Cerebrospinal fluid flow dynamics in Huntington's disease evaluated by phase contrast MRI

Abstract

Multiple targeted therapeutics for Huntington's disease are now in clinical trials, including intrathecally‐delivered compounds. Previous research suggests CSF dynamics may be altered in Huntington's disease, which could be of paramount relevance to intrathecal drug delivery to the brain.

To test this hypothesis we conducted a prospective cross‐sectional study comparing people with early stage Huntington's disease with age‐ and gender‐matched healthy controls. CSF peak velocity, mean velocity and mean flow at the level of the cerebral aqueduct, and sub‐arachnoid space in the upper and lower spine, were quantified using phase contrast MRI. We calculated Spearman's rank correlations, and tested inter‐group differences with Wilcoxon rank‐sum test.

Ten people with early Huntington's disease, and 10 controls were included. None of the quantified measures was associated with potential modifiers of CSF dynamics (demographics, osmolality, and brain volumes), or by know modifiers of Huntington's disease (age and CAG‐repeat); and no significant differences were found between the two studied groups.

While external validation is required, the attained results are sufficient to conclude tentatively that a clinically‐relevant alteration of CSF dynamics – i.e. one that would justify dose‐adjustments of intrathecal drugs – is unlikely to exist in Huntington's disease.

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