The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa

Cilia, Roberto; Akpalu, Albert; Sarfo, Fred Stephen; Cham, Momodou; Amboni, Marianna; Cereda, Emanuele; Fabbri, Margherita; Adjei, Patrick; Akassi, John; Bonetti, Alba; Pezzoli, Gianni

doi:10.1093/brain/awu195

Cited by 277 publications

(240 citation statements)

References 61 publications

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“…This finding, together with the usual young disease onset of dyskinetic patients2, might support the notion of a neuroprotective effect of the cholinergic system on nigrostriatal dopamine‐containing neurons 49, 50, 51. In this study, we were not able to properly address a putative neuroprotective effect of the cholinergic system on nigrostriatal dopamine‐containing neurons and disease progression.…”

Section: Discussionmentioning

confidence: 61%

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Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Brumberg

Küsters

Al‐Momani

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease.MethodsThis study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[123I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [123I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[18F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed.ResultsDensity of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side.InterpretationOur findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.

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Section: Discussionmentioning

confidence: 61%

“…In particular, 40% of PD patients may develop enduring motor fluctuations1 such as levodopa‐induced dyskinesias (LIDs), which may be severely incapacitating. Young age at onset and high levodopa doses are known risk factors for its onset 2. At present, few therapeutic options exist for the treatment of LIDs.…”

Section: Introductionmentioning

confidence: 99%

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Brumberg

Küsters

Al‐Momani

et al. 2017

Ann Clin Transl Neurol

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“…This finding is supportive of a few studies indicating that early initiation of levodopa might be a risk factor for motor complications (Schrag & Quinn, 2000; Denny & Behari, 1999) but contrary to some other surveys suggesting that delaying the start of levodopa therapy is not associated with a smaller risk of motor complications in the long term (Scott et al., 2016; Cilia et al., 2014). Our results support the opinion that younger age at onset of PD seems to be a risk factor for motor complications per se (Hashim et al., 2014; García‐Ruiz et al., 2012; Bjornestad et al., 2016; Warren Olanow et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

“…There is growing evidence suggesting that delaying the start of levodopa therapy might not be associated with smaller risk of motor complications in the long term (Scott et al., 2016; Cilia et al., 2014). The relationship between motor complications and distinct clinical motor phenotypes of PD has not been studied enough.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with motor complications in Parkinson's disease

et al. 2017

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ObjectivesLevodopa is the most effective therapy for treating Parkinson's disease (PD); however, side effects such as dyskinesias and motor fluctuations may occur after some years of its usage. The aims of this study were to assess the frequency of and factors associated with motor complications among PD patients on levodopa treatment.MethodsIn a cross‐sectional study carried out in 2010–2013, clinical data and treatment details were collected. Logistic regression expressed by odd ratios (OR) and 95% confidence intervals (CI) was conducted to examine the effects of several independent variables on the occurrence of motor complications.ResultsA total of 455 patients were enrolled, among whom 374 were on levodopa. Analysis was performed in 328 patients whose exact duration of levodopa treatment was known. Among patients included in the analysis, 25.9% experienced motor complications; of these, 21% had dyskinesias and 20.1% had motor fluctuations. Based on logistic regression, statistically significant factors associated with the occurrence of motor complications were younger age at onset of the disease, higher levodopa equivalent daily dose (LEDD), shorter time to levodopa initiation, and akinetic‐rigid dominant phenotype of PD.ConclusionsThis study suggests that postponing the start of levodopa therapy and maintaining low daily doses of levodopa might reduce the risk of motor complications. Our results confirm that due to higher risk of motor complications, effectively treating patients with akinetic‐rigid dominant phenotype of PD might be more challenging than for patients whose dominant symptom is tremor.

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“…The ELLDOPA study, a multicenter placebo-controlled clinical trial, concluded that levodopa treatment did not accelerate the rate of PD progression and was possibly neuroprotective [22]. There is now compelling evidence that duration and severity of disease [23] and high dosages of levodopa [24] (but not duration of levodopa treatment) are major risk factors for inducing levodopa-induced dyskinesias. Although some investigators consider noncontinuous delivery of levodopa to be a risk factor for this complication, this has not been proven and is best considered a hypothesis.…”

Section: Monoamine Oxidase-b (Mao-b) Inhibitorsmentioning

confidence: 99%

Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson’s Disease

Robakis

Fahn

2015

CNS Drugs

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Inhibitors of monoamine oxidase-B (MAO-B) occupy an important place in the treatment of Parkinson's disease. Selegiline was the first MAO-B to be used therapeutically, while rasagiline is a second-generation drug with higher potency and selectivity. Safinamide is an investigational MAO-B inhibitor with non-dopaminergic properties that may provide advantages over its predecessors. As a class, MAO-B inhibitors are safe and well tolerated and provide symptomatic benefit both as monotherapy and in combination with other antiparkinsonian medications from early to late stages of disease. In combination with levodopa, MAO-B inhibitors may improve motor fluctuations and allow for lower total doses of levodopa. Patient characteristics and preferences can be important factors in deciding between agents. As a class, MAO-B inhibitors have shown promise as disease-modifying agents, but the clinical trial evidence to date has not been strong enough to afford them such a label. Future research may help further elucidate their relative merits and clarify their role in altering disease progression. Key PointsRasagiline and selegiline are two monoamine oxidase-B (MAO-B) inhibitors commonly used in the treatment of Parkinson's disease (PD), while safinamide is an investigational agent of the same class.MAO-B inhibitors are safe, with few serious side effects, and provide mild but worthwhile improvements in the motor symptoms of PD, either as monotherapy or adjunctive to levodopa.The possibility that MAO-B inhibitors could slow down the progression of PD has been suggested by some studies but not by others and remains an open question.

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The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa

Cited by 277 publications

References 61 publications

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Factors associated with motor complications in Parkinson's disease

Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson’s Disease

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