Exekutivfunktionsleistungen bei Patienten mit multipler Sklerose

Zusammenfassung

Kognitive Defizite bei multipler Sklerose (MS) haben in den letzten Jahren wachsende Beachtung gefunden. In dieser Untersuchung verglichen wir die Leistung von 40 MS-Patienten und 18 Kontrollpersonen anhand von Verfahren zu den Exekutivfunktionen, zum sprachlichen Gedächtnis und zur kognitiven Verarbeitungsgeschwindigkeit. Außerdem wurde das Ausmaß der depressiven Symptomatik und der psychosomatischen Beschwerden in der MS-Gruppe erhoben. Ausgangspunkt war die These, dass die häufige Lage der MS-spezifischen Entzündungsherde im Bereich des periventrikulären Marklagers speziell zu Einbußen im Arbeitsgedächtnis und in den Exekutivfunktionen führen sollte. Das Ergebnis zeigte eine deutliche Korrelation des klinischen Status der Patienten (EDSS-Wert) mit der kognitiven Verarbeitungsgeschwindigkeit und der Abrufleistung des sprachlichen Gedächtnisses. Patienten mit sekundär chronisch progredienter MS waren in praktisch allen Exekutivfunktionsparametern beeinträchtigt. Für die Gesamtgruppe der MS-Patienten wie für die Gruppe mit schubförmiger MS fand sich dagegen ein signifikanter Unterschied in einer einfachen Arbeitsgedächtnis- und in einer Reaktionswechselaufgabe, d. h. in zwei Aspekten der Exekutivfunktionen. Die Studie zeigt, dass kognitive Defizite bei MS-Patienten signifikant gehäuft auftreten und es möglich sein könnte, klinisches Stadium, Verlaufsform und allgemeine Erkrankung an MS mittels spezifischer neuropsychologischer Verfahren zu differenzieren.

Abstract

During the last years, research on cognitive deficits in patients with multiple sclerosis (MS) has been intensified. Since MS-specific lesions are often found in the periventricular cerebral white matter, impairments in working memory and executive functions should prevail. The present study compares 40 MS patients and 18 controls in tests on executive function, verbal memory and attention. In addition we gathered data on depression and the extent of psychosomatic complaints in the MS group. The analysis revealed a significant correlation between the patients' clinical status (EDSS score), attention, and free recall. Patients with secondary chronic progressive MS were impaired in virtually all parameters of executive functions. We found a significant difference in a simple working memory task and a reaction alteration task for the MS group as a whole and for the group with relapsing-remitting MS. MS patients therefore suffer from cognitive deficits in considerable numbers. Our results demonstrate that it may be possible to differentiate the stages of MS and make assessments of the course and type of the disease by means of specific neuropsychological procedures.

