• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of transbhomepageaboutsubmitalertseditorial board
Philos Trans R Soc Lond B Biol Sci. Oct 29, 1999; 354(1390): 1649–1673.
PMCID: PMC1692682

The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease.

Abstract

The pathophysiology of multiple sclerosis is reviewed, with emphasis on the axonal conduction properties underlying the production of symptoms, and the course of the disease. The major cause of the negative symptoms during relapses (e.g. paralysis, blindness and numbness) is conduction block, caused largely by demyelination and inflammation, and possibly by defects in synaptic transmission and putative circulating blocking factors. Recovery from symptoms during remissions is due mainly to the restoration of axonal function, either by remyelination, the resolution of inflammation, or the restoration of conduction to axons which persist in the demyelinated state. Conduction in the latter axons shows a number of deficits, particularly with regard to the conduction of trains of impulses and these contribute to weakness and sensory problems. The mechanisms underlying the sensitivity of symptoms to changes in body temperature (Uhthoff's phenomenon) are discussed. The origin of 'positive' symptoms, such as tingling sensations, are described, including the generation of ectopic trains and bursts of impulses, ephaptic interactions between axons and/or neurons, the triggering of additional, spurious impulses by the transmission of normal impulses, the mechanosensitivity of axons underlying movement-induced sensations (e.g. Lhermitte's phenomenon) and pain. The clinical course of the disease is discussed, together with its relationship to the evolution of lesions as revealed by magnetic resonance imaging and spectroscopy. The earliest detectable event in the development of most new lesions is a breakdown of the blood-brain barrier in association with inflammation. Inflammation resolves after approximately one month, at which time there is an improvement in the symptoms. Demyelination occurs during the inflammatory phase of the lesion. An important mechanism determining persistent neurological deficit is axonal degeneration, although persistent conduction block arising from the failure of repair mechanisms probably also contributes.

Full Text

The Full Text of this article is available as a PDF (860K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Avis SP, Pryse-Phillips WE. Sudden death in multiple sclerosis associated with sun exposure: a report of two cases. Can J Neurol Sci. 1995 Nov;22(4):305–307. [PubMed]
  • Baker M, Bostock H. Ectopic activity in demyelinated spinal root axons of the rat. J Physiol. 1992;451:539–552. [PMC free article] [PubMed]
  • Barnes D, Munro PM, Youl BD, Prineas JW, McDonald WI. The longstanding MS lesion. A quantitative MRI and electron microscopic study. Brain. 1991 Jun;114(Pt 3):1271–1280. [PubMed]
  • Baron-Van Evercooren A, Avellana-Adalid V, Lachapelle F, Liblau R. Schwann cell transplantation and myelin repair of the CNS. Mult Scler. 1997 Apr;3(2):157–161. [PubMed]
  • Bellinger FP, Madamba S, Siggins GR. Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res. 1993 Nov 19;628(1-2):227–234. [PubMed]
  • Berger JR, Sheremata WA. Persistent neurological deficit precipitated by hot bath test in multiple sclerosis. JAMA. 1983 Apr 1;249(13):1751–1753. [PubMed]
  • Bever CT., Jr The current status of studies of aminopyridines in patients with multiple sclerosis. Ann Neurol. 1994;36 (Suppl):S118–S121. [PubMed]
  • Bever CT, Jr, Young D, Anderson PA, Krumholz A, Conway K, Leslie J, Eddington N, Plaisance KI, Panitch HS, Dhib-Jalbut S, et al. The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. Neurology. 1994 Jun;44(6):1054–1059. [PubMed]
  • Bianchi M, Sacerdote P, Ricciardi-Castagnoli P, Mantegazza P, Panerai AE. Central effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity. Neurosci Lett. 1992 Dec 14;148(1-2):76–80. [PubMed]
  • Black JA, Waxman SG. Sodium channel expression: a dynamic process in neurons and non-neuronal cells. Dev Neurosci. 1996;18(3):139–152. [PubMed]
  • Black JA, Felts P, Smith KJ, Kocsis JD, Waxman SG. Distribution of sodium channels in chronically demyelinated spinal cord axons: immuno-ultrastructural localization and electrophysiological observations. Brain Res. 1991 Mar 22;544(1):59–70. [PubMed]
  • Blakemore WF, Smith KJ. Node-like axonal specializations along demyelinated central nerve fibres: ultrastructural observations. Acta Neuropathol. 1983;60(3-4):291–296. [PubMed]
  • Blight AR, Toombs JP, Bauer MS, Widmer WR. The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial. J Neurotrauma. 1991 Summer;8(2):103–119. [PubMed]
  • Bö L, Dawson TM, Wesselingh S, Mörk S, Choi S, Kong PA, Hanley D, Trapp BD. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol. 1994 Nov;36(5):778–786. [PubMed]
  • Bolaños JP, Peuchen S, Heales SJ, Land JM, Clark JB. Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes. J Neurochem. 1994 Sep;63(3):910–916. [PubMed]
  • Bolaños JP, Almeida A, Stewart V, Peuchen S, Land JM, Clark JB, Heales SJ. Nitric oxide-mediated mitochondrial damage in the brain: mechanisms and implications for neurodegenerative diseases. J Neurochem. 1997 Jun;68(6):2227–2240. [PubMed]
  • BORNSTEIN MB, CRAIN SM. FUNCTIONAL STUDIES OF CULTURED BRAIN TISSUES AS RELATED TO "DEMYELINATIVE DISORDERS". Science. 1965 May 28;148(3674):1242–1244. [PubMed]
