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 Neonates: 20 mg/kg IV q8h for 21 days; Children and Adults with normal renal function: 10 mg/kg IV q8h for 14-21 days 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 Neonates: 20 mg/kg IV q8h; Children and Adults with normal renal function: 10 mg/kg IV q8h 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 Neonates: 20 mg/kg IV q8h; Children and Adults with normal renal function: 10 mg/kg IV q8h PLUS ▸ Corticosteroids (dexamethasone) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day

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 Neonates: 20 mg/kg IV q8h for 21 days; Children and Adults with normal renal function: 10 mg/kg IV q8h for 14-21 days Varicella-zoster virus Preferred Regimen ▸ Acyclovir Neonates: 20 mg/kg IV q8h; Children and Adults with normal renal function: 10-15 mg/kg IV q8h for 10-14 days PLUS ▸ Corticosteroids (dexamethasone) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day Alternative Regimen ▸ Ganciclovir 5 mg/kg IV q12h for 14-21 days PLUS ▸ Corticosteroids (dexamethasone) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day 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) initial 10 mg IV, then 4 mg IM q6h or 2 mg PO 2x-3x/day† † 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 benzathine 2.4 million units/4mL syringe IM qWeek x3 Treponema pallidum Preferred Regimen ▸ Penicillin G benzathine 2.4 million units/4mL syringe IM qWeek x3 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 400 mg PO on day 1, followed by 200 mg PO qDay Alternative Regimen ▸ Itraconazole 200 mg PO q8hr for 3-4 days, followed by 200-400 mg/day for at least 3 months OR ▸ Voriconazole 6 mg/kg IV q12hr for 24 hours, followed by 4 mg/kg IV q12hr or 200 mg PO q12hr OR ▸ Amphotericin B (IV or Intratechal) start with load dose: 0.25-0.5 mg/kg IV infused over 2-6h, followed by maintenance dose: 0.25-1 mg/kg IV qDay Cryptococcus neoformans Preferred Regimen ▸ Amphotericin B start with load dose: 0.25-0.5 mg/kg IV infused over 2-6h, followed by maintenance dose: 0.25-1 mg/kg IV qDay PLUS ▸ Flucytosine 50-150 mg/kg/day PO divided q6hr Alternative Regimen ▸ Lipid formulation of amphotericin B 6 mg/kg IV qDay PLUS ▸ Flucytosine 50-150 mg/kg/day PO divided q6hr Histoplasma capsulatum Preferred Regimen ▸ Liposomal Amphotericin B 6 mg/kg IV qDay PLUS ▸ Itraconazole 200 mg PO q8hr for 3-4 days, followed by 200-400 mg/day for at least 3 months Acanthamoeba Preferred Regimen ▸ Trimethoprim-Sulfametoxazole 10-20 mg TMP/kg/day IV divided q6-12h PLUS ▸ Rifampin 600 mg q12hr for 2 days PLUS ▸ Ketoconazole 200-400 mg/day PO Alternative Regimen ▸ Fluconazole 400 mg PO on Day 1, then 200 mg PO qDay PLUS ▸ Sulfadiazine 1-1.5 g 4x/day, for 3-4 weeks; prophylaxis in HIV patients: 0.5-1 g q6h with pyrimethamine (25-75 mg/day PO) & Folinic acid (10-25 mg/day PO) PLUS ▸ Pyrimethamine 50-75 mg qDay PO, for 1-3 weeks; then 25-37.5 mg qDay PO for 4-5 weeks Balamuthia mandrillaris Preferred Regimen ▸ Pentamidine 2-4 mg/kg IM q24-48hr PLUS ▸ Macrolide (Azithromycin 500 mg PO once, then 250 mg once daily; or Clarithromycin 500 mg PO q12hr) PLUS ▸ Fluconazole 400 mg PO on Day 1, then 200 mg PO qDay PLUS ▸ Sulfadiazine 1-1.5 g 4x/day, for 3-4 weeks; prophylaxis in HIV patients: 0.5-1 g q6h with pyrimethamine (25-75 mg/day PO) & Folinic acid (10-25 mg/day PO) PLUS ▸ Flucytosine 50-150 mg/kg/day PO divided q6hr 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 600 mg q12hr for 2 days Plasmodium falciparum Preferred Regimen† ▸ Quinine 648 mg PO q8hr, for 3-7 days OR ▸ Quinidine 300-600 mg or 10 mg/kg PO q8hr, for 5-7 days OR ▸ Artemether Administer 24 tablets over 3 days: Day 1: 4 tablets initially and 4 tablets after 8h; Day 2 and 3: 4 tablets 2x/day (1 tablet= 20mg/120mg) Alternative Regimen ▸ Atovaquone-proguanil 1 g/400 mg PO daily, for 3 days † Exchange transfusion recommended for patients with cerebral malaria or more than 10% parasitemia. Toxoplasma gondii Preferred Regimen ▸ Pyrimethamine 50-75 mg qDay PO for 1-3 weeks, then 25-37.5 mg qDay PO for 4-5 weeks PLUS ▸ Sulfadiazine 1-1.5 g 4x/day, for 3-4 weeks; prophylaxis in HIV patients: 0.5-1 g q6h with pyrimethamine (25-75 mg/day PO) & Folinic acid (10-25 mg/day PO) OR ▸ Clindamycin 300 mg PO 4x/day, for 6 weeks Alternative Regimen ▸ Trimethoprim 10 mg/kg/day - Sulfametoxazole 50 mg/kg/day, for 4 weeks OR ▸ Pyrimethamine 100mg loading dose PO followed by 25-50 mg/day, for 6 weeks PLUS ▸ Atovaquone 750 mg 2x/day, for 6 weeks OR ▸ Clarithromycin 500 mg PO q12hr OR ▸ Azithromycin 500 mg/day, for 6 weeks OR ▸ Dapsone 100 mg PO qDay Trypanosoma brucei gambiense Preferred Regimen ▸ Eflornithine 400 mg/kg/day IV divided 4x/day, for 14 days, then 300 mg/kg/day PO, for 3-4 weeks Alternative Regimen ▸ Melarsoprol 2-3.6 mg/kg/day IV, for 3 days; after 1 week: 3.6 mg/kg/day IV, for 3 days; then repeat again after 10-21 days: 3.6 mg/kg/day 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 400 mg PO x1 day 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 (more than 60 kgs) 400 mg PO 2x/day, for 8-30 days; (less than 60 kg) 15 mg/kg/day PO divided 2x/day, for 8-30 days; no more than 800 mg/day PLUS ▸ Corticosteroids Alternative Regimen ▸ Praziquantel 10-20 mg/kg x1 † Evaluate need for treatment

Pathogen-Based Therapy — Postinfectious or Postvaccination status

▸ Click on the following categories to expand treatment regimens.

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