Peripheral neuropathy associated with levodopa–carbidopa intestinal infusion: a long‐term prospective assessment

Merola, Aristide; Romagnolo, Alberto; Zibetti, Maurizio; Bernardini, Andrea; Cocito, Dario; Lopiano, Leonardo

doi:10.1111/ene.12846

Cited by 66 publications

(82 citation statements)

References 27 publications

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“…It was predominantly axonal in nature. This proportion was much vaster than previously reported prevalences, which range from 5% to ~40% (Ceravolo et al., 2013; Jugel et al., 2013; Merola et al., 2014, 2016; Rajabally & Martey, 2011; Shahrizaila et al., 2013; Toth, Brown, Furtado, Suchowersky, & Zochodne, 2008; Toth et al., 2010). The frequency in our LCIG group was 100% (6 of 6), in the oral group 73% (8 of 11).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, pyridoxine deficiency increases homocysteine levels, and high doses of pyridoxine have been shown to reduce homocysteine levels (Miodownik, Lerner, Vishne, Sela, & Levine, 2007). Hyperhomocysteinemia is a common finding in levodopa therapy (Antonini, Bondiolotti, Natuzzi, & Bareggi, 2010; Mancini et al., 2014; Miller et al., 2003), and has been suggested to be a cause of neuropathy via a neurotoxic effect (Merola et al., 2016; Muller, 2008; Muller et al., 2013), as it is associated with reduced sensory nerve amplitudes (Muller, Renger, & Kuhn, 2004). We cannot rule out that cobalamin and folate play a role in the genesis of neuropathy, but our data strongly indicate that pyridoxine deficiency is a major factor.…”

Section: Discussionmentioning

confidence: 99%

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Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy

et al. 2017

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ObjectivesTo determine the possible interactions between levodopa therapy and plasma levels of B vitamins in patients with advanced idiopathic Parkinson's disease (IPD) in the context of either oral levodopa therapy or levodopa/carbidopa intestinal gel (LCIG). Secondly, to determine the prevalence of neuropathy and its relation to plasma levels of B vitamins and homocysteine.MethodsMedication doses, neurographies, and serum levels of pyridoxine, cobalamin, folate, and homocysteine of eight LCIG and 13 orally treated advanced IPD patients matched for age, Hoehn & Yahr stage, and UPRDS III were collected. This data was analyzed for correlation with daily levodopa dose (LDD).Results LICG patients had a longer disease duration and higher LDD. All LCIG patients and most orally treated patients had sensorimotor axonal polyneuropathy. Of all plasma vitamin levels, pyridoxine was decreased most and significantly lower in the LCIG group. Cobalamin and folate, however, were within the lower reference range, and homocysteine highly elevated, all without any significant difference between both groups. LDD correlated significantly with pyridoxine deficiency (p = .02) irrespective of the route of application and with hyperhomocysteinemia in the LCIG group (p = .03). At LDDs above 2,000 mg, pyridoxine deficiency was almost always detectable.ConclusionsPyridoxine deficiency and hyperhomocysteinemia are dependent on the daily levodopa/carbidopa dose, while levels of cobalamin and folate are not. The mode of application of levodopa/carbidopa has no impact on B‐vitamin levels. Neuropathy is very frequent in advanced IPD; however, it remains to be investigated further whether neuropathy is more frequent in LCIG than in orally levodopa/carbidopa‐treated advanced IPD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy

et al. 2017

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“…First, the sample size was too small to get statistical power and also detailed information on the effects of zinc deficiency. We have not experienced cases with peripheral neuropathy, but in previous studies, it has been reported to occur as a side effect of LCIG treatment, and homocysteine level and high dose L‐dopa were correlated to chronic peripheral neuropathy (Merola et al, , ). Obviously, it is important to accumulate more number of cases in the future.…”

Section: Discussionmentioning

confidence: 90%

Proposition of zinc supplementation during levodopa–carbidopa intestinal gel treatment

et al. 2018

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ObjectivesLevodopa–carbidopa intestinal gel (LCIG) infusion is a useful therapy for the wearing‐off phenomenon of advanced Parkinson's disease (PD) patients. Recently, we found three PD patients that may have had a zinc deficiency after the LCIG infusion, possibly due to the zinc‐chelating action of levodopa. This study aims to evaluate changes in serum zinc levels in three patients that received LCIG treatment and to determine possible remedies for zinc deficiency during treatment.Materials and MethodsWe performed a prospective blood analysis of serum zinc levels before, when possible, and after LCIG treatment in our three PD patients.ResultsThe serum zinc levels of the first patient before treatment and 4 months after beginning LCIG treatment were 69 and 58 μg/dl, respectively. For the second patient, serum zinc levels before treatment and two months after starting LCIG treatment were 87 and 46 μg/dl, respectively. The baseline serum zinc level for the third patient was not examined, but was 48 μg/dl 5 months after starting the LCIG infusion.ConclusionsLevodopa–carbidopa intestinal gel infusion might have caused a zinc deficiency through levodopa zinc chelation. Zinc deficiency with LCIG infusion has not yet been reported, though preventing zinc deficiency may be an important factor in future LCIG treatment strategies.

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“…Routine monitoring of vitamin and homocysteine levels is recommended, given the association between levodopa treatment, vitamin B6 deficiencies, homocysteine elevation, and peripheral neuropathy . Cases of symptomatic and subclinical peripheral neuropathy (more frequently the latter) have been observed among patients treated with LCIG . Clinicians should be mindful of peripheral neuropathy symptoms (e.g., paresthesia, pain, gait abnormalities) when evaluating patients receiving LCIG and should monitor them as they would individuals receiving oral levodopa treatment.…”

Section: Monitoring and Maintenancementioning

confidence: 99%

Implementing Levodopa‐Carbidopa Intestinal Gel for Parkinson Disease: Insights from US Practitioners

Burack

Aldred

Zadikoff

et al. 2018

Movement Disord Clin Pract

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Background Levodopa‐carbidopa intestinal gel (LCIG, designated in the United States as carbidopa‐levodopa enteral suspension, CLES) was approved in