  • Bostock H, Grafe P. Activity-dependent excitability changes in normal and demyelinated rat spinal root axons. J Physiol. 1985 Aug;365:239–257. [PMC free article] [PubMed]
  • Bostock H, Sears TA. Continuous conduction in demyelinated mammalian nerve fibers. Nature. 1976 Oct 28;263(5580):786–787. [PubMed]
  • Bostock H, Sears TA. The internodal axon membrane: electrical excitability and continuous conduction in segmental demyelination. J Physiol. 1978 Jul;280:273–301. [PMC free article] [PubMed]
  • Bostock H, Sherratt RM, Sears TA. Overcoming conduction failure in demyelinated nerve fibres by prolonging action potentials. Nature. 1978 Jul 27;274(5669):385–387. [PubMed]
  • Bostock H, Sears TA, Sherratt RM. The effects of 4-aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres. J Physiol. 1981;313:301–315. [PMC free article] [PubMed]
  • Bowe CM, Kocsis JD, Targ EF, Waxman SG. Physiological effects of 4-aminopyridine on demyelinated mammalian motor and sensory fibers. Ann Neurol. 1987 Aug;22(2):264–268. [PubMed]
  • Breland AE, Currier RD. Scorpion venom and multiple sclerosis. Lancet. 1983 Oct 29;2(8357):1021–1021. [PubMed]
  • BRICKNER RM. The significance of localized vasoconstrictions in multiple sclerosis; transient, sudden miniature attacks of multiple sclerosis. Res Publ Assoc Res Nerv Ment Dis. 1950;28:236–244. [PubMed]
  • Brinkmeier H, Kaspar A, Wiethölter H, Rüdel R. Interleukin-2 inhibits sodium currents in human muscle cells. Pflugers Arch. 1992 Apr;420(5-6):621–623. [PubMed]
  • Brinkmeier H, Wollinsky KH, Seewald MJ, Hülser PJ, Mehrkens HH, Kornhuber HH, Rüdel R. Factors in the cerebrospinal fluid of multiple sclerosis patients interfering with voltage-dependent sodium channels. Neurosci Lett. 1993 Jun 25;156(1-2):172–175. [PubMed]
  • Brinkmeier H, Seewald MJ, Wollinsky KH, Rüdel R. On the nature of endogenous antiexcitatory factors in the cerebrospinal fluid of patients with demyelinating neurological disease. Muscle Nerve. 1996 Jan;19(1):54–62. [PubMed]
  • Brismar T. Specific permeability properties of demyelinated rat nerve fibres. Acta Physiol Scand. 1981 Oct;113(2):167–176. [PubMed]
  • Brosnan CF, Litwak MS, Schroeder CE, Selmaj K, Raine CS, Arezzo JC. Preliminary studies of cytokine-induced functional effects on the visual pathways in the rabbit. J Neuroimmunol. 1989 Dec;25(2-3):227–239. [PubMed]
  • Brosnan CF, Cannella B, Battistini L, Raine CS. Cytokine localization in multiple sclerosis lesions: correlation with adhesion molecule expression and reactive nitrogen species. Neurology. 1995 Jun;45(6 Suppl 6):S16–S21. [PubMed]
  • Brown GC, Bolaños JP, Heales SJ, Clark JB. Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration. Neurosci Lett. 1995 Jul 7;193(3):201–204. [PubMed]
  • Brück W, Bitsch A, Kolenda H, Brück Y, Stiefel M, Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol. 1997 Nov;42(5):783–793. [PubMed]
  • Bunge MB. Transplantation of purified populations of Schwann cells into lesioned adult rat spinal cord. J Neurol. 1994 Dec;242(1 Suppl 1):S36–S39. [PubMed]
  • Burchiel KJ. Abnormal impulse generation in focally demyelinated trigeminal roots. J Neurosurg. 1980 Nov;53(5):674–683. [PubMed]
  • Burchiel KJ. Ectopic impulse generation in demyelinated axons: effects of PaCO2, pH, and disodium edetate. Ann Neurol. 1981 Apr;9(4):378–383. [PubMed]
  • Burke D. Microneurography, impulse conduction, and paresthesias. Muscle Nerve. 1993 Oct;16(10):1025–1032. [PubMed]
  • Calvin WH, Loeser JD, Howe JF. A neurophysiological theory for the pain mechanism of tic douloureux. Pain. 1977 Apr;3(2):147–154. [PubMed]
  • Carels G, Cerf JA. Functional alterations produced in an isolated nerve center by serum from patients with multiple sclerosis. Int Arch Allergy Appl Immunol. 1969;36(Suppl):608–628. [PubMed]
  • Carrieri PB, Provitera V, De Rosa T, Tartaglia G, Gorga F, Perrella O. Profile of cerebrospinal fluid and serum cytokines in patients with relapsing-remitting multiple sclerosis: a correlation with clinical activity. Immunopharmacol Immunotoxicol. 1998 Aug;20(3):373–382. [PubMed]
  • Celesia GG, Daly RF. Visual electroencephalographic computer analysis (VECA). A new electrophysiologic test for the diagnosis of optic nerve lesions. Neurology. 1977 Jul;27(7):637–641. [PubMed]
  • Cerf JA, Carels G. Multiple sclerosis: serum factor producing reversible alterations in bioelectric responses. Science. 1966 May 20;152(3725):1066–1068. [PubMed]
  • Chalk JB, McCombe PA, Pender MP. Conduction abnormalities are restricted to the central nervous system in experimental autoimmune encephalomyelitis induced by inoculation with proteolipid protein but not with myelin basic protein. Brain. 1994 Oct;117(Pt 5):975–986. [PubMed]
  • Chalk JB, McCombe PA, Pender MP. Restoration of conduction in the spinal roots correlates with clinical recovery from experimental autoimmune encephalomyelitis. Muscle Nerve. 1995 Oct;18(10):1093–1100. [PubMed]
  • Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE, Gearing AJ. Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview. J Neuroimmunol. 1997 Feb;72(2):155–161. [PubMed]
  • Chao CC, Hu S, Peterson PK. Glia, cytokines, and neurotoxicity. Crit Rev Neurobiol. 1995;9(2-3):189–205. [PubMed]
  • Chiu SY, Ritchie JM. Evidence for the presence of potassium channels in the paranodal region of acutely demyelinated mammalian single nerve fibres. J Physiol. 1981;313:415–437. [PMC free article] [PubMed]
