The onset and progression of the lesion in multiple sclerosis

https://doi.org/10.1016/0022-510X(75)90138-0Get rights and content

Abstract

The active established plaque in multiple sclerosis is characterized by hypercellularity at its edge and lipid phagocytosis (gitter cells). The hyperactive early plaque shows cells throughout the lesion. Active plaques seem to extend at their edges; proteolysis of myelin basic protein is perhaps an important factor in the myelin breakdown at the rim of these lesions.

The hyperactive early plaque usually shows infiltration with monocytes, lymphocytes and plasma cells around its central vein. The phagocytic element is presumably a response to myelin breakdown, but the significance of the lymphocytes in these lesions is uncertain.

Perivenular infiltrates that are predominantly composed of lymphocytes are seen around veins and venules in the vicinity of established lesions in some patients who died during an acute episode. Serial section shows that these veins are not draining the lesion, but very distant veins and venules are not involved. These lymphocyte infiltrations often show no surrounding demyelination, but not infrequently areas of inactive demyelination are seen around them. It is suggested that, if the lymphocytic infiltration is an early event, it may either proceed to a hyperactive plaque (and in the process becomes enriched with monocytes), or it may become aborted or itself aborts the pathogenic process. Areas of intense myelin pallor and oedema associated with lymphocyte cuffs might represent an intermediate stage between the simple infiltrate and the explosive hyperactive plaque.

The active perivenous lesion seems to extend along a vein and coalesces with neighbouring perivenous lesions; in this way some plaques are seen to follow the course of a vein over a considerable distance. Selective loss of basic proteins does not appear from limited evidence to be a feature around such perivenous lymphocytic infiltrates, but proteolytic activity has not yet been tested in them.

References (54)

  • R.D. Adams et al.

    The demyelinative diseases of the human nervous system

  • C.W.M. Adams et al.

    Histochemistry of myelin, Part 2 (Proteins, lipid-protein dissociation and proteinase activity in Wallerian degeneration)

    J. Neurochem.

    (1961)
  • C.W.M. Adams et al.

    Phagocytosis, lipid-removal and atherosclerosis

    J. Path.

    (1975)
  • C.W.M. Adams et al.

    Histochemistry of myelin, Part 13 (Digestion of basic protein outside acute plaques of multiple sclerosis)

    J. Neurochem.

    (1971)
  • C.W.M. Adams et al.

    Demyelination

  • A.U. Arstila et al.

    Lysosomes in demyelination in the CNS white matter outside plaques

    Europ. Neurol.

    (1973)
  • O.B. Bayliss et al.

    Cellular lipid inclusions in the white matter in multiple sclerosis

    Nature (Lond.)

    (1971)
  • A. Bignami et al.

    Biochemical studies of myelin in Wallerian degeneration of rat optic nerve

    J. Neurochem.

    (1973)
  • J.L. Birley et al.

    A clinical and experimental contribution to the pathogenesis of disseminated sclerosis

    Brain

    (1921)
  • D.M. Bowen et al.

    Carboxypeptidases of human brain: Hydrolysis of benzyloxy-carbonyl-glubamyl-1-tyrosine in normal and diseased tissue

    J. Neurochem.

    (1974)
  • J.W. Dawson

    The histology of disseminated sclerosis, Part 2 (Histological study)

    Edinb. med. J., N.S.

    (1916)
  • J.W. Dawson

    The histology of disseminated sclerosis. Part 3 (Pathogenesis and etiology, a critical discussion)

    Edinb. med. J., N.S.

    (1916)
  • E.R. Einstein et al.

    Proteolytic activity and basic protein loss in and around multiple sclerosis plaques - Combined biochemical and histochemical observations

    J. Neurochem.

    (1972)
  • T. Fog

    Vessel-plaque relations, and cerebrospinal fluid and brain tissue changes in multiple sclerosis

    Acta scand.

    (1964)
  • R.L. Friede

    Enzyme histochemical studies in multiple sclerosis

    Arch. Neurol. (Chic.)

    (1961)
  • R.L. Friede et al.

    Quantitative enzyme profiles of plaques of multiple sclerosis

    Experientia

    (1964)
  • J.G. Greenfield et al.

    Observations on the histopathology of cerebral lesions in disseminated sclerosis

    Brain

    (1936)
  • Cited by (80)

    • The central vein sign is present in most infratentorial multiple sclerosis plaques

      2022, Multiple Sclerosis and Related Disorders
      Citation Excerpt :

      Multiple sclerosis (MS) pathology studies have shown white matter lesions (WMLs) develop surrounding small veins (Adams, 1975).

    • Revealing vascular abnormalities and measuring small vessel density in multiple sclerosis lesions using USPIO

      2021, NeuroImage: Clinical
      Citation Excerpt :

      With the development of susceptibility-based venography in the late 1990s (Reichenbach et al., 1997), there has been a steady emphasis on the “central vein sign” or CVS hypothesis as a marker for and precursor to the development of new MS lesions (Gaitán et al., 2013; Maggi et al., 2015; Sati et al., 2016b; Tan et al., 2000). The perivascular space surrounding these veins is thought to be a privileged site for immune cells to interact with antigen-presenting cells, which can then trigger an inflammatory cascade leading to the formation of lesions around the veins (Adams, 1975; Barnett and Prineas, 2004). Studies have demonstrated that inflammation and injury to the blood–brain barrier of post-capillary venules enables the migration of blood constituents, including erythrocytes, lymphocytes, cytokines, glial cells etc.

    • Investigation of cerebral microbleeds in multiple sclerosis as a potential marker of blood-brain barrier dysfunction

      2016, Multiple Sclerosis and Related Disorders
      Citation Excerpt :

      In MS, the situation appears to be different to those disorders with a primarily vascular pathology. Firstly histopathological studies demonstrate that in MS subcortical white matter lesions develop as a consequence of inflammation around small veins that drain into deep and superficial venous pathways (Adams, 1975; Fog, 1964), while the arterial vasculature does not seem to be affected. Secondly, structural changes of the vasculature have not been documented in MS patients.

    • Observations on the brain vasculature in multiple sclerosis: A historical perspective

      2014, Multiple Sclerosis and Related Disorders
      Citation Excerpt :

      For example, McAlpine et al. in their 1955 textbook reviewed this literature extensively and concluded that ‘while the veins and venules have some influence in determining the sites of origin of the plaques they do not determine the subsequent evolution or form of the plaque and that thombosis, when it occurs, is a secondary process due to absorption of thromboplastic substance from the plaque’ (McAlpine et al., 1955). During the 1970s various authors confirmed the observation of a perivascular distribution of inflammation, and noted that this was more typical of the acute rather than chronic phase of the plaque (Adams, 1975; Guseo and Jellinger, 1975; Tanaka et al., 1975). Further work by Adams and colleagues documented perivenous iron deposition and other vascular damage in MS (Adams et al., 1985; Adams, 1988).

    • Bacterial toxins and Multiple Sclerosis

      2007, Journal of the Neurological Sciences
    View all citing articles on Scopus

    This paper was read at the Symposium on Multiple Sclerosis, organized by the Medical Research Council and the Multiple Sclerosis Society, held in London on 17–18 October, 1974.

    View full text