Guillain-Barré syndrome is a rare neurological condition which can occur following Zika virus infection.
Clinical presentation and symptoms
Guillain-Barré syndrome (GBS) is an autoimmune condition in which the individual’s immune system inappropriately attacks components of their peripheral nerves. This results in muscle weakness in the legs and/or arms, which can spread to other parts of the body. GBS was first described in 1916 by French neurologists.
GBS occurs worldwide but is a rare condition with an overall incidence of 0.8 to 1.9 per 100,000 people per year (WHO Interim Guidance Update: Assessment and management of Guillain-Barré syndrome in the context of Zika virus infection, 18 August 2016). People of all ages can be affected, but it is more common in adults and males.
Symptoms usually start with weakness or tingling in the legs and the weakness can spread to the arms and face. Weakness is often symmetrical. For some people these symptoms can lead to paralysis of the legs, arms or muscles in the face. Severe weakness or paralysis of the chest muscles occurs in 20 to 30% of GBS patients, making breathing difficult.
Symptoms are usually self-limiting, typically lasting a few weeks, with most individuals recovering without long-term or severe neurological complications.
Variant forms of GBS, such as Miller Fisher syndrome (ophthalmoplegia with ataxia and areflexia), present differently from classical GBS and may be associated with detection of specific autoantibodies and/or specific neurophysiological abnormalities.
Diagnosis requires specific clinical signs and symptoms to be present as many other neurological conditions present with similar clinical features.
Features that support the diagnosis of GBS include:
progressive bilateral limbs weakness (which may extend to the trunk and muscles controlled by cranial nerves)
absent or depressed deep tendon reflexes
abnormal findings from neurophysiological studies
elevated protein in cerebrospinal fluid, without a significant increase in white cells
relatively symmetrical weakness
mild sensory symptoms/signs
autonomic dysfunction (eg abnormal heart rhythms, abnormalities in blood pressure, retention of urine)
The precipitating trigger of GBS cannot always be determined, but two thirds of patients report an antecedent, acute infectious illness, most commonly a respiratory-tract infection or gastroenteritis that has resolved by the time neuropathic symptoms begin.
Campylobacter jejuni is the most frequently identified infection associated with GBS with an estimated 30% of cases of GBS attributable to Campylobacter, followed by cytomegalovirus. However, GBS has also been reported following a wide range of other infections, including HIV, dengue and influenza.
It is believed that GBS occurs when antibodies produced in response to an infection cross-react with peripheral nerve components, through molecular mimicry. Less commonly, GBS may be triggered by immunisation, surgery, trauma or bone marrow transplantation.
Treatment of GBS combines supportive treatment and immunotherapy. There is evidence that intravenous immunoglobulin or plasma exchange equally hasten recovery in non-ambulatory patients. Up to 30% of patients need ventilatory support or airway protection.
Mortality from GBS varies between 3 to 5% even in more developed countries (but may be higher in resource-poor areas). In addition, up to 20% remain severely disabled.
GBS and Zika virus infection
Based on a systematic review of the literature up to 30 May 2016, WHO concluded that Zika virus infection is a trigger of Guillain-Barré syndrome (see WHO causality statement, 7 September 2016). The link with Zika virus infection is plausible as GBS cases have been documented following dengue virus infection, another flavivirus transmitted by the same Aedes mosquitoes.
The association of Zika with GBS was first reported in 2014, during an outbreak of Zika virus disease in French Polynesia (ECDC 2014).
A recently published case-control study (Cao-Lormeau et al. 2016) assessed 42 patients who had GBS and serological evidence of Zika virus infection during this outbreak. Of the 42 patients, 37 (88%) had a history of a viral illness a median of 6 days prior to onset of GBS; rash, arthralgia and fever were most the most commonly reported symptoms. The GBS-Zika cases were compared against 98 matched control patients who presented with a non-febrile illness, and 70 matched control patients who presented with acute Zika virus disease and no neurological symptoms.
This study found that the estimated incidence of GBS cases during the French Polynesia outbreak was 0.24 per 1,000 Zika virus infections; importantly, this is lower than the estimated incidence of GBS following Campylobacter jejuni infections (0.25 to 0.65 per 1000 cases) or primary cytomegalovirus infections (0.6 to 2.2 per 1000 cases) (Yuki and Harthung 2012).
Since the first autochthonous transmission of Zika was confirmed in north-east Brazil in May 2015, several countries in South and Central America have reported unusual increases in GBS. Some of these had laboratory-confirmed Zika virus infection preceding GBS, however, the majority reported preceding illnesses that were compatible with Zika virus infection but without laboratory confirmation.
A number of countries have reported an unusual increase in GBS above baseline coinciding with the Zika virus outbreak in the country, including Brazil, Colombia, El Salvador, French Polynesia, Suriname and Venezuela. These observations, along with the findings of the recent case-control study from the French Polynesia outbreak, support the role of Zika virus infection as a trigger event for GBS.
However, it should be borne in mind that other infectious diseases that are prevalent in the Americas and the Caribbean are known to be associated with GBS, and that the estimated risk of GBS following Zika virus infection appears to be lower than the estimated risk for GBS following the most commonly associated trigger, Campylobacter infection.
World Health Organization (October 2016): Guillain-Barré syndrome - Fact Sheet
World Health Organization: Zika virus disease page
ECDC (2014): Zika virus infection outbreak, French Polynesia
Cao-Lormeau et al. (2016) Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet, published online 29 February 2016.
Oehler E, Watrin L, Larre P et al (2014). Zika virus infection complicated by Guillain-Barré syndrome - a case report, French Polynesia, December 2013. Eurosurveillance 19(9):pii=20720
Hughes RA, Swan AV, Raphael JC, et al. (2007). Immunotherapy for Guillain-Barré syndrome: a systematic review. Brain, 2007;130:2245-2257.
Yuki N, Hartung H-P (2012). Gullain-Barré syndrome. New England Journal of Medicine, 2012;366(24):2294-2304.