Optimisation of dopaminergic therapy may alleviate fluctuation-related pain in Parkinson's disease (PD). Opicapone (OPC) is a third-generation, once-daily catechol-O-methyltransferase inhibitor shown ...to be generally well tolerated and efficacious in reducing OFF-time in two pivotal trials in patients with PD and end-of-dose motor fluctuations. The OpiCapone Effect on motor fluctuations and pAiN (OCEAN) trial aims to investigate the efficacy of OPC 50 mg in PD patients with end-of-dose motor fluctuations and associated pain, when administered as adjunctive therapy to existing treatment with levodopa/dopa decarboxylase inhibitor (DDCi).
OCEAN is a Phase IV, international, multicentre, randomised, double-blind, placebo-controlled, parallel-group, interventional trial in PD patients with end-of-dose motor fluctuations and associated pain. It consists of a 1-week screening period, 24-week double-blind treatment period and 2-week follow-up period. Eligible patients will be randomised 1:1 to OPC 50 mg or placebo once daily while continuing current treatment with levodopa/DDCi and other chronic, stable anti-PD and/or analgesic treatments. The primary efficacy endpoint is change from baseline in Domain 3 (fluctuation-related pain) of the King's Parkinson's disease Pain Scale (KPPS). The key secondary efficacy endpoint is change from baseline in Domain B (anxiety) of the Movement Disorder Society-sponsored Non-Motor rating Scale (MDS-NMS). Additional secondary efficacy assessments include other domains and total scores of the KPPS and MDS-NMS, the Parkinson's Disease Questionnaire (PDQ-8), the MDS-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts III and IV, Clinical and Patient's Global Impressions of Change, and change in functional status via Hauser's diary. Safety assessments include the incidence of treatment-emergent adverse events. The study will be conducted in approximately 140 patients from 50 clinical sites in Germany, Italy, Portugal, Spain and the United Kingdom. Recruitment started in February 2021 and the last patient is expected to complete the study by late 2022.
The OCEAN trial will help determine whether the use of adjunctive OPC 50 mg treatment can improve fluctuation-associated pain in PD patients with end-of-dose motor fluctuations. The robust design of OCEAN will address the current lack of reliable evidence for dopaminergic-based therapy in the treatment of PD-associated pain.
EudraCT number 2020-001175-32 ; registered on 2020-08-07.
The benefit of deep brain stimulation (DBS) in controlling the motor symptoms of Parkinson's disease is well established, however, the impact on the non-motor symptoms (NMS) remains to be elucidated, ...although the growing investigative efforts are promising. This article reviews the reported data and considers the level of evidence available with regard to the effect of DBS on NMS total burden and on the cognitive, neuropsychiatric, sleep, pain, dysautonomic, and weight domains. Multiple case series suggest that DBS improves the burden of NMS by reducing prevalence, intensity, and non-motor fluctuations. There is level I evidence on the effect of DBS on cognition and mood. Slight cognitive decline has been reported in most class I studies, although the functional effect is probably minimal. Two randomized prospective studies reported no change in depression while improvement of anxiety has been reported by a class I trial. Prospective cohort studies point to improvement of hyperdopaminergic behaviors, such as impulse control disorders, while others report that hypodopaminergic states, like apathy, can appear after DBS. There is only class III evidence supporting the benefit of DBS on other NMS such as nocturnal sleep, pain, dysautonomia (urinary, gastrointestinal, cardiovascular, and sweating), and weight loss. Although preliminary results are promising, randomized prospectively controlled trials with NMS as primary end points are necessary to further explore the effect of DBS on these often invalidating symptoms and offer conclusions about efficacy.
