Skip to main content
Erschienen in: Journal of Neurology 6/2013

01.06.2013 | Review

Treatment of cognitive impairment in multiple sclerosis: position paper

verfasst von: Maria Pia Amato, Dawn Langdon, Xavier Montalban, Ralph H. B. Benedict, John DeLuca, Lauren B. Krupp, Alan J. Thompson, Giancarlo Comi

Erschienen in: Journal of Neurology | Ausgabe 6/2013

Einloggen, um Zugang zu erhalten

Abstract

Cognitive impairment in multiple sclerosis (MS) is common, debilitating and burdensome. Key evidence from trials was reviewed to enable recommendations to be made to guide clinical practice and research. Behavioural and pharmacological interventions on cognition reported in published studies were reviewed. Most studies evaluating behavioural treatment for impairment in learning and memory, deficits of attention and executive function have demonstrated some improvement. Controlled studies in relapsing remitting MS indicate interferon (IFN) β-1b and IFN β-1a were associated with modest cognitive improvement. The effects of symptomatic therapies such as modafinil and donepezil are inconsistent. Most studies yielding positive findings have significant methodological difficulties limiting the confidence in making any broad treatment recommendations. There are no published reports of glatiramer acetate, natalizumab and fingolimod being effective in improving cognition in controlled trials. The effects of disease modifying therapies in other forms of MS and clinically isolated syndrome have not yielded positive results. Data linking behavioural therapy, symptomatic treatment or disease modifying treatment, to either reducing cognitive decline or improving impaired cognition are limited and inconsistent. The treatment and prevention of cognitive impairment needs to remain a key research focus, identifying new interventions and improving clinical trial methodology.
Literatur
1.
Zurück zum Zitat Peyser JM, Rao SM, LaRocca NG, Kaplan E (1990) Guidelines for neuropsychological research in multiple sclerosis. Arch Neurol 47:94–97PubMedCrossRef Peyser JM, Rao SM, LaRocca NG, Kaplan E (1990) Guidelines for neuropsychological research in multiple sclerosis. Arch Neurol 47:94–97PubMedCrossRef
2.
Zurück zum Zitat Rao S, Leo G, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis: frequency, patterns, and predictions. Neurology 41:685–691PubMedCrossRef Rao S, Leo G, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis: frequency, patterns, and predictions. Neurology 41:685–691PubMedCrossRef
3.
Zurück zum Zitat Rao SM (1997) Neuropsychological aspects of multiple sclerosis. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. Chapman & Hall, London, pp 357–362 Rao SM (1997) Neuropsychological aspects of multiple sclerosis. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. Chapman & Hall, London, pp 357–362
4.
Zurück zum Zitat Benedict RH, Cookfair D, Gavett R et al (2006) Validity of the minimal assessment of cognitive function in multiple sclerosis. J Int Neuropsychol Soc 12:549–558PubMedCrossRef Benedict RH, Cookfair D, Gavett R et al (2006) Validity of the minimal assessment of cognitive function in multiple sclerosis. J Int Neuropsychol Soc 12:549–558PubMedCrossRef
6.
Zurück zum Zitat Amato MP, Portaccio E, Goretti B et al (2010) Cognitive impairment in early stages of multiple sclerosis. Neurol Sci 31(Suppl 2):S211–S214PubMedCrossRef Amato MP, Portaccio E, Goretti B et al (2010) Cognitive impairment in early stages of multiple sclerosis. Neurol Sci 31(Suppl 2):S211–S214PubMedCrossRef
7.
Zurück zum Zitat Amato MP, Zipoli V, Portaccio E (2008) Cognitive changes in multiple sclerosis. Expert Rev Neurother 8:1585–1596PubMedCrossRef Amato MP, Zipoli V, Portaccio E (2008) Cognitive changes in multiple sclerosis. Expert Rev Neurother 8:1585–1596PubMedCrossRef
8.
Zurück zum Zitat Benedict RH, Bruce JM, Dwyer MG, Abdelrahman N, Hussein S, Weinstock-Guttman B, Garg N, Munschauer F, Zivadinov R (2006) Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 63(9):1301–1306PubMedCrossRef Benedict RH, Bruce JM, Dwyer MG, Abdelrahman N, Hussein S, Weinstock-Guttman B, Garg N, Munschauer F, Zivadinov R (2006) Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 63(9):1301–1306PubMedCrossRef
9.
Zurück zum Zitat Amato MP, Portaccio E, Goretti B et al (2010) Relevance of cognitive deterioration in early relapsing-remitting MS: a 3-year follow-up study. Mult Scler 16:1474–1482PubMedCrossRef Amato MP, Portaccio E, Goretti B et al (2010) Relevance of cognitive deterioration in early relapsing-remitting MS: a 3-year follow-up study. Mult Scler 16:1474–1482PubMedCrossRef
10.
Zurück zum Zitat Zipoli V, Goretti B, Hakiki B et al (2010) Cognitive impairment predicts conversion to multiple sclerosis in clinically isolated syndromes. Mult Scler 16:62–67PubMedCrossRef Zipoli V, Goretti B, Hakiki B et al (2010) Cognitive impairment predicts conversion to multiple sclerosis in clinically isolated syndromes. Mult Scler 16:62–67PubMedCrossRef
11.
