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The Italian Journal of Neurological Sciences

, Volume 19, Supplement 6, pp S443–S447 | Cite as

Pathophysiology of cognitive impairment in multiple sclerosis

  • G. Comi
  • V. Martinelli
Cognitive Dysfunction in MS

Abstract

Only in the last decade has significant progress been reached in understanding the pathophysiology of cognitive impairment in multiple sclerosis (MS). Edema, inflammation, demyelination and axonal loss may have different consequences on nerve fiber conduction, causing temporal disorganization or disruption of the inputs travelling along the intrahemispheric and interhemispheric connections among associative areas as well as between cortical and subcortical structures involved in mental functions.

Neuropsychological, electrophysiological, metabolic and magnetic resonance imaging (MRI) studies have provided converging evidence that the most common type of cognitive dysfunction observed in MS patients, the so-called subcortical dementia, is an almost invariable complication of the advanced phases of the disease. In these phases, large amounts of brain white matter may be affected by microscopic and macroscopic lesions characterized by pronounced axonal loss.

However, the acute occurence of transitory and isolated selective cognitive deficits or reversible dementia has been observed in a few patients. In these cases a pathogenetic role of the inflammatory process in cognitive changes is to be considered. In fact, antineural antibodies, proinflammatory cytokines and other neurotoxic substances may induce or regulate several critical cellular and electrophysiologic functions. Understan-ding how the cellular and humoral responses may be differently associated with acute or chronic disease evolution and with macroscopic and microscopic brain changes is essential for the formulation of a unifying pathogenetic model of cognitive impairment in MS.

Key words

Multiple sclerosis Cognitive dysfunction PET Event-related potentials 

Sommario

Solo negli ultimi anni sono stati raggiunti significativi risultati nella conoscenza della fisiopatologia dei disturbi cognitivi nella sclerosi multipla (SM). La risonanza magnetica ha consentito di rilevare correlazioni tra disturbi cognitivi ed entità del carico lesionale globale e regionale oltre che con indici di atrofia cerebrale. Più recenti studi neurofisiologici (potenziali evento correlati, studio della coerenza dell'elettroencefalogramma) e l'uso di tecniche non convenzionali di risonanza magnetica hanno inoltre permesso di definire con più precisione il substrato patologico e funzionale delle lesioni macroscopiche. La interruzione o disfunzione parziale delle connessioni tra diverse aree corticali o tra strutture corticali e sottocorticali é alla base della cosiddetta demenza sottocorticale, irreveribile e progressiva, osservata generalmente nei pazienti con SM di una certa durata e gravità, associata principalmente a perdita assonale e a grave demielinizzazione. È comunque sempre più frequente l'osservazione di pazienti SM con disturbi cognitivi, selettivi o globali, ad esordio acuto e transitori, nei quali può essere ipotizzato un coinvolgimento diretto del processo infiammatorio. Anticorpi contro antigeni neuronali, citochine proinfiammatorie e neurotossine possono infatti, con diversi meccanismi, interferire sia sul funzionamento cellulare sia sulla conduzione nervosa delle strutture coinvolte nelle funzioni cognitive.

