Kognitive Dysfunktion bei Multipler Sklerose

Zusammenfassung

Kognitive Beeinträchtigungen treten bei etwa jedem zweiten MS-Betroffenen unabhängig von der Verlaufsform auf. Sie zeigen weder Linearität zum körperlichen Beeinträchtigungsgrad gemessen mittels Expanded Disability Status Scale (EDSS), noch gibt es eine direkte Relation zur Erkrankungsdauer. Kognitive Defizite können bereits früh im Krankheitsgeschehen, beispielsweise bei einem Clinically Isolated Syndrome (CIS) oder Radiologically Isolated Syndrome (RIS) auftreten und werden auch bei Patienten mit einem benignen Verlauf beobachtet. Obgleich die Progression als eher moderat betrachtet werden kann, wirken sich kognitive Einbußen in beinahe jedem Stadium stark negativ auf die Lebensqualität und die Therapieadhärenz aus. Diagnostisch sind wir in der Lage mittels sensitiver Screeninginstrumente diejenigen kognitiven Teilfunktionen zu erfassen, die bei MS-Patienten am häufigsten beeinträchtigt sind. Wie so häufig in der Medizin hinkt jedoch die Therapie dem Fortschritt bei der Diagnostik hinterher, sodass wir keine zuverlässige evidenzbasierte symptomatische Therapie zur Behandlung kognitiver Defizite bei MS zur Verfügung haben. Derzeit sind nonpharmakologische Ansätze, mit dem Ziel die kognitive Reserve des Gehirns zu stärken, Erfolg versprechend. Methodisch saubere Wirksamkeitsstudien stehen allerdings noch aus.

Summary

With a prevalence of 50%, cognitive impairment belongs to the major symptoms in multiple sclerosis affecting patients irrespective of their disease course, disease severity as measured by the Expanded Disability Status Scale (EDSS) or their disease duration. Cognitive deficits can already occur at the very early stages of the disease such as in patients with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS). Further, even in patients with a so-called “benign” disease course, cognitive dysfunction has been described. Although the progression of the deficits can be regarded as moderate, cognitive impairment at all stages negatively impacts on quality of life. From a diagnostic point of view we have made progress in developing sensitive screening instruments to reliably assess the cognitive core deficits in MS. However as often seen in medicine development of therapeutic approaches lags behind the progress of diagnostics. Thus at present there is no reliable evidence-based symptomatic treatment for cognitive impairment in MS. However, nonpharmacological approaches targeted towards supporting cognitive brain reserve look promising though large methodologically precise effectiveness studies are still an unmet need.

Schlüsselwörter

Multiple Sklerose - Kognition - Neurodegeneration - Neuroinflammation - kognitive Rehabilitation

Keywords

Multiple sclerosis - cognition - neurodegeneration - neuroinflammation - cognitive rehabilitation

