File Name: progressive multiple sclerosis pathology and pathogenesis .zip
- The dynamics of multiple sclerosis
- Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis
- Progressive multiple sclerosis: pathology and pathogenesis
Multiple Sclerosis MS is a chronic inflammatory, demyelinating, and neurodegenerative disorder of the central nervous system CNS that affects the white and grey matter of the brain, spinal cord, and optic nerve.
The dynamics of multiple sclerosis
All rights reserved. Multiple sclerosis MS is a chronic immune-mediated demyelinating disease of the central nervous system CNS. Understanding the neurodegenerative processes involved in MS, particularly the role of white matter WM and grey matter GM , may help clinicians to diagnose the disease earlier and maximize opportunities to preserve neurological reserve. This article reviews MS pathogenesis and rationale for maintaining neurological reserve. The pathogenesis of MS involves the initiation and perpetuation of inflammatory mediators, which leads to apoptosis of oligodendrocytes and damage to the myelin sheath of the axon.
Multiple sclerosis MS , also known as encephalomyelitis disseminata , is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. While the cause is unclear, the underlying mechanism is thought to be either destruction by the immune system or failure of the myelin -producing cells. There is no known cure for multiple sclerosis. Multiple sclerosis is the most common immune-mediated disorder affecting the central nervous system. A person with MS can have almost any neurological symptom or sign, with autonomic , visual, motor, and sensory problems being the most common. Difficulties thinking and emotional problems such as depression or unstable mood are also common. Relapses are usually not predictable, occurring without warning.
Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis
In the majority of patients multiple sclerosis starts with a relapsing remitting course RRMS , which may at later times transform into secondary progressive disease SPMS. In a minority of patients the relapsing remitting disease is skipped and the patients show progression from the onset primary progressive MS, PPMS. We suggest that in MS patients two types of inflammation occur, which develop in parallel but partially independent from each other. The first is the focal bulk invasion of T- and B-lymphocytes with profound blood brain barrier leakage, which predominately affects the white matter, and which gives rise to classical active demyelinated plaques. The other type of inflammation is a slow accumulation of T-cells and B-cells in the absence of major blood brain barrier damage in the connective tissue spaces of the brain, such as the meninges and the large perivascular Virchow Robin spaces, where they may form aggregates or in most severe cases structures in part resembling tertiary lymph follicles. This type of inflammation is associated with the formation of subpial demyelinated lesions in the cerebral and cerebellar cortex, with slow expansion of pre-existing lesions in the white matter and with diffuse neurodegeneration in the normal appearing white or gray matter.
Ysrraelit, Marcela P. During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established.
Correspondence Address: Dr. Owain W. E-mail: o. Aim: Multiple sclerosis MS is an inflammatory demyelinating and neurodegenerative disease. Much of the complex symptomatology relates to pathology outside the classic white matter plaque, whereby lesions of the cortical grey matter, which are difficult to resolve by conventional clinical imaging, are in part predictive of outcome. We investigated the extent of grey matter pathology in whole coronal macrosections to reassess the contribution of cortical pathology to total demyelinating lesion area in progressive MS.
Progressive multiple sclerosis: pathology and pathogenesis
Major progress has been made during the past three decades in understanding the inflammatory process and pathogenetic mechanisms in multiple sclerosis MS. Consequently, effective anti-inflammatory and immunomodulatory treatments are now available for patients in the relapsing-remitting stage of the disease. This Review summarizes studies on the pathology of progressive MS and discusses new data on the mechanisms underlying its pathogenesis.
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