Certain spinal cord lesions may be markers of early MS damage
Some lesions show nerve fiber damage despite normal myelin
Certain lesions in the spinal cords of people with multiple sclerosis (MS) show damage to nerve fibers despite having normal myelin, according to a study done on postmortem samples using powerful MRI scans paired with detailed tissue analyses.
The identification of these lesions “provides a novel opportunity to detect [nerve fiber damage] before significant [nerve fiber] loss, or atrophy, occurs,” Kedar Mahajan, MD, PhD, co-author of the study and a neurologist at Cleveland Clinic, said in a clinic news story.
The identification of these lesions “may open a window for earlier therapeutic intervention targeting … inflammation and neuroprotection,” Mahajan said.
The study, “Neurodegeneration and Demyelination in the Multiple Sclerosis Spinal Cord Clinical, Pathological, and 7T MRI Perspectives,” was published in Neurology.
MS is caused by inflammation in the brain and spinal cord that damages the myelin sheath, a fatty covering around nerve fibers that helps nerves to send electrical signals. MRI scans are an imaging tool commonly used to track MS-related nerve damage.
Spinal cord lesions and MS disability
On MRI scans, spots where nerves or myelin have been damaged are visible as abnormally darker or lighter regions called lesions. MRIs also can be used to track brain and spinal cord atrophy (shrinkage), which indicates the extent of neurodegeneration over time.
The spinal cord is key for nerve signals that control movement and sensation. Lesions and atrophy in the spinal cord play a major role in driving disabling symptoms in MS. The researchers said they wanted to characterize MS-related spinal cord damage in more detail than can be done with conventional clinical tests “to identify neurodegenerative changes.”
They used spinal cord samples from 40 people with MS collected after death. Spinal cord tissue from nine people without MS was used for comparison.
The researchers conducted detailed analyses of spinal cord tissue, including looking at the tissue under a microscope and imaging it with powerful MRI scans.
MRIs use powerful magnets to detect signals from water molecules in the body’s tissues. Most clinical MRI scans use a magnet with a power of 1.5 to 3 Tesla (T, a unit of magnetic force). For this study, the researchers used a more powerful MRI with a 7 T magnet, allowing better resolution.
By comparing results from these analyses done after death to clinical MRI scans of live patients, the researchers noted that there were lesions that hadn’t been detected on clinical scans but were clearly detectable by 7 T MRI and tissue analysis.
“Clear gaps in detection of lesions from [clinical scans done during life and detailed analyses after death] are apparent,” the researchers wrote.
In most cases, lesions detected by 7 T MRI showed signs of myelin loss. Lesions with myelin damage were statistically associated with clinical measures of disability, as well as with the extent of spinal cord atrophy.
However, some lesions detected by 7 T MRI were myelinated or had reduced myelin content. These lesions had some detectable damage to axons (nerve fibers), but were not associated with clinical disability measures. The researchers said these lesions may reflect areas where nerve damage had just started to occur.
These lesions “may be a window into neurodegenerative changes that may precede irreversible axonal loss in some individuals with MS and a progressive disease course,” Mahajan said.
If these lesions are signs of early nerve damage, they may be useful markers of MS disease activity that can be detected before substantial damage has accrued, the scientists said, though they noted that further research will be needed to see if such lesions can be detected in the brain as well as the spinal cord.
“While spinal cord atrophy has long been considered a predictor of progression in MS, this is inherently retrospective — by the time atrophy is detectable, axonal loss has already occurred,” Mahajan said. “The true challenge lies in identifying biomarkers of neurodegeneration before irreversible structural loss occurs.”
The study “challenges the prevailing notion that spinal cord [lesions] merely reflect demyelination, and suggests the potential to capture earlier neurodegenerative processes within the MS spinal cord before irreversible axonal loss occurs,” he said.
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