Zika virus infection–associated acute transient polyneuritis
Citation Manager Formats
Make Comment
See Comments

Zika virus (ZIKV) has been associated with various neurologic complications in adults, including Guillain-Barré syndrome (GBS), transverse myelitis, meningoencephalitis, and ophthalmologic manifestations. Though some of these syndromes may be due to a postinfectious (molecular mimicry) mechanism, a direct viral pathogenic mechanism may be responsible in others. We present 3 cases of a newly described syndrome of ZIKV-associated acute transient polyneuritis.
Methods.
This article describes a case series of 3 patients admitted to a tertiary hospital in Rio de Janeiro during the 2016 outbreak of Zika virus infection in Brazil.
Standard protocol approvals, registrations, and patient consents.
This study was approved by the HUAP-UFF institutional review board. All patients or their surrogates were consented for participation in this study.
Zika virus diagnosis.
Blood and CSF collected at admission were tested in duplicate using real-time reverse transcriptase PCR (rRT-PCR) for ZIKV following published methods at the Oswaldo Cruz Foundation Flavivirus Laboratory. Urine rRT-PCR was tested in one case.
Other diagnostics.
Electrophysiology studies (EMG and nerve conduction studies) were performed by certified neurologists with specialty training in neuromuscular disease using criteria endorsed by the European Federation of Neurological Societies/Peripheral Nerve Society and American Association of Neuromuscular and Electrodiagnostic Medicine (e-Methods at Neurology.org). All examinations included nerve testing in both upper and lower extremities and F wave testing. Nerve ultrasound was performed of the bilateral median nerves (1–2 cm proximal to the carpal tunnel) and bilateral superficial peroneal nerves (5 cm above the medial malleolus). Brain and spine 3T MRI with gadolinium administration and nerve ultrasound were interpreted by independent, board-certified neuroradiologists. Other blood testing was conducted to rule out alternative causes of muscular/peripheral nerve disease (e-Methods).
Results.
Three patients presented to the Antonio Pedro University Hospital of Universidade Federal Fluminense in Rio de Janeiro, Brazil, with signs and symptoms of distal pain, stocking-glove hypoesthesia, mild distal weakness, and hyporeflexia within 1–2 days of ZIKV symptom onset. Clinical examination, imaging, electrophysiologic, and outcome findings for these patients are delineated in the table. Nerve ultrasound demonstrated bilaterally enlarged median nerves in patients 1 and 2 (figure e-1). Mental status, cranial nerves, and cerebellar examination were normal for all patients, as were muscle enzyme testing, inflammatory serology testing, and other routine laboratory studies. No patient met Brighton1 or electrophysiologic criteria for GBS.
Clinical and laboratory findings in patients with Zika virus–associated polyneuritis
Discussion.
We report acute ZIKV infection accompanied by clinical findings consistent with a mild, self-limited, distal, sensorimotor neuropathy. Because nerve ultrasound in 2 patients demonstrated enlargement of symptomatic nerves, followed by concomitant improvement in symptoms and nerve diameter on serial ultrasound, the mechanism of this syndrome may be related to nerve swelling. It has been described that some forms of infections might result in segmental nerve inflammation with edema, compromising nerve function in an acute fashion.2,3 For the most part, the Schwann cells are the target of the infectious agent resulting in demyelination, which could evolve into a rapid resolution or further progress, depending on the host's immune response.2,3 Since symptoms and imaging findings tracked closely with ZIKV viremia, we hypothesize that there may be a direct neuropathic effect of ZIKV leading to inflammation and nerve swelling. Others have published reports of weakness developing soon after the first few days of ZIKV infection symptoms, considered early for postinfectious molecular mimicry mechanism of nerve injury, but in this case series the patients developed clinical, laboratory, and electrophysiologic findings highly suggestive of GBS.4 We report 3 cases that do not fit the usual criteria for GBS, as weakness was mild and limited to the extremities, a predominance of sensory symptoms was observed, and rapid improvement of symptoms within the first 7–10 days with associated unrevealing electrophysiologic and CSF testing (repeated weeks later) was noted.
Preliminary research using human neural progenitor cells have shown that ZIKV infection increases cell death and dysregulates cell cycle progression.5 Other flaviviruses, such as West Nile virus, can lead to direct neurotropic injuries as well.
Though nerve conduction studies were normal, mild syndromes with clinical manifestations may manifest with minimal electrophysiologic abnormalities.6,7 Since the syndrome we describe primarily involves distal nerves, normal electrophysiologic studies are not inconsistent with an acute neuropathy. Negative serum and CSF laboratory studies and normal gadolinium-enhanced MRI of the brain and spine diminish the likelihood of a brain, spinal cord, or muscular etiology for our patients' clinical presentations.
Our cases suggest a newly described ZIKV-associated acute transient polyneuritis. It will be important for practitioners to recognize this benign syndrome and differentiate it from other ZIKV-related complications.
Acknowledgments
Acknowledgment: The authors thank Dr. Richard Hughes for his comments on this manuscript and acknowledge coauthor Dr. Daniel A. Amitrano who died prior to publication of this article.
Footnotes
Coinvestigators are listed at Neurology.org.
Supplemental data at Neurology.org
Author contributions: Dr. Nascimento contributed with study design, data analysis, and manuscript writing. Dr. Frontera contributed with study design, data analysis, and manuscript writing. Dr. Amitrano contributed with study design, data analysis, and manuscript writing. Dr. Bispo de Filippis contributed with study design and samples testing. Dr. Da Silva contributed with data collection, study design, data analysis, and manuscript writing. The authors wrote on behalf of the RIO-GBS-ZIKV Research Group (see supplemental data).
Study funding: This study was funded by the Cleveland Clinic Foundation, award RPC194-S2.
Disclosure: O. Nascimento, J. Frontera, and D. Amitrano report no disclosures relevant to the manuscript. A. Bispo de Fillipis receives grants from Conselho Nacional de Desenvolvimento e Pesquisa (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). I. Da Silva reports no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
- Received November 2, 2016.
- Accepted in final form March 22, 2017.
- © 2017 American Academy of Neurology
References
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Hastening the Diagnosis of Amyotrophic Lateral Sclerosis
Dr. Brian Callaghan and Dr. Kellen Quigg
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Article
Long-term outcome in neuroZikaWhen biological diagnosis mattersAnnie Lannuzel, Jean-Louis Fergé, Quentin Lobjois et al.Neurology, April 26, 2019 -
Review
Zika virus disease for neurologistsDaniel E. Smith, J. David Beckham, Kenneth L. Tyler et al.Neurology: Clinical Practice, October 13, 2016 -
Clinical/Scientific Notes
Zika virus infection and myasthenia gravis: report of 2 casesNicolas Molko, Olivier Simon, David Guyon et al.Neurology, February 10, 2017 -
Clinical/Scientific Notes
Acute Zika infection with concurrent onset of Guillain-Barré SyndromeRonald Siu, Wajih Bukhari, Angela Todd et al.Neurology, July 27, 2016