Neurologia i neurochirurgia polska · 2025
Thalamic and cerebral white matter volumes allow for identification of cognitively impaired patients with early relapsing-remitting multiple sclerosis.
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Wnuk Marcin, Lasek Julia, Gliniak Matylda, Schneider Zofia, Marona Monika, Kaczówka Klaudia, Bryll Amira, Popiela Tadeusz, Krzyżak Artur, Słowik Agnieszka, Drabik Leszek
Аннотация
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.
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.