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Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

ABSTRACT: Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

SUBMITTER: Adams Waldorf KM

PROVIDER: S-EPMC5839998 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

Adams Waldorf Kristina M KM Nelson Branden R BR Stencel-Baerenwald Jennifer E JE Studholme Colin C Kapur Raj P RP Armistead Blair B Walker Christie L CL Merillat Sean S Vornhagen Jay J Tisoncik-Go Jennifer J Baldessari Audrey A Coleman Michelle M Dighe Manjiri K MK Shaw Dennis W W DWW Roby Justin A JA Santana-Ufret Veronica V Boldenow Erica E Li Junwei J Gao Xiaohu X Davis Michael A MA Swanstrom Jesica A JA Jensen Kara K Widman Douglas G DG Baric Ralph S RS Medwid Joseph T JT Hanley Kathryn A KA Ogle Jason J Gough G Michael GM Lee Wonsok W English Chris C Durning W McIntyre WM Thiel Jeff J Gatenby Chris C Dewey Elyse C EC Fairgrieve Marian R MR Hodge Rebecca D RD Grant Richard F RF Kuller LaRene L Dobyns William B WB Hevner Robert F RF Gale Michael M Rajagopal Lakshmi L

Nature medicine 20180205 3

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular ...[more]

PMID: 29400709

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Project description:IntroductionCongenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children.MethodsFollowing IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI).ResultsTwenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases.ConclusionNeurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families.

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Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

Publications

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

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