No abstract

Objectives To identify MRI biomarkers associated with long-term disability progression in patients with multiple sclerosis (MS), and to define the rate of evolution of global, tissue-specific and regional atrophy in patients with MS over long-term. Methods MRI of the brain and clinical neurological assessment was performed in 81 patients at time of first visit and after 5 and 10 years of follow-up. MRI was acquired on 1.5 T scanners. T1-lesion and T2-lesion volumes (LVs) were calculated. Global and tissue-specific atrophy changes were longitudinally assessed, using a direct measurement approach, by calculating percentage volume changes between different time points. Regional tissue volumes for the subcortical deep grey matter (SDGM) structures were also obtained. Disability progression was defined as an increase in Expanded Disability Status Scale of ≥1.0 compared to baseline at 5-year and 10-year follow-up. Results Over 5 years, patients with disability progression showed significantly increased loss of whole brain (−3.8% vs −2.0%, p<0.001), cortical (−3.4% vs −1.8%, p=0.009) and putamen volume changes (−10.6% vs −3.8%, p=0.003) compared to patients with no disability progression. No significant change in white matter (WM) volume was observed when comparing progressing and non-progressing patients. Over 10 years, there was a trend for greater decrease in whole brain volume (−5.5% vs −3.7%, p=0.015) in the progressing patients. No significant changes in LV measures were detected between the patients with and without disability progression. Conclusion This long-term study shows that whole brain, cortical and putamen atrophy occurs throughout the 10-year follow-up of this MS cohort and is more pronounced in the group that showed disability progression at 5, but not at 10 years of follow-up. Overall, GM atrophy showed better association with disease progression than WM atrophy over 5-year and 10-year follow-up.

Measurement of thalamic atrophy and increase in ventricular size in CIS is associated with CDMS development and should be used in addition to the assessment of new T2 and CE lesions.

In this retrospective, pilot, observational longitudinal study, the presence of LM CE was associated with progression of cortical atrophy over 5 years.

Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy.

WB and cortical atrophy, and enlargement of vCSF spaces are associated with development of CDP on serial yearly MRI assessments over a period of 10 years.

In multiple sclerosis, pathological changes of both tissue iron and myelin occur, yet these factors have not been characterized in a longitudinal fashion using the novel iron- and myelin-sensitive quantitative susceptibility mapping (QSM) MRI technique. We investigated disease-relevant tissue changes associated with myelin loss and iron accumulation in multiple sclerosis deep gray matter (DGM) over two years. One-hundred twenty (120) multiple sclerosis patients and 40 age- and sex-matched healthy controls were included in this prospective study. Written informed consent and local IRB approval were obtained from all participants. Clinical testing and QSM were performed both at baseline and at follow-up. Brain magnetic susceptibility was measured in major DGM structures. Temporal (baseline vs. follow-up) and cross-sectional (multiple sclerosis vs. controls) differences were studied using mixed factorial ANOVA analysis and appropriate t-tests. At either time-point, multiple sclerosis patients had significantly higher susceptibility in the caudate and globus pallidus and lower susceptibility in the thalamus. Over two years, susceptibility increased significantly in the caudate of both controls and multiple sclerosis patients. Inverse thalamic findings among MS patients suggest a multi-phase pathology explained by simultaneous myelin loss and/or iron accumulation followed by iron depletion and/or calcium deposition at later stages.

Over the decades, various studies have established an association between accumulation of iron and both aging and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Excess levels of iron can lead to increased oxidative stress through Fenton chemistry, and depletion of iron can similarly have deleterious effects. In addition, metal ions are known to be involved in both Alzheimer's disease and Parkinson's disease protein aggregation. Metal ion chelators have been extensively investigated in preclinical models, and may prove to be appropriate for modulating brain iron levels in age-related neurodegenerative disorders. Investigating age-related iron deposition is vital, and can possibly aid in determining at-risk groups and diagnosing neurodegenerative diseases at an early stage. Novel imaging methods have enabled researchers to examine iron deposition in vivo, and offer a noninvasive method of monitoring the progression of accumulation, and possible therapeutic effects of chelating compounds.