Bakgrund: Parkinsons Sjukdom (PS) är en kronisk progressiv neurodegenerativ sjukdom som ger både motoriska och icke-motoriska symtom. Ett vanligt icke-motoriskt symtom vid PS är depression. Depression påverkas, enligt forskning, positivt av fysisk aktivitet (FA) men stark evidens saknas för sambandet mellan dem. Syfte: Syftet med studien var att undersöka sambandet mellan FA och depression hos personer med PS. Metod: Femtioåtta deltagare rekryterades till denna tvärsnittsstudie. The International Physical Activity Questionnaire modified for the elderly (IPAQ-E) användes som mätmetod för FA, och var angiven i form av låg, måttlig och hög fysisk aktivitetsnivå samt i MET-minuter/vecka. Montegomery-Åstrand Depression Rating Scale (MADRS-S) användes för depression och angavs i totalpoäng. Frågeformulärerna sammanställdes till en webbenkät varifrån datan samlades in. Sambandet beräknades med Spearmans rangkorrelation. Resultat: Av samtliga deltagare hade 15 (26%) låg fysisk aktivitetsnivå, 18 (31%) måttlig och 25 (43%) hade hög fysisk aktivitetsnivå. Bland deltagarna hade 15 (26%) ingen depression, 27 (47%) mild, 14 (24%) måttlig och 2 (3%) svår depression. Sambandet mellan låg, måttlig och hög fysisk aktivitetsnivå enligt IPAQ-E och totalpoäng i MADRS-S visade r = -0.2 och p = 0.14. Sambandet mellan MET-minuter/vecka enligt IPAQ-E och totalpoäng i MADRS-S visade r = -0.15 och p = 0.26. Konklusion: Resultaten visade ett svagt negativt samband men sannolikheten att resultatet beror på slumpen är hög. Det krävs fler studier i framtiden för att säkerställa sambandet mellan FA och depression hos personer med PS. / Background: Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease with both motor and non-motor symptoms. Depression is a common non-motor symptom in PD. According to research, physical activity (PA) has a positive effect on depression; however, strong evidence supporting the relation between them is lacking. Purpose: The purpose of this study was to examine the relation between PA and depression in patients with PD.  Method: Fifty-eight participants were recruited to this cross-sectional study. The International Physical Activity Questionnaire modified for the elderly was used to measure PA, presented in low, moderate and high physical activity levels and MET-minutes/week. Montegomery-Åstrand Depression Rating Scale was used to assess depression and was presented in total score. The questionnaires were formed into a survey from which the data was collected. Spearman’s rank correlation was used to calculate the relation.  Results: Among the participants, 15 (26%) had a low level of PA, 18 (31%) moderate and 25 (43%) high level of PA. Further, 15 (26%) were non-depressed, 27 (47%) had mild depression, 14 (24%) moderate and 2 (3%) severe depression. Evaluating the relation using the two different presentations of PA along with depression scores, results showed r= -0.2 (p= 0.26) and r= -0.15 (p= 0.26), respectively. Conclusion: The result showed a weak negative relation, but the probability of the result being due to coincidence is high. To ensure the relation between PA and depression in patients with PD, further studies are needed in the future.

The telemedicine’s capabilities are rapidly expanding due to technological advances in a smarphone development. The goal of this thesis was to suggest the architecture and prepare the design providing acquisition, processing and synchronization of voice para- meters recorded by patients with Parkinson’s disease and to implement such system. The architecture was completed successfully, it consists of the mobile application able to record patient’s calls, the server application introducing an interface to store and synchronize the data and to provide them to the web application, where doctors can see the data and analyze it. Implementation of the server application was finished according to the design and to the requirements for robustness and security as well as the web application. By an extension of the existing mobile application for recording voice calls there was developed a huge system for the analysis of this disease.

This master’s thesis takes aim with the use of statistical methods for progression evaluation of Parkinson’s disease. There is a brief description of Parkinson’s disease. It is further stated processing and evaluation of values of speech parameters which are affected by Parkinson’s disease. The thesis describes the process using the values of classification and regression trees and evaluate results using the mean absolute error and estimated error. Processing and evaluation of values was done in MATLAB software.

