Encephalitis resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D.

Synonyms and Keywords: encephalitis management, encephalitis workup, encephalitis approach,encephalitis management, encephalitis treatment, encephalitis diagnosis


Encephalitis refers to the inflammation of the brain parenchyma acompanied of neurological dysfunction. The causes of encephalitis are mostly infectious, being viruses, bacteria, fungi, or parasites the possible agents. Presentation usually involves headache, fever, confusion, neck stiffness (Kernig and Brudzinski signs), and vomiting. Diagnosis is typically based on clinical presentation and supported by blood tests, medical imaging, and analysis of cerebrospinal fluid. Rapid identification of encephalitis is crucial to reduce sequelae. Management is directed against the affecting agent (antivirals, antibiotics), reducing swelling, and supportive measures.


Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

Common Causes



Shown below is an algorithm summarizing the diagnosis of encephalitis according to the International Encephalitis Consortium guidelines:[1]

Patient suspicious for encephalitis
• CSF analysis
• Routine blood testing
• Blood cultures
• HSV-1/2 PCR
• Enterovirus PCR
• Cryptococcal antigen and/or India Ink staining
• Oligoclonal bands and IgG index
• HIV serology
• Hold acute serum and collect convalescent serum 10–14 d later for paired antibody testing
• Neuroimaging (MRI preferred to CT, if available)
• Chest imaging (Chest x-ray and/or CT)
Evaluate further testing if additional risk factors are present
Host factors
Geographic factors
Season and exposure
Specific signs and symptoms
Laboratory features
Neuroimaging features
• HHV6/7 PCR
• Toxoplasma gondii serology and/or PCR
• MTB testing
• Fungal testing
• WNV testing
• Malaria (blood smear)
• Trypanosomiasias (blood/CSF smear
• Serology from serum and CSF)
• Dengue testing
• Arbovirusd and tick-borne disease testing
Psychotic features or movement disorder:
• Anti-NMDAR antibody (serum, CSF)
• Rabies testing
• Screen for malignancy
• Creutzfeld-Jakobs disease
Elevated transaminases:
• Rickettsia serology
• Tick borne diseases testing
Frontal lobe:
• Naegleria fowleri testing (CSF wet mount and PCRg)
• Japanese encephalitis virus testing
• Dengue testing
• Malaria (blood smear)
• Nipah virus testing
Cat exposure (particularly if with seizures, paucicellular CSF):
• Bartonella antibody (serum), ophthalmologic evaluation
Prominent limbic symptoms:
• Autoimmune limbic encephalitis testing
• HHV6/7 PCR (CSF)
• Screen for malignancy
CSF protein >100 mg/dL, or CSF glucose <2/3 peripheral glucose, or lymphocytic pleocytosis with subacute symptom onset:
• MTBtestingb
• Fungal testing
Temporal lobe:
• VGKC antibodies (serum and CSF)
• HHV 6/7 PCR (CSF)
• Murray Valley encephalitis virus testingd
• Kunjin virus testingd
• Australian Bat Lyssavirus (ABLV) testing
Tick exposure:
• Tick borne disease testing
Rapid decompensation (particularly with animal bite history or prior travel to rabies-endemic areas):
• Rabies testing
CSF protein >100 mg/dL or CSF glucose <2/3 peripheral glucose and neutrophilic predominance with acute symptom onset and recent antibiotic use:
• CSF PCR for S. pneumoniae and N. meningiditis
Basal ganglia and/or thalamus:
• Arbovirusd testing
• MTB testing
• Tick-borne encephalitis virus (serology)
Animal bite/bat exposure:
• Rabies testing
Respiratory symptoms:
• Mycoplasma pneumoniae serology and throat PCR (if either positive, then do CSF PCR)
• Respiratory virus testing
CSF eosinophilia:
• MTB testingb
• Fungal testingc
• Baylisascaris procyonis antibody (serum)
• Angiostrongylus cantonensis and Gnathostomasp. testing
• Arbovirus testingd
• Listeria PCR(if available)
• Brucella antibody (serum)
• MTB testing
Southern Europe:
• WNV testing
• Toscana virus testing
Swimming or diving in warm freshwater or nasal/sinus irrigation:
• Naegleria fowleri (CSF wet mount and PCR)
Acute flaccid paralysis:
• Arbovirus testingd
• Rabies testing
RBCs in CSF:
• Naegleria fowleri testing
• EBV PCR (CSF) and serology
Central and South America:
• Dengue testingd
• Malaria (blood smear)
• Venezuelan equine encephalitis testing
• Arbovirus testingd
• Toxoplasma serology
• VGKC antibody (serum)
• MTB testing
Diffuse cerebral edema:
• Respiratory virus testing
North America:
• Geographically appropriate arboviral testing (eg, WNV, Powassan, LaCrosse, Eastern Equine Encephalitis virusesd, Lyme(serum ELISA and Western blot)
Nonhealing skin lesions:
• Balamuthia mandrillaris
• Acanthamoeba testing
Space occupying and/or ring-enhancing lesions:
• MTB testingb
• Fungal testingc
• Balamuthia mandrillaris and Acanthamoeba testingg
• Toxoplasma serology
Hydrocephalus and/or basilar meningeal enhancement:
• MTB testingb
• Fungal testing
Infarction or hemorrhage:
• MTB testing
• Fungal testing
• Respiratory virus testing

Diagnostic Criteria for Encephalitis and Encephalopathy of Presumed Infectious or Autoimmune Etiology according to the International Encephalitis Consortium

Major Criterion (required):
Patients presenting to medical attention with altered mental status (defined as decreased or altered level of consciousness, lethargy, or personality change) lasting ≥24 h with no alternative cause identified.
Minor Criteria (2 required for possible encephalitis; ≥3 required for probable or confirmeda encephalitis):
Documented fever ≥38° C (100.4°F) within the 72 h before or after presentation.
Generalized or partial seizures not fully attributable to a preexisting seizure disorder.
New onset of focal neurologic findings.
CSF WBC count ≥5/cubic mm.
Abnormality of brain parenchyma on neuroimaging suggestive of encephalitis that is either new from prior studies or appears acute in onset.
Abnormality on electroencephalography that is consistent with encephalitis and not attributable to another cause.
Do not modify


Shown below is an algorithm summarizing treatment of herpetic encephalitis according to the Glasgow Institute of Neurological Sciences guidelines:[2]

Suspected Herpes Simplex Encephalitis (HSE)
Administer Acyclovir
CT/MRI scan
No mass but severe edema
HSE proven
• 14-day course
Possible HSE
• 10-day course
Other diagnosis
• Stop acyclovir
No mass or severe edema
Lumbar puncture
Manitol and/or steroids
Supportive or alternative diagnosis




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