Objective:
Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson’s disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of our study was therefore to evaluate whether 1) DAT availability changes within one year of STN-DBS and whether 2) the clinical outcome is predictable by DAT availability before surgical procedure (pre-op).
Methods:
Twenty-seven PD patients (age: 62.7 ± 8.9 years (y); duration of illness: 13.0 ± 4.9y; PD subtypes: akinetic-rigid n=11, equivalence n=13, tremor-dominant n=3) underwent [123I]FP-CIT single-photon emission computed tomography (SPECT) pre-op and one year after STN-DBS (post-op). DAT availability (specific-to-unspecific binding ratio, SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side.
Results:
1) Unified Parkinson’s Disease Rating Scale (UPDRS) III (pre-op on: on medication; pre-op off: off medication; post-op on/on: on medication/on stimulation; post-op on/off: on medication/off stimulation) improved significantly (pre-op on: 25.6 ± 12.3, pre-op off: 42.3 ± 15.2, post-op on/off: 41.4 ± 13.2; post-op on/on: 16.1 ± 9.4; pre-op on vs. post-op on/on: p = 0.006) while L-dopa equivalent daily dose (LEDD) was reduced (pre-op 957 ± 440 mg, post-op 313 ± 189 mg; p < 0.001). SBR did not differ significantly before and one year after DBS, regardless of PD subtypes.
2) Pre-op DAT availability was not related to the change in UPDRS III but the change in DAT availability was significantly correlated with the change in UPDRS III (contralateral head of the caudate VOI: p=0.014, contralateral putamen VOI: p=0.018).
Conclusion
Overall, DAT availability did not change significantly after one-year of STN-DBS. However, on an individual base, the improvement in UPDRS III was associated with an increase of DAT availability while DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of pre-op DAT availability can become a reliable predictor for successful STN-DBS has to be evaluated in larger study cohorts.:Introduction 2
1.1 Parkinson’s Disease Pathophysiology 2
1.2 Parkinson’s Disease Clinical Manifestation 4
1.2.1 Parkinson’s Disease Diagnosis 5
1.2.1.1 Unified Parkinson’s Disease Rating Scale 5
1.2.1.2 Imaging 6
1.2.2 Parkinson’s Disease Subtypes 6
1.3 Parkinson’s Disease Therapy 7
1.3.1 Pharmacologic Therapy 7
1.3.2 Surgical Therapy – Deep Brain Stimulation 9
1.3.2.1 Patient Selection 9
1.3.2.2 Operative Technique 9
1.3.2.3 Efficacy 10
1.3.2.4 Complications 11
1.3.2.5 Mechanism of action 11
2 Publication 15
3 Summary of Work 23
3.1 Background 23
3.2 DAT availability changes after STN-DBS 24
3.3 Pre-op DAT availability predicts the clinical outcome 25
3.4 DBS has a neuroprotective effect 25
3.5 Limitations and future direction 26
3.6 Conclusion 26
4 References 27
5 Attachments 35
5.1 Index of Abbreviations 35
5.2 List of figures 36
5.3 Academic Contribution 37
5.4 Declaration of the independent writing of this thesis 39
5.5 Declaration of Submission 40
5.6 Curriculum Vitae 41
5.7 Acknowledgements 43
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:79068 |
| Date | 05 May 2022 |
| Creators | Löser, Julia |
| 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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