Parkinson's disease (PD) is a progressive disorder that affects movement, muscle control and balance. Second only to Alzheimer's disease, PD is one of the most common neurodegenerative disorders in the United States (Lai & Tsui, 2001:135), affecting approximately one million people in the U.S. alone (Parkinson's disease Foundation [PDF], 2009). While the cause of Parkinson's disease remains unknown, there are certain known risk factors associated with the disease. One of the risk factors is increasing age. PD is most frequently associated with older adulthood, affecting one in 100 Americans 60 years and older (PDF). Over the next five decades, the incidence of PD is expected to triple, as the average age of the population increases (Lai & Tsui, 2001:135). Parkinson's disease is a chronic, progressive disorder, with no known cause or promising cure. While substantial information is known about the medical aspect of Parkinson's disease, little is known about the illness experience of living with the disease. The goal of this study was to explore and describe the experiences of people living with Parkinson's disease. The guiding research question was: What are the experiences of people living with Parkinson's disease? A qualitative research approach was followed, with a collective case study research design. The population for this study included people who are in the late stage of Parkinson's disease, thus being diagnosed with Parkinson's disease before 2012 and who are receiving support services from Parkinson's Association of South Africa (PASA). Non-probability purposive sampling was utilized to generate a sample. Ten participants who met the criteria were selected for this study. Semi-structured individual interviews were conducted with participants. Interviews were voice recorded with the permission of the participants and were transcribed. The data gathered were analysed by the researcher and themes and sub-themes were identified. The research findings were presented and critically discussed. Literature control and verbatim quotes were used to support the findings. The conclusions of this study reflected that the experiences of people living with Parkinson's disease are complex. Throughout the study it was found that Parkinson's disease impacts significantly on the physical, psychological and social well-being of people living with this disease in a number of ways. The recommendations offered by this study can be used by professionals working in the field of chronic, geriatric and neurodegenerative illnesses to understand the experiences of people living with Parkinson's disease. / Mini Dissertation (MSW)--University of Pretoria, 2016. / Social Work and Criminology / MSW / Unrestricted

Background: Parkinson's disease (PD) is a debilitating progressive neurological disorder. The main clinical features of PD are: rigidity, bradykinesia, akinesia, and resting tremor. People living with PD often present with impaired gross- and fine upper-limb motor control and ocular tracking. The impaired motor control associated with PD results in difficulty performing basic- and instrumental activities of daily living (BADLs and IADLs). Virtual reality (VR) therapy is an emerging treatment strategy used to address movement impairment in people with neurological diseases, but has not been extensively researched in the rehabilitation of people with PD. This study aimed to determine the effectiveness of VR therapy as a treatment modality for the rehabilitation of upper-limb function during BADLs and IADLs and ocular tracking for people with PD, when compared to conventional physiotherapy. Methods: A single blind randomised control trial was done. Participants were randomly allocated to either the conventional therapy (control) or VR therapy (experimental) groups using the concealed opaque envelope method. Twenty-two participants who gave informed consent were included, if they met the following criteria: Confirmed PD diagnoses; scored above 24/30 for the Mini Mental State Examination; and did not suffer from uncontrolled co-morbid diseases. The control- and experimental groups underwent twelve intervention session of 45 minutes. The control group participated in conventional physiotherapy sessions and the experimental group used the X-box Kinect© VR apparatus during treatment. Participants were assessed at baseline and post-intervention (directly following the 12 session) with the: 9 Hole Peg Test (9HPT), Test d'Evaluation des Membres Superieurs De Personnes Agees (TEMPA) and the King Devick Test. Results: The TEMPA was used to determine unilateral- and bilateral upper-limb function during IADLs and BADLs. Three of the four items of the TEMPA that assessed bilateral upper-limb function indicated statistically significant improvement when the difference between the control and experimental groups were compared post-intervention (Task1 p=0.611; Task 2 p=0.0043; Task 3 p=0.0078; Task 4 p=0.0002). Similarly, three of the four items of the TEMPA that assessed unilateral upper-limb function indicated statistically significant improvement for the experimental group, when compared to the control- group post-intervention (Task 5 p=0.0151; Task 6 p=0.4118; Task 7 p=0.0064; Task 8 p=0.0009). The 9HPT assessed in-hand manipulation and fine upper-limb function. Results from the 9HPT for the left- and right hands of both groups showed clinically significant improvements from baseline to post-intervention, but there was no statistically significant difference between the two groups. The King Devick test was used to assess ocular tracking. The comparison of change between the two groups from baseline to post-intervention on the King Devick did not indicate clinically- or statistically significant change. Discussion and Conclusion: The findings from the bilateral IADL and BADL tasks as measured with the TEMPA are similar to findings in the literature. The results show that VR therapy improve motor control of the upper-limb significantly when both hands work together and when the upper-limbs are moving unilaterally. VR therapy might be more effective than conventional physiotherapy because it allowed for repetitive practice of functional activities, which aided the development of limb control and functional muscle strength. The VR therapy also allowed task-oriented training to occur repetitively. Task-oriented training is known to aid neural plasticity and facilitate functional rehabilitation. The insignificant differences between the groups on the 9HPT is an indication that the task performed for this outcome measure is not specific enough to detect hand function and grip strength. The King Devick test did not indicate change for the control- or experimental groups, which indicates that specific ocular tracking exercises should be included in therapy to address this impairment. / Dissertation (MPhysiotherapy)--University of Pretoria, 2016. / Physiotherapy / MPhysiotherapy / Unrestricted

