MRI of the corpus callosum in multiple sclerosis: association with disability.

Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = -0.29, -0.30, and -0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.

Corticospinal tract abnormalities are associated with weakness in multiple sclerosis.

BACKGROUND AND PURPOSE: The association of MR imaging abnormalities with clinical disability in multiple sclerosis (MS) has been disappointing. This association might be improved by imaging specific functional systems in the central nervous system-for example, the motor system in a patient with weakness. Our aim was to assess the relationship between muscle strength in MS and corticospinal tract (CST) abnormalities detected with multimodality MR imaging of the brain. MATERIALS AND METHODS: In 47 individuals with MS, diffusion tensor imaging (DTI) at 3T was used to reconstruct the intracranial CSTs. Tract profiles depicted the variation in T2 relaxation time, magnetization transfer ratio (MTR), and DTI-derived indices (fractional anisotropy and diffusivity) as a function of normalized position along the tract. Brain parenchymal fraction was calculated as a normalized measure of brain volume. Stepwise linear regression modeling was used to determine the MR imaging indices most closely related to ankle dorsiflexion and hip flexion strength assessed with quantitative dynamometry. RESULTS: Individuals with MS were significantly weak: Average ankle strength fell 1.7 SDs below the age-, handedness-, and sex-corrected healthy mean. Brain parenchymal fraction was not associated with weakness. A parsimonious model that includes MTR in the brain stem and MS clinical subtype explained 30%-45% of the variance in ankle and hip strength. The model was successfully applied to scans and strength data from the same individuals at an earlier time point. CONCLUSION: MR imaging abnormalities specific to the motor tract are associated with clinical dysfunction related to that tract. The relevant abnormalities are found in the brain stem, distant from the periventricular inflammatory lesions that are common in MS. This suggests that neurodegeneration, rather than primary inflammation, at least partially explains the findings.

Optical coherence tomography and disease subtype in multiple sclerosis.

OBJECTIVE: To examine retinal nerve fiber layer (RNFL) thickness, macular volumes (MV), and visual acuity in multiple sclerosis (MS) eyes, with and without history of acute optic neuritis (ON). METHODS: RNFL thickness was measured in 326 MS and 94 control eyes using optical coherence tomography (OCT). MV and vision testing were done in a subset of the cohort. MS subtype was classified as relapsing-remitting (RRMS, n = 135), primary progressive (PPMS, n = 12), and secondary progressive (SPMS, n = 16). RESULTS: MS ON eyes had decreased RNFL thickness (84.2 microm) compared to controls (102.7 microm) (p < 0.0001). Unaffected fellow eyes of MS ON eyes (93.9 microm) (p < 0.01) and patients with MS with no history of ON (95.9 microm) (p < 0.05) also had decreased RNFL. RRMS (94.4 microm) (p < 0.001), PPMS (88.9 microm) (p < 0.01), and SPMS (81.8 microm) (p < 0.0001) (adjusted for age and duration of disease) had decreased RNFL compared to controls. There were significant differences in RNFL thickness within quadrants of peripapillary retina comparing relapsing to progressive MS subtypes. MV was decreased in MS ON eyes (6.2 mm(3)) (p < 0.0001) and SPMS subjects (6.2 mm(3)) (p < 0.05) compared to controls (6.8 mm(3)). CONCLUSION: Retinal nerve fiber layer (RNFL) is significantly decreased in multiple sclerosis (MS) optic neuritis (ON) eyes, unaffected fellow eyes of patients with MS ON, and MS eyes not affected by ON in our cohort. Macular volumes (MV) showed a significant decrease in MS ON eyes. Progressive MS cases showed more marked decreases in RNFL and MV than relapsing-remitting MS. OCT is a promising tool to detect subclinical changes in RNFL and MV in patients with MS and should be examined in longitudinal studies as a potential biomarker of retinal pathology in MS.

Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis.

OBJECTIVE: Optical coherence tomography (OCT) noninvasively quantifies retinal nerve fiber layer (RNFL) thickness. Studies show RNFL thinning in multiple sclerosis (MS), and we assessed its association with brain atrophy. METHODS: RNFL thickness was measured in 40 patients with MS and 15 controls. Brain parenchymal fraction (BPF) and partial brain volumes were estimated from cranial MRI scans using SIENA-X. Multiple linear regression modeling assessed the association between OCT and MRI measures of atrophy. RESULTS: Minimum RNFL thickness and subject age together predict 21% (p = 0.005) of the variance in BPF in all patients with MS and 43% (p = 0.003) of the variance in BPF in the subgroup with relapsing remitting MS (RRMS; n = 20). The partial correlation coefficient between BPF and minimum RNFL thickness, controlling for age, is 0.46 (p = 0.003) in all patients with MS and 0.69 (p = 0.001) in patients with RRMS. These associations are driven by CSF volume but not by gray or white matter volume. There is no significant association of these variables among controls. CONCLUSIONS: In multiple sclerosis (MS), retinal nerve fiber layer thickness is associated with brain parenchymal fraction and CSF volume. These data suggest that quantification of axonal thickness in the retina by optical coherence tomography (OCT) provides concurrent information about MRI brain abnormality in MS. OCT should be examined in longitudinal studies to determine if it could be used as an outcome measure in clinical trials of neuroprotective drugs.