, Volume 18, Issue 6, pp 265–290 | Cite as

The sad plight of multiple sclerosis research (low on fact, high on fiction): critical data to support it being a neurocristopathy

  • Peter O. Behan
  • Abhijit Chaudhuri
Research Article


The literature for evidence of autoimmunity in multiple sclerosis (MS) is analysed critically. In contrast to the accepted theory, the human counterpart of the animal model experimental autoimmune demyelinating disease, experimental allergic encephalomyelitis (EAE), is not MS but a different demyelinating disorder, i.e. acute disseminated encephalomyelitis and acute haemorrhagic leucoencephalitis. Extrapolation of EAE research to MS has been guided largely by faith and a blind acceptance rather than sound, scientific rationale. No specific or sensitive immunological test exists that is diagnostic of MS despite the extensive application of modern technology. Immunosuppression has failed to have any consistent effect on prognosis or disease progression. The available data on MS immunotherapy are conflicting, at times contradictory and are based on findings in animals with EAE. They show predominantly a 30% effect in relapsing/remitting MS which suggests powerful placebo effect. Critical analysis of the epidemiological data shows no association with any specific autoimmune diseases, but does suggest that geographic factors and age at development posit an early onset possibly dependent on environmental influences. Certain neurological diseases are, however, found in association with MS, namely hypertrophic peripheral neuropathy, neurofibromatosis-1, cerebral glioma, glioblastoma multiforme and certain familial forms of narcolepsy. These share a common genetic influence possibly from genes on chromosome 17 affecting cell proliferation. A significant number of these disorders are of neural crest origin, the classical example being abnormalities of the Schwann cell. These and other data allow us to propose that MS is a developmental neural crest disorder, i.e. a cristopathy, implicating glial cell dysfunction with diffuse blood–brain barrier breakdown. The data on transcription factor SOX10 mutations in animals may explain these bizarre clinical associations with MS and the phenotypic variability of such alterations (Cossais et al. 2010). Research directed to the area of neural crest associations is likely to be rewarding.


Multiple sclerosis Neurocristopathies Neurodegenerative disorders Peripheral neuropathies Genetics Therapeutics Immunosuppressives Immunomodulation Autoimmunity 



Acute disseminated encephalomyelitis


Acute haemorrhagic leucoencephalomyelitis


Central nervous system


Experimental allergic encephalomyelitis


Histocompatibility antigen (human leucocyte antigen)


Multiple sclerosis


Major histocompatibility complex


Magnetic resonance imaging


Magnetic resonance spectroscopy


Proton magnetic resonance spectroscopic imaging


N-acetyl aspartate


Normal appearing white matter


Peripheral nervous system


Ribonucleic acid



This work was supported by the Sir David and Sir Frederick Barclay Foundation.


