International Journal of Infectious Diseases
Volume 14, Issue 2 , Pages e161-e163, February 2010

Severe Guillain–Barré syndrome following primary infection with varicella zoster virus in an adult

Department of Medicine, St George's Hospital, Blackshaw Road, London SW17 0QT, UK

Received 15 September 2008; accepted 21 March 2009. published online 08 June 2009.

Corresponding Editor: William Cameron, Ottawa, Canada

Article Outline

Summary 

Varicella zoster virus (VZV) infection may trigger Guillain–Barré syndrome (GBS), but this is rare and almost always in the context of reactivation disease from latent VZV, ‘shingles’. We report here a case of severe GBS following primary VZV infection in an adult. A 40-year-old man of Indian origin developed features of GBS including quadriplegia, bulbar paralysis, and bilateral facial nerve palsies 14 days after primary VZV infection contracted from a known case in a family member. Nerve conduction studies confirmed acute inflammatory demyelinating polyneuropathy. Anti-ganglioside antibodies were negative. The mechanism of Schwann cell attack following VZV infection is poorly understood but this case suggests that primary VZV infection may be a sufficient stimulus to drive antibody generation and precipitate severe clinical symptomatology. The morbidity associated with the complications of VZV infection in adulthood could be avoided if patients who are seronegative for VZV (frequently from the Asian subcontinent) are offered prophylaxis after an exposure in adulthood.

Keywords: Guillain–Barré syndrome, Primary varicella zoster virus

 

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Introduction 

Guillain–Barré syndrome (GBS) usually occurs as a post-infective immune-mediated phenomenon. Many precipitants have been recognized and it is known that varicella zoster virus (VZV) infection may trigger GBS. However this is rare; fewer then 50 such cases have been reported in the literature, and, when it does occur, it is almost always in the context of reactivation disease from latent VZV, following herpes zoster (‘shingles’). We report here a case of severe GBS following primary VZV infection (‘chickenpox’).

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Case report 

A 40-year-old man, UK-resident but of Indian origin, presented with a 4-day history of cough, fever, and widespread vesicular rash. His 14-year-old son had recently had clinically confirmed chickenpox. The patient had no history of chickenpox in childhood. On examination he had a widespread vesicular/pustular rash typical of chickenpox; the rash was extensive and severe. Primary VZV infection was diagnosed and he was treated with a single dose of acyclovir (10mg/kg intravenously), followed by valacyclovir (1g three times daily orally for 7 days). The patient initially made a good recovery; his rash, respiratory and systemic symptoms all improved over the next week.

Fourteen days after his initial presentation he developed a tingling sensation in his lower extremities, leg weakness, and an unsteady gait. The following day this progressed to a left-sided facial droop and slurred speech and he was re-admitted. At this time he was afebrile, had a normal respiratory rate, 100% saturation on air, and was normotensive, although slightly tachycardic (sustained at around 100 bpm). Over the subsequent 24hours his neurological deficit progressed rapidly; he developed bilateral complete VIIth nerve palsies and reduced power in sternocleidomastoids and trapezii bilaterally; speech was slurred and his swallow was impaired. Muscle tone was globally decreased with weakness, worst in the proximal upper limbs (upper limbs: 2/5 proximally, 4-/5 distally; lower limbs: 4/5, proximal and distal). Reflexes were absent but sensation intact.

Investigations revealed a normal computed tomography scan of the brain and magnetic resonance imaging scan of the brain and spinal cord. The cerebrospinal fluid (CSF) was acellular and glucose normal, but CSF protein was high (1.0g/l). CSF-PCR for VZV DNA was negative. Nerve conduction studies showed increased latency and decreased amplitudes. Motor nerve velocities in the left ulnar, right lateral popliteal, and right median were 43, 45, and 36m/s, respectively, and sensory velocities in the right sural nerve, 48m/s, findings suggestive of an acute inflammatory demyelinating polyneuropathy.

Post-VZV GBS was diagnosed and treatment with intravenous immunoglobulin (Vigam 0.4mg/kg/day, for 5 days) commenced. He required nasogastric feeding and his vital capacity fell to 0.2 l with a brief episode of tachycardia of 110 bpm. He did not begin to improve clinically until approximately 10 days after onset of his neurological symptoms. Subsequently, he made a full recovery of power in his arms and legs, but two months on is still receiving speech and language therapy, as his facial nerve palsies and speech have been slower to improve.

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Discussion 

This patient has all the cardinal clinical features of GBS; weakness, paresthesias, and diminished or absent deep tendon reflexes.1 Typically, nerve conduction studies often show slowing and decreased amplitude, as in this case (although they may be normal). CSF protein is typically raised, as in this patient, reported ranges being 0.5–3.0g/l.2 VZV, however, is a rare antecedent for GBS. In a study examining antecedent infections in GBS, Jacobs et al. found only one case out of 154 that could be attributed to VZV.3 Of the fewer than 50 reported cases in the literature, only six involved primary infection and of these none involved adults.4, 5, 6, 7 GBS following herpes zoster typically has a latent period of two weeks to two months. Shorter latent periods, as in this case, are associated with more severe illness.8