Literatur

• 1 Prosiegel M, Michael C. Neuropsychology and multiple sclerosis: diagnostic and rehabilitative approaches.  J Neurol Sci. 1993;  115, Suppl 51-54
• 2 Rao S M. Neuropsychology of multiple sclerosis.  Curr Opin Neurol. 1995;  8 216-220
• 3 Wishart H, Sharpe D. Neuropsychological aspects of multiple sclerosis: A quantitative review.  J Clin Exp Neuropsychol. 1997;  19 810-824
• 4 Brassington J C, Marsh N V. Neuropsychological aspects of multiple sclerosis.  Neuropsychol Rev. 1998;  8 43-77
• 5 McDonald W I, Ron M A. Multiple sclerosis: the disease and its manifestations. Philosoph Transact Royal Soc Lond B.  Biol Sci. 1999;  354 1615-1622
• 6 Zakzanis K K. Distinct neurocognitive profiles in multiple sclerosis subtypes.  Arch Clin Neuropsychol. 2000;  15 115-136
• 7 Kujala P, Portin R, Revonsuo A, Ruutiainen J. Attention related performance in two cognitively different subgroups of patients with multiple sclerosis.  J Neurol Neurosurg Psychiatry. 1995;  59 77-82
• 8 Kessler H R, Cohen R A, Lauer K, Kausch D F. The relationship between disability and memory dysfunction in multiple sclerosis.  Int J Neurosci. 1992;  62 17-34
• 9 Higginson C I, Arnett P A, Voss W D. The ecological validity of clinical tests of memory and attention in multiple sclerosis.  Arch Clin Neuropsychol. 2000;  15 185-204
• 10 Rao S M, Leo G J, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction.  Neurology. 1991;  41 685-691
• 11 Amato M P, Ponziani G, Pracucci G. et al . Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up.  Arch Neurol. 1995;  52 168-172
• 12 Krupp L B, LaRocca N G, Muir-Nash J, Steinberg A D. The fatigue severity scale.  Arch Neurol. 1989;  46 1121-1123
• 13 Norman D A, Shallice T. Attention to action: Willed and automatic control of behaviour. University of California; CHIP Report 1980
• 14 Baddeley A. Working memory. Oxford; Oxford University Press 1986
• 15 Jonides J, Marshuetz C, Smith E E. et al . Age differences in behavior and PET activation reveal differences in interference resolution in verbal working memory.  J Cog Neurosci. 2000;  12 188-196
• 16 Posner M I, DiGirolamo G J. Executive attention: Conflict, target detection, and cognitive control. In: Parasuraman R (ed) The Attentive Brain. Cambridge; MIT Press 1998: 401-424
• 17 Cabeza R, Nyberg L. Imaging cognition II: An empirical review of 275 PET and fMRI studies.  J Cog Neurosci. 2000;  12 1-47
• 18 Sperling R A, Guttmann C RG, Hohol M J. et al . Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis.  Arch Neurol. 2001;  58 115-121
• 19 Rao S M. Overview: History of cognitive dysfunction and current evaluation methods used in MS. In: Kinkel, RP, Rao SM, Bourdette DN (eds) Cognitive Dysfunctions in MS. Cleveland; Universitätsverlag 2001
• 20 Ryan L, Clark C M, Klonoff H. Patterns of cognitive impairment in relapsing-remitting multiple sclerosis and their relationship to neuropathology on magnetic resonance images.  Neuropsychology. 1996;  2 176-193
• 21 Miller D H, Barkhof F, Frank J A. et al . Measurement of atrophy in multiple sclerosis: Pathological basis, methodological aspects and clinical relevance.  Brain. 2002;  125 1676-1695
• 22 Dalton C M, Brex P A, Jenkins R. et al . Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis.  J Neurol Neurosurg Psychiatry. 2002 Aug;  73 141-147
• 23 Rovaris M, Iannucci G, Falautano M. et al . Cognitive dysfunction in patients with mildly disabling relapsing-remitting multiple sclerosis: an exploratory study with diffusion tensor MR imaging.  J Neurol Sci. 2002 Mar 30;  195 103-109
• 24 Goldman-Rakic P S, Friedman H R. The circuitry of working memory revealed by anatomy and metabolic imaging. In: Levin HS, Eisenberg HM, Benton AL (eds) Frontal Lobe Function and Dysfunction. Oxford; Oxford University Press 1991: 72-91
• 25 Foong J, Rozewicz L, Quaghebeur G. et al . Executive function in multiple sclerosis. The role of frontal lobe pathology.  Brain. 1997;  120 15-26
• 26 Arnett P A, Rao S M, Grafman J. et al . Executive functions in multiple sclerosis: an analysis of temporal ordering, semantic encoding, and planning abilities.  Neuropsychology. 1997;  11 535-544
• 27 D'Esposito M, Onishi H, Thompson J. et al . Working memory impairments in multiple sclerosis: Evidence from a dual-task paradigm.  Neuropsychology. 1996;  1 51-56
• 28 Gronwall D M. Paced auditory serial addition task: A measure of recovery from concussion.  Perception and Motor Skills. 1977;  44 363-373
• 29 Cutter G R, Baier M L, Rudick R A. et al . Development of a multiple sclerosis functional composite as a clinical trial outcome measure.  Brain. 1999;  122 871-882
• 30 Staffen W, Mair A, Zauner H. et al . Cognitive function and fMRI in patients with multiple sclerosis: Evidence for compensatory cortical activation during an attention task.  Brain. 2002;  125 1275-1282
• 31 Veiel H OF. A preliminary profile of neuropsychological deficits associated with major depression.  J Clin Exp Neuropsychology. 1997;  19 587-603