  1. Aarli JJ, Mork SJ, Myrseth E et al (1989) Glioblastoma associated with multiple sclerosis: coincidence of induction? Eur Neurol 29:312–316PubMedCrossRefGoogle Scholar
  2. Acar MA, Birch MK, Abbott R, Rosenthal AR (1993) Chronic granulomatous anterior uveitis associated with multiple sclerosis. Graefes Arch Clin Exp Opthalmol 231:166–168CrossRefGoogle Scholar
  3. Acar G, Tanriover G, Demir N, Kayisli UA, Sati GL, Yaba A, Idiman E, Demir R (2004) Ultrastructural and immunohistochemical similarities of two distinct entities; multiple sclerosis and hereditary motor sensory neuropathy. Acta Histochem 106(5):363–371PubMedCrossRefGoogle Scholar
  4. Adams RD (1959) A comparison of the morphology of the human demyelinating diseases and experimental “allergic encephalomyelitis”. In: Kies MW, Alvord EC (eds) “Allergic” encephalomyelitis, chap 5. Charles C Thomas, Washington, DC, pp 183–209Google Scholar
  5. Adams CWM (1977) Pathology of multiple sclerosis: progression of the lesion. Br Med Bull 3:15–20Google Scholar
  6. Adams CWM (1989) Histology and cellular features of multiple sclerosis. In: A colour atlas of multiple sclerosis and other myelin disorders. Wolfe Medical Pubs Ltd, London, pp 130–139Google Scholar
  7. Adams RD, Sidman RL (1968) The glial cells and their pathological reactions. In: Introduction to neuropathology. McGraw-Hill, New York, p 33Google Scholar
  8. Adams RD, Sidman RL (1968) Introduction to neuropathology. McGraw-Hill, New York, p 34Google Scholar
  9. Adams CWM, Poston RN, Buk SJ et al (1985) Inflammatory vasculitis in multiple sclerosis. J Neurol Sci 69:269–283PubMedCrossRefGoogle Scholar
  10. Aihara N, Tanno H, Hall JJ et al (1994) Immunocytochemical localisation of immunoglobulins in the rat brain: relationship to the blood-brain barrier. J Comp Neurol 342:481–496PubMedCrossRefGoogle Scholar
  11. Aita FJ, Snyder HD, Reichl W (1974) Myasthenia gravis and multiple sclerosis: an unusual combination of diseases. Neurology 24:72–75PubMedGoogle Scholar
  12. Alfonso S, Roquer J, Pou A (1996) Multiple sclerosis and neurofibromatosis 1. Neurologia 11(6):233–235 (in Spanish)PubMedGoogle Scholar
  13. Almsaddi M, Bertorini TE, Seltzer WK (1998) Demyelinating neuropathy in a patient with multiple sclerosis and genotypical HMSN-1. Neuromusc Dis 8:87–89PubMedCrossRefGoogle Scholar
  14. Alter M, Sawyer GT, Latham K (1970) The frequency of diabetes mellitus in families of patients with multiple sclerosis. Neurology 20:619–621PubMedGoogle Scholar
  15. Amato MP, Ponziani G, Bartolozzi ML et al (1999) A prospective study on the natural history of multiple sclerosis: clues to the conduct and interpretation of clinical trials. J Neurol Sci 168:96–106PubMedCrossRefGoogle Scholar
  16. Antel JP, Arnason BGW, Medof ME (1979) Suppressor cell function in multiple sclerosis; correlation with clinical disease activity. Ann Neurol 5:338–349PubMedCrossRefGoogle Scholar
  17. Antel JP, Nicholas MK, Bania MB et al (1986) Comparison of T8+ cell-mediated suppressor and cytotoxic functions in multiple sclerosis. J Neuroimmunol 12:215–224PubMedCrossRefGoogle Scholar
  18. Argyrakis A (1980) Ultrastructural changes in peripheral nerves in multiple sclerosis and subacute sclerosing panencephalitis. In: Bauer HJ, Poser S, Ritter G (eds) Progress in multiple sclerosis research. Springer, Berlin, pp 360–364Google Scholar
  19. Arnold DL, Reiss GT, Matthews PM et al (1994) Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis. Ann Neurol 36:76–82PubMedCrossRefGoogle Scholar
  20. Arstila AU, Riekkinen PJ, Rinne UK et al (1973) Studies of the pathogenesis of multiple sclerosis. Participation of lysosomes in demyelination in the CNS white matter. Europ Neurol 9:1–21PubMedCrossRefGoogle Scholar
  21. Aubert L, Arroyo H, Dumas B et al (1968) Un can d’association entre sclerose en plaques et glioblastome cerebral. Rev Neurol 119:374–376PubMedGoogle Scholar
  22. Aujeszky A (1900) Ueber Immunisirung gegen Wut mit normaler Nervensubstanz. Centralbl Bakt Jena 27:5–10Google Scholar
  23. Baker D, Rosenwasser OA, O’Neil JK et al (1995) Genetic analysis of experimental allergic encephalomyelitis in mice. J Immunol 155:4046–4051PubMedGoogle Scholar
  24. Baranzini SE, Mudge J, van Velkinburgh JC et al (2010) Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature 464(7293):1351–1356PubMedCrossRefGoogle Scholar
  25. Barnard RO, Geddes JF (1987) The incidence of multifocal cerebral gliomas. Cancer 60:1519–1531PubMedCrossRefGoogle Scholar
  26. Barnard RO, Jellinek EH (1967) Multiple sclerosis with amyotrophy complicated by oligodendroglioma. J Neurol Sci 5:441–455PubMedCrossRefGoogle Scholar
  27. Bartt RE (2006) Multiple sclerosis, natalizumab therapy, and progressive multifocal leukoencephalopathy. Curr Opin Neurol 19:341–349PubMedCrossRefGoogle Scholar
  28. Bassoe P, Grinker RR (1930) Human rabies and rabies vaccine encephalomyelitis: a clinicopathological study. Arch Neurol Psychiatry 23:1138–1160Google Scholar
  29. Beaulieu C, Allen PS (1994) Determinants of anisotropic water diffusion in nerves. Magn Reson Med 31:394–400PubMedCrossRefGoogle Scholar
  30. Beecher HK (1955) The powerful placebo. JAMA 159:1602–1606Google Scholar
  31. Behan PO (1980) Dorsal column stimulation in multiple sclerosis. BMJ 2:1287–1288Google Scholar
  32. Behan PO, Currie S (1978) Acute disseminated encephalomyelitis. In: Clinical neuroimmunology, chap 4. Saunders, London, pp 49–61Google Scholar
  33. Behan PO, Haniffah BAG (1994) The genetics of myasthenia gravis. In: Lisak RP (ed) Handbook of myasthenia gravis and myasthenic syndromes. Marcel Dekker Inc, pp 165–191Google Scholar
  34. Behan PO, Geshwind N, Lamarche JB et al (1968) Delayed hypersensitivity to encephalitogenic protein in disseminated encephalitis. Lancet ii:1009–1012Google Scholar
  35. Behan PO, Behan WMH, Feldman RG et al (1972) Cell-mediated hypersensitivity to neural antigens. Arch Neurol 27:145–152PubMedGoogle Scholar
  36. Behan PO, Kies MW, Lisak RP et al (1973) Immunologic mechanisms in experimental encephalomyelitis in non-human primates. Arch Neurol 29:4–9PubMedGoogle Scholar
  37. Behan PO, Melville ID, Durward WF et al (1976) Transfer-factor therapy in multiple sclerosis. Lancet i:988–990Google Scholar
  38. Behan PO, Chaudhuri A, Roep BO (2002) The pathogenesis of multiple sclerosis revisited. J R Coll Physicians Edinb 32:244–265Google Scholar
  39. Bell J, Lathrop G (1996) Multiple loci for multiple sclerosis. Nat Genet 13:377–378PubMedCrossRefGoogle Scholar
  40. Ben-Nun A, Liblau RS, Cohen L et al (1991) Restricted T-cell receptor gene usage by myelin basic protein-specific T-cell clones in multiple sclerosis. Predominant genes vary in individuals. Proc Natl Acad Sci USA 88:2466–2470PubMedCrossRefGoogle Scholar
  41. Berger JR, Sheremata WA, Resnick L et al (1989) Multiple sclerosis-like illness occurring with human immunodeficiency virus infection. Neurology 39:324–329PubMedGoogle Scholar
