Sodium accumulation is associated with disability and a progressive course in multiple sclerosis

Area of Science:

• Neuroimaging
• Neurology
• Biochemistry

Background:

• Neuroaxonal loss in multiple sclerosis (MS) causes irreversible disability, but its underlying mechanisms remain unclear.
• Intracellular sodium accumulation and expanded extracellular space due to neuroaxonal loss are hypothesized contributors to MS pathophysiology.
• Sodium magnetic resonance imaging (sMRI) offers a non-invasive method to assess brain sodium concentrations, potentially revealing neuroaxonal dysfunction and loss in vivo.

Purpose of the Study:

• To investigate brain sodium concentrations using sMRI in patients with relapsing-remitting (RRMS), secondary-progressive (SPMS), and primary-progressive (PPMS) multiple sclerosis.
• To compare sodium concentrations across different MS subtypes and healthy controls.
• To explore the association between brain sodium concentrations and clinical disability in MS patients.

Main Methods:

• A cross-sectional study involving 27 healthy controls and cohorts of RRMS, SPMS, and PPMS patients (n=27, 23, and 20, respectively).
• Sodium magnetic resonance imaging (sMRI) was performed to measure total sodium concentration in various brain regions, including cortical grey matter, deep grey matter, normal-appearing white matter, and T1 lesions.
• Clinical disability was assessed using the Expanded Disability Status Scale (EDSS), timed 25-foot walk test, nine-hole peg test, and paced auditory serial addition test.

Main Results:

• All MS subgroups exhibited significantly higher cortical sodium concentrations compared to controls.
• SPMS and PPMS patients showed elevated sodium concentrations in deep grey matter and normal-appearing white matter compared to controls.
• Sodium concentrations were higher in SPMS compared to RRMS patients across cortical grey matter, normal-appearing white matter, and deep grey matter.
• Both T1 isointense and T1 hypointense lesions demonstrated higher sodium concentrations than normal-appearing white matter.
• T1 hypointense lesions in SPMS and PPMS patients had higher sodium concentrations than in RRMS patients.
• Deep grey matter sodium concentration was independently associated with EDSS scores and 25-foot walk speed.
• T1 lesion sodium concentration was independently associated with performance on the nine-hole peg test and paced auditory serial addition test.

Conclusions:

• Increased sodium concentration is present in lesions, normal-appearing white matter, and grey matter in multiple sclerosis patients.
• Higher sodium concentrations are observed in progressive MS subtypes (SPMS and PPMS) and correlate with greater clinical disability.
• Elevated total brain sodium concentration likely reflects underlying neuroaxonal pathophysiology, contributing to disease progression and disability in multiple sclerosis.