Cerebrospinal fluid flow dynamics in Huntington's disease evaluated by phase contrast MRI. (19th February 2019)

• Record Type: Journal Article
• Authors: Rodrigues, Filipe B.; Byrne, Lauren M.; De Vita, Enrico; Johnson, Eileanoir B.; Hobbs, Nicola Z.; Thornton, John S.; Scahill, Rachael I.; Wild, Edward J.
• Is Part Of: European journal of neuroscience. Volume 49:Number 12(2019)
• Page Start: 1632
• Page End: 1639
• Publication Date: 2019-02-19
• Subjects: cerebrospinal fluid -- humans -- Huntington disease -- magnetic resonance imaging; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.14356
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Multiple targeted therapeutics for Huntington's disease are now in clinical trials, including intrathecally delivered compounds. Previous research suggests that 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 known modifiers of Huntington's disease (age and HTT CAG repeat length); 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 – that is, one that would justify dose‐adjustments of intrathecal drugs – is unlikely to exist in Huntington's disease. Abstract : Intrathecal drugs for Huntington's disease are now in clinical trials, but some evidence suggests that disease‐associated changes may alter the delivery of the drug to the brain. Rodrigues et al. report that MRI‐evaluated cerebrospinal fluid dynamics are not altered in Huntington's disease, and although preliminary, these results offer reassurance for planning future trials.