Continuous dopaminergic delivery to minimize motor complications in Parkinson’s disease

Wright, Brenton A.; Waters, Cheryl

doi:10.1586/ern.13.47

Cited by 37 publications

(20 citation statements)

References 71 publications

(106 reference statements)

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“…50 In addition, the Earlier versus Later Levodopa Therapy in Parkinson Disease (ELLDOPA) study showed that complications can occur within the first year. 51 A recent study designed to evaluate the presence of motor and non-motor fluctuations using a specific questionnaire, the 19- 53,54 Therefore, in the clinic, HRQoL assessments should be easy to use and complement traditional diagnostic evaluations used by physicians. Since these traditional approaches can be time-consuming, laborious and require specialist training, HRQoL scales may offer a broader evaluation of the disease in routine practice that is both simple and rapid.…”

Section: The Clinical Perspectivementioning

confidence: 99%

Quality of Life in Parkinson’s Disease – Patient, Clinical and Research Perspectives

Stocchi¹,

Martinez‐Martín

Reichmann

2014

European Neurological Review

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Parkinson's disease (PD) has a severely negative impact on the quality of life (QoL) of patients and their caregivers. Health-related QoL (HRQoL) is a patient-reported component of QoL that includes physical, mental and social domains and in PD is an increasingly important part of patient monitoring. HRQoL in PD is assessed using a range of different generic (e.g. Short Form-36) and PD-specific (e.g. 39-item Parkinson's Disease Questionnaire) instruments/questionnaires. It is important that HRQoL is regularly determined in patients with PD to identify determinants of their HRQoL deterioration and appropriately manage them. The perspectives of PD patients, clinicians and researchers, however, can be different. In PD, motor symptoms such as slowness or tremor are the most visible manifestations of the disease and these tend to be concentrated on by doctors. PD patients, however, are likely to also have a range of non-motor symptoms such as nocturia, urinary frequency, fatigue, drooling and forgetfulness, which can be more troubling than motor symptoms. These can increase distress and social isolation but are often unreported or overlooked. In addition, morning akinesia and wearing-off phenomena may cause additional difficulty. However, these symptoms and patient concerns can be readily identified using simple HRQoL measures. The management of PD should therefore take into account patient, clinical and research perspectives of HRQoL in order to recognise and adequately address the consequences of motor and non-motor symptoms in PD.

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Section: The Clinical Perspectivementioning

confidence: 99%

Quality of Life in Parkinson’s Disease – Patient, Clinical and Research Perspectives

Stocchi¹,

Martinez‐Martín

Reichmann

2014

European Neurological Review

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“…Meanwhile, motor complications are associated with non-physiologic intermittent or pulsatile stimulation of dopamine receptors40. Based on such theory, CDS has been shown to reduce motor complications in advanced PD patients, and has been hypothesized to prevent their incidence when given as early therapy in PD13. Indeed, some basic researches showed treatment with intermittent injections of a short-acting dopamine agonist induced motor complications while continuous infusion of the same agent did not11.…”

Section: Discussionmentioning

confidence: 99%

“…What is more, clinical studies of L-dopa/carbidopa intraduodenal gel infusion revealed marked reductions in ‘off’ time along with improvement in ‘on’ time when compared with conventional treatment12. Recent numerous evidences suggest wide-ranging symptoms improvement with CDS in patients with severe motor complication, which has beneficial implications for the management of patients with advanced PD in clinical practice13. This theory proposes that CDS can provide more continuous stimulation of brain dopaminergic receptors than intermittent doses of oral L-dopa, which is indicate dyskinesia and motor fluctuations could be delayed even though prevented by realizing continuous stimulation of striatal dopamine receptors using long-acting medicines such as dopamine agonists14.…”

mentioning

confidence: 98%

Continuous dopaminergic stimulation (CDS)-based treatment in Parkinson's disease patients with motor complications: A systematic review and meta-analysis

Xie

Wang

Zhang

et al. 2014

Sci Rep

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A systematic review of the literature was conducted to identify randomized trials involving continuous dopaminergic stimulation (CDS) in PD patients with motor complications. Difference between n groups was assessed by partitioning heterogeneity and using the χ2 distribution with n-1 degrees of freedom, where n equals the number of groups. We looked for publication bias using funnel plotting, Egger's test and Begg's test. Twenty Randomized Controlled Trials (RCTs) were included. The results showed that CDS could evidently improve the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (p < 0.0001), part III (P < 0.00001) and UPDRS total score (p < 0.00001). There was also a statistical discrepancy in off time reduction (p < 0.00001) and prolongation of on time (p < 0.00001) by the CDS therapy compared with control groups. Meanwhile, the results of this study showed obvious side effects in the CDS therapy compared with the placebo, especially at the expense of increased dyskinesia (23.4% vs 11.7%). The present study showed that CDS was beneficial in the treatment of PD patients with motor complications. But the incidence of the side events is more common than placebo.

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“…The theories of development of LID are reviewed extensively by Bastide et al and Bezard et al (106,107). Motor complications are reduced when levodopa is given continuously (20,(108)(109)(110), resulting in a more continuous stimulation of the dopaminergic receptors. Previous studies have shown that continuous dopaminergic stimulation (CDS) seems to induce plasticity changes of the dopaminergic postsynaptic receptors reducing motor complications (20,111,112) and possibly restoring the receptor changes caused by previous PD medication.…”

Section: Motor Complicationsmentioning

confidence: 99%

Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

Nord¹

2017

Linköping University Medical Dissertations

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Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients. In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment. To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.Parkinsons sjukdom (PS) är en av de vanligaste s.k. neurodegenerativasjukdomarna och orsakas av förlust av dopamin(DA)producerande nervceller i hjärnan. Detta orsakar motoriska symptom såsom skakningar, stelhet och förlångsammade rörelser. Levodopa (LD) är ett ämne, som kan omvandlas till DA i hjärnan och ge symptomlindrin...

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Continuous dopaminergic delivery to minimize motor complications in Parkinson’s disease

Cited by 37 publications

References 71 publications

Quality of Life in Parkinson’s Disease – Patient, Clinical and Research Perspectives

Quality of Life in Parkinson’s Disease – Patient, Clinical and Research Perspectives

Continuous dopaminergic stimulation (CDS)-based treatment in Parkinson's disease patients with motor complications: A systematic review and meta-analysis

Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

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