Tumefactive Multiple Sclerosis - Pathology

Pathology

Multiple sclerosis is an autoimmune response and the breach of the blood-brain barrier by inflammatory molecules cause the demyelinating process. T lymphocytes or T-cells, involved in the immune system, are activated by binding to a specific antigen. Upon activation, the T-cells are able to penetrate through the blood-brain barrier (BBB) and enter the central nervous system (CNS). The blood-brain barrier separates blood from the cerebrospinal fluid (CSF) in the CNS. It is made of endothelial cells tightly packed together, making the barrier selectively permeable to small molecules like carbon dioxide and oxygen. This barrier serves to protect the brain from bacterial infections. This breach of the BBB results in the increased permeability of the barrier to other inflammatory cells and macrophages. Peripheral cell-signalling molecules which enter the CNS through the BBB activate microglia cells, which protect the CNS by removing infectious agents, damaged neurons and plaques. Microglia cells behave like macrophages and it is believed that they are responsible for the production of the antigens that activate the T-cells and in the secretion of cytokines which may control inflammatory pathways. Subjects with tumefactive multiple sclerosis display elevated levels of choline (Cho)/creatine ratio and increased lactate which is associated with demylinating diseases. Cases also display oligo-clonal bands in the cerebrospinal fluid.

As of today, the initiation process of demyelination is not clearly understood but it is believed to be receptor-mediated. These macrophages attach onto the myelin sheaths and degrade the myelin, leaving the axons demyelinated. During the process of demyelination, macrophages produce toxins like nitric oxide and enzymes which cause damage to the surrounding myelin sheaths. These T-cells produce high levels of tumor necrosis factor alpha (TNFα) which have been shown to be toxic towards the oligodendrocytes and as such, the process of myelination is interrupted in addition to the demyelination that is occurring.