Encephalitis, Table 5
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Diagnostic Algorithm
ROUTINE STUDIES |
CSFb |
Collect at least 5 cc fluid, if possible; freeze unused fluid for additional testing |
Opening pressure, WBC count with differential, RBC count, protein, glucose |
Gram stain and bacterial culture |
HSV-1/2 PCR (if test available, consider HSV CSF IgG and IgM in addition) |
Enterovirus PCR |
SERUM |
Routine blood cultures |
EBV serology (VCA IgG and IgM and EBNA IgG) |
Mycoplasma pneumoniae IgM and IgG |
Hold acute serum and collect convalescent serum 10–14 d later for paired antibody testing |
IMAGING |
Neuroimaging (MRI preferred to CT, if available) |
NEUROPHYSIOLOGY |
EEG |
OTHER TISSUES/FLUIDS |
Mycoplasma pneumoniae PCR from throat sample |
Enterovirus PCR and/or culture of throat and stool |
When clinical features of extra-CNS involvement are present, we recommend additional testing (eg, biopsy of skin lesions; bronchoalveolar lavage and/or endobronchial biopsy in those with pneumonia/pulmonary lesions; throat swab PCR/culture in those with upper respiratory illness; stool culture in those with diarrhea); also see below |
CONDITIONAL STUDIES |
HOST FACTORS |
Age < 3 y—Parechovirus PCR (CSF) |
Immunocompromised—CMV PCR, HHV6/7 PCR, HIV PCR (CSF); cryptococcal antigen; Toxoplasma gondii serology and/or PCR; MTB testingc; fungal testingd; WNV testinge |
GEOGRAPHIC FACTORS |
Africa—malaria (blood smear); trypanosomiasias (blood/CSF smear, serology from serum and CSF); dengue testinge |
Asia—Japanese encephalitis virus testinge; dengue testinge; malaria (blood smear); Nipah virus testing (serology from serum and CSF; PCR, immunohistochemistry, and virus isolation in a BSL4 lab can also be used to substantiate diagnosis) |
Australia—Murray Valley encephalitis virus testinge; Kunjin virus testinge, Australian Bat Lyssavirus (ABLV) testingf |
Europe—Tick-borne encephalitis virus (serology); if Southern Europe, consider WNV testinge, Toscana virus testinge |
Central and South America—dengue testinge; malaria (blood smear) |
North America—Geographically—appropriate arboviral testing (eg, WNV, Powassan, LaCrosse, Eastern equine encephalitis viruses,e Lyme (serum ELISA and Western blot) |
SEASON AND EXPOSURE |
Summer/Fall: Arboviruse and tick-borne diseaseg testing |
Cat (particularly if with seizures, paucicellular CSF)—Bartonella antibody (serum), ophthalmologic evaluation |
Tick exposure– Tick borne disease testingg |
Animal bite/bat exposure—rabies testingf |
Swimming or diving in warm freshwater or nasal/sinus irrigation– Naegleria fowleri (CSF wet mount and PCRh) |
SPECIFIC SIGNS AND SYMPTOMS |
Abnormal behavior (eg, new onset temper tantrums, agitation, aggression), psychotic features, seizures or movement disorder– NMDAR antibody (serum, CSF), oligoclonal bands, IgG index, rabies testingf |
Behavior changes followed by myoclonic spasms/jerks: measles IgG (CSF and serum) |
Vesicular rash—VZV PCR from CSF (sensitivity may be low; if test available, consider CSF IgG and IgM); VZV IgG and IgM from serum |
Rapid decompensation (particularly with animal bite history or prior travel to rabies-endemic areas)—rabies testingf |
Respiratory symptoms—chest imaging (chest X-ray and/or CT scan); respiratory virus testingi; Mycoplasma pneumoniae PCR (CSF) |
Acute flaccid paralysis—Arbovirus testinge; rabies testingf |
Parkinsonism –Arbovirus testinge; Toxoplasma serology |
Nonhealing skin lesions—Balamuthia, Acanthamoeba testingh |
Prominent limbic symptoms—Autoimmune limbic encephalitis testingj, HHV6/7 PCR (CSF) |
LABORATORY FEATURES |
