The thesis investigated objective neuroimaging biomarkers in parkinsonian syndromes, which could be applied to increase diagnostic accuracy. To find convergence of the literature concerning disease-specific patterns in Parkinson’s disease and progressive supranuclear palsy, we conducted meta-analyses. In Parkinson’s disease glucose hypometabolism was re- vealed in bilateral inferior parietal cortex and left caudate nucleus and focal gray matter atrophy in the middle occipital gyrus. In progressive supranu- clear palsy we identified gray matter atrophy in the midbrain and white mat- ter atrophy in the cerebral/cerebellar pedunculi and midbrain. In sum, in Parkinson’s disease hypometabolism outperforms atrophy and in progres- sive supranuclear palsy we validated pathognomonic markers as disease- specific. Our studies create a novel framework to investigate disease- specific regional alterations for use in clinical routine. Further, we inves- tigated neural correlates by voxel-based morphometry and discriminated disease and clinical syndrome by multivariate pattern recognition in sin- gle patients with corticobasal syndrome and corticobasal syndrome with a unique syndrome - alien/ anarchic limb phenomenon. We found gray matter volume differences between patients and controls in asymmetric frontotem- poral/ occipital regions, motor areas, and insulae. The frontoparietal gyrus including the supplementary motor area contralateral to the side of the af- fected limb was specific for alien/ anarchic limb phenomenon. The predic- tion of the disease among controls was 79.0% accurate. The prediction of the specific syndrome within a disease reached an accuracy of 81.3%. In conclusion, we reliably classified patients and controls by objective pattern recognition. Moreover, we were able to predict a specific clinical syndrome within a disease, paving the way to individualized disease prediction.:SELBSTSTÄNDIGKEITSERKLÄRUNG I
ACKNOWLEDGMENTS II
SUMMARY III
ZUSAMMENFASSUNG VIII
BIBLIOGRAPHISCHE DARSTELLUNG XIV
CONTENTS XVI
1 GENERAL INTRODUCTION 1
1.1 ParkinsonianSyndromes .................... 2
1.2 Parkinson’sDisease ....................... 2
1.2.1 DiagnosticCriteria .................... 3
1.3 ProgressiveSupranuclearPalsy ................ 4
1.3.1 DiagnosticCriteria .................... 5
1.4 CorticobasalDegeneration ................... 5
1.4.1 DiagnosticCriteria .................... 7
1.5 ImagingBiomarkers ....................... 7
1.6 CurrentThesis .......................... 9 1.6.1
MotivationandFramework ............... 9 1.6.2
ResearchQuestions................... 9
2 GENERAL MATERIALS AND METHODS 12
2.1 MagneticResonanceImaging.................. 12
2.2 AnalyticalMethods........................ 13
2.2.1 Meta-Analysis ...................... 13
2.2.2 Voxel-BasedMorphometry ............... 14
2.2.3 Support-Vector Machine Classification . . . . . . . . . 15
2.3 Multi-CentricData ........................ 16
2.4 ClinicalAssessment ....................... 17
3 Study 1
4 Study 2
5 Study 3
6 Study 4
7 Study 5
8 DISCUSSION 73
8.1 MainFindings........................... 73
8.2 Statistical Approaches to Find Imaging Biomarker . . . . . . 76
8.3 Brain Alterations and their Utility as Imaging Biomarker . . . . 77
8.4 Limitations ............................ 78
8.5 Contributions of the Current Thesis and Future Directions . . 79
9 REFERENCES
APPENDIX XVIII
LIST OF AUTHORSHIP XXVII
CURRICULUM VITÆ XXXVIII
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:35719 |
| Date | 16 October 2019 |
| Creators | Albrecht, Franziska |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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