  • Crain SM, Bornstein MB. Depression of complex bioelectric discharges in cerebral tissue cultures by thermolabile complement-dependent serum factors. Exp Neurol. 1975 Oct;49(1 Pt 1):330–335. [PubMed]
  • Cross AH, Manning PT, Keeling RM, Schmidt RE, Misko TP. Peroxynitrite formation within the central nervous system in active multiple sclerosis. J Neuroimmunol. 1998 Aug 1;88(1-2):45–56. [PubMed]
  • Cummins TR, Waxman SG. Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J Neurosci. 1997 May 15;17(10):3503–3514. [PubMed]
  • D'Arcangelo G, Grassi F, Ragozzino D, Santoni A, Tancredi V, Eusebi F. Interferon inhibits synaptic potentiation in rat hippocampus. Brain Res. 1991 Nov 15;564(2):245–248. [PubMed]
  • Davie CA, Hawkins CP, Barker GJ, Brennan A, Tofts PS, Miller DH, McDonald WI. Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain. 1994 Feb;117(Pt 1):49–58. [PubMed]
  • Davie CA, Barker GJ, Webb S, Tofts PS, Thompson AJ, Harding AE, McDonald WI, Miller DH. Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain. 1995 Dec;118(Pt 6):1583–1592. [PubMed]
  • Davis FA. Neurological deficits following the hot bath test in multiple sclerosis. JAMA. 1985 Jan 11;253(2):203–203. [PubMed]
  • Davis FA, Jacobson S. Altered thermal sensitivity in injured and demyelinated nerve. A possible model of temperature effects in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1971 Oct;34(5):551–561. [PMC free article] [PubMed]
  • Davis FA, Schauf CL. Approaches to the development of pharmacological interventions in multiple sclerosis. Adv Neurol. 1981;31:505–510. [PubMed]
  • Davis FA, Becker FO, Michael JA, Sorensen E. Effect of intravenous sodium bicarbonate, disodium edetate (Na2EDTA), and hyperventilation on visual and oculomotor signs in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1970 Dec;33(6):723–732. [PMC free article] [PubMed]
  • Davis FA, Michael JA, Tomaszewski JS. Fluctuation of motor function in multiple sclerosis related to circadian temperature variations. Dis Nerv Syst. 1973 Jan;34(1):33–36. [PubMed]
  • Davis FA, Schauf CL, Reed BJ, Kesler RL. Experimental studies of the effects of extrinsic factors on conduction in normal and demyelinated nerve. 1. Temperature. J Neurol Neurosurg Psychiatry. 1976 May;39(5):442–448. [PMC free article] [PubMed]
  • Davis FA, Bergen D, Schauf C, McDonald I, Deutsch W. Movement phosphenes in optic neuritis: a new clinical sign. Neurology. 1976 Nov;26(11):1100–1104. [PubMed]
  • De Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD, Van der Valk P. Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol. 1997 Jan;56(1):10–20. [PubMed]
  • Dugandzija-Novaković S, Shrager P. Survival, development, and electrical activity of central nervous system myelinated axons exposed to tumor necrosis factor in vitro. J Neurosci Res. 1995 Jan 1;40(1):117–126. [PubMed]
  • Dugandzija-Novaković S, Koszowski AG, Levinson SR, Shrager P. Clustering of Na+ channels and node of Ranvier formation in remyelinating axons. J Neurosci. 1995 Jan;15(1 Pt 2):492–503. [PubMed]
  • England JD, Gamboni F, Levinson SR, Finger TE. Changed distribution of sodium channels along demyelinated axons. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6777–6780. [PMC free article] [PubMed]
  • England JD, Levinson SR, Shrager P. Immunocytochemical investigations of sodium channels along nodal and internodal portions of demyelinated axons. Microsc Res Tech. 1996 Aug 1;34(5):445–451. [PubMed]
  • Felts PA, Smith KJ. Conduction properties of central nerve fibers remyelinated by Schwann cells. Brain Res. 1992 Mar 6;574(1-2):178–192. [PubMed]
  • Felts PA, Smith KJ. The use of potassium channel blocking agents in the therapy of demyelinating diseases. Ann Neurol. 1994 Sep;36(3):454–454. [PubMed]
  • Felts PA, Kapoor R, Smith KJ. A mechanism for ectopic firing in central demyelinated axons. Brain. 1995 Oct;118(Pt 5):1225–1231. [PubMed]
  • Felts PA, Baker TA, Smith KJ. Conduction in segmentally demyelinated mammalian central axons. J Neurosci. 1997 Oct 1;17(19):7267–7277. [PubMed]
  • FRANKENHAEUSER B, HODGKIN AL. The action of calcium on the electrical properties of squid axons. J Physiol. 1957 Jul 11;137(2):218–244. [PMC free article] [PubMed]
  • Franklin RJ, Blakemore WF. Requirements for Schwann cell migration within CNS environments: a viewpoint. Int J Dev Neurosci. 1993 Oct;11(5):641–649. [PubMed]
  • Ghatak NR, Hirano A, Lijtmaer H, Zimmerman HM. Asymptomatic demyelinated plaque in the spinal cord. Arch Neurol. 1974 Jun;30(6):484–486. [PubMed]
  • Ghezzi A, Montanini R, Basso PF, Zaffaroni M, Massimo E, Cazzullo CL. Epilepsy in multiple sclerosis. Eur Neurol. 1990;30(4):218–223. [PubMed]
  • Gideon P, Henriksen O, Sperling B, Christiansen P, Olsen TS, Jørgensen HS, Arlien-Søborg P. Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study. Stroke. 1992 Nov;23(11):1566–1572. [PubMed]
  • Giovannoni G, Heales SJ, Silver NC, O'Riordan J, Miller RF, Land JM, Clark JB, Thompson EJ. Raised serum nitrate and nitrite levels in patients with multiple sclerosis. J Neurol Sci. 1997 Jan;145(1):77–81. [PubMed]
  • Gledhill RF, McDonald WI. Morphological characteristics of central demyelination and remyelination: a single-fiber study. Ann Neurol. 1977 Jun;1(6):552–560. [PubMed]
  • Goodkin DE. Interferon beta therapy for multiple sclerosis. Lancet. 1998 Nov 7;352(9139):1486–1487. [PubMed]
  • Goodwin JL, Uemura E, Cunnick JE. Microglial release of nitric oxide by the synergistic action of beta-amyloid and IFN-gamma. Brain Res. 1995 Sep 18;692(1-2):207–214. [PubMed]
