Clinical and MRI features contributing to the clinico-radiological dissociation in a large cohort of people with multiple sclerosis

Abstract

Background: People with Multiple Sclerosis (PwMS) often show a mismatch between disability and T2-hyperintense white matter (WM) lesion volume (LV), that in general is referred to as the clinico-radiological paradox.

Objectives: This study aimed to understand how an extensive clinical, neuropsychological, and MRI analysis could better elucidate the clinico-radiological dissociation in a large cohort of PwMS.

Methods: Clinical scores, such as Expanded Disability Status Scale (EDSS), 9 Hole Peg Test (9HPT), 25-foot Walking Test (25-FWT), Paced Auditory Serial Addition Test at 3 s (PASAT3), Symbol digit Modalities Test (SDMT), demographics, and 3 T-MRI of 717 PwMS and 284 healthy subjects (HS) were downloaded from the INNI database. Considering medians of LV and EDSS scores, PwMS were divided into four groups: low LV and disability (LL/LD); high LV and low disability (HL/LD); low LV and high disability (LL/HD); high LV and disability (HL/HD). MRI measures included: volumes of gray matter (GM), WM, cerebellum, basal ganglia and thalamus, spinal cord (SC) area, and functional connectivity of resting-state networks.

Results: The clinico-radiological dissociation involved 36% of our sample. HL/LD showed worse SDMT scores and lower global and deep GM volumes than HS and LL/LD. LL/HD showed lower GM, thalamus, and cerebellum volumes, and SC area than HS, and lower SC area than LL/LD.

Conclusions: A more extensive clinical assessment, including cognitive tests, and MRI evaluation including deep GM and SC, could better describe the real status of the disease and help clinicians in early and tailored treatment in PwMS.

Keywords: Clinico-radiological dissociation; Magnetic resonance imaging (MRI); Multiple Sclerosis.

Fig. 1

Boxplot showing global and regional brain volumes normalized to total intracranial volume (fraction %) and spinal cord area (cm2) in the four groups of people with multiple sclerosis (PwMS) and healthy controls (HS). Significant differences are reported as ***(p < 0.001), ** (p < 0.01), and * (p < 0.05), after multiple comparison corrections

Fig. 2

Group differences in resting-state functional connectivity between people with multiple sclerosis (PwMS) and healthy controls (HS) in the sensorimotor network (SMN). Results (p < 0.05, FDR corrected) are overlaid onto the F map (green) in the MNI152 standard brain. The red-yellow color indicates areas of higher functional connectivity (FC), while the blue–light blue color indicates areas of lower FC in PwMS than healthy controls. The color bars represent t values

Fig. 3

Group differences in resting-state functional connectivity between people with multiple sclerosis (PwMS) and healthy controls (HS) in the default mode network (DMN). Results (p < 0.05, FDR corrected) are overlaid onto the F map (green) in the MNI152 standard brain. Blue–light blue indicates areas of lower functional connectivity (FC) in PwMS than healthy controls. The color bars represent t values

Fig. 4

Group differences in resting-state functional connectivity among four groups of people with multiple sclerosis (PwMS) in the sensorimotor network (SMN). LL/LD low lesion volume and low disability, HL/LD high lesion volume and low disability, LL/HD low lesion volume and high disability, HL/HD high lesion volume and high disability. Results (p < 0.05, FDR corrected) are overlaid onto the F map (green) in the MNI152 standard brain. The red–yellow color indicates areas of higher functional connectivity (FC) in A. LL/LD than HL/LD; B. LL/HD than HL/HD; C. LL/LD than LL/HD; D. HL/LD than HL/HD; E. HL/LD than LL/HD. The color bars represent t values

Fig. 5

Group differences in resting-state functional connectivity among four groups of people with multiple sclerosis (PwMS) in the default mode network (DMN). LL/LD low lesion volume and low disability, HL/LD high lesion volume and low disability, LL/HD low lesion volume and high disability, HL/HD high lesion volume and high disability. Results (p < 0.05, FDR corrected) are overlaid onto the F map (green) in the MNI152 standard brain. The red–yellow color indicates areas of higher functional connectivity (FC) in A. LL/LD than HL/LD; B. LL/HD than HL/HD; C. HL/LD than HL/HD; D. LL/HD than HL/LD. The color bars represent t values