If EBV serology is suggestive of acute infection, perform EBV PCR (CSF) |
Elevated transaminases—Rickettsia serology, tick-borne diseases testingg |
CSF protein >100 mg/dL, or CSF glucose < 2/3 peripheral glucose, or lymphocytic pleocytosis with subacute symptom onset—MTB testingc, fungal testingd, Balamuthia mandrillaris testingh |
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 |
CSF eosinophilia –MTB testingc; fungal testingd; Baylisascaris procyonis antibody (serum and CSF); Angiostrongylus cantonensis, Gnathostoma sp. testingk |
Hyponatremia—MTB testingc |
Mycoplasma pneumoniae serology or throat PCR positive— Mycoplasma pneumoniae PCR (CSF) |
NEUROIMAGING FEATURES |
Frontal lobe—Naegleria fowleri (CSF wet mount and PCRh) |
Temporal lobe—HHV 6/7 PCR (CSF) |
Basal ganglia and/or thalamus—Respiratory virus testingi; Arbovirus testinge; MTB testingc |
Brainstem—respiratory virus testingi; Arbovirus testinge; Listeria PCR (if available); Brucella antibody (serum); MTB testingc |
Cerebellum—VZV PCR from CSF (sensitivity may be low; if test available, consider CSF IgG and IgM); VZV IgG and IgM from serum; EBV PCR (CSF) |
Diffuse cerebral edema—respiratory virus testingi |
Space occupying and/or ring-enhancing lesions—MTB testingc; fungal testingd; Balamuthia mandrillaris and Acanthamoeba testingh, Toxoplasma gondii serology |
Hydrocephalus and/or basilar meningeal enhancement—MTB testingc; fungal testingd; Balamuthia mandrillaris testingh; Infarction or hemorrhage—MTB testingc; fungal testingd; respiratory virus testingi; |
White matter lesions—Oligoclonal bands, IgG index, Lyme (serum ELISA and Western blot); Brucella (serology or CSF culture) |
Measles virus testing for SSPE; Baylisascaris procyonis antibody (serum and CSF); Balamuthia mandrillaris testingh |
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Diagnostic Algorithm
ROUTINE STUDIES |
CSFb |
Collect at least 5 cc fluid, if possible; freeze unused fluid for additional testing |
Opening pressure, WBC count with differential, RBC count, protein, glucose |
Gram stain and bacterial culture |
HSV-1/2 PCR (if test available, consider HSV CSF IgG and IgM in addition) |
Enterovirus PCR |
SERUM |
Routine blood cultures |
EBV serology (VCA IgG and IgM and EBNA IgG) |
Mycoplasma pneumoniae IgM and IgG |
Hold acute serum and collect convalescent serum 10–14 d later for paired antibody testing |
IMAGING |
Neuroimaging (MRI preferred to CT, if available) |
NEUROPHYSIOLOGY |
EEG |
OTHER TISSUES/FLUIDS |
Mycoplasma pneumoniae PCR from throat sample |
Enterovirus PCR and/or culture of throat and stool |
When clinical features of extra-CNS involvement are present, we recommend additional testing (eg, biopsy of skin lesions; bronchoalveolar lavage and/or endobronchial biopsy in those with pneumonia/pulmonary lesions; throat swab PCR/culture in those with upper respiratory illness; stool culture in those with diarrhea); also see below |
CONDITIONAL STUDIES |
HOST FACTORS |
Age < 3 y—Parechovirus PCR (CSF) |
Immunocompromised—CMV PCR, HHV6/7 PCR, HIV PCR (CSF); cryptococcal antigen; Toxoplasma gondii serology and/or PCR; MTB testingc; fungal testingd; WNV testinge |
GEOGRAPHIC FACTORS |
Africa—malaria (blood smear); trypanosomiasias (blood/CSF smear, serology from serum and CSF); dengue testinge |
Asia—Japanese encephalitis virus testinge; dengue testinge; malaria (blood smear); Nipah virus testing (serology from serum and CSF; PCR, immunohistochemistry, and virus isolation in a BSL4 lab can also be used to substantiate diagnosis) |
Australia—Murray Valley encephalitis virus testinge; Kunjin virus testinge, Australian Bat Lyssavirus (ABLV) testingf |
