Description

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

Epidemiology

• Exact incidence is unknown, but infants and children are predominantly affected.
• Encephalitis due to enterovirus or arbovirus has a peak incidence between summer and early autumn. Many cases of viral encephalitis occur in epidemics.

Risk Factors

• Unimmunized state (measles, mumps, rubella, influenza)
• Travel or residence in an 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 the blood-borne route, 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., acute disseminated encephalomyelitis [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.

Etiology

• In most cases, the underlying cause remains unknown. Of those with known etiology, the majority are due to viral agents, followed by bacterial, autoimmune, parasitic, and fungal causes.
• The most common viral causes include HSV-1 and HSV-2, enteroviruses, arboviruses (West Nile virus [WNV]), and other herpesviruses (CMV, EBV, HHV-6, VZV).
  • HSV-1 typically presents with focal seizures, often of temporal lobe origin and encephalopathy.
  • HSV-2 is the predominant cause of neonatal HSV infection.
  • Enteroviruses and arboviruses typically cause disease in the summer and fall.
  • WNV presents as an acute flaccid paralysis, extrapyramidal symptoms, and cranial nerve palsies.
  • Zika virus may rarely result in meningoencephalitis but is more commonly associated with low-grade fever and rash and with congenital microcephaly.
  • Other viruses may be considered given specific historical features (rabies with animal bite or bat exposure or with prominent hydrophobia) or history of travel (Japanese encephalitis virus).
• 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.
• Parainfectious etiologies include ADEM, acute hemorrhagic leukoencephalitis, postinfectious cerebellitis, and Mycoplasma encephalopathy. ADEM typically presents with encephalopathy and focal neurologic symptoms, with an MRI showing multifocal white matter lesions.
• Other inflammatory or paraneoplastic etiologies include anti-NMDA receptor encephalitis, voltage-gated potassium channel complex antibody, aquaporin-4 autoimmunity, SREAT (steroid-responsive encephalopathy associated with thyroid disease), systemic lupus erythematosus, and other vasculitis. Anti-NMDA receptor encephalitis typically presents subacutely with encephalopathy, sleep disturbance, seizures, perioral dyskinesias, and autonomic disturbances.

Commonly Associated Conditions

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