Enlarged brain spaces tied to Parkinson’s dyskinesia, per study

Perivascular spaces could be used as imaging markers for LID

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A widening of tiny, fluid-filled spaces in certain brain regions could be used as an imaging marker of levodopa-induced dyskinesia (LID) in people with Parkinson’s disease, a study showed.

Perivascular spaces, or PVSs, were larger in Parkinson’s patients with LID — a condition in which standard Parkinson’s medications lead to involuntary movements — than in healthy people or Parkinson’s patients without LID in a brain area implicated in motor control. The larger the PVS in that area, the more substantial the dyskinesia symptoms were.

“Our investigation may offer a potential supplement for the diagnosis, prognosis, and intervention of dyskinesia,” the researchers wrote. “Manipulating factors of the PVS system appear to be valid approaches for LID treatment.”

Their study, “Altered perivascular spaces in subcortical white matter in Parkinson’s disease patients with levodopa-induced dyskinesia,” was published in npj Parkinson’s Disease.

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Perivascular spaces are the fluid-filled areas surrounding the brain’s small blood vessels. They play an important role in circulation and drainage of fluids and clearance of waste products.

These tiny spaces naturally enlarge, or dilate, with age, and become progressively more visible on MRI scans. PVS dilation has also been linked to various neurological diseases in which toxic protein accumulation, neuroinflammation, and other cellular changes are believed to obstruct these spaces and cause them to enlarge.

In Parkinson’s patients, PVS enlargement in certain brain regions has been found to correlate with motor symptom severity and cognitive declines. Researchers have proposed that PVS obstruction and dysfunction could lead to problems with  drainage and waste clearance that further enable alpha-synuclein, the protein that accumulates in the Parkinson’s brain, to gather.

LID is a common complication in Parkinson’s disease. The medications used to control motor symptoms lead to dyskinesia, especially when used long term.

“Currently, the intricate pathogenesis of LID remains incompletely elucidated,” the scientists wrote. They speculated that perivascular space dilation might be linked to LID, but PVS patterns in patients with the debilitating symptom hadn’t been explored.

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To learn more, they used MRI imaging to evaluate changes in PVS among 42 Parkinson’s patients with LID, comparing them with 45 Parkinson’s patients without LID and 45 healthy people.

They were looking at subcortical brain regions, where neurodegeneration in Parkinson’s is observed.

All Parkinson’s patients had significantly enlarged PVSs compared with healthy people, and those with LID had significantly larger PVSs than Parkinson’s patients without LID.

LID patients showed significant PVS dilation in the inferior frontal gyrus region on the right side of the brain compared with non-LID patients and healthy people.

This part of the brain connects to several others that are involved in motor inhibition, or the ability to suppress unwanted motor behaviors. The researchers likened it to a brake that stops or pauses movements. The scientists believe the PVS elevation they observed in LID patients could reflect impairments in or damage to this inhibitory system that ultimately contribute to dyskinesia.

Indeed, the greater the PVS dilation in the inferior frontal gyrus, the more severe the dyskinesia symptoms among LID patients.

PVS dilation in that area could also be used to distinguish LID patients from patients without LID or healthy people with more than 80% diagnostic accuracy, and thus “could act as an imaging marker” for LID, the researchers said.

Parkinson’s patients in both groups had significantly greater PVS dilation in superior temporal brain regions, which are known to be involved in cognitive function, than healthy people.

While Parkinson’s patients exhibited lower cognitive function than healthy people, no correlations were observed between cognitive performance and PVS in superior temporal regions.

The researchers wrote that PVS evaluations “might provide a more accurate biomarker for early diagnosis and differentiation of diseases.”

”Future studies with continuous and long-term monitoring of PVS will provide “a more complete understanding of the relationship between PVS levels and the progression of LID,” they wrote.

Research suggests that PVS dilation is reversible, and so could be targeted therapeutically. Good sleep hygiene, physical exercise, and management of other health conditions linked to PVS dilation, such as high blood pressure, may all be beneficial, the team said.