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Neurodegenerative Erkrankungen

  • A.-S. Biesalski
  • J. Becktepe
  • T. Bartsch
  • C. Franke

Zusammenfassung

Neurodegenerative Erkrankungen sind progredient verlaufende Krankheiten des Nervensystems. In diesem Kapitel werden die drei Hauptformen neurodegenerativer Erkrankungen – die amyotrophe Lateralsklerose (ALS), die Demenzen sowie Parkinson-Syndrome – dargestellt und hinsichtlich ihrer zugrundeliegenden Pathomechanismen besprochen. Grundlegende Veränderungen, wie das Auftreten abnorm gefalteter und aggregierter Proteine, die sich in Zellen des Nervensystems anreichern und zum Funktionsverlust und schließlich Niedergang unterschiedlicher Zellpopulationen führen, werden besprochen. Zudem werden genetische Grundlagen sowie unterschiedliche Hypothesen zur Ausbreitung der Neurodegeneration behandelt und die wesentlichen beteiligten neuroanatomischen Strukturen aufgezeigt.

Literatur

Literatur zu Abschn. 4.1

  1. Berlit P (Hrsg) (2012) Klinische Neurologie 3. Aufl. Springer, Berlin Heidelberg New York, S. 507Google Scholar
  2. Braak H, Brettschneider J, Ludolph AC, Lee VM, Trojanowski JQ, Del Tredici K (2013) Amyotrophic lateral sclerosis – a model of corticofugal axonal spread. Nat Rev Neurol 9 (12): 708–14CrossRefPubMedPubMedCentralGoogle Scholar
  3. Brettschneider J, Arai K, Del Tredici K et al. (2014) TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord. Acta Neuropathol 128 (3): 423–37CrossRefPubMedPubMedCentralGoogle Scholar
  4. Brettschneider J, Del Tredici K, Toledo JB et al. (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 74 (1): 20–38CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chiò A, Pagani M, Agosta F, Calvo A, Cistaro A, Filippi M (2014). Neuroimaging in amyotrophic lateral sclerosis: Insights into structural and functional changes. Lancet Neurol 13: 1228–1240CrossRefPubMedGoogle Scholar
  6. Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10: 75–82CrossRefPubMedGoogle Scholar
  7. Hacke W (Hrsg) (2016) Neurologie, 14. Auflage. Springer, Berlin Heidelberg New York, Abb. 33.3Google Scholar
  8. Geevasinga N, Menon P, Özdinler PH, Kiernan MC, Vucic S (2016) Pathophysiological and diagnostic implications of cortical dysfunction in ALS. Nat Rev Neurol 12 (11): 651–661CrossRefPubMedGoogle Scholar
  9. Hübers A, Ludolph AC, Rosenbohm A, Pinkhardt EH, Weishaupt JH, Dorst J (2016) Amyotrophe Lateralsklerose. Eine Multisystemdegeneration. Nervenarzt 87: 179–188CrossRefGoogle Scholar
  10. Hübers A, Weishaupt JH, Ludolph AC (2013) Genetik der Amyotrophen Lateralsklerose. Nervenarzt 84: 1213–1219CrossRefPubMedGoogle Scholar
  11. Kassubek J, Müller HP, Del Tredici K et al. (2014) Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology. Brain 137 (Pt 6): 1733–40CrossRefPubMedGoogle Scholar
  12. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, Burrell JR, Zoing MC (2011) Amypotrophic lateral sclerosis. Lancet 377: 942–955CrossRefGoogle Scholar
  13. Klöppel G, Kreipe HH, Remmele W, Paulus W Schröder JM (Hrsg.) Neuropathologie 3. Aufl. Springer-Verlag 2011Google Scholar
  14. Ludolph AC, Brettschneider J (2015) TDP-43 in amyotrophic lateral sclerosis – is it a prion disease? Eur J Neurol 22: 753–761CrossRefPubMedGoogle Scholar
  15. Neumann M, Sampathu DM et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314 (5796): 130–133CrossRefGoogle Scholar
  16. Oakes JA, Davies MC, Collins MO (2017) TBK1: a new player in ALS linking autophagy and neuroinflammation. Mol Brain10 (1): 5Google Scholar
  17. O’Reilly ÉJ, Wang H, Weisskopf MG, Fitzgerald KC, Falcone G, McCullough ML et al. (2013). Premorbid body mass index and risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 14, 205–211CrossRefPubMedGoogle Scholar
  18. Ravits J (2014) Focality, stochasticity and neuroanatomic propagation in ALS pathogenesis. Exp Neurol 262: 121–126CrossRefPubMedGoogle Scholar
  19. Renton AE, Chiò A, Traynor BJ (2014) State of play in amyotrophic lateral sclerosis genetics. Nature Neurosci 17: 17–23CrossRefPubMedPubMedCentralGoogle Scholar
  20. Remmele W (2012) Neuropathologie, 3. Aufl. Springer, Berlin Heidelberg New York, S. 231Google Scholar
  21. Shynrye L, Hyung-Jun K (2014) Prion-like Mechanism in Amyotrophic Lateral Sclerosis: are Protein Aggregates the Key? Exp Neurobiol 24 (1): 1–7Google Scholar
  22. Synofzik M, Otto M, Ludolph AC, Weishaupt JH (2017) Genetische Architektur der amyotrophen Lateralsklerose und frontotemporalen Demenz. Überlappung und Unterschiede. Nervenarzt 88: 728–735CrossRefPubMedGoogle Scholar
  23. Tesfaye W. Tefera TW, Borges K (2016) Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments. Front Neurosci. 2016; 10: 611Google Scholar
  24. Zhang Y (2011) Tunneling-nanotube. A new way of cell-cell communication. Commun Integr Biol 4 (3): 324–325CrossRefGoogle Scholar

