eMedicine Specialties > Emergency Medicine > Neurology

Encephalitis: Differential Diagnoses & Workup

Author: Marjorie Lazoff, MD, Editor-in-Chief, Medical Computing Review
Contributor Information and Disclosures

Updated: Jul 16, 2009

Differential Diagnoses

Brain Abscess
Subarachnoid Hemorrhage
Catscratch Disease
Systemic Lupus Erythematosus
Herpes Simplex
Tick-Borne Diseases, Lyme
Herpes Simplex Encephalitis
Tick-Borne Diseases, Rocky Mountain Spotted Fever
Hypoglycemia
Toxoplasmosis
Leptospirosis in Humans
Tuberculosis
Meningitis
Pediatrics, Meningitis and Encephalitis
Status Epilepticus

Other Problems to Be Considered

Acute CNS events, such as hemorrhagic stroke
Acute confusional states secondary to drugs, toxins, psychosis
Amoeba (Naegleria, Acanthamoeba)
Head trauma
CNS syphilis
Ehrlichiosis
Intracranial hemorrhage
Intracranial tumor
Trauma

Workup

Laboratory Studies

  • Complete blood count (CBC) with differential: Findings are usually within the reference range.
  • Serum electrolytes: These are usually within the reference range. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurs in 25% of patients with St Louis encephalitis.)
  • Serum glucose level: Use this level as a baseline for determining normal CSF glucose values. The result may be low if glycogen stores are depleted or high in infected patients with diabetes mellitus.
  • BUN/creatinine and liver function tests (LFTs): Assess organ function and the need to adjust the antibiotic dose.
  • Platelet test and a coagulation profile: These are indicated in patients with chronic alcohol use, liver disease, or if disseminated intravascular coagulation (DIC) is suspected. The patient may require platelets or fresh-frozen plasma (FFP) before lumbar puncture (LP).
  • Urinary electrolyte test: Perform this assessment if SIADH is suspected.
  • Urine and/or serum toxicology screening: Perform 1 or both of these tests, if indicated.
  • Other laboratory tests
    • CSF polymerase chain reaction (PCR): A PCR for DNA HSV is 100% specific and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react, but no cross-reactivity with other herpes viruses occurs. Arguably, a series of quantitative PCRs documenting the decline of viral load with acyclovir treatment may clinch diagnosis without brain biopsy.
    • HSV cultures: These are used to test lesions (also Tzanck smear), CSF (rarely positive), and blood.
    • Viral serology: Complement fixation antibodies are useful in identifying arbovirus. Cross-reactivity exists among one subgroup of arboviruses, the flaviviruses (eg, St Louis encephalitis, JE, WNE), and with antibodies raised in persons inoculated with the yellow fever vaccine.
    • Viral serology: Complement fixation antibodies are useful in identifying arbovirus.
    • Heterophile antibody and cold agglutinins for EBV: These tests may be helpful.
    • Serologic tests for toxoplasmosis: These can be helpful in light of an abnormal CT scan, particularly in the case of single lesions. However, the overlap in titer between previously exposed but presently uninfected and reactivated groups may complicate interpretation.

Imaging Studies

  • Perform head CT, with and without contrast agent, in virtually all patients with encephalitis before LP to search for evidence of elevated intracerebral pressure (ICP), obstructive hydrocephalus, or mass effect. It is helpful also in differential diagnosis. MRI is more likely to show abnormalities earlier in disease course than head CT.
  • In HSE, an MRI may show several foci of increased T2 signal intensity in medial temporal lobes and inferior frontal gray matter. Head CT may show petechial hemorrhage in the same areas.
  • EEE and tick-borne encephalitis may show similar increased signal intensity in the basal ganglia and thalami.
  • In toxoplasmosis, contrast-enhanced head CT typically reveals several nodular or ring-enhancing lesions. Because lesions may be missed without contrast, MRI should be performed in patients for whom use of contrast material is contraindicated.

Other Tests

Electroencephalography

In HSE, characteristic paroxysmal lateral epileptiform discharges (PLEDs) often are observed, even before neuroradiographic changes.