  42. Betemps EJ, Buncher CR (1993) Birthplace as a risk factor in motor neurone disease and Parkinson’s disease. Int J Epidemiol 22(5):898–904PubMedCrossRefGoogle Scholar
  43. Betters E, Liu Y, Kjaeldgaard A, Sundström E, García-Castro MI (2010) Analysis of early human neural crest development. Dev Biol 344(2):578–592Google Scholar
  44. Bielekova B, Richert N, Howard T, Blevins G, Markovic-Plese S, McCartin J, Frank JA, Würfel J, Ohayon J, Waldmann TA, McFarland HF, Martin R (2004) Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon β. Proc Natl Acad Sci USA 101:8705–8708PubMedCrossRefGoogle Scholar
  45. Bjartmar C, Kinkel RP, Kidd G et al (2001) Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57:1248–1252PubMedGoogle Scholar
  46. Boyazis RM, Martin L, Bouteille M et al (1968) Images histochimiques et ultrastructurales dans un cas de sclerose en plaques associee a un spongioblastome. Riv Pat Nerv Ment 88:1–20Google Scholar
  47. Brain W, Wilkinson M (1957) The association of cervical spondylosis and disseminated sclerosis. Brain 80:456–478PubMedCrossRefGoogle Scholar
  48. Brandt S, Gyldensted C, Offner H et al (1981) Multiple sclerosis with onset in a two-year old boy. Neuropaediatrics 12(1):75–82CrossRefGoogle Scholar
  49. Breger BC, Leopold IH (1966) The incidence of uveitis in multiple sclerosis. Am J Opthalmol 62:540–545Google Scholar
  50. Brihaye J, Perier O, Stenuit J (1963) Multiple sclerosis associated with a cerebral glioma. J Neuropath Exp Neurol 22:128–137PubMedCrossRefGoogle Scholar
  51. Brinkman CJJ, Nillesen WM, Hommes OR et al (1982) Cell-mediated immunity in multiple sclerosis as determined by sensitivity of different lymphocyte populations to various brain tissue antigens. Ann Neurol 11:450–455PubMedCrossRefGoogle Scholar
  52. Broadley SA, Deans J, Sawcer SJ et al (2000) Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey. Brain 123:1102–1111PubMedCrossRefGoogle Scholar
  53. Burgerman R, Rigaminto E, Randle JM et al (1992) The association of cervical spondylosis and multiple sclerosis. Surg Neurol 38:265–270PubMedCrossRefGoogle Scholar
  54. Burns J, Rosenweig A, Zweiman B et al (1983) Isolation of myelin basic protein-reactive T-cell lines from normal human blood. Cell Immunol 81:435–440PubMedCrossRefGoogle Scholar
  55. Calabresi PA (2002) Considerations in the treatment of relapsing-remitting multiple sclerosis. Neurology 58(Suppl 4):S10–S22PubMedGoogle Scholar
  56. Cannella B, Pitt D, Marchionni M et al (1999) Neuregulin and erbB receptor expression in normal and diseased human white matter. J Neuroimmunol 100(1–2):233–242PubMedCrossRefGoogle Scholar
  57. Cardoso F, Jankovic J (1995) Peripherally induced tremor and parkinsonism. Arch Neurol 52:263–270PubMedGoogle Scholar
  58. Carson KR, Focosi D, Major EO et al (2009) Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) project. Lancet Oncol 10:816–824PubMedCrossRefGoogle Scholar
  59. Chataway J, Mander A, Robertson N et al (2001) Multiple sclerosis in sibling pairs: an analysis of 250 families. J Neurol Neurosurg Psychiatry 71:757–761PubMedCrossRefGoogle Scholar
  60. Chaudhuri A, Behan PO (2001) Acute cervical hyperextension-hyperflexion injury may precipitate and/or exacerbate symptomatic multiple sclerosis. Eur J Neurol 8:659–664PubMedCrossRefGoogle Scholar
  61. Chaudhuri A, Behan PO (2004) Multiple sclerosis is not an autoimmune disease. Arch Neurol 61:1610–1612PubMedCrossRefGoogle Scholar
  62. Chaudhuri A, David K (2009) Behan Po. Cervical cord demyelination due to physical trauma. J Neurol Sci 285(S1):S155–S339Google Scholar
  63. Clarke M, Alderson P, Chalmers I (2002) Discussion sections in reports of controlled trials published in general medical journals. JAMA 287:2799–2801PubMedCrossRefGoogle Scholar
  64. Cohen JA, Lisak RP (1987) Acute disseminated encephalomyelitis. In: Aarli JA, Behan WMH, Behan PO (eds) Clinical neuroimmunology, vol 15. Blackwell, Oxford, pp 192–213Google Scholar
  65. Coles A, Compston DA et al (2008) (The CAMMS223 Trial Investigators) alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359:1786–1801PubMedCrossRefGoogle Scholar
  66. Compston A (1998) Treatment and management of multiple sclerosis. In: Compston A, Ebers G, Lassmann H et al (eds) McApline’s multiple sclerosis. Churchill Livingstone, Edinburgh, pp 437–498Google Scholar
  67. Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231PubMedCrossRefGoogle Scholar
  68. Confavreux C, Vukusic S, Moreau T et al (2000) Relapses and progression of disability in multiple sclerosis. N Eng J Med 343:1430–1438CrossRefGoogle Scholar
  69. Confraveux C (2002) Relapses, progression, inflammation and neurodegeneration in multiple sclerosis: a changing view. Adv Clin Neurosci Rehabil 2(1):7–9Google Scholar
  70. Cook SD, Devereux C, Troiano R et al (1986) Effect of total lymphoid irradiation in chronic progressive multiple sclerosis. Lancet 1:1405–1409PubMedCrossRefGoogle Scholar
  71. Cook SD, Devereux C, Troiano R et al (1987) Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course. Ann Neurol 22:634–638PubMedCrossRefGoogle Scholar
  72. Cook SD, Troiano R, Zito G et al (1989) Deaths after total lymphoid irradiation for multiple sclerosis. Lancet 2:277–278PubMedCrossRefGoogle Scholar
  73. Cook SD, Devereux C, Triano R et al (1995) Combination total lymphoid irradiation and low dose corticosteroid therapy for progressive multiple sclerosis. Acta Neurol Scand 91:22–27PubMedGoogle Scholar
  74. Cossais F, Wahlbuhl M, Kriesch J, Wegner M (2010) SOX10 structure-function analysis in the chicken neural tube reveals important insights into its role in human neurocristopathies. Hum Mol Genet 19(12):2409–2420PubMedCrossRefGoogle Scholar
  75. Costa MF, Novis SAP, Filho PN et al (2000) Esclerose Multipla, Ependimoma Medular E Meningioma Intracraniano. Arq Neuropsiquiatr 58(4):1133–1137PubMedGoogle Scholar
  76. Currie S, Urich H (1974) Concurrence of multiple sclerosis and glioma. J Neurol Neurosurg Psychiatry 37:598–605PubMedCrossRefGoogle Scholar
  77. Davie CA, Barker GJ, Webb S et al (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118:1583–1592PubMedCrossRefGoogle Scholar
  78. Dawson J (1916) The histology of disseminated sclerosis. Trans R Soc Edinb 50:517–540Google Scholar
  79. De Caso R (2000) Esclerose Multipla, ependimoma medular e meningioma intracraniano. Arq Neuropsiquiatr 58:1133–1137Google Scholar
  80. Devereux CK, Vidaver R, Hafstein MP et al (1988) Total lymphoid irradiation for multiple sclerosis. Int J Radiat Oncol Biol Phys 14:197–203PubMedGoogle Scholar
  81. Dhib-Jalbut S (2002) Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology 58(Suppl 4):S3–S9PubMedGoogle Scholar
  82. Edwards LJ, Constantinescu CS (2004) A prospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic. Mult Scler 10:575–581PubMedCrossRefGoogle Scholar
