• Direct or delayed (postinfectious) reaction by the immune system to a virus, bacteria, fungus, or parasite
• Organisms enter the CNS via the systemic circulation, direct inoculation (trauma), or neural pathways (rabies, herpes simplex virus [HSV]).
• Infiltration of inflammatory cells into the CNS
• Inclusion bodies (intranuclear; HSV, subacute sclerosing panencephalitis [SSPE], viral, intracytoplasmic; rabies), CSF, and serology changes

• Depends on age, geographic location, and season
• The most common causes of encephalitis are viruses:
  • Summer (enteroviruses)
    • Summer and fall (Western and Eastern equine encephalitis, St. Louis encephalitis, La Crosse encephalitis)
  • Winter (varicella)
• Nonviral causes (tuberculosis, Lyme disease, toxoplasmosis, cat-scratch disease, rickettsial disease, tick-borne infections) are associated with specific environmental or geographic exposure.
• The most common cause of sporadic encephalitis is HSV (rabies and HIV also occur in all seasons).

• Ingestions
• Reye syndrome
• Acute hemorrhagic leukoencephalitis (postinfectious, etiology unknown, associated Mycoplasma infection, destruction of white and gray matter)
• Intracranial hemorrhage
• Pituitary infarction
• Acute obstructive hydrocephalus or ventriculoperitoneal shunt obstruction
• Sinus thrombosis
• Subdural empyema
• Stroke or septic embolization (endocarditis)
• Brain abscess or subdural empyema
• Malignant hyperthermia
• Status epilepticus
• Other considerations include bacterial meningitis (Neisseria meningitidis, Haemophilus influenzae type b, group B streptococcus in the neonate, Escherichia coli in the neonate) parasites, acute disseminated encephalomyelitis (ADEM), and vasculitis.
• Diagnosis of specific causes of true encephalitis depends on geographic location, age, and clinical and associated laboratory findings.
• Microbes to consider:
  • Herpes viruses (in the child and adult, herpes has preference for the medial temporal lobe)
  • Lyme disease; possible coinfection with ehrlichiosis, babesiosis
  • Varicella (postinfectious encephalitis)
  • Cat-scratch and rickettsial diseases
  • Tuberculosis
  • Fungal (cryptosporidiosis)
  • Parasitic (amebae, Toxoplasma, cysticercosis)
  • Toxoplasma
• Meningitis:
  • Meningitis may cause secondary parenchymal inflammation of the brain
  • Mental status changes are usually more prominent in primary encephalitis as compared with meningitis

• Ask about a viral prodrome with symptoms such as upper respiratory infection, cough, coryza, malaise, anorexia, decreased enteral intake, diarrhea, nausea, and vomiting.
• Encephalitis is often heralded by headaches, photophobia, a stiff neck, increased sleeping, a change in mental status, irritability, confusion, hallucinations, and seizures.
• Prodromal symptoms can range from hours to weeks.
• Inquire about recent travel history, pets, and tick bites.

• Changing vital signs may suggest impending herniation due to brain swelling (hypertension, bradycardia, apnea).
• Neck: The patient may have meningismus and positive Kernig and Brudzinski signs.
• Diffuse adenopathy
• Chest: signs of pneumonia, rales, rhonchi
• Abdomen: hepatosplenomegaly
• Skin: may show various types of rashes, from petechial in meningococcemia to an erythematous nonspecific viral rash
• Neurologic examination: rapid or slow changes in mental status ranging from mild confusion to hallucinations to stupor and coma
• Aphasia (suggestive of herpes) is distinguished from psychomotor slowing by prominence of grammatic errors and dysarthria and normal alertness.
• There may be pupillary abnormalities with nystagmus: Funduscopic examination may reveal papilledema as a sign of increased intracranial pressure (ICP). Cranial neuropathies, increased muscle tone, pathologic deep tendon reflexes, Babinski sign, clonus, ataxia, and so forth, may be encountered.

