Medical Rounds

Visualizing ‘Brain Fog’ in Post-Treatment Lyme Disease

By Marin Hedin

More than one in 10 people successfully treated with antibiotics for Lyme disease go on to develop chronic, sometimes debilitating and poorly understood symptoms of fatigue and brain fog that may last for years after their initial infection has cleared up.

Now, a Johns Hopkins team has used an advanced form of brain scan to show that 12 people with documented post-treatment Lyme disease syndrome (PTLDS) all show elevation of a chemical marker of widespread brain inflammation, compared with 19 healthy controls.

Results of the study, published in Journal of Neuroinflammation, suggest new avenues for treating the long-term fatigue, pain, sleep disruption and “brain fog” associated with PTLDS. “There’s been literature suggesting that patients with PTLDS have some chronic inflammation somewhere, but until now we weren’t able to safely probe the brain itself to verify it,” says Jennifer Coughlin, a senior author and associate professor of psychiatry and behavioral sciences.

Over the last decade, Coughlin and her colleagues optimized a positron emission tomography (PET) imaging technique in which specially labeled molecules—or radiotracers—bind to a protein called translocator protein (TSPO). In the brain, TSPO is released primarily by two types of brain immune cells (microglia and astrocytes), so levels of TSPO are higher when brain inflammation is present. With this type of PET scan, Coughlin’s team says it can visualize levels of TSPO—and therefore levels of inflammation, or astrocyte and microglia activation—throughout the brain.

In the new study, Coughlin’s group teamed up with Johns Hopkins Lyme disease researchers and compared PET scans of 12 patients with a diagnosis of PTLDS and 19 without. The scans revealed that across eight different regions of the brain, PTLDS patients had significantly higher levels of TSPO compared with controls. “We thought there might be certain brain regions that would be more vulnerable to inflammation and would be selectively affected, but it really looks like widespread inflammation all across the brain,” says Coughlin.

“What this study does is provide evidence that the brain fog in patients with post-treatment Lyme disease syndrome has a physiological basis and isn’t just psychosomatic or related to depression or anxiety,” says John Aucott, director of the Johns Hopkins Lyme Disease Research Center.

In addition, the results suggest that drugs designed to curb neuroinflammation may be able to treat PTLDS, although clinical trials are needed first to determine the safety and benefit of such therapy, Aucott says.