Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology.

OBJECTIVE: Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. METHODS: We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. RESULTS: Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing-remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. CONCLUSIONS: Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS.

Visual Pathway Measures are Associated with Neuropsychological Function in Multiple Sclerosis.

PURPOSE: To determine the relationships between visual function and ganglion cell and inner plexiform layer thickness and neuropsychological measures in multiple sclerosis (MS). METHODS: Ninety-five relapsing-remitting MS (RRMS) and 36 progressive MS patients underwent 100%-contrast visual acuity (VA), 2.5%- and 1.25%-contrast letter acuity (LA) testing, Cirrus-HD-optical coherence tomography, and neuropsychological assessments. Mixed-effects regression models were used to assess relationships. RESULTS: Across the cohort, 1.25%-contrast LA was associated with Symbol Digit Modalities Test (SDMT; ß = 2.17, p = 0.005) and Brief Visuospatial Memory Test-Revised (BVMT-R) total recall (TR) and delayed recall (DR) scores (ß = 0.31, p < 0.001; ß = 0.15, p = 0.039, respectively). 2.5%-contrast LA was associated with BVMT-R TR scores (ß = 0.27, p = 0.006). In the RRMS cohort, 1.25%-contrast LA was generally more significantly associated with cognitive measures: SDMT (ß = 2.97, p = 0.001) and BVMT-R TR (ß = 0.32, p < 0.001) and DR (ß = 0.22, p = 0.012). CONCLUSION: This study suggests that visual pathway measures, particularly visual function measures, reflect aspects of cognitive function in MS, further supporting their roles as complementary outcomes in MS neuroprotection trials.

Longitudinally extensive optic neuritis as an MRI biomarker distinguishes neuromyelitis optica from multiple sclerosis.

OBJECTIVE: To differentiate MRI characteristics of optic neuritis associated with neuromyelitis optica (NMO) and relapsing remitting multiple sclerosis (RRMS). BACKGROUND: Optic neuritis is a common presenting feature of both neuromyelitis optica and multiple sclerosis. Distinguishing between NMO and RRMS is important in guiding treatment, but biomarkers of NMO and MS can be absent early in the disease process. We looked for differences in MRI characteristics of optic neuritis associated with NMO and MS that provide an early clue in the diagnostic workup. DESIGN/METHODS: We conducted a retrospective analysis of 26 NMO and 26 RRMS patients presenting to the Johns Hopkins Hospital with MRI-confirmed acute optic neuritis. MRIs were assessed to identify the location and longitudinal extent of each contrast enhancing lesion. For the purposes of this study, the optic nerve was divided into intraorbital, canalicular, pre-chiasmal, chiasmal, and optic tract. RESULTS: There are distinct differences in MRI characteristics between NMO- and RRMS-associated optic neuritis. The majority of NMO lesions were longitudinally extensive measuring at least 17.6mm in length and involving at least three optic nerve segments. At a cutoff of 17.6mm lesion length, the specificity for NMO is 76.9% with a sensitivity of 80.8% and positive likelihood ratio of 3.50. Conversely, MS lesions were more commonly focal in one optic nerve segment localized anteriorly. CONCLUSIONS: Optic neuritis in NMO has a distinct pattern on MRI as compared with RRMS and can help differentiate these two neuroinflammatory diseases at presentation.

Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis.

OBJECTIVE: To assess relationships between spinal cord MRI (SC-MRI) and retinal measures, and to evaluate whether these measures independently relate to clinical disability in multiple sclerosis (MS). METHODS: One hundred two patients with MS and 11 healthy controls underwent 3-tesla brain and cervical SC-MRI, which included standard T1- and T2-based sequences and diffusion-tensor and magnetization-transfer imaging, and optical coherence tomography with automated segmentation. Clinical assessments included visual acuity (VA), Expanded Disability Status Scale, MS functional composite, vibration sensation threshold, and hip-flexion strength. Regions of interest circumscribing SC cross-sections at C3-4 were used to obtain cross-sectional area (CSA), fractional anisotropy (FA), perpendicular diffusivity (λ⊥), and magnetization transfer ratio. Multivariable regression assessed group differences and SC, retinal, and clinical relationships. RESULTS: In MS, there were correlations between SC-CSA, SC-FA, SC-λ⊥, and peripapillary retinal nerve fiber layer (pRNFL) (p = 0.01, p = 0.002, p = 0.001, respectively) after adjusting for age, sex, prior optic neuritis, and brain atrophy. In multivariable clinical models, when SC-CSA, pRNFL, and brain atrophy were included simultaneously, SC-CSA and pRNFL retained independent relationships with low-contrast VA (p = 0.04, p = 0.002, respectively), high-contrast VA (p = 0.06, p = 0.008), and vibration sensation threshold (p = 0.01, p = 0.05). SC-CSA alone retained independent relationships with Expanded Disability Status Scale (p = 0.001), hip-flexion strength (p = 0.001), and MS functional composite (p = 0.004). CONCLUSIONS: In this cross-sectional study of patients with MS, correlations exist between SC-MRI and retinal layers, and both exhibit independent relationships with clinical dysfunction. These findings suggest that the SC and optic nerve reflect ongoing global pathologic processes that supplement measures of whole-brain atrophy, highlighting the importance of combining measures from unique compartments to facilitate a thorough examination of regional and global disease processes that contribute to clinical disability in MS.