Elsevier

The Journal of Pediatrics

Volume 126, Issue 2, February 1995, Pages 234-241
The Journal of Pediatrics

Expanded spectrum of herpes simplex encephalitis in childhood,☆☆,,★★

https://doi.org/10.1016/S0022-3476(95)70550-3Get rights and content

Abstract

We designed a polymerase chain reaction method to detect herpes simplex virus (HSV) DNA in spinal fluid from patients with encephalitis. The polymerase chain reaction amplified a 211 base-pair segment of the HSV DNA polymerase gene. Applying this method, we diagnosed HSV type 1 infection in three young children, aged 7 to 13 months, who had atypical forms of the illness. On the basis of magnetic resonance imaging, their disease was diffuse or multifocal in two cases and, in all three, lacked the temporal lobe involvement considered characteristic of HSV encephalitis beyond the neonatal period. Most of the diffuse or multifocal abnormalities detected by magnetic resonance imaging were not apparent by computed tomography. Restriction enzyme analysis of the polymerase chain reaction products from all three patients indicated that their disease was caused by HSV type 1. We conclude that in preschool-age children beyond the neonatal period, the spectrum of HSV encephalitis includes multifocal or diffuse involvement of the brain, which may be detected most efficiently by magnetic resonance imaging. The polymerase chain reaction method has the potential for providing an early diagnosis, but further studies are required to define the sensitivity and specificity of the polymerase chain reaction before it can be used for routine clinical decision making. (J PEDIATR 1995;126:234-41)

Section snippets

Polymerase chain reaction (DNA polymerase gene)

The PCR was performed on 10 μl untreated CSF. Two 18-base oligonucleotides were selected from regions of homology in the published sequences of the DNA polymerase genes of HSV types 1 and 2.16, 17, 18 The primer sequences were 5′GACTACCTGGAGATCGAG′3 and 5′TGAACCCGTACACCGAGT′3. These primers amplify a 211 base-pair segment corresponding to bases 56,057 through 56,250 (genomic number) in HSV-1 strain 17.17 Within this segment there is greater than 90% homology between HSV-1 and HSV-2 but no

RESULTS

Selected clinical and laboratory data from the three patients are summarized in Table I. Serologic data from patients 1 and 2 are summarized in Table II.

Patient 1

Patient 1 was a 13-month-old, previously healthy black female infant who had fever and generalized seizures. The CSF on the second day of illness had 4 · 106 erythrocytes/L (4 erythrocytes/mm3) and 5 · 106 leukocytes/L (5 leukocytes/mm3) with 75% neutrophils, protein 0.21 gm/L (21 mg/dl), and glucose 3.6 mmol/L (65 mg/dl) (Table I). Bacterial and viral cultures were negative. The seizure activity persisted, and the infant was admitted to an outside hospital; anticonvulsant therapy was started.

DISCUSSION

These patients illustrate the importance of two techniques, MRI and PCR, which together provide new insight into the clinical spectrum of HSV encephalitis in this age group. The MRI revealed diffuse or multifocal involvement of the brain in two patients and a frontoparietal lobe lesion in the third. These patients lacked the temporal lobe localization thought to be characteristic of the nonneonatal form of HSV encephalitis. Nevertheless, PCR revealed the presence of HSV DNA in the CSF of each

References (32)

  • Center for Disease Control

    Encephalitis surveillance: annual summary 1978

  • AJ Nahmias et al.

    Herpes simplex virus encephalitis in pediatrics

    Pediatr Rev

    (1981)
  • RJ Whitley et al.

    Herpes simplex encephalitis: clinical assessment

    JAMA

    (1982)
  • AL Frank et al.

    Isolation of herpes simplex type 1 from ventricular fluid of an infant with encephalitis

    J PEDIATR

    (1978)
  • AJ Nahmias et al.

    Herpes simplex virus encephalitis: laboratory evaluations and their diagnostic significance

    J Infect Dis

    (1982)
  • RJ Whitley et al.

    Diseases that mimic herpes simplex encephalitis: diagnosis, presentation and outcome

    JAMA

    (1989)
  • S Kohl et al.

    Herpes simplex virus encephalitis during childhood: importance of brain biopsy diagnosis

    J PEDIATR

    (1985)
  • RJ Whitley et al.

    Drug therapy: acyclovir: a decade later

    N Engl J Med

    (1992)
  • RD Zimmerman et al.

    The role of MR imaging in the diagnosis of infections of the central nervous system

    Curr Clin Top Infect Dis

    (1989)
  • LE Albertyn

    Magnetic resonance imaging in herpes simplex encephalitis

    Australas Radiol

    (1990)
  • AP Gasecki et al.

    Correlation of early MRI with CT scan, EEG, and CSF: analysis in a case of biopsy-proven herpes simplex encephalitis

    Eur Neurol

    (1991)
  • E Aurelius et al.

    Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid

    Lancet

    (1991)
  • H Kimura et al.

    Relapse of herpes simplex encephalitis in children

    Pediatrics

    (1992)
  • Y Ando et al.

    Quantitative analysis of herpes simplex virus DNA incerebrospinal fluid of children with herpes simplex encephalitis

    J Med Virol

    (1993)
  • J Troendle-Atkins et al.

    Rapid diagnosis of herpes simplex virus encephalitis by using the polymerase chain reaction

    J PEDIATR

    (1993)
  • EC Uren et al.

    Herpes simplex virus encephalitis in pediatrics: diagnosis by detection of antibodies and DNA in cerebrospinal fluid

    Pediatr Infect Dis J

    (1993)
  • Cited by (0)

    From the Departments of Pediatrics, Neurology, Radiology, Medicine, and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri

    ☆☆

    Supported in part (Dr. Schlesinger) by the American Physician Fellowship, Inc., for Medicine in Israel.

    Reprint requests: Gregory A. Storch, MD, Department of Pediatrics, Washington University School of Medicine at Children's Hospital, One Children's Place, St. Louis, MO 63110.

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    0022/3476/95/$3.00 + 0 9/20/46186

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