Encephalitis, Table 4
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Diagnostic Algorithm
ROUTINE STUDIES |
CSF |
Collect at least 20 cc fluid, if possible; freeze at least 5–10 cc fluid, if possible |
Opening pressure, WBC count with differential, RBC count, protein, glucos |
Gram stain and bacterial culture |
HSV-1/2 PCR (if test available, consider HSV CSF IgG and IgM in addition) |
VZV PCR (sensitivity may be low; if test available, consider VZV CSF IgG and IgM in addition) |
Enterovirus PCR |
Cryptococcal antigen and/or India Ink staining |
Oligoclonal bands and IgG index |
VDRL |
SERUM |
Routine blood cultures |
HIV serology (consider RNA) |
Treponemal testing (RPR, specific treponemal test) |
Hold acute serum and collect convalescent serum 10–14 d later for paired antibody testing |
IMAGING |
Neuroimaging (MRI preferred to CT, if available) |
Chest imaging (Chest x-ray and/or CT) |
NEUROPHYSIOLOGY |
EEG |
OTHER TISSUES/FLUIDS |
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 |
Immunocompromised—CMV PCR, HHV6/7 PCR, HIV PCR (CSF); Toxoplasma gondii serology and/or PCR; MTB testingb; fungal testingc; WNV testingd |
GEOGRAPHIC FACTORS |
Africa—malaria (blood smear), trypanosomiasias (blood/CSF smear, serology from serum and CSF); dengue testingd |
Asia—Japanese encephalitis virus testingd; dengue testingd; 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 testingd, Kunjin virus testingd, Australian Bat Lyssavirus (ABLV) testinge |
Europe—Tick-borne encephalitis virus (serology); if Southern Europe, consider WNV testingd, Toscana virus testingd |
Central and South America—dengue testingd; malaria (blood smear); WNV, Venezuelan equine encephalitis testingd |
North America—Geographically appropriate arboviral testing (eg, WNV, Powassan, LaCrosse, Eastern equine encephalitis virusesd, Lyme (serum ELISA and Western blot) |
SEASON AND EXPOSURE |
Summer/Fall: Arbovirusd and tick-borne diseasef testing |
Cat (particularly if with seizures, paucicellular CSF)—Bartonella antibody (serum), ophthalmologic evaluation |
Tick exposure—tick-borne disease testingf |
Animal bite/bat exposure—rabies testinge |
Swimming or diving in warm freshwater or nasal/sinus irrigation—Naegleria fowleri (CSF wet mount and PCRg) |
SPECIFIC SIGNS AND SYMPTOMS |
Psychotic features or movement disorder—anti-NMDAR antibody (serum, CSF); rabies testinge; screen for malignancy, Creutzfeld-Jakob disease |
Prominent limbic symptoms—Autoimmune limbic encephalitis testingh; HHV6/7 PCR (CSF); screen for malignancy |
Rapid decompensation (particularly with animal bite history or prior travel to rabies-endemic areas)—rabies testinge |
Respiratory symptoms—Mycoplasma pneumoniae serology and throat PCR (if either positive, then do CSF PCR); respiratory virus testingi |
Acute flaccid paralysis—Arbovirus testingd; rabies testinge |
Parkinsonism –Arbovirus testingd; Toxoplasma serology |
Nonhealing skin lesions—Balamuthia mandrillaris, Acanthamoeba testingg |
LABORATORY FEATURES |
Elevated transaminases—Rickettsia serology, tick borne diseases testingf |
CSF protein >100 mg/dL, or CSF glucose < 2/3 peripheral glucose, or lymphocytic pleocytosis with subacute symptom onset—MTB testingb, fungal testingc |
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 testingb; fungal testingc; Baylisascaris procyonis antibody (serum); Angiostrongylus cantonensis and Gnathostoma sp. testingj |
RBCs in CSF—Naegleria fowleri testingg |
Hyponatremia—anti-VGKC antibody (serum); MTB testinga |
NEUROIMAGING FEATURES |
Frontal lobe—Naegleria fowleri testing (CSF wet mount and PCRg) |
Temporal lobe—VGKC antibodies (serum and CSF); HHV 6/7 PCR (CSF) |
Basal ganglia and/or thalamus—Arbovirusd testing; MTB testinga |
Brainstem—Arbovirus testingd; Listeria PCR(if available); Brucella antibody (serum); MTB testingb |
Cerebellum—EBV PCR (CSF) and serology |
Diffuse cerebral edema—Respiratory virus testingi |
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 testingc |
Infarction or hemorrhage—MTB testingb; fungal testingc; respiratory virus testingi |
