CSF biomarkers at time of diagnosis may aid in MS prognosis: Study

Certain biomarkers in the cerebrospinal fluid (CSF) — the fluid surrounding the brain and spinal cord — around the time of a multiple sclerosis (MS) diagnosis may help predict the time to reaching certain disability milestones among people with a relapsing-remitting (RRMS) disease course, according to findings from a recent study.

Such markers also were associated with short-term relapse rates, but were not able to predict disability progression in patients with primary progressive MS (PPMS), who had a different CSF profile than their RRMS counterparts, the researchers noted.

While it already was known that CSF markers might be useful for diagnosing the neurodegenerative disease, these new findings support the idea that such biomarkers also might help in predicting its course.

“This study illustrates that routine CSF analysis offers prognostic in addition to diagnostic information,” the researchers wrote, noting that using such CSF findings could “aid in patient counseling, clinical decision-making and treatment decisions.”

The study, “Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study,” was published in the Journal of Neurology, Neurosurgery & Psychiatry.

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Spinal tap commonly used as part of diagnostic workup in MS

When a person is undergoing a diagnostic workup for suspected MS, a sample of cerebrospinal fluid, known as CSF for short, is commonly obtained via a lumbar puncture, also known as a spinal tap.

Doctors specifically will examine the fluid to look for what’s known as oligoclonal bands, or OCBs, which are made up of antibodies called immunoglobulins that indicate the presence of inflammation in the central nervous system, comprised of the brain and spinal cord. These OCBs help support an MS diagnosis.

Yet, the utility of CSF analyses for predicting MS disease course and prognosis is not as well established. Some studies have suggested that OCBs might be associated with a more severe disease course, while others don’t support such a relationship, according to the scientists — a large team from institutions globally.

Moreover, there is contradicting evidence about whether other CSF biomarkers, such as CSF pleocytosis — an increased number of immune cells — might have utility for predicting MS prognosis.

The goal of the team’s study was thus to look at whether various CSF parameters at diagnosis could predict future disability progression and relapse rates among MS patients.

To that end, the scientists examined CSF data from 11,245 MS patients included in MSBase, a large, international MS registry. Most participants (93.7%) were diagnosed with RRMS and the rest with PPMS. At the time of the analysis, participants had been followed for a median of about 10-13 years.

Disability was monitored with the Expanded Disability Status Scale (EDSS), which ranges from a score of 0, indicative of no disability, to 10, for death due to MS.

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The results showed that the presence of OCBs at diagnosis in RRMS patients was associated with a higher risk of reaching confirmed disability milestones, namely EDSS scores of 4, 6, and 7, compared with patients without OCBs.

An EDSS score of 4 indicates significant disability, but without walking impairments, while a score of 6 indicates the need for a walking aid like a cane or crutch. Once an EDSS score of 7 is reached, a person can not walk for more than a few feet, even with an aid, and requires a wheelchair to move around.

In particular, the findings showed that OCB-positive patients were at a 27.2% higher risk of reaching confirmed EDSS 4 and a 31.4% greater risk of confirmed EDSS 6. The risk of reaching confirmed EDSS 7 was 68.6% higher.

Conversely, the presence of CSF pleocytosis was associated with 22.6% lower odds of reaching an EDSS score of 4 in RRMS patients, but also was linked to a higher relapse rate in the first two years after diagnosis among these same patients.

The scientists believe this finding might indicate that CSF pleocytosis is reflective of the acute inflammatory activity that’s linked to relapses, rather than long-term disability accrual.

CSF analysis provides prognostic information which could aid in clinical and therapeutic decision-making.

In contrast, no CSF variables were associated with disability milestones in PPMS patients, which suggests “that mechanisms apart from neuroinflammation might contribute to disability accrual in PPMS,” the researchers wrote.

Certain differences were observed in the CSF biomarkers between RRMS and PPMS patients, with the primary progressive group having a significantly higher proportion of OCB-positive patients at diagnosis (88.8% versus 84.4%).

While the proportion of OCB-positive RRMS patients steadily increased over time, such a trend was not really observed in PPMS patients, with positive rates remaining relatively steady.

Altogether, “CSF analysis provides prognostic information which could aid in clinical and therapeutic decision-making,” the researchers wrote.

Future research will need to determine how these CSF biomarkers will inform MS management strategies, and how they change in the long-term with treatment, according to the scientists.