Leaky Blood-Brain Barrier Causes Brain Damage Before MRI Catches Lesions

MRI brain scans may be too late to identify the beginning stages of brain damage caused by a leaky blood-brain barrier in patients with cerebral small vessel disease.

Imaging is typically used to pinpoint brain lesions that are associated with cerebral small vessel disease, a condition that can lead to thinking and memory problems, as well as stroke. But, results from a new study published March 24 in Neurology indicate those lesions may not be the first signs of brain damage in this patient group.

Instead, said a team led by Danielle Kerkhofs, M.D., doctoral student at Maastricht University Medical Center in The Netherlands, the initial culprit is likely a leaky blood-brain barrier. And, this knowledge, she said, could lead to better future treatments.

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“Previous research has shown that disruption of the blood-brain barrier is increased in people with cerebral small vessel disease,” Kerkhofs said. “People with cerebral small vessel disease also may have brain lesions called white matter hyperintensities. Such lesions are visible by MRI and believed to be signs of brain damage and a marker of the severity of disease. For our study, we wanted to see if a leaky blood-brain barrier was linked to degeneration of brain tissue even before these brain lesions appear.”

To do so, they examined tissue they considered “at risk” – normal brain tissue surrounding or close to brain lesions – in 43 people with cerebral small vessel disease. At the beginning of the study, they measured the leakiness of the blood-brain barrier with MRI. With an additional imaging technique, they measured the integrity of the microstructure of the tissue surrounding lesions both at baseline and after two years.

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Based on their analysis, the team discovered that patients who had more tissue volume with blood-brain barrier leakage at study-start lost more brain tissue integrity around brain lesions over the two-year period. Specifically, for every 10 percent of leakage volume at baseline, the investigators identified a 1.4-percent increase in brain tissue diffusivity after two years, indicating a drop in brain tissue integrity. In addition, they determined that higher leakage rates were associated with more loss of tissue microstructure around existing brain lesions.

“Our results support the theory that a compromised blood-brain barrier may play an early role in loss of brain tissue integrity as part of the cerebral small vessel disease process, even before brain lesions are visible on MRI,” Kerkhofs explained. “The change in the integrity of brain tissue at risk, close to the brain lesions, could be a promising biomarker in future cerebral small vessel disease studies examining possible prevention strategies and treatment options.”

Additional research with larger patient populations is needed, she said.