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Diagnostic Algorithm
ROUTINE STUDIES |
CSF |
Collect at least 20 cc fluid, if possible; freeze at least 5–10 cc fluid, if possible |
Opening pressure, WBC count with differential, RBC count, protein, glucos |
Gram stain and bacterial culture |
HSV-1/2 PCR (if test available, consider HSV CSF IgG and IgM in addition) |
VZV PCR (sensitivity may be low; if test available, consider VZV CSF IgG and IgM in addition) |
Enterovirus PCR |
Cryptococcal antigen and/or India Ink staining |
Oligoclonal bands and IgG index |
VDRL |
SERUM |
Routine blood cultures |
HIV serology (consider RNA) |
Treponemal testing (RPR, specific treponemal test) |
Hold acute serum and collect convalescent serum 10–14 d later for paired antibody testing |
IMAGING |
Neuroimaging (MRI preferred to CT, if available) |
Chest imaging (Chest x-ray and/or CT) |
NEUROPHYSIOLOGY |
EEG |
OTHER TISSUES/FLUIDS |
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 |
Immunocompromised—CMV PCR, HHV6/7 PCR, HIV PCR (CSF); Toxoplasma gondii serology and/or PCR; MTB testingb; fungal testingc; WNV testingd |
GEOGRAPHIC FACTORS |
Africa—malaria (blood smear), trypanosomiasias (blood/CSF smear, serology from serum and CSF); dengue testingd |
Asia—Japanese encephalitis virus testingd; dengue testingd; 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 testingd, Kunjin virus testingd, Australian Bat Lyssavirus (ABLV) testinge |
Europe—Tick-borne encephalitis virus (serology); if Southern Europe, consider WNV testingd, Toscana virus testingd |
Central and South America—dengue testingd; malaria (blood smear); WNV, Venezuelan equine encephalitis testingd |
North America—Geographically appropriate arboviral testing (eg, WNV, Powassan, LaCrosse, Eastern equine encephalitis virusesd, Lyme (serum ELISA and Western blot) |
SEASON AND EXPOSURE |
Summer/Fall: Arbovirusd and tick-borne diseasef testing |
Cat (particularly if with seizures, paucicellular CSF)—Bartonella antibody (serum), ophthalmologic evaluation |
Tick exposure—tick-borne disease testingf |
Animal bite/bat exposure—rabies testinge |
Swimming or diving in warm freshwater or nasal/sinus irrigation—Naegleria fowleri (CSF wet mount and PCRg) |
SPECIFIC SIGNS AND SYMPTOMS |
Psychotic features or movement disorder—anti-NMDAR antibody (serum, CSF); rabies testinge; screen for malignancy, Creutzfeld-Jakob disease |
Prominent limbic symptoms—Autoimmune limbic encephalitis testingh; HHV6/7 PCR (CSF); screen for malignancy |
Rapid decompensation (particularly with animal bite history or prior travel to rabies-endemic areas)—rabies testinge |
Respiratory symptoms—Mycoplasma pneumoniae serology and throat PCR (if either positive, then do CSF PCR); respiratory virus testingi |
Acute flaccid paralysis—Arbovirus testingd; rabies testinge |
Parkinsonism –Arbovirus testingd; Toxoplasma serology |
Nonhealing skin lesions—Balamuthia mandrillaris, Acanthamoeba testingg |
LABORATORY FEATURES |
Elevated transaminases—Rickettsia serology, tick borne diseases testingf |
CSF protein >100 mg/dL, or CSF glucose < 2/3 peripheral glucose, or lymphocytic pleocytosis with subacute symptom onset—MTB testingb, fungal testingc |
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 testingb; fungal testingc; Baylisascaris procyonis antibody (serum); Angiostrongylus cantonensis and Gnathostoma sp. testingj |
RBCs in CSF—Naegleria fowleri testingg |
Hyponatremia—anti-VGKC antibody (serum); MTB testinga |
NEUROIMAGING FEATURES |
Frontal lobe—Naegleria fowleri testing (CSF wet mount and PCRg) |
Temporal lobe—VGKC antibodies (serum and CSF); HHV 6/7 PCR (CSF) |
Basal ganglia and/or thalamus—Arbovirusd testing; MTB testinga |
Brainstem—Arbovirus testingd; Listeria PCR(if available); Brucella antibody (serum); MTB testingb |
Cerebellum—EBV PCR (CSF) and serology |
Diffuse cerebral edema—Respiratory virus testingi |
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 testingc |
Infarction or hemorrhage—MTB testingb; fungal testingc; respiratory virus testingi |
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