Zurück zum Zitat Reuter F, Zaaraoui W, Crespy L, Faivre A, Rico A, Malikova I et al (2011) Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis. J Neurol Neurosurg Psychiatry 82(10):1157–1159PubMedCrossRef Reuter F, Zaaraoui W, Crespy L, Faivre A, Rico A, Malikova I et al (2011) Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis. J Neurol Neurosurg Psychiatry 82(10):1157–1159PubMedCrossRef
12.
Zurück zum Zitat Lebrun C, Blanc F, Brassat D, Zephir H, de Seze J, CFSEP (2010) Cognitive function in radiologically isolated syndrome. Mult Scler 16(8):919–925PubMedCrossRef Lebrun C, Blanc F, Brassat D, Zephir H, de Seze J, CFSEP (2010) Cognitive function in radiologically isolated syndrome. Mult Scler 16(8):919–925PubMedCrossRef
13.
Zurück zum Zitat Amato MP, Hakiki B, Goretti B, et al (2012) Association of T1 lesion volume and neocortical atrophy with cognitive impairment in radiologically isolated syndromes. Neurology (in press) Amato MP, Hakiki B, Goretti B, et al (2012) Association of T1 lesion volume and neocortical atrophy with cognitive impairment in radiologically isolated syndromes. Neurology (in press)
14.
Zurück zum Zitat Amato MP, Zipoli V, Goretti B et al (2006) Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort. J Neurol 253:1054–1059PubMedCrossRef Amato MP, Zipoli V, Goretti B et al (2006) Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort. J Neurol 253:1054–1059PubMedCrossRef
15.
Zurück zum Zitat Benedict RH, Zivadinov R (2011) Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol 7(6):332–342PubMedCrossRef Benedict RH, Zivadinov R (2011) Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol 7(6):332–342PubMedCrossRef
16.
Zurück zum Zitat Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7:1139–1151PubMedCrossRef Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7:1139–1151PubMedCrossRef
17.
Zurück zum Zitat Comi G (2010) Effects of disease modifying treatments on cognitive dysfunction in multiple sclerosis. Neurol Sci 31(Suppl 2):S261–S264PubMedCrossRef Comi G (2010) Effects of disease modifying treatments on cognitive dysfunction in multiple sclerosis. Neurol Sci 31(Suppl 2):S261–S264PubMedCrossRef
18.
Zurück zum Zitat Sumowski JF, Wylie GR, Chiaravalloti ND, DeLuca J (2010) Intellectual enrichment lessens the effect of brain atrophy on learning and memory in MS. Neurology 74:1942–1945PubMedCrossRef Sumowski JF, Wylie GR, Chiaravalloti ND, DeLuca J (2010) Intellectual enrichment lessens the effect of brain atrophy on learning and memory in MS. Neurology 74:1942–1945PubMedCrossRef
19.
Zurück zum Zitat Benedict RH, Cox D, Thompson LL, Foley F, Weinstock-Guttman B, Munschauer F (2004) Reliable screening for neuropsychological impairment in multiple sclerosis. Mult Scler 10(6):675–678PubMedCrossRef Benedict RH, Cox D, Thompson LL, Foley F, Weinstock-Guttman B, Munschauer F (2004) Reliable screening for neuropsychological impairment in multiple sclerosis. Mult Scler 10(6):675–678PubMedCrossRef
20.
Zurück zum Zitat Sonder J, Bosma L, van der Linden F, Knol D, Polman C, Uitdehaag B (2012) Proxy measurements in multiple sclerosis: agreement on different patient-reported outcome scales. Mult Scler 18(2):196–201PubMedCrossRef Sonder J, Bosma L, van der Linden F, Knol D, Polman C, Uitdehaag B (2012) Proxy measurements in multiple sclerosis: agreement on different patient-reported outcome scales. Mult Scler 18(2):196–201PubMedCrossRef
21.
Zurück zum Zitat Rudick R, Antel J, Confavreux C et al (1997) Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force. Ann Neurol 42:379–382PubMedCrossRef Rudick R, Antel J, Confavreux C et al (1997) Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force. Ann Neurol 42:379–382PubMedCrossRef
22.
Zurück zum Zitat Rao SM (1990) A manual for the brief, repeatable battery of neuropsychological tests in multiple sclerosis. Milwaukee, Wisconsin Rao SM (1990) A manual for the brief, repeatable battery of neuropsychological tests in multiple sclerosis. Milwaukee, Wisconsin
23.
Zurück zum Zitat Benedict RH, Fischer JS, Archibald CJ et al (2002) Minimal neuropsychological assessment of MS patients: a consensus approach. Clin Neuropsychol 16:381–397PubMedCrossRef Benedict RH, Fischer JS, Archibald CJ et al (2002) Minimal neuropsychological assessment of MS patients: a consensus approach. Clin Neuropsychol 16:381–397PubMedCrossRef
24.
Zurück zum Zitat Strober L, Englert J, Munschauer F, Weinstock-Guttman B, Rao S, Benedict RH (2009) Sensitivity of conventional memory tests in multiple sclerosis: comparing the Rao Brief Repeatable Neuropsychological Battery and the Minimal Assessment of Cognitive Function in MS. Mult Scler 15:1077–1084PubMedCrossRef Strober L, Englert J, Munschauer F, Weinstock-Guttman B, Rao S, Benedict RH (2009) Sensitivity of conventional memory tests in multiple sclerosis: comparing the Rao Brief Repeatable Neuropsychological Battery and the Minimal Assessment of Cognitive Function in MS. Mult Scler 15:1077–1084PubMedCrossRef
25.
