Neuropediatrics 2004; 35(6): 371-376
DOI: 10.1055/s-2004-830372
Short Communication

Georg Thieme Verlag KG Stuttgart · New York

Relapse of Herpes Encephalitis after Acyclovir Therapy: Report of Two New Cases and Review of the Literature

I. Valencia1 , D. K. Miles1 , J. Melvin1 , D. Khurana1 , S. Kothare1 , H. Hardison1 , A. Legido1
  • 1Section of Neurology, Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, USA
Further Information

Publication History

Received: September 15, 2003

Accepted after Revision: September 16, 2004

Publication Date:
15 November 2004 (online)

Abstract

Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported infrequently in children beyond the neonatal period. The pathogenic mechanism of the recurrence is not fully understood. We report two new cases that support a mechanism of latent HSV infection with reactivation of the disease. Our patients were 2 years (#1) and 8 months (#2) old at initial infection. Both presented with fever, lethargy, focal seizures, and focal motor abnormalities. Serum HSV antibodies (Abs) were negative. The patients were treated with acyclovir for 14 and 21 days, respectively. They were readmitted at 1 month, and 4 days after discharge, respectively, with recurrent lethargy, seizures, and choreo-athetoid movements. Serum and CSF HSV Abs were significantly increased. CSF PCR was positive. In patient # 2 acyclovir-sensitive HSV was isolated from a brain biopsy. Both patients were re-treated with acyclovir, but progressed to a neurovegetative state. In our cases, latent HSV infection and reactivation is the most likely explanation for recurrent encephalitis. The immuno-pathogenic mechanisms of the infection recurrence are discussed. Based on the reported cases in the literature, patients younger than 2 years of age and with lower total dose of acyclovir treatments have a higher risk of recurrence.

