Sandbox encephalitis2

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

• Acyclovir 10 mg/kg IV q8h

• Acyclovir 10 mg/kg IV q8h

• Acyclovir 20 mg/kg IV q8h

Antimicrobial Regimen – Pathogen-Based Therapy

Viruses

• Epidemiological or clinical features:

• Children or immunocompromised patients
• Associated with pneumonia

• Recommended therapy:

• Supportive care

• 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:

• 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:

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

• 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:

• 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
• Acute progression; poliomyelitis-like paralysis

• Recommended therapy:

• Supportive care

• 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:

• 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:

• 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:

• 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:

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

• Recommended therapy:

• Ganciclovir OR foscarnet

• 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:

• 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:

• 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:

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

• 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:

• 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

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.