Brain Fluid Flow Associated With MS Pathogenesis, Progression

Researchers determined that patients with multiple sclerosis (MS) present with significant Aqueduct of Sylvius (AoS) enlargement over time, which may be attributable to regional atrophy changes and ex vacuo expansion of the aqueduct, according to a study recently published in Fluids and Barriers of the CNS.

White matter lesions in the brain, along with neurodegenerative and vascular abnormalities, are all characteristics of MS. “Hemodynamic changes such as inflammation-driver hyperperfusion or atrophy-driven hypoperfusion will significantly influence the overall brain volume,” the researchers wrote. They continued, “It is currently unknown whether the changes in cerebral fluid dynamics are driven by forces within the CSF space or due to atrophy-driven passive expansion.”

To investigate the dynamics of cerebrospinal fluid (CSF) flow, researchers performed 3T magnetic resonance imaging with cine phase contrast with velocity-encoded pulse-gated sequence on 40 patients with MS and 20 healthy controls (HCs). Images taken at baseline and after a 5-year follow-up were compared between the cohorts.

In addition, to determine atrophy, patients with MS underwent additional high-resolution 3D T1-weighted imaging throughout the study period. “Measures of AoS cross-sectional area (CSA), average systolic and diastolic velocity peaks, maximal systolic and diastolic velocity peaks, and average CSF flow rates were determined,” along with brain atrophy and ventricular CSF (vCSF) expansion rates.

The study found that over 5 years patients with MS showed a significant increase in:

• Maximal diastolic peak, from 7.23 cm/s to 7.86 cm/s (nonadjusted P = .037)
• Diastolic peak flow rate, from 7.76 mL/min to 9.33 mL/min (non-adjusted P = .023)
• AoS CSA, from 3.12 mm² to 3.69 mm² (adjusted P = .001)

“The only diferentiator between MS patients and HCs was the greater AoS CSA (3.58 mm² vs 2.57 mm², age- and sex-adjusted analysis of covariance [ANCOVA] P = .045). The AoS CSA change was associated with vCSF expansion rate (age- and sex-adjusted Spearman’s correlation P = .019) and not with baseline nor change in maximal velocity,” the authors wrote.

Of the 40 patients with MS included in the study, 26 had relapsing-remitting MS and 14 had progressive MS. In this population, patients demonstrated an average increases of 13.8% in total T2 lesion volume, 2.6% in whole brain atrophy rate, and 13.7% in vCSF space expansion rate.

“If brain fluid dynamics contribute towards the multifaceted pathophysiological MS mechanisms, either pharmacological or rehabilitative treatments may alleviate some of the aforementioned abnormalities,” researchers concluded.

Future studies should consider analysis between longitudinal changes in CSF measures and clinical disability accrual/phenotype progression, researchers noted.

Reference

Jakimovski D, Zivadinov R, Weinstock-Guttman B, et al. Longitudinal analysis of cerebral aqueduct flow measures: multiple sclerosis flow changes driven by brain atrophy. Fluids Barriers CNS. 2020;12(1):9. doi: 10.1186/s12987-020-0172-3.