RRMS patients with high chloride levels may be at more relapse risk

Relapsing-remitting multiple sclerosis (RRMS) patients with elevated levels of chloride in their cerebrospinal fluid (CSF), the fluid that bathes the central nervous system, may be at a higher risk of relapse, according to a study from China.

Researchers propose that CSF chloride levels equal to or higher than 123.2 mmol/L may indicate the need for stronger immunosuppressive treatments.

The study, “Cerebrospinal Fluid Chloride Is Associated with Disease Activity of Relapsing–Remitting Multiple Sclerosis: A Retrospective Cohort Study,” was published in the journal Brain Sciences.

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MS patients have different composition of their cerebrospinal fluid

In people with MS, the composition of the CSF, the fluid that surrounds the brain and spinal cord, is markedly distinct from that of healthy individuals. This is the result of an impaired blood-brain barrier, a selective filter that protects the brain from harmful substances in the bloodstream.

Previous studies suggested that changes in the CSF, such as levels of the neurofilament light chain protein, fats, or immune cells, may correlate with disease progression, supporting its analysis as a way to diagnose and monitor the disease.

Chloride helps maintain the proper balance of fluids and other minerals in the central nervous system (brain and spinal cord). Abnormal chloride levels have been reported as an indicator of underlying neurological conditions. Whether levels of CSF chloride may also correlate with disease activity in MS patients remains not well-understood.

In the study, researchers in China investigated how CSF composition, especially its chloride levels, at the time of the first spinal tap may correlate with the risk of relapse and disability progression in people with RRMS.

Study included clinical data from 77 RRMS patients in China

They conducted a retrospective analysis of clinical data from 77 RRMS patients (50 women and 27 men; mean age of 28.8 years) who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2012 to December 2020.

All patients had undergone a spinal tap for CSF collection during the initial diagnostic process. Follow-up lasted a mean of 57.2 months (around 4.8 years). The majority (63.6%) were not taking any disease-modifying therapy (DMT).

At the first CSF collection, median chloride levels were 123.2 mmol/L and no significant differences were seen between men and women. During follow-up, a total of 112 relapses were registered. More than half of patients (58.4%) had at least one relapse.

A first statistical analysis showed that the risk of relapse decreased with older age at onset and that patients not taking a DMT had a 2.35 times greater risk of relapse. Also, elevated CSF levels of chloride and glucose (a sugar), as well as of proteins in the blood correlated with a higher risk of relapse.

The researchers then conducted a multivariate statistical analysis where they took into account variables that included age at disease onset, sex, and maintenance treatment.

Results confirmed that high CSF chloride, CSF glucose, and blood proteins correlated with a higher risk of relapse, as did high levels of white blood cells (part of the immune system).

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Higher levels of chloride, glucose, white blood cells in CSF linked to relapse risk

The researchers then established that a median cut-off value of CSF chloride equal or above 123.2 mmol/L correlated with a 120% increased risk of relapse compared to lower levels. CSF glucose levels equal or above 3.3 mmol/L had a 141% increased risk of relapse relative to lower levels. Also, an 84% increased risk of relapse was seen in patients with CSF white blood cell counts of two cells or more per microliter.

Disease progression, assessed using the Multiple Sclerosis Severity Score, correlated with CSF white blood cell counts at the first spinal tap, a correlation also seen among participants not on DMTs.

Overall, “this study found that CSF chloride, glucose, and white blood cell count at the first onset were associated with a higher risk of relapse, which may predict a more active disease course and eventually indicate the need for a more active therapeutic approach,” the researchers concluded.

Among the study’s limitations was the relatively small group of patients, who were all Asian. “Further prospective studies with larger sample sizes are required to validate our findings,” the scientists noted.