The results of complex studies were used to formulate a concept of the development of neurological impairments in multiple sclerosis (MS). Acutely developing impairments to spike propagation, reaching the level of conduction blockade, due to the active pathological process with demyelinating and axonal damage to the CNS lead to the formation of neurological impairments in exacerbations of MS, while complete or partial reversion (regression) of these symptoms in the stage of remission results from compensatory changes in the nature of conduction, which were not, however, accompanied by recovery of electrophysiological measures. The development of stable neurological deficit in secondary-progressive MS is determined by impairments to spike conduction processes associated with significant levels of demyelination and atrophic changes in the CNS, with myelin loss and axon death. Finally, the severity of cognitive changes is determined by differences in the severities of both the focal demyelinating process and diffuse damage to brain substance in MS, including the neurodegenerative component. The main factor in transient increases in symptoms is the universal lability of electrophysiological parameters, including those developing on the background of ion and neurotransmitter imbalance.
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References
E. V. Baidina, Lability of Neurological Symptoms in Multiple Sclerosis (Clinical, Electrophysiological, and Biochemical Studies) [in Russian], Author's Abstract of Master's Thesis in Medical Sciences, Moscow (2004).
V. P. Barkhatova, “Pathophysiology of the demyelinating process,” in: Multiple Sclerosis: Selected Questions in Theory and Practice [in Russian], I. A. Zavalishin and V. I. Golovkin (eds.), Elf IRP, Moscow (2000), pp. 185–203.
M. V. Krotenkova, The State of the Brain Matter and Liquor System in Multiple Sclerosis (a Clinical-MRI Study) [in Russian], Author's Abstract of Master's Thesis in Medical Sciences, Moscow (2002).
A. V. Peresedova, Pathophysiological Mechanisms of Formation of Neurological Impairments in Multiple Sclerosis [in Russian], Author's Abstract of Master's Thesis in Medical Sciences, Moscow (2006).
O. V. Trifonov, Cognitive Changes in Patients with Multiple Sclerosis (Clinical, Neuropsychological, and Electrophysiological Studies) [in Russian], Author's Abstract of Master's Thesis in Medical Sciences, Moscow (2006).
K. Abe, and H. Saito, “Involvement of Na+-K+ pump in L-glutamate clearance by cultured rat cortical astrocytes,” Biol. Pharm. Bull., 23, 1051–1054 (2000).
S. Bajada, F. L. Mastaglia, J. L. Black, and D. W. K. Collins, “Effects of induced hyperthermia on visual evoked potentials and saccade parameters in normal subjects and multiple sclerosis patients,” J. Neurol. Neurosurg. Psychiat., 43, 849–852 (1980).
C. Bjartmar and B. D. Trapp, “Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences,” Curr. Opin. Neurol., 14, 271–278 (2001).
J.-Y. Chatton, L. Pellerin, and P. J. Magistretti, “GABA uptake into astrocytes is not associated with significant metabolic cost: implications for brain imaging of inhibitory transmission,” Proc. Natl. Acad. Sci. USA, 100, 12456–12461 (2003).
M. Clanet and X. Montalba (Chairmen), The Future of Multiple Sclerosis Therapies, PAREXEL MMS Eur. Ltd. (2006).
G. D'Intimo, M. Paradisi, M. Fernandez, et al., “Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats,” Proc. Natl. Acad. Sci. USA, 102, 3070–3075 (2005).
J. D. England, F. Gamboni, S. R. Levinson, and T. E. Finger, “Changed distribution of sodium channels along demyelinated axons,” Proc. Natl. Acad. Sci. USA, 87, 6777–6786 (1990).
P. A. Felts and K. J. Smith, “Conduction properties of central nerve fibers remyelinated by Schwann cells,” Brain Res., 574, 178–192 (1992).
P. A. Felts, T. A. Baker, and K. J. Smith, “Conduction in segmentally demyelinated mammalian central axons,” J. Neurosci., 17, 7267–7277 (1997).
R. E. Foster, C. C. Whalen, and S. G. Waxman, “Reorganization of the axon membrane in demyelinated peripheral nerve fibers: morphological evidence,” Science, 210, 661–663 (1980).
P. T. Gray and J. M. Ritchie, “Ion channels in Schwann and glial cells,” Trends Neurosci., 8, 411–415 (1985).
O. Honmou, P. A. Felts, S. G. Waxman, and J. D. Kocsis, “Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells,” J. Neurosci., 16, 3199–3208 (1996).
A. M. Humm, S. Beer, J. Kool, et al., “Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study,” Clin. Neurophysiol., 115, 2493–2501 (2004).
J. V. Jestico and P. D. Ellis, “Changes in nystagmus on raising body temperature in clinically suspected and proved multiple sclerosis,” Brit. Med. J., 2, 970–972 (1976).
L. B. Krupp, C. Christodoulou, P. Melville, et al., “Donepezil improves memory in multiple sclerosis in a randomized clinical trial,” Neurology, 63, 1579–1585 (2004).