References

  • 1 Abramson J S, Roach E S, Levy H B. Postinfectious encephalopathy after treatment of herpes simplex encephalitis with acyclovir.  Pediatr Infect Dis. 1984;  3 146-147
  • 2 American Academy of Pediatrics .Herpes Simplex. Pickering LK 2003 Red Book: Report of the Committee On Infectious Diseases. Elk Grove Village, IL; American Academy of Pediatrics 2003 346-349 729
  • 3 Barthez M A, Billard C, Santini J J, Ruchoux M M, Grangeponte M C. Relapse of herpes simplex encephalitis.  Neuropediatrics. 1987;  18 3-7
  • 4 Barthez-Carpentier M A, Rozenberg F, Dussaix E, Lebon P, Goudeau A, Billard C. et al . Relapse of herpes simplex encephalitis.  J Child Neurol. 1995;  10 363-368
  • 5 Bergstrom T, Trollfors B. Recurrent herpes simplex virus type 2 encephalitis in a preterm neonate. Favourable outcome after prolonged acyclovir treatment.  Acta Paediatr Scand. 1991;  80 878-881
  • 6 Bourgeois M, Vinikoff L, Lellouch-Tubiana A, Sainte-Rose C. Reactivation of herpes virus after surgery for epilepsy in a pediatric patient with mesial temporal sclerosis: case report.  Neurosurgery. 1999;  44 633-635
  • 7 Dalai S K, Pesnicak L, Miller G F, Straus S E. Prophylactic and therapeutic effects of human immunoglogbulin pathobiology of HSV-1 infection, latency and reactivation in mice.  J Neurovirol. 2002;  8 35-44
  • 8 Dankner W M, Spector S A. Recurrent herpes simplex in a neonate.  Pediatr Infect Dis. 1986;  5 582-586
  • 9 Davis L E, McLaren L C. Relapsing herpes simplex encephalitis following antiviral therapy.  Ann Neurol. 1983;  13 192-195
  • 10 Dennett C, Klapper P E, Cleator G M. Polymerase chain reaction in the investigation of “relapse” following herpes simplex encephalitis.  J Med Virol. 1996;  48 129-132
  • 11 Domjan J, Millar J. The MRI appearances of anterior opercular syndrome in a child with recurrent herpes simplex encephalitis.  Clin Radiol. 2000;  55 574-575
  • 12 Erlandsson A C, Bladh L G, Stierna P, Yucel-Lindberg T, Hammarsten O, Modeer T. et al . Herpes simplex virus type 1 infection and glucocorticoid treatment regulate viral yield, glucocorticoid receptor and NF-kappa B levels.  J Endocrinol. 2002;  175 165-176
  • 13 Field H J, Tewari D, Sutton D, Thackray A M. Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model.  Antimicrob Agents Chemother. 1995;  39 1114-1119
  • 14 Field H J, Thackray A M. Early therapy with valaciclovir or famciclovir reduces but does not abrogate herpes simplex virus neuronal latency.  Nucleosides Nucleotides Nucleic Acids. 2000;  19 461-470
  • 15 Gascon G G, al-Jarallah A A, Okamoto E, al Ahdal M, Kessie G, Frayha H. Chorea as a presentation of herpes simplex encephalitis relapse.  Brain Dev. 1993;  15 178-181
  • 16 Ito Y, Kimura H, Yabuta Y, Ando Y, Murakami T, Shiomi M. et al . Exacerbation of herpes simplex encephalitis after successful treatment with acyclovir.  Clin Infect Dis. 2000;  30 185-187
  • 17 Jones C. Herpes simplex virus type 1 and bovine herpesvirus 1 latency.  Clinical Microbiology Reviews. 2003;  16 79-95
  • 18 Kimberlin D, Powell D, Gruber W, Diaz P, Arvin A, Kumar M. et al . Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial.  Pediatr Infect Disease J. 1996;  15 247-254
  • 19 Kimberlin D W, Prober C G. Antiviral agents. Long SS, Pickering LK, Prober CG Principles and Practice of Pediatric Infectious Diseases. Philadelphia; Churchill Livingstone 2003: 1527-1542
  • 20 Kimura H, Aso K, Kuzushima K, Hanada N, Shibata M, Morishima T. Relapse of herpes simplex encephalitis in children.  Pediatrics. 1992;  89 891-894
  • 21 Knezevic W, Carroll W M. Relapse of herpes simplex encephalitis after acyclovir therapy.  Aust NZ J Med. 1983;  13 625-626
  • 22 LeBlanc R A, Pesnicak L, Cabral E S, Godleski M, Straus S E. Lack of interleukin-6 (IL-6) enhances susceptibility to infection but does not alter latency or reactivation of herpes simplex virus type 1 in IL-6 knockout mice.  J Virol. 1999;  73 8145-8151
  • 23 Mandyla H, Anagnostakis D, Koutsovitis P, Siahanidou T, Youroukos S. Late recurrence of herpes simplex virus meningoencephalitis in two infants.  Eur J Pediatr. 2001;  160 732-735
  • 24 Martin J R, Suzuki S. Targets of infection in a herpes simplex-reactivation model.  Acta Neuropathol. 1989;  77 402-411
  • 25 Nicolaidou P, Iacovidou N, Youroukos S, Liacopoulou-Tsitsipi T, Kattamis C. Relapse of herpes simplex encephalitis after acyclovir therapy.  Eur J Pediatr. 1993;  152 737-738
  • 26 Norose K, Yano A, Zhang X M, Blankenhorn E, Heber-Katz E. Mapping of genes involved in murine herpes simplex virus keratitis: identification of genes and their modifiers.  J Virol. 2002;  76 3502-3510
  • 27 Opitz J C, Kettrick M A, Sullivan B J. Recurrent neonatal herpes presenting initially with hoarseness.  Am J Perinatol. 1989;  6 307-309
  • 28 Paillard C, Vanhulle C, Devaux A M, Ensel P, Monroc-Morval M, Blanc T. [Recurrence of herpes simplex encephalitis].  Arch Pediatr. 1999;  6 1081-1085
  • 29 Pavone P, Trobia G L, Ruggieri M, Greco F, D'Agata A, Musumeci S. [Early relapse of herpes simplex encephalitis. Clinical and therapeutic implications].  Minerva Pediatr. 1999;  51 395-398
  • 30 Pike M G, Kennedy C R, Neville B G, Levin M. Herpes simplex encephalitis with relapse.  Arch Dis Child. 1991;  66 1242-1244
  • 31 Prober C G. Herpes simplex virus. Long SS, Pickering LK, Prober CG Principles and Practice of Pediatric Infectious Diseases. Philadelphia; Churchill Livingstone 2003: 1032-1040
  • 32 Seto A, Morikawa S, Isono T, Ogawa K, Inubushi T. Genetic susceptibility to herpetic encephalitis of inbred rabbits of B/Jas strain.  J Med Virol. 1995;  46 224-229
  • 33 Shanks D E, Blasco P A, Chason D P. Movement disorder following herpes simplex encephalitis.  Dev Med Child Neurol. 1991;  33 348-352
  • 34 Stanberry L R. Herpes. Vaccines for HSV.  Dermat Clin. 1998;  16 811-816
  • 35 Taskinen E, Koskiniemi M L, Vaheri A. Herpes simplex virus encephalitis. Prolonged intrathecal IgG synthesis and cellular activity in the cerebrospinal fluid with transient impairment of blood-brain barrier.  J Neurol Sciences. 1984;  63 331-338
  • 36 Thackray A M, Field H J. Comparison of effects of famciclovir and valaciclovir on pathogenesis of herpes simplex virus type 2 in a murine infection model.  Antimicrob Agents Chemother. 1996;  40 846-851
  • 37 Thackray A M, Field H J. Famciclovir and valaciclovir differ in the prevention of herpes simplex virus type 1 latency in mice: a quantitative study.  Antimicrob Agents Chemother. 1998;  42 1555-1562
  • 38 Thackray A M, Field H J. Persistence of infectious herpes simplex virus type 2 in the nervous system in mice after antiviral chemotherapy.  Antimicrob Agents Chemother. 2000;  44 97-102
  • 39 VanLandingham K E, Marsteller H B, Ross G W, Hayden F G. Relapse of herpes simplex encephalitis after conventional acyclovir therapy.  JAMA. 1988;  259 1051-1053
  • 40 Wang H S, Kuo M F, Huang S C, Chou M L. Choreoathetosis as an initial sign of relapsing of herpes simplex encephalitis.  Pediatr Neurol. 1994;  11 341-345
  • 41 Yamada S, Kameyama T, Nagaya S, Hashizume Y, Yoshida M. Relapsing herpes simplex encephalitis: pathological confirmation of viral reactivation.  J Neurol Neurosurg Psychiatry. 2003;  74 262-264

M.D. Ignacio Valencia

Department of Pediatrics
Section of Neurology
St. Christopher's Hospital for Children

Erie Avenue at Front Street

Philadelphia, PA 19134

USA

Email: Ignacio.Valencia@drexel.edu

    >