General Introduction

General Introduction

2015 Sep 10 | Caspar E.P. van Munster, Laura E. Jonkman, Henry C. Weinstein, Bernard M.J. Uitdehaag, Jeroen J.G. Geurts
Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease affecting the central nervous system (CNS), with an estimated 2.5 million cases worldwide. It is more common in women than men, and its clinical manifestations vary widely, often beginning with optic neuritis. While early research focused on white matter (WM) pathology, gray matter (GM) damage has become increasingly important in MS research. Lesions in the brain stem, cerebellum, and spinal cord disrupt motor and sensory functions. Physical disability is assessed using scales like the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC), which include cognitive testing. Cognitive impairment is common in MS, affecting processing speed, visual learning, and memory. MS has several clinical subtypes, including relapsing-remitting (RR), secondary-progressive (SP), primary-progressive (PP), and progressive-relapsing (PR). RRMS is the most common, with about 80-85% of patients initially diagnosed. Over time, many progress to SPMS, while PPMS is characterized by a gradual progressive course. MRI is crucial for diagnosing MS, revealing lesions in the brain and spinal cord. CSF analysis can indicate intra-CNS inflammation. Although MS is incurable, treatments like interferon beta and Natalizumab reduce relapse frequency but carry risks. Genetic factors, such as the HLA-DRB1*1501 allele, influence MS susceptibility and disease severity. Lesion pathology includes demyelination, axonal loss, and gliotic scarring. Cortical GM lesions are often overlooked due to limited MRI detection, but advanced techniques like 7T MRI and quantitative MRI (qMRI) improve visualization. qMRI methods such as magnetization transfer ratio (MTR), quantitative R2*, and diffusion tensor imaging (DTI) help characterize GM and WM lesions. These techniques provide insights into myelin content, axonal damage, and tissue structure. The thesis aims to improve MRI visualization and characterization of GM and WM abnormalities, explore genetic and clinical correlations, and translate findings to clinical applications. Advanced MRI sequences enhance lesion detection, particularly in cortical GM, and improve differentiation between lesion types. These advancements aid in understanding MS pathology, monitoring disease progression, and evaluating treatment effects.Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease affecting the central nervous system (CNS), with an estimated 2.5 million cases worldwide. It is more common in women than men, and its clinical manifestations vary widely, often beginning with optic neuritis. While early research focused on white matter (WM) pathology, gray matter (GM) damage has become increasingly important in MS research. Lesions in the brain stem, cerebellum, and spinal cord disrupt motor and sensory functions. Physical disability is assessed using scales like the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC), which include cognitive testing. Cognitive impairment is common in MS, affecting processing speed, visual learning, and memory. MS has several clinical subtypes, including relapsing-remitting (RR), secondary-progressive (SP), primary-progressive (PP), and progressive-relapsing (PR). RRMS is the most common, with about 80-85% of patients initially diagnosed. Over time, many progress to SPMS, while PPMS is characterized by a gradual progressive course. MRI is crucial for diagnosing MS, revealing lesions in the brain and spinal cord. CSF analysis can indicate intra-CNS inflammation. Although MS is incurable, treatments like interferon beta and Natalizumab reduce relapse frequency but carry risks. Genetic factors, such as the HLA-DRB1*1501 allele, influence MS susceptibility and disease severity. Lesion pathology includes demyelination, axonal loss, and gliotic scarring. Cortical GM lesions are often overlooked due to limited MRI detection, but advanced techniques like 7T MRI and quantitative MRI (qMRI) improve visualization. qMRI methods such as magnetization transfer ratio (MTR), quantitative R2*, and diffusion tensor imaging (DTI) help characterize GM and WM lesions. These techniques provide insights into myelin content, axonal damage, and tissue structure. The thesis aims to improve MRI visualization and characterization of GM and WM abnormalities, explore genetic and clinical correlations, and translate findings to clinical applications. Advanced MRI sequences enhance lesion detection, particularly in cortical GM, and improve differentiation between lesion types. These advancements aid in understanding MS pathology, monitoring disease progression, and evaluating treatment effects.
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