  83. Eisen A, Yufe R, Trop D et al (1978) Reduced neuromuscular transmission safety factor in multiple sclerosis. Neurology 28:498–602Google Scholar
  84. Eisen A, Paty D, Hoirch M (1982) Altered supernormality in multiple sclerosis peripheral nerve. Muscle Nerve 5:411–414PubMedCrossRefGoogle Scholar
  85. Engelhardt JI, Tajti J, Appel SH (1993) Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch Neurol 50:30–36PubMedGoogle Scholar
  86. Esiri MM, Gay D (1997) The immunocytochemistry of multiple sclerosis plaques. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenic basis. Chapman & Hall, London, pp 173–186Google Scholar
  87. Espicom Business Intelligence Ltd (2008) CNS drug discoveries: multiple sclerosis chapter. Espicom Business Intelligence Ltd., p 128. Accessed 01 May 2009
  88. Evangelou N, Esiri MM, Smith S et al (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 47:391–395PubMedCrossRefGoogle Scholar
  89. Feigen I (1969) Mesenchymal tissues of the nervous system, the indigenous origin of brain macrophages in hypoxic states and in multiple sclerosis. J Neuropathol Exp Neurol 28:6–23CrossRefGoogle Scholar
  90. Feigen I, Ogata J (1971) Schwann cells and peripheral myelin within human central nervous tissues: the mesenchymal character of Schwann cells. J Neuropathol Exp Neurol 30:603–612CrossRefGoogle Scholar
  91. Ferner RE, Chaudhuri R, Bingham J et al (1993) MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry 56:492–495PubMedCrossRefGoogle Scholar
  92. Ferner RE, Hughes RAC, Johnson MR (1995) Neurofibromatosis1 and multiple sclerosis. J Neurol Neurosurg Psychiatry 58:582–585PubMedCrossRefGoogle Scholar
  93. Feuillet L, Boudinet H, Casseron W, Uzenot D, Pelletier J, Ali Cherif A (2004) Multiple sclerosis associated with neurofibromatosis type I. Rev Neurol 160(4 Pt 1):447–451 (in French)Google Scholar
  94. Fillipi M, Rocca MA, Minicucci L et al (1999) Magnetization transfer imaging of patients with definite MS and negative conventional MRI. Neurology 52:845–848Google Scholar
  95. Fillipi M, Cercignani M, Inglese M et al (2001) Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology 56:304–311Google Scholar
  96. Frasson E, Polo A, Di Summa A, Fabrizi GM, Taioli F, Fiaschi A, Rizzuto N, Moretto G (1997) Multiple sclerosis associated with duplicated CMT1A: a report of two cases. J Neurol Neurosurg Psychiatry 63(3):413–414PubMedCrossRefGoogle Scholar
  97. Freedman MS, Muth KL, Trotter JL et al (1992) Prospective serial analysis of interleukin-2 receptor in relapsing-remitting multiple sclerosis. Neurology 42:1596–1601PubMedGoogle Scholar
  98. Freund J, Stern ER, Pisani TM (1947) Isoallergic encephalomyelitis and radiculitis in guinea pigs after one injection of brain and mycobacteria in water-in-oil emulsion. J Immunol 57:179–194PubMedGoogle Scholar
  99. Fritz RB, Skeen MJ, Jen-Chou CH et al (1985) Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J Immunol 134:2328–2332PubMedGoogle Scholar
  100. Fu L, Matthews PM, De Stefano N et al (1998) Imaging axonal damage in the normal appearing white matter in multiple sclerosis. Brain 121:103–113PubMedCrossRefGoogle Scholar
  101. Ganter P, Prince C, Esiri MM (1999) Spinal cord axonal loss in multiple sclerosis: a post-mortem study. Neuropathol Appl Neurobiol 25:459–467PubMedCrossRefGoogle Scholar
  102. Gibbs E, Tremlett H, Ball N, Hasimoto S (2008) Malignant melanoma in a multiple sclerosis patient with persistent neutralising antibodies to interferon-beta. Eur J Neurol 15:e4PubMedCrossRefGoogle Scholar
  103. Glanzmann E (1927) Die Nervosen Komplicationen der Varizellen der Variola und Vakzine. Schweiz Med Wochenschr 57:145–154Google Scholar
  104. Gonen O, Catalaa I, Babb JS et al (2000) Total brain N-acetylaspartate: a new measure of disease load in multiple sclerosis. Neurology 54:15–19PubMedGoogle Scholar
  105. Graham DI, Behan PO, More IAR (1979) Brain damage complicating septic shock. J Neurol Neurosurg Psychiatry 42:19–28PubMedCrossRefGoogle Scholar
  106. Greve B, Simonenko R, Illes Z, Peterfalvi A, Hamdi N, Mycko MP, Selmaj KW, Rozsa C, Rajczy K, Bauer P, Berger K, Weissert R (2008) Multiple sclerosis and the CTLA4 autoimmunity polymorphism CT60: no association in patients from Germany, Hungary and Poland. Mult Scler 14:153–158PubMedCrossRefGoogle Scholar
  107. Griffin WST (2008) Perispinal etanercept: potential as an Alzheimer therapeutic. J Neuroinflammation 5:3PubMedCrossRefGoogle Scholar
  108. Griffin JW, Sheikh K (1999) Schwann cell-axon interactions in Charcot-Marie-Tooth disease. Ann N Y Acad Sci 883:77–90PubMedCrossRefGoogle Scholar
  109. Guilhoto LMRR, Osorio CAM, Machado LB (1995) Paediatric multiple sclerosis report of 14 cases. Brain Dev 17:9–12PubMedGoogle Scholar
  110. Gulcher JR, Vartanian T, Stefansson K (1994) Is multiple sclerosis an autoimmune disease? Clin Neurosci 2:246–252PubMedGoogle Scholar
  111. Guo AC, Petrella JR, Kurtzberg J et al (2001) Evaluation of white matter anisotropy in Krabbe disease using diffusion tensor MR imaging; initial experience. Radiology 218:809–815PubMedGoogle Scholar
  112. Guo AC, MacFall JR, Provenzale JM (2002) Multiple sclerosis: diffusion tensor MR imaging for evaluation of normal appearing white matter. Radiology 222:729–736PubMedCrossRefGoogle Scholar
  113. Guseo A, Jellinger K (1975) The significance of perivascular infiltrations in multiple sclerosis. J Neurol 211:51–60PubMedCrossRefGoogle Scholar
  114. Hafler DA (2004) Multiple sclerosis. J Clin Invest 113:788–794PubMedGoogle Scholar
  115. Hafler DA, Buchsbaum M, Johnson D et al (1985) Phenotypic and functional analysis of T-cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis. Ann Neurol 18:451–458PubMedCrossRefGoogle Scholar
  116. Haines J et al (1998) Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. Hum Mol Genet 7:1229–1234PubMedCrossRefGoogle Scholar
  117. Hajnal JV, Dornan M, Hall AS et al (1999) Clinical use of diffusion-tensor imaging for diseases causing neuronal and axonal damage. Am J Neuroradiol 20:1044–1048Google Scholar
  118. Hasson J, Terry RD, Zimmerman M (1958) Peripheral neuropathy in multiple sclerosis. Neurology 8(7):503–510PubMedGoogle Scholar
  119. Hauser SL, Dawson DM, Lehrich JR et al (1993) Intensive immunosuppression in progressive multiple sclerosis: a randomised, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Eng J Med 308:173–180CrossRefGoogle Scholar
  120. Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358:676–688PubMedCrossRefGoogle Scholar
  121. Heinzlef O, Alamowitch S, Sazdovitch S et al (1999) Autoimmune disease in families of French patients with multiple sclerosis. Acta Neurol Scand 100:1–5Google Scholar
  122. Hinks LJ, Price SE, Mason CR, Thompson RJ (1995) Single strand conformation analysis of two genes contained within the first intron of the neurofibromatosis type I gene in patients with multiple sclerosis. Neuropathol Appl Neurobiol 21(3):201–207PubMedCrossRefGoogle Scholar