A. Lambet, P. Laduron, C. Mourre, et al., “Axonal transport of the voltage-dependent Na channel protein identified by its tetrodotoxin-binding site in rat sciatic nerves,” Brain Res., 345, 153–158 (1985).
G. Lovas, N. Szilagyi, K. Majtenyi, et al., “Axonal changes in chronic demyelinated cervical spinal cord plaques,” Brain, 123, 308–317 (2000).
A. Lycklama, G. J. Nijeholt, M. A. A. Walderveen, et al., “Brain and spinal cord abnormalities in multiple sclerosis: correlation between MRI parameters, clinical subtypes and symptoms,” Brain, 121, 687–697 (1998).
D. B. McGavern, P. D. Murray, C. Rivera-Quicones, et al., “Axonal loss results in spinal cord atrophy, electrophysiological abnormalities and neurological deficits following demyelination in a chronic inflammatory model of multiple sclerosis,” Brain, 123, 519–531 (2000).
M. Nedergaard, T. Takano, and A. J. Hansen, “Beyond the role of glutamate as a neurotransmitter,” Nat. Rev. Neurosci., 3, 748–755 (2002).
M. Oka, Y. Itoh, and Y. Ukai, “Involvement of Na+ and Ca2+ channel activation and resultant nitric oxide synthesis in glutamate-mediated hypoxic injury in rat cerebrocortical slices,” Life Sci., 67, 2331–2343 (2000).
K. Okada, U. Yamashita, and S. Tsuji, “Modulation of Na(+)-dependent glutamate transporter of murine astrocytes by inflammatory mediators,” J. UOEH, 27, 161–170 (2005).
H. E. Personn and C. Sachs, “VEPs during provoked visual impairment in multiple sclerosis,” in: Evoked Potentials, C. Barber (ed.), University Park Press, Baltimore (1980), 575–579.
J. W. Prineas, R. O. Barnard, E. E. Kwon, et al., “Multiple sclerosis: remyelination of nascent lesions,” Ann. Neurol., 33, 137–151 (1993).
J. W. Prineas, R. O. Barnard, T. Revesz, et al., “Multiple sclerosis. Pathology of recurrent lesions,” Brain, 116, 681–693 (1993).
M. Rasminsky, “The effect of temperature on conduction in demyelinated single nerve fibers,” Arch. Neurol., 28, 287–292 (1973).
H. Reddy, S. Narayanan, R. Arnoutelis, et al., “Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis,” Brain, 123, 2314–2320 (2000).
D. Regan, T. J. Murray, and R. Silver, “Effect of body temperature on visual evoked potential delay and visual perception in multiple sclerosis,” J. Neurol. Neurosurg. Psychiat., 40, 1083–1091 (1977).
C. Rivera-Quicones, D. McGavern, and J. D. Schmelzer, “Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis,” Nature Med., 4, 187–193 (1998).
C. L. Schauf and F. A. Davis, “Circulating toxic factors in multiple sclerosis: a perspective,” Adv. Neurol., 31, 267–280 (1981).
K. J. Smith and S. M. Hall, “Nerve conduction during peripheral demyelination and remyelination,” J. Neurol. Sci., 48, 201–219 (1980).
B. Voutsinos-Porche, G. Bonvento, K. Tanaka, et al., “Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex,” Neuron, 37, 275–286 (2003).
S. G. Waxman, J. A. Black, J. D. Kocsis, and J. M. Ritchie, “Low density of sodium channels supports action potential conduction in axons of neonatal rat optic nerve,” Proc. Natl. Acad. Sci. USA, 86, 1406–1410 (1989).
S. G. Waxman, “The perinodal astrocytes functional and developmental considerations,” in: Biology and Pathobiology of Astrocyte-Neuron Interactions, S. Fedoroff, R. Doucette, and B. H. Juurlink (eds.), Plenum, New York (1993), pp. 15–29.
S. G. Waxman, “Pathophysiology of demyelinated and remyelinated axons,” in: Handbook of Multiple Sclerosis, S. D. Cook (ed.), Marcel Dekker Inc. (1996), 2nd edition, pp. 257–293.
S. G. Waxman, “Loss and restoration of impulse conduction in disorders of myelin,” in: Handbook of Multiple Sclerosis, S. D. Cook (ed.), Marcel Dekker Inc. (2001), 3rd edition, pp. 257–288.
B. D. Youl, G. Turano, D. H. Miller, et al., “The pathophysiology of acute optic neuritis. An association of gadolinium-leakage with clinical and electrophysiological deficits,” Brain, 114, 2437–2450 (1991).
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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Multiple Sclerosis, Supplement, No. 4, pp. 50–56, 2007.
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Peresedova, A.V., Baidina, E.V., Trifonova, O.V. et al. Pathophysiological aspects of the formation of neurological deficit in multiple sclerosis. Neurosci Behav Physi 39, 39–45 (2009). https://doi.org/10.1007/s11055-008-9101-7
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DOI: https://doi.org/10.1007/s11055-008-9101-7