Circuit-based lesion analysis may help diagnose memory, other deficits in MS

Key takeaways:

• Researchers conducted a study of 431 adults with multiple sclerosis.
• Data showed lesion volume and damage were associated with memory dysfunction.

Tracking data from white matter lesions on structural imaging via a circuit-based approach may assist in prognosis of memory and other higher order deficits for those with multiple sclerosis, per research published in Journal of Neurology.

“Accumulation of [white matter lesions] is associated with both worsening cognition and worsening memory,” Isaiah Kletenik, MD, a neurologist in the division of cognitive and behavioral neurology at Brigham and Women’s Hospital in Boston, and colleagues wrote. “However, this finding is not specific to memory as total lesion burden has also been associated with worsening fatigue, depression and gait dysfunction.”

Kletenik and colleagues sought to determine whether memory dysfunction in MS is associated with white matter lesions involving a specific brain circuit.

Their retrospective cross-sectional study included 431 adults with MS (mean age 49.2 years; 71.9% female) from the SysteMS study conducted at Brigham and Women’s Hospital between September 2015 and December 2019, which involved analysis of standard structural images and verbal memory scores as assessed by immediate recall trials.

Kletenik and colleagues conducted four tests: associations between memory dysfunction and total MS lesion volume; associations between memory dysfunction and lesion intersection with an a priori memory circuit derived from stroke lesions; mediation analyses to determine which variable was most associated with memory dysfunction; data-driven analysis to derive de novo brain circuits for MS memory dysfunction using both functional and structural connectomes. White matter lesion locations from each participant were mapped using a validated algorithm, and a “network damage score” was compiled for each and analyzed in a Pearson correlation along with individual memory scores.

The researchers found data was consistent with prior literature, in that both total lesion volume (R=0.31, P<0.001) and lesion damage to the a priori memory circuit (R=0.34, P<0.001) were associated with memory dysfunction.

However, lesion damage to the memory circuit fully mediated the association of lesion volume with memory performance.

In addition, researchers’ data-driven analysis yielded multiple connections associated with memory dysfunction, including peaks within several regions of the brain involving memory processing. Further, the overall topography of the data-driven MS memory circuit matched our a priori stroke-derived memory circuit.

“This circuit-based localization approach could be employed to other MS symptoms commonly associated with lesion burden,” Kletenik and colleagues wrote.