Encephalitis resident survival guide

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

Overview

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.

Causes

Life Threatening Causes

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

• All causes of encephalitis may be potentially fatal or disabiling if left untreated in 24 hours; among them:
  • Infectious
    • Bacterial
      • Tuberculosis
      • Treponema pallidum
      • Mycoplasma
      • Listeria monocytogenes
      • Borrelia burgdorferi
      • Brucellosis
    • Viral
      • Herpes simplex
      • Mumps
      • Rubella
      • Epstein-Barr virus
      • Varicella zoster
      • Rabies
      • HIV
      • Cytomegalovirus
      • West Nile virus
      • St. Louis encephalitis virus
      • Japanese encephalitis virus
    • Fungal
      • Coccidioidomycosis
      • Blastomycosis
      • Histoplasmosis
      • Cryptococcosis
    • Protozoan
      • Granulomatous amebic
      • Toxoplasma
      • Bartonella Henselae
  • Autoimmune
  • Encephalitis lethargica
  • Limbic encephalitis

Common Causes

Infectious

• Herpes simplex
• Mumps
• Rubella
• Epstein-Barr virus
• Varicella zoster

Diagnosis

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

Patient suspicious for encephalitis

PERFORM: • CSF analysis • Routine blood testing • Blood cultures • HSV-1/2 PCR • VZV PCR • Enterovirus PCR • Cryptococcal antigen and/or India Ink staining • Oligoclonal bands and IgG index • VDRL • 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) • EEG

Evaluate further testing if additional risk factors are present

Host factors

Geographic factors

Season and exposure

Specific signs and symptoms

Laboratory features

Neuroimaging features

Immunocompromised: • CMV PCR • HHV6/7 PCR • HIV PCR (CSF) • Toxoplasma gondii serology and/or PCR • MTB testing • Fungal testing • WNV testing

Africa: • Malaria (blood smear) • Trypanosomiasias (blood/CSF smear • Serology from serum and CSF) • Dengue testing

Summer/Fall: • 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)

Asia: • 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)

Australia: • 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

Europe: • 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

Brainstem: • 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

Cerebellum: • EBV PCR (CSF) and serology

Central and South America: • Dengue testingd • Malaria (blood smear) • WNV • Venezuelan equine encephalitis testing

Parkinsonism: • Arbovirus testingd • Toxoplasma serology

Hyponatremia—anti: • 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       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

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

Treatment

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

Do's

• Rule-out other causes of decreased level of consciousness and personality change, such as drug abuse.
• Take a carefull history to relatives when managing a comatose patient.
• Perform routine full haematological and biochemical blood screen.
• When performing a CSF analysis, collect at least 20 ml, if possible; freeze at least 5-10 ml fluid; document opening pressure, WBC count with differential, RBC count, protein, and glucose; Gram stain and bacterial culture.
• Be aware that the abscense of leukocytosis, focal neurological signs, fever, headache, and pleocytosis, is more suggestive of encephalopathy rather than encephalitis.
• Perform a PCR for HSV-1/2, VZV, and enterovirus viruses.
• RPR is prefered over VDRL for treponemal detection.
• MRI is prefered over CT scan for neuroimaging.
• When significant edema is present in imaging, give steroids and/or mannitol to reduce the intracranial pressure before lumbar puncture.
  

Don'ts

• Do not delay antiviral treatment, since mortality may reach up to 70% when not given.
• Do no perform lumbar puncture before neuroimaging.