Multiple Sclerosis
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Lectures:   Pathology

  • Pathological Hallmarks of Multiple Sclerosis

Disseminated white matter lesions of the CNS were first described by a French neurologist Charcot in late XIX. century. On histological sections these lesions were demonstrated to contain perivascular inflammation and demyelination. These features now are pathological hallmarks for MS.

  • Distribution of Demyelinating Plaques in CNS

Plaques were demonstrated to occur anywhere within the white matter of the CNS, but the most frequently affected sites are the optic nerves, the brainstem, the cerebellum and the spinal cord. Lesions in these locations often correlate with clinical symptoms. In the cerebral hemispheres periventricular distribution of plaques is often seen. When plaques are adjacent to the cortex, subcortical myelinated fibers are often spared. Plaques located nearby the gray matter may rarely spread into the gray matter, including deep nuclei and the cortex. There often is axon sparing within the plaque.

  • Mechanisms of Plaque Evolution

It is not clear how the plaque evolves over time. MRI investigations have shown that blood-brain barrier is disrupted at the onset of symptoms, but it is not known yet whether demyelination precedes or is secondary to inflammation. The current view on this matter is that acute inflammatory response of lymphocytes, plasma cells and macrophages can produce demyelination by direct or indirect mechanisms. The macrophages in those lesions contain myelin fragments or myelin breakdown products. Lymphocytes contribute to pathologic processes by means of antibody- and cell-mediated immunity (direct mechanism) or by secretion of lymphokines and cytokines (indirect mechanism.)

  • Ultrastructural Characteristics of plaques

The following ultrastructural characteristics are frequently found in the plaque:

  • separation of the outer lamellae of the myelin sheath,

  • degenerative changes in myelin,

  • infiltration with macrophages or microglia with phagocytosis of myelin,

  • preservation of axons.

According to histologic criteria, the CNS lesions in MS are classified as early active, inactive, early remyelinating, and late remyelinating. The precise pathological distinctions between these is beyond the scope of this review.

  • Assessment of Severity and Possibility for Remyelination

The severity of demyelination may be assessed by relative preservation or destruction of oligodendrogliocytes. It is demonstrated that early in the course of the disease, more oligodendrogliocytes are preserved in the plaque; thus some degree of remyelination remains possible. In other patients, there is a complete loss of oligodendrogliocytes. In this group of patients, possibility of remyelination is dramatically decreased. These observations may also imply that heterogeneous mechanisms are responsible for the disease induction in different patents.

  • Results of Demyelination

Whatever route the pathological process takes from inflammation to demyelination, the effects of loss of myelin by the nerve fibers are quite dramatic. Saltatory conduction is much more energy efficient than nerve impulses transmitted along the entire length of the nerve fiber. Loss of myelin results in one or all of the following:

  • conduction block at the site of lesion

  • slower conduction time along the affected nerve

  • increased subjective feeling of fatigue secondary to compensation for neurologic deficits

  • Illustrations