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The dynamics of multiple sclerosis

The Charcot lecture

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Abstract

The history of our understanding of the pathogenesis and pathophysiology of multiple sclerosis are reviewed in the context of Charcot's contribution. The implications for treatment of the new knowledge gained from studies during life of pathology and pathogenesis (by MRI) and pathophysiology (by evoked potentials) are reviewed.

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References

  1. Arnold AC, Pepose JS, Hepler RS, Foos RY (1984) Retinal periphlebitis and retinitis in multiple sclerosis. I. Pathologic characteristics. Ophthalmology 91:255–262

    Google Scholar 

  2. Austims Research Group (1989) Interferon-α and transfer factor in the treatment of multiple sclerosis: a double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry 52:566–574

    Google Scholar 

  3. Babinski J (1985) Recherches sur l'anatomie pathologique de la sclérose en plaues et étude comparative des diverses variétés de scléroses de la moelle. Arch Physiol Norm Pathol 5 (series 3):186–207

    Google Scholar 

  4. Bamford CR, Ganley JP, Sibley WA, Laguna JF (1978) Uveitis, perivenous sheating and multiple sclerosis. Neurology 28:119–124

    Google Scholar 

  5. Barnes D, Munro PMG, Youl BD, Prineas JW, McDonald WI (1991) The longstanding MS lesion: a quantitative and electron microscopic study. Brain 114:1271–1280

    Google Scholar 

  6. Barratt HJ, Miller D, Rudge P (1988) The site of the lesion causing deafness in multiple sclerosis. Scand Audiol 17:67–71

    Google Scholar 

  7. Bornstein MB, Miller A, Slagle S, Weitzman M, Crystal H, Drexler E, Keilson M, Merriam A, Wassertheil-Smoller S, Spada V, Weiss W, Arnon R, Jacobsohn I, Teitelbaum D, Sela M (1987) A pilot trial of COP 1 in exacerbating-remitting multiple sclerosis. N Engl J Med 317:408–414

    Google Scholar 

  8. Bornstein MB, Miller A, Slagle S, Weitzman M, Drexler E, Keilson M, Spada V, Weiss W, Appel S, Rolak L, Harati Y, Brown S, Arnon R, Jacobsohn I, Teitelbaum D, Sela M (1991) A placebo-controlled, double-blind, randomized, two-centre, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology 41:533–539

    Google Scholar 

  9. Carswell R (1838) Pathological anatomy. Illustrations of the elementary forms of disease. Longman, Orme, Brown, Green and Longman, London

    Google Scholar 

  10. Charcot M (1868) Histologie de le sclérose en plaques. Gaz Hôp Paris 141:554–555, 557–558

    Google Scholar 

  11. Charcot JM (1877) Lectures on diseases of the nervous system. Translated by G. Sigerson. The New Sydenham Society, London, pp 158–222

    Google Scholar 

  12. Compston A (1988) The 150th anniversary of the first depiction of the lesions of multiple sclerosis. J Neurol Neurosurg Psychiatry 51:1249–1252

    Google Scholar 

  13. Compston DAS (1990) The dissemination of multiple sclerosis. J Coll Phys Lond 24:207–218

    Google Scholar 

  14. Compston DAS (1991) Limiting and repairing the damage in multiple sclerosis. J Neurol Neurosurg Psychiatry 54:945–948

    Google Scholar 

  15. Cruveilhier J (19842) Anatomie pathologique du corps humain; descriptions avec figures lithographiées et coloriées; des diverses alterations morbides dont le corps humain est susceptible. Baillière, Paris

  16. Davis FA, Stefoski D, Rush J (1990) Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis. Ann Neurol 27:186–192

    Google Scholar 

  17. Dawson GD, Scott JW (1949) The recording of nerve action potentials through skin in man. J Neurol Neurosurg Psychiatry 12:259–267

    Google Scholar 

  18. Denny-Brown D, Brenner C (1944) Paralysis of nerve induced by direct pressure and by tourniquet. Arch Neurol Psychiatry 51:1–26

    Google Scholar 

  19. Denny-Brown D, Brenner C (1944) Lesion in peripheral nerve resulting from compression by spring clip. Arch Neurol Psychiatry 52:1–19

    Google Scholar 

  20. Devereux C, Troiano R, Zito G, Devereux RB, Kopecky KJ, Friedman R, Dowling PC, Hafstein MP, Rohowsky-Kochan C, Cook SD (1988) Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment — the pros. Neurology 38 [Suppl 2]:32–37