• Literatur

• 1 Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41: 685-91.
• 2 Benedict RH. et al. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc 2006; 12 (04) 549-58.
• 3 Amato MP. et al. Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort. J Neurol 2006; 253 (08) 1054-9.
• 4 Amato MP, Ponziani G, Siracusa G, Sorbi S. Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years. Arch Neurol 2001; 58: 1602-6.
• 5 Glanz BI, Healy BC, Hviid LE, Chitnis T, Weiner HL. Cognitive deterioration in patients with early multiple sclerosis: a 5-year study. J Neurol Neurosurg Psychiatry 2012; 83: 38-43.
• 6 Reuter F. et al. Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis. J Neurol Neurosurg Psychiatry 2011; 82 (10) 1157-9.
• 7 Calabrese P, Penner IK. Cognitive dysfunctions in multiple sclerosis – a “multiple disconnection syndrome?”. J Neurol 2007; 254: 18-21.
• 8 Kujala P, Portin R, Revonsuo A, Ruutiainen J. Automatic and controlled information processing in MS. Brain 1994; 117: 1115-26.
• 9 Armstrong C. et al. Serial position and temporal cue effects in multiple sclerosis: two subtypes of defective memory mechanisms. Neuropsychologia 1996; 34: 853-62.
• 10 Amato MP, Ponziani G, Pracucci G, Bracco L, Siracusa G, Amaducci L. Cognitive impairment in early-onset multiple sclerosis: Pattern, predictors, and impact on everyday life in a 4-year follow-up. Arch Neurol 1995; 52: 168-72.
• 11 Beatty WW, Blanco CR, Wilbanks SL, Paul RH, Hames KA. Demographic, clinical, and cognitive characteristics of MS patients who continue to work. Neurorehabilitation and neural repair 1995; 09: 167-73.
• 12 McDonald W. et al. Recommended diagnostic criteria for Multiple Sclerosis: Guidelines from the international panel on the diagnosis of Multiple Sclerosis. Ann Neurol 2001; 50: 121-7.
• 13 Camp SJ. et al. Cognitive function in primary progressive and transitional progressive multiple sclerosis. A controlled study with MRI correlates. Brain 1999; 122: 1341-8.
• 14 Fulton JC. et al. MR lesion load and cognitive function in patients with relapsing-remitting multiple sclerosis. American Journal of Neuroradiology 1999; 20: 1951-5.
• 15 Rovaris M. et al. Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis. Neurology 1998; 50 (06) 1601-8.
• 16 Pujol J. et al. The effect of medial frontal and posterior parietal demyelinating lesions on Stroop interference. NeuroImage 2001; 13: 68-75.
• 17 Sperling RA. et al. Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis. Arch Neurol 2001; 58: 115-21.
• 18 Benedict RH, Carone DA, Bakshi R. Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis. J Neuroimaging 2004; 14: 36S-45S.
• 19 Deloire MS, Ruet A, Hamel D, Bonnet M, Dousset V, Brochet B. MRI predictors of cognitive outcome in early multiple sclerosis. Neurology 2011; 76 (13) 1161-7.
• 20 Tiemann L, Penner IK, Haupts M, Schlegel U, Calabrese P. Cognitive decline in multiple sclerosis: impact of topographic lesion distribution on differential cognitive deficit patterns. Mult Scler 2009; 15 (10) 1164-74.
• 21 Deloire MSA. et al. Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2005; 76: 519-26.
• 22 Khalil M. et al. Cognitive impairment in relation to MRI metrics in patients with clinically isolated syndrome. Mult Scler 2011; 17 (02) 173-80.
• 23 Kutzelnigg A, Lassmann H. Cortical demyelination in multiple sclerosis: A substrate for cognitive deficits?. J Neurol Sci 2006; 245: 123-6.
• 24 Calabrese M. et al. Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 2009; 66 (09) 1144-50.
• 25 Roosendaal SD. et al. Accumulation of cortical lesions in MS: relation with cognitive impairment. Mult Scler 2009; 15 (06) 708-14.
• 26 Papadopoulou A. et al. Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler 2013; 19 (10) 1290-6.
• 27 Audoin B. et al. Functional magnetic resonance imaging and cognition at the very early stage of MS. J Neurol Sci 2006; 245: 87-91.
• 28 Audoin B. et al. Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp 2003; 20: 51-8.
• 29 Penner IK, Rausch M, Kappos L, Opwis K, Radü EW. Analysis of impairment related functional architecture in MS patients during performance of different attention tasks. J Neurol 2003; 250: 461-72.
• 30 Penner IK, Opwis K, Kappos L. Relation between functional brain imaging, cognitive impairment and cognitive rehabilitation in patients with multiple sclerosis. J Neurol 2007; 254 (Suppl. 02) 53-7.
• 31 Park HJ, Friston K. Structural and functional brain networks: from connections to cognition. Science 2013; 342 (6158): 1238411.
• 32 Rocca MA. et al. Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology 2010; 74 (16) 1252-9.
