Journal of the neurological sciences
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There are two components to the treatment of multiple sclerosis (MS); the first is to prevent damage occurring, and the second is to repair the residual damage. While considerable progress has been made in the recent years with the former through the development of anti-inflammatory and immunomodulatory therapies, there are currently no effective repair therapies routinely used in MS patients. ⋯ In this article we argue that a clear understanding of the repair mechanisms following CNS demyelination is fundamental to filling this gap. We discuss (1) the cellular events involved in remyelination, (2) changes in transcription factor expression within oligodendrocyte precursor cells associated with their activation in response to demyelination, (3) the role of platelet derived growth factor in the OPC recruitment phase of remyelination, and (4) the significance of the inflammatory response associated with demyelination in creating a signalling environment that favours remyelination.
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Coronary artery bypass grafting (CABG) is the most common major surgical procedure performed worldwide. Neuropsychological deficits are frequent following CABG occurring in up to 80% in the early postoperative period, 20-50% at 6 weeks and 10-30% of patients at 6 months. Transcranial Doppler monitoring is well suited for monitoring the brain during surgery. ⋯ This method can also monitor cerebral hemodynamics during surgery and alert the surgical team when a fall in perfusion pressure occurs. Magnetic resonance imaging (MRI) studies have found evidence which suggests increased water content in the brain following "on-pump" CABG. New postoperative cerebral lesions have also been found in many patients using diffusion-weighted MRI.
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Small fiber neuropathy (SFN) is a neuropathy selectively involving small diameter myelinated and unmyelinated nerve fibers. Interest in this disorder has considerably increased during the past few years. ⋯ Among others, these tests include assessment of epidermal nerve fiber density, temperature sensation tests for sensory fibers and sudomotor and cardiovagal testing (QSART) for autonomic fibers. Unless an underlying disease is identified, treatment is usually symptomatic and directed towards alleviation of neuropathic pain.
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Evidence for the effectiveness of immunosuppressive agents in MS is scanty. There are few good quality trials; most have methodological limitations, such as a small sample size and short duration. ⋯ Although azathioprine appears to reduce the relapse rate in MS patients, its effect on disability progression has not been demonstrated. Methotrexate may alter the course of disease favourably in patients with progressive MS, but the evidence is again sparse.
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Based on the encouraging results of transplantation in animals with experimental autoimmune encephalomyelitis (EAE), small-scale phase I/II trials of autologous hematopoietic stem cell transplantation (autoHSCT) were initiated in 1995 for the treatment of severe cases of multiple sclerosis (MS). More than 200 patients with treatment-resistant multiple sclerosis have been transplanted so far, mainly in Europe and the USA. The results of these studies appear promising in terms of impact on MRI disease parameters and, to a lesser extent, clinical stabilization or even improvement. Despite concerns raised by the morbidity and mortality noted in the initial pilot studies, a controlled, randomized, phase III trial of autoHSCT against the best currently available treatment, i.e., mitoxantrone, seems justified and is under way.