Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

BACKGROUND: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. OBJECTIVE: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. METHODS: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. RESULTS: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized ß = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized ß = -0.14, p = 0.028) in a linear regression model. CONCLUSIONS: PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

Quantifying disease pathology and predicting disease progression in multiple sclerosis with only clinical routine T2-FLAIR MRI.

BACKGROUND: Although quantitative measures from research-quality MRI provide a means to study multiple sclerosis (MS) pathology in vivo, these metrics are often unavailable in legacy clinical datasets. OBJECTIVE: To determine how well an automatically-generated quantitative snapshot of brain pathology, measured only on clinical routine T2-FLAIR MRI, can substitute for more conventional measures on research MRI in terms of capturing multi-factorial disease pathology and providing similar clinical relevance. METHODS: MRI with both research-quality sequences and conventional clinical T2-FLAIR was acquired for 172 MS patients at baseline, and neurologic disability was assessed at baseline and five-years later. Five measures (thalamus volume, lateral ventricle volume, medulla oblongata volume, lesion volume, and network efficiency) for quantifying disparate aspects of neuropathology from low-resolution T2-FLAIR were applied to predict standard research-quality MRI measures. They were compared in regard to association with future neurologic disability and disease progression over five years. RESULTS: The combination of the five T2-FLAIR measures explained most of the variance in standard research-quality MRI. T2-FLAIR measures were associated with neurologic disability and cognitive function five-years later (R2 = 0.279, p < 0.001; R2 = 0.382, p < 0.001), similar to standard research-quality MRI (R2 = 0.279, p < 0.001; R2 = 0.366, p < 0.001). They also similarly predicted disability progression over five years (%-correctly-classified = 69.8, p = 0.034), compared to standard research-quality MRI (%-correctly-classified = 72.4%, p = 0.022) in relapsing-remitting MS. CONCLUSION: A set of five T2-FLAIR-only measures can substitute for standard research-quality MRI, especially in relapsing-remitting MS. When only clinical T2-FLAIR is available, it can be used to obtain substantially more quantitative information about brain pathology and disability than is currently standard practice.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis in Japan.

BACKGROUND: The Brief International Cognitive Assessment for MS (BICAMS) is a practical battery for measuring cognitive function in multiple sclerosis (MS). OBJECTIVES: We aimed to validate a Japanese version of the BICAMS in patients with MS and healthy controls. METHODS: The Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-Second Edition (CVLT2) and the Brief Visuospatial Memory Test Revised (BVMTR) were administered to 156 patients with MS and 126 healthy controls (HCs). The BICAMS was re-administered in a subset of 27 MS patients and 30 HCs. RESULTS: The mean (±SD) raw scores in the MS and HC groups were as follows: SDMT: MS 47.9 ± 14.0, HC 61.0 ± 9.5; CVLT2: MS 48.6 ± 12.6, HC 55.7 ± 10.5; BVMTR: MS 23.5 ± 8.4, HC 28.3 ± 5.4, respectively, and significant differences were found between the two groups on all tests (p < 0.0001). Cohen's d values were 1.07, 0.60, and 0.67 in SDMT, CVLT2, and BVMTR, respectively. The test-retest reliability coefficients for each test were as follows: SDMT: r = 0.93; CVLT2: r = 0.82; and BVMTR: r = 0.77 (p < 0.0001). CONCLUSIONS: This study provides results that support the reliability and validity of the BICAMS in Japan.