Zurück zum Zitat Jønsson A, Korfitzen EM, Heltberg A, Ravnborg MH, Byskov-Ottosen E (1993) Effects of neuropsychological treatment in patients with multiple sclerosis. Acta Neurol Scand 88:394–400PubMedCrossRef Jønsson A, Korfitzen EM, Heltberg A, Ravnborg MH, Byskov-Ottosen E (1993) Effects of neuropsychological treatment in patients with multiple sclerosis. Acta Neurol Scand 88:394–400PubMedCrossRef
26.
Zurück zum Zitat Solari A (2010) Methodological aspects of randomized controlled trials on cognitive interventions. Neurol Sci 31(2):279–282CrossRef Solari A (2010) Methodological aspects of randomized controlled trials on cognitive interventions. Neurol Sci 31(2):279–282CrossRef
27.
Zurück zum Zitat O’Brien AR, Chiaravalloti N, Goverover Y, Deluca J (2008) Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: a review of the literature. Arch Phys Med Rehabil 89:761–769PubMedCrossRef O’Brien AR, Chiaravalloti N, Goverover Y, Deluca J (2008) Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: a review of the literature. Arch Phys Med Rehabil 89:761–769PubMedCrossRef
28.
Zurück zum Zitat das Nair R, Ferguson H, Stark DL, Lincoln NB (2012) Memory Rehabilitation for people with multiple sclerosis. Cochrane Database Syst Rev 14(3):CD008754 das Nair R, Ferguson H, Stark DL, Lincoln NB (2012) Memory Rehabilitation for people with multiple sclerosis. Cochrane Database Syst Rev 14(3):CD008754
29.
Zurück zum Zitat DeLuca J, Barbieri-Berger S, Johnson SK (1994) The nature of memory impairments in multiple sclerosis: acquisition versus retrieval. J Clin Exp Neuropsychol 16(2):183–189PubMedCrossRef DeLuca J, Barbieri-Berger S, Johnson SK (1994) The nature of memory impairments in multiple sclerosis: acquisition versus retrieval. J Clin Exp Neuropsychol 16(2):183–189PubMedCrossRef
30.
Zurück zum Zitat DeLuca J, Gaudino EA, Diamond BJ, Christodoulou C, Engel RA (1998) Acquisition and storage deficits in multiple sclerosis. J Clin Exp Neuropsychol 20:376–390PubMedCrossRef DeLuca J, Gaudino EA, Diamond BJ, Christodoulou C, Engel RA (1998) Acquisition and storage deficits in multiple sclerosis. J Clin Exp Neuropsychol 20:376–390PubMedCrossRef
31.
Zurück zum Zitat Gaudino EA, Chiaravalloti ND, DeLuca J, Diamond BJ (2001) A comparison of memory performance in relapsing-remitting, primary progressive and secondary progressive, multiple sclerosis. Neuropsychiatry Neuropsychol Behav Neurol 14(1):32–44PubMed Gaudino EA, Chiaravalloti ND, DeLuca J, Diamond BJ (2001) A comparison of memory performance in relapsing-remitting, primary progressive and secondary progressive, multiple sclerosis. Neuropsychiatry Neuropsychol Behav Neurol 14(1):32–44PubMed
32.
Zurück zum Zitat Goverover Y, Chiaravalloti N, DeLuca J (2008) Self-generation to improve learning and memory of functional activities in persons with multiple sclerosis: meal preparation and managing finances. Arch Phys Med Rehabil 89:1514–1521PubMedCrossRef Goverover Y, Chiaravalloti N, DeLuca J (2008) Self-generation to improve learning and memory of functional activities in persons with multiple sclerosis: meal preparation and managing finances. Arch Phys Med Rehabil 89:1514–1521PubMedCrossRef
33.
Zurück zum Zitat Basso MR, Lowery N, Ghormley C, Combs D, Johnson J (2006) Self-generated learning in people with multiple sclerosis. J Int Neuropsychol Soc 12:640–648PubMedCrossRef Basso MR, Lowery N, Ghormley C, Combs D, Johnson J (2006) Self-generated learning in people with multiple sclerosis. J Int Neuropsychol Soc 12:640–648PubMedCrossRef
34.
Zurück zum Zitat Basso MR, Ghormley C, Lowery N, Combs D, Bornstein RA (2002) Self-generated learning in people with multiple sclerosis: an extension of Chiaravalloti and DeLuca (2002). J Clin Exp Neuropsychol 30:63–69CrossRef Basso MR, Ghormley C, Lowery N, Combs D, Bornstein RA (2002) Self-generated learning in people with multiple sclerosis: an extension of Chiaravalloti and DeLuca (2002). J Clin Exp Neuropsychol 30:63–69CrossRef
35.
Zurück zum Zitat Goverover Y, Hillary FG, Chiaravalloti N, Arango-Lasprilla JC, DeLuca J (2009) A functional application of the spacing effect to improve learning and memory in persons with multiple sclerosis. J Clin Exp Neuropsychol 31:513–522PubMedCrossRef Goverover Y, Hillary FG, Chiaravalloti N, Arango-Lasprilla JC, DeLuca J (2009) A functional application of the spacing effect to improve learning and memory in persons with multiple sclerosis. J Clin Exp Neuropsychol 31:513–522PubMedCrossRef
36.
