Neurological Sciences

, Volume 29, Issue 6, pp 435–444

Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome

  • Belgin Kocer
  • Tugba Unal
  • Bijen Nazliel
  • Zeynep Biyikli
  • Zulal Yesilbudak
  • Sirel Karakas
  • Ceyla Irkec
Original Article



This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs).


Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls.


Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05).


Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.


Clinically isolated syndromes Cognitive dysfunction Event-related potentials (P300) Multiple sclerosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fillipi M (2001) Magnetic resonance imaging findings predicting subsequent disease course in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neurol Sci 22:49–51CrossRefGoogle Scholar
  2. 2.
    Miller D, Barkhof F, Montalban X et al (2005) Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 4:281–288PubMedCrossRefGoogle Scholar
  3. 3.
    Schulz D, Kopp B, Kunkel A, Faiss JH (2006) Cognition in the early stage of multiple sclerosis. J Neurol 253:1002–1010PubMedCrossRefGoogle Scholar
  4. 4.
    Kesselring J, Klement U (2001) Cognitive and affective disturbances in multiple sclerosis. J Neurol 248:180–183PubMedCrossRefGoogle Scholar
  5. 5.
    Pinkston JB, Kablinger A, Alekseeva N (2007) Multiple sclerosis and behavior. Int Rev Neurobiol 79:323–339PubMedCrossRefGoogle Scholar
  6. 6.
    Achiron A, Doniger GM, Harel Y et al (2007) Prolonged response times characterize cognitive performance in multiple sclerosis. Eur J Neurol 14:1102–1108PubMedCrossRefGoogle Scholar
  7. 7.
    Huijbregts SCJ, Kalkers NF, de Sonneville LM et al (2006) Cognitive impairment and decline in different MS subtypes. J Neurol Sci 245:187–194PubMedCrossRefGoogle Scholar
  8. 8.
    Piras MR, Magnano I, Canu EDG et al (2003) Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiological findings. J Neurol Neurosurg Psychiatry 74:878–885PubMedCrossRefGoogle Scholar
  9. 9.
    Hohol MJ, Guttmann CR, Orav J et al (1997) Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis. Arch Neurol 54:1018–1025PubMedGoogle Scholar
  10. 10.
    Feinstein A, Kartsounis LD, Miller DH et al (1992) Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study. J Neurol Neurosurg Psychiatry 55:869–876PubMedCrossRefGoogle Scholar
  11. 11.
    Glanz BI, Holland CM, Gauthier SA et al (2007) Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis. Mult Scler 13:1004–1010PubMedCrossRefGoogle Scholar
  12. 12.
    Ellger T, Bethke F, Frese A et al (2002) Event-related potentials in different subtypes of multiple sclerosis: a cross-sectional study. J Neurol Sci 205:35–40PubMedCrossRefGoogle Scholar
  13. 13.
    Honig LS, Ramsay RE, Sheremata WA (1992) Event-related potential P300 in multiple sclerosis. Relation to magnetic resonance imaging and cognitive impairment. Arch Neurol 49:44–50PubMedGoogle Scholar
  14. 14.
    Triantafyllou NI, Voumvourakis K, Zalonis I et al (1992) Cognition in relapsing-remitting multiple sclerosis: a multichannel event-related potential (P300) study. Acta Neurol Scand 85:10–13PubMedCrossRefGoogle Scholar
  15. 15.
    Casanova-Gonzalez MF, Cabrera-Gomez JA, Aquino-Cias J et al (1999) Neurophysiological assessment in patients with clinically defined multiple sclerosis with special reference to P300 wave study. Rev Neurol 29:1134–1137PubMedGoogle Scholar
  16. 16.
    Magnie MN, Bensa C, Laloux L et al (2007) Contribution of cognitive evoked potentials for detecting early cognitive disorders in multiple sclerosis. Rev Neurol 163:1065–1074PubMedCrossRefGoogle Scholar
  17. 17.
