Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. The diagnosis is based on clinical suspicion, and once suspected, immediate empiric treatment is warranted to prevent catastrophic and long-term neurologic sequelae. Encephalitis is managed with supportive measures and antiviral therapy. Focal neurologic defects are common after encephalitis, and hence, physiotherapy is usually required.

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Encephalitis is an inflammation of the brain parenchyma caused by an infection that is usually viral and presents as diffuse or focal neuropsychologic dysfunction.


  • True incidence unknown
  • The most common causes are of viral infectious etiology. 
  • HSV is the most common cause of sporadic encephalitis in the Western world.
  • Arboviruses are the most common causes of episodic encephalitis in the United States (require insect vector).
  • West Nile virus is the most common cause of proven encephalitis in the United States.
  • Japanese encephalitis is the most common in Asian countries.
  • Extreme age groups are at the highest risk and experience a severe illness. 
  • High mortality rate: around 10%
  • Cognitive and neurologic disabilities are observed in most survivors.


There are 2 main types of encephalitis: 

  • Primary: 
    • Infection occurs directly in the brain tissue.
    • Infection can also be the reactivation of a dormant virus from a previous infection.  
  • Postinfectious:
    • Also known as acute disseminated encephalomyelitis (ADEM)
    • Infection occurs elsewhere in the body.
    • Neurons are spared, but there is evidence of perivascular inflammation and demyelination.
    • Likely immune-mediated disease


Viral encephalitis is the most common form of encephalitis. Bacterial, fungal, and parasitic encephalitides are extremely rare.

Viral causes:

  • HSV-1 and HSV-2
  • Arboviruses (transmitted by mosquitoes):
    • Eastern equine virus
    • Western equine virus 
    • Venezuelan equine virus
    • St. Louis virus
    • West Nile virus
  • Varicella zoster virus (VZV)
  • Epstein–Barr virus 
  • Rabies virus 
  • Japanese encephalitis virus
  • Chikungunya virus   

Other causes:   

  • Syphilis 
  • Mycoplasma spp.
  • Toxoplasma gondii 
  • Autoimmune 

Risk factors:

  • Immunocompromised or weak immune system 
  • Extreme age groups: infants and older adults 
  • Residence in areas infested with mosquitos and ticks

Pathophysiology and Clinical Presentation



  • Inhalation of respiratory droplets from an infected person
  • Contaminated food or drink 
  • Insect bites, especially in areas infested with mosquitos and ticks 
  • Reactivation of dormant virus in the trigeminal ganglia (HSV)


  • The virus replicates outside the CNS and binds to specific receptors on cell membranes. 
  • The virus spreads to the CNS through a hematogenous route or by retrograde neuronal dissemination. 
  • Once inside the neurons, the virus disrupts normal function and causes perivascular congestion, hemorrhage, and a diffuse inflammatory response.
  • Some viruses exhibit regional tropism (e.g., HSV has predilection for medial and inferior temporal lobes).
  • Primary encephalitis directly affects gray matter; postinfectious encephalitis causes widespread demyelination.

Clinical presentation

Adults/older children: 

  • Drowsiness 
  • Fever 
  • Headache
  • Seizures  
  • Muscle and joint pain 
  • Fatigue 
  • Confusion 
  • Problems in speech or hearing 
  • Paralysis of the face or certain parts of the body
  • Exaggerated deep tendon reflexes


  • A bulge in the fontanel 
  • Nausea and vomiting 
  • Stiff body 
  • Irritability 
  • Refusal to feed  

Distinguishing features (point toward a certain etiology):

  • Parotitis in mumps 
  • Grouped vesicular dermatomal rash in VZV
  • Features common in West Nile virus: 
    • Flaccid paralysis
    • Maculopapular rash
  • Features common in rabies:
    • Hydrophobia
    • Pharyngeal spasms
    • Myoclonus
    • Hyperactivity 
  • Features common in St. Louis virus:
    • Tremors in the eyelids 
    • Tremors in the tongue
    • Tremors in the lips
    • Tremors in the extremities 
  • Meningoencephalitis (when meninges are also inflamed):
    • Stiff neck
    • Photophobia



  • Geographic exposure
  • Arthropod bite
  • Animal bite
  • Known history of HSV infection


  • CT scan: mostly useful to rule out tumors
  • MRI:
    • Test of choice
    • HSV encephalitis often manifests in the temporal lobes.
    • West Nile encephalitis: basal ganglia, thalamus, cerebellum, brainstem, and temporal structures involved
    • Hydrocephalus would suggest nonviral etiologies.
    • Postinfectious encephalitis: multifocal white matter lesions
Contrast enhancement in the posterior side of the bilateral insular cortex, right hypothalamus, and inferior left frontal cortex consistent with encephalitis

MRI showing Epstein–Barr viral encephalitis:
Contrast enhancement in the posterior side of the bilateral insular cortex, right hypothalamus, and inferior left frontal cortex shows features consistent with encephalitis.

Image: “Contrast enhancement” by Division of Pediatric Infectious Diseases, Department of Pediatrics, Marmara University School of Medicine, 34890 Istanbul, Turkey. License: CC BY 4.0, cropped by Lecturio.
HSV encephalitis

MRI shows increased signal intensity in the temporal lobe of a confirmed case of HSV-1 encephalitis.

