Study Finds Differences in Cerebrospinal Fluid Dynamics in ALS

There are differences in the way the fluid around the brain and spinal cord moves in people with amyotrophic lateral sclerosis (ALS), and understanding these could have implications for the development of future therapies, a study suggests.

The study, “Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients,” was published in Fluids and Barriers of the CNS.

The brain and spinal cord are surrounded by cerebrospinal fluid (CSF). Because this fluid sits so close to the nervous system, researchers have been trying to deliver therapies for neurological conditions, including ALS, via injection directly into the CSF. This is called an intrathecal injection (IT).

A full understanding of the fluid dynamics of CSF, particularly in terms of how these change in particular conditions, is necessary if IT is to be used to deliver therapeutics. A therapeutic compound injected into the CSF needs to travel to the nervous tissue where it acts, and this could vary among individuals based on the fluid dynamics of the CSF.

Researchers analyzed CSF fluid dynamics in eight people with ALS (seven males and one female, with an average age of 56) and in 10 people without ALS (six males, four females, average age 59) using magnetic resonance imagine (MRI)-based technologies.

The study adds to a growing body of literature that supports using MRI-based technologies to measure CSF dynamics.

Although the small sample size “limits statistical confidence about the differences observed in this study,” the researchers wrote, “it was possible to measure and quantify inter-individual and cohort variability in a non-invasive manner.”

The speed at which CSF moved through certain areas of the spinal cord was significantly faster, on average, in people with ALS. Similarly, CSF pulse wave velocity (the rate at which pressure moves) along the spine tended to be higher among people with ALS.

There were also notable differences in the amplitude (changes in flow rate over time) of CSF movements in various parts of the spine. This was higher in ALS patients in some regions of the spine, but similar or lower in other regions.

One person in the ALS group had “near zero [CSF] flow at all locations,”the researchers said. This individual was excluded from the statistical analyses as an outlier. Nonetheless, the presence of such an outlier suggests there could be substantial variability in these measurements in people with ALS, depending on various related factors.

“With the high degree of heterogeneity that exists among ALS cases, it may be beneficial to conduct larger, longitudinal studies to determine how changes in CSF flow correlate with disease progression,” the researchers wrote. Such studies could have important implications for IT therapies targeted at ALS. Some of these therapies, such as NurOwn, are in clinical trials.