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

Acyclovir (10–20 mg/kg IV q8h) should be administered to all patients with suspected encephalitis as early as possible to reduce the risk of neurologic sequelae. Doxycycline should be added to empirical regimen if epidemiological or clinical clues suggest rickettsial or ehrlichial infection. Despite the wide range of viruses that cause encephalitis, specific antiviral agent is generally limited to infections caused by the herpesviridae and human immunodeficiency virus (HIV). Treatment for other viral encephalitis is largely 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.

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.

Antimicrobial Regimen – Empiric Therapy

Adapted from The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America:

• Acyclovir 10 mg/kg IV q8h

• Acyclovir 10 mg/kg IV q8h

• Acyclovir 20 mg/kg IV q8h

Antimicrobial Regimen – Pathogen-Based Therapy

Adapted from The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America:

Viruses

• Epidemiological or clinical features:

• Children or immunocompromised patients
• Associated with pneumonia

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Transmitted by bites or scratches from macaques
• Vesicular eruption at site of bite or scratch, followed by neurologic symptoms in 3–7 days
• Transverse myelitis

• Recommended therapy:

• Wound decontamination
• Acyclovir OR valacyclovir OR ganciclovir for established disease
• Prophylactic valacyclovir after bite or scratch

• Epidemiological or clinical features:

• Immunocompromised hosts (particularly those with AIDS)
• Retinitis, pneumonitis, adrenalitis, myelitis, polyradiculopathy

• Recommended therapy:

• Ganciclovir AND
• Foscarnet

• Epidemiological or clinical features:

• North America (especially Atlantic and Gulf states)
• Mainly affects children and elderly persons
• Abrupt onset with fulminant course
• Seizures, headache, or altered consciousness

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Exposure to saliva from those with asymptomatic shedding
• Seizures, coma, personality changes, cerebellar ataxia, cranial nerve palsies
• Transverse myelitis

• Recommended therapy:

• Supportive care
• May consider corticosteroids

• Epidemiological or clinical features:

• Australia
• Transmitted through excretions from infected horses
• Fever, drowsiness, seizures, and coma accompanying severe flulike illness

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Immunocompromised hosts (particularly in transplant recipients)
• Recent exantham ; seizures
• Delirium occurs more commonly than seizures

• Recommended therapy:

• Ganciclovir OR foscarnet

• Epidemiological or clinical features:

• Acute encephalopathy with seroconversion
• Most commonly presents as HIV dementia (forgetfulness, loss of concentration, cognitive dysfunction, psychomotor retardation)

• Recommended therapy:

• HAART

• Epidemiological or clinical features:

• Most common causes of identified sporadic encephalitis worldwide
• Fever, hemicranial headache, language and behavioral abnormalities, memory impairment, seizures, or SIADH

• Recommended therapy:

• Acyclovir

• Epidemiological or clinical features:

• Often affects children
• Prior or concomitant respiratory tract symptoms
• Associated with bilateral thalamic necrosis (also called acute necrotizing encephalopathy)

• Recommended therapy:

• Oseltamivir

• Epidemiological or clinical features:

• Japan, China, Korea, Taiwan, Southeast Asia, India, Nepal, northern Australia
• Mainly children
• Seizures, parkinsonian features, poliomyelitis-like flaccid paralysis

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Cell-mediated immunodeficiencies or immunomodulating therapy (natalizumab, rituximab)
• Cognitive dysfunction
• Limb weakness, gait disturbance, or coordination difficulties, visual field cuts

• Recommended therapy:

• Reversal of immunosuppression
• Administer HAART in AIDS patients

• Epidemiological or clinical features:

• Midwestern and eastern United States
• School-aged children
• Fulminant onset, with seizures, paralysis, focal weakness

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Unvaccinated children and adults
• Decline of consciousness, seizures, or focal neurologic signs

• Recommended therapy:

• Ribavirin for life-threatening disease
• Intrathecal ribavirin for SSPE

• Epidemiological or clinical features:

• Unvaccinated individuals
• Previous parotitis
• Headaches, vomiting, seizures, altered consciousness, sensorineural hearing loss

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Australia, New Guinea
• Aboriginal children
• Rapid disease progression in infants

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• South Asia
• Close exposure to infected pigs or bats
• Fever, headache, altered mental status, dizziness, and vomiting
• Headaches, vomiting, seizures, altered consciousness, sensorineural hearing loss
• Myoclonus, dystonia, areflexia, and hypotonia; pneumonitis

• Recommended therapy:

• Supportive care
• May consider ribavirin

• Epidemiological or clinical features:

• Late summer and early fall
• Aseptic meningitis occurs more commonly than encephalitis
• Enterovirus 71 causes rhombencephalitis (myoclonus, tremors, ataxia, and cranial nerve defects)

• Recommended therapy:

• Supportive care
• Intraventricular gamma-globulin for severe disease

• Epidemiological or clinical features:

• Unvaccinated infants in Africa and Asia
• Disturbances in consciousness, seizures, or flaccid paralysis

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• New England states, Canada, Asia
• Focal neurologic deficits in > 50% of patients