Literatur zu Abschn. 4.2

  1. American Psychiatric Association – APA (2013). Diagnostic and statistical manual of mental disorders. Arlington: American Psychiatric PublishingGoogle Scholar
  2. Ashford JW (2004) APOE genotype effects on Alzheimer’s disease onset and epidemiology. J Mol Neurosci 23 (3): 157–165Google Scholar
  3. Bang J, Spina S, Miller BL (2015) Frontotemporal dementia. Lancet 386 (10004): 1672–1682CrossRefGoogle Scholar
  4. Bartsch TP (2015) Störungen der Gedächtnisfunktion: Ein Überblick. Springer, Berlin Heidelberg New YorkCrossRefGoogle Scholar
  5. Bartsch T, Falkai P (2014) Gedächtnisstörungen: Diagnostik und Rehabilitation, Springer, Berlin Heidelberg New YorkGoogle Scholar
  6. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82 (4): 239–259CrossRefPubMedGoogle Scholar
  7. Brettschneider J, Del Tredici K, Irwin DJ et al. (2014) Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD) Acta Neuropathol 127 (3): 423–439CrossRefPubMedPubMedCentralGoogle Scholar
  8. Brettschneider J, Del Tredici K, Lee VM,Trojanowski JQ (2015) Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci 16 (2): 109–120CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dilling H, Mombour W, Schmidt MH; WHO (1991) Internationale Klassifikation psychischer Störungen: ICD-10, Kapitel V (F, klinisch-diagnostische Leitlinien)Google Scholar
  10. Goedert M (2015) Neurodegeneration. Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Abeta, tau, and alpha-synuclein. Science 349 (6248): 1255555CrossRefPubMedGoogle Scholar
  11. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297 (5580): 353–356CrossRefPubMedPubMedCentralGoogle Scholar
  12. Heneka MT, Carson MJ, El Khoury J et al. (2015) Neuroinflammation in Alzheimer‹s disease. Lancet Neurol 14 (4): 388–405CrossRefPubMedPubMedCentralGoogle Scholar
  13. Irwin DJ (2016) Tauopathies as clinicopathological entities. Parkinsonism Relat Disord 22 Suppl 1: S29–33CrossRefGoogle Scholar
  14. Jonsson T, Atwal JK, Steinberg S et al. (2012) A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature 488 (7409): 96–99CrossRefPubMedGoogle Scholar
  15. Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501 (7465): 45–51CrossRefPubMedPubMedCentralGoogle Scholar
  16. Majcher V, Goode A, James V, Layfield R (2015) Autophagy receptor defects and ALS-FTLD. Molecular and Cellular Neuroscience 66: 43–52CrossRefPubMedGoogle Scholar
  17. Schneider F, Fink GR (2013) Funktionelle MRT in Psychiatrie und Neurologie. Springer, Berlin Heidelberg New YorkGoogle Scholar
  18. Thal DR, Rub U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58 (12): 1791–1800CrossRefGoogle Scholar
  19. Walker Z, Possin KL, Boeve BF, Aarsland D (2015) Lewy body dementias. Lancet 386 (10004): 1683–1697CrossRefGoogle Scholar
  20. Witt K, Deuschl G, Bartsch T (2013) Frontotemporal dementias. Nervenarzt 84 (1): 20–32Google Scholar

