AT ACTRIMS FORUM 2016
NEW ORLEANS (FRONTLINE MEDICAL NEWS) – Protein profiling of cerebrospinal fluid and MRI has revealed the involvement of exacerbated gray matter demyelination and brain atrophy in the progression of multiple sclerosis.
The pattern of the cerebrospinal fluid (CSF) biomarkers, which correspond to the extent of gray matter damage, have potential value in stratifying patients in terms of disease severity from the onset of multiple sclerosis (MS), Roberta Magliozzi, Ph.D., of the University of Verona (Italy) said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Gray matter atrophy and the accumulation of cortical lesions are central to the progressive clinical deterioration that occurs in MS. The damage involves a “compartmentalized immune response” featuring meningeal infiltration of certain immune cells, which is associated with increased cortical demyelination and meningeal inflammation. The gray matter damage and inflammation are harbingers of earlier onset and rapid progression of neurological damage in MS, and a more severe disease outcome.
“We sought to find a combination of CSF biomarkers [and] neuropathological and early neuroimaging correlates of disease progression in order to predict onset and rate of MS progression,” Dr. Magliozzi explained.
The investigators assessed gray matter damage with MRI and analyzed CSF proteins in 36 MS patients and 12 healthy controls and also acquired and analyzed meningeal and CSF samples after death from 20 individuals with secondary progressive MS (SPMS) and 10 healthy individuals to detect inflammatory mediators associated with meningeal infiltration that were released to the CSF.
MS patients with meningeal infiltration displayed more extensive gray matter demyelination and more rapid disease progression. They also demonstrated a “pronounced proinflammatory CSF profile” featuring overexpression of an array of molecules associated with chronic inflammation. Patients with less gray matter damage displayed a pattern of increased regulatory molecules. Consistent with the patient data, similar expression patterns were evident in the meninges and CSF samples of postmortem SPMS cases with a higher level of meningeal inflammation and gray matter demyelination.
“Meningeal infiltrates may represent the main source of intrathecal inflammatory activity mediating the gradient of cortical tissue injury since early disease stages and in progressive MS,” Dr. Magliozzi said.
The markedly different CSF profiles in patients with more and less extensive gray matter damage may be an exploitable characteristic to stratify patients early in the course of MS, with benefits in disease prognosis and monitoring, and treatment that is more rationally geared to the patient’s condition.
“The results indicate that we may be able to get an image-based functional profile of patients in relapse, which would be a phenomenal finding,” Dr. Jerry Wolinsky of the University of Texas Health Science Center at Houston, commented in a press conference following the presentation.
The study was funded by Progressive MS Alliance. Dr. Magliozzi had no disclosures.
