Control Of Motor Fluctuations Research Articles

Apomorphine: a powerful ally in Parkinson's disease

Apomorphine, a D1-D2 dopamine agonist, is the oldest drug with proven efficacy in the treatment of Parkinson's disease (PD), and the only with similar symptomatic power to levodopa. Its usefulness in the control of motor fluctuations, both as intermittent injections and in continuous subcutaneous infusion, has been demonstrated in open label and placebo controlled trials. To analyse the role of apomorphine in the varied clinical symptoms and different clinical stages of PD through a narrative review of scientific literature (1951-2020). Beyond on-time increase, off-time decrease, off dystonia and quality of life improvement in advanced PD, there is evidence to support a role of apomorphine in less known clinical areas of PD, such as non motor symptoms, a lower risk of impulse control disorders, potential to ameliorate visual hallucinations, improve neuropsychiatric symptoms and dyskinesia and even axial features. Nevertheless, the optimal timing of apomorphine treatment remains controversial, and its implementation of this valuable drug in clinical practice has been historically hindered by several factors. Apomorphine is a unique drug in the PD treatment scenario, with a number of potential applications beyond motor fluctuations control. Acknowledging these properties, selecting the patient most likely to benefit from it and finding the right timing may be key in the symptomatic control of this complex disease.

Optimized clinical management of Parkinson's disease with opicapone. Recommendations from Spanish experts.

Motor fluctuations are frequently seen in Parkinson disease patients on chronic treatment with levodopa. Management of motor fluctuation includes the addition of catechol-O-methyl transferase (COMT) inhibitors. Opicapone is a recent and selective third-generation COMT inhibitor which achieves marked increase in the bioavailability of levodopa. We present a consensus of a group of Spanish neurologists with extensive experience in the clinical management of motor fluctuations. The clinical experience of this group of experts is in line with clinical trials and confirms that opicapone is an effective drug in the control of motor fluctuations, regardless of the daily levodopa dose, or the use of other antiparkinsonian drugs. However, in the opinion of these experts, the ideal patient with Parkinson's disease to initiate treatment with opicapone is the one with mild motor fluctuations, since the ratio between clinical efficacy and adverse effects is more favorable. In general, it is an easy-to-use drug both in those first treated with a COMT inhibitor or those already on entacapone. In any case, the secondary side effects are easily managed.

Adjunctive Therapies in Parkinson's Disease: How to Choose the Best Treatment Strategy Approach.

End-of-dose motor fluctuations are regarded as one of the core troublesome symptoms by patients with Parkinson's disease (PD). Treatment of levodopa (L-dopa)-induced motor fluctuations is still an unmet medical need. L-dopa is the gold standard in the treatment of motor PD symptoms; notwithstanding, a wide range of adjunct therapies are currently available for the treatment of end-of-dose motor fluctuations. Additionally, device-aided therapies, such as deep brain stimulation, L-dopa-carbidopa intestinal gel infusion, and on-demand injection or continuous apomorphine infusion, may be considered when oral treatments are not sufficient to control motor fluctuations. In spite of the several evidence-based reviews and guidelines available, there is no agreement on which add-on therapy should be started first or its optimal timing. Equally challenging is the choice and timing between device-aided therapies. Herein, we propose a general overview of oral and device-aided treatments for PD patients with end-of-dose motor fluctuations, offering two possible algorithms that can guide clinicians during the therapeutic decision process.

Apomorphine infusion in advanced Parkinson disease.

The TOLEDO study provides new evidence to support the use of subcutaneous apomorphine infusion to control motor fluctuations in patients with advanced Parkinson disease. The findings should encourage neurologists to consider implementing apomorphine infusion or other device-aided therapies earlier in the disease course, before the emergence of troublesome dyskinesias.

Levodopa-Carbidopa Intestinal Gel in a Pediatric Parkinsonism-plus Syndrome.

In Parkinson's disease, levodopa-carbidopa intestinal gel (LCIG) is indicated in control of motor fluctuations, dyskinesias1 and non-motor symptoms. We here report the first case of LCIG pediatric use. Our patient presented with upper limb tremor at 6 months and subsequently with axial hypotonia, dysphagia and generalized dystonia. He did not achieve the milestones in psychomotor development: he could not stand, walk, nor manipulate objects; verbal production was never acquired. At 14 months, brain magnetic resonance was normal and cerebrospinal fluid examination showed low levels of homovanillic acid, neopterin and biopterin. This article is protected by copyright. All rights reserved.

An Observational Study of the Effect of Levodopa-Carbidopa Intestinal Gel on Activities of Daily Living and Quality of Life in Advanced Parkinson's Disease Patients.