Literatur zu Abschn. 4.3

  1. Aarsland D, Perry R, Brown A, Larsen JP, Ballard C (2005) Neuropathology of dementia in Parkinson’s disease: a prospective, community-based study. Ann Neurol 58 (5): 773–6CrossRefPubMedGoogle Scholar
  2. Adler CH, Beach TG (2016) Neuropathological basis of nonmotor manifestations of Parkinson’s disease. Mov Disord 31 (8): 1114–9CrossRefPubMedPubMedCentralGoogle Scholar
  3. Aminian KS, Strafella, AP (2013) Affective disorders in Parkinson’s disease. Current Opinion in Neurology 26 (4): 339–44CrossRefPubMedPubMedCentralGoogle Scholar
  4. Antonini A, DeNotaris R (2004) PET and SPECT functional imaging in Parkinson’s disease. Sleep Med 5 (2): 201–6CrossRefPubMedGoogle Scholar
  5. Arai R, Karasawa N, Geffard M, Nagatsu I (1995) L-DOPA is converted to dopamine in serotonergic fibers of the striatum of the rat: a double-labeling immunofluorescence study. Neurosci Lett 11;195 (3): 195–8CrossRefPubMedGoogle Scholar
  6. Attems J and Jellinger KA (2008) The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease. Neuropathol. Appl. Neurobiol 34 (4): 466–7Google Scholar
  7. Barone P, Antonini A, Colosimo C et al. (2009) The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 15;24 (11): 1641–9CrossRefPubMedGoogle Scholar
  8. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004)Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318: 121–134CrossRefPubMedGoogle Scholar
  9. Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric a-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 20;396 (1): 67–72CrossRefPubMedGoogle Scholar
  10. Buddhala C, Loftin SK, Kuley BM, Cairns NJ, Campbell MC, Perlmutter JS (2015) Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease. Annals of Clinical Translational Neurology 2 (10): 949–959CrossRefPubMedPubMedCentralGoogle Scholar
  11. Carta M, Carlsson T, Kirik D, Björklund A (2007) Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain 130 (Pt 7): 1819–33CrossRefPubMedGoogle Scholar
  12. Carta M, Carlsson T, Muñoz A, Kirik D, Björklund A (2010) Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson’s disease. Mov Disord 25 Suppl 1: 174–9CrossRefPubMedGoogle Scholar
  13. Cenci MA, Lundblad M (2006) Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia. J Neurochem 99 (2): 381–92CrossRefPubMedGoogle Scholar
  14. Cersosimo MG, Benarroch EE (2008) Neural control of the gastrointestinal ract: implications for Parkinson disease. Mov Disord 15;23 (8): 1065–75CrossRefPubMedGoogle Scholar
  15. Chahine LM, Rebeiz J, Rebeiz JJ et al. (2014) Corticobasal syndrome: Five new things. Neurol Clin Pract 4 (4): 304–312Google Scholar
  16. Cho SS, Aminian K, Li C, Lang AE, Houle S, Strafella AP (2017) Fatigue in Parkinson’s disease: The contribution of cerebral metabolic changes. Human Brain Mapping 38 (1): 283–292CrossRefPubMedGoogle Scholar
  17. de Rijk MC, Tzourio C, Breteler MM, Dartigues JF, Amaducci L, Lopez-Pousa S et al. (1997) Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997 62 (1): 10–5Google Scholar
  18. Deng H, Wang P, Jankovic J (2017) The genetics of Parkinson disease. Ageing Res Rev 42: 72–85CrossRefPubMedGoogle Scholar
  19. Desplats P, Lee HJ, Bae EJ, Patrick C et al. (2009) Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA 4;106 (31): 13010–5Google Scholar
  20. Dickinson DW (2017) Neuropathology of Parkinson disease. Parkinsonism Relat Disord 46 Suppl 1: 30–33Google Scholar
  21. Dickson DW, Bergeron C, Chin SS et al. (2002) Office of Rare Diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 61 (11): 935–46CrossRefGoogle Scholar