Eventually, PLEDs are positive in 80% of cases. The presence of PLEDs is not pathognomonic for HSE.

CSF analysis is essential.

General patterns in bacterial and fungal (cryptococcal) meningitis found during the measurement of CSF pressure and CSF analysis may support a diagnosis (see the Table below).

The most important diagnostic test in the ED to rule out bacterial meningitis is well-performed Gram staining and, if available, polymerase chain reaction of the CSF in patients with suspected HSV encephalitis.

CSF Findings by Type of Organism

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Table
CSF Finding (Normal)Bacterial MeningitisViral Meningitis*Fungal Meningitis
Pressure (5-15 cm H2 O)
  • Increased
  • Normal or mildly increased
  • Normal or mildly increased in tuberculosis (TB)
  • May be increased
  • Patients with AIDS and cryptococcal meningitis at increased risk of blindness and death unless pressure maintained at <30 cm
Cell counts, mononuclear cells/mm3
 Preterm (0-25)
 Term (0-22)
 6 mo+ (0-5)
  • No cell count excludes bacterial meningitis
  • Typically thousands of polymorphonuclear cells, but counts may not change dramatically or even be normal (classically in very early meningococcal meningitis or in extremely ill neonates)
  • Lymphocytosis with normal CSF chemistry results observed in 15-25% of patients, especially if counts <1000 or if patient is partially treated
  • About <90% of patients with ventriculoperitoneal shunts and CSF WBC count >100 cells/mm3 are infected; CSF glucose level usually normal, and these patients' pathogens are less pathogenic than others'
  • Cell count and chemistry levels normalize slowly (days) with antibiotics
  • Usually <500, nearly 100% mononuclear
  • <48 hours, clinically significant polymorphonuclear pleocytosis may be indistinguishable from early bacterial meningitis, particularly with EEE
  • Nontraumatic RBCs in 80% of patients with HSV meningoencephalitis, though 10% have normal CSF results
  • 100s of mononuclear cells
Microorganisms (none)
  • Gram stain 80% effective
  • Inadequate decolorization may cause Haemophilus influenzae to be mistaken for gram-positive cocci
  • Pretreatment with antibiotics may affect stain uptake, causing gram-positive species to appear to be gram-negative and decrease culture yield by an average of 20
  • No organism
  • India ink 80-90% effective for detecting fungi
  • Acid-fast bacillus (AFB) stain 40% effective for TB; increase yield by staining supernatant from at least 5 mL of CSF
Glucose†
 Euglycemia (>50% serum)
 Hyperglycemia (>30% serum)
  • Decreased
  • Normal
  • Sometimes decreased
  • Aside from fulminant bacterial meningitis, TB, primary amebic meningoencephalitis, and neurocysticercosis cause lowest glucose levels
Protein
 Preterm (65-150 mg/dL)
 Term (20-170 mg/dL
 6 mo+ (15-45 mg/dL)
  • Usually >150 mg/dL
  • May be >1000 mg/dL
  • Mildly increased
  • Increased >1000 mg/dL, with relatively benign clinical presentation suggestive of fungal disease
CSF Finding (Normal)Bacterial MeningitisViral Meningitis*Fungal Meningitis
Pressure (5-15 cm H2 O)
  • Increased
  • Normal or mildly increased
  • Normal or mildly increased in tuberculosis (TB)
  • May be increased
  • Patients with AIDS and cryptococcal meningitis at increased risk of blindness and death unless pressure maintained at <30 cm
Cell counts, mononuclear cells/mm3
 Preterm (0-25)
 Term (0-22)
 6 mo+ (0-5)
  • No cell count excludes bacterial meningitis
  • Typically thousands of polymorphonuclear cells, but counts may not change dramatically or even be normal (classically in very early meningococcal meningitis or in extremely ill neonates)
  • Lymphocytosis with normal CSF chemistry results observed in 15-25% of patients, especially if counts <1000 or if patient is partially treated
  • About <90% of patients with ventriculoperitoneal shunts and CSF WBC count >100 cells/mm3 are infected; CSF glucose level usually normal, and these patients' pathogens are less pathogenic than others'
  • Cell count and chemistry levels normalize slowly (days) with antibiotics
  • Usually <500, nearly 100% mononuclear
  • <48 hours, clinically significant polymorphonuclear pleocytosis may be indistinguishable from early bacterial meningitis, particularly with EEE
  • Nontraumatic RBCs in 80% of patients with HSV meningoencephalitis, though 10% have normal CSF results
  • 100s of mononuclear cells
Microorganisms (none)
  • Gram stain 80% effective
  • Inadequate decolorization may cause Haemophilus influenzae to be mistaken for gram-positive cocci
  • Pretreatment with antibiotics may affect stain uptake, causing gram-positive species to appear to be gram-negative and decrease culture yield by an average of 20
  • No organism
  • India ink 80-90% effective for detecting fungi
  • Acid-fast bacillus (AFB) stain 40% effective for TB; increase yield by staining supernatant from at least 5 mL of CSF
Glucose†
 Euglycemia (>50% serum)
 Hyperglycemia (>30% serum)
  • Decreased
  • Normal
  • Sometimes decreased
  • Aside from fulminant bacterial meningitis, TB, primary amebic meningoencephalitis, and neurocysticercosis cause lowest glucose levels
Protein
 Preterm (65-150 mg/dL)
 Term (20-170 mg/dL
 6 mo+ (15-45 mg/dL)
  • Usually >150 mg/dL
  • May be >1000 mg/dL
  • Mildly increased
  • Increased >1000 mg/dL, with relatively benign clinical presentation suggestive of fungal disease

