Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide first evidence of the feasibility of triple quantum filtered ²³Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 heathy controls. Global grey matter and white matter total sodium concentration (respectively P < 0.05 and P < 0.01), and intracellular sodium concentration (both P < 0.001) were higher while grey matter and white matter intracellular sodium volume fraction (indirect measure of extracellular sodium concentration) were lower (respectively P = 0.62 and P < 0.001) in patients compared with healthy controls. At a brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P < 0.05 family-wise error corrected for total sodium concentration, P < 0.05 uncorrected for multiple comparisons for intracellular sodium concentration and intracellular sodium volume fraction). Measures of total sodium concentration and intracellular sodium volume fraction, but not measures of intracellular sodium concentration were correlated with T₂-weighted and T₁-weighted lesion volumes (0.05 < P < 0.01) and with Expanded Disability Status Scale (P < 0.05). Thus, suggesting that while intracellular sodium volume fraction decrease could reflect expansion of extracellular space due to tissue loss, intracellular sodium concentration increase could reflect neuro-axonal metabolic dysfunction.

Objective To investigate global and lobular cerebellar volumetries in patients with progressive multiple sclerosis (MS), testing the contribution of cerebellar lobular atrophy to both motor and cognitive performances. Methods Eighty-two patients with progressive MS and 46 healthy controls (HC) were enrolled in this cross-sectional study. Clinical evaluation included motor and cognitive testing: Expanded Disability Status Scale, cerebellar Functional System score, Timed 25-Foot Walk Test, 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test–Revised (BVMT) and California Verbal Learning Test II (CVLT). Cerebellar volumes were automatically obtained using the Spatially Unbiased Infratentorial Toolbox. A hierarchical multiple linear regression analysis was performed to assess the relationship between MRI variables of supratentorial and cerebellar damage (grey matter fraction, T2 lesion volume, metrics of cerebellar atrophy and cerebellar lesion volume) and motor/cognitive scores. Results Patients with MS exhibited lower cerebellar volumes compared with HC. Regression analysis showed that cerebellar metrics accounted for extra variance in both motor and cognitive performances, with cerebellar lesion volume, cerebellar Lobules VI, Crus I and VIIIa atrophy being independent predictors of 9-HPT, SDMT, BVMT and CVLT performances. Conclusions Atrophy of specific cerebellar lobules explains different aspects of motor and cognitive disability in patients with progressive MS. Investigation of cerebellar involvement provides further insight into the pathophysiological basis of clinical disability in progressive MS.

Cerebellum and neurodegenerative diseases: Beyond conventional magnetic resonance imaging

Retinal atrophy in multiple sclerosis (MS) is secondary to optic nerve focal inflammation and to injury of the posterior visual pathway. To investigate the contribution of cortical lesions (CLs) to retinal pathology in primary-progressive multiple sclerosis (PPMS). We performed a cross-sectional evaluation of 25 patients and 20 controls, relating magnetic resonance imaging (MRI) metrics of visual pathway integrity with parameters derived from spectral-domain optical coherence tomography (peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell + inner plexiform layer (GCIPL) thickness, and macular volume (MV)). Mean RNFL, GCIPL thickness, and MV were significantly reduced in patients compared to controls. MV and GCIPL thickness were significantly correlated with visual acuity. RNFL thinning was associated with thalamus and visual cortex volume (respectively, p = 0.01 and p < 0.05). In addition to thalamic volume, GCIPL thinning was associated with CLs and intracortical lesion number and volume, leucocortical lesion volume (all p ⩽ 0.05) while MV decrease was associated with CLs volume (p = 0.05) and intracortical lesion number and volume (p < 0.05). Our results suggest that RNFL thinning and GCIPL thinning/MV decrease may be explained by alternative mechanisms including retrograde trans-synaptic degeneration and/or a common pathophysiologic process affecting both the brain with CLs and the retina with neuronal loss.