  22. Dilling H, Mombour W, Schmidt M (Hrsg) (2015) ICD-10 – Internationale Klassifikation psychischer Störungen, 10. Aufl. Hogrefe Verlag, GöttingenGoogle Scholar
  23. Doppler K (2017) Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease. Acta Neuropathol 133 (4): 535–545CrossRefPubMedPubMedCentralGoogle Scholar
  24. Ehgoetz Martens, KA & Lewis, SJ (2017) Pathology of behavior in PD: What is known and what is not? J Neurol Sci 15;374: 9–16CrossRefPubMedGoogle Scholar
  25. Engelender S, Isacson O (2017) The Threshold Theory for Parkinson’s Disease. Trends Neursci 40 (1): 4–14CrossRefPubMedGoogle Scholar
  26. Fahn S, Cohen G (1992) The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 32 (6): 804–12CrossRefPubMedGoogle Scholar
  27. Ferreira D, Guerra A (2015) Depression and Parkinson’s disease: Role of the locus coeruleus. European Psychiatry 30, Suppl 1; 28–31CrossRefGoogle Scholar
  28. Fitts W, Weintraub D, Massimo L, Chahine L, Chen-Plotkin A, Duda JE (2015) Caregiver report of apathy predicts dementia in Parkinson’s disease. Parkinsonism & Related Disord 21 (8): 992–5CrossRefGoogle Scholar
  29. Gagnon JF, Bedard MA, Fantini ML, Petit D, Panisset M, Rompré S, Carrier J, Montplaisir J (2002) REM sleep behaviour disorder and REM sleep without atonia in Parkinson’s disease. Neurology 27;59 (4): 585–9CrossRefPubMedGoogle Scholar
  30. Gallagher DA, Schrag A (2012) Psychosis, apathy, depression and anxiety in Parkinson’s disease. Neurobiol Dis 46 (3): 581–9CrossRefPubMedGoogle Scholar
  31. Gasser T (2005) Genetics of Parkinson’s Disease. Curr Opin Neurol 18 (4): 363–9Google Scholar
  32. Hacke W (Hrsg) (2016) Neurologie, 14. Auflage. Springer, Berlin Heidelberg New York, Abb. 24.1, 33.3Google Scholar
  33. Hawkes CH, Del Tredici K, Braak H (2007) Parkinson’s disease: a dual hit hypothesis. Neuropathol Appl Neurobiol 33 (6): 599–614CrossRefPubMedGoogle Scholar
  34. Jellinger KA (2010) Neuropathology in Parkinson’s disease with mild cognitive impairment. Acta Neuropathol 20 (6): 829–30CrossRefPubMedGoogle Scholar
  35. Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47 (6 Suppl 3): 161–70CrossRefGoogle Scholar
  36. Kaufmann H, Nahm K, Purohit D, Wolfe D (2004) Autonomic failure as the initial manifestation of Parkinson’s disease and dementia with Lewy bodies. Neurology 28;63 (6): 1093–5CrossRefPubMedGoogle Scholar
  37. Langston JW, Ballard P, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 25;219 (4587): 979–80CrossRefPubMedGoogle Scholar
  38. Levy R, Dubois B (2006) Apathy and the functional anatomy of the prefrontal cortexbasal ganglia circuits. Cerebral Cortex 16 (7): 916–28CrossRefPubMedGoogle Scholar
  39. Litvan I (2003) Update on epidemiological aspects of progressive supranuclear palsy. Mov Disord 18 Suppl 6: S43–50Google Scholar
  40. Liu B, Fang F, Pedersen NL, Tillander A, Ludvigsson JF, Ekbom A, Svenningsson P, Chen H, Wirdefeldt K (2017) Vagotomy and Parkinson disease. A Swedish register-based match-cohort study. Neurology 23;88 (21): 1996–2002CrossRefPubMedPubMedCentralGoogle Scholar
  41. Maede T, Nagata K, Yoshida Y, Kannari K (2005) Serotonergic hyperinnervation into the dopaminergic denervated striatum compensates for dopamine conversion from exogenously administered L-DOPA. Brain Res 7;1046 (1–2): 230–3Google Scholar
  42. Mena MA, de Yébenes JG (2006) Drug-induced parkinsonism. Expert Opin Drug Saf 5 (6): 759–71CrossRefPubMedGoogle Scholar
  43. Michel PP, Hirsch EC, Agid Y (2002) Parkinson’s disease: cell death mechanisms. Rev Neurol 158 (122): 24–32Google Scholar
