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


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 


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.


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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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