• Never assume that a CSF pleocytosis is secondary to seizures. Institute antiviral and antibacterial therapy promptly; it can always be discontinued once an organism is identified or cultures are negative.
• Children with immunodeficiency are at higher risk for fungal meningoencephalitis, which may be missed unless appropriate studies are sent.
• Amebic infection of the brain should be considered in children with exposure to fresh water sources.
• Cysticercosis is common in tropical and underdeveloped areas. Ring-enhancing lesions may point to this diagnosis.

• CT or MRI of the brain with and without contrast medium should be performed urgently to rule out surgically remediable conditions (empyema, abscess).
• Typical changes in encephalitis include parenchymal, meningeal, and focal or diffuse enhancement of the brain. (HSV has a preference for the medial temporal lobe, with hemorrhagic and cystic changes.)
• Hydrocephalus, obstructive or communicating, may occur as a result of the encephalitis.

• Opening pressure is frequently elevated.
• Pleocytosis is lymphocytic if viral, and usually neutrophilic if bacterial.
• Protein will be increased, glucose will be decreased, and RBCs may be present (particularly in HSV).
• CSF should be sent for bacterial and viral culture. Order a fungal culture if suspected.
• If HSV is suspected, PCR should be obtained, as the virus is difficult to grow in vitro.
• Gram stain and acid-fast bacillus, cryptococcal antigen, and yeast tests also should be ordered.

• Blood electrolytes, BUN, glucose, calcium, magnesium, phosphorus, blood count with differential, blood and urine culture, and toxicology screen
• An EEG may be helpful, particularly if HSV is suspected; it may show periodic lateralizing epileptiform discharges (PLEDs), which are suggestive, but not diagnostic, of herpes.

• General: Patients with encephalitis frequently require ICU care with cardiorespiratory support. Mini-dose subcutaneous heparin is standard for prophylaxis of intravascular thrombosis in acutely ill adults, but is untested in the pediatric age group. Early involvement of physical and occupational therapy is important.
• Treatment of intracranial hypertension includes mannitol and hyperventilation, usually with assistance from intensivists or neurology/neurosurgery consultants; these measures should be reserved for situations in which vital or neurologic signs indicate impending herniation.
• Antiinfective agents: Initial treatment should be with antibacterial and antiviral agents (acyclovir: monitor renal function) until the cause becomes clear or cultures are negative.
• Fluids: Avoidance of fluid overload, which may exacerbate cerebral edema, requires strict attention to fluid/osmotic balance. Normal saline is preferred; electrolytes are closely monitored, anticipating possible SIADH or diabetes insipidus.
• Anticonvulsants are reserved for clinical or electrographic evidence of seizure/epileptic activity; usual choices include phenytoin, phenobarbital, and carbamazepine. Treatment of PLEDs without associated convulsions is controversial. Potential side effects and sedation from anticonvulsants should be considered in this decision.
• Consultation with an infectious disease specialist, neurologist, or neurosurgeon may be helpful.

• Completion of routine immunizations (varicella, H-flue type b, etc.) and routine hygiene (hand washing) are the best preventive measures.
• Other measures should be taken according to the infection (e.g., skin testing contacts in cases of tuberculosis).
• Isolation of hospitalized patient: depends on organism suspected. Airborne, droplet, and contact precautions are frequently used together during the first 24 hours, pending a more specific diagnosis from cultures. The infectious disease department will determine type and duration of isolation and whether family members need to be treated.

Q: My child has been diagnosed with encephalitis; will he be mentally retarded?
A: The complications following encephalitis vary greatly from severe mental retardation and cerebral palsy to full recovery. There is a correlation between degree of brain destruction and outcome. However, children frequently recover better than adults with a similar degree of illness.

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Whitley RJ, Lakeman F. Herpes simplex virus infections of the central nervous system: therapeutic and diagnostic considerations. Clin Infect Dis 1995;20(2):414–420.