  44. Mu L, Sobotka S, Chen J et al. (2013) Arizona Parkinson’s Disease Consortium. Parkisnon disease affects peripheral sensory nerves in the pharynx. J Neuropathol Exp Neurol 72 (7): 614–23CrossRefGoogle Scholar
  45. Nutt JG (2003) Long-term L-DOPA therapy: challenges to our understanding and for the care of people with Parkinson’s disease. Exp Neurol 184 (1): 9–13CrossRefPubMedGoogle Scholar
  46. Obeso JA, Grandas F, Vaamonde J, Luquin MR, Artieda J, Lera G, Rodriguez ME, Martinez-Lage JM (1989) Motor complications associated with chronic levodopa therapy in Parkinson’s disease. Neurology 39 (11 Suppl 2): 11–9Google Scholar
  47. Olanow W, Schapira AH, Rascol O (2000) Continuous dopamine-receptor stimulation in early Parkinson’s disease. Trends Neurosci 23 (10 Suppl): 117–26CrossRefPubMedGoogle Scholar
  48. Pauletti C, Mannarelli D, Locuratolo N, Pollini L, Curra A, Marinelli L (2017) Attention in Parkinson’s disease with fatigue: Evidence from the attention network test. J Neural Transmission 124 (3): 335–345CrossRefPubMedGoogle Scholar
  49. Postuma RB, Berg D, Stern M et al. (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30 (12): 1591–601CrossRefPubMedGoogle Scholar
  50. Remmele W (2012) Neuropathologie, 3. Aufl. Springer, Berlin Heidelberg New YorkGoogle Scholar
  51. Santiago, RM, Vital, MABF, Sato, MDO, Adam, GP (2016) Depression in Parkinson’s disease is associated with a serotoninergic system change secondary to neuroinflammation. Int J Neurol Neurother 3: 061Google Scholar
  52. Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18 (7): 435–450CrossRefPubMedGoogle Scholar
  53. Sixel-Döring F, Trautmann E, Mollenhauer B, Trenkwalder C (2011) Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology 13;77 (11): 1048–54CrossRefPubMedGoogle Scholar
  54. Stern G (2014) Niemann-Pick’s and Gaucher’s diseases. Parkinsonism Relat Disord 20 Suppl 1: 143–6CrossRefGoogle Scholar
  55. Suzuki M, Sango K, Wada K, Nagai Y (2018) Pathological role of lipid interaction with a-Synuclein in Parkinsons disease. NeurochemInt 3: 197–186 (17)30445-XGoogle Scholar
  56. Svensson E, Horváth-Puhó E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, Sorenson HT (2015) Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 78 (4): 522–9CrossRefPubMedGoogle Scholar
  57. Tanaka H, Kannari K, Maeda T, Tomiyama M, Suda T, Matsunaga M (1999) Role of serotonergic neurons in L-DOPA-derived extracellular dopamine in the striatum of 6-OHDA-lesioned rats. Neuroreport 25;10 (3): 631–4CrossRefPubMedGoogle Scholar
  58. Tofaris GK, Spillantini MG (2007) Physiological and pathological properties of alpha-synuclein. Cell Life Mol Sci 64 (17): 2194–201Google Scholar
  59. Toledo JB, Gopal P, Raible K, Irwin DJ, Brettschneider J, Sedor S (2016) Pathological alpha-synuclein distribution in subjects with coincident Alzheimer’s and Lewy body pathology. Acta Neuropathologica 131 (3): 393–409Google Scholar
  60. Weintraub D, Simuni T, Caspell-Garcia C, Coffey C, Lasch S, Siderowf A (2015) Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson’s disease. Mov Disord 30 (7): 919–27CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.St.-Josef-Hospital, Klinik für NeurologieRuhr-Universität BochumBochumDeutschland
  2. 2.Klinik für Neurologie, NeurozentrumUniversitätsklinikum Schleswig-HolsteinKielDeutschland
  3. 3.Klinik für Neurologie mit experimenteller NeurologieUniversitätsmedizin BerlinBerlinDeutschland

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