Ferreira, Joaquim, 1968-Sampaio, Cristina, 1963-Coelho, Miguel Vilhena Soares, 1972-2017-01-272017-01-2720162015http://hdl.handle.net/10451/26272Tese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2016Parkinson`s disease (PD) is an age-related neurodegenerative disorder with progressive disability. Its incidence is expected to increase substantially owing to ageing of world population. Better general healthcare, and better understanding of complications and clinical management of PD is likely to increase in the future the prevalence of PD patients in very advanced stages of disease, when disability is most severe. These very advanced patients will represent an important burden for families and the healthcare and social systems, and a new challenge for healthcare personnel. Nevertheless, the clinical characteristics of these late-stage PD (LS-PD) patients have been only partially described in the pre-levodopa or post-levodopa era. Since knowledge of the health needs of these patients is crucial to plan effective health resources that cover patients and caregivers needs, we aimed to study the clinical features and handicap of LS-PD patients attending two tertiary centres, selected on the basis of motor disability. We also aimed to study whether the handicap of LS-PD patients differs from that of classical advanced stage PD patients, i.e., patients manifesting disabling levodopa-induced motor complications, and, if so, whether that modifies the way we conceive today the natural history of PD. Finally, we reviewed the pharmacological and non-pharmacological interventions available to treat the non-motor symptoms of LS-PD, using a systematic approach. Participants were LS-PD (stage 4 or 5 of Hoehn & Yahr scale in on state) and advanced stage PD patients (patients with disabling levodopa-induced motor complications selected to deep brain stimulation), and their informal caregivers. Cross-sectional data were obtained using comprehensive clinical assessment. Handicap was assessed using the London Handicap Scale (LHS). Descriptive and regression analysis was performed. To review the treatment available for non-motor symptoms in LS-PD, we extracted the controlled clinical trials for PD dementia, psychosis, falls, bone fractures, joint and skeletal deformities, pain, orthostatic hypotension, gastrointestinal abnormalities and urological dysfunction; we chose these symptoms because they were considered as the most disabling for LS-PD patients, based on our results and published data. 50 LS-PD patients (mean age 74.1 years and mean disease duration 17.9 years) were studied. Severe akinetic symmetric parkinsonism was present in most, with negligible rigidity and tremor, and most patients were wheelchair-bound. Postural instability and freezing of gait, causing frequent falls and fractures, and prominent dysarthria and dysphagia dominated the motor syndrome. Levodopa, used as monotherapy in one-third of the cases, remained partially effective in most patients but with limited clinical relevance. Dosage of antiparkinsonian drugs was probably influenced by the frequent occurrence of neuropsychiatric symptoms. Motor fluctuations and dyskinesias were frequent but not disabling. All had neuropsychiatric and dysautonomic symptoms, namely dementia and visual hallucinations in half and depression in two-thirds of the patients. Lack of tremor and absence of depression were independently associated with dementia. Greatest impact on perceived health status was due to motor and non-motor levodopa-resistant symptoms. The LHS was easy to use in these patients and their caregivers. Handicap was severe and determined by dementia, behavioural complaints and the severity of non-dopaminergic motor features. Most affected domain of handicap was Orientation. Co-morbidities and past medical conditions were frequent. Patients visited doctors infrequently and made low use of health resources, while unpaid caregivers reported a high burden which correlated with patients’ handicap. The LHS was also easily completed by 100 advanced stage PD patients (mean age 61 years and mean disease duration 12.2 years) and their carers. Handicap was moderate-to-severe, although less than that of LS-PD patients. In contrast to the latter, Physical Independence and Social Integration were the most affected domains, and the determinants of handicap were disability in ADL and dyskinesias. The clinical features, severity and determinants of handicap of PD patients in late-stage differ from those in advanced stage, although they are nowadays classified under the generic category of advanced stage patients. LS-PD patients are severely handicapped from axial motor and non-motor symptoms unresponsive to levodopa, and they are very dependent on caregivers. Data suggest that LS-PD is a very distinct sub-group of advanced stage PD, and we propose an operational definition for LS-PD that anchors on (lack) of functionality regardless the cause is motor or non-motor symptomatology, using the Schwab and England scale in on. Unfortunately, few controlled clinical trials are available to treat most non-motor symptoms that disable LS-PD patients. Best evidence exists for the treatment of dementia, psychosis, osteoporosis and prevention of fractures, and sialorrhea. The present study provides cross-sectional evidence that LS-PD is a distinct sub-group of advanced stage PD, and that LS-PD patients manifest a clinical picture dominated by a severe akinetic symmetric non-dopaminergic motor phenotype and by severe non-motor features, which are overall poorly responsive to levodopa. LHS is easily completed by PD patients and handicap can be further explored as a patient-centred outcome in PD. Caregivers have a high burden that is correlated with patients’ handicap. In face of an expected increase in the prevalence of LS-PD and lack of efficacious therapies for most disabling symptoms, future research and allocation of funds should focus on non-levodopa responsive aspects of the disease and the needs of caregivers.engDoença de ParkinsonDemênciaDoenças neurodegenerativasCérebroNeurologiaTeses de doutoramento - 2016doctoral thesis101366256