References

  1. 1.
    Peyser JM, Rao SM, Larocca NG, Kaplan E (1990) Guidelines for neuropsychological research in multiple sclerosis. Arch Neurol 47:94–97Google Scholar
  2. 2.
    Beatty WW (1993) Memory and frontal lobe dysfunction in multiple sclerosis. J Neurol Sci 115:S38-S41Google Scholar
  3. 3.
    Rao SM (1986) Neuropsychology of multiple sclerosis: A critical review. J Clin Exp Neuropsychol 5:503–542.Google Scholar
  4. 4.
    Filley CM, Heaton RK, Nelson LM et al (1989) A comparison of dementia in Alzheimer's disease and multiple sclerosis. Arch Neurol 46:157–161Google Scholar
  5. 5.
    Comi G, Filippi M, Martinelli V et al (1993) Brain magnetic resonance imaging correlates of cognitive impairment in mutiple sclerosis. J Neurol Sciences 115:S66-S73Google Scholar
  6. 6.
    Amato MP, Ponziani G, Pracucci G et al (1995) Cognitive impairment in early onset multiple sclerosis. Arch Neurol 52:168–172Google Scholar
  7. 7.
    Kujala P, Portin R, Ruutiainen J (1997) The progress of cognitive decline in multiple sclerosis. A controlled 3-year follow-up. Brain 120:289–297Google Scholar
  8. 8.
    Lyon-Caen O, Jouvent R, Hauser S et al (1986) Cognitive function in recent onset demyelinating diseases. Arch Neurol 43:1138–1141Google Scholar
  9. 9.
    Callanan MM, Logsdail SJ, Ron MA et al (1989) Cognitive impairment in patients with clinically isolated lesions of the type seen in multiple sclerosis. Brain 112:361–364Google Scholar
  10. 10.
    Rao SM, Leo GJ, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns and predictions. Neurology 41:685–691Google Scholar
  11. 11.
    Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology 41:692–696Google Scholar
  12. 12.
    Anzola GP, Bevilacqua L, Cappa SF et al (1990) Neuropsychological assessment in patients with relapsing-remitting multiple sclerosis and mild functional impairment. Correlation with MRI. J Neurol Neurosurg Psychiatry 53:142–145Google Scholar
  13. 13.
    Franklin GM, Nelson LM, Filter CM, Heaton RK (1989) Cognitive loss in multiple sclerosis. Arch Neurol 46:162–167Google Scholar
  14. 14.
    Filippi M, Campi A, Mammi S, Martinelli V, Locatelli T, Scotti G, Amadio S, Canal N, Comi G (1995) Brain magnetic resonance imaging and multimodal evoked potentials in benign and secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 58:31–37Google Scholar
  15. 15.
    Rao, SM, Leo GJ, St. Hubin Faubert P (1989) On the nature of memory disturbance in multiple sclerosis. J Clin Exp Neuropsychol 11:699–712Google Scholar
  16. 16.
    Swirsky-Sacchetti T, Mitchell DR, Seward J et al (1992) Neuropsychological and structural brain lesions in multiple sclerosis: A regional analysis. Neurology 42:1291–1295Google Scholar
  17. 17.
    Medaer R, Nelissen E, Appel B et al (1987) Magnetic resonance imaging and cognitive functioning in multiple sclerosis. J Neurol 235:86–89Google Scholar
  18. 18.
    Rovaris M, Filippi M, Falautano M et al (1998) Relation between MR abnormalities and pattern of cognitive impairment in MS. Neurology 50:1601–1608Google Scholar
  19. 19.
    Damian MS, Shilling G, Bachmann G et al (1994) White matter lesions and cognitive deficits: Relevance of lesion pattern? Acta Neurol Scand 90:430–436Google Scholar
  20. 20.
    Lassmann H (1983) Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis. Schriftenr Neurol 25:1–135Google Scholar
  21. 21.
    Lucchinetti CF, Bruck W, Rodriguez M et al (1996) Distinct pattern of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol 6:259–274Google Scholar
  22. 22.
    Comi G, Filippi M, Martinelli V et al (1995) Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis. J Neurol Sci 132:222–227Google Scholar
  23. 23.
    Leocani L, Locatelli T, Martinelli V et al (1996) EEG coherence in multiple sclerosis: Correlation with clinical, neuropsychological and MRI findings. Electroencephalogr Clin Neurophysiol 99:P349Google Scholar
  24. 24.
    Honig LS, Ramsay RE, Sheremata WA (1992) Event related potential P300 in multiple sclerosis. Relation to magnetic resonance imaging and cognitive impairment. Arch Neurol 49(1):44–50Google Scholar
  25. 25.
    Paulesu E, Perani D, Fazio F et al (1996) Functional basis of memory impairment in multiple sclerosis: A 18F FDG PET study. Neuroimage 4:87–96Google Scholar
  26. 26.
    William CS, Rivera VM, Breitbach W et al (1991) Reversible acute dementia in multiple sclerosis. Neurology 41 [Suppl]:215Google Scholar
  27. 27.
    Foong J, Rozewicz I, Auaghebeur G et al (1998) Neuropsychological deficits in multiple sclerosis after acute relapse. J Neurol Neurosurg Psychiatry 64:529–532Google Scholar
  28. 28.
    Gladman DD, Urowitz MB (1994) Systemic lupus erythematosus. Clinical features. In: Klippel JH, Dieppe PA (eds) Rheumatology. Mosby-Year Book Europe, London, pp 1–8Google Scholar
  29. 29.
    Sibbitt WL, Sibbitt RR, Griffey RH et al (1989) magnetic resonance and computed tomographic imaging in the evaluation of acute neuropsychiatric disease in systemic lupus erythematosus. Ann Rheum Dis 48:1014–1022Google Scholar
  30. 30.
    Wilson HA, Winfield JB, Lahita RG et al (1979) Association of IgG antibrain antibodies with central nervous systemic dysfunction in systemic lupus erythematosus. Arthritis Rheum 22:458–462Google Scholar
  31. 31.
    Robbins ML, Kornguth SE, Bell CL et al (1988) Antineurofilament antibody evaluation in neuropsychiatric systemic lupus erythematosus: Combination with anticardi olipin antibody assay and magnetic resonance imaging. Arthritis Rheum 31:623–641Google Scholar
  32. 32.
    Koller H, Sielber M, Hartung HP (1997) Immunologically induced electrophysiological dysfunction: Implications for inflammatory diseases of the CNS and PNS. Prog Neurobiol 52:1–26Google Scholar
  33. 33.
    33.Lypton SA, Gendelman HE (1995) Dementia associated with the acquired immunodeficiency syndrome. N Eng J Med 332:934–940Google Scholar

Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • G. Comi
    • 1
  • V. Martinelli
    • 1
  1. 1.Multiple Sclerosis CentreScientific Institute Ospedale San RaffaeleMilanoItaly

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