  123. Ho KL, Wolfe DE (1981) Concurrence of multiple sclerosis and primary intracranial neoplasms. Cancer 47:2913–2919PubMedCrossRefGoogle Scholar
  124. Holfield R, Wiendl H (2002) The ups and downs of multiple sclerosis therapeutics. Ann Neurol 49(3):281–284Google Scholar
  125. Hopf HC (1963) Electromyographic study on so-called mononeuritis. Arch Neurol 9:307–312PubMedGoogle Scholar
  126. Hopf HC, Eysholdt M (1978) Impaired refractory periods of peripheral sensory nerves in multiple sclerosis. Ann Neurol 4:499–501PubMedCrossRefGoogle Scholar
  127. Huppi PS, Murphy B, Maier SE et al (2001) Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging. Paediatrics 107:455–460CrossRefGoogle Scholar
  128. Huson SM, Harper PS, Compston DAS (1988) Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales. Brain 111:1355–1381PubMedCrossRefGoogle Scholar
  129. Iannucci G, Tortorella C, Rovaris M et al (2000) Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation. Am J Neuroradiol 21:1034–1038PubMedGoogle Scholar
  130. Ifergan I, Wosik K, Cayrol R, Kébir H, Auger C, Bernard M, Bouthillier A, Moumdjian R, Duquette P, Prat A (2006) Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis. Ann Neurol 60(1):45–55PubMedCrossRefGoogle Scholar
  131. Inglese M, Salvi F, Iannucci G et al (2002) Magnetization transfer and diffusion tensor MR imaging of acute disseminated encephalomyelitis. Am J Neuroradiol 23:267–272PubMedGoogle Scholar
  132. Isaac C, Li DKB, Genton M et al (1998) Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology 38:1511–1515Google Scholar
  133. Isoardo G, Di Vito N, Nobile M, Benetton G, Fassio F (2005a) X-linked Charcot-Marie-Tooth disease and progressive-relapsing central demyelinating disease. Neurology 65(10):1672–1673PubMedCrossRefGoogle Scholar
  134. Isoardo G, Fassio F, Nobile M, DiVito (2005) Charcot-Marie-Tooth disease Type 1X and progressive relapsing multiple sclerosis. A case report. 2005 meeting of the Peripheral Nerve Society July 9–13, 2005. J Peripher Nerv Syst (Suppl 10):36Google Scholar
  135. Jankovic J (1994) Post-traumatic movement disorders: central and peripheral mechanisms. Neurology 44:2006–2014PubMedGoogle Scholar
  136. Jessen KR, Mirsky R (1983) Astrocyte-like glia in the peripheral nervous system: an immunohistochemical study of enteric glia. J Neurosci 3:2206–2218PubMedGoogle Scholar
  137. Johnson DA, Hafler DA, Fallis RJ et al (1986) Cell-mediated immunity to myelin-associated glycoprotein, proteo-lipid protein, and myelin basic protein in multiple sclerosis. J Neuroimmunol 13:99–108PubMedCrossRefGoogle Scholar
  138. Johnson MR, Ferner RE, Bobrow M, Hughes RA (2000) Detailed analysis of the oligodendrocyte myelin glycoprotein gene in four patients with neurofibromatosis 1 and primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 68(5):643–646PubMedCrossRefGoogle Scholar
  139. Johnston BL, Conly JM (2006) Alemtuzumab and natalizumab: the monoclonal antibody story continues. Can J Infect Dis Med Microbiol 17:327–329PubMedGoogle Scholar
  140. Kabat EA, Solf A, Bezer AE (1946) Rapid production of acute disseminated encephalomyelitis in rhesus monkeys by injection of brain tissue with adjuvants. Science 104:362–363CrossRefGoogle Scholar
  141. Kalimo H, Frey H, Raine CS et al (1979) Late-onset malignant astrocytoma in a case of multiple sclerosis. Acta Neuropathol 46:231–234PubMedCrossRefGoogle Scholar
  142. Kalman B, Leist TP (2003) A mitochondrial component of neurodegeneration in multiple sclerosis. Neuromolecular Med 3:147–157PubMedCrossRefGoogle Scholar
  143. Kalman B, Lublin FD (1999) The genetics of multiple sclerosis. A review. Biomed Pharmacother 53(8):358–370PubMedCrossRefGoogle Scholar
  144. Kelly PJ, Shapiro BE (2001) Amyotrophic lateral sclerosis and other motor neurone disorders. In: Bachelor T, Gudkowicz MR (eds) Principles of neuroepidemiology. Butterworth, Boston, pp 265–287Google Scholar
  145. Kirk J, Plumb J, Meenakshi M, McQuaid S (2003) Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination. J Pathol 201:319–327PubMedCrossRefGoogle Scholar
  146. Kurtzke JF, Beebe GW (1980) Epidemiology of amyotrophic lateral sclerosis: 1. A case-control comparison based on ALS deaths. Neurology 30:453–462PubMedGoogle Scholar
  147. Kwon JY, Kim JY, Jeong JH, Park KD (2008) Multiple sclerosis and peripheral multifocal demyelinating neuropathies occurring in a same patient. J Clin Neurol 4(1):51–57PubMedCrossRefGoogle Scholar
  148. Lahl R (1980) Combination of multiple sclerosis and cerebral glioblastoma. Eur Neurol 19:192–197PubMedCrossRefGoogle Scholar
  149. Lamarche JB, Behan PO, Segarra JM et al (1972) Recurrent acute necrotising haemorrhagic encephalopathy. Acta Neuropathol 22:79–87PubMedCrossRefGoogle Scholar
  150. Langer-Gould A, Albers KB, Van Den Eeden SK, Nelson LM (2010) Autoimmune diseases prior to the diagnosis of multiple-sclerosis: a population-based case-control study. Mult Scler 16(7):855–861PubMedCrossRefGoogle Scholar
  151. Lassmann H, Buidka H, Schnaberth G (1981) Inflammatory demyelinating polyradiculitis in a patient with multiple sclerosis. Arch Neurol 38:99–102PubMedGoogle Scholar
  152. Levine S (1971) Relationship of experimental allergic encephalomyelitis to human disease. In: Rowland LP (ed) Immunological disorders of the nervous system. Williams & Wilkins, BaltimoreGoogle Scholar
  153. Levine S, Hoenig EM (1968) Induced localisation of allergic adrenalitis and encephalomyelitis at sites of thermal injury. J Immunol 100(6):1310–1318PubMedGoogle Scholar
  154. Lightman S, McDonald WI, Bird AC et al (1987) Retinal venous sheathing in optic neuritis. Its significance for the pathogenesis of multiple sclerosis. Brain 110:405–414PubMedCrossRefGoogle Scholar
  155. Likosky WH, Fireman B, Elmore R et al (1991) Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study. J Neurol Neurosurg Psychiatry 54:1055–1060PubMedCrossRefGoogle Scholar
  156. Lucchinetti CF, Brueck W, Rodriguez M et al (1998) Multiple sclerosis: lessons from neuropathology. Semin Neurol 18:337–345PubMedCrossRefGoogle Scholar
  157. Lumsden CE (1955) Pathology of multiple sclerosis and allied demyelinating diseases. In: McAlpine D, Compston ND, Lumsden CE (eds) Multiple sclerosis. Livingstone, Edinburgh, pp 208–293Google Scholar
  158. Lumsden C (1970) The neuropathology of multiple sclerosis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology. Vol. 9. Multiple sclerosis and other demyelinating diseases. North Holland, Amsterdam, pp 217–309Google Scholar
  159. Lynch PG (1974) Multiple sclerosis and malignant gliomas. BMJ 3:577Google Scholar
  160. Majoie CB, Akkerman EM, Blank C et al (2002) Mitochondrial encephalomyopathy: comparison of conventional MR imaging with diffusion-weighted and diffusion tensor imaging: case report. Am J Neuroradiol 23:13–16Google Scholar