IntroductionContinuous delivery of levodopa–carbidopa intestinal gel (LCIG) by percutaneous endoscopic gastrojejunostomy (PEG-J) in advanced Parkinson’s disease (PD) patients reduces variability in plasma levels, providing better control of motor fluctuations (“on” and “off” states). The MONOTREAT study assessed the effect of LCIG on activities of daily living, motor and non-motor symptoms, and quality of life in advanced PD patients.MethodsThis prospective, observational study included patients with advanced, levodopa-responsive PD with either 2–4 h of “off” time or 2 h of dyskinesia daily. Patients received LCIG via PEG-J for 16 h continuously. Effectiveness was assessed using Unified PD Rating Scale parts II and III, the Non-Motor Symptom Scale, and the PD Questionnaire-8.ResultsThe mean (SD) treatment duration was 275 (157) days. Patients experienced significant improvement from baseline in activities of daily living at final visit (p < 0.05) as well as at months 3 and 6 (p < 0.0001). Patients also experienced significant improvements from baseline in quality of life and non-motor symptoms at all time points (p < 0.001 for all). Specifically, patients manifested significant improvements in mean change from baseline at every study visit in five of nine non-motor symptom score domains: sleep/fatigue, mood/cognition, gastrointestinal tract, urinary, and miscellaneous. One-third of patients (32.8%) experienced an adverse event; 21.9% experienced a serious adverse event; 11.1% discontinued because of an adverse event.ConclusionThis study demonstrated significant and clinically relevant improvements in measures of activities of daily living, quality of life, and a specific subset of non-motor symptoms after treatment with LCIG.FundingAbbVie Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0571-2) contains supplementary material, which is available to authorized users.

DOPAMINE DYSREGULATION SYNDROME IN PARKINSON’S DISEASE AND APPROACHES TO ITS CORRECTION WITH DRUGS

The objective is to describe a clinical case of dopamine dysregulation syndrome (DDS) with compulsive intake of large doses of levodopa in a patient with Parkinson’s disease (PD). Materials and methods. Male patient R., born in 1956, has had PD since 2004 when he noticed changes in his handwriting, difficulties to perform small movements with the right hand. Therapy with levodopa/benserazide was started at 300 mg/day. With time symptoms of the disease escalated: gait impairment and motor fluctuations started. Action duration after administration of levodopa/benserazide sin gle dose shortened to 2 hours, peak dose dyskinesia developed, as well as instability with frequent falls. In 2012, clinical picture of the disease included symptoms of DDS. The patient independently increased the drug dose, decreased time between doses, didn’t follow the doctor’s recommendations. Relatives noticed a state of euphoria in the patient after taking a dose of levodopa/benserazide. At the time of visiting the Department of Neurology of the Russian Medical Academy of Continuous Professional Education in the beginning of 2016, the daily equivalent levodopa dose was 2000 mg, and 800 mg of it were taken at night. Results. The patient was transferred to a three-component modern levodopa drug Stalevo (levodopa + carbidopa + entacapone) 150 mg + levodopa/benserazide 50 mg 6 times a day (daily dose 1200 mg). Decreased levodopa daily dose achieved by transferring the patient to a three-component drug with better bioavailability lead to significant reduction of motor and non-motor symptoms, significant increase in effect duration after a single dose of levodopa. In a year of follow-up, DDS symptoms gradually regressed, time between drug administration increased, the patient stopped taking the drug at night, fluctuations and drug-induced dyskinesias significantly decreased. Conclusion. In this clinical case, manifestations of DDS caused by long-term compulsive levodopa intake at doses significantly exceeding daily dose (necessary for control of motor symptoms) are described. One of the approaches to reduction of high doses of levodopa and control of motor fluctuations is prescription of Stalevo which stabilizes levodopa level in plasma and provides a more continuous stimulation of dopamine receptors in the striatum.

Experience with duodenal levodopa infusion in advanced Parkinson's disease in our hospital

BackgroundContinuous levodopa delivery by enteral infusion is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesia in advanced Parkinson's disease (PD).PurposeThe objective was to...

Experiencia con la infusión continua de levodopa intraduodenal (Duodopa ®) en pacientes con enfermedad de Parkinson avanzada en un hospital de segundo nivel asistencial

Introduction Continuous levodopa delivery by enteral infusion (Duodopa ®) is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We report our experience with Duodopa ® therapy in 11 patients with advanced PD. Methods We retrospectively assessed clinical and quality of life changes in all patients with PD with severe motor fluctuations and dyskinesias who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy from September 2006 (Duodopa ® was approved for advanced PD treatment in Spain at that date) until April 2010 at the A. Marcide Hospital of Spain. Results Nine patients received Duodopa ® [62.7 ± 10.6 (44-74) years, 63.6% male)]. Pre-Duodopa ® clinical characteristics of patients were: disease duration 14.5 ± 8.9 (3-34) years, oral levodopa dose 918.2 ± 277.7 (450-1300) mg/day, and Hoehn and Yahr staging 3.7 ± 0.5 (3-4). Nine patients are still receiving Duodopa ®. Patients improved motor fluctuations (72.7% significant improvement), dyskinesia (55.5% significant improvement), daily off-time (90.9%) and daily duration dyskinesia (66.6%) after total infusion time of 170.5 months (3-31). The improvement in Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39) and Schwab&England Capacity for Daily Living Scale were 38.5 ± 19.8 and 24 ± 12.5 respectively ( P < 0.05). Equivalent daily dose of levodopa (April 2010) was 1683.4 ± 295.8 (1234-2216) mg/day. Conclusions Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

