Some 10% to 20% of the nearly half a million Americans who contract Lyme disease annually go on to develop post-treatment Lyme disease. The chronic illness can be marked by fatigue, muscular pain, insomnia, depression and cognitive difficulties, such as trouble with concentration and memory.
These individuals generally have no obvious clinical or laboratory evidence of ongoing issues. Now, in a study using specialized imaging techniques, Johns Hopkins Medicine researchers report distinctive changes in the “white matter” and other brain tissue physiology of those with post-treatment Lyme disease. Their results were published in PLOS One.
The study’s findings substantiate and help validate that memory and other cognitive difficulties experienced long term by individuals with post-treatment Lyme disease are linked to functional and structural changes in the brain.
“Objective biologic measures of post-treatment Lyme symptoms typically can’t be identified using regular MRI scans, CT scans or blood tests. We needed to expand our methods of evaluation,” says John Aucott, director of the Johns Hopkins Lyme Disease Clinical Research Center.
Spearheaded by lead author and neurologist Cherie Marvel, the team recruited 12 male and female patients with post-treatment Lyme disease and 18 participants without a history of Lyme to undergo fMRI scans — which detect changes in brain blood flow — while performing a short-term memory task.
The imaging tests revealed unusual activity in the frontal lobe, an area of the brain responsible for cognitive tasks such as memory recall and concentration, among those with post-treatment Lyme disease. “We saw certain areas in the frontal lobe underactivating and others that were overactivating, which was somewhat expected,” says Marvel. The researchers did not see this same white matter activity in those without a history of Lyme.
The researchers then used a second form of imaging called diffusion tensor imaging — which detects the direction of water movement within brain tissue — on all 12 participants with Lyme and 12 of the 18 non-Lyme participants. This imaging corroborated their fMRI findings and revealed something new: Water was diffusing along the Lyme patients’ axons within the same white matter regions identified in the fMRI.
Surprisingly, researchers also found that axonal leakage in white matter correlated with fewer cognitive deficits and better outcomes among the patients with post-treatment Lyme disease they studied.
The increased activity the researchers saw in white matter may reflect a helpful immune response in the patients with post-treatment Lyme, as it correlated with better disease outcomes. However, this finding was also correlated to the patients with post-treatment Lyme needing longer periods of time to complete the memory task — indicative that the white matter response could be an adaptive one, but that the white matter’s physiology and function have been changed, which could come at a cost.
Marvel and Aucott say this research may help illuminate underlying mechanisms and potential therapeutic targets for neurologic Lyme disease, and have relevance to other infection-associated chronic illnesses, including long COVID-19 and chronic fatigue syndrome.