  • Goureau O, Amiot F, Dautry F, Courtois Y. Control of nitric oxide production by endogenous TNF-alpha in mouse retinal pigmented epithelial and Muller glial cells. Biochem Biophys Res Commun. 1997 Nov 7;240(1):132–135. [PubMed]
  • Guthikonda P, Baker J, Mattson DH. Interferon-beta-1-b (IFN-B) decreases induced nitric oxide (NO) production by a human astrocytoma cell line. J Neuroimmunol. 1998 Mar 1;82(2):133–139. [PubMed]
  • GUTHRIE TC. Visual and motor changes in patients with multiple sclerosis; a result of induced changes in environmental temperature. AMA Arch Neurol Psychiatry. 1951 Apr;65(4):437–451. [PubMed]
  • Hall GL, Compston A, Scolding NJ. Beta-interferon and multiple sclerosis. Trends Neurosci. 1997 Feb;20(2):63–67. [PubMed]
  • Halliday AM, McDonald WI, Mushin J. Delayed visual evoked response in optic neuritis. Lancet. 1972 May 6;1(7758):982–985. [PubMed]
  • Halliday AM, McDonald WI, Mushin J. Visual evoked response in diagnosis of multiple sclerosis. Br Med J. 1973 Dec 15;4(5893):661–664. [PMC free article] [PubMed]
  • Harbison JW, Calabrese VP, Edlich RF. A fatal case of sun exposure in a multiple sclerosis patient. J Emerg Med. 1989 Sep-Oct;7(5):465–467. [PubMed]
  • Hartung HP, Archelos JJ, Zielasek J, Gold R, Koltzenburg M, Reiners KH, Toyka KV. Circulating adhesion molecules and inflammatory mediators in demyelination: a review. Neurology. 1995 Jun;45(6 Suppl 6):S22–S32. [PubMed]
  • Hjorth RJ, Willison RG. The electromyogram in facial myokymia and hemifacial spasm. J Neurol Sci. 1973 Oct;20(2):117–126. [PubMed]
  • Hölscher C. Nitric oxide, the enigmatic neuronal messenger: its role in synaptic plasticity. Trends Neurosci. 1997 Jul;20(7):298–303. [PubMed]
  • Honmou O, Utzschneider DA, Rizzo MA, Bowe CM, Waxman SG, Kocsis JD. Delayed depolarization and slow sodium currents in cutaneous afferents. J Neurophysiol. 1994 May;71(5):1627–1637. [PMC free article] [PubMed]
  • Honmou O, Felts PA, Waxman SG, Kocsis JD. Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells. J Neurosci. 1996 May 15;16(10):3199–3208. [PMC free article] [PubMed]
  • Hopper CL, Matthews CG, Cleeland CS. Symptom instability and thermoregulation in multiple sclerosis. Neurology. 1972 Feb;22(2):142–148. [PubMed]
  • Howe JF, Calvin WH, Loeser JD. Impulses reflected from dorsal root ganglia and from focal nerve injuries. Brain Res. 1976 Oct 29;116(1):139–144. [PubMed]
  • Hu S, Sheng WS, Peterson PK, Chao CC. Differential regulation by cytokines of human astrocyte nitric oxide production. Glia. 1995 Dec;15(4):491–494. [PubMed]
  • Hua LL, Liu JS, Brosnan CF, Lee SC. Selective inhibition of human glial inducible nitric oxide synthase by interferon-beta: implications for multiple sclerosis. Ann Neurol. 1998 Mar;43(3):384–387. [PubMed]
  • Huizar P, Kuno M, Miyata Y. Electrophysiological properties of spinal motoneurones of normal and dystrophic mice. J Physiol. 1975 Jun;248(1):231–246. [PMC free article] [PubMed]
  • Hume AL, Waxman SG. Evoked potentials in suspected multiple sclerosis: diagnostic value and prediction of clinical course. J Neurol Sci. 1988 Feb;83(2-3):191–210. [PubMed]
  • Imaizumi T, Lankford KL, Waxman SG, Greer CA, Kocsis JD. Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord. J Neurosci. 1998 Aug 15;18(16):6176–6185. [PMC free article] [PubMed]
  • Isaac C, Li DK, Genton M, Jardine C, Grochowski E, Palmer M, Kastrukoff LF, Oger J, Paty DW. Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology. 1988 Oct;38(10):1511–1515. [PubMed]
  • Jacobs L, Kaba S, Pullicino P. The lesion causing continuous facial myokymia in multiple sclerosis. Arch Neurol. 1994 Nov;51(11):1115–1119. [PubMed]
  • Jeffery ND, Blakemore WF. Locomotor deficits induced by experimental spinal cord demyelination are abolished by spontaneous remyelination. Brain. 1997 Jan;120(Pt 1):27–37. [PubMed]
  • Johnson AW, Land JM, Thompson EJ, Bolaños JP, Clark JB, Heales SJ. Evidence for increased nitric oxide production in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1995 Jan;58(1):107–107. [PMC free article] [PubMed]
  • Kaji R, Sumner AJ. Effect of digitalis on central demyelinative conduction block in vivo. Ann Neurol. 1989 Feb;25(2):159–165. [PubMed]
  • Kaji R, Sumner AJ. Ouabain reverses conduction disturbances in single demyelinated nerve fibers. Neurology. 1989 Oct;39(10):1364–1368. [PubMed]
  • Kaji R, Suzumura A, Sumner AJ. Physiological consequences of antiserum-mediated experimental demyelination in CNS. Brain. 1988 Jun;111(Pt 3):675–694. [PubMed]
  • Kaji R, Happel L, Sumner AJ. Effect of digitalis on clinical symptoms and conduction variables in patients with multiple sclerosis. Ann Neurol. 1990 Oct;28(4):582–584. [PubMed]
  • Kanchandani R, Howe JG. Lhermitte's sign in multiple sclerosis: a clinical survey and review of the literature. J Neurol Neurosurg Psychiatry. 1982 Apr;45(4):308–312. [PMC free article] [PubMed]
  • Kapoor R, Brown P, Thompson PD, Miller DH. Propriospinal myoclonus in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1992 Nov;55(11):1086–1088. [PMC free article] [PubMed]
  • Kapoor R, Smith KJ, Felts PA, Davies M. Internodal potassium currents can generate ectopic impulses in mammalian myelinated axons. Brain Res. 1993 May 14;611(1):165–169. [PubMed]
  • Kapoor R, Li YG, Smith KJ. Slow sodium-dependent potential oscillations contribute to ectopic firing in mammalian demyelinated axons. Brain. 1997 Apr;120(Pt 4):647–652. [PubMed]