Zurück zum Zitat Goverover Y, Basso MR, Wood H, Chiaravalloti N, DeLuca J (2011) Examining the benefits of combining two learning strategies on recall of functional information in persons with multiple sclerosis. Mult Scler 17(12):1488–1497PubMedCrossRef Goverover Y, Basso MR, Wood H, Chiaravalloti N, DeLuca J (2011) Examining the benefits of combining two learning strategies on recall of functional information in persons with multiple sclerosis. Mult Scler 17(12):1488–1497PubMedCrossRef
37.
Zurück zum Zitat Chiaravalloti ND, DeLuca J, Moore NB, Ricker JH (2005) Treating learning impairments improves memory performance in multiple sclerosis: a randomized clinical trial. Mult Scler 11:58–68PubMedCrossRef Chiaravalloti ND, DeLuca J, Moore NB, Ricker JH (2005) Treating learning impairments improves memory performance in multiple sclerosis: a randomized clinical trial. Mult Scler 11:58–68PubMedCrossRef
38.
Zurück zum Zitat Chiaravalloti ND, Wylie G, Leavitt V, DeLuca J (2012) Increased cerebral activation after behavioral treatment for memory deficits in MS. J Neurol 259(7):1337–1346 Chiaravalloti ND, Wylie G, Leavitt V, DeLuca J (2012) Increased cerebral activation after behavioral treatment for memory deficits in MS. J Neurol 259(7):1337–1346
39.
Zurück zum Zitat Brenk A, Laun K, Haase CG (2008) Short-term cognitive training improves mental efficacy and mood in patients with multiple sclerosis. Eur Neurol 60:304–309PubMedCrossRef Brenk A, Laun K, Haase CG (2008) Short-term cognitive training improves mental efficacy and mood in patients with multiple sclerosis. Eur Neurol 60:304–309PubMedCrossRef
40.
Zurück zum Zitat Tesar N, Bandion K, Baumhackl U (2005) Efficacy of a neuropsychological training programme for patients with multiple sclerosis—a randomised controlled trial. Wien Klin Wochenschr 117:747–754PubMedCrossRef Tesar N, Bandion K, Baumhackl U (2005) Efficacy of a neuropsychological training programme for patients with multiple sclerosis—a randomised controlled trial. Wien Klin Wochenschr 117:747–754PubMedCrossRef
41.
Zurück zum Zitat Hildebrandt H, Lanz M, Hahn HK et al (2007) Cognitive training in MS: effects and relation to brain atrophy. Res Neurol Neurosci 25:33–43 Hildebrandt H, Lanz M, Hahn HK et al (2007) Cognitive training in MS: effects and relation to brain atrophy. Res Neurol Neurosci 25:33–43
42.
Zurück zum Zitat Mendozzi L, Pugnetti L, Motta A, Barbieri E, Gambini A, Cazzullo CL (1998) Computer-assisted memory retraining of patients with multiple sclerosis. Ital J Neurol Sci 19:S431–S438CrossRef Mendozzi L, Pugnetti L, Motta A, Barbieri E, Gambini A, Cazzullo CL (1998) Computer-assisted memory retraining of patients with multiple sclerosis. Ital J Neurol Sci 19:S431–S438CrossRef
43.
Zurück zum Zitat DeLuca J, Chelune GJ, Tulsky DS, Lengenfelder J, Chiaravalloti ND (2004) Is speed of processing or working memory the primary information processing deficit in multiple sclerosis? J Clin Exp Neuropsychol 26:550–562PubMedCrossRef DeLuca J, Chelune GJ, Tulsky DS, Lengenfelder J, Chiaravalloti ND (2004) Is speed of processing or working memory the primary information processing deficit in multiple sclerosis? J Clin Exp Neuropsychol 26:550–562PubMedCrossRef
44.
Zurück zum Zitat Acevedo A, Loewenstein DA (2007) Nonpharmacological cognitive interventions in aging and dementia. J Geriatr Psychiatry Neurol 20(4):239–249PubMedCrossRef Acevedo A, Loewenstein DA (2007) Nonpharmacological cognitive interventions in aging and dementia. J Geriatr Psychiatry Neurol 20(4):239–249PubMedCrossRef
45.
Zurück zum Zitat Ball K, Edwards JD, Ross LA (2007) The impact of speed of processing training on cognitive and everyday functions. J Gerontol Ser B Psychol Sci Soc Sci 1:19–31CrossRef Ball K, Edwards JD, Ross LA (2007) The impact of speed of processing training on cognitive and everyday functions. J Gerontol Ser B Psychol Sci Soc Sci 1:19–31CrossRef
46.
Zurück zum Zitat Plohmann AM, Kappos L, Ammann W et al (1998) Computer assisted retraining of attentional impairments in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 64:455–462PubMedCrossRef Plohmann AM, Kappos L, Ammann W et al (1998) Computer assisted retraining of attentional impairments in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 64:455–462PubMedCrossRef
47.
Zurück zum Zitat Solari A, Motta A, Mendozzi L et al (2004) Computer-aided retraining of memory and attention in people with multiple sclerosis: a randomized, double-blind controlled trial. J Neurol Sci 222:99–104PubMedCrossRef Solari A, Motta A, Mendozzi L et al (2004) Computer-aided retraining of memory and attention in people with multiple sclerosis: a randomized, double-blind controlled trial. J Neurol Sci 222:99–104PubMedCrossRef
48.
