Critical Review of Existing Trials
Epidemiological studies indicate that about 90% of multiple sclerosis (MS) patients experience a progression of the disease at some time during their life [1, 2]. In about 15% of patients, the disease starts with an insidious onset followed by a progressive phase, with or without phases of stability; the so-called primary progressive (PP) MS. In all other patients, the early phase of MS is marked by acute attacks characterized by unifocal (2/3 of patients) or multifocal white matter disease . Attacks are usually followed by complete or almost complete recovery; however, pathological studies demonstrate the presence of an axonal transection inside the lesion [4, 5, 6]. Axonal loss is predominant in lesions appearing in the early phases of the disease  and decreases over time. A large amount of damage occurs in areas with a considerable infiltration of T lymphocytes (especially CD8+ T cells) and macrophages , indicating a correlation between inflammation and axonal damage - a relationship which has also been shown by magnetic resonance imaging (MRI) studies. The acute axonal damage also occurs because of the products of inflammation, such as nitric oxide and tumor necrosis factor . Recent studies indicate that a high level of electrical activity may increase the axonal degeneration of partially or completely demyelinated lesions at the nodes of Ranvier, as a consequence of the activation of glutamate receptors increasing the entry of calcium into the axon . Recent studies suggest that axonal damage may also be independent of demyelination  and may be caused by antibodies against axonal antigens .
KeywordsMultiple Sclerosis Glatiramer Acetate Progressive Multiple Sclerosis Clinically Isolate Syndrome Secondary Progressive Multiple Sclerosis
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