Thalamic and cerebral white matter volumes allow for identification of cognitively impaired patients with early relapsing-remitting multiple sclerosis.

AIM OF THE STUDY: To identify magnetic resonance imaging (MRI) predictors of cognitive decline among early relapsing-remitting multiple sclerosis (RRMS) patients and, additionally, assess whether these parameters allowed for differentiation between subjects with RRMS and volunteers in the control group.

CLINICAL RATIONALE FOR THE STUDY: As detailed neuropsychological testing and advanced neuroimaging modalities are time- -consuming and mainly used for scientific purposes, we have searched for MRI predictors of cognitive decline easily available in everyday clinical practice.

MATERIAL AND

METHODS

Between 2021 and 2022, RRMS patients aged ≤ 50, with Expanded Disability Status Scale (EDSS) ≤ 6.5, treated with disease-modifying therapies (DMTs) in University Hospital in Krakow, Poland, and volunteers underwent clinical evaluation and brain MRI. Cognitive functions were screened with Symbol Digit Modalities Test (SDMT) with cut-offs based on age, sex and education. Additionally, participants were evaluated with the use of Timed 25-Foot Walk Test (T25-FWT), Nine- -Hole Peg Test (9-HPT), and Fatigue Scale for Motor and Cognitive Functions (FSMC). SynthSeg software was used to segment T1-weighted brain MRI into anatomical structures automatically and measure their volumes.

RESULTS

We included 86 controls and 130 patients (65.9% women, median EDSS 1.0 [IQR 1.0-2.0], median disease duration 8 [IQR 5-12] years, 86.9% treated with platform DMTs, mostly dimethyl fumarate [47.7%], 46.9% treatment-naïve). In the multivariable model, predictors for differentiating MS patients with preserved cognition from control group were: T25-FWT (OR = 2.18, 95% CI: 1.48-3.22 per second, p < 0.001), FSMC score (OR = 1.05, 95% CI: 1.02-1.09 per point, p = 0.005), third ventricle width (OR = 2.09, 95% CI: 1.42-3.06 per mm, p < 0.001), and thalamic volume ≥ 14.034 cm3 (OR = 0.30, 95% CI: 0.12-0.79, p = 0.014). RRMS patients deemed cognitively impaired on the SDMT did worse on the 9-HPT, had higher EDSS, and smaller thalamic, other deep gray matter structures, and cerebral white matter volumes compared to remainders. In the multivariable model, thalamic volume ≥ 14.008 cm3 and cerebral white matter volume ≥ 412.326 cm3 were independent predictors of cognitive decline in RRMS patients (OR = 0.11, 95% CI: 0.03-0.48, p = 0.003 and OR = 0.22, 95% CI: 0.07-0.74, p = 0.014, respectively). The thalamic volume of ≥ 14.008 cm3 exhibited the highest discriminatory ability to differentiate between MS subjects with and without cognitive impairment, with a 5.4-fold lesser prevalence in cognitively affected patients (8.7% vs. 46.7%). Utilizing this cut-off value, the sensitivity, specificity, positive predictive value and negative predictive value were determined to be 46.7%, 91.3%, 96.2% and 26.9%, respectively.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Thalamic and cerebral white matter volumes measured on T1-weighted brain MRI allow for identification of cognitively impaired RRMS patients in a real-world clinical setting.