Universität zu Köln

Jost, Stefanie Theresa ORCID: 0000-0003-0477-2289 (2021). Long-term effects of deep brain stimulation on non-motor symptoms in Parkinson’s disease. PhD thesis, Universität zu Köln.

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Abstract

Non-motor symptoms (NMS), such as neuropsychiatric, neuropsychological, autonomic, sensory, and sleep symptoms, are a key component in Parkinson’s disease (PD) with a major influence on quality of life (QoL). Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves QoL, motor symptoms and NMS in PD patients. Non-motor effects have been observed in uncontrolled studies with follow-up periods up to two years in clinician-rated and laboratory-based investigations. However, little is known about the progression of NMS beyond the two-year follow-up period. Furthermore, it is unclear, which parameters influence the evolution of long-term QoL, as there is a large proportion of patients who do not experience clinically relevant QoL improvement following STN-DBS. Moreover, studies comparing non-motor effects of different DBS targets, such as the STN and the Globus pallidus internus (GPi) are lacking. The aim of the first study was to examine 36-month effects of STN-DBS on NMS in a prospective, observational, controlled, international multicentre design with a control group receiving standard-of-care medical treatment (MED). Propensity score matching was used to balance baseline demographic and clinical characteristics between the STN-DBS and MED groups. We observed beneficial effects of STN-DBS compared with MED on QoL, NMS overall burden and specific non-motor aspects including sleep/fatigue, urinary symptoms, inability to smell/taste, and pain. Non-motor outcomes were significantly correlated with improvements of QoL. Sleep disturbances and neuropsychiatric symptoms, such as depression and anxiety, are amongst the most common NMS in PD and are major predictors of negative health-related QoL. Therefore, the second study aimed at investigating the long-term effects of STN-DBS and MED on quality of sleep and neuropsychiatric symptoms in a more detailed analysis. This analysis was based on the results of a former study of our group, reporting non-motor effects of STN-DBS on quality of sleep in an uncontrolled design at 24-month follow-up (fourth study in this thesis). At 36-month follow-up, we observed beneficial effects of STN-DBS compared to MED on overall quality of nights’ sleep, sleep onset and maintenance insomnia, nocturia, nocturnal motor symptoms, and sleep refreshment, whereas no differences were found for depressive and anxiety symptoms. Sleep quality, depressive and anxiety symptoms were separately influenced by STN-DBS and not associated with changes in dopaminergic medication requirements. The third study examined predictors of long-term QoL outcome after STN-DBS. At 36-month follow-up, 61.6% were classified as “QoL non-responders”. We observed that patients with younger age at intervention, worse baseline QoL, and specific NMS profiles, including a higher burden of anhedonia and concentration impairment and less severe fainting experienced greater QoL improvement. Clinically relevant QoL improvement at 36-month follow-up could be predicted with 75% accuracy. In the fifth study, non-motor effects of STN- and GPi-DBS at short-term follow-up were compared. Both, STN- and GPi-DBS improved global NMS burden, however, distinct profiles were found for specific NMS: The attention/memory and miscellaneous domains only improved in the STN-DBS group, whereas cardiovascular and sexual function domains solely improved in the GPi-DBS group. In conclusion, this thesis provides Class IIb evidence for beneficial effects of STN-DBS on NMS at 36-month follow-up, which also correlated with QoL improvements. The mechanisms that may mediate the observed effects are discussed. Our results further provide evidence that 36-month QoL changes depend on baseline QoL and NMS burden. These findings highlight the importance of a comprehensive assessment of QoL and a wide range of non-motor and motor symptoms when selecting individuals for DBS therapy and choosing a DBS target. Implementing these assessments in clinical practice, could pave the way to personalized patient care in PD.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Jost, Stefanie Theresa Stefanie.Jost@uk-koeln.de orcid.org/0000-0003-0477-2289 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-524194
Date:	2021
Language:	English
Faculty:	Faculty of Human Sciences
Divisions:	Faculty of Human Sciences > Department Psychologie
Subjects:	Psychology Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Non-motor symptoms English Parkinson's disease English Deep brain stimulation English Quality of life English
Date of oral exam:	21 June 2021
Referee:	Name Academic Title Vossel, Simone Jun.-Prof. Dr. Kessler, Josef Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/52419