  161. Malmgren RM, Detels R, Verity MA (1984) Co-occurrence of multiple sclerosis and glioma—case report and neuropathologic and epidemiologic review. Clin Neuropathol 3(1):1–9PubMedGoogle Scholar
  162. Martin R, McFarland HF (1997) Immunology of multiple sclerosis and experimental allergic encephalomyelitis. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis. Chapman & Hall, London, pp 221–239Google Scholar
  163. Martin R, Voskuhl R, Flerlage M et al (1993) Myelin basic protein-specific T-cell responses in identical twins discordant or concordant for multiple sclerosis. Ann Neurol 34:524–535PubMedCrossRefGoogle Scholar
  164. Masson C, Colombani JM (1997) Neurofibromatosis 1 and multiple sclerosis. Apropos of a case. Rev Neurol 153(11):684–686 (in French)Google Scholar
  165. Mathews T, Moosy J (1972) Mixed glioma, multiple sclerosis & Charcot-Marie-Tooth disease. Arch Neurol 27:263–268PubMedGoogle Scholar
  166. Matthew PM, De Stefano N, Narayanan S et al (1998) Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin Neurol 18:327–336CrossRefGoogle Scholar
  167. Matthews WB (1962) Epilepsy and disseminated sclerosis. Q J Med 31:141–155PubMedGoogle Scholar
  168. Mayor S (2002) Researchers claim clinical trials are reported with misleading statistics. BMJ 324:1353CrossRefGoogle Scholar
  169. McDonald WI et al (2001) Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127PubMedCrossRefGoogle Scholar
  170. McGrath J (2001) Does ‘imprinting’ with low prenatal vitamin D contribute to the risk of various adult disorders? Med Hypotheses 56(3):367–371PubMedCrossRefGoogle Scholar
  171. McGuinness MC, Smith KD (1999) Cerebral inflammation in X-linked adrenoleukodystrophy (review). Arch Immunol Ther Exp 47(5):281–187Google Scholar
  172. McNair Scott TF (1967) Post-infectious and vaccinial encephalitis. In: Sweeney FJ Jr (Ed) Medical clinics of North America, vol 51, chap 14. W.B. Saunders, Philadelphia, pp 701–717Google Scholar
  173. Metz LM, Zhang Y, Yeung M, Patry DG, Bell RB, Stoian CA, Yong VW, Patten SB, Duquette P, Antel JP, Mitchell JR (2004) Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 55:756PubMedCrossRefGoogle Scholar
  174. Mills KR, Murray NM (1986) Neurophysiological evaluation of associated demyelinating peripheral neuropathy and multiple sclerosis: a case report. J Neurol Neurosurg Psychiatry 49:320–323PubMedCrossRefGoogle Scholar
  175. Mittler RS, Foell J, McCausland M, Strahotin S, Niu L, Bapat A, Hewes LB (2004) Anti-CD137 antibodies in the treatment of autoimmune disease and cancer. Immunol Res 29:197–208PubMedCrossRefGoogle Scholar
  176. Moreau T, Thorpe J, Miller D et al (1994) Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis. Lancet 344:298–301; erratum 486Google Scholar
  177. Morris HW, Moriabadi NF, Lees AJ et al (1998) Parkinsonism following electrical injury to the hand. Mov Disord 13(3):600–602PubMedCrossRefGoogle Scholar
  178. Mullen JT, Vartainan TK, Atkins MB (2008) Melanoma complicating treatment with natalizumab for multiple sclerosis. N Eng J Med 358:647–648CrossRefGoogle Scholar
  179. Munch-Peterson CJ (1949) Case of disseminated sclerosis and glioma of the brain in the same patient. Acta Psychiat Neurol Scand 24:599–605CrossRefGoogle Scholar
  180. Nahser HC, Vieregge P, Nau HE et al (1986) Coincidence of multiple sclerosis and glioma. Surg Neurol 26:45–51PubMedCrossRefGoogle Scholar
  181. Narayana PA, Doyle TJ, Lai D et al (1998) Serial proton magnetic resonance spectroscopy imaging, contrast enhanced magnetic resonance imaging and quantitative lesion volumetry in multiple sclerosis. Ann Neurol 43:56–71PubMedCrossRefGoogle Scholar
  182. Noble LJ, Wrathall JR (1989) Distribution and time course of protein extravasation in the rat spinal cord after contusive injury. Brain Res 482:57–66PubMedCrossRefGoogle Scholar
  183. Noseworthy JH (1999) Progress in determining the causes and treatment of multiple sclerosis. Nature 399:A40–A47PubMedGoogle Scholar
  184. O’Riordan JI, Thompson AJ, Kingsley DP et al (1998) The prognostic value of brain MRI in clinically isolated syndromes of the CNS: a 10-year follow-up. Brain 121:495–503PubMedCrossRefGoogle Scholar
  185. Okun MR, Bowman T (1999) Mitotic and amitotic cell replication in malignant melanoma: the role of subdivisional cell replication. Speculations Sci Technol 21:321–328CrossRefGoogle Scholar
  186. Okun MR, Edelstein LM (1967) Cell reproduction by subdivision? Lancet 1:1056–1057CrossRefGoogle Scholar
  187. Oldendorf WH, Cornford EM (1997) A comparison of total body and local spinal cord irradiation in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 36:50–61CrossRefGoogle Scholar
  188. Oppenheimer DR (1969) Acute encephalopathy in children. In: Whitty CWM, Hughes JT, MacCallum FO (eds) Virus diseases and the nervous system. Blackwell, OxfordGoogle Scholar
  189. Oppenheimer DR (1978) The cervical spine in multiple sclerosis. Neuropathol Appl Neuobiol 4:151–162CrossRefGoogle Scholar
  190. Pál E, Gömöri EE, Gáti I (2001) Neurofibromatosis and glioblastoma in a case of multiple sclerosis. Eur J Neurol 8(6):717–718PubMedCrossRefGoogle Scholar
  191. Palo J, Duchesne J, Wikstrom J (1977) Malignant disease among patients with multiple sclerosis. J Neurol 216:217–222PubMedCrossRefGoogle Scholar
  192. Parman Y, Ciftci F, Poyraz M, Halefoglu AM, Oge AE, Eraksoy M, Saruhan-Direskeneli G, Deymeer F, Battaloglu E (2007) X-linked Charcot-Marie-Tooth disease and multiple sclerosis. J Neurol 254((7):953–955PubMedCrossRefGoogle Scholar
  193. Paterson PY (1987) Neuroimmunology: an overview and personal perspective. In: Aarli JA, Behan WMH, Behan PO (eds) Clinical neuroimmunology. Blackwell, Oxford, pp 3–25Google Scholar
  194. Perilongo G, Moras P, Carollo C et al (1999) Spontaneous partial regression of low-grade glioma in children with neurofibromatosis-1: a real possibility. J Child Neurol 14:352–356PubMedCrossRefGoogle Scholar
  195. Perini P, Gallo P (2001) The range of multiple sclerosis associated with neurofibromatosis type 1. J Neurol Neurosurg Psychiatry 71(5):679–681PubMedCrossRefGoogle Scholar
  196. Peterson K, Rosenblum MK, Powers JM et al (1993) Effect of brain irradiation on demyelinating lesions. Neurology 43:2105–2112PubMedGoogle Scholar
  197. Pezeshkpour GH, Dalakas MC (1988) Long-term changes in the spinal cords of patients with old poliomyelitis. Arch Neurol 45:505–508PubMedGoogle Scholar
  198. Pierpaoli C, Jezzard P, Basser PJ et al (1996) Diffusion tensor MR imaging of the human brain. Radiology 201:637–648PubMedGoogle Scholar
  199. Pollock M, Calder C, Allpress S (1977) Peripheral nerve abnormality in multiple sclerosis. Ann Neurol 2:41–48PubMedCrossRefGoogle Scholar
  200. Popovich PG, Stokes BT, Whitacre CC (1996) Concept of autoimmunity following spinal cord injury: possible roles for T lymphocytes in the traumatised central nervous system. J Neurosci Res 45:349–363PubMedCrossRefGoogle Scholar