  • Goldsmith P, Rowe D, Jäger R, Kapoor R. Focal vertebral artery dissection causing Brown-Séquard's syndrome. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):415–416. [PMC free article] [PubMed]
  • Kara P, Friedlander MJ. Dynamic modulation of cerebral cortex synaptic function by nitric oxide. Prog Brain Res. 1998;118:183–198. [PubMed]
  • Katz D, Taubenberger JK, Cannella B, McFarlin DE, Raine CS, McFarland HF. Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis. Ann Neurol. 1993 Nov;34(5):661–669. [PubMed]
  • Kermode AG, Thompson AJ, Tofts P, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, Rudge P, McDonald WI. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain. 1990 Oct;113(Pt 5):1477–1489. [PubMed]
  • Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T. Cortical lesions in multiple sclerosis. Brain. 1999 Jan;122(Pt 1):17–26. [PubMed]
  • Kilbinger H. Modulation of acetylcholine release by nitric oxide. Prog Brain Res. 1996;109:219–224. [PubMed]
  • Koles ZJ, Rasminsky M. A computer simulation of conduction in demyelinated nerve fibres. J Physiol. 1972 Dec;227(2):351–364. [PMC free article] [PubMed]
  • Köller H, Buchholz J, Siebler M. Cerebrospinal fluid from multiple sclerosis patients inactivates neuronal Na+ current. Brain. 1996 Apr;119(Pt 2):457–463. [PubMed]
  • Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444–1452. [PubMed]
  • Largo C, Cuevas P, Somjen GG, Martín del Río R, Herreras O. The effect of depressing glial function in rat brain in situ on ion homeostasis, synaptic transmission, and neuron survival. J Neurosci. 1996 Feb 1;16(3):1219–1229. [PubMed]
  • Larsson HB, Frederiksen J, Kjaer L, Henriksen O, Olesen J. In vivo determination of T1 and T2 in the brain of patients with severe but stable multiple sclerosis. Magn Reson Med. 1988 May;7(1):43–55. [PubMed]
  • Lee SC, Dickson DW, Brosnan CF. Interleukin-1, nitric oxide and reactive astrocytes. Brain Behav Immun. 1995 Dec;9(4):345–354. [PubMed]
  • Levine RA, Gardner JC, Fullerton BC, Stufflebeam SM, Furst M, Rosen BR. Multiple sclerosis lesions of the auditory pons are not silent. Brain. 1994 Oct;117(Pt 5):1127–1141. [PubMed]
  • Lewis RA, Sumner AJ, Brown MJ, Asbury AK. Multifocal demyelinating neuropathy with persistent conduction block. Neurology. 1982 Sep;32(9):958–964. [PubMed]
  • Li Z, Chapleau MW, Bates JN, Bielefeldt K, Lee HC, Abboud FM. Nitric oxide as an autocrine regulator of sodium currents in baroreceptor neurons. Neuron. 1998 May;20(5):1039–1049. [PubMed]
  • Liu J, Zhao ML, Brosnan CF, Lee SC. Expression of type II nitric oxide synthase in primary human astrocytes and microglia: role of IL-1beta and IL-1 receptor antagonist. J Immunol. 1996 Oct 15;157(8):3569–3576. [PubMed]
  • Losseff NA, Webb SL, O'Riordan JI, Page R, Wang L, Barker GJ, Tofts PS, McDonald WI, Miller DH, Thompson AJ. Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain. 1996 Jun;119(Pt 3):701–708. [PubMed]
  • Lumsden CE, Howard L, Aparicio SR. Anti-synaptic antibody in allergic encephalomyelitis. I. Neurophysiological studies, in guinea pigs, on the exposed cerebral cortex and peripheral nerves, following immunological challenges with myelin and synaptosomes. Brain Res. 1975 Aug 8;93(2):267–282. [PubMed]
  • Lumsden CE, Howard L, Aparicio SR, Bradbury M. Anti-synaptic antibody in allergic encephalomyelitis. II. The synapse-blocking effects in tissue culture of demyelinating sera from experimental allergic encephalomyelitis. Brain Res. 1975 Aug 8;93(2):283–299. [PubMed]
  • McDonald WI. Mechanisms of functional loss and recovery in spinal cord damage. Ciba Found Symp. 1975;(34):23–33. [PubMed]
  • McDonald WI, Sears TA. Effect of demyelination on conduction in the central nervous system. Nature. 1969 Jan 11;221(5176):182–183. [PubMed]
  • McDonald WI, Sears TA. The effects of experimental demyelination on conduction in the central nervous system. Brain. 1970;93(3):583–598. [PubMed]
  • Maingret F, Fosset M, Lesage F, Lazdunski M, Honoré E. TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem. 1999 Jan 15;274(3):1381–1387. [PubMed]
  • Malhotra AS, Goren H. The hot bath test in the diagnosis of multiple sclerosis. JAMA. 1981 Sep 4;246(10):1113–1114. [PubMed]
  • Martiney JA, Litwak M, Berman JW, Arezzo JC, Brosnan CF. Pathophysiologic effect of interleukin-1b in the rabbit retina. Am J Pathol. 1990 Dec;137(6):1411–1423. [PMC free article] [PubMed]
  • Matthews WB. Paroxysmal symptoms in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1975 Jun;38(6):617–623. [PMC free article] [PubMed]
  • Merrill JE, Benveniste EN. Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci. 1996 Aug;19(8):331–338. [PubMed]
  • Miller DH, Rudge P, Johnson G, Kendall BE, Macmanus DG, Moseley IF, Barnes D, McDonald WI. Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain. 1988 Aug;111(Pt 4):927–939. [PubMed]
  • Miller LG, Fahey JM. Interleukin-1 modulates GABAergic and glutamatergic function in brain. Ann N Y Acad Sci. 1994 Oct 31;739:292–298. [PubMed]
  • Milner BA, Regan D, Heron JR. Differential diagnosis of multiple sclerosis by visual evoked potential recording. Brain. 1974 Dec;97(4):755–772. [PubMed]
  • Mimura Y, Gotow T, Nishi T, Osame M. Mechanisms of hyperpolarization induced by two cytokines, hTNF alpha and hIL-1 alpha in neurons of the mollusc, Onchidium. Brain Res. 1994 Aug 8;653(1-2):112–118. [PubMed]
