Gray Matter in Hippocampus Can Help Distinguish Between Two MS Types
Subtle changes in structure in the hippocampus — a region of the brain involved in processing memories — can differentiate between relapsing-remitting and primary progressive multiple sclerosis, according to a new study.
The study, “Unraveling the MRI-Based Microstructural Signatures Behind Primary Progressive and Relapsing–Remitting Multiple Sclerosis Phenotypes,” was published in the Journal of Magnetic Resonance Imaging.
Most people with multiple sclerosis (MS) are first diagnosed with a specific type called relapsing-remitting MS (RRMS), which is characterized by instances when symptoms worsen (relapses) followed by periods of less severe symptoms (remission). Individuals with primary progressive MS (PPMS) experience a gradual worsening, or progression, of symptoms.
The differences in patterns of disease progression among RRMS and PPMS are thought to be reflective of different biological mechanisms underlying each type. For example, whereas RRMS tends to be characterized by greater inflammation, progressive disease is usually characterized mainly by neurodegeneration (the damage and death of nerve cells). Understanding the exact mechanistic differences between MS types is an area of active investigation.
In the new study, a team led by researchers at the University of Verona in Italy used magnetic resonance imaging (MRI) to compare structural features of the brain between people with RRMS and those with PPMS.
Specifically, the researchers looked for changes in the brain’s gray matter. Brain tissue can be broadly divided into two types: gray matter and white matter. Gray matter contains the cell bodies of neurons (nerve cells), whereas white matter represents connections between different regions of gray matter.
White matter gets its name from the white myelin sheath that surrounds axons, the projections neurons use for communication. Because MS is caused by the immune system attacking the myelin sheath, research on brain structure changes in MS has generally focused on white matter. However, new research has revealed that gray matter has a role in the disease as well.
In the study, the team used MRI to analyze the gray matter of 45 people with PPMS and 45 with RRMS. The PPMS group was significantly older on average, with a significantly longer disease duration and more substantial disability. Both groups were mostly female.
A single MRI scanner was used on each participant for a series of imaging techniques, each examining different structures or morphologies in the brain.
The researchers then used a battery of statistical analyses and machine learning algorithms to find significant differences between the two MS subtypes. Their analyses identified 12 regions with substantial variations.
Ten of these 12 regions were in a part of the brain called the hippocampus, a complex structure that plays a central role in learning and memory. Together, these 12 features were able to discriminate between RRMS and PPMS patients with an accuracy of 83%.
The researchers acknowledged several limitations to this analyses, most notably the small sample size and the lack of a control group (i.e., people without MS against which to make comparisons).
However, the team concluded that the gray matter region “most sensitive to group differences was the hippocampus, suggesting a central role of this region in disease progression and calling for further investigation.”