Image: “Hsv encephalitis” by Dr. Laughlin Dawes. License: CC BY 3.0

CSF analysis by lumbar puncture

  • Could be normal
  • Cell counts (elevated lymphocytes; WBCs < 250/mm³ )
  • Protein (mild elevation; < 150 mg/dL)
  • Glucose (normal or moderately reduced)
  • CSF culture: viral culture not reliable
  • CSF PCR testing (largely replaced by culture): 
    • HSV-1, HSV-2
    • Enteroviruses
    • VZV
    • CMV


EEG is abnormal in acute encephalitis.

Blood tests

  • WBC count with differential
  • A blood culture may be done to rule out a bacterial cause (in cases of meningoencephalitis).
  • Additional testing is considered on the basis of the clinical presentation and exposure history:
    • Serology for the arboviruses
    • HIV testing


Immediate response to encephalitis is crucial because it can quickly progress to complications.


  • Supportive therapy: 
    • Careful respiratory and cardiovascular monitoring 
    • Administration of IV fluids to maintain hydration and provide hemodynamic support 
    • Anti-inflammatory medication: corticosteroids (benefit unproven)
    • Mannitol to lower intracranial pressure (benefit unproven in viral encephalitis)
    • Anticonvulsants: phenytoin
  • Antiviral therapy: 
    • Acyclovir: 
      • Empiric treatment for suspected HSV encephalitis 
      • Should be started immediately to decrease morbidity and mortality
    • Ganciclovir 
    • Foscarnet 
  • Postencephalitis therapy: 
    • Physiotherapy to improve strength and mobility 
    • Occupational therapy to aid in daily activities 
    • Speech therapy 
    • Psychotherapy to improve behavioral health sequelae


  • Complications are common in survivors and depend on:
    • Age of the individual affected 
    • Duration of the illness 
    • Immune status of the individual 
    • Etiology of infection 
  • Complications that can occur:
    • Memory loss 
    • Muscle weakness and deterioration in coordination 
    • Change in personality 
    • Paralysis 
    • Loss of vision or hearing 
    • Speech impairment 
    • Epilepsy 
    • Difficulty breathing  
    • Coma

Differential Diagnosis

  • Meningitis: inflammation of the meninges usually caused by a bacterial or viral infection: Clinically, meningitis presents with headache, fever, and nuchal rigidity. Diagnosis is by clinical presentation, CSF analysis, and blood workup. Management (antimicrobials) depends on the etiology, but supportive treatment in all cases of meningitis is similar.
  • Subarachnoid hemorrhage: bleeding within the subarachnoid space that occurs spontaneously or following head trauma: Subarachnoid hemorrhage presents with neck and shoulder pain, numbness throughout the body, seizures, confusion and irritability, diplopia, and sudden headache. Diagnosis is by history, signs and symptoms, imaging, and cerebral angiography. Subarachnoid hemorrhage is managed surgically. Antihypertensive agents are recommended.
  • Subdural empyema: collection of pus between the dura mater and the arachnoid mater: Subdural empyema presents with fever, headache, lethargy, focal neurologic deficits, and seizures. Diagnosis is by imaging, the most common being contrast-enhanced MRI. Management is surgical and with antibiotics.
  • Brain abscess: collection of pus in response to an infection or trauma that presents clinically with fever, headache, seizures, nausea, and vomiting: Diagnosis is by evaluation of signs and symptoms, blood tests, and imaging. Management includes antibiotic therapy and surgery to drain the abscess. 
  • Stroke: damage to the brain due to interrupted blood supply: Stroke presents with difficulty walking, facial paralysis, blurred vision, slurred speech, and paresthesia. Diagnosis is by history and imaging. Management depends on the type of stroke. 
  • Hypoglycemia: condition in which blood glucose levels are lower than normal: Hypoglycemia is an emergency condition that presents with rapid heart rate, tremors, diaphoresis, confusion, blurred vision, and seizures. Diagnosis is by signs and symptoms and blood glucose levels. Management depends on the severity. Severe hypoglycemia is treated by IV glucose and/or glucagon injection.
  • Delirium tremens: severe form of ethanol withdrawal that presents clinically with global confusion, agitation, hallucinations, fever, and diaphoresis: Diagnosis is by history and signs and symptoms. Management is with supportive therapy, benzodiazepines, and thiamine.


  1. Venkatesan A. (2015). Epidemiology and outcomes of acute encephalitis. Current Opinions in Neurology. https://journals.lww.com/co-neurology/Abstract/2015/06000/Epidemiology_and_outcomes_of_acute_encephalitis.12.aspx
  2. Healthline. (2017). Encephalitis. Retrieved April 26, 2021, from https://www.healthline.com/health/encephalitis#complications
  3. Mayo Clinic (2020). Encephalitis. https://www.mayoclinic.org/diseases-conditions/encephalitis/symptoms-causes/syc-20356136
  4. Howes DS, Lazoff M. (2018). Encephalitis. Medscape. https://emedicine.medscape.com/article/791896-overview#a4
  5. John Hopkins Medicine. (n.d.). Encephalitis. Retrieved April 26, 2021, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/encephalitis
  6. Gluckman SJ. (2019). Viral encephalitis in adults. UpToDate. Retrieved April 25, 2021, from https://www.uptodate.com/contents/viral-encephalitis-in-adults

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