The Neurocognitive and MRI Outcomes of West Nile Virus Infection: Preliminary Analysis Using an External Control Group

Abstract

To understand the long-term neurological outcomes resultant of West Nile virus (WNV) infection, participants from a previously established, prospective WNV cohort were invited to take part in a comprehensive neurologic and neurocognitive examination. Those with an abnormal exam finding were invited for MRI to evaluate cortical thinning and regional brain atrophy following infection. Correlations of presenting clinical syndrome with neurologic and neurocognitive dysfunctions were evaluated, as well as correlations of neurocognitive outcomes with MRI results. From 2002 to 2012, a total of 262 participants with a history of WNV infection were enrolled as research participants in a longitudinal cohort study, and 117 completed comprehensive neurologic and neurocognitive evaluations. Abnormal neurological exam findings were identified in 49% (57/117) of participants, with most abnormalities being unilateral. The most common abnormalities included decreased strength (26%; 30/117), abnormal reflexes (14%; 16/117), and tremors (10%; 12/117). Weakness and decreased reflexes were consistent with lower motor neuron damage in a significant proportion of patients. We observed a 22% overall rate of impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), with impairments observed in immediate (31%) and delayed memory (25%). On MRI, participants showed significant cortical thinning as compared to age- and gender-matched controls in both hemispheres, with affected regions primarily occurring in the frontal and limbic cortices. Regional atrophy occurred in the cerebellum, brain stem, thalamus, putamen, and globus pallidus. This study provides valuable new information regarding the neurological outcomes following WNV infection, with MRI evidence of significant cortical thinning and regional atrophy; however, it is important to note that the results may include systemic bias due to the external control group. Considering no effective treatment measures are available, strategies to prevent infection are key.

Keywords: Repeatable Battery for the Assessment of Neuropsychological Status; West Nile virus; cortical thinning; neurocognitive outcomes; neurological outcomes; regional brain atrophy.

Figure 1

Study participant enrollment. From 2002 to 2012, a total of 262 patients with a history of West Nile virus (WNV) infection have been enrolled as research participants in this longitudinal cohort. Of the 262 potential participants, 190 were invited to participate. A total of 72 enrolled participants were not invited due to death (n = 29), additional tests determined a false positive WNV status (n = 11), lost-to-follow-up since initial enrollment (n = 26), or declined further participation since initial enrollment (n = 6). Of the 190 invited participants, 117 took part in the neurologic and the neurocognitive evaluations. Failure to take part was due to lack of desire to participate, inability to come to the Texas Medical Center for extensive testing, or unspecified reasons.

Figure 2

Cortical thinning and regional atrophy analyses. (A) Volumetric MRI. Left (first column) and right (second column) hemispheres showing cortical thinning in West Nile infected individuals as compared to a database of MRIs from healthy controls with lateral (top row) and medial (bottom row) views. Colored regions indicate areas of thinning. In the left hemisphere, parts of the posterior cingulate cortex (pink), parts of the superior frontal cortex and medial-orbito frontal region (magenta), anterior cingulate cortex and inferior frontal cortex (violet blue), parts of the cuneus (orange) and para hippocampal region (pale green) were identified. In the right hemisphere, parts of the middle and inferior temporal cortex, and supramarginal region (light blue), inferior frontal region and insular cortex (bright green and red), parts of the superior frontal cortex (light green, blue, and violet), cingulate cortex (light purple), and inferior frontal region (blue) were identified. (B) Tensor-based morphometry (TBM) analysis of regional atrophy. Regions with regional atrophy as detected by TBM are identified in red.

Figure 3

Non-pairwise scatterplots of raw data compairing total Repeatable Battery for the Assessment of Neuropsychological Status score (y-axis) to cortical thickness (x-axis) by region and hemisphere of the brain among the 30 West Nile virus participants who underwent MRI.