Europe—Tick-borne encephalitis virus (serology); if Southern Europe, consider WNV testinge, Toscana virus testinge |
Central and South America—dengue testinge; malaria (blood smear) |
North America—Geographically—appropriate arboviral testing (eg, WNV, Powassan, LaCrosse, Eastern equine encephalitis viruses,e Lyme (serum ELISA and Western blot) |
SEASON AND EXPOSURE |
Summer/Fall: Arboviruse and tick-borne diseaseg testing |
Cat (particularly if with seizures, paucicellular CSF)—Bartonella antibody (serum), ophthalmologic evaluation |
Tick exposure– Tick borne disease testingg |
Animal bite/bat exposure—rabies testingf |
Swimming or diving in warm freshwater or nasal/sinus irrigation– Naegleria fowleri (CSF wet mount and PCRh) |
SPECIFIC SIGNS AND SYMPTOMS |
Abnormal behavior (eg, new onset temper tantrums, agitation, aggression), psychotic features, seizures or movement disorder– NMDAR antibody (serum, CSF), oligoclonal bands, IgG index, rabies testingf |
Behavior changes followed by myoclonic spasms/jerks: measles IgG (CSF and serum) |
Vesicular rash—VZV PCR from CSF (sensitivity may be low; if test available, consider CSF IgG and IgM); VZV IgG and IgM from serum |
Rapid decompensation (particularly with animal bite history or prior travel to rabies-endemic areas)—rabies testingf |
Respiratory symptoms—chest imaging (chest X-ray and/or CT scan); respiratory virus testingi; Mycoplasma pneumoniae PCR (CSF) |
Acute flaccid paralysis—Arbovirus testinge; rabies testingf |
Parkinsonism –Arbovirus testinge; Toxoplasma serology |
Nonhealing skin lesions—Balamuthia, Acanthamoeba testingh |
Prominent limbic symptoms—Autoimmune limbic encephalitis testingj, HHV6/7 PCR (CSF) |
LABORATORY FEATURES |
If EBV serology is suggestive of acute infection, perform EBV PCR (CSF) |
Elevated transaminases—Rickettsia serology, tick-borne diseases testingg |
CSF protein >100 mg/dL, or CSF glucose < 2/3 peripheral glucose, or lymphocytic pleocytosis with subacute symptom onset—MTB testingc, fungal testingd, Balamuthia mandrillaris testingh |
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 |
CSF eosinophilia –MTB testingc; fungal testingd; Baylisascaris procyonis antibody (serum and CSF); Angiostrongylus cantonensis, Gnathostoma sp. testingk |
Hyponatremia—MTB testingc |
Mycoplasma pneumoniae serology or throat PCR positive— Mycoplasma pneumoniae PCR (CSF) |
NEUROIMAGING FEATURES |
Frontal lobe—Naegleria fowleri (CSF wet mount and PCRh) |
Temporal lobe—HHV 6/7 PCR (CSF) |
Basal ganglia and/or thalamus—Respiratory virus testingi; Arbovirus testinge; MTB testingc |
Brainstem—respiratory virus testingi; Arbovirus testinge; Listeria PCR (if available); Brucella antibody (serum); MTB testingc |
Cerebellum—VZV PCR from CSF (sensitivity may be low; if test available, consider CSF IgG and IgM); VZV IgG and IgM from serum; EBV PCR (CSF) |
Diffuse cerebral edema—respiratory virus testingi |
Space occupying and/or ring-enhancing lesions—MTB testingc; fungal testingd; Balamuthia mandrillaris and Acanthamoeba testingh, Toxoplasma gondii serology |
Hydrocephalus and/or basilar meningeal enhancement—MTB testingc; fungal testingd; Balamuthia mandrillaris testingh; Infarction or hemorrhage—MTB testingc; fungal testingd; respiratory virus testingi; |
White matter lesions—Oligoclonal bands, IgG index, Lyme (serum ELISA and Western blot); Brucella (serology or CSF culture) |
Measles virus testing for SSPE; Baylisascaris procyonis antibody (serum and CSF); Balamuthia mandrillaris testingh |
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