Spinal Cord Abnormalities Correlate With Disease Severity in FA
Results show utility of MRI as biomarker in tracking disease progression
People with Friedreich’s ataxia show marked abnormalities in the structure of the upper spinal cord, some of which are correlated with measures of disease duration and severity, a study reports.
“These results provide new insights about [the development of Friedreich’s ataxia] and indicate that spinal cord MRI may be a useful biomarker to track disease progression,” the researchers wrote.
The study, “Progressive Spinal Cord Degeneration in Friedreich’s Ataxia: Results from ENIGMA-Ataxia,” was published in Movement Disorders.
Friedreich’s ataxia causes neurological problems and abnormalities in the structure of the nervous system have been reported with the disease. An international team of scientists analyzed MRI data to assess how it affects the top four vertebrae of the cervical spinal cord (neck).
“Several aspects of spinal cord changes in people with [Friedreich’s ataxia] remain unclear,” the researchers wrote, Understanding these changes is important “not only to understand the underlying biology of the disorder but also to uncover potential imaging-based biomarkers.”
Analyzing cross-sectional area, eccentricity in MRI data
They analyzed cervical spinal cord MRI data from 256 people with a confirmed diagnosis of Friedreich’s ataxia, as well as 223 people without ataxia similar in age and sex who served as controls. The data were gathered from sites in the ENIGMA-Ataxia working group, an international effort that collects MRI data from people with ataxia.
From the MRI data, the researchers assessed two measures, called cross-sectional area (CSA) and eccentricity.
According to the scientists, eccentricity reflects damage to part of the cervical spinal cord called the dorsal column, responsible for transmitting information about fine touch and vibration from the body to the brain. CSA reflects damage to the dorsal column as well as a separate region called the corticospinal tract, which transmits information related to movement between the brain and the body.
Results showed, compared to controls, those with Friedreich’s ataxia had significantly reduced CSA and significantly higher eccentricity. These differences were found across all four evaluated vertebrae in the cervical spine.
Significant abnormalities were found among patients across disease duration and disease severity. Abnormalities in CSA appeared to become more pronounced over time and showed significant correlations with measures of disease severity. By contrast, although eccentricity was abnormal at every disease stage, it showed no clear relationship with disease duration or severity.
“Subgroup analyses based on disease duration and severity showed that CSA and eccentricity are already abnormal in the early stages of the disease and that CSA likely declines with disease progression, whereas eccentricity remains stable,” the researchers wrote.
In the patients, CSA appeared to show a progressive decline with age.
These findings indicate CSA may be a “potential MRI biomarker candidate for clinical tracking” in Friedreich’s ataxia, they said.
The results also suggest Friedreich’s ataxia has distinct effects on the health of nerve cells in the cervical spinal cord, the researchers said. Specifically, since eccentricity was abnormal, but remained generally stable over time, the results suggest dorsal column abnormalities likely arise early in Friedreich’s ataxia, but then remain largely stable over time. By comparison, the gradual deterioration in CSA suggests abnormalities are present early and get worse as a person ages.
“Our data support the hypothesis that damage to the spinal dorsal column and corticospinal tract follow distinct courses in the disease: developmental damage likely defines the former, while alterations in the latter may be both developmental and degenerative in origin,” the researchers wrote.
The scientists noted these results were specific to the cervical spinal cord and that extrapolating to other regions of the spine “must be approached with caution.” They also emphasized their study is limited by its cross-sectional design, underscoring that more longitudinal studies that track how spinal cord abnormalities progress in patients over time are needed.
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