#ACTRIMS2019 – Cerebrospinal Fluid, Meninges Inflammation Profile Can Stratify MS Patients

by Jonathan Grinstein | March 4, 2019

A method based on cerebrospinal fluid measurements and magnetic resonance imaging (MRI) can aid in stratifying patients with multiple sclerosis (MS) at the time of diagnosis, which may help identify a tailored therapeutic approach for each patient from early disease stages.

The data was presented by Roberta Magliozzi, from the University of Verona, Italy, on March 2 at the 4^th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, in Dallas, Texas. The presentation was titled “Immunobiological and radiological markers of MS endophenotypes.”

Degeneration of cerebral grey matter — the major component of the nervous system, consisting of neuron cell bodies — is well-tied to MS disease progression. Indeed, the speed at which MS develops physically and cognitively in both relapsing and progressive stages of the disease is tied to the degree of cerebral grey matter degeneration.

However, although it is known that cell loss and inflammation are involved, how exactly these grey matter lesions occur, and how to best image them through magnetic resonance imaging (MRI) is poorly characterized.

Recent studies suggested that extensive grey matter damage and more rapid disease progression were tied to high levels of inflammation in the meninges — the layers that line the skull and vertebrae to enclose the brain and spinal cord with cerebrospinal fluid.Therefore, researchers in Italy hypothesized that intrathecal inflammation — in the meninges and cerebrospinal fluid — “might have a major role in mediating cortical damage and rapid progressive evolution of the disease,” they said.The team combined MRI imaging data, neuropathology analysis, and cerebrospinal fluid measurements to investigate a possible link between intrathecal inflammation and nerve cell damage in grey matter and the rapid progression of MS.Both MS patients at the time of disease diagnosis and samples from post-mortem patients were analyzed.Analysis of meningeal infiltrates and cerebrospinal fluid samples in autopsies of MS patients showed that meningeal infiltrates are the main source of inflammatory factors diffusing through the cerebrospinal fluid. These factors “possibly mediate a gradient of cortical tissue injury from the earliest stages of disease,” Magliozzi said.Along with meningeal inflammation, the researchers found that a specific cerebrospinal fluid inflammatory pattern — “including high protein levels of CXCL13, IFNγ, TNF, CXCL12, IL6, IL10, and LIGHT,” according to the team — was able to predict the degree of cell loss in grey matter in a subgroup of MS patients, either in vivo MS patients or in post-mortem MS samples.

According to Magliozzi, “progressive MS cases with higher degree of meningeal inflammation present increased level of grey matter” demyelination (loss of myelin, the protective coat surrounding neurons and a hallmark of MS).

Concerning the cerebrospinal fluid inflammatory pattern found, the team further showed that CXCL13 (a biomarker of inflammation) was the most predictive marker of the number of relapses in patients, and the appearance of MRI lesions.

Overall, the results suggested that greater inflammation in cerebrospinal fluid and meninges is linked with a greater degree of disease progression and cortical damage, both at time of diagnosis and at death.

“A specific combined cerebrospinal fluid and MRI pattern might represent a useful surrogate marker of meningeal inflammation able to stratify MS patients according to the level of intrathecal inflammation and cortical lesion load at diagnosis,” the team concluded.

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