Medical and surgical management of advanced Parkinson's disease

Abstract

Advanced Parkinson's disease is characterized by the presence of motor fluctuations, various degree of dyskinesia, and disability with functional impact on activities of daily living and independence. Therapeutic management aims to extend levodopa benefit while minimizing motor complications and includes, in selected cases, the implementation of drug infusion and surgical techniques. In milder forms of motor complications, these can often be controlled with manipulation of levodopa dose and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, and dopamine agonists including apomorphine. Clinical experience and evidence from published studies indicate that when these agents cannot satisfactorily control motor complications, patients should be assessed and considered for device-aided therapies. This review article summarizes some of the newer available therapeutic opportunities such as use of enzyme inhibitors like opicapone and safinamide, adenosine A receptor antagonists, apomorphine and levodopa/carbidopa intestinal gel infusion, deep brain stimulation including the role of closed-loop and adaptive stimulation, and MRI-guided focused ultrasound. © 2018 International Parkinson and Movement Disorder Society.

Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease: a multi-country Delphi-panel approach

“…those also having non-motor issues) who may have been excluded in the trials. Additional challenges in the identification of "advanced" PD patients further hinder timely initiation of appropriate treatments and sharing of relevant information in a timely manner 9,41,46 . Recently published systematic reviews and consensus articles acknowledge that there is a growing need to establish guidelines and pragmatic clinical management approaches for the different treatment choices for PD patients requiring device-aided interventions [47][48][49][50] .…”

“…Attempts have been made to chart the clinical progression of PD and define appropriate treatment and severity milestones 6 . As PD progresses, patients may become increasingly dependent on caregivers, and disability is dominated by motor symptoms (MS) and non-motor symptoms (NMS) that may be resistant to dopaminergic mediation and/or oral administration of medications 2,[7][8][9] . Management of advanced PD (APD) symptoms, particularly motor fluctuations, dyskinesia and off-time, may require optimizing of oral therapies (including polypharmacy, dose fractioning, and dose tapering) or the use of advanced therapies such as deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion (CSAI), or levodopa-carbidopa intestinal gel (LCIG) infusion 1,[10][11][12] .…”

Randomized phase I clinical trial of anti–α‐synuclein antibody BIIB054

“…It is estimated that the number of people with PD will double from 6.9 million in 2015 to 14.2 million in 2040 . Current treatments provide only partial relief of motor symptoms and may worsen other symptoms . There are no approved therapies that slow disease progression or adequately treat levodopa‐unresponsive symptoms (eg, cognitive or autonomic).…”

Should there be less emphasis on levodopa‐induced dyskinesia in Parkinson's disease?

“…Dyskinesia did not feature in the top 10 “bothersome symptoms” reported by 173 patients with at least 6 years of disease duration whereas nonmotor symptoms dominated this list . In addition, the use of DBS and continuous drug‐delivery strategies by transdermal or dopaminergic infusion therapies has also served to reduce the number of severe cases of dyskinesia …”