Disrupted white matter microstructure in chronic Zika virus-infected adults

Systemic viral infections with neurotropic potential continue to pose significant global health challenges. The Zika virus (ZIKV) is known for its pronounced neurotropism. Research on ZIKV has predominantly centered on congenital and infant populations, where the virus’ detrimental effects on brain development are well-documented. However, increasing evidence suggests that the mature central nervous system (CNS) is also susceptible to ZIKV. Despite this, no study has comprehensively investigated the potential long-term structural and functional changes in the adult human brain.

To address this gap, we studied a group of rare adult ZIKV patients presenting with both peripheral and, importantly, CNS-related neurological symptoms. We compared these patients to healthy controls and to patients with Guillain-Barre Syndrome of non-ZIKV etiology, which predominantly affects the peripheral nervous system. Here, we focused on structural (cortical thickness, white matter hyperintensities, and diffusion measures) and functional (hippocampus-dependent resting state connectivity) changes in the brain associated with ZIKV at the chronic stage, i.e. 5 to 12 months from the infection.

We observed decreased mean diffusivity in the inferior fronto-occipital fasciculus and the forceps major in the ZIKV-CNS-GBS group compared to other groups. Notably, some of the CNS-related neurological symptoms of the ZIKV patients corresponded with the functional role of these affected white matter tracts. However, we found no evidence for long-term changes in cortical thickness, white matter hyperintensities, or functional connectivity.

Our findings suggest that the more pronounced and prolonged changes in white matter, compared to gray matter, may reflect the greater metabolic demands and prolonged timecourse of white matter repair, particularly in the context of inflammation and oxidative stress in the brain associated with ZIKV infection. This case-control study provides first evidence for the long-term impact of ZIKV infection on the adult human brain, emphasizing the importance of extending ZIKV research and health policy considerations to the adult population.