  201. Poser CM (1987) The peripheral nervous system in multiple sclerosis. A review and pathogenetic hypothesis. J Neurol Sci 79((1-2)):83–90PubMedCrossRefGoogle Scholar
  202. Poser CM (2000) Trauma to the central nervous system may result in formation or enlargement of multiple sclerosis plaques. Arch Neurol 57:1074–1076PubMedCrossRefGoogle Scholar
  203. Prineas J (1975) Pathology of the early lesion in multiple sclerosis. Hum Pathol 6:531–554PubMedCrossRefGoogle Scholar
  204. Prineas JW (1985) The neuropathology of multiple sclerosis. In: Koetsier JC (ed) Handbook of clinical neurology, vol 47. Elsevier, Amsterdam, pp 213–257Google Scholar
  205. Prineas JW, Kwon EE, Sternberger NH et al (1984) The distribution of myelin-associated glycoprotein and myelin basic protein in actively demyelinating multiple sclerosis lesions. J Neuroimmunol 6:251–264PubMedCrossRefGoogle Scholar
  206. Puri BK, Bydder GM, Chaudhuri KR, Al Saffar BY, Curati WL, White SJ, Mitchell L, Hajnal JV, Horrobin DF (2001) MRI changes in multiple sclerosis following treatment with iofepramine and l-phenylalanine. Neuroreport 12:1821–1824PubMedCrossRefGoogle Scholar
  207. Purmann J, Arendt G, Cleveland S, Borchard F, Fürst W, Gemsa R, Bertrams J, Hengels KJ (1992) Association of Crohn’s disease and multiple sclerosis. Is there a common background? J Clin Gastroenterol 14:43–46CrossRefGoogle Scholar
  208. Quan D, Kleinschmidt-DeMasters BK (2005) A 71-year-old male with 4 decades of symptoms referable to both central and peripheral nervous system. Brain Pathol 15(4):369–370, 373Google Scholar
  209. Quan D, Kleinschmidt-DeMasters BK (2005b) Case of the month: May 2005. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with onion bulb formation in hypertrophic nerves and coexistent multiple sclerosis (MS). Brain Pathol 15(4):369–370PubMedCrossRefGoogle Scholar
  210. Quan D, Pelak VS, Tanabe J, Durairaj V, Kleinschmidt-DeMasters BK (2005) Symptomatic spinal and cranial hypertrophic neuropathy in multiple sclerosis. Muscle Nerve 6:772–779CrossRefGoogle Scholar
  211. Quattrocchi KB, Frank EH, Miller CE et al (1990) Suppression of cellular immune activity following severe head injury. J Neurotrauma 7(2):77–87PubMedCrossRefGoogle Scholar
  212. Quinn S (2001) Human trials. Scientists, investors and patients in the quest for a cure. Perseus Publishing, CambridgeGoogle Scholar
  213. Raine CS (1994) The Dale E. McFarlin memorial lecture: the immunology of the multiple sclerosis lesion. Ann Neurol 36:S61–S72PubMedCrossRefGoogle Scholar
  214. Rajabally YA, Abbott RJ (2005) Charcot-Marie-Tooth disease due to the Thr124Met mutation in the myelin protein zero gene associated with multiple sclerosis. J Peripher Nerv Syst 10(4):388–389PubMedCrossRefGoogle Scholar
  215. Ransohoff RM (2007) Natalizumab for multiple sclerosis. N Engl J Med 356:2622–2629PubMedCrossRefGoogle Scholar
  216. Ratner N, Daston MM (2001) Genetic and cellular mechanisms of Schwann cell tumour formation: neurofibromatosis type 1 and neurofibromatosis type 2. In: Jessen KR, Richardson WD (eds) Glial cell development, 2nd edn. Oxford University Press, Oxford, pp 355–378Google Scholar
  217. Reagan TJ, Frieman IS (1973) Multiple cerebral gliomas in multiple sclerosis. J Neurol Neurosurg Psychiatry 36:523–528PubMedCrossRefGoogle Scholar
  218. Remlinger P (1928) Les paralysies du traitement antirabique. Ann Inst Pasteur Lille 42(Suppl 71)Google Scholar
  219. Revesz T, Kidd D, Thompson AJ et al (1994) Comparison of the pathology of primary and secondary progression of multiple sclerosis. Brain 117:759–765PubMedCrossRefGoogle Scholar
  220. Rice GPA, Incorvaia B, Munari L et al (2002) Interferon in relapsing-remitting multiple sclerosis (Cochrane review). In: The Cochrane library 1. Update Software, OxfordGoogle Scholar
  221. Richert JR, McFarlin DE, Rose JW et al (1983) Expansion of antigen-specific T-cells from cerebrospinal fluid of patients with multiple sclerosis. J Neuroimmunol 5:317–324PubMedCrossRefGoogle Scholar
  222. Rivers TM, Schwentker FF (1935) Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys. J Exp Med 61:689–702PubMedCrossRefGoogle Scholar
  223. Ro YI, Alexander CB, Oh SJ (1983) Multiple sclerosis and hypertrophic demyelinating peripheral neuropathy. Muscle Nerve 6:312–316PubMedCrossRefGoogle Scholar
  224. Rohowsky-Kochan C, Eiman D, Troiano R et al (1990) Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases. J Neuroimmunol 28:161–166PubMedCrossRefGoogle Scholar
  225. Rosenberg NL, Bourdette D (1983) Hypertrophic neuropathy and multiple sclerosis. Neurology 33:1361–1364PubMedGoogle Scholar
  226. Rovaris M, Viti B, Ciboddo G et al (2000) Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry 68:170–177PubMedCrossRefGoogle Scholar
  227. Rubin M, Karpati G, Carpenter S (1987) Combined central and peripheral myelinopathy. Neurology 37:1287–1290PubMedGoogle Scholar
  228. Russell DS (1955) The neurological unity of acute haemorrhagic leukoencephalitis and acute disseminated encephalomyelitis. Brain 78:369–376PubMedGoogle Scholar
  229. Russell DS, Rubenstein LJ (1977) Pathology of tumours of the nervous system, 4th edn. Arnold, London, p 103, 151f, 240fGoogle Scholar
  230. Scherer JJ (1938) La “Glioblastomatose en plaques”. J Belge Neurol Psychiatr 38:1–17Google Scholar
  231. Scherer JJ (1940) The forms of growth in gliomas and their pathological significance. Brain 63:1–35Google Scholar
  232. Schoene WC, Carpenter S, Behan PO, Geschwind N (1977) ‘Onion bulb’ formations in the central and peripheral nervous system in association with multiple sclerosis and hypertrophic polyneuropathy. Brain 100:755–773PubMedCrossRefGoogle Scholar
  233. Schwentker FF, Rivers TM (1934) The antibody response of rabbits to injections of emulsions and extracts of homologous brain. J Exp Med 60:559–574PubMedCrossRefGoogle Scholar
  234. Scully RE, Galdabani JJ, McNeely BU (1978) Weekly clinicopathological exercise—case 44. N Eng J Med 299:1060–1067CrossRefGoogle Scholar
  235. Seitelberger F (1960) Histochemistry of demyelinating diseases proper including allergic encephalomyelitis and Perlizaeus-Merzbacher’s disease. In: Cummings NJ (ed) Modern scientific aspects of neurology. Edward Arnold, London, pp 146–187Google Scholar
  236. Shakir RA, Hussien JM, Trontelj JJ (1983) Myasthenia gravis and neuromyelitis optica. J Neuroimmunol 4:161–165PubMedCrossRefGoogle Scholar
  237. Shankar SK, Rao TV, Srivastav VK et al (1989) Balo’s concentric sclerosis: a variant of multiple sclerosis associated with oligodendroglioma. Neurosurgery 25(6):982–986PubMedCrossRefGoogle Scholar
  238. Sharma KR, Saadia D, Facca AG, Bhatia R, Ayyar DR, Sheremata W (2008) Chronic inflammatory demyelinating polyradiculoneuropathy associated with multiple sclerosis. J Clin Neuromuscul Dis 9(4):385–396Google Scholar
  239. Shaw CM, Alvord EC (1987) Multiple sclerosis beginning in infancy. J Child Neurol 2:252–256PubMedCrossRefGoogle Scholar
