Clinical practice guidelines for management of parkinson’s disease : a systematic critical appraisal

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Impact of pallidotomy on physiological articulation function and speech intelligibility in Parkinsons disease

The objective of this study was to evaluate the effects of posteroventral pallidotomy on perceptual and physiological measures of articulatory function and speech intelligibility in Parkinson disease (M). The study examined 11 participants with M who underwent posteroventral pallidotomy Physiological measures of hp and tongue function. and perceptual measures of speech intelligibility were obtained prepallidotomy and 3 months postpallidotomy. The participants with PD were also assessed on the Unified Parkinsons Disease Rating Scale (UPDRS Part III) In addition, the study included a group of 16 participants with PD who did not undergo pallidotomy and a group of 30 nonneurologically impaired participants. Analyses of physiological articulatory function and speech intelligibility did not reveal corresponding improvements in motor speech function as observed in general limb motor function postpallidotomy. Overall, individual reliable change analyses revealed that the majority of surgical PD participants demonstrated no reliable change on perceptual and physiological measures of articulation. The cur rent study revealed preliminary evidence that articulatury function and speech intelligibility did not change following posteroventral pallidotomy in a group of individuals with PD.

High-accuracy discrimination of Parkinson’s Disease participants from healthy controls using smartphones

Objective: To test the practicality and effectiveness of cheap, ubiquitous, consumer-grade smartphones to discriminate Parkinson’s disease (PD) subjects from healthy controls, using self-administered tests of gait and postural sway. Background: Existing tests for the diagnosis of PD are based on subjective neurological examinations, performed in-clinic. Objective movement symptom severity data, collected using widely-accessible technologies such as smartphones, would enable the remote characterization of PD symptoms based on self-administered, behavioral tests. Smartphones, when backed up by interviews using web-based videoconferencing, could make it feasible for expert neurologists to perform diagnostic testing on large numbers of individuals at low cost. However, to date, the compliance rate of testing using smart-phones has not been assessed. Methods: We conducted a one-month controlled study with twenty participants, comprising 10 PD subjects and 10 controls. All participants were provided identical LG Optimus S smartphones, capable of recording tri-axial acceleration. Using these smartphones, patients conducted self-administered, short (less than 5 minute) controlled gait and postural sway tests. We analyzed a wide range of summary measures of gait and postural sway from the accelerometry data. Using statistical machine learning techniques, we identified discriminating patterns in the summary measures in order to distinguish PD subjects from controls. Results: Compliance was high all 20 participants performed an average of 3.1 tests per day for the duration of the study. Using this test data, we demonstrated cross-validated sensitivity of 98% and specificity of 98% in discriminating PD subjects from healthy controls. Conclusions: Using consumer-grade smartphone accelerometers, it is possible to distinguish PD from healthy controls with high accuracy. Since these smartphones are inexpensive (around $30 each) and easily available, and the tests are highly non-invasive and objective, we envisage that this kind of smartphone-based testing could radically increase the reach and effectiveness of experts in diagnosing PD.

Motor complications in an incident Parkinson’s disease cohort

Funded by •Parkinson's UK •Scottish Chief Scientist Office •BMA Doris Hillier Award •RS Macdonald Trust •BUPA Foundation •NHS Grampian Endowments •SPRING •National Institute of Health Research, and Engineering and Physical Sciences Research Council

Motor complications in an incident Parkinson’s disease cohort

Funded by •Parkinson's UK •Scottish Chief Scientist Office •BMA Doris Hillier Award •RS Macdonald Trust •BUPA Foundation •NHS Grampian Endowments •SPRING •National Institute of Health Research, and Engineering and Physical Sciences Research Council

A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterised by motor and non-motor symptoms, resulting from the degeneration of nigrostriatal dopaminergic neurons and peripheral autonomic neurons. Given the limited success of neurotrophic factors in clinical trials, there is a need to identify new small molecule drugs and drug targets to develop novel therapeutic strategies to protect all neurons that degenerate in PD. Epigenetic dysregulation has been implicated in neurodegenerative disorders, while targeting histone acetylation is a promising therapeutic avenue for PD. We and others have demonstrated that histone deacetylase inhibitors have neurotrophic effects in experimental models of PD. Activators of histone acetyltransferases (HAT) provide an alternative approach for the selective activation of gene expression, however little is known about the potential of HAT activators as drug therapies for PD. To explore this potential, the present study investigated the neurotrophic effects of CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), which is a potent small molecule activator of the histone acetyltransferase p300/CBP, in the SH-SY5Y neuronal cell line. We report that CTPB promoted the survival and neurite growth of the SH-SY5Y cells, and also protected these cells from cell death induced by the neurotoxin 6-hydroxydopamine. This study is the first to investigate the phenotypic effects of the HAT activator CTPB, and to demonstrate that p300/CBP HAT activation has neurotrophic effects in a cellular model of PD.

