Neudefinition atypischer Parkinson-Syndrome

Zusammenfassung

Die Definition der atypischen Parkinson-Syndrome befindet sich im Wandel. Der Oberbegriff atypische Parkinson-Syndrome umfasst Erkrankungen mit unterschiedlichen zugrundeliegenden Pathologien. Dies sind zum einen die Multisystematrophie (MSA) und die Demenz mit Lewy-Körpern (DLK), die beide durch intrazelluläre Aggregate des Proteins alpha-Synuklein gekennzeichnet sind; zum anderen die Kortikobasale Degeneration (CBD) und die Progressive Supranukleäre Blickparese (PSP), die sich durch Aggregate des Proteins Tau auszeichnen. Die aktuelle Syndrom-basierte Klassifikation dieser Erkrankungen entspricht nicht mehr den Anforderungen der Zeit, da 1) zahlreiche klinisch-pathologische Studien gezeigt haben, dass das klinische Syndrom oft nicht mit der molekular-pathologischen Diagnose übereinstimmt, 2) ein klinisches Parkinson Syndrom mitunter in Patienten mit pathologischer Diagnose eines atypischen Parkinson Syndroms sogar fehlt und 3) aktuelle Therapie-Studien, die in die molekularen Krankheitsmechanismen eingreifen, keine Symptom-orientierte, sondern eine pathogenetisch orientierte Diagnose erfordern. Die frühe und korrekte Vorhersage der zugrundeliegenden molekularen Pathologie als Voraussetzung für eine ursächliche Therapie stellt daher eine Herausforderung dar, der das alte Krankheitskonzept nicht mehr gewachsen ist.

Abstract

The definition of atypical parkinsonian syndromes is changing. The umbrella term of atypical parkinsonian syndrome includes diseases with different underlying pathologies. These are, on the one hand, multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), both characterized by intracellular aggregates of the protein alpha-synuclein and on the other hand, corticobasal degeneration (CBD) and progressive supranuclear gaze visualization (PSP), which are characterized by aggregates of the protein tau. The current syndrome-based classification of these diseases no longer meets current requirements since 1) numerous clinical pathological studies have shown that the clinical syndrome often does not coincide with the molecular-pathological diagnosis, 2) sometimes in patients with a pathological diagnosis of an typical parkinsonian syndrome, a clinical parkinsonian syndrome is even missing and 3) current therapeutical trials based on the molecular disease mechanisms require not a symptom-oriented, but a pathogenetically oriented diagnosis. The early and correct identification of the underlying molecular pathology as a prerequisite for a causative therapy therefore presents a challenge that the old disease concept is no longer capable of meeting.