  240. Sibley WA, Bamford CR, Clark K et al (1991) A prospective study of physical trauma and multiple sclerosis. J Neurol Neurosurg Psychiatry 54:584–589PubMedCrossRefGoogle Scholar
  241. Simpson JA (1960) Myasthenia gravis. A new hypothesis. Scot Med J 5:419–436Google Scholar
  242. Sluga E (1969) Beitrag zur Feinstruktur der Lasionen bei der multiplen Sklerose des Menschen. Wein Z Nervenheilkd Grenzgeb (Suppl):2, 59–69Google Scholar
  243. Sorensen AG, Wu O, Copen WA et al (1999) Human acute cerebral ischaemia; detection of changes by water diffusion anisotropy by using MR imaging. Radiology 212:785–792PubMedGoogle Scholar
  244. Spaar FW, Wikstrom J (1978) Multiple sclerosis and malignant neoplasm of the central nervous system. A clinical anatomical report of three cases. J Neurol 218:23–33PubMedCrossRefGoogle Scholar
  245. Steiner I, Wirguin I (2000) Multiple sclerosis—in need of a critical reappraisal. Med Hypotheses 54(1):99–106PubMedCrossRefGoogle Scholar
  246. Stone LA, Frank JA, Albert PS et al (1995) The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann Neurol 37:611–619PubMedCrossRefGoogle Scholar
  247. Tachi N, Ishikawa Y, Tsuzuki A, Minami R, Sasaki K, Shinoda M (1985) A case of childhood multiple sclerosis with peripheral neuropathy. Neuropediatrics 16:231–234PubMedCrossRefGoogle Scholar
  248. Tanaka R, Iwasaki Y, Koprowski H (1975) Ultrastructural studies of perivascular cuffing cells in multiple sclerosis brain. Am J Pathol 81(3):467–478PubMedGoogle Scholar
  249. Taylor D, Cuendet F (1986) Optic neuritis in childhood. In: Hess RF, Plant GT (eds) Optic neuritis. Cambridge University Press, Cambridge, pp 73–85Google Scholar
  250. The Canadian Cooperative Multiple Sclerosis Study Group (1991) The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet 337:441–446Google Scholar
  251. The Multiple Sclerosis Study Group (1990) Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomised, double-blinded, placebo-controlled clinical trial. Ann Neurol 27:591–605CrossRefGoogle Scholar
  252. Thomas DGT, Lannigan CB, Behan PO (1975) Impaired cell-mediated immunity in human brain tumours. Lancet i:1389–1390Google Scholar
  253. Thomas PK, Walker RWH, Rudge P, Morgan-Hughes JA, King RHM, Jacobs JM et al (1987) Chronic demyelinating peripheral neuropathy associated with multifocal central nervous system demyelination. Brain 110:53–76PubMedCrossRefGoogle Scholar
  254. Tivesky AL, Ptak T, Farkas J (1999) Investigation of apparent diffusion coefficient and diffusion tensor anisotropy in acute and chronic multiple sclerosis lesions. Am J Neuroradiol 20:1491–1499Google Scholar
  255. Tobinick EL, Gross H (2008) Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration. J Neuroinflammation 5:2PubMedCrossRefGoogle Scholar
  256. Tortorella C, Viti B, Bozzali M et al (2000) A magnetization transfer histogram study of normal appearing brain tissue in MS. Neurology 54:186–193PubMedGoogle Scholar
  257. Tournier-Lasserve E, Hashim GA, Bach MA (1988) Human T-cell response to myelin basic protein in multiple sclerosis patients and healthy subjects. J Neurosci Res 19:149–156PubMedCrossRefGoogle Scholar
  258. Tourtellotte WW, Tumani H (1997) Multiple sclerosis cerebrospinal fluid. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenic basis. Chapman & Hall, London, pp 57–79Google Scholar
  259. Tourtellotte WW, Potvin AR, Baumhefner RW et al (1980) Multiple sclerosis de novo CNS IgG synthesis: effect of CNS irradiation. Arch Neurol 37:620–624PubMedGoogle Scholar
  260. Truyen L, Gheuens J, Parizel PM et al (1991) Long-term follow-up of multiple sclerosis by standardised, non-contrast-enhanced magnetic resonance imaging. J Neurol Sci 106:35–40PubMedCrossRefGoogle Scholar
  261. Umehara F, Qin YF, Goto M et al (1990) Experimental autoimmune encephalomyelitis in the maturing central nervous system. Transfer of myelin basic protein-specific T line lymphocytes to neonatal Lewis rats. Lab Invest 62(2):147–155PubMedGoogle Scholar
  262. van Noort J, van Sechel AC, Bajramovic et al (1995) The small heat-shock protein and β crystalline as candidate autoantigen in multiple sclerosis. Nature 375:798–810Google Scholar
  263. van Waderveen MAA, Truyen L, van Oosten BW et al (1999) Development of hypointense lesions in T1-weighted spin-echi magnetic resonance images in multiple sclerosis: relation to inflammatory activity. Arch Neurol 56:345–351CrossRefGoogle Scholar
  264. van Waesberghe JHTM, van Walderveen MAA, Catelijns JA et al (1998) Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. Am J Neuroradiol 19:675–683PubMedGoogle Scholar
  265. van Waesberghe JHTM, Kamphorst W, De Groot CJA et al (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 46:747–754PubMedCrossRefGoogle Scholar
  266. Vieregge P, Nahser HC, Gerhard L et al (1984) Multiple sclerosis and cerebral tumour. Clin Neuropathol 3(1):10–21PubMedGoogle Scholar
  267. von Andrian UH, Engelhardt B (2003) α4 Integrins as therapeutic targets in autoimmune disease. N Engl J Med 348:68–72CrossRefGoogle Scholar
  268. von Deimling A, Krone W, Menon AG (1995) Neurofibromatosis type 1: Pathology, clinical features and molecular genetics. Brain Pathol 5:153–162CrossRefGoogle Scholar
  269. Warren SA, Warren KG (1982) Multiple sclerosis and diabetes mellitus: further evidence of a relationship. Can J Neurol Sci 9:415–419PubMedGoogle Scholar
  270. Weir A, Hansen S, Ballantyne JP (1979) Single fiber electromyographic jitter in multiple sclerosis. J Neurol Neurosurg Psychiatry 42:1146–1150PubMedCrossRefGoogle Scholar
  271. Werring DJ, Clar CA, Barker GJ et al (1999) Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis. Neurology 52:1626–1632PubMedGoogle Scholar
  272. Wolfgram F (1979) What if multiple sclerosis isn’t an immunological or a viral disease? The case for a circulating toxin. Neurochem Res 4:1–14PubMedCrossRefGoogle Scholar
  273. Wrabetz ML, Feltin CO, Hanemann et al (2001) The molecular genetics of hereditary demyelinating neuropathies. In: Jessen KR, Richardson WD (eds) Glial cell development. Oxford University Press, Oxford, pp 331–354Google Scholar
  274. Yudkin PL, Ellison GW, Ghezzi A et al (1991) Overview of azathioprine treatment in multiple sclerosis. Lancet 338:1051–1055PubMedCrossRefGoogle Scholar
  275. Zamvil SS, Steinman L (1990) The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol 8:579–621PubMedCrossRefGoogle Scholar
  276. Zimmerman HM, Netsky MG (1950) The pathology of multiple sclerosis. Res Publ Assoc Nerv Ment Dis 28:271–312Google Scholar

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© Springer Basel AG 2010

Authors and Affiliations

  1. 1.Department of NeurologyInstitute of Neurological Sciences, Glasgow UniversityGlasgowScotland, UK
  2. 2.School of Life SciencesGlasgow Caledonian UniversityGlasgowScotland, UK
  3. 3.Department of NeurologyQueen’s HospitalRomfordUK
  4. 4.GlasgowScotland, UK

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