  • Moll C, Mourre C, Lazdunski M, Ulrich J. Increase of sodium channels in demyelinated lesions of multiple sclerosis. Brain Res. 1991 Aug 16;556(2):311–316. [PubMed]
  • Moreau T, Coles A, Wing M, Isaacs J, Hale G, Waldmann H, Compston A. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain. 1996 Feb;119(Pt 1):225–237. [PubMed]
  • Namerow NS. Circadian temperature rhythm and vision in multiple sclerosis. Neurology. 1968 May;18(5):417–422. [PubMed]
  • Navikas V, Link H. Review: cytokines and the pathogenesis of multiple sclerosis. J Neurosci Res. 1996 Aug 15;45(4):322–333. [PubMed]
  • Nordin M, Nyström B, Wallin U, Hagbarth KE. Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves, dorsal roots and dorsal columns. Pain. 1984 Nov;20(3):231–245. [PubMed]
  • Novakovic SD, Deerinck TJ, Levinson SR, Shrager P, Ellisman MH. Clusters of axonal Na+ channels adjacent to remyelinating Schwann cells. J Neurocytol. 1996 Jun;25(6):403–412. [PubMed]
  • Novakovic SD, Levinson SR, Schachner M, Shrager P. Disruption and reorganization of sodium channels in experimental allergic neuritis. Muscle Nerve. 1998 Aug;21(8):1019–1032. [PubMed]
  • Oleszak EL, Zaczynska E, Bhattacharjee M, Butunoi C, Legido A, Katsetos CD. Inducible nitric oxide synthase and nitrotyrosine are found in monocytes/macrophages and/or astrocytes in acute, but not in chronic, multiple sclerosis. Clin Diagn Lab Immunol. 1998 Jul;5(4):438–445. [PMC free article] [PubMed]
  • Ormerod IE, Miller DH, McDonald WI, du Boulay EP, Rudge P, Kendall BE, Moseley IF, Johnson G, Tofts PS, Halliday AM, et al. The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study. Brain. 1987 Dec;110(Pt 6):1579–1616. [PubMed]
  • O'Riordan JI, Losseff NA, Phatouros C, Thompson AJ, Moseley IF, MacManus DG, McDonald WI, Miller DH. Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem, and spinal cord syndromes suggestive of demyelination. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):353–357. [PMC free article] [PubMed]
  • Osterman PO. Paroxysmal itching in multiple sclerosis. Br J Dermatol. 1976 Nov;95(5):555–558. [PubMed]
  • Ostermann PO, Westerberg CE. Paroxysmal attacks in multiple sclerosis. Brain. 1975 Jun;98(2):189–202. [PubMed]
  • Paintal AS. The influence of diameter of medullated nerve fibres of cats on the rising and falling phases of the spike and its recovery. J Physiol. 1966 Jun;184(4):791–811. [PMC free article] [PubMed]
  • Park HJ, Won CK, Pyun KH, Shin HC. Interleukin 2 suppresses afferent sensory transmission in the primary somatosensory cortex. Neuroreport. 1995 May 9;6(7):1018–1020. [PubMed]
  • Pencek TL, Schauf CL, Low PA, Eisenberg BR, Davis FA. Disruption of the perineurium in amphibian peripheral nerve: morphology and physiology. Neurology. 1980 Jun;30(6):593–599. [PubMed]
  • Pender MP. The pathophysiology of acute experimental allergic encephalomyelitis induced by whole spinal cord in the Lewis rat. J Neurol Sci. 1988 Apr;84(2-3):209–222. [PubMed]
  • Pender MP. The pathophysiology of myelin basic protein-induced acute experimental allergic encephalomyelitis in the Lewis rat. J Neurol Sci. 1988 Sep;86(2-3):277–289. [PubMed]
  • Pender MP. Recovery from acute experimental allergic encephalomyelitis in the Lewis rat. Early restoration of nerve conduction and repair by Schwann cells and oligodendrocytes. Brain. 1989 Apr;112(Pt 2):393–416. [PubMed]
  • Pender MP, Sears TA. The pathophysiology of acute experimental allergic encephalomyelitis in the rabbit. Brain. 1984 Sep;107(Pt 3):699–726. [PubMed]
  • Petersen P, Kastrup J, Zeeberg I, Boysen G. Chronic pain treatment with intravenous lidocaine. Neurol Res. 1986 Sep;8(3):189–190. [PubMed]
  • Phadke JG, Best PV. Atypical and clinically silent multiple sclerosis: a report of 12 cases discovered unexpectedly at necropsy. J Neurol Neurosurg Psychiatry. 1983 May;46(5):414–420. [PMC free article] [PubMed]
  • Prineas JW, Connell F. Remyelination in multiple sclerosis. Ann Neurol. 1979 Jan;5(1):22–31. [PubMed]
  • Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES. Multiple sclerosis: remyelination of nascent lesions. Ann Neurol. 1993 Feb;33(2):137–151. [PubMed]
  • Rasminsky M. The effects of temperature on conduction in demyelinated single nerve fibers. Arch Neurol. 1973 May;28(5):287–292. [PubMed]
  • Rasminsky M. Ectopic generation of impulses and cross-talk in spinal nerve roots of "dystrophic" mice. Ann Neurol. 1978 Apr;3(4):351–357. [PubMed]
  • Rasminsky M. Ephaptic transmission between single nerve fibres in the spinal nerve roots of dystrophic mice. J Physiol. 1980 Aug;305:151–169. [PMC free article] [PubMed]
  • Rasminsky M. Hyperexcitability of pathologically myelinated axons and positive symptoms in multiple sclerosis. Adv Neurol. 1981;31:289–297. [PubMed]
  • Rasminsky M. Spontaneous activity and cross-talk in pathological nerve fibers. Res Publ Assoc Res Nerv Ment Dis. 1987;65:39–49. [PubMed]
  • Rasminsky M, Sears TA. Internodal conduction in undissected demyelinated nerve fibres. J Physiol. 1972 Dec;227(2):323–350. [PMC free article] [PubMed]
  • Redford EJ, Kapoor R, Smith KJ. Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible. Brain. 1997 Dec;120(Pt 12):2149–2157. [PubMed]
  • Revesz T, Kidd D, Thompson AJ, Barnard RO, McDonald WI. A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain. 1994 Aug;117(Pt 4):759–765. [PubMed]
  • Ridet JL, Malhotra SK, Privat A, Gage FH. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci. 1997 Dec;20(12):570–577. [PubMed]
