided in 2 doses, for 3 days; then 1 mg/kg/day for 6 days + 1.5 mg/day intrathecal for 2 days; then 1 mg/day intrathecal for 8 days PLUS ▸ Rifampin Plasmodium falciparum Preferred Regimen† ▸ Quinine OR ▸ Quinidine OR ▸ Artemether Alternative Regimen ▸ Atovaquone-proguanil † Exchange transfusion recommended for patients with cerebral malaria or more than 10% parasitemia. Toxoplasma gondii Preferred Regimen ▸ Pyrimethamine PLUS ▸ Sulfadiazine OR ▸ Clindamycin Alternative Regimen ▸ Trimethoprim-Sulfametoxazole OR ▸ Pyrimethamine PLUS ▸ Atovaquone OR ▸ Clarithromycin OR ▸ Azithromycin OR ▸ Dapsone Trypanosoma brucei gambiense Preferred Regimen ▸ Eflornithine Alternative Regimen ▸ Melarsoprol Trypanosoma brucei rhodesiense Preferred Regimen ▸ Melarsoprol 2-3.6 mg/kg/day IV for 3 days; then repeat after 7 days; then repeat for 3rd time, 7 days after the 2nd course Baylisascaris procyonis Preferred Regimen† ▸ Albendazole PLUS ▸ Diethycarbamazine † Consider adjunctive corticosteroids Gnathostoma species Preferred Regimen ▸ Albendazole 400 mg PO q24h or twice a day, for 21 days OR ▸ Ivermectin 200 μg/kg/day PO, for 2 days Taenia solium Preferred Regimen† ▸ Albendazole PLUS ▸ Corticosteroids Alternative Regimen ▸ Praziquantel † Evaluate need for treatment

Pathogen-Based Therapy — Postinfectious or Postvaccination status

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Postinfectious/postvaccination status   ▸  Acute disseminated encephalomyelitis

Acute Disseminated Encephalomyelitis Preferred Regimen† ▸ High dose Corticosteroids Alternative Regimen ▸ Plasma exchange OR ▸ Intravenous immunoglobulin

Follow Up Therapy

• Physiotherapy
• Occupational therapy
• Speech therapy
• Psychotherapy