Rasagilina: eficacia y protección en la enfermedad de Parkinson

Parkinson's disease (PD) is the second most frequent neurodegenerative disease in the general population after Alzheimer's disease. Its diagnosis is based on the presence of characteristic motor symptoms due to the striatal dopaminergic depletion caused by progressive neuronal death in the pars compacta substantiae nigrae. Thus, not only is it necessary to restore the neurochemical deficits that are present from the initial phases of the disease onwards, but therapeutic strategies also need to be developed to stop the degenerative process. Rasagiline is a monoamine oxidase-B inhibitor whose dopaminergic stimulation has proved to be effective in monotherapy or in combined therapy for improving the motor symptoms in patients with PD in the initial and advanced phases. Likewise, it is also effective in diminishing motor fluctuations. Comparatively, rasagiline has proved to be at least as effective as entacapone in the control of motor fluctuations. With regard to the possible effect and the neuroprotective properties of rasagiline in vitro and in vivo, it is the first pharmaceutical to have displayed a change in the developmental course of PD after 72 weeks' treatment.

Experience with continuous levodopa enteral infusion (Duodopa ®)in patients with advanced Parkinson's disease in a secondary level hospital

Introduction Continuous levodopa delivery by enteral infusion (Duodopa ®) is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We report our experience with Duodopa ® therapy in 11 patients with advanced PD. Methods We retrospectively assessed clinical and quality of life changes in all patients with PD with severe motor fluctuations and dyskinesias who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy from September 2006 (Duodopa ® was approved for advanced PD treatment in Spain at that date) until April 2010 at the A. Marcide Hospital of Spain. Results Nine patients received Duodopa ® [62.7±10.6 (44–74) years, 63.6% male)]. Pre- Duodopa ® clinical characteristics of patients were: disease duration 14.5±8.9 (3–34) years, oral levodopa dose 918.2±277.7 (450–1300) mg/day, and Hoehn and Yahr staging 3.7±0.5 (3–4). Nine patients are still receiving Duodopa ®. Patients improved motor fluctuations (72.7% significant improvement), dyskinesia (55.5% significant improvement), daily off-time (90.9%) and daily duration dyskinesia (66.6%) after total infusion time of 170.5 months (3–31). The improvement in Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39) and Schwab&England Capacity for Daily Living Scale were 38.5±19.8 and 24±12.5 respectively (P<0.05). Equivalent daily dose of levodopa (April 2010) was 1683.4±295.8 (1234–2216) mg/day. Conclusions Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease

Apomorphine and levodopa infusion therapies for advanced Parkinson's disease.

Continuous infusion of levodopa or apomorphine provide constant dopaminergic stimulations are good alternatives to deep brain stimulation to control motor fluctuations in patients with advanced Parkinson’s disease (PD). Apomorphine provides motor benefit similar to dopamine, but its long-term use is limited by compliance, mostly injection site skin reactions. Administration of levodopa/carbidopa by continuous duodenal infusion allows replacement of all oral medications and permits achievement of a satisfactory therapeutic response paralleled by a reduction in motor complication severity. However, this procedure is more invasive than apomorphine as it requires a percutaneous endoscopic gastrostomy Clinical experience with infusions shows that continuous dopaminergic stimulation of dopaminergic medications reduces dyskinesia and widens the therapeutic window in advanced PD.

A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa.

To compare the safety and efficacy of ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the level of daily dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist before study entry. Patient response was defined as at least a 20% reduction in daily L-dopa dose plus: for patients with no prior treatment and no motor fluctuations, a 20% reduction in UPDRS motor score; for patients with motor fluctuations, a 20% reduction in time spent "off"; and for patients already taking an agonist, an improvement on the CGI scale. Safety assessments showed no significant differences in the two treatment groups for patients without prior dopamine-agonist therapy. In the group of patients with prior dopamine-agonist therapy, more patients reported adverse events in the ropinirole group (90% versus 79%, p < 0.001). The proportions of responders tended to be higher in ropinirole groups compared with bromocriptine groups and, in the subgroup with motor fluctuations, this difference was statistically significant (9.1% versus 0.0%, respectively; p < 0.05). Both drugs were well tolerated. In patients receiving a relatively high dose of L-dopa and requiring the addition of a dopamine agonist to control motor fluctuations or dyskinesias, ropinirole was significantly more effective than bromocriptine.

How many inpatient paediatric units do we need?

Continuous duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established treatment to control motor fluctuations in Parkinson’s disease. Duodenal infusion allows a steady absorption of the drug in the small bowel, reducing plasmatic fluctuations of levodopa. Some complications may occur during the treatment, often related to intrajejunal percutaneous endoscopic gastrostomy (PEG-J). We report a case of duodenal ulcer associated with a phytobezoar involving the end of jejunal probe, in a patient who underwent PEG-J for LCIG infusion. In the last 2 weeks, the patient suffered from abdominal pain and dyspepsia. Oesophagogastroduodenoscopy showed an ulcerative lesion of the duodenum due to traction of the jejunal tube; the end of the jejunal tube was wrapped in a phytobezoar. This case is interesting because of the extension of the ulcerative lesion due to PEG-J dislocation and because of the subtle symptoms associated with it.