Guillain-Barré syndrome associated with Zika virus infection

Abstract

A 24-year-old housekeeper presented to hospital in Rio de Janeiro in June, 2014, with headache, fever, and a rash, 5 days after waking with a severe generalised headache, retro-orbital pain, weakness, and paraesthesia of the hands and feet. 2 days later she developed fever (axillary temperature 42°C), chills, and a pruritic rash on the face, abdomen, chest, and arms. By day 4, she was afebrile but had painful swelling of the hands (appendix) and feet, diffi culty walking, and disseminated rash. She had had dengue 5 years previously, had not travelled recently, and did not recall any tick or mosquito bites. On examination, she was alert and fully oriented. Axillary temperature was 36·7°C, pulse 90 beats per min, blood pressure 100/60 mm Hg, and respiratory rate 20 breaths per min. She had a diff use erythematous macular rash, bilateral non-purulent conjunctival hyperaemia, enanthema of the palate, one enlarged painless cervical lymph node, and swelling of the hands and feet, but no signs of meningism. She had reduced strength in the legs, absent deep tendon refl exes at the knees and ankles, and both plantars were absent; sensation to light touch was reduced in the legs, but she had no urinary retention or ataxia. Examination, including neurological examination of the arms, was otherwise normal. Lumbar puncture (day 6), nerve conduction studies and an electromyogram (day 10), and a non-enhanced MRI (day 13) were normal. From day 10 the rash and swelling began to resolve with supportive treatment. By day 13 she was fully mobile and could be discharged. At follow-up on day 41, her only remaining symptom was persistent headache. We investigated her serum and cerebrospinal fl uid (CSF) for dengue, chikungunya, and Zika viruses. Realtime PCR for dengue and chikungunya was negative, but PCR was positive for Zika virus in serum (day 5), CSF (day 6), saliva (day 10), and urine (day 11). The CSF and acute and convalescent serum were negative for dengue and chikungunya by IgM-capture ELISA. Zika ELISA was not available. To identify the Zika virus genotype we sequenced 327 base pair amplicons encompassing the envelope protein, and identifi ed the Asian lineage of Zika in the CSF (fi gure). Like dengue and chikungunya, Zika virus causes a febrile illness with rash. During the 2013 outbreak of Zika virus in French Polynesia an apparent increase in Guillain-Barre syndrome incidence was noted but with no baseline data for comparison. One case had antibodies against Zika and dengue viruses (which can also trigger Guillain-Barre syndrome), but no virus was detected. Our patient had no evidence of dengue or chikungunya infection, but Zika was found in the CSF by PCR, and unusually she also had high grade fever and clinical features consistent with paraparetic Guillain-Barre syndrome, a rare atypical presentation. CSF and neurophysiological investigations were normal, as is often found early in Guillain-Barre syndrome. She met Level III of diagnostic certainty for Guillain-Barre syndrome in the Brighton classifi cation (consistent clinical features, but no supporting CSF or neurophysiology evidence). Our case highlights the potential for neurotropism of Zika virus, and the need to consider this emerging virus as a mosquito-borne cause of fever, rash, and neurological disease.