Functional Magnetic Resonance Imaging Neurofeedback and Motor training for Parkinson’s Disease: Randomised Trial

Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient’s own brain activity to self-regulate brain networks which in turn could lead to a change in behaviour and clinical symptoms. The objective was to determine the effect of neurofeedback and motor training and motor training (MOT) alone on motor and non-motor functions in Parkinson’s disease (PD) in a 10-week small Phase I randomised controlled trial. Methods: 30 patients with PD (Hoehn & Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with motor training. Group 2 (MOT: 15 patients) received motor training alone. The primary outcome measure was the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post-intervention ‘off-medication’. The secondary outcome measures were the ‘on-medication’ MDS-UPDRS, the Parkinson’s disease Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. Results: Patients in the NF group were able to upregulate activity in the supplementary motor area by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the ‘off-medication’ state (95% confidence interval: -2.5 to -6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to -6.8). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. Interpretation: This Phase I study suggests that NF combined with motor training is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions. Clinical Trial website : Unique Identifier: NCT01867827 URL: https://clinicaltrials.gov/ct2/show/NCT01867827?term=NCT01867827&rank=1

Effect of investigation intensity and treatment differences on prostate cancer survivor's physical symptoms, psychological well-being and health-related quality of life: a two country cross-sectional study.

Aim: To investigate effects on men's health and well-being of higher prostate cancer (PCa) investigation and treatment levels in similar populations. Participants: PCa survivors in Ireland where the Republic of Ireland (RoI) has a 50% higher PCa incidence than Northern Ireland (NI). Method: A cross-sectional postal questionnaire was sent to PCa survivors 2–18 years post-treatment, seeking information about current physical effects of treatment, health-related quality of life (HRQoL; EORTC QLQ-C30; EQ-5D-5L) and psychological well-being (21 question version of the Depression, Anxiety and Stress Scale, DASS-21). Outcomes in RoI and NI survivors were compared, stratifying into ‘late disease’ (stage III/IV and any Gleason grade (GG) at diagnosis) and ‘early disease’ (stage I/II and GG 2–7). Responses were weighted by age, jurisdiction and time since diagnosis. Between-country differences were investigated using multivariate logistic and linear regression. Results: 3348 men responded (RoI n=2567; NI n=781; reflecting population sizes, response rate 54%). RoI responders were younger; less often had comorbidities (45% vs 38%); were more likely to present asymptomatically (66%; 41%) or with early disease (56%; 35%); and less often currently used androgen deprivation therapy (ADT; 2%; 28%). Current prevalence of incontinence (16%) and impotence (56% early disease, 67% late disease) did not differ between RoI and NI. In early disease, only current bowel problems (RoI 12%; NI 21%) differed significantly in multivariate analysis. In late disease, NI men reported significantly higher levels of gynaecomastia (23% vs 9%) and hot flashes(41% vs 19%), but when ADT users were analysed separately, differences disappeared. For HRQoL, in multivariate analysis, only pain (early disease: RoI 11.1, NI 19.4) and financial difficulties (late disease: RoI 10.4, NI 7.9) differed significantly between countries. There were no significant between-country differences in DASS-21 or index ED-5D-5L score. Conclusions: Treatment side effects were commonly reported and increased PCa detection in RoI has left more men with these side effects. We recommended that men be offered a PSA test only after informed discussion.

Morphosyntactic and syntactic priming: an investigation of underlying processing mechanisms and the effects of Parkinson’s disease

There is now considerable evidence to suggest that non-demented people with Parkinson's disease (PD) experience difficulties using the morphosyntactic aspects of language. It remains unclear, however, at precisely which point in the processing of morphosyntax, these difficulties emerge. The major objective of the present study was to examine the impact of PD on the processes involved in accessing morphosyntactic information in the lexicon. Nineteen people with PD and 19 matched control subjects participated in the study which employed on-line word recognition tasks to examine morphosyntactic priming for local grammatical dependencies that occur both within (e.g. is going) and across (e.g. she gives) phrasal boundaries (Experiments 1 and 2, respectively). The control group evidenced robust morphosyntactic priming effects that were consistent with the involvement of both pre- (Experiment 1) and post-lexical (Experiment 2) processing routines. Whilst the participants with PD also recorded priming for dependencies within phrasal boundaries (Experiment 1), priming effects were observed over an abnormally brief time course. Further, in contrast to the controls, the PD group failed to record morphosyntactic priming for constructions that crossed phrasal boundaries (Experiment 2). The results demonstrate that attentionally mediated mechanisms operating at both the pre- and post-lexical stages of processing are able to contribute to morphosyntactic priming effects. In addition, the findings support the notion that, whilst people with PD are able to access morphosyntactic information in a normal manner, the time frame in which this information remains available for processing is altered. Deficits may also be experienced at the post-lexical integrational stage of processing.