Zurück zum Zitat Mattioli F, Stampatori C, Zanotti D, Parrinello G, Capra R (2010) Efficacy and specificity of intensive rehabilitation of attention and executive functions in multiple sclerosis. J Neurol Sci 288:101–105PubMedCrossRef Mattioli F, Stampatori C, Zanotti D, Parrinello G, Capra R (2010) Efficacy and specificity of intensive rehabilitation of attention and executive functions in multiple sclerosis. J Neurol Sci 288:101–105PubMedCrossRef
49.
Zurück zum Zitat O’Brien A, Chiaravalloti N, Arango-Lasprilla JC, Lengenfelder J, DeLuca J (2007) An investigation of the differential effect of self-generation to improve learning and memory in multiple sclerosis and traumatic brain injury. Neuropsychol Rehabil 17:273–292PubMedCrossRef O’Brien A, Chiaravalloti N, Arango-Lasprilla JC, Lengenfelder J, DeLuca J (2007) An investigation of the differential effect of self-generation to improve learning and memory in multiple sclerosis and traumatic brain injury. Neuropsychol Rehabil 17:273–292PubMedCrossRef
50.
Zurück zum Zitat Sastre-Garriga J, Alonso J, Renom M et al (2011) A functional magnetic resonance proof of concept pilot trial of cognitive rehabilitation in multiple sclerosis. Mult Scler 17:457–476PubMedCrossRef Sastre-Garriga J, Alonso J, Renom M et al (2011) A functional magnetic resonance proof of concept pilot trial of cognitive rehabilitation in multiple sclerosis. Mult Scler 17:457–476PubMedCrossRef
51.
Zurück zum Zitat Birnboim S, Miller A (2004) Cognitive strategies application of multiple sclerosis patients. Mult Scler 10:67–73PubMedCrossRef Birnboim S, Miller A (2004) Cognitive strategies application of multiple sclerosis patients. Mult Scler 10:67–73PubMedCrossRef
52.
Zurück zum Zitat Fink F, Rischkau E, Butt M, Klein J, Eling P, Hildebrandt H (2010) Efficacy of an executive function intervention programme in MS: a placebo-controlled and pseudo-randomized trial. Mult Scler 16:1148–1151PubMedCrossRef Fink F, Rischkau E, Butt M, Klein J, Eling P, Hildebrandt H (2010) Efficacy of an executive function intervention programme in MS: a placebo-controlled and pseudo-randomized trial. Mult Scler 16:1148–1151PubMedCrossRef
53.
Zurück zum Zitat Allen DN, Goldstein G, Heyman RA, Rondinelli T (1998) Teaching memory strategies to persons with multiple sclerosis. J Rehabil Res Dev 35:405–410PubMed Allen DN, Goldstein G, Heyman RA, Rondinelli T (1998) Teaching memory strategies to persons with multiple sclerosis. J Rehabil Res Dev 35:405–410PubMed
54.
Zurück zum Zitat Brissart H, Leroy M, Debouverie M (2010) Cognitive rehabilitation in multiple sclerosis: preliminary results and presentation of a new program, PROCOG-SEP]. Rev Neurol (Paris) 166:406–411CrossRef Brissart H, Leroy M, Debouverie M (2010) Cognitive rehabilitation in multiple sclerosis: preliminary results and presentation of a new program, PROCOG-SEP]. Rev Neurol (Paris) 166:406–411CrossRef
55.
Zurück zum Zitat Chiaravalloti ND, DeLuca J (2002) Self-generation as a means of maximizing learning in multiple sclerosis: an application of the generation effect. Arch Phys Med Rehabil 83:1070–1079PubMedCrossRef Chiaravalloti ND, DeLuca J (2002) Self-generation as a means of maximizing learning in multiple sclerosis: an application of the generation effect. Arch Phys Med Rehabil 83:1070–1079PubMedCrossRef
56.
Zurück zum Zitat Shatil E, Metzer A, Horvitz O, Miller A (2010) Home-based personalized cognitive training in MS patients: a study of adherence and cognitive performance. Neuro Rehabil 26:143–153 Shatil E, Metzer A, Horvitz O, Miller A (2010) Home-based personalized cognitive training in MS patients: a study of adherence and cognitive performance. Neuro Rehabil 26:143–153
57.
Zurück zum Zitat Sumowski JF, Chiaravalloti N, DeLuca J (2010) Retrieval practice improves memory in multiple sclerosis: clinical application of the testing effect. Neuropsychology 24:267–272PubMedCrossRef Sumowski JF, Chiaravalloti N, DeLuca J (2010) Retrieval practice improves memory in multiple sclerosis: clinical application of the testing effect. Neuropsychology 24:267–272PubMedCrossRef
58.
Zurück zum Zitat Vogt A, Kappos L, Calabrese P et al (2009) Working memory training in patients with multiple sclerosis. Restor Neurol Neurosci 27:225–235PubMed Vogt A, Kappos L, Calabrese P et al (2009) Working memory training in patients with multiple sclerosis. Restor Neurol Neurosci 27:225–235PubMed
59.
Zurück zum Zitat Archibald CJ, Fisk JD (2000) Information processing efficiency in patients with multiple sclerosis. J Clin Exp Neuropsychol 22:686–701PubMedCrossRef Archibald CJ, Fisk JD (2000) Information processing efficiency in patients with multiple sclerosis. J Clin Exp Neuropsychol 22:686–701PubMedCrossRef
60.
Zurück zum Zitat Rao SM (1989) On the nature of memory disturbance in multiple sclerosis. J Clin Exp Neuropsychol 11:699–712PubMedCrossRef Rao SM (1989) On the nature of memory disturbance in multiple sclerosis. J Clin Exp Neuropsychol 11:699–712PubMedCrossRef
61.