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Transmitted by the bite of an infected animal
• Furious form: agitation, hydrophobia, bizarre behavior, and delirium progressing to disorientation, stupor, and coma
• Paralytic form: ascending paralysis and later cerebral involvement
• Most commonly presents as HIV dementia (forgetfulness, loss of concentration, cognitive dysfunction, psychomotor retardation)

• Recommended therapy:

• Supportive care
• Postexposure prophylaxis with immunoglobulin and vaccine

• Epidemiological or clinical features:

• Unvaccinated adults
• Rash followed within 1–6 days by headache, dizziness, behavioral abnormalities, seizures

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• North America (endemic in western United States, with periodic outbreaks in eastern United States), Central and South America
• Urinary symptoms (dysuria, urgency, and incontinence) followed by tremors, seizures, headache, nausea, vomiting, stupor, or paresis

• Recommended therapy:

• Supportive care
• May consider IFN alpha 2b

• Epidemiological or clinical features:

• Eastern Russia, central Europe, Far East
• Unpasteurized milk consumption
• Acute progression; poliomyelitis-like paralysis

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Abrupt onset of encephalopathy
• Focal neurologic deficits 2–30 days after vaccination
• Disturbances in consciousness, seizures, or flaccid paralysis

• Recommended therapy:

• Supportive care
• May consider corticosteroids

• Epidemiological or clinical features:

• Florida and southwestern United States, Central and South America
• Prominent myalgias; headache; pharyngitis

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• Recrudescent disease occurs in immunocompromised hosts
• Cerebellar involvement in children
• Delirium occurs more commonly than seizures
• Herpes zoster ophthalmicus

• Recommended therapy:

• Acyclovir OR ganciclovir
• May consider corticosteroids

• Epidemiological or clinical features:

• North and Central America, Africa, parts of Asia, Middle East, and southern Europe
• Older patients (age > 50 years) and immunocompromised hosts
• Abrupt onset of fever, headache, neck stiffness, and vomiting
• Tremors, myoclonus, parkinsonism, and poliomyelitis-like flaccid paralysis

• Recommended therapy:

• Supportive care

• Epidemiological or clinical features:

• North America (west of the Mississippi), Central and South America
• Headache, altered consciousness, seizures

• Recommended therapy:

• Supportive care

Bacteria

• Epidemiological or clinical features:

• Europe and mid-Atlantic and northern United States
• Abrupt onset of fever, headache, and myalgias followed by altered mental status

• Recommended therapy:

• Doxycycline

• Epidemiological or clinical features:

• Middle altitudes of Andes mountains
• Acute onset of severe headache
• Seizures, hallucinations, delirium, or altered mental status
• Profound hemolytic anemia

• Recommended therapy:

• Chloramphenicol OR Ciprofloxacin OR Doxycycline OR Ampicillin OR TMP-SMZ

• Epidemiological or clinical features:

• Bites or scratches from cats or other animals
• Regional lymphadenopathy, seizures, neuroretinitis

• Recommended therapy:

• Doxycycline OR Azithromycin with or without Rifampin

• Epidemiological or clinical features:

• North America, Europe, and Asia
• Neurologic symptoms may develop shortly after erythema migrans or with arthritis
• Facial nerve palsy, particularly bilateral, meningitis, or radiculitis

• Recommended therapy:

• Ceftriaxone OR Cefotaxime OR Penicillin G

• Epidemiological or clinical features:

• Contact with cats, sheep, goats (particularly placental tissues)
• Seizures and coma

• Recommended therapy:

• Doxycycline AND
• Fluoroquinolone AND
• Rifampin

• Epidemiological or clinical features:

• South central, southeastern, mid-Atlantic, and coastal states of the United States
• Confusion, photophobia, stupor, or hallucinations

• Recommended therapy:

• Doxycycline

• Epidemiological or clinical features:

• Neonates < 1 month of age or adults >50 years of age
• Pregnancy, alcohol abuse, and defects in cell-mediated immunity
• Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)

• Recommended therapy:

• Ampicillin OR TMP-SMZ AND
• Gentamicin

• Epidemiological or clinical features:

• Most commonly presents with basilar meningitis followed by lacunar infarctions and hydrocephalus
• Dementia, ophthalmoplegia, myoclonus, cerebellar ataxia, or psychiatric signs
• Oculomasticatory myorhythmia

• Recommended therapy:

• Isoniazid AND
• Rifampin AND
• Pyrazinamide AND
• Ethambutol
• Add dexamethasone in patients with meningitis

• Epidemiological or clinical features:

• More common in children
• Previous upper or lower respiratory tract disease
• Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)

• Recommended therapy:

• Azithromycin OR Fluoroquinolone OR Doxycycline

• Epidemiological or clinical features:

• North, Central, and South America
• Maculopapular, petechial rash on wrists and ankles beginning 3–5 days after onset of illness with rapid spread to palms and soles
• Altered mental status or intractable seizures

• Recommended therapy:

• Doxycycline OR Chloramphenicol (for pregnant patients)

• Epidemiological or clinical features:

• Transmitted through sexual contact
• General paresis, rapidly progressive dementia
• Psychiatric features