    Google Scholar 

  21. Eichler W (1937) Ober die Abteilung der Aktionspotentiale von menschlichen Nerven in situ. Z Biol 98:182–214

    Google Scholar 

  22. Firth D (1948) The case of Augustus d'Esté. Cambridge University Press, Cambridge

    Google Scholar 

  23. Fog T (1965) The topography of plaques in multiple sclerosis with special reference to cerebral plaques. Acta Neurol Scand 41[Suppl 15]:3–161

    Google Scholar 

  24. Frommann C (1867) Untersuchungen über die normale and pathologische Anatomie des Rückenmarks, zweiter Theil. Frommann, Jena

    Google Scholar 

  25. Graham EM, Francis DA, Sanders MD, Rudge P (1989) Ocular inflammatory changes in established multiple sclerosis. J Neurol Neurosurg Psychiatry 52:1360–1363

    Google Scholar 

  26. Graves RJ (1858) Clinical lectures on the practice of medicine, 2nd edn, vol 1. Longman, London, p 43 (I have quoted here Graves' original text, rather than a retranslation into English of the French translation referred to in [28])

    Google Scholar 

  27. Grossman RI, Gonzalez-Scarano F, Atlas SW, Galetta S, Silberberg DH (1986) Multiple sclerosis: gadolinium enhancement in MR imaging. Radiology 161:721–725

    Google Scholar 

  28. Guillain G (1959) J.-M. Charcot 1825–1893. His life — his work. Edited and translated by P. Bailey. Pitman Medical, London

    Google Scholar 

  29. Halliday AM, McDonald WI, Mushin J (1972) Delayed visual evoked response in optic neuritis. Lancet 1:982–985

    Google Scholar 

  30. Halliday AM, McDonald WI, Mushin J (1973) Delayed pattern-evoked responses in optic neuritis in relation to visual acuity. Trans Opthalmol See UK 93:315–324

    Google Scholar 

  31. Harvey AM, Kuffler SW, Tredway JB (1945) Peripheral neuritis. Bull Johns Hopkins Hosp 77:83–103

    Google Scholar 

  32. Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, Millis JA, Weiner HL (1983) Intensive immune-suppression in progressive multiple sclerosis. N Engl J Med 308:173–180

    Google Scholar 

  33. Hawkins CP, MacKenzie F, Tofts P, Boulay EPGH du, McDonald WI (1991) Patterns of blood-brain barrier brewakdown in inflammatory demyelination. Brain 114:801–810

    Google Scholar 

  34. Heinbecker P, Bishop GH, O'Leary JL (1936) Functional and histologic studies of somatic and autonomic nerves of man. Arch Neurol Pychiatry 35:1233–1255

    Google Scholar 

  35. Huxley AF, Stämpfli R (1949) Evidence for saltatory conduction in peripheral myelinated nerve fibres. J Physiol (Lond) 108:315–339

    Google Scholar 

  36. Isaac C, Li DK, Genton M, Jardine C, Growchowski E, Palmer M, Kastrukoff LF, Oger J, Paty DW (1988) Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology 38:1511–1515

    Google Scholar 

  37. Kappos L, Patzold U, Dommasch D, Poser S, Haas J, Krauseneck P, Malin J-P, Fierz W, Graffenried BU, Gugerli US (1988) Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis: results of the German multicentre study. Ann Neurol 23:56–63

    Google Scholar 

  38. Kappos L, Gold R, Hofmann E, Keil W, Clauss W (1990) Multiple sclerosis: diagnostic criteria and the role of contrast enhanced MRI. In: Bydder GM, Felix R, Bucheler E, et al (eds) Contrast media in MRI. Medicom Europe, Bussum, pp 127–135

    Google Scholar 

  39. Katz D, Taubenberger J, Raine C, McFarlin D, McFarland H (1990) Gadolinium-enhancing lesions on magnetic resonance imaging: neuropathological findings. Ann Neurol 28:243

    Google Scholar 

  40. Kermode AG, Thompson AT, Tofts P, Machanus DG, Kendall BE, Kingsley DPE, Moseley IF, Rudge P, McDonald WI (1990) Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis: pathogenetic and clinical implications. Brain 113:1477–1489

    Google Scholar 

  41. Kermode AG, Tofts PS, Thompson AJ, Machanus DG, Rudge P, Kendall BE, Kingsley DPE, Moseley IF, Boulay EPGH du, McDonald WI (1990) Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study with gadolinium-DTPA enhancement. Neurology 40:229–235