Zurück zum Zitat Geisler MW, Sliwinski M, Coyle PK, Masur DM, Doscher C, Krupp LB (1996) The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis. Arch Neurol 53:185–188PubMedCrossRef Geisler MW, Sliwinski M, Coyle PK, Masur DM, Doscher C, Krupp LB (1996) The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis. Arch Neurol 53:185–188PubMedCrossRef
62.
Zurück zum Zitat Smith A (1982) Symbol digit modalities test: manual. Western Psychological Services, Los Angeles Smith A (1982) Symbol digit modalities test: manual. Western Psychological Services, Los Angeles
63.
Zurück zum Zitat Benedict RH (2005) Effects of using same- versus alternate-form memory tests during short-interval repeated assessments in multiple sclerosis. J Int Neuropsychol Soc 11:727–736PubMedCrossRef Benedict RH (2005) Effects of using same- versus alternate-form memory tests during short-interval repeated assessments in multiple sclerosis. J Int Neuropsychol Soc 11:727–736PubMedCrossRef
64.
Zurück zum Zitat Harel Y, Appleboim N, Lavie M, Achiron A (2009) Single dose of methylphenidate improves cognitive performance in multiple sclerosis patients with impaired attention process. J Neurol Sci 276:38–40PubMedCrossRef Harel Y, Appleboim N, Lavie M, Achiron A (2009) Single dose of methylphenidate improves cognitive performance in multiple sclerosis patients with impaired attention process. J Neurol Sci 276:38–40PubMedCrossRef
65.
Zurück zum Zitat Benedict RH, Munschauer F, Zarevics P et al (2008) Effects of l-amphetamine sulfate on cognitive function in multiple sclerosis patients. J Neurol 255:848–852PubMedCrossRef Benedict RH, Munschauer F, Zarevics P et al (2008) Effects of l-amphetamine sulfate on cognitive function in multiple sclerosis patients. J Neurol 255:848–852PubMedCrossRef
66.
Zurück zum Zitat Morrow SA, Kaushik T, Zarevics P et al (2009) The effects of l-amphetamine sulfate on cognition in MS patients: results of a randomized controlled trial. J Neurol 256:1095–1102PubMedCrossRef Morrow SA, Kaushik T, Zarevics P et al (2009) The effects of l-amphetamine sulfate on cognition in MS patients: results of a randomized controlled trial. J Neurol 256:1095–1102PubMedCrossRef
67.
Zurück zum Zitat Sumowski JF, Chiaravalloti N, Erlanger D, Kaushik T, Benedict RH, Deluca J (2011) l-amphetamine improves memory in MS patients with objective memory impairment. Mult Scler 17(9):1141–1145PubMedCrossRef Sumowski JF, Chiaravalloti N, Erlanger D, Kaushik T, Benedict RH, Deluca J (2011) l-amphetamine improves memory in MS patients with objective memory impairment. Mult Scler 17(9):1141–1145PubMedCrossRef
68.
Zurück zum Zitat Möller F, Poettgen J, Broemel F, Neuhaus A, Daumer M, Heesen C (2011) HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis. Mult Scler 17(8):1002–1009PubMedCrossRef Möller F, Poettgen J, Broemel F, Neuhaus A, Daumer M, Heesen C (2011) HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis. Mult Scler 17(8):1002–1009PubMedCrossRef
69.
Zurück zum Zitat Lange R, Volkmer M, Heesen C, Liepert J (2009) Modafinil effects in multiple sclerosis patients with fatigue. J Neurol 256:645–650PubMedCrossRef Lange R, Volkmer M, Heesen C, Liepert J (2009) Modafinil effects in multiple sclerosis patients with fatigue. J Neurol 256:645–650PubMedCrossRef
70.
Zurück zum Zitat Brickenkamp R (2002) Test d2. Aufmerksamkeits-Belastungs-Test, 9th edn. The d2 test. Test of attention under pressure, 9th edn. Hogrefe, Göttingen Brickenkamp R (2002) Test d2. Aufmerksamkeits-Belastungs-Test, 9th edn. The d2 test. Test of attention under pressure, 9th edn. Hogrefe, Göttingen
71.
Zurück zum Zitat Stankoff B, Waubant E, Confavreux C et al (2005) Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology 64:1139–1143PubMedCrossRef Stankoff B, Waubant E, Confavreux C et al (2005) Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology 64:1139–1143PubMedCrossRef
72.
Zurück zum Zitat Wilken JA, Sullivan C, Wallin M et al (2008) Treatment of multiple sclerosis-related cognitive problems with adjunctive modafinil: rationale and preliminary supportive data. Int J MS Care 10:1–10CrossRef Wilken JA, Sullivan C, Wallin M et al (2008) Treatment of multiple sclerosis-related cognitive problems with adjunctive modafinil: rationale and preliminary supportive data. Int J MS Care 10:1–10CrossRef
73.
Zurück zum Zitat Waxman SG (1982) Membranes, myelin, and the pathophysiology of multiple sclerosis. N Engl J Med 306:1529–1533PubMedCrossRef Waxman SG (1982) Membranes, myelin, and the pathophysiology of multiple sclerosis. N Engl J Med 306:1529–1533PubMedCrossRef
74.
