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Herpes Simplex Encephalitis: Differential Diagnoses & Workup

Author: Todd Pritz, MD, Intensivist, St Anthony's Medical Center and St John's Mercy Medical Center, St Louis, Missouri
Contributor Information and Disclosures

Updated: Aug 24, 2009

Differential Diagnoses

Brain Abscess
Pediatrics, Febrile Seizures
Encephalitis
Pediatrics, Meningitis and Encephalitis
Epidural and Subdural Infections
Stroke, Hemorrhagic
Neoplasms, Brain
Stroke, Ischemic

Other Problems to Be Considered

Workup

Laboratory Studies

  • Serologic analysis
    • Serologic evaluation of blood or CSF may be useful for retrospective diagnosis, but it has no role in the acute diagnosis and treatment of patients.
    • Strategies based on increases in antibody levels and on the ratio of antibody levels in serum and CSF have not proven to be clinically useful.
  • CSF analysis
    • Patients with HSE typically have mononuclear pleocytosis of 10-500 WBCs/µL (average, 100 WBCs/µL).
    • As a result of the hemorrhagic nature of the underlying pathologic process, the RBC count may be elevated (10-500 RBCs/µL).
    • Protein levels are elevated to the range 60-700 mg/dL (average, 100 mg/dL).
    • Glucose values may be normal or mildly decreased (30-40 mg/dL).
    • In about 5-10% of patients, especially children, initial CSF results may be normal.13 However, on serial examinations, the cell counts and protein values increase.
    • Viral cultures of CSF are rarely positive and should not be relied on to confirm the diagnosis.
  • Polymerase chain reaction14,15
    • PCR analysis of CSF for the detection of HSV DNA has virtually replaced brain biopsy as the criterion standard for diagnosis.
    • PCR is highly sensitive (94-98%) and specific (98-100%).
    • Results become positive within 24 hours of the onset of symptoms and remain positive for at least 5-7 days after the start of antiviral therapy.
    • Clinical severity and outcome appear to correlate with viral load as assessed by quantitative PCR techniques,16 but not all investigators have confirmed this.17
    • False-negative findings may occur early in the course of the disease when viral DNA levels are low (within 72 h of the onset of symptoms) or when blood is present in the CSF, as hemoglobin may interfere with PCR.18
    • Pretest probability should be considered in interpretation of results. A negative result obtained less than 72 hours after the onset of symptoms in a patient with a high pretest probability (fever, focal neurological abnormalities, CSF pleocytosis) should be repeated.
    • False-positive test results are rare and usually reflect accidental contamination of the specimen in the laboratory.

Imaging Studies

  • Magnetic resonance imaging
    • MRI of the brain is the preferred imaging study. Abnormalities are found in 90% of patients with HSE; MRI may be normal early in the course of illness.
    • Findings of localized temporal abnormalities are highly suggestive of HSE, but confirmation of the diagnosis depends on the identification of HSV by means of PCR or brain biopsy.
    • MRI can noninvasively establish many of the potential alternative diagnoses of HSE.
  • Computed tomography
    • Head CT may show changes in the temporal and/or frontal lobe, but CT is less sensitive than MRI.
    • Approximately one third of patients with HSE have normal CT findings on presentation.

Other Tests

  • Electroencephalography
    • Electroencephalography (EEG) shows focal abnormalities, such as spike and slow- or periodic sharp-wave patterns over the involved temporal lobes.
    • EEG is 84% sensitive to abnormal patterns in HSE but lacks specificity (32%).

Procedures

  • Brain biopsy
    • Historically, brain biopsy has been considered the only definitive means of diagnosing HSE. With the advent of PCR technology, the role of brain biopsy is diminishing.
    • Brain biopsy carries a complication rate of about 3%.
    • The results of brain biopsy can establish alternative diagnoses, both treatable (eg, brain tumor) and nontreatable (eg, non-HSV viral encephalitis).
    • Studies have demonstrated that PCR testing of CSF is as accurate as brain biopsy in confirming the diagnosis of HSE.
  • Lumbar puncture (see Lab Studies)

More on Herpes Simplex Encephalitis

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

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Further Reading

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Keywords

herpes simplex encephalitis, HSE, herpes encephalitis, herpes simplex virus, HSV, herpes simplex virus type 1, HSV-1, herpes simplex virus type 2, HSV-2, sporadic fatal encephalitis, sporadic lethal encephalitis, viral encephalitis

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Contributor Information and Disclosures

Author

Todd Pritz, MD, Intensivist, St Anthony's Medical Center and St John's Mercy Medical Center, St Louis, Missouri
Todd Pritz, MD is a member of the following medical societies: Massachusetts Medical Society and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Robin R Hemphill, MD, MPH, Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University
Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency 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

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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