Objective: To elucidate the dynamics of CSF flow through the neuraxis in Huntington’s disease (HD) using phase contrast magnetic resonance imaging (PCMRI).

Background: HD is a fatal neurodegenerative condition. Multiple targeted therapeutics are now in the early clinical stage, including intrathecally-delivered compounds. Preclinical and clinical research suggests cerebrospinal fluid dynamics may be altered in HD, which could be of paramount relevance to intrathecal drug delivery to the brain.

Methods: Ten manifest gene expansion carriers and 10 age- and gender-matched healthy controls were recruited. All participants underwent extensive clinical assessment and PCMRI at the level of the cerebral aqueduct, T1 and T8. CSF velocities and flow measurements were derived using a semi-automated method. The influence of age, gender, CAG repeat-length, serum osmolality, and brain volumes on these measurements were tested using Spearman correlations or Fisher’s exact tests. Group comparisons between healthy controls and manifest carriers were achieved via two-sample Wilcoxon rank-sum tests. All tests were two-sided with a significance level of 0.05, and corrected for multiple comparisons.

Results: All participants were well matched across study groups. Measures of CSF dynamics were consistent across raters. None of the studied covariates was found to have an effect on the CSF velocities and flow measurements after corrected for multiple comparisons. No statistically significant difference was found across groups in any of the measures studied. Sample size calculations have shown that for the most clinically significant effect size attained, 993 participants per group would be needed to show a significant difference between two groups with 90% power.

Conclusions: While external validation is required, the attained effect sizes in this exploratory study are sufficient to conclude tentatively that a clinically-relevant alteration of cerebrospinal fluid flow dynamics – i.e. one that would justify dose-adjustments of intrathecal drugs – is unlikely to exist in Huntington’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-flow-dynamics-in-huntingtons-disease-evaluated-by-phase-contrast-mri/