Zurück zum Zitat Bever CT Jr, Anderson PA, Leslie J et al (1996) Treatment with oral 3,4 diaminopyridine improves leg strength in multiple sclerosis patients: results of a randomized, double- blind, placebo-controlled, crossover trial. Neurology 47:1457–1462PubMedCrossRef Bever CT Jr, Anderson PA, Leslie J et al (1996) Treatment with oral 3,4 diaminopyridine improves leg strength in multiple sclerosis patients: results of a randomized, double- blind, placebo-controlled, crossover trial. Neurology 47:1457–1462PubMedCrossRef
75.
Zurück zum Zitat Bever CT Jr, Young D, Anderson PA et al (1994) The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. Neurology 44:1054–1059PubMedCrossRef Bever CT Jr, Young D, Anderson PA et al (1994) The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. Neurology 44:1054–1059PubMedCrossRef
76.
Zurück zum Zitat Rossini PM, Pasqualetti P, Pozzilli C et al (2001) Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine. Mult Scler 7:354–358PubMed Rossini PM, Pasqualetti P, Pozzilli C et al (2001) Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine. Mult Scler 7:354–358PubMed
77.
Zurück zum Zitat Krupp LB, Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE (2004) Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology 63:1579–1585PubMedCrossRef Krupp LB, Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE (2004) Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology 63:1579–1585PubMedCrossRef
78.
Zurück zum Zitat Krupp LB, Christodoulou C, Melville P et al (2011) Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 76:1500–1507PubMedCrossRef Krupp LB, Christodoulou C, Melville P et al (2011) Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 76:1500–1507PubMedCrossRef
79.
Zurück zum Zitat Shaygannejad V, Janghorbani M, Ashtari F, Zanjani HA, Zakizade N (2008) Effects of rivastigmine on memory and cognition in multiple sclerosis. Can J Neurol Sci 35:476–481PubMed Shaygannejad V, Janghorbani M, Ashtari F, Zanjani HA, Zakizade N (2008) Effects of rivastigmine on memory and cognition in multiple sclerosis. Can J Neurol Sci 35:476–481PubMed
80.
Zurück zum Zitat Smits RC, Emmen HH, Bertelsmann FW, Kulig BM, van Loenen AC, Polman CH (1994) The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study. Neurology 44:1701–1705PubMedCrossRef Smits RC, Emmen HH, Bertelsmann FW, Kulig BM, van Loenen AC, Polman CH (1994) The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study. Neurology 44:1701–1705PubMedCrossRef
81.
Zurück zum Zitat Lovera JF, Frohman E, Brown TR et al (2010) Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial. Mult Scler 16(6):715–723PubMedCrossRef Lovera JF, Frohman E, Brown TR et al (2010) Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial. Mult Scler 16(6):715–723PubMedCrossRef
82.
Zurück zum Zitat Gold R, Wolinsky JS, Amato MP, Comi G (2010) Evolving expectations around early management of multiple sclerosis. Ther Adv Neurol Disord 3(6):351–367PubMedCrossRef Gold R, Wolinsky JS, Amato MP, Comi G (2010) Evolving expectations around early management of multiple sclerosis. Ther Adv Neurol Disord 3(6):351–367PubMedCrossRef
83.
Zurück zum Zitat Pliskin NH, Hamer DP, Goldstein DS, Towle VL, Reder AT, Noronha A (1996) Improved delayed visual reproduction test performance in multiple sclerosis patients receiving interferon beta-1b. Neurology 47:1463–1468PubMedCrossRef Pliskin NH, Hamer DP, Goldstein DS, Towle VL, Reder AT, Noronha A (1996) Improved delayed visual reproduction test performance in multiple sclerosis patients receiving interferon beta-1b. Neurology 47:1463–1468PubMedCrossRef
84.
Zurück zum Zitat Barak Y, Achiron A (2002) Effect of interferon-beta-1b on cognitive functions in multiple sclerosis. Eur Neurol 47:11–14PubMedCrossRef Barak Y, Achiron A (2002) Effect of interferon-beta-1b on cognitive functions in multiple sclerosis. Eur Neurol 47:11–14PubMedCrossRef
85.
Zurück zum Zitat Fischer JS, Priore RL, Jacobs LD et al (2000) Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group. Ann Neurol 48:885–892PubMedCrossRef Fischer JS, Priore RL, Jacobs LD et al (2000) Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group. Ann Neurol 48:885–892PubMedCrossRef
86.
Zurück zum Zitat Patti F, Amato MP, Bastianello S et al (2010) Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis. Mult Scler 16:68–77PubMedCrossRef Patti F, Amato MP, Bastianello S et al (2010) Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis. Mult Scler 16:68–77PubMedCrossRef
87.
Zurück zum Zitat Weinstein A, Scwid SI, Schiffer RB, McDermott MP, Giang DW, Goodman AD (1999) Neuropsychologic status in multiple sclerosis after treatment with glatiramer. Arch Neurol 56:319–324PubMedCrossRef Weinstein A, Scwid SI, Schiffer RB, McDermott MP, Giang DW, Goodman AD (1999) Neuropsychologic status in multiple sclerosis after treatment with glatiramer. Arch Neurol 56:319–324PubMedCrossRef
88.
Zurück zum Zitat Schwid SR, Goodman AD, Weinstein A, McDermott MP, Johnson KP (2007) Cognitive function in relapsing multiple sclerosis: minimal changes in a 10-year clinical trial. J Neurol Sci 255:57–63PubMedCrossRef Schwid SR, Goodman AD, Weinstein A, McDermott MP, Johnson KP (2007) Cognitive function in relapsing multiple sclerosis: minimal changes in a 10-year clinical trial. J Neurol Sci 255:57–63PubMedCrossRef
89.
