eMedicine Specialties > Neurology > Neurological Infections

Herpes Simplex Encephalitis: Differential Diagnoses & Workup

Author: Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Contributor Information and Disclosures

Updated: Sep 2, 2009

Differential Diagnoses

Acute Disseminated Encephalomyelitis
Generalized EEG Waveform Abnormalities
Aphasia
Haemophilus Meningitis
Aseptic Meningitis
HIV-1 Associated CNS Complications (Overview)
Benign Childhood Epilepsy
Intracranial Epidural Abscess
Benign Neonatal Convulsions
Intracranial Hemorrhage
Childhood Migraine Variants
Lennox-Gastaut Syndrome
Complex Partial Seizures
Leptomeningeal Carcinomatosis
Confusional States and Acute Memory Disorders
Migraine Headache
Dissection Syndromes
Migraine Headache: Pediatric Perspective
Early Myoclonic Encephalopathy
Migraine Variants
EEG in Common Epilepsy Syndromes
Neurosyphilis
EEG in Dementia and Encephalopathy
Paraneoplastic Encephalomyelitis
EEG in Status Epilepticus
Seizures and Epilepsy: Overview and Classification
Epileptiform Discharges
Simple Partial Seizures
Frontal Lobe Epilepsy
Status Epilepticus
Frontal Lobe Syndromes
Temporal Lobe Epilepsy

Other Problems to Be Considered

Complex partial status epilepticus
Myoclonus
Partial seizures with secondary generalization
Seizure, partial (focal)
Benign epilepsy syndromes
Management of increased intracranial pressure in the neuro ICU
Management of intracranial hemorrhage in the neuro ICU
EEG in coma
Increased intracranial pressure
Neuro-Behçet disease

Workup

Laboratory Studies

  • In suspected HSE, the workup must be initiated rapidly and should not delay treatment.
  • General laboratory studies are not helpful in diagnosis but may show evidence of infection or detect renal disease (in which case, treatment must be adjusted).
  • Schloss and colleagues report that while quantitative PCR is more rational than a nested PCR, the former has little prognostic use.13

Imaging Studies

  • CT scan
    • Low-density lesions may be found in two thirds of cases, especially in the temporal lobes, but they may not appear until 3-4 days after onset.
    • Edema and hemorrhages may be present.
    • After 1 week, contrast enhancement may be detectable.
  • MRI
    • Being more sensitive than CT scan, MRI is now the imaging study of choice.
    • Temporal lobe involvement, sometimes hemorrhagic, and early involvement of white matter are typical. The inferomedial portion of the temporal lobe is most commonly affected on MRI, sometimes in association with abnormalities of the cingulate gyrus.
    • Proton-density and T2 images may be more helpful than T1 images.

Other Tests

  • Electroencephalography
    • EEG is quite sensitive and shows abnormalities in four fifths of biopsy-proven cases of HSE.
    • Focal temporal changes or diffuse slowing may be observed.
    • Periodic complexes and periodic lateralizing epileptiform discharges (PLEDs), in the proper clinical context, are strongly suggestive of HSE.
    • However, Beneto et al reported 9 patients with confirmed HSE who had no PLED activity or had other EEG patterns.14

Procedures

  • Once a space-occupying lesion has been excluded by imaging, lumbar puncture always should be performed in suspected HSE.
    • Acutely, a typical "viral profile" is identified, with mildly elevated protein, normal glucose, and a moderate pleocytosis (mostly mononuclear cells).
    • Red blood cells and xanthochromia may be seen.
    • The fluid should be sent for HSV-1 and HSV-2 polymerase chain reaction (PCR) to detect HSV DNA.
    • In general, cerebrospinal fluid (CSF) yield is proportional to the volume analyzed; an adequate volume of CSF should be obtained (>10 mL).
  • PCR is highly specific. Importantly, it remains positive up to 5 days after initiation of treatment.
  • Intrathecal antibodies can be quantified, thus giving evidence for a CNS antibody response.

Histologic Findings

Orbitofrontal or limbic encephalitis may be seen. One hallmark of the condition is significant hemorrhage in these locations. Cowdry A inclusions are seen.

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
References
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References

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  2. Whitley RJ, Soong SJ, Dolin R, et al. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med. Aug 11 1977;297(6):289-94. [Medline].

  3. Elbers JM, Bitnun A, Richardson SE. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease?. Pediatrics. Feb 2007;119(2):e399-407. [Medline].

  4. Shelley BP, Raniga SB, Al-Khabouri J. An unusual late complication of intracerebral haematoma in herpes encephalitis after successful acyclovir treatment. J Neurol Sci. Jan 31 2007;252(2):177-80. [Medline].

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  11. Geiger KD, Nash TC, Sawyer S, et al. Interferon-gamma protects against herpes simplex virus type 1-mediated neuronal death. Virology. Nov 24 1997;238(2):189-97. [Medline].

  12. Cathomas R, Pelosi E, Smart J. Herpes simplex encephalitis as a complication of adjuvant chemotherapy treatment for breast cancer. Clin Oncol (R Coll Radiol). Jun 2005;17(4):292-3. [Medline].

  13. Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E. Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol. Jun 23 2009;81(8):1432-1437. [Medline].

  14. Beneto A, Gomez E, Rubio P, et al. [Periodical EEG pattern modifications in herpetic encephalitis treated with acyclovir]. Rev Neurol. Jul 1996;24(131):829-32. [Medline].

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  22. Jereb M, Lainscak M, Marin J, Popovic M. Herpes simplex virus infection limited to the brainstem. Wien Klin Wochenschr. Jul 2005;117(13-14):495-9. [Medline].

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  24. Shian WJ, Chi CS. Magnetic resonance imaging of herpes simplex encephalitis. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. Jan-Feb 1996;37(1):22-6. [Medline].

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Further Reading

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Keywords

herpes, genital herpes, herpes encephalitis, encephalitis, HSE, HSV-1, HSV-2, cold sores, fever blisters, herpes simplex virus, human herpesvirus, HHV, HHV-1, herpes simplex virus type 1, herpes simplex virus type 2, herpes simplex encephalitis

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Contributor Information and Disclosures

Author

Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Wayne E Anderson, DO is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Law Medicine and Ethics, California Medical Association, and San Francisco Medical Society
Disclosure: Cephalon Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; King Honoraria Consulting

Medical Editor

Ramon Diaz-Arrastia, MD, PhD, Assistant Professor, Department of Neurology, Comprehensive Epilepsy Center, University of Texas Southwestern
Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, New York Academy of Sciences, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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