    Google Scholar 

  42. Koles ZJ, Rasminsky M (1972) A computer simulation of conduction in demyelinated nerve fibres. J Physiol (Lond) 227:351–364

    Google Scholar 

  43. Larsson HBW, Frederiksen J, Kjaer L, Henriksen O, Olesen J (1988) In vivo determination of T1 and T2 in the brain of patients with severe but stable multiple sclerosis. Magn Reson Med 7:43–55

    Google Scholar 

  44. Lassmann H (1983) Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis. Springer, Berlin Heidelberg New York

    Google Scholar 

  45. Lightman S, McDonald WI, Bird AC, Francis DA, Hoskins A, Batchelor JR, Halliday AM (1987) Retinal venous sheathing in optic neuritis. Its significance for the pathogenesis of multiple sclerosis. Brain 110:405–414

    Google Scholar 

  46. Likosky WH, Fireman B, Elmore R, Eno G, Gale K, Browne Goode G, Ikeda K, Laster J, Mosher C, Rozance J, Richmon J, Rosenberg S, Samman A, Sternbach R, Whaley J, Fehrenbacher L (1991) Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study. J Neurol Neurosurg Psychiatry 54:1055–1060

    Google Scholar 

  47. McDonald WI (1963) The effects of experimental demyelination on conduction in peripheral nerve: a histological and electrophysiological study. II. Electrophysiological observations. Brain 86:501–524

    Google Scholar 

  48. McDonald WI (1986) The mystery of the origin of multiple sclerosis. J Neurol Neurosurg Psychiatry 49:113–123

    Google Scholar 

  49. McDonald WI, Sears TA (1970) The effects of experimental demyelination on conduction in the central nervous system. Brain 93:583–598

    Google Scholar 

  50. McDonald WI, Miller DH, Barnes D (1992) The pathological evolution of multiple sclerosis. Neuropathol Appl Neurobiol (in press)

  51. McFarlin DE, McFarland HIT (1982) Multiple sclerosis. N Engl J Med 307:1183–1118, 1246–1251

    Google Scholar 

  52. Meige H (1925) Charcot artiste. Masson, Paris, p 45

    Google Scholar 

  53. Miller DH, Newton MR, Poel JC van der, Boulay EPGH du, Halliday AM, Kendall BE, Johnson G, Machanus DG, Moseley IF, McDonald WI (1988) Magnetic resonance imaging of the optic nerve in optic neuritis. Neurology 38:175–179

    Google Scholar 

  54. Miller DH, Rudge P, Johnson G, Kendall BE, Machanus DG, Moseley IF, Barnes D, McDonald WI (1988) Serial Gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain 111:927–939

    Google Scholar 

  55. Miller DH, Barkhof F, Berry I, Kappos L, Scotti G, Thompson AJ (1991) Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines. J Neurol Neurosurg Psychiatry 54:683–688

    Google Scholar 

  56. Miller DH, Thompson AJ, Morrissey SP, Machanus DG, Moore SG, Kendall BE, Moseley IF, McDonald Wl (1992) High dose steroids in acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect. J Neurol Neurosurg Psychiatry (in press)

  57. Milligan NM, Newcombe A, Compston DAS (1987) A doubleblind controlled trial of high dose methylprednisolone in patients with multiple sclerosis. I. Clinical effects. J Neurol Neurosurg Psychiatry 50:511–516

    Google Scholar 

  58. Meyer LW, Ellison GW, Fahey JL, Tesler A, Gottlieb MS (1988) Clinical drawbacks of total lymphoid irradiation: the cons. Neurology 38 [Suppl 2]:38–40

    Google Scholar 

  59. Noseworthy JH, Ebers GC, Gent M (1991) The Canadian cooperative trial of cyclophosphamide and plamsa-exchange in progressive multiple sclerosis. Lancet 337:441–446

    Google Scholar 

  60. Ormerod IEC, Miller DH, McDonald WI, Boulay EPGH du, Rudge P, Kendall BEW, Moseley IF, Johnson G, Tofts PS, Halliday AM, Bronstein AM, Scaravilli F, Harding AE, Barnes D, Zilkha KJ (1987) The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study. Brain 110:1579–1616