• 32 Zakzanis K K, Leach L, Kaplan E. Neuropsychological differential diagnosis. Lisse; Swets & Zeitlinger 1999
• 33 Zorzon M. Depression and anxiety in multiple sclerosis. A clinical and MRI study in 95 subjects.  J Neurol. 2001;  248 416-421
• 34 Lehrl S, Merz J, Burkard G, Fischer B. Mehrfachwahl-Wortschatz-Intelligenztest (MWT - A). Erlangen; Perimed Fachbuchverlagsgesellschaft 1991
• 35 Horn W. Leistungsprüfsystem (LPS). Bern; Hans Huber Verlag 1983
• 36 Zimmermann P, Fimm B. Testbatterie zur Aufmerksamkeitsprüfung. Freiburg; PsyTest 1992
• 37 Ilmberger J. Deutsche Version des CVLT. München; Institut für Medizinische Psychologie der Universität 1988
• 38 Hildebrandt H, Gießelmann G, Sachsenheimer W, Schwendemann G. Topisch-neuropsychologische Diagnostik sprachlicher Gedächtnisdefizite.  Fortschr Neurol Psychiatrie. 2001;  69 32-41
• 39 Nelson H E. A modified card-sorting test sensitive to frontal lobe defects.  Cortex. 1976;  12 313-324
• 40 Braver T S, Cohen J D, Nystrom L E. et al . A parametric study of prefrontal cortex involvement in human working memory.  Neuroimage. 1997;  5 49-62
• 41 Callicott J H, Mattay V S, Bertolino A. et al . Physiological characteristics of capacity constraints in working memory as revealed by functional MRI.  Cerebral Cortex. 1999;  9 20-26
• 42 Kammer T, Bellemann M E, Göckel F. et al . Functional MR Imaging of the prefrontal cortex: Specific activation in a working memory task.  Mag Res Imag. 1997;  15 879-889
• 43 Gold J M, Berman K F, Randolph C. et al . PET Validation of a Novel Prefrontal Task: Delayed Response Alternation.  Neuropsychol. 1996;  10 3-10
• 44 von Zerssen D. Die Beschwerdenliste. Weinheim; Beltz 1976
• 45 Montgomery S A, Asberg M. A new depression scale designed to be sensitive to change.  British Journal of Psychiatry. 1979;  134 382-389
• 46 Hildebrandt H, Schwendemann G. Kognitive Beeinträchtigungen bei Multipler Sklerose. Bad Honnef; Hippokampus Verlag 003
• 47 Voss W D, Arnett P A, Higginson C I. et al . Contributing factors to depressed mood in Multiple Sclerosis.  Arch Clin Neuropsychol. 2002;  17 103-115
• 48 Kujala P, Portin R, Ruutiainen J. The progress of cognitive decline in multiple sclerosis. A controlled 3-year follow-up.  Brain. 1997;  120 289-297
• 49 Archibald C J, Fisk J D. Information processing efficiency in patients with multiple sclerosis.  J Clin Exp Neuropsychol. 2000;  22 686-701
• 50 Kurtzke J F. Natural history and clinical outcome measures for multiple sclerosis studies. Why at the present time does EDSS scale remain a preferred outcome measure.  Neurol Sci. 2000;  21 339-341
• 51 Flachenecker P, Hartung H-P. Krankheitsverlauf und Prognose der multiplen Sklerose.  Nervenarzt. 1996;  67 435-451
• 52 Collins L F, Long C J. Visual reaction time and its relationship to neuropsychological test performance.  Arch Clin Neuropsychol. 1996;  7 613-623
• 53 Western S, Long C J. Relationship between reaction time and neuropsychological test performance.  Arch Clin Neuropsychol. 1996;  11 557-571
• 54 DeSonneville L MJ, Boringa J B, Reuling I EW. et al . Information processing characteristics in subtypes of multiple sclerosis.  Neuropsychologia. 2002;  40 1751-1765
• 55 Stuss D T, Levine B, Alexander M P. et al . Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: Effects of lesion location and test structure.  Neuropsychologia. 2000;  38 388-402
• 56 Fisk J D, Archibald C J. Limitations of the Paced Auditory Serial Addition Test as a measure of working memory in patients with multiple sclerosis.  J Int Neuropsychol Soc. 2001;  7 363-372
• 57 Brokate B, Hildebrandt H, Eling P. et al .Frontal functions in Korsakoff's syndrome and chronic alcoholism: Continuity or discontinuity in the affection?.  Submitted 2002
• 58 Jonides J, Smith E E, Marshuetz C. et al . Inhibition in verbal working memory revealed by brain activation.  Proc Nat Acad Sci. 1998;  95 8410-8413
• 59 Smith E E, Jonides J. Neuroimaging analyses of human working memory.  Proc Nat Acad Sci. 1998;  95 12061-12068
• 60 Hoogervorst E L, Polman C H, Barkhof F. Cerebral volume changes in multiple sclerosis patients treated with high-dose intravenous methylprednisolone.  Multiple Sclerosis. 2002;  8 415-419
• 61 Rao A, Richert N, Howard T. et al . Methylprednisolone effect on brain volume and enhancing lesions in multiple sclerosis before and during IGNbeta-1b.  Neurology. 2002;  59 688-694
• 62 Patzold T, Schwengelbeck M, Ossege L M. et al . Changes of the MS functional composite and EDSS during and after treatment with methylprednisolone in patients with multiple sclerosis.  Acta Neurol Scand. 2002;  105 164-168
• 63 Oliveri R L, Sibilia G, Valentino P. et al . Pulsed methylprednisolone induces a reversible impairment of memory in patients with relapsing-remitting multiple sclerosis.  Acta Neurol Scand. 1998;  97 366-369
• 64 Naber D, Dand P, Heigl B. Psychopathological and neuropsychological effects of 8-days' corticosteroid treatment. A prospective study.  Psychoneuroendrocrinology. 1996;  21 25-31