Background: Lack of a global consensus on the definition of advanced Parkinson's disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care.
Objectives: ...To reach consensus among movement disorder specialists regarding key patient characteristics indicating transition to APD and guiding appropriate use of device-aided therapies in the management of PD symptoms.
Methods: A Delphi-panel approach was utilized to synthesize opinions of movement disorder specialists and build consensus.
Results: A panel was comprised of movement disorder specialists from 10 European countries with extensive experience of treating PD patients (mean =24.8 ± 7.2 years). Consensus on indicators of suspected APD and eligibility for device-aided therapies were based on motor symptoms, non-motor symptoms, and functional impairments. Key indicators of APD included: (i) motor-moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h "off" symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor-mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment-repeated falls despite optimal treatment, and difficulty with activities of daily living. Patients with good levodopa response, good cognition, and <70 years of age were deemed as good candidates for all three device-aided therapies. Patients with troublesome dyskinesia were considered good candidates for both levodopa-carbidopa intestinal gel and Deep Brain Stimulation (DBS). PD patients with levodopa-resistant tremor were considered good candidates for DBS.
Conclusion: Identifying patients progressing to APD and suitable for device-aided therapies will enable general neurologists to assess the need for referral to movement disorder specialists and improve the quality of care and patient outcomes.
The power of a placebo to effect clinically meaningful neurobiological change comparable to pharmacological therapies has been demonstrated, although the mechanisms are not fully understood. ...Predicting placebo responsiveness has only recently received more attention, but psychological disposition, contextual and biological factors are now known to dramatically affect a person's susceptibility to the placebo effect. The placebo effect depends upon expectancies that can be modified in a number of ways, including conditioning through explicit or implicit learned associations. Based on the dopaminergic response to anticipation of benefit in Parkinson's disease, it was suggested that the placebo effect can be seen as analogous to the expectation of reward. Dopaminergic pathways have since been implicated in the placebo response in pain and depression. Additionally, endogenous opioid release is known to mediate many forms of placebo analgesia. We provide an overview of the mechanisms and the therapeutic implications of the placebo effect in neurological and psychiatric conditions. We include evidence for detrimental effects arising from seemingly inert interventions, termed the 'nocebo effect.' Neuroimaging has critically advanced the study of the placebo effect and provides some of the strongest evidence for the mechanisms of this phenomenon prevalent across an array of human health-related circumstances. This review specifically focuses on mechanisms of the placebo effect in the three conditions that have most significantly demonstrated this effect and for which a plausible physiological basis can be identified: pain, PD and depression. Other neurological and psychiatric diseases reviewed include multiple sclerosis, Huntington's disease, Alzheimer's disease, schizophrenia and epilepsy.
Summary Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the ...pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson's disease from healthy controls, and show great promise for differentiation between Parkinson's disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson's disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson's disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression.
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