There is a growing interest in functional movement disorders (FMD). However, epidemiological data from large cohorts of patients with FMD are scarce and come mainly from General Neurology and ...Movement Disorders Clinics. Recently, specialized FMD clinics have been developed and epidemiological data from such clinics may provide useful information. We aimed to describe the clinical and sociodemographic features of patients diagnosed with FMD at our specialized FMD clinic. A standardized form was used to extract data from electronic records from the first-100 consecutive patients who were evaluated and diagnosed with FMD at our clinic from 2017 to 2019. Mean age was 40.88 ± (14.02) years, 63% females. Most patients were within working-age range, but only 16% were working at the time of consultation. Mean disease duration was 3.74 ± 5.73 years and was longer among men. The most common FMD were gait disturbance (42%), tremor (22%) and dystonia (15%). A precipitating event (mainly physical) was reported by 74%. The onset was mostly acute (83%) and the clinical course fluctuating (62%). Pain (64%) and fatigue (44%) were common comorbidities. Potential joint-hypermobility was present in 21%, mostly women (90%) and related to the presence of dystonia. FMD affects men and women mostly in working-age. Gait disturbance was the most common diagnosis, possibly because it causes a higher level of disability that may lead to consultation in a specialized clinic. Non-motor symptoms (pain and fatigue) were frequent in this cohort. Further data from specialized units may contribute to both understanding and management of FMD.
Patients with movement disorders have a high prevalence of sleep disturbances that can be classified as (1) nocturnal sleep symptoms, such as insomnia, nocturia, restless legs syndrome (RLS), ...periodic limb movements (PLM), obstructive sleep apnea (OSA), and REM sleep behavior disorder; and (2) diurnal problems that include excessive daytime sleepiness (EDS) and sleep attacks. The objective of this review is to provide a practical overview of the most relevant scales that assess these disturbances to guide the choice of the most useful instrument/s depending on the line of research or clinical focus. For each scale, the reader will find a brief description of practicalities and psychometric properties, use in movement disorder cohorts and analyzed strengths and limitations. To assess insomnia, the Pittsburgh Sleep Quality Index, a generic scale, and three disease-specific scales: the Parkinson Disease Sleep Scale (PDSS), the PDSS-2, and Scales for outcomes in Parkinson's disease (PD)-Sleep-Nocturnal Sleep subscale are discussed. To evaluate nocturia, there are no specific tools, but some extensively validated generic urinary symptom scales (the Overall Bladder Questionnaire and the Overactive Bladder Symptom Score) and some PD-specific scales that include a nocturia item are available. To measure RLS severity, there are currently four domain-specific generic scales: The International Restless Legs Scale, the Johns Hopkins Restless Legs Severity Scale, the Restless Legs Syndrome-6 measure, a Pediatric RLS Severity Scale, and the Augmentation Severity Rating Scale (a scale to evaluate augmentation under treatment) and several instruments that assess impact on quality of sleep and health-related quality of life. To evaluate the presence of PLM, no clinical scales have been developed to date. As far as OSA, commonly used instruments such as the Sleep Apnea Scale of the Sleep Disorders Questionnaire, the STOP-Bang questionnaire, and the Berlin Questionnaire are reviewed. Three scales have been extensively used to assess EDS: the generic Epworth Sleepiness Scale, the Stanford Sleepiness Scale, and the PD-specific Scales for outcomes in PD-Sleep-Daytime sleepiness subscale. To date, only the Inappropriate Sleep Composite Score specifically evaluates propensity to sleep attacks.
Functional movement disorders are commonly seen in neurology services and may coexist with other neurological diseases. This combination is known as “functional overlay” and an increasing interest on ...this topic has emerged in the past decade as the field of functional neurological disorders has moved forward. Some neurological diseases may be more prone to develop “functional overlay” than others, and within the field of movement disorders, most studies have focused on patients with Parkinson's disease. This review comprehensively summarizes the current body of knowledge on this topic and provides an expert opinion to equip clinicians with a pragmatic approach to recognize functional movement disorders in patients with Parkinson's disease, to communicate the diagnosis and to become familiar with potential therapies in this complex clinical scenario. Potential underlying mechanisms and risk factors that may play a role in increasing the vulnerability of Parkinson's disease patients to develop functional movement disorder comorbidity are also discussed within the framework of modern neurobiological theories of brain functioning.
•Functional movement disorder (FMD) comorbidity is common in Parkinson's Disease (PD).•FMD can occur at any time during the disease course, even prior to PD diagnosis.•Frequent phenotypes include gait disturbance and tremor.•Recognition is based on positive signs from clinical history and neurological exam.•Diagnosis of FMD comorbity is important to treat accordingly and avoid iatrogenesis.
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