![]() We wanted to test the models developed on the cross-sectional dataset (see “Statistical Analysis” section for details) on an independent longitudinal dataset. Patient Population for Longitudinal Analysis of Transition from RRMS to SPMS Our study was performed with institutional review board approval. All patients were treated, and the type of treatment varied across the patients. Table 1 shows the characteristics of the patient cohort. During the clinical visit, the physician determined the disease category, ambulation index, and the Expanded Disability Status Scale (EDSS). The time interval between the MR imaging examination date and the clinical visit date was <5 weeks for all patients. 17 Each patient was clinically evaluated by an MS specialist at the Partners Multiple Sclerosis Center of the Brigham and Women's Hospital in Boston, Mass. The diagnosis of clinically definite MS was made according to the International Panel criteria, 15, 16 and all patients were also categorized as having either RRMS, SPMS, or PPMS. The MR images of 64 patients with MS from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) study 14 were analyzed to build a classifier based on a decision tree analysis. Patient Population for Cross-Sectional Analysis The combination of corpus callosum and MOV metrics differentiate well between clinical MS phenotypes and might be useful as surrogate measures more directly linked to underlying neurodegenerative processes. Our results show that classification techniques can be used to unveil differences in affected neuroanatomic regions in subtypes of MS. The corpus callosum, on the other hand, projects to a very large fraction of the overall cerebral white matter, potentially providing a sensitive and methodologically simple reflection of total cerebral white matter damage. 13 Because current clinical definitions of SPMS are heavily reliant on motor performance, size assessment of white matter pathways in the medulla oblongata may be a good candidate for a surrogate marker for this phase of disease. Although both of these regions of interest target white matter tracts, they are specific to different functional systems, namely the sensory-motor pathways (MOV) versus callosal interhemispheric association fibers (corpus callosum). This approach also tests the hypothesis that the different clinical subtypes of MS have underlying differences in affected neuroanatomic regions. In this study, we evaluated the ability of cross-sectional measures from 2 white matter tracts associated with different functional systems, the medulla oblongata volume (MOV) and the area of the corpus callosum, to distinguish RRMS, SPMS, and PPMS. Recent work has reported an association between subolivary medulla oblongata cross-sectional measurement and progressive MS, suggesting that such measures may be somewhat specific for the degree of axonal involvement in the degenerative process. 9 – 11 Cross-sectional and volumetric measures of white matter regions have more recently been complemented by more detailed and complex measures such as diffusion tensor imaging and magnetization transfer ratio. Global gray matter volume, cortical thickness mapping, and measures of subcortical nuclei have all been used to assess the impact of MS on neuronal populations. 1, 2, 8 Although brain parenchymal fraction is a complex reflection of different degenerative aspects such as demyelination, axonal degeneration, and neuronal loss, it has been proposed that separate measures of gray matter and white matter atrophy might more specifically reflect the underlying histopathology and provide better correlates with functional deficits. It has been reported that the assessment of global atrophy is an appealing and robust measure for the quantification of neurodegeneration. 7 MR imaging−based tissue volumetry such as T2 lesion volume and brain parenchymal fraction has been used to measure inflammatory and neurodegenerative aspects of MS. MR imaging is the most important imaging technique for the diagnosis and monitoring of patients with MS. 3 – 5 Primary-progressive MS (PPMS) appears to be characterized by a prevalently neurodegenerative process from the onset of disease, though this has been a topic of debate. 3 In the early RR phase of the disease, an autoimmune inflammatory process seems to be predominant, 3 – 5 whereas in the SP phase, neurodegeneration becomes more evident. 3 Time to conversion to SPMS varies significantly, with a reported mean of 10 years. ![]() ![]() ![]() 1, 2 The most frequent form of MS presents initially as relapsing-remitting (RR), followed subsequently by a secondary-progressive (SP) phase in approximately 50% of patients. Multiple sclerosis (MS) is a chronic multifactorial disease with a strong neurodegenerative component associated with progressive atrophy of the brain and spinal cord.
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