Abstract
As atrophy represents the most relevant driver of progression in multiple sclerosis (MS), we investigated the impact of different patterns of brain and spinal cord atrophy on disability worsening in MS. We acquired clinical and MRI data from 90 patients with relapsing–remitting MS and 24 healthy controls (HC). Clinical progression at follow-up (mean 3.7 years) was defined according to the Expanded Disability Status Scale-Plus. Brain and spinal cord volumes were computed on MRI brain scans. After normalizing each participants’ brain and spine volume to the mean of the HC, z-score cut-offs were applied to separate pathologically atrophic from normal brain and spine volumes (accepting a 2.5% error probability). Accordingly, MS patients were classified into four groups (Group I: no brain or spinal cord atrophy N = 40, Group II: brain atrophy/no spinal cord atrophy N = 11, Group III: no brain atrophy/ spinal cord atrophy N = 32, Group IV: both brain and spinal cord atrophy N = 7). All patients’ groups showed significantly lower brain volume than HC (p < 0.0001). Group III and IV showed lower spine volume than HC (p < 0.0001 for both). Higher brain lesion load was identified in Group II (p = 0.049) and Group IV (p = 0.023) vs Group I, and in Group IV (p = 0.048) vs Group III. Spinal cord atrophy (OR = 3.75, p = 0.018) and brain + spinal cord atrophy (OR = 5.71, p = 0.046) were significant predictors of disability progression. The presence of concomitant brain and spinal cord atrophy is the strongest correlate of progression over time. Isolated spinal cord atrophy exerts a similar effect, confirming the leading role of spinal cord atrophy in the determination of motor disability.
Highlights
Multiple Sclerosis (MS) is one of the most common causes of disability in young adults and leads to progressive accumulation of motor and cognitive deficits, with a severe impact on quality of life [1]
In the patients group 40 subjects were classified in Group I, 11 were categorized in Group II, 32 were identified as belonging to Group III and 7 were included in Group IV according to their individual brain and spinal cord volume z-score (Fig. 1)
Patients classified as Group II and Group IV presented higher brain lesion load than patients classified in Group I, and patients classified as Group IV(brain and spinal cord atrophy) presented higher brain lesion load than patients belonging to Group III (9.31 ± 6.24 ml vs 3.93 ± 2.68, p = 0.048)
Summary
Multiple Sclerosis (MS) is one of the most common causes of disability in young adults and leads to progressive accumulation of motor and cognitive deficits, with a severe impact on quality of life [1]. A full characterization of the imaging correlates of motor impairment in MS is still lacking, several works have highlighted how the rate of cerebral atrophy is able to. Infratentorial and spinal cord damage, as well as damage to the corticospinal tract, explain to a varying degree both walking and hand dexterity impairment in MS [7]. This evidence is in line with several works across literature, showing an association between decreased spinal cord volume and disability in MS [8, 9]. Spinal cord atrophy occurs frequently in MS patients and it is present from the early stages of the disease [10], it is more pronounced in progressive patients compared to individuals with either radiologically isolated syndrome or relapsing–remitting (RR) MS [11]
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