Background In the as of yet uncurable Parkinson´s disease aggregation of α-syn is an accelerator of pathogenesis. Oligomers of α-synuclein is considered to be neurotoxic hence blocking the endocytosis of aggregated α-syn is possibly a way of preventing pathogenesis. With a protein construct of the Receptor X (RX) previously shown to bind α-syn, it can be possible to bind soluble aggregated α-syn and decrease neuron endocytosis.  Aim The aim of this study was to express, purify and trimerize two different protein constructs of RX to study the binding to α-syn monomers & oligomers and if the proteins have higher affinity to α-syn oligomers. Methods In this study two RX constructs was produced with mammalian cell transfection and purified with Strep-Tactin affinity chromatography; D1, D123mut and D123 which affinity to α-syn monomers and oligomers were studied with ELISAs. Indirect ELISAs were optimized and conducted, a competitive ELISA with D123 was tested with poor reliability.  Results The results show that D1 could not be determined pure enough to examine its α-syn binding ability. D123mut was pure enough for ELISAs but did not show adequate binding to α-syn. D123 did show binding to α-syn in an indirect ELISA.  Conclusion The results were not as promising as expected and did not distinctly help strengthen the theory of a recombinant RX protein as a viable drug. Although there is potential, optimization of both protein constructs and methods used is essential for future studies of RX as a therapeutic protein.

No description available.

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

The classic rodent model of Parkinson’s disease (PD) is produced by unilateral lesioning of pars compacta substantia nigra (SNpc) in adult rats, producing unilateral motor deficits which can be assessed by dopamine (DA) D2 receptor (D2-R) agonist induction of measurable unilateral rotations. Bilateral SNpc lesions in adult rats produce life-threatening aphagia, adipsia, and severe motor disability resembling paralysis-a PD model that is so compromised that it is seldom used. Described in this paper is a PD rodent model in which there is bilateral 99% loss of striatal dopaminergic innervation, produced by bilateral intracerebroventricular or intracisternal 6-hydroxydopamine (6-OHDA) administration to perinatal rats. This procedure produces no lethality and does not shorten the life span, while rat pups continue to suckle through the pre-weaning period; and eat without impairment post-weaning. There is no obvious motor deficit during or after weaning, except with special testing, so that parkinsonian rats are indistin-guishable from control and thus allow for behavioral assessments to be conducted in a blinded manner. L-DOPA (L-3,4-dihydroxyphenylalanine) treatment increases DA content in striatal tissue, also evokes a rise in extraneuronal (i.e.,in vivo microdialysate) DA, and is able to evoke dyskinesias. D2-R agonists produce effects similar to those of L-DOPA. In addition, effects of both D1-and D2-R agonist effects on overt or latent receptor supersensitization are amenable to study. Elevated basal levels of reactive oxygen species (ROS), namely hydroxyl radical, occurring in dopaminergic denervated striatum are suppressed by L-DOPA treatment. Striatal serotoninergic hyperinnervation ensuing after perinatal dopaminergic denervation does not appear to interfere with assessments of the dopaminergic system by L-DOPA or D1-or D2-R agonist challenge. Partial lesioning of serotonin fibers with a selective neurotoxin either at birth or in adulthood is able to eliminate sero-toninergic hyperinnervation and restore the normal level of serotoninergic innervation. Of all the animal models of PD, that produced by perinatal 6-OHDA lesioning provides the most pronounced destruction of nigrostriatal neurons, thus representing a model of severe PD, as the neurochemical outcome resembles the status of severe PD in humans but without obvious motor deficits.

The molecular mechanism responsible for degenerative process in the nigrostriatal dopaminergic system in Parkinson’s disease (PD) remains unknown. One major advance in this field has been the discovery of several genes associated to familial PD, including alpha synuclein, parkin, LRRK2, etc., thereby providing important insight toward basic research approaches. There is an consensus in neurodegenerative research that mitochondria dysfunction, protein degradation dysfunction, aggregation of alpha synuclein to neurotoxic oligomers, oxidative and endoplasmic reticulum stress, and neuroinflammation are involved in degeneration of the neuromelanin-containing dopaminergic neurons that are lost in the disease. An update of the mechanisms relating to neurotoxins that are used to produce preclinical models of Parkinson´s disease is presented. 6-Hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and rotenone have been the most wisely used neurotoxins to delve into mechanisms involved in the loss of dopaminergic neurons containing neuromelanin. Neurotoxins generated from dopamine oxidation during neuromelanin formation are likewise reviewed, as this pathway replicates neurotoxin-induced cellular oxidative stress, inactivation of key proteins related to mitochondria and protein degradation dysfunction, and formation of neurotoxic aggregates of alpha synuclein. This survey of neurotoxin modeling—highlighting newer technologies and implicating a variety of processes and pathways related to mechanisms attending PD—is focused on research studies from 2012 to 2014.