The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series

<div><p>Background</p><p>During 2015–16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (GBS) in adults but other neurological associations are uncertain. Chikungunya virus has caused outbreaks in Brazil since 2014 but associated neurological disease has rarely been reported here. We investigated adults with acute neurological disorders for Zika, chikungunya and dengue, another arbovirus circulating in Brazil.</p><p>Methods</p><p>We studied adults who had developed a new neurological condition following suspected Zika virus infection between 1^st November 2015 and 1^st June 2016. Cerebrospinal fluid (CSF), serum, and urine were tested for evidence of Zika, chikungunya, and dengue viruses.</p><p>Results</p><p>Of 35 patients studied, 22 had evidence of recent arboviral infection. Twelve had positive PCR or IgM for Zika, five of whom also had evidence for chikungunya, three for dengue, and one for all three viruses. Five of them presented with GBS; seven had presentations other than GBS, including meningoencephalitis, myelitis, radiculitis or combinations of these syndromes. Additionally, ten patients positive for chikungunya virus, two of whom also had evidence for dengue virus, presented with a similar range of neurological conditions.</p><p>Conclusions</p><p>Zika virus is associated with a wide range of neurological manifestations, including central nervous system disease. Chikungunya virus appears to have an equally important association with neurological disease in Brazil, and many patients had dual infection. To understand fully the burden of Zika we must look beyond GBS, and also investigate for other co-circulating arboviruses, particularly chikungunya.</p></div

Individual clinical features of 22 patients presenting with neurological disease associated with Zika, chikungunya and/or dengue virus infection, ordered by date of admission.

<p>Individual clinical features of 22 patients presenting with neurological disease associated with Zika, chikungunya and/or dengue virus infection, ordered by date of admission.</p

Clinical characteristics of 22 patients presenting with neurological disease associated with Zika, chikungunya and/or dengue virus infection.

<p>Clinical characteristics of 22 patients presenting with neurological disease associated with Zika, chikungunya and/or dengue virus infection.</p

Virological evidence for Zika, chikungunya and/or dengue virus infection in 22 patients presenting with acute neurological disease, ordered by date of admission.

<p>Virological evidence for Zika, chikungunya and/or dengue virus infection in 22 patients presenting with acute neurological disease, ordered by date of admission.</p

Venn diagram for 22 patients showing virological evidence of CNS or systemic infection with Zika, chikungunya and/or dengue, and clinical presentation with CNS or peripheral nervous system disease.

<p>We distinguish <i>virological</i> evidence of CNS or systemic infection (based on PCR/antibody testing) from <i>clinical</i> evidence of CNS or peripheral nervous system disease (based on clinical features). Patients in the inner darker circles have evidence of CNS +/- systemic infection with the respective virus. Those in the outer paler circles have evidence of only systemic infection with the respective virus. Note that patients 1 and 3 had confirmed Zika, +/- dengue; patients 2 and 7 had Zika or dengue or both.</p

Central nervous system (CNS) imaging abnormalities in patients with evidence of Zika, chikungunya and/or dengue virus infection.

<p>A: Encephalomyelitis in a patient with CNS Zika and systemic dengue infection (patient 3). Fluid attenuation inversion recovery [FLAIR] signal abnormality involving the middle cerebellar peduncles, more marked on the right (axial scan). B: Acute disseminated encephalomyelitis in a patient with systemic chikungunya infection (patient 20). Confluent areas of T2 signal abnormality suggesting neuroinflammation consistent with demyelination (coronal scan). C, D, E: Encephalomyelitis with subclinical meningitis in a patient with CNS Zika + chikungunya infection (patient 9). FLAIR signal abnormality involving the medial temporal lobes, amygdala, and a small area of abnormality adjacent to the temporal horn of the left lateral ventricle (C, axial scan). High signal intensity on T2-weighted images in the anterior medulla, and anterior cervical and thoracic cord (D and E, sagittal scans). F, G, H: Myelitis in a patient with CNS Zika + dengue and systemic chikungunya infection (patient 2). Extensive intramedullary signal abnormality of the cervical cord, without evidence of contrast enhancement (F, sagittal T2-weighted scan; G, sagittal T1-weighted scan with gadolinium; H, axial T2-weighted scan). I, J: Facial diplegia with paraesthesia in patient with CNS Zika + chikungunya infection (patient 4). Bilateral facial nerve enhancement on T2-weighted images with gadolinium (axial scan).</p