• 33 Cruz-Gomez AJ, Ventura-Campos N, Belenguer A, Avila C, Forn C. The link between resting-state functional connectivity and cognition in MS patients. Mult Scler. 2013 epub ahead of print.
• 34 Rao SM. Cognitive Function Study Group. A manual for the brief, repeatable battery of neuropsychological tests in Multiple Sclerosis. Milwaukee: Medical College of Wisconsin; 1990
• 35 Janssen AL, Boster A, Patterson BA, Abdujalil A, Prakash RS. Resting-state functional connectivity in multiple sclerosis: An examination of group differences and individual differences. Neuropsychologia 2013; 51: 2918-29.
• 36 Gronwall D. Advances in the assessment of attention and information processing after head injury. In: Levin HS, Grafman J, Eisenberg HM. (eds.). Neurobehavioral recovery from head injury. New York: Oxford University Press; 1977: 355-71.
• 37 Smith A. Symbol Digit Modalities Test. Los Angeles: Western Psychological Services; 1973
• 38 Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test, second edition (CVLTII). San Antonio, TX: Psychological Corporation; 2000
• 39 Helmstaedter C, Lendt M, Lux S. editors. VLMT – Verbaler Lern- und Merkfähigkeitstest. Manual. Göttingen: Beltz Test GmbH; 2001
• 40 Benedict RH. (ed.). Brief Visuospatial Memory Test-Revised (BVMT-R). In: Lutz FL: Psychological Assessment Resources Inc; 1997
• 41 Langdon DW. et al. Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler 2012; 18 (06) 891-8.
• 42 Fischer JS. et al. Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group. Ann Neurol 2000; 48: 885-92.
• 43 Penner IK. et al. Effects of interferon beta-1b on cognitive performance in patients with a first event suggestive of multiple sclerosis. Mult Scler 2012; 18 (10) 1466-71.
• 44 Patti F. et al. Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis. Mult Scler 2010; 16 (01) 68-77.
• 45 Patti F. et al. Longitudinal changes in social functioning in mildly disabled patients with relapsingremitting multiple sclerosis receiving subcutaneous interferon beta-1a: results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study (II). Qual Life Res 2012; 21 (07) 1111-21.
• 46 Krupp LB, Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE. Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology 2004; 63: 1579-85.
• 47 Krupp LB. et al. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 2011; 76 (17) 1500-7.
• 48 Cader S, Palace J, Matthews PM. Cholinergic agonism alters cognitive processing and enhances brain functional connectivity in patients with multiple sclerosis. J Psychopharmacol (Oxf) 2009; 23 (06) 686-96.
• 49 Mäurer M. et al. Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients. Mult Scler. 2012 Epub ahead of print.
• 50 Oken BS. et al. Randomized controlled trial of yoga and exercise in multipe sclerosis. Neurology 2004; 62 (11) 2058-64.
• 51 Romberg A, Virtanen A, Ruutiainen J. Long-term exercise improves functional impairment but not quality of life in multiple sclerosis. J Neurol 2005; 252 (07) 839-45.
• 52 Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychological Science 2003; 14 (02) 125-30.
• 53 Colcombe SJ. et al. Cardiovascular fitness, cortical plasticity, and aging. PNAS 2004; 101: 3316-21.
• 54 Jedrziewski MK, Ewbank DC, Wang H, Trojanowski JQ. Exercise and cognition: results from the National Long Term Care Survey. Alzheimer’s and Dementia 2010; 06 (06) 448-55.
• 55 Prakash RS. et al. Cardiorespiratory fitness: A predictor of cortical plasticity in multiple sclerosis. NeuroImage 2007; 34 (03) 1238-44.
• 56 Penner IK, Kappos L. Retraining attention in MS. J Neurol Sci 2006; 245: 147-51.
• 57 Penner IK, Kobel M, Opwis K. BrainStim – A recently developed tool to train different aspects of working memory. Proceedings of the INS/GNP Conference 2006; 17-8.
• 58 Vogt A. et al. Working memory training in patients with multiple sclerosis – comparison of two different training schedules. Restorative Neurology and Neuroscience 2009; 27: 225-35.
• 59 Chiaravalloti ND, Wylie G, Leavitt V, DeLuca J. Increased cerebral activation after behavioral treatment for memory deficits in M. J Neurol 2012; 259 (07) 1337-46.
• 60 Filippi M. et al. Multiple sclerosis: effects of cognitive rehabilitation on structural and functional MR imaging measures – an explorative study. Radiology 2012; 262 (03) 932-40.
• 61 Penner IK, Kappos L, Rausch M, Opwis K, Radü EW. Therapy-induced plasticity of cognitive functions in MS patients: Insights from fMRI. Journal of Physiology Paris 2006; 99: 455-62.
• 62 Sastre-Garriga J. et al. A functional magnetic resonance proof of concept pilot trial of cognitive rehabilitation in multiple sclerosis. Mult Scler 2011; 17 (04) 457-67.