Subtypen der Parkinson-Krankheit

Parkinson ist ein Krankheitsbild mit von Mensch zu Mensch sehr unterschiedlichen Symptomkonstellationen und Verlaufsformen. Im klinischen Alltag werden oft für die Gesamtgruppe der Betroffenen definierte Therapiestrategien eingesetzt, die dann allerdings zu sehr variablen Ergebnissen führen. Die Definition von verschiedenen Parkinson-Subtypen soll dazu dienen, den individuellen Krankheitsverlauf besser einschätzen zu können und die für verschiedene Untergruppen am besten geeigneten Behandlungsmöglichkeiten zu finden.

Kernaussagen

• Motorische Subtypen (z.B. tremordominant versus PIGD=postural Instabiliy/Gait Disorder) haben unterschiedliche prognostische und therapeutischen Konsequenzen.

• Das Alter bei Erkrankungsbeginn ist eine wichtige Determinante für den Krankheitsverlauf und die Pharmakoresponsivität.

• Nicht-motorische Symptome können für eine therapeutisch relevante Definition von Subtypen verwendet werden.

• Bei den genetisch definierten Subtypen haben GBA- und LRRK2-Mutationen besonders große Bedeutung.

• Durch moderne statistische Verfahren können aus einer hohen Zahl klinischer Variablen therapierelevante Subtypen abgeleitet werden.

Schlüsselwörter

Parkinson-Krankheit - Bewegungsstörungen - neurologische Erkrankung - Levodopa - postural Instability and Gait Disorder

Publication History

Article published online:
09 September 2024

• Literatur

• 1 Weiner WJ. There is no Parkinson disease. Arch Neurol 2008; 65: 705-8
• 2 Marras C, Fereshtehnejad SM, Berg D. et al. Transitioning from subtyping to precision medicine in parkinson's disease: a purpose-driven approach. Mov Disord 2024; 39: 462-71
• 3 von Coelln R, Gruber-Baldini AL, Reich SG. et al. The inconsistency and instability of Parkinson’s disease motor subtypes. Parkinsonism Relat Disord 2021; 88: 13-8
• 4 Mestre TA, Fereshtehnejad SM, Berg D. et al. Parkinson’s disease subtypes: critical appraisal and recommendations. J Parkinsons Dis 2021; 11: 395-404
• 5 Betrouni N, Delval A, Chaton L. et al. Electroencephalography-based machine learning for cognitive profiling in Parkinson’s disease: preliminary results. Mov Disord 2019; 34: 210-7
• 6 Landau S, Harris V, Burn DJ. et al. Anxiety and anxious-depression in Parkinson’s disease over a 4-year period: a latent transition analysis. Psychol Med 2016; 46: 657-67
• 7 Jankovic J, McDermott M, Carter J. et al. Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 1990; 40: 1529-34
• 8 van der Heeden JF, Marinus J, Martinez-Martin P. et al. Postural instability and gait are associated with severity and prognosis of Parkinson disease. Neurology 2016; 86: 2243-50
• 9 Simuni T, Caspell-Garcia C, Coffey C. et al. How stable are Parkinson’s disease subtypes in de novo patients: analysis of the PPMI cohort?. Parkinsonism Relat Disord 2016; 28: 62-7
• 10 Pagano G, Ferrara N, Brooks DJ. et al. Age at onset and Parkinson disease phenotype. Neurology 2016; 86: 1400-7
• 11 Mehanna R, Smilowska K, Fleisher J. et al. Age cutoff for early-onset Parkinson’s disease: recommendations from the International Parkinson and Movement Disorder Society Task Force on Early Onset Parkinson’s Disease. Mov Disord Clin Pract 2022; 9: 869-78
• 12 Marras C, Chaudhuri KR. Nonmotor features of Parkinson’s disease subtypes. Mov Disord 2016; 31: 1095-102
• 13 Borghammer P, Horsager J. et al. Neuropathological evidence of body-first vs. brain-first Lewy body disease. Neurobiol Dis 2021; 161: 105557
• 14 Knudsen K, Fedorova TD, Horsager J. et al. Asymmetric dopaminergic dysfunction in brain-first versus body-first Parkinson’s disease subtypes. J Parkinsons Dis 2021; 11: 1677-87
• 15 Fereshtehnejad SM, Postuma RB. Subtypes of Parkinson’s disease: what do they tell us about disease progression?. Curr Neurol Neurosci Rep 2017; 17: 34
• 16 De Pablo-Fernandez E, Lees AJ. et al. Prognosis and neuropathologic correlation of clinical subtypes of Parkinson disease. JAMA Neurol 2019; 76: 470-9
• 17 Lawton M, Ben-Shlomo Y, May MT. et al. Developing and validating Parkinson’s disease subtypes and their motor and cognitive progression. J Neurol Neurosurg Psychiatry 2018; 89: 1279-87
• 18 Trezzi JP, Galozzi S, Jaeger C. et al. Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease. Mov Disord 2017; 32: 1401-8
• 19 Iwaki H, Blauwendraat C, Leonard HL. et al. Genetic risk of Parkinson disease and progression: an analysis of 13 longitudinal cohorts. Neurol Genet 2019; 5: e348
• 20 Sidransky E, Nalls MA, Aasly JO. et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med 2009; 361: 1651-61
• 21 Brockmann K, Srulijes K, Pflederer S. et al. GBA-associated Parkinson’s disease: reduced survival and more rapid progression in a prospective longitudinal study. Mov Disord 2015; 30: 407-11
• 22 Healy DG, Falchi M, O'Sullivan SS. et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol 2008; 7: 583-90
• 23 Pirker W, Katzenschlager R, Hallett M. et al. Pharmacological treatment of tremor in Parkinson’s disease revisited. J Parkinsons Dis 2023; 13: 127-44
• 24 Li H, Han S, Feng J. Delirium after Deep Brain Stimulation in Parkinson's Disease. Parkinsons Dis 2021; 2021: 8885386
• 25 Dafsari HS, Reker P, Stalinski L. et al. Quality of life outcome after subthalamic stimulation in Parkinson's disease depends on age. Mov Disord 2018; 33: 99-107
• 26 Marras C, Chaudhuri KR, Titova N. et al. Therapy of Parkinson’s disease subtypes. Neurotherapeutics 2020; 17: 1366-77
• 27 Chan GH. The role of genetic data in selecting device-aided therapies in patients with advanced Parkinson’s disease: a mini-review. Front Aging Neurosci 2022; 14: 895430
• 28 Pagano G, Taylor KI, Anzures-Cabrera J. et al. Trial of prasinezumab in early-stage Parkinson’s disease. N Engl J Med 2022; 387: 421-32
• 29 Cavallieri F, Fraix V, Bove F. et al. Predictors of long-term outcome of subthalamic stimulation in Parkinson disease. Ann Neurol 2021; 89: 587-97
• 30 Cheshire P, Bertram K, Ling H. et al. Influence of single nucleotide polymorphisms in COMT, MAO-A and BDNF genes on dyskinesias and levodopa use in Parkinson’s disease. Neurodegener Dis 2014; 13: 24-8
• 31 Weintraub D, Posavi M, Fontanillas P. et al. Genetic prediction of impulse control disorders in Parkinson’s disease. Ann Clin Transl Neurol 2022; 9: 936-49
• 32 Titova N, Chaudhuri KR. Personalized medicine in Parkinson’s disease: Time to be precise. Mov Disord 2017; 32: 1147-54