    Van Dijk JG, Jennekens-Schinkel A, Caekebeke JF, Zwinderman AH (1992) Are event-related potentials in multiple sclerosis indicative of cognitive impairment? Evoked and event-related potentials, psychometric testing and response speed: a controlled study. J Neurol Sci 109:18–24PubMedCrossRefGoogle Scholar
  18. 18.
    Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRefGoogle Scholar
  19. 19.
    Benton AL, Spreen O, Varney NR, Hamsher KdeS (1983) Contributions to neuropsychological assessment: a clinical manual. Oxford University Press, OxfordGoogle Scholar
  20. 20.
    Bush RM, Frazier TW, Haggerty KA, Kubu CS (2005) Utility of the Boston naming test in predicting ultimate side of surgery in patients with medically intractable temporal lobe epilepsy. Epilepsia 46:1773–1779CrossRefGoogle Scholar
  21. 21.
    Grammaldo LG, Giampa T, Quarato PP et al (2006) Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy. Eur J Neurol 13:371–376PubMedCrossRefGoogle Scholar
  22. 22.
    Karakas S, Eski R, Oktem-Tanor O et al (2004) Sayi dizisi ö renme testi, çizgi yönünü belirleme testi, i aretleme testi, Raven standart progresif matrisler testi uygulama ve puanlama yönergesi. In: Karakas S (ed) Bilrot bataryasi el kitabi: Noropsikolojik testler icin arastirma ve gelistirme calismalari. Dizayn Ofset, Ankara, pp 257–302Google Scholar
  23. 23.
    Bland JM, Altman DG (1995) Multiple significance tests: the Bonferroni method. BMJ 310:170PubMedGoogle Scholar
  24. 24.
    McDonald WI, Compston A, Edan G 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
  25. 25.
    Thornton AE, Raz N, Tucker KA (2002) Memory in multiple sclerosis: contex-tual encodings deficits. J Int Neuropsychol Soc 8:395–409PubMedCrossRefGoogle Scholar
  26. 26.
    Williams J, O’Rourke K, Hutchinson M, Tubridy N (2006) The Face-Symbol Test and The Symbol-Digit Test are not reliable surrogates for the Paced Auditory Serial Addition Test in multiple sclerosis. Mult Scler 12:599–604PubMedCrossRefGoogle Scholar
  27. 27.
    Amato MP, Portaccio E, Goretti B et al (2006) The Rao’s Brief Repeatable Battery and Stroop test: normative values with age, education and gender corrections in an Italian population. Mult Scler 12:786–793CrossRefGoogle Scholar
  28. 28.
    Dalton CM, Chard DT, Davies GR et al (2004) Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 127:1101–1107PubMedCrossRefGoogle Scholar
  29. 29.
    Zivadinov R, Sepcic J, Nasuelli D et al (2001) A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 70:773–780PubMedCrossRefGoogle Scholar
  30. 30.
    Calabrese M, Atzori M, Bernardi V et al (2007) Cortical atrophy is relevant in multiple sclerosis at clinical onset. J Neurol 254:1212–1220PubMedCrossRefGoogle Scholar
  31. 31.
    Locatelli L, Zivadinov R, Grop A, Zorzon M (2004) Frontal paren chymal atrophy measures in multiple sclerosis. Mult Scler 10:562–568PubMedCrossRefGoogle Scholar
  32. 32.
    Gil R, Zai L, Neau JP et al (1993) Event-related auditory evoked potentials and multiple sclerosis. Electroencephalogr Clin Neurophysiol 88:182–187PubMedCrossRefGoogle Scholar
  33. 33.
    Giesser BS, Schroeder MM, LaRocca NG et al (1992) Endogenous event-related potentials as indices of dementia in multiple sclerosis patients. Electroencephalogr Clin Neuro - physiol 82:320–329CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2008

Authors and Affiliations

  • Belgin Kocer
    • 1
  • Tugba Unal
    • 1
  • Bijen Nazliel
    • 1
  • Zeynep Biyikli
    • 2
  • Zulal Yesilbudak
    • 1
  • Sirel Karakas
    • 3
  • Ceyla Irkec
    • 1
  1. 1.Department of NeurologyGazi University Medical FacultyBeşevler, ÇankayaTurkey
  2. 2.Department of BiostatisticsAnkara University Medical FacultyAnkaraTurkey
  3. 3.Department of Experimental PsychologyHacettepe UniversityAnkaraTurkey

Personalised recommendations