Low Cholesterol May Reflect More Aggressive Disease Progression

People with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome (CIS) have lower cholesterol levels in their blood and cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord, compared with those without MS, a study reports.

These lower cholesterol levels might correlate with a more severe disease course, the researchers said, noting more studies are needed.

The study, “Cholesterol levels in plasma and cerebrospinal fluid in patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis” was published in Neurobiology of Disease.

The loss of myelin — protective sheaths around nerve fibers — in multiple sclerosis (MS) and the failure of remyelination is associated with disease progression.

Myelin contains a high lipid/fat (70%) content, of which more than 25% corresponds to cholesterol. Thus, cholesterol plays a key role in its formation.

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Oligodendrocytes are cells in the central nervous system mainly responsible for myelin production. Mature oligodendrocytes are also the main cholesterol producers of the brain.

It’s been proposed that cholesterol levels regulate the mechanisms involved in remyelination and immune responses in the brain. Too high or too low cholesterol levels have a negative impact on remyelination.

“It has been shown that increased cholesterol accumulation after myelin damage in animal models of demyelination [myelin loss] disturbs the immune response and prevents the control of the inflammatory process and remyelination,” the researchers wrote. “In contrast, low cholesterol availability … decrease remyelination.”

In MS patients, cholesterol metabolism in the serum — that part of the blood remaining after blood cells and clotting proteins have been removed — and CSF has been suggested to be altered, and to be associated with disease progression and disability.

“However, it is unclear whether lack of remyelination results from an insufficient capacity of OPC [oligodendrocyte precursor cells] to differentiate [into mature oligodendrocytes] or from cholesterol insufficiency,” the researchers wrote.

Researchers in Greece investigated a possible association between cholesterol and MS progression by measuring its levels in the plasma and CSF of patients with RRMS or CIS.

The research team also analyzed the relation of cholesterol with oligoclonal bands, antibodies (also known as immunoglobulins) that indicate inflammation and a possible MS diagnosis.

In total, 62 people with CIS (ages 19-56) and 46 with RRMS (ages 20-50) were analyzed. The CIS group included patients with a first demyelinating episode and at least one asymptomatic lesion shown by MRI. All had a good clinical record with a low disability level with an expanded disability status scale (EDSS) score of 0 to 4.

Participants were medication-free at the time of the assessment and underwent CSF analysis to detect for oligoclonal bands. The team analyzed 48 participants without signs of neurological disease and in the same age range as the MS group to serve as controls.

Significantly lower plasma and CSF cholesterol levels were seen in patients compared to controls. In plasma, cholesterol levels were at a mean value of 215 milligrams per deciliter (mg/dl) in controls versus 192 mg/dl in patients, while CSF levels were 0.34 mg/dl in controls versus 0.28 ng/dl in patients.

A positive correlation was found between plasma cholesterol and age, with older patients having higher cholesterol levels; and between CSF cholesterol levels and disability (EDSS score), with higher disability associated with an increased concentration of cholesterol.

The team also found that patients with oligoclonal bands had significantly lower levels of both CSF and plasma cholesterol compared to controls. No significant difference was found in plasma cholesterol levels between patients with and without oligoclonal bands, whereas differences were seen in CSF concentrations between the two patient groups. Patients with oligoclonal bands had significantly lower levels of CSF cholesterol compared to patients without oligoclonal bands.

EDSS scores did not differ between patients with or without oligoclonal bands in the CSF.

Based on the results, the team suggested that “low CSF cholesterol in MS patients with [oligoclonal bands] might be related to [an antibody-related immune response against] components such as cholesterol,” they wrote, adding this “might reflect extensive demyelination and a more aggressive disease course.”

However, “only a moderate positive association of CSF cholesterol to EDSS was found, given the sample size,” the team wrote, noting larger studies are needed to “further elucidate the important role of cholesterol in the pathophysiology of MS and evaluate whether low levels of cholesterol in the CSF could be considered as a potential marker of more overt demyelination and aggressive disease.”