Background The dynamics of cerebrospinal fluid (CSF) flow have never been studied in Huntington’s disease (HD), and could have a clinically significant impact on the expected distribution of central nervous system delivered drugs such as huntingtin-lowering therapies. Phase contrast MRI (PCMRI) generates a signal contrast between flowing and stationary nuclei, enabling the characterisation of fluid dynamics in vivo.
Objectives The objective of this study was to generate pilot data on CSF flow dynamics in HD using PCMRI, to inform the design of future intrathecal drug trials in HD.
Methods We performed a prospective cross-sectional analysis of 10 age- and gender-matched healthy controls and 10 manifest HD gene expansion carriers. All participants underwent extensive clinical evaluation and cardiac-gated 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, whole-brain volume, and ventricle volume 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 Twenty participants were recruited, and no significant age- and gender-imbalances were found. None of the studied covariables was found to have an effect on the CSF velocities and flow measurements after corrected for multiple comparisons. No apparent differences were found between study groups in regards to CSF velocities and flow measurements.
Conclusions Although exploratory, our pilot results add to the view that CSF dynamics are not altered in HD. These results need external validation but offer reassurance that clinically-relevant disease-related alterations in CSF flow, that might justify dose-adjustments of intrathecal drugs, are very unlikely to exist.
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