Early brain changes in Lyme disease are associated with clinical outcomes
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Background and Objectives
In Lyme disease (LD), 10-20% of patients develop persistent symptoms following antibiotic treatment (i.e., post-treatment Lyme disease (PTLD)), which often includes neurological symptoms. Little is known about how the brain is affected by LD. This study tested the hypothesis that brain changes occur early in LD and influence clinical outcomes.
Methods
In this case-control study, a working memory task was administered during functional MRI (fMRI), in conjunction with cognitive assessments and health surveys, in people with acute LD after antibiotic treatment [i.e., “baseline”] and six months later. A healthy control (HC) group was also assessed six months apart. The LD group was retrospectively categorized into those who returned to health (RTH) and those who reported persistent symptoms (sPTLD). FMRI data from both LD subgroups were compared to the HC group at both time points. Brain regions of interest (ROI) values were obtained from the fMRI results and correlated to cognitive performance and health survey scores.
Results
There were no differences in demographic characteristics [n, % male, mean age (range), mean days after end of initial antibiotic treatment (range)] among RTH [11, 45%, 56.5 (28.4- 78.2), 16.9 (-1.0-51.0)], sPTLD (9, 67%, 47.1 (26.2-66.6), 13.0 (6.0-20.0), and HC [19, 32%, 46.5 (19.4-59.9)]. Baseline brain activity in RTH increased relative to sPTLD and HC, p <.0025 and p <.001, respectively. Notably, 64% of the RTH group’s activation clusters were in white matter, confirmed by segmentation analysis. ROIs created from the RTH vs. HC fMRI results, including white matter regions, correlated with higher (better) health survey scores. At the 6-month follow-up, most of the RTH group’s activity had normalized compared to HC. The sPTLD group showed few fMRI activation differences versus the HC group at either time point, and no significant associations were observed between ROI values and health survey scores.
Discussion
Increased brain activity in early LD was associated with better health survey scores and RTH status six months later. The absence of such brain changes was associated with persistent symptoms. Understanding how increased brain activity contributes to RTH in LD will aid early identification of those most vulnerable to developing PTLD and guide treatment intervention.
