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Title:Neuro-zika: Brain structure and functional organization of adult humans with zika virus infection and severe neurological complications
Author(s):Bido Medina, Richard Oliver
Director of Research:Sadaghiani, Sepideh
Doctoral Committee Chair(s):Sadaghiani, Sepideh
Doctoral Committee Member(s):Heller, Wendy; Llano, Daniel A.; Gratton, Gabriele
Department / Program:Neuroscience Program
Discipline:Neuroscience
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Zika virus, Guillain-Barre Syndrome, resting state functional connectivity, VBM
Abstract:Since its outbreak in the Americas in 2015, Zika virus (ZIKV) has become a major global health threat due to its potential to affect the nervous system. Although most adult cases show no or mild symptoms, some patients exhibit severe neurological complications. While these complications often present as Guillain-Barre Syndrome (GBS)-like manifestations confined to the peripheral nervous system (PNS), they extend to symptoms of the central nervous system (CNS) in a subset of severely affected patients. Yet, reports on the adult CNS have remained confined to a few single cases of structural brain changes. Further, no functional neuroimaging studies have been carried out to investigate how ZIKV affects adult human brain function. In this first case-control neuroimaging study, we investigated nine rare adult patients with ZIKV-related neurological complications of the CNS during the subacute phase (3 females, Age=35±4.46, range 30-45 years, 5±0.5 months since symptoms onset) compared to nine healthy age- and sex-matched controls. Our clinical observations comprised atypical descending and rapidly progressing PNS manifestations, and additional CNS presentations such as perceptual deficits. In light of the persistent cognitive deficits and neurological symptoms, a comprehensive and exhaustive follow up to the patients was performed. This evaluation, performed 2 years after the neurological manifestations onset included clinical assessments, behavioral questionnaires, electrophysiological studies and FLAIR images automated lesion detection. These deviations from typical GBS urgently call for a characterization of a potential impact on the brain. Neuroimaging revealed gray matter volume reductions bilaterally in motor areas (supplementary motor cortex, specifically Frontal Eye Fields) and beyond (left inferior frontal sulcus). Additionally, gray matter volume increased in right middle frontal gyrus. Functional connectivity increased in a widespread network within and across temporal lobes. Here, preliminary evidence is provided for a link between ZIKV neurological complications and changes in adult human brain structure and functional organization, comprising both motor-related regions potentially secondary to prolonged PNS weakness, and non-somatomotor regions indicative of PNS-independent alterations. The latter included the temporal lobes, particularly vulnerable in a range of neurological conditions. While future studies into the ZIKV-related neuroinflammatory mechanisms in adults are urgently needed, the current study indicates that ZIKV infection can lead to an impact on the brain.
Issue Date:2019-04-16
Type:Text
URI:http://hdl.handle.net/2142/105043
Rights Information:Copyright 2019 Richard Bido Medina
Date Available in IDEALS:2019-08-23
Date Deposited:2019-05


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