Abstract
This thesis has utilised the data collected in the Clinical Response of Impulsivity to Deep Brain Stimulation in Parkinson's Disease (CRISP) study. The CRISP study is a prospective observational multicentre study established to understand, explore, and examine one of the most frequently asked questions in deep brain stimulation (DBS) clinics: Whether DBS worsens impulsive behaviours in Parkinson's disease (PD) patients. Impulsive behaviours are commonly reported among PD patients and are commonly considered to be a side effect of anti-Parkinson's medication. As a PhD student, I established the CRISP study with a team of experienced multidisciplinary clinicians and PD nurses from seven DBS clinics across the UK, who maintained the collaboration during the COVID-19 pandemic to provide insight into this ongoing and lingering debate. Participants in the CRISP study are asked to complete a set of self-rated and clinician-rated questionnaires. These scales assess psychiatric symptoms, motor symptoms, quality of life, personality traits and carer1 burden and are administered once before DBS activation and three, six and twelve months subsequently. Because of reasons that are explained in detail later in this chapter, only data collected up to the 6 months after the operation is analysed and presented here.The clinical response of impulsive behaviours following DBS was the primary outcome of the CRISP Study and the current thesis. However, changes in other measured psychiatric symptoms are also discussed as secondary outcomes. Lastly, the burden on carers is reviewed among the cohort. In addition to the CRISP study, I have conducted a single-centre retrospective review as part of a clinical audit. This retrospective review examines clinical notes in the database of one of the participating DBS centres, King's College Hospital. This was to compare the prevalence and course of psychiatric symptoms (if any) within a similar cohort between a prospective study with multiple assessment tools (The CRISP study) and a retrospective study reviewing routine clinical notes. This thesis is divided between 4 parts, with 7 chapters in between. In the chapter 1, an introduction on Parkinson's disease prevalence, pathology, risk factors and prevalence of psychiatric symptoms are presented. Later in the chapter, DBS has been discussed as an alternative therapy for Parkinson's disease and its relationship with impulsivity. In Chapter 2, a narrative review is presented, which was conducted for the current literature on the effects of DBS therapy on psychiatric symptoms in Parkinson's disease. Various themes are utilised to stratify the results, including early and longterm outcomes for various psychiatric symptoms (like psychosis, mood, suicidality, apathy, impulsivity, and personality traits). Two sections are also included to review the results of studies that have examined the impact of DBS parameters on psychiatric symptoms and compared the effects of DBS targets on psychiatric symptoms in Parkinson's disease.
Furthermore, details of the background, rationale, methodology and materials and results of the CRISP study are presented in the chapter 3. The main findings of the CRISP study at 6-month follow-up include significant improvement in impulsivity total scores on the QUIP-RS, hypersexuality and hobbyism-punding, with compulsive shopping showing a trend towards a significant improvement. At baseline, anhedonia showed a predictive value for significantly improving total impulsivity scores. Anhedonia, along with the elation scores, predicted the improvement in hypersexuality.
Additionally, there was a significant reduction in total LEDD and anxiety, but the depression did not improve significantly, and apathy significantly worsened. Personality traits showed a significant increase in traits related to impulsivity. Lastly, the carer burden was significantly reduced. As for the retrospective review, the main findings were the significantly older age of the retrospective cohort and lower frequency of psychiatric symptoms compared to the matched CRISP cohort. In the chapter 4, the rationale, objective, methodology, results and the translational outcomes of the single site audit are presented. In the chapter 5 a discussion is presented in the context of the results of the CRISP study, the narrative review and the audit. For the CRISP study, the relevance of the characteristics of participants, including age, gender, and ethnicity, is discussed. Moreover, the improvement in impulsivity is discussed in the cognitive and psychosocial contexts. The non-significant changes in gambling, binge eating and dopamine dysregulation syndrome are also discussed relying on different neuropsychological contexts. Lastly, other psychiatric outcomes are discussed in detail. As for the retrospective review, it is discussed how adding brief, valid questionnaires can improve the pre-DBS screening process without burdening DBS clinics. Finally, I have added a section in the discussion chapter on the pandemic's impacts on my thesis and the CRISP study. I briefly discussed how an observational multicentre study could be 'pandemic proof' in the future based on my experience. The conclusion and summary points are presented in the chapter 6.
| Date of Award | 1 Aug 2024 |
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| Original language | English |
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| Supervisor | John Shotbolt (Supervisor), David Okai (Supervisor) & Michael Samuel (Supervisor) |