Perivascular spaces impact disease severity, delivery of treatment in Huntington’s disease

Dilated perivascular spaces correlated with disease severity in Huntington’s disease and could affect the administration of certain treatments, according to findings published in Neurology.

“Increased and enlarged [perivascular spaces] have been shown to be correlated with age in several neurodegenerative disorders,” the researchers wrote. “In this study, we tested the hypothesis that brain [perivascular spaces] burden would increase early in [Huntington’s disease] compared to healthy age-matched controls.”

The researchers also examined how increased perivascular spaces impacted the administration and efficacy of intrathecal treatments or intraparenchymal gene and cell therapies for patients with Huntington’s disease, “which could drain futilely through [perivascular spaces] channels and out of targeted tissues.”

Suk Tak Chan, PhD, instructor in radiology at Harvard Medical School and assistant in biomedical engineering at Massachusetts General Hospital, and colleagues performed MRIs on patients with Huntington’s disease and healthy, age-matched controls. The researchers examined the imaging data to quantify regional volume of perivascular spaces and used logistic regression analysis to calculate the link between perivascular spaces volume and disease designation (in both patients with Huntington’s disease and controls) and disease severity as determined by normalized caudate volume.

The study included 25 patients with Huntington’s disease and 23 healthy, age-matched controls, with an average age of 50 years in the Huntington’s disease group and 48 in the control group. Chan and colleagues reported that the groups were similar regarding age and sex; more patients in the Huntington’s disease group were women (56% vs. 48%). Patients with Huntington’s disease were in stage 1 or 2, with an average CAG repeat length of 43 (range, 42-44), an average disease burden score of 359 (range, 319-423) and an average total functional capacity score of 10 (range, 9-11).

The researchers found that patients with Huntington’s disease had the highest percent volume of dilated perivascular spaces in the putamen (left putamen, OR = 2.06; 95% CI, 1.62-2.62; Huntington’s disease = 3.27%; 95% CI, 2.83-3.78 vs. controls = 1.62%; 95% CI, 1.32-1.97; P [false discovery rate] < 0.001; right putamen, OR = 1.66; 95% CI, 1.33-2.08; Huntington’s disease = 3.43%; 95% CI, 2.94-4.01 vs. controls = 2.09%; 95% CI, 1.79-2.45; P [false discovery rate] < 0.001) and several subcortical white matter regions compared with controls.

The findings from Chan and colleagues showed an inverse relationship between caudate volume and perivascular spaces in the putamen, thalamus, insula white matter, precuneus white matter, posterior cingulate white matter and lateral-orbito-frontal white matter. These results indicated that perivascular spaces burden increased with disease severity, according to the researchers.

Chan and colleagues also discussed the impact of their findings on treatment for patients with Huntington’s disease.

“Since a compromised blood-brain barrier or altered glymphatic system might affect the delivery and success of intrathecal treatments, such as antisense oligonucleotides or intraparenchymal gene and cell therapies for [patients with Huntington’s disease], which could drain futilely through [perivascular space] channels and out of targeted tissues, the quantifications of [perivascular space] burden might provide a means of assessing [perivascular space] development as [Huntington’s disease] progresses and potentially serve as a relevant factor in determining eligibility for treatment,” the researchers wrote.