Schlüsselwörter

Parkinson-Syndrome - Neudefinition - Diagnose

Keywords

parkinsonian syndromes - new definition - diagnosis

• Literatur

• 1 Levin J, Kurz A, Arzberger T. et al. Differenzialdiagnose und Therapie der atypischen Parkinson-Syndrome. Dtsch Arztebl Int 2016; 113: 61-69
• 2 Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy. A heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol 1964; 10: 333-359
• 3 Litvan I, Agid Y, Calne D. et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996; 47: 1-9
• 4 Rebeiz JJ, Kolodny H, Richardson EP. Corticodentatonigral Degeneration mit achromasia. Arch Neurol 1968; 18: 20-33
• 5 Roy S, Datta CK, Hirano A. et al. Electron microscopic study of neurofibrillary tangles in Steele-Richardson-Olszewski Syndrome Acta. Neuropath (Berl.) 1974; 29: 175-179
• 6 Bancher C, Lassmann H, Budka H. et al. Neurofibrillary tangles in Alzheimer’s disease and progressive supranuclear palsy: antigenic similarities and differences. Microtubule-associated protein tau antigenicity is prominent in all types of tangles. Acta Neuropathol 1987; 74: 39-46
• 7 Flament S, Delacourte A, Verny M. et al. Abnormal Tau proteins in progressive supranuclear palsy. Similarities and differences with the neurofibrillary degeneration of the Alzheimer type. Acta Neuropathol 1991; 81: 591-596
• 8 Dickson DW, Kouri N, Murray ME. et al. Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). J Mol Neurosci 2011; 45: 384-389
• 9 Höglinger GU, Melhem NM, Dickson DW. et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet 2011; 43: 699-705
• 10 Kouri N, Ross OA, Dombroski B. et al. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nature Communications 2015; 6: 7247
• 11 Respondek G, Stamelou M, Kurz C. et al. The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases. Mov Disord 2014; 29: 1758-1766
• 12 Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 2009; 8: 270-279
• 13 Dickson DW. Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol 1999; 246 (Suppl. 02) II 6-15 Review
• 14 Chahine LM, Rebeiz T, Rebeit JJ. et al. Corticobasal syndrome: Five new things. Neurol Clin Pract 2014; 4: 304-312
• 15 Armstrong MJ, Litvan I, Lang AE. et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80: 496-503
• 16 Kertesz A, McMonagle P, Blair M. et al. The evolution and pathology of frontotemporal dementia. Brain 2005; 128: 1996-2005
• 17 Seelaar H, Rohrer JD, Pijnenburg YA. et al. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry 2011; 82: 476-486
• 18 Weintraub S, Mesulam M. With or without FUS: It is the anatomy that dictates the dementia phenotype. Brain 2009; 11: 2906-2908
• 19 Pottier C, Ravenscroft TA, Sanchez-Contreras M. et al. Genetics of FTLD: overview and what else we can expect from genetic studies. J Neurochem 2016; 138 (Suppl. 01) 32-53 Review
• 20 Van Langenhove T, van der Zee J, Sleegers K. et al. Genetic contribution of FUS to frontotemporal lobar degeneration. Neurology 2010; 74: 366-371
• 21 Van Deerlin VM, Sleiman PM, Martinez-Lage M. et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat Genet 2010; 1: 234-239
• 22 Gilman S, Wenning GK, Low PA. et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71 670-676
• 23 McKeith IG, Dickson DW, Lowe J. et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005; 65: 1863-1872
• 24 Höglinger GU, Stamelou M, Kurz C et al. MDS-Clinical Diagnostic Criteria for Progressive Supranuclear Palsy (PSP). In: 20th International Congress of Parkinson’s Disease and Movement Disorders; June 19–23 2016; Berlin, Germany. Abstract number: SG35
• 25 Respondek G, Roeber S, Kretzschmar H. et al. Accuracy of the National Institute for Neurological Disorders and Stroke/Society for Progressive Supranuclear Palsy and neuroprotection and natural history in Parkinson plus syndromes criteria for the diagnosis of progressive supranuclear palsy. Mov Disord 2013; 28: 504-509
• 26 Koga S, Aoki N, Uitti RJ. et al. Neurology 2015; 85: 404-412
• 27 Catafau AM, Bullich S, Non-amyloid PET. imaging biomarkers for neurodegeneration: Focus on tau, alpha-synuclein and neuroinflamation. Curr Alzheimer Res. 2016 [Epub ahead of print]
• 28 Rodríguez-Leyva I, Chi-Ahumada E, Carrizales J. et al. Parkinson disease and progressive supranuclear palsy: protein expression in skin. Ann Clin Transl Neurol 2016; 3: 191-199
• 29 Beach TG, Adler CH, Serrano G. et al. Prevalence of Submandibular Gland Synucleinopathy in Parkinson’s Disease, Dementia with Lewy Bodies and other Lewy Body Disorders. J Parkinsons Dis 2016; 6: 153-163
• 30 Malek N, Swallow D, Grosset KA. et al. Alpha-synuclein in peripheral tissues and body fluids as a biomarker for Parkinson’s disease – a systematic review. Acta Neurol Scand 2014; 130: 59-72
• 31 Paré B, Touzel-Deschênes L, Lamontagne R. et al. Early detection of structural abnormalities and cytoplasmic accumulation of TDP-43 in tissue-engineered skins derived from ALS patients. Acta Neuropathol Commun 2015; 3: 5
• 32 Zarei S, Carr K, Reiley L. et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int 2015; 6: 171