Immigrants to Europe and America are at risk of acquiring adult VZV infection as infection in childhood is less frequent in the Asian subcontinent.9 Seronegative patients exposed to the virus may avoid symptomatic illness by taking prophylactic antiviral therapy. A one-week course of acyclovir at treatment doses, starting one week after exposure to VZV allows a virema and seroconversion, but may prevent systemic and neurological disease, thus avoiding the heightened morbidity associated with VZV infection in adulthood.10, 11

In GBS, two distinct pathophysiological patterns are observed. The demyelinating pattern predominates in North America and Europe, whereas axonal variants occur more frequently in China.12 The electrophysiology in this patient suggests that he experienced a demyelinating pattern. Certain subtypes of GBS are associated with antibodies to gangliosides. Antibodies to the ganglioside GQ1b are virtually pathognomonic of the Miller Fisher variant of GBS (which presents with a descending paralysis) and antibodies to GM-1 and GD1a occur frequently in acute motor axonal neuropathy (AMAN).13 There are cases of anti-ganglioside antibodies in association with acute inflammatory demyelinating polyneuropathy (AIDP), but in general anti-ganglioside antibodies appear to be less frequently associated with AIDP than with AMAN.14, 15 In this case of AIDP the anti-GM1, anti-GM2, and anti-GQ1b were negative. This suggests there is an alternative mode of pathogenesis in AIDP, which is currently poorly understood.

It is thought that the well-described association of GBS with Campylobacter jejuni infection arises because the lipopolysaccharides of these organisms contain epitopes that are similar to peripheral nerve gangliosides. They act as ‘molecular mimics’, driving production of antibodies with anti-ganglioside specificity, which result in injury to peripheral nerve fibers.12 In AIDP the attack appears to be directed to a component of the Schwann cell, but the precise nature of antigenic targets is still not clear.16 Whether a similar ‘molecular mimicry’ occurs with post-VZV GBS remains speculative. Such antibody generation may occur at higher titers and more frequently in the secondary response associated with VZV reactivation (shingles), but this case suggests that primary VZV infection per se may sometimes be a sufficient stimulus to drive antibody generation and precipitate severe clinical symptomatology.

Conflict of interest: No conflict of interest to declare.

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References 

  1. Ropper AH, Wijdicks EP, Truax BT. Guillain–Barré syndrome. Philadelphia: FA Davis; 1991;
  2. Goetz CG. Textbook of clinical neurology. 3rd ed.. USA: Elseviers; 1999;
  3. Jacobs BC, Rothbarth PH, van der Meche FG, Herbrink P, Schmitz PI, de Klerk MA, et al. The spectrum of antecedant infections in Guillain–Barré syndrome: a case–control study. Neurology. 1998;51:1110–1115
  4. Pavone P, Maccarrone F, Sorge A, Piccolo G, Greco F, Caruso P, et al. Guillain–Barré syndrome after varicella zoster virus infections. A case report. Minerva Pediatr. 2002;54:259–262
  5. da Rosa-Santos OL, Moreira AM, Golfetto CA, Maceira JP, Ramos-e-Silva M. Guillain–Barré syndrome associated with varicella-zoster infection. Int J Dermatol. 1996;35:603–604
  6. Arruda WO, Aguiar LR, Sandoval PR. Guillain–Barré syndrome after varicella-zoster infection. Case report. Arq Neuropsiquiatr. 1987;45:430–433
  7. Sanders EA, Peters AC, Gratana JW, Hughes RA. Guillain–Barré syndrome after varicella-zoster infection. Report of two cases. J Neurol. 1987;234:437–439
  8. Rabbani M, Gupta D. Guillain–Barré syndrome following herpes zoster: a case report and review of literature. Jpn J Med. 1990;29:397–398
  9. Lee B. Review of varicella zoster seroepidemiology in India and South-east Asia. Trop Med Int Health. 1998;3:886–890
  10. Yoshikawa T, Suga S, Kozawa T, Kawaguchi S, Asano Y. Persistence of protective immunity after postexposure prophylaxis of varicella with oral aciclovir in the family setting. Arch Dis Child. 1998;78:61–63
  11. White CB, Hawley WZ, Harford DJ. The pediatric resident susceptible to varicella: proving immunity through postexposure prophylaxis with oral acyclovir. Pediatr Infect Dis J. 1994;13:743–745
  12. Sheikh KA, Ho TW, Nachamkin I, Li CY, Cornblath DR, Asbury AK, et al. Molecular mimicry in Guillain–Barré syndrome. Ann N Y Acad Sci. 1998;845:307–321
  13. The Nerve Research Foundation. Annual report 2006. Sydney, Australia: The Nerve Research Foundation; 2006, p. 8-9.
  14. Hiraga A, Kuwabara S, Ogawara K, Misawa S, Kanesaka T, Koga M, et al. Patterns and serial changes in electrodiagnostic abnormalities of axonal Guillain–Barré syndrome. Neurology. 2005;64:856–860
  15. Yuki N, Kuwabara S, Koga M, Hirata K. Acute motor axonal neuropathy and acute motor-sensory neuropathy share a common immunological profile. J Neurol Sci. 1999;168:121–126
  16. Ho TW, Willison HJ, Nachamkin I, Li CY, Veitch J, Ung H, et al. Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain–Barré syndrome. Ann Neurol. 1999;45:168–173

PII: S1201-9712(09)00155-6

doi:10.1016/j.ijid.2009.03.019

International Journal of Infectious Diseases
Volume 14, Issue 2 , Pages e161-e163, February 2010

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