*Some bacteria (eg, Mycoplasma, Listeria, Leptospira, Borrelia burgdorferi [Lyme disease]) cause alterations in spinal fluid that resemble the viral profile. An aseptic profile is also typical of partially treated bacterial infections (>33%, especially those in children, are treated with antimicrobials) and of the 2 most common causes of encephalitis—the arboviruses and the potentially curable HSV.
† Wait 4 h after glucose load.

Procedures

  • Brain biopsy is the criterion standard because of its 96% sensitivity and 100% specificity.

More on Encephalitis

Overview: Encephalitis
Differential Diagnoses & Workup: Encephalitis
Treatment & Medication: Encephalitis
Follow-up: Encephalitis
References
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References

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Further Reading

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Keywords

encephalitis, West nile virus, cerebritis, acute encephalitis, herpes simplex encephalitis, HSE, varicella-zoster encephalitis, VZ encephalitis, West Nile encephalitis, St Louis encephalitis, SLE, California virus encephalitis, LaCross encephalitis, eastern equine encephalitis, western equine encephalitis, Powassan virus, Japanese virus encephalitis, JE, arboviral JE, subacute encephalopathies, chronic encephalopathies, acute arboviral encephalitides, acute viral encephalitides, cytomegalovirus encephalitis, CMV encephalitis, sclerosing panencephalitis, progressive multifocal leukoencephalopathy, HSV Cowdry type A inclusions, acute disseminated encephalitis, postinfectious encephalomyelitis, Epstein-Barr virus, EBV encephalitis, subacute sclerosing panencephalitis, rabies encephalitis, acute disseminated encephalitis, stiff neck, photophobia, lethargy, toxoplasma encephalopathy, meningismus

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Contributor Information and Disclosures

Author

Marjorie Lazoff, MD, Editor-in-Chief, Medical Computing Review
Marjorie Lazoff, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American Medical Informatics Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Steven A Conrad, MD, PhD, Chief, Department of Emergency Medicine; Chief, Multidisciplinary Critical Care Service, Professor, Department of Emergency and Internal Medicine, Louisiana State University Health Sciences Center
Steven A Conrad, MD, PhD is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American College of Emergency Physicians, American College of Physicians, International Society for Heart and Lung Transplantation, Louisiana State Medical Society, Shock Society, Society for Academic Emergency Medicine, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, University Hospitals, Case Medical Center
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

 
 
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