  • Rivera-Quiñones C, McGavern D, Schmelzer JD, Hunter SF, Low PA, Rodriguez M. Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis. Nat Med. 1998 Feb;4(2):187–193. [PubMed]
  • Rizzo MA, Kocsis JD, Waxman SG. Mechanisms of paresthesiae, dysesthesiae, and hyperesthesiae: role of Na+ channel heterogeneity. Eur Neurol. 1996;36(1):3–12. [PubMed]
  • Robinson K, Rudge P. Abnormalities of the auditory evoked potentials in patients with multiple sclerosis. Brain. 1977 Mar;100(Pt 1):19–40. [PubMed]
  • Rosenbluth J, Blakemore WF. Structural specializations in cat of chronically demyelinated spinal cord axons as seen in freeze-fracture replicas. Neurosci Lett. 1984 Jul 27;48(2):171–177. [PubMed]
  • Rosenbluth J, Tao-Cheng JH, Blakemore WF. Dependence of axolemmal differentiation on contact with glial cells in chronically demyelinated lesions of cat spinal cord. Brain Res. 1985 Dec 9;358(1-2):287–302. [PubMed]
  • Schauf CL, Davis FA. Impulse conduction in multiple sclerosis: a theoretical basis for modification by temperature and pharmacological agents. J Neurol Neurosurg Psychiatry. 1974 Feb;37(2):152–161. [PMC free article] [PubMed]
  • Schauf CL, Davis FA. The occurrence, specificity, and role of neuroelectric blocking factors in multiple sclerosis. Neurology. 1978 Sep;28(9 Pt 2):34–39. [PubMed]
  • Schauf CL, Davis FA. Circulating toxic factors in multiple sclerosis: a perspective. Adv Neurol. 1981;31:267–280. [PubMed]
  • Schauf CL, Davis FA, Sack DA, Reed BJ, Kesler RL. Neuroelectric blocking factors in human and animal sera evaluated using the isolated frog spinal cord. J Neurol Neurosurg Psychiatry. 1976 Jul;39(7):680–685. [PMC free article] [PubMed]
  • Schauf CL, Schauf V, Davis FA, Mizen MR. Complement-dependent serum: neuroelectric blocking activity in multiple sclerosis. Neurology. 1978 May;28(5):426–430. [PubMed]
  • Schwarz JR, Grigat G. Phenytoin and carbamazepine: potential- and frequency-dependent block of Na currents in mammalian myelinated nerve fibers. Epilepsia. 1989 May-Jun;30(3):286–294. [PubMed]
  • Schwid SR, Petrie MD, McDermott MP, Tierney DS, Mason DH, Goodman AD. Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis. Neurology. 1997 Apr;48(4):817–821. [PubMed]
  • Sclabassi RJ, Namerow NS, Enns NF. Somatosensory response to stimulus trains in patients with multiple sclerosis. Electroencephalogr Clin Neurophysiol. 1974 Jul;37(1):23–33. [PubMed]
  • Sears TA, Bostock H. Conduction failure in demyelination: is it inevitable? Adv Neurol. 1981;31:357–375. [PubMed]
  • Sears TA, Bostock H, Sheratt M. The pathophysiology of demyelination and its implications for the symptomatic treatment of multiple sclerosis. Neurology. 1978 Sep;28(9 Pt 2):21–26. [PubMed]
  • Seil FJ, Smith ME, Leiman AL, Kelly JM., 3rd Myelination inhibiting and neuroelectric blocking factors in experimental allergic encephalomyelitis. Science. 1975 Mar 14;187(4180):951–953. [PubMed]
  • Seil FJ, Leiman AL, Kelly JM., 3rd Neuroelectric blocking factors in multiple sclerosis and normal human sera. Arch Neurol. 1976 Jun;33(6):418–422. [PubMed]
  • Selhorst JB, Saul RF. Uhthoff and his symptom. J Neuroophthalmol. 1995 Jun;15(2):63–69. [PubMed]
  • Sherratt RM, Bostock H, Sears TA. Effects of 4-aminopyridine on normal and demyelinated mammalian nerve fibres. Nature. 1980 Feb 7;283(5747):570–572. [PubMed]
  • Shibasaki H, McDonald WI, Kuroiwa Y. Racial modification of clinical picture of multiple sclerosis: comparison between British and Japanese patients. J Neurol Sci. 1981 Feb;49(2):253–271. [PubMed]
  • Shrager P. Axonal coding of action potentials in demyelinated nerve fibers. Brain Res. 1993 Aug 13;619(1-2):278–290. [PubMed]
  • Shrager P, Rubinstein CT. Optical measurement of conduction in single demyelinated axons. J Gen Physiol. 1990 May;95(5):867–889. [PMC free article] [PubMed]
  • Shrager P, Custer AW, Kazarinova K, Rasband MN, Mattson D. Nerve conduction block by nitric oxide that is mediated by the axonal environment. J Neurophysiol. 1998 Feb;79(2):529–536. [PubMed]
  • Silver NC, Good CD, Barker GJ, MacManus DG, Thompson AJ, Moseley IF, McDonald WI, Miller DH. Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium dose, magnetization transfer contrast and delayed imaging. Brain. 1997 Jul;120(Pt 7):1149–1161. [PubMed]
  • Sims TJ, Gilmore SA, Waxman SG. Radial glia give rise to perinodal processes. Brain Res. 1991 May 17;549(1):25–35. [PubMed]
  • Small DG, Matthews WB, Small M. The cervical somatosensory evoked potential (SEP) in the diagnosis of multiple sclerosis. J Neurol Sci. 1978 Feb;35(2-3):211–224. [PubMed]
  • Smith KJ. Conduction properties of central demyelinated and remyelinated axons, and their relation to symptom production in demyelinating disorders. Eye (Lond) 1994;8(Pt 2):224–237. [PubMed]
  • Smith KJ, McDonald WI. Spontaneous and mechanically evoked activity due to central demyelinating lesion. Nature. 1980 Jul 10;286(5769):154–155. [PubMed]
  • Smith KJ, McDonald WI. Spontaneous and evoked electrical discharges from a central demyelinating lesion. J Neurol Sci. 1982 Jul;55(1):39–47. [PubMed]
  • Smith KJ, Blakemore WF, McDonald WI. Central remyelination restores secure conduction. Nature. 1979 Aug 2;280(5721):395–396. [PubMed]
  • Smith KJ, Blakemore WF, McDonald WI. The restoration of conduction by central remyelination. Brain. 1981 Jun;104(2):383–404. [PubMed]
  • Smith KJ, Bostock H, Hall SM. Saltatory conduction precedes remyelination in axons demyelinated with lysophosphatidyl choline. J Neurol Sci. 1982 Apr;54(1):13–31. [PubMed]
  • Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience. 1997 Nov;81(1):255–262. [PubMed]
  • Stefoski D, Schauf CL, McLeod BC, Haywood CP, Davis FA. Plasmapheresis decreases neuroelectric blocking activity in multiple sclerosis. Neurology. 1982 Aug;32(8):904–907. [PubMed]
  • Stephanova DI, Chobanova M. Action potentials and ionic currents through paranodally demyelinated human motor nerve fibres: computer simulations. Biol Cybern. 1997 Apr;76(4):311–314. [PubMed]
  • Stewart VC, Giovannoni G, Land JM, McDonald WI, Clark JB, Heales SJ. Pretreatment of astrocytes with interferon-alpha/beta impairs interferon-gamma induction of nitric oxide synthase. J Neurochem. 1997 Jun;68(6):2547–2551. [PubMed]
  • Stewart WA, Hall LD, Berry K, Paty DW. Correlation between NMR scan and brain slice data in multiple sclerosis. Lancet. 1984 Aug 18;2(8399):412–412. [PubMed]
  • Stys PK, Sontheimer H, Ransom BR, Waxman SG. Noninactivating, tetrodotoxin-sensitive Na+ conductance in rat optic nerve axons. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6976–6980. [PMC free article] [PubMed]
  • Tancredi V, D'Arcangelo G, Grassi F, Tarroni P, Palmieri G, Santoni A, Eusebi F. Tumor necrosis factor alters synaptic transmission in rat hippocampal slices. Neurosci Lett. 1992 Nov 9;146(2):176–178. [PubMed]
  • Targ EF, Kocsis JD. 4-Aminopyridine leads to restoration of conduction in demyelinated rat sciatic nerve. Brain Res. 1985 Mar 4;328(2):358–361. [PubMed]
  • Thompson AJ, Kermode AG, Wicks D, MacManus DG, Kendall BE, Kingsley DP, McDonald WI. Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol. 1991 Jan;29(1):53–62. [PubMed]
  • TITCOMBE AF, WILLISON RG. Flicker fusion in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1961 Aug;24:260–265. [PMC free article] [PubMed]
  • Truyen L, van Waesberghe JH, van Walderveen MA, van Oosten BW, Polman CH, Hommes OR, Adèr HJ, Barkhof F. Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology. 1996 Dec;47(6):1469–1476. [PubMed]
  • Utzschneider DA, Archer DR, Kocsis JD, Waxman SG, Duncan ID. Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):53–57. [PMC free article] [PubMed]
  • van Walderveen MA, Kamphorst W, Scheltens P, van Waesberghe JH, Ravid R, Valk J, Polman CH, Barkhof F. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology. 1998 May;50(5):1282–1288. [PubMed]
  • Waxman SG. Clinicopathological correlations in multiple sclerosis and related diseases. Adv Neurol. 1981;31:169–182. [PubMed]
  • Waxman SG. Demyelination in spinal cord injury. J Neurol Sci. 1989 Jun;91(1-2):1–14. [PubMed]
  • Waxman SG. Sodium channel blockade by antibodies: a new mechanism of neurological disease? Ann Neurol. 1995 Apr;37(4):421–423. [PubMed]
  • Waxman SG, Brill MH. Conduction through demyelinated plaques in multiple sclerosis: computer simulations of facilitation by short internodes. J Neurol Neurosurg Psychiatry. 1978 May;41(5):408–416. [PMC free article] [PubMed]
  • Waxman SG, Foster RE. Ionic channel distribution and heterogeneity of the axon membrane in myelinated fibers. Brain Res. 1980 Oct;203(2):205–234. [PubMed]
  • Waxman SG, Geschwind N. Major morbidity related to hyperthermia in multiple sclerosis. Ann Neurol. 1983 Mar;13(3):348–348. [PubMed]
  • Waxman SG, Ritchie JM. Molecular dissection of the myelinated axon. Ann Neurol. 1993 Feb;33(2):121–136. [PubMed]
  • Waxman SG, Utzschneider DA, Kocsis JD. Enhancement of action potential conduction following demyelination: experimental approaches to restoration of function in multiple sclerosis and spinal cord injury. Prog Brain Res. 1994;100:233–243. [PubMed]
  • Weiller C, Ramsay SC, Wise RJ, Friston KJ, Frackowiak RS. Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction. Ann Neurol. 1993 Feb;33(2):181–189. [PubMed]
  • Willoughby EW, Grochowski E, Li DK, Oger J, Kastrukoff LF, Paty DW. Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients. Ann Neurol. 1989 Jan;25(1):43–49. [PubMed]
  • Woolf CJ, Allchorne A, Safieh-Garabedian B, Poole S. Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. Br J Pharmacol. 1997 Jun;121(3):417–424. [PMC free article] [PubMed]
  • Wu JV, Shrager P. Resolving three types of chloride channels in demyelinated Xenopus axons. J Neurosci Res. 1994 Aug 15;38(6):613–620. [PubMed]
  • Wu JV, Rubinstein CT, Shrager P. Single channel characterization of multiple types of potassium channels in demyelinated Xenopus axons. J Neurosci. 1993 Dec;13(12):5153–5163. [PubMed]
  • Yamashita T, Ando Y, Obayashi K, Uchino M, Ando M. Changes in nitrite and nitrate (NO2-/NO3-) levels in cerebrospinal fluid of patients with multiple sclerosis. J Neurol Sci. 1997 Dec 9;153(1):32–34. [PubMed]
  • Youl BD, Turano G, Miller DH, Towell AD, MacManus DG, Moore SG, Jones SJ, Barrett G, Kendall BE, Moseley IF, et al. The pathophysiology of acute optic neuritis. An association of gadolinium leakage with clinical and electrophysiological deficits. Brain. 1991 Dec;114(Pt 6):2437–2450. [PubMed]
  • Young W, Rosenbluth J, Wojak JC, Sakatani K, Kim H. Extracellular potassium activity and axonal conduction in spinal cord of the myelin-deficient mutant rat. Exp Neurol. 1989 Oct;106(1):41–51. [PubMed]
  • Yu B, Shinnick-Gallagher P. Interleukin-1 beta inhibits synaptic transmission and induces membrane hyperpolarization in amygdala neurons. J Pharmacol Exp Ther. 1994 Nov;271(2):590–600. [PubMed]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...