• Recommended therapy:

• Penicillin G OR Ceftriaxone

• Epidemiological or clinical features:

• Most commonly presents with progressive subacute encephalopathy
• Dementia, ophthalmoplegia, myoclonus, cerebellar ataxia, or psychiatric signs
• Oculomasticatory myorhythmia

• Recommended therapy:

• Ceftriaxone for 2–4 weeks, followed by TMP-SMZ OR Cefixime for 1–2 years

Fungi

• Epidemiological or clinical features:

• Semi-arid regions of the southwestern United States, Mexico, and South America
• Disorientation, lethargy, confusion, or memory loss

• Recommended therapy:

• Fluconazole OR Itraconazole OR Voriconazole OR Amphotericin B

• Epidemiological or clinical features:

• Often occurs in immunocompromised hosts
• Disorientation, lethargy, confusion, or memory loss

• Recommended therapy:

• Amphotericin B PLUS Flucytosine x 2 weeks, then Fluconazole x 8 weeks
• Amphotericin B PLUS Flucytosine x 6–10 weeks
• Consider V-P shunt in patients with persistent IICP

• Epidemiological or clinical features:

• Endemic in Ohio and Mississippi River valleys in the United States
• More common in immunocompromised hosts

• Recommended therapy:

• Amphotericin B lipid complex x 4–6 weeks, then Itraconazole x 1 year until resolution of CSF abnormalities

Protozoa

• Epidemiological or clinical features:

• Chronic alcoholism or immunocompromised hosts
• Commonly present with altered mental status and/or focal neurologic deficits
• Seizures, hemiparesis, and fever

• Preferred regimen:

• TMP-SMZ AND
• Rifampin AND
• Ketoconazole

• Alternative regimen:

• Fluconazole AND
• Sulfadiazine AND
• Pyrimethamine

• Epidemiological or clinical features:

• Both immunocompetent or immunocompromised hosts
• Fever, headache, vomiting, ataxia, hemiparesis, or cranial nerve palsies
• Seizures, hemiparesis, and fever

• Recommended therapy:

• Azithromycin OR Clarithromycin AND
• Pentamidine AND
• Flucytosine AND
• Fluconazole AND
• Sulfadiazine AND
• Thioridazine OR Trifluoperazine

• Epidemiological or clinical features:

• Swimming in lakes and brackish water
• Change in taste or smell 2–5 days after swimming
• Meningismus, papilledema, nystagmus, cranial nerve palsies, and ataxia
• Acute progression to coma and death

• Recommended therapy:

• Amphotericin B AND
• Rifampin AND
• Azithromycin OR Sulfisoxazole OR Miconazole

• Epidemiological or clinical features:

• Travel to tropical and subtropical areas of endemicity
• Impaired consciousness, seizures, focal neurologic deficits, and/or psychosis

• Preferred regimen:

• Quinine OR Quinidine OR Artesunate

• Alternative regimen:

• Atovaquone proguanil
• Exchange transfusion with > 10% parasitemia or cerebral malaria

• Epidemiological or clinical features:

• Reactivation in immunocompromised hosts
• Intrauterine infection may lead to severe necrotizing encephalitis
• Extrapyramidal signs, seizures, hemiparesis, or cranial nerve palsies

• Preferred regimen:

• Pyrimethamine AND
• Sulfadiazine OR Clindamycin

• Alternative regimen:

• TMP-SMZ

• Epidemiological or clinical features:

• Chronic disease with late CNS sequelae developing in months to years
• Irritabililty, personality changes, inability to concentrate, sleep disturbances, severe headache, ataxia, or extrapyramidal signs

• Recommended therapy:

• Eflornithine OR Melarsoprol

• Epidemiological or clinical features:

• Acute disease with early CNS disease
• Sleep disturbances, refractory headaches leading to death within weeks to months

• Recommended therapy:

• Melarsoprol

Helminths

• Epidemiological or clinical features:

• Children with raccoon exposure or playing in or eating dirt contaminated with raccoon feces
• CNS dysfunction, neurologic deficits, coma, death

• Recommended therapy:

• Albendazole AND
• Diethylcarbamazine AND
• Corticosteroids

• Epidemiological or clinical features:

• Southeast Asia (particularly Thailand and Japan) and Latin America
• Ingestion of undercooked fish, frogs, snakes, or fowl
• Headache, radicular pain, paralysis, and urinary incontinence

• Recommended therapy:

• Albendazole OR Ivermectin

• Epidemiological or clinical features:

• Mexico, Central America, South America, Southeast Asia
• Ingestion of undercooked fish, frogs, snakes, or fowl
• Seizures, hydrocephalus, chronic meningitis

• Recommended therapy:

• Corticosteroids AND
• Albendazole OR Praziquantel

Prion

• Epidemiological or clinical features:

• Sporadic CJD: dementia and ataxia followed by myoclonic jerks or other movement disorders, rapidly progressive dementia, and ultimately death
• Variant CJD: early psychiatric and sensory abnormalities, followed by cerebellar ataxia and rapidly progressive dementia

• Recommended therapy:

• Supportive care

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.