Thanks to Greg Folkers for sending the link to this editorial in NEJM: Zika Getting on Your Nerves? The Association with the Guillain–Barré Syndrome. The conclusion:
As is true with most clinical studies, proving a causal relationship between ZIKV infection and the Guillain–Barré syndrome is challenging. In keeping with Hill criteria for causality, the authors show a consistent, specific, temporal relationship, which is analogous to relationships between ZIKV infection and the Guillain–Barré syndrome observed in other countries.
What is more difficult to demonstrate is pathophysiological plausibility. The authors point out that 20 patients had neurologic symptoms immediately after the viral syndrome (only 9 of 20 had definite laboratory-proven ZIKV) and speculate that other mechanisms, including a hyperacute immune response or direct viral neuropathic mechanisms, may be in effect, rather than postinfectious molecular mimicry.
Although studies using human neural progenitor cells have shown that ZIKV infection increases cell death and dysregulates cell-cycle progression, evidence of direct neurotropism in adult neuronal cells is still lacking. A recent study showed that there is a high peptide overlap between the ZIKV polyprotein and human proteins related to myelin and axons, which suggests that an immune-mediated mechanism may be more likely.
Although protein epitopes and antibodies that are normally involved in the genesis of the Guillain–Barré syndrome seem not to be highly involved in one cohort with ZIKV-associated acute motor axonal neuropathy, it is possible that differences in subtypes of the Guillain–Barré syndrome and host genetic factors may lead to varying immune-mediated mechanisms in different populations.
Overall, the study by Parra and colleagues supports the association between ZIKV and the Guillain–Barré syndrome, although confirmation in another cohort would strengthen this assertion. Although high rates of seropositivity may prove protective against further waves of ZIKV-related Guillain–Barré syndrome in Central and South America, the ZIKV pandemic is just beginning in North America and Africa, and an increase in the incidence of the Guillain–Barré syndrome may follow.
