DESCRIPTION

Encephalitis is inflammation of the brain parenchyma, which results in alterations in mental status, motor or sensory symptoms, speech problems, or seizures. It is generally nonpurulent, in contrast to cerebritis. This inflammation may be due to direct brain invasion by an infectious pathogen or immune-mediated from inflammatory processes due to acute or chronic illnesses.

EPIDEMIOLOGY

• 7.3 cases per 100,000 person-years in the United States between 2000 and 2010, with the highest rates in infants (13.5 per 100,000 person-years)
• Encephalitis due to enterovirus or arbovirus has a peak incidence between summer and early autumn.
• Many cases of viral encephalitis occur in epidemics.

ETIOLOGY

• An etiology is identified in approximately 50% of cases of encephalitis in children, and the range of etiologies is broad, including infectious, immune-mediated, rheumatologic, neoplastic, and toxic causes.
• Infectious causes are most frequent and include viruses, atypical bacteria, fungi, and parasites. The most common viral causes include herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), enteroviruses, arboviruses (West Nile virus [WNV]), and other herpesviruses (CMV, EBV, HHV-6, VZV).
• Bacterial causes include Listeria, Francisella tularensis, Bartonella, Mycobacterium, Rickettsia, Mycoplasma, Borrelia, and Chlamydia.
• Fungal and parasitic causes include Cryptococcus, Blastomyces, Histoplasma, Paracoccidioides, Naegleria, Toxoplasma, Plasmodium, and Toxocara.
• Immune-mediated causes account for the majority of culture-negative cases. These can include not only parainfectious etiologies such as acute disseminated encephalomyelitis (ADEM), acute hemorrhagic leukoencephalitis, postinfectious cerebellitis, and Mycoplasma encephalopathy or neuronal antibody-mediated conditions, most commonly anti-N-methyl-d-aspartate (NMDA) receptor encephalitis but also voltage-gated potassium channel complex antibody, aquaporin-4 autoimmunity, steroid-responsive encephalopathy associated with thyroid disease (SREAT), systemic lupus erythematosus, and other vasculitis.

RISK FACTORS

• Unimmunized status (measles, mumps, rubella, influenza)
• Travel or residence in endemic region

GENERAL PREVENTION

• Routine immunization for measles, mumps, rubella, and influenza and, if travelling to endemic area (e.g., Southeast Asia), consideration of immunization for Japanese encephalitis
• Careful hand washing, avoid tick and mosquito exposure (DEET [N,N-diethyl-meta-toluamide] repellant, mosquito netting, appropriate dress), and insect control (drainage of stagnant water, insecticides)

PATHOPHYSIOLOGY

• Transmission of infectious pathogens can be by direct invasion of the CNS (such as arbovirus), by retrograde spread through peripheral nerves (such as HSV or rabies), or rarely by direct inoculation of the brain.
• Encephalitis may also result indirectly, by immune-mediated injury due to parainfectious (i.e., ADEM or mycoplasma) or inflammatory/paraneoplastic causes (i.e., anti-NMDA receptor encephalitis). Such immune-mediated mechanisms involve cytokine effects and cytotoxic antibodies on neurons.

COMMONLY ASSOCIATED CONDITIONS

Children with autoimmune encephalitis have higher rates of other autoimmune disorders such as diabetes mellitus or juvenile rheumatoid arthritis.