Motor features and response to oral levodopa in patients with Parkinson’s disease under continuous dopaminergic infusion or deep brain stimulation

Elia, Antonio E.; Dollenz, C; Soliveri, Paola; Albanese, Alberto

doi:10.1111/j.1468-1331.2011.03437.x

Cited by 27 publications

(34 citation statements)

References 37 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We found that LCIG improves motor fluctuations in spite of the target and results of DBS, but that best outcome is observed in patients who had previously undergone bilateral STN DBS, as confirmed by the only two studies describing the combination use of LCIG and DBS . This finding is also in keeping with a previous study showing that patients on STN DBS are less prone to develop dyskinesias when challenged with high doses of l ‐dopa …”

supporting

confidence: 90%

Levodopa‐carbidopa intestinal gel therapy after deep brain stimulation

et al. 2017

View full text Add to dashboard Cite

supporting

confidence: 90%

Levodopa‐carbidopa intestinal gel therapy after deep brain stimulation

et al. 2017

View full text Add to dashboard Cite

“…This delay to best motor "On" could arise from the absence of an initial highflow-rate morning dose of jejunal levodopa as was used in the current work, resulting in a longer time required to reach therapeutic levodopa plasma levels (29). This possibility is supported by the fact that the time to best motor "On" was improved when a morning oral dose of levodopa was added in the study of Elia et al (39). Our study is limited in that the effects of LCIG on motor symptoms were not assessed.…”

Section: Discussionsupporting

confidence: 69%

Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients

Nyholm

Odin

Johansson

et al. 2012

AAPS J

View full text Add to dashboard Cite

Abstract. Motor complications of Parkinson's disease (PD) are a consequence of pulsatile dopaminergic stimulation from standard oral levodopa therapy. Levodopa-carbidopa intestinal gel (LCIG) is infused continuously via an intrajejunal percutaneous gastrostomy tube. This was the first study designed to characterize the full pharmacokinetic profiles of levodopa, carbidopa, and levodopa metabolite, 3-Omethyldopa (3-OMD) with 16-h LCIG infusion. Nineteen advanced PD patients (mean age, 65 years) who were on LCIG therapy for ≥30 days were enrolled. Patients received their individualized LCIG infusion doses, and serial pharmacokinetic samples were collected. Eighteen patients completed the study; 19 were assessed for safety. Mean (SD) total levodopa and carbidopa doses were 1,580 (403) and 395 (101)mg, respectively. Mean (SD) C avg (μg/mL) were 2.9 (0.84) for levodopa, 17.1 (4.99) for 3-OMD, and 0.22 (0.08) for carbidopa. The degree of fluctuation [defined as (C max −C min )/C avg ] in levodopa, 3-OMD, and carbidopa plasma concentrations was very low (0.52, 0.21, and 0.96, respectively) during hours 2-16 of infusion. Accordingly, the within-subject coefficients of variation in levodopa, 3-OMD, and carbidopa concentrations were low (13%, 6%, and 19%, respectively). Three patients (16%) reported ≥1 treatment-emergent adverse event; none were considered severe. Continuous intrajejunal LCIG infusion maintained stable plasma levodopa levels over 16 h. Consistent exposure has been shown to reduce motor and nonmotor complications associated with oral medications. LCIG was well tolerated, consistent with previous reports.

show abstract

“…A study comparing STN DBS and LCIG reported an overall similar short‐term effect on motor fluctuations, although STN DBS may have been more effective against LID and associated with fewer adverse events . A pharmacological study comparing the acute and chronic effects of L‐dopa in a relatively small group of patients receiving either STN DBS, LCIG, or CSAI concluded that DBS was the best strategy for LID reduction …”

Section: Managementmentioning

confidence: 99%

Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts

Espay

Morgante

Merola

et al. 2018

Annals of Neurology

249

204

View full text Add to dashboard Cite

Levodopa-induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa-to-dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine-releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in-development treatments for peak-dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. ANN NEUROL 2018;84:797-811 D yskinesia, often referred to as L-dopa-induced dyskinesia (LID) to recognize L-dopa as the major contributor, is a motor complication arising in patients with Parkinson disease (PD) on chronic L-dopa treatment, largely in a dose-dependent fashion-except when given as an infusion, such as in L-dopa/carbidopa intestinal gel. 1 LID is phenomenologically recognized as chorea/choreoathetoid movements appearing initially on the more affected body side. LID occurs in 40% of patients after 4 years on L-dopa treatment, with risk especially high in younger patients treated with higher doses of L-dopa. 2 This review focuses on aspects of phenomenology, pathophysiology, and therapeutics that have undergone revisions or updates in recent years, emphasizing those of most relevance for modern clinical care and future research. We highlight the under-recognized diphasic dyskinesia, which is often mischaracterized as a peak-dose phenomenon and therefore mismanaged. We review evidence that corrects the misinterpretation of prior clinical trial data surmising LID as a function of duration of Ldopa exposure rather than duration of disease, justifying the inappropriate but still lingering recommendation to postpone L-dopa treatment as long as possible to "delay" the appearance of LID. 3 We also review the latest pathophysiologic concepts at the molecular, synaptic, and network levels, to provide the rationale for currently available as well as emerging treatments. Peak-Dose versus Diphasic DyskinesiaPeak-Dose Dyskinesia. Chorea that may be generalized or affect the more affected side or upper body often occurs during the therapeutic window of a L-dopa dose cycle View this article online at wileyonlinelibrary.com.

show abstract

Motor features and response to oral levodopa in patients with Parkinson’s disease under continuous dopaminergic infusion or deep brain stimulation

Cited by 27 publications

References 37 publications

Levodopa‐carbidopa intestinal gel therapy after deep brain stimulation

Levodopa‐carbidopa intestinal gel therapy after deep brain stimulation

Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients

Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts

Contact Info

Product

Resources

About