Zurück zum Zitat Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW, AFFIRM Investigators (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354(9):899–910PubMedCrossRef Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW, AFFIRM Investigators (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354(9):899–910PubMedCrossRef
90.
Zurück zum Zitat Rudick RA, Stuart WH, Calabresi PA, SENTINEL Investigators et al (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354(9):911–923PubMedCrossRef Rudick RA, Stuart WH, Calabresi PA, SENTINEL Investigators et al (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354(9):911–923PubMedCrossRef
91.
Zurück zum Zitat Mattioli F, Stampatori C, Capra R (2011) The effect of natalizumab on cognitive function in patients with relapsing-remitting multiple sclerosis: preliminary results of a 1-year follow-up study. Neurol Sci 32:83–88PubMedCrossRef Mattioli F, Stampatori C, Capra R (2011) The effect of natalizumab on cognitive function in patients with relapsing-remitting multiple sclerosis: preliminary results of a 1-year follow-up study. Neurol Sci 32:83–88PubMedCrossRef
92.
Zurück zum Zitat Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362(5):402–415PubMedCrossRef Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362(5):402–415PubMedCrossRef
93.
Zurück zum Zitat Kappos L, Polman C, Pozzilli C, Thompson A, Beckmann K, Dahlke F, European Study Group in Final analysis of the European multicenter trial on IFNbeta-1b in secondary-progressive MS (2001) Interferon beta-1b in Secondary-Progressive MS. Neurology 57(11):1969–1975PubMedCrossRef Kappos L, Polman C, Pozzilli C, Thompson A, Beckmann K, Dahlke F, European Study Group in Final analysis of the European multicenter trial on IFNbeta-1b in secondary-progressive MS (2001) Interferon beta-1b in Secondary-Progressive MS. Neurology 57(11):1969–1975PubMedCrossRef
94.
Zurück zum Zitat Panitch H, Miller A, Paty D, Weinshenker B, North American Study Group on Interferon beta-1b in Secondary Progressive MS (2004) Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 63(10):1788–1795PubMedCrossRef Panitch H, Miller A, Paty D, Weinshenker B, North American Study Group on Interferon beta-1b in Secondary Progressive MS (2004) Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 63(10):1788–1795PubMedCrossRef
95.
Zurück zum Zitat Cohen JA, Cutter GR, Fischer JS et al (2002) Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 59:679–687PubMedCrossRef Cohen JA, Cutter GR, Fischer JS et al (2002) Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 59:679–687PubMedCrossRef
96.
Zurück zum Zitat Leary SM, Miller DH, Stevenson VL, Brex PA, Chard DT, Thompson AJ (2003) Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 60(1):44–51PubMedCrossRef Leary SM, Miller DH, Stevenson VL, Brex PA, Chard DT, Thompson AJ (2003) Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 60(1):44–51PubMedCrossRef
97.
Zurück zum Zitat Montalban X, Sastre-Garriga J, Tintoré M et al (2009) A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis. Mult Scler 15:1195–1205PubMedCrossRef Montalban X, Sastre-Garriga J, Tintoré M et al (2009) A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis. Mult Scler 15:1195–1205PubMedCrossRef
98.
Zurück zum Zitat Wolinsky JS, Narayana PA, O’Connor P et al (2007) Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 61(1):14–24PubMedCrossRef Wolinsky JS, Narayana PA, O’Connor P et al (2007) Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 61(1):14–24PubMedCrossRef
99.
Zurück zum Zitat Kappos L, Polman CH, Freedman MS et al (2006) Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 67(7):1242–1249PubMedCrossRef Kappos L, Polman CH, Freedman MS et al (2006) Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 67(7):1242–1249PubMedCrossRef
100.
Zurück zum Zitat Kappos L, Freedman MS, Polman CH, BENEFIT Study Group et al (2007) Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 370(9585):389–397PubMedCrossRef Kappos L, Freedman MS, Polman CH, BENEFIT Study Group et al (2007) Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 370(9585):389–397PubMedCrossRef
101.
Zurück zum Zitat Kappos L, Freedman MS, Polman CH et al (2009) Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol 8(11):987–997PubMedCrossRef Kappos L, Freedman MS, Polman CH et al (2009) Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol 8(11):987–997PubMedCrossRef
102.
Zurück zum Zitat Langdon DW, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, Hämäläinen P, Hartung HP, Krupp L, Penner IK, Reder AT, Benedict RH (2012) Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler 18(6):891–898PubMedCrossRef Langdon DW, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, Hämäläinen P, Hartung HP, Krupp L, Penner IK, Reder AT, Benedict RH (2012) Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler 18(6):891–898PubMedCrossRef
Metadaten
Titel
Treatment of cognitive impairment in multiple sclerosis: position paper
verfasst von
Maria Pia Amato
Dawn Langdon
Xavier Montalban
Ralph H. B. Benedict
John DeLuca
Lauren B. Krupp
Alan J. Thompson
Giancarlo Comi
Publikationsdatum
01.06.2013
Verlag
Springer-Verlag
Erschienen in
Journal of Neurology / Ausgabe 6/2013
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-012-6678-0

Weitere Artikel der Ausgabe 6/2013

Journal of Neurology 6/2013 Zur Ausgabe

Pioneers in Neurology

Robert Remak (1815–1865)

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.