Discourse priming of homophones in individuals with dominant subcortical lesions, cortical lesions, and Parkinson’s disease

An on-line priming experiment was used to investigate discourse-level processing in four matched groups of subjects: individuals with nonthalamic subcortical lesions (NSL) ( n =10), normal control subjects ( n =10), subjects with Parkinsons disease (PD) ( n =10), and subjects with cortical lesions ( n =10). Subjects listened to paragraphs that ended in lexical ambiguities, and then made speeded lexical decisions on visual letter strings that were: nonwords, matched control words, contextually appropriate associates of the lexical ambiguity, contextually inappropriate associates of the ambiguity, and inferences (representing information which could be drawn from the paragraphs but was not explicitly stated). Targets were presented at an interstimulus interval (ISI) of 0 or 1000ms. NSL and PD subjects demonstrated priming for appropriate and inappropriate associates at the short ISI, similar to control subjects and cortical lesion subjects, but were unable to demonstrate selective priming of the appropriate associate and inference words at the long ISI. These results imply intact automatic lexical processing and a breakdown in discourse-based meaning selection and inference development via attentional/strategic mechanisms.

Test–retest repeatability of self-reported environmental exposures in Parkinson’s disease cases and healthy controls

There is substantial disagreement among published epidemiological studies regarding environmental risk factors for Parkinson’s disease (PD). Differences in the quality of measurement of environmental exposures may contribute to this variation. The current study examined the test–retest repeatability of self-report data on risk factors for PD obtained from a series of 32 PD cases recruited from neurology clinics and 29 healthy sex-, age-and residential suburb-matched controls. Exposure data were collected in face-to-face interviews using a structured questionnaire derived from previous epidemiological studies. High repeatability was demonstrated for ‘lifestyle’ exposures, such as smoking and coffee/tea consumption (kappas 0.70–1.00). Environmental exposures that involved some action by the person, such as pesticide application and use of solvents and metals, also showed high repeatability (kappas>0.78). Lower repeatability was seen for rural residency and bore water consumption (kappa 0.39–0.74). In general, we found that case and control participants provided similar rates of incongruent and missing responses for categorical and continuous occupational, domestic, lifestyle and medical exposures.

Prevalence of Parkinson’s disease in metropolitan and rural Queensland: A general practice survey

The prevalence of idiopathic Parkinson’s disease (IPD) in Australia is unclear. We estimated the prevalence of IPD, and other forms of parkinsonism, through the study of typical caseloads in general practice. A random sample of general practitioners (GPs) throughout Queensland (401 responses from 528 validated practice addresses) was asked to estimate the numbers of patients with IPD and parkinsonism seen in the preceding year. The estimated prevalence of diagnosed IPD in Queensland was 146 per 100 000 (95% CI = 136–155). A further 51 per 100 000 in the population were suspected by doctors to have IPD without formal diagnosis, whereas another 51 per 100 000 people may have non-idiopathic parkinsonism. Idiopathic Parkinson’s disease was more common in rural than metropolitan areas. Although most GPs were confident in making diagnoses of IPD, the majority had little or no confidence in their ability to treat the disease, especially in its later stages. Support from neurologists was perceived by GPs to be very good in cities, but poor in remote areas.

Changes in physical symptoms during the menopause transition

This article analyzes physical symptoms experienced by mid-age Australian women in different stages of the menopause transition. A total of 8,623 women, aged 45 to 50 years in 1996, who participated the mid-age cohort of the Australian Longitudinal Study on Women's Health, completed Survey I in 1996 and Survey 2 in 1998. Women were assigned to I of 6 menopause groups according to their menopausal status at Surveys 1 and 2, and compared on symptoms experienced at Surveys I and 2, adjusted for lifestyle, behavioral and demographic factors. At Survey 1, the most commonly reported symptoms were headaches, back pain, stiff joints, tiredness, and difficulty sleeping. Perimenopausal women were more likely than premenopausal or postmenopausal women to report these symptoms. Hot flushes and night sweats were more common among postmenopausal women. Compared with those who remained premenopausal, women who were in the early stages of menopause or perimenopausal were more likely to report tiredness, stiff joints, difficulty sleeping, and hot flushes at Survey 2. Women who remained perimenopausal were also more likely to report back pain and leaking urine. Compared with premenopausal women, odds ratios for night sweats increased for women in consecutive stages of the menopause transition and remained high in the postmenopausal women.

Algorithm for the Parkinson’s disease behavioural models characterization using a biosensor

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica