Acute Zika infection with concurrent onset of Guillain-Barré Syndrome

We thank Gerardin et al. for the comments on our Zika virus (ZIKV) clinical/scientific note [1]. Our patient was of particular interest because he suffered an illness clinically and electrophysiologically indistinguishable from Guillain-Barré syndrome (GBS) which developed within a few days of acute ZIKV infection, in the context of contemporaneous Zika vireamia. [1] Concurrently obtained CSF was negative for ZIKV. Brain and spine MRI were also normal. Importantly, there was no serologic evidence of priming by previous dengue or other flaviviruses.

These clinical data suggested a direct ZIKV neural-injury mechanism, without a requirement for priming. We postulated that although molecular mimicry between ZIKV and peripheral nerve components might be relevant to antibody-induced GBS, such a rapidly developing polyradiculoneuritis mimicking GBS might also have been mediated by a direct pathogenic ZIKV effect on peripheral nerves. [2,3] This observation and ZIKV neurotropsim may also account for delayed CNS ZIKV effects in some patients. The fact that our patient was ZIKV negative in CSF suggests efficacy of the blood-brain barrier to ZIKV at that time point and strengthens the suggestion that ZIKV CNS invasion may be via neuronal transmission rather than directly across the blood brain barrier.

1. Siu R, Bukhari W, Todd A, et al. Acute Zika infection with concurrent onset of Guillain-Barré Syndrome. Neurology 2016;87:1623-1624.

2. Neal JW. Flaviviruses are neurotropic, but how do they invade the CNS? J Infect 2014;69:203-215.

3. Velandia ML, Castellanos JE. Flavivirus Neurotropism, Neuroinvasion, Neurovirulence and Neurosusceptibility: Clues to Understanding Flavivirus- and Dengue-Induced Encephalitis. In: Garcia ML, Romanowski V, editors. Viral Genomes - Molecular Structure, Diversity, Gene Expression Mechanisms and Host-Virus Interactions. Rijeka, Croatia: InTech; 2012:219-240.

For disclosures, please contact the editorial office at [email protected].

Siu et al. reported the concurrent onset of polyradiculoneuritis and acute Zika virus (ZIKV) infection, while the virus was not cleared from the serum. [1] Guillain-Barre syndrome (GBS) is usually described as a post-infectious disease during which progressive flaccid paralysis develops after a phase of latency following infection. In the most common pathogenetic framework, this free interval permits the generation of sufficient levels of antibodies that crossreact by molecular mimicry with specific components of peripheral nerves, causing myelin or axonal injury, as previously documented with ZIKV infection. [2] However, this case report suggested other mechanisms. Given ZIKV cross-reactivity with dengue virus and increasing reports of ZIKV-associated GBS in dengue seropositive patients, [1,3] a hyperacute immune response is possible. [4] Given prolonged ZIKV shedding in bodily fluids, and the overlap between GBS onset and persistent shedding in fomites, a direct viral neuropathic effect may also contribute to ZIKV-associated GBS. [4] Indeed, ZIKV is able to infect cranial neural-crest cells that stem Schwann cell formation. [5] ZIKV-associated GBS could reflect a direct viral neuropathic effect on the blood-nerve barrier, allowing cross-reactive antibodies formed during previous infections to have a deleterious effect on nerve function.

1. Siu R, Bukhari W, Todd A, et al. Acute Zika infection with concurrent onset of Guillain-Barre Syndrome. Neurology 2016;87:1623-1624.

2. Cao-Lormeau VM, Blake A, Mons S, et al. Guillain-Barre syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016;387:1531-1539.

3. Parra B, Lizarazo J, Jimenez-Arango JA, et al. Guillain-Barre syndrome associated with Zika virus in Colombia. N Engl J Med 2016;375:1513-1523.

4. Dejnirattisai W, Supasa P, Wongwiwat W, et al. Dengue virus sero-cross-reactivity drives antibody dependent enhancement of infection with Zika virus. Nat Immunol 2016;17:1102-1108.

5. Bayless NL, Greenberg RS, Swigut T, Wysocka J, Blish CA. Zika Virus Infection Induces Cranial Neural Crest Cells to Produce Cytokines at Levels Detrimental for Neurogenesis. Cell Host Microbe 2016;20:423-428.

For disclosures, please contact the editorial office at [email protected].