    Google Scholar 

  61. Painter GD (1965) Marcel Proust. A biopgraphy, vol 2. Chatto and Windus, London, p 279

    Google Scholar 

  62. Panitch HS, Hirsch RL, Haley AS, Johnson KP (1987) Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet I:893–894

    Google Scholar 

  63. Prineas JW, Connell F (1978) The fine structure of chronically active multiple sclerosis plaques. Neurology 28:68–75

    Google Scholar 

  64. Proust M (1981) Remembrance of things past, vol 2. Translated by C. K. Scott Moncrieff and Terrence Kilmartin. Chatto and Windus, London, p 910

    Google Scholar 

  65. Rindfleisch E (1863) Histologisches Detail zu der grauen Degeneration von Gehirn und Rückenmark. (Zugleich ein Beitrag zu der Lehre von der Entstehung und Verwandlung der Zelle.) Arch Pathol Anat Physiol Klin 26:474–483

    Google Scholar 

  66. Rokitansky (1857) Bericht der Akadmie der Wissenschaft zu Wien 24. Cited by Charcot [10, 11]

  67. Rose AS, Kuzma JW, Kurtzke JF, Namerow NS, Sibley WA, Tourtellotte WW (1970) Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs placebo — final report. Neurology 20:1–59

    Google Scholar 

  68. Rucker CW (1944) Shearing of the retinal veins in multiple sclerosis. Proc Staff Meet Mayo Clin 19:176–178

    Google Scholar 

  69. Rudge P, Koetsier JC, Mertin J, Mispelblom Beyer JO, Walbeek HK van, Clifford Jones R, Harrison J, Robinson K, Mellein B, Poole T, Stokvis JCJM, Timonen P (1989) Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiatry 52:559–565

    Google Scholar 

  70. Souques A (1925) Charcot Intime. Press Med 33:693–698

    Google Scholar 

  71. Steinman L, Rosenbaum JT, Sriram S, McDevitt HO (1981) In vivo effects of antibodies to immune response gene products: prevention of experimental allergic encephalitis. Proc Natl Acad Sci USA 78:7111–7114

    Google Scholar 

  72. Stewart WA, Hall LD, Berry K, Paty DW (1984) Correlation between NMR scan and brain slice data in multipe sclerosis. Lancet II:412

    Google Scholar 

  73. Tasaki I (1953) Nervous transmission. Thomas, Springfield, Ill

    Google Scholar 

  74. The Multiple Sclerosis Study Group (1990) Efficacy and toxicity of cyclosporine in the chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. Ann Neurol 27:591–605

    Google Scholar 

  75. Thomas AJ, Kennard C, Swash M, Summers B, Yuill GM, Shepherd DI, Roche S, Perkin GD, Loizou LA, Ferner R, Hughes RAC, Thompson M, Hand J (1989) Relative efficacy of intravenous methlyprednisolone and ACTH in the treatment of acute relapse in MS. Neurology 39:969–971

    Google Scholar 

  76. Thompson AJ, Kermode AG, Wicks D, MacManus DG, Kendall BE, Kingsley DPE, McDonald WI (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29:53–62

    Google Scholar 

  77. Van Diemen HAM, Polman CH, Dongen MMMM van, Loenen AC van, Nauta JJP, Taphoorn MJB, Walbeek HK van, Koetsier JC (1992) The effect of 4-aminopyridine on the clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. Ann Neurol (in press)

  78. Willoughby EW, Grochowski E, Li DKB, Oger J, Kastrukoff LF, Paty DW (1989) Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients. Ann Neurol 25:43–49

    Google Scholar 

  79. Youl BD, Turano G, Miller DH, Towell AD, MacManus DG, Moore SG, Jones SJ, Barrett G, Kendall BE, Moseley IF, Tofts PS, Halliday AM, McDonald WI (1991) The pathophysiology of acute optic neuritis: an association of gadolinium leakage with clinical and electrophysiological deficits. Brain 114:2437–2450

    Google Scholar 

  80. Young IR, Hall AS, Pallis CA, Legg NJ, Bydder GM, Steiner RE (1981) Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 11:1063–1066

    Google Scholar 

  81. Yudkin PL, Ellison GW, Ghezzi A, Goodkin DE, Hughes RAC, McPherson K, Mertin J, Milanese C (1991) Overview of azathioprine treatment in multiple sclerosis. Lancet 338:1051–1055

    Google Scholar 

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Based on the Charcot lecture given to the International Federation of Multiple Sclerosis Societies, Amsterdam, October 1991

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McDonald, W.I. The dynamics of multiple sclerosis. J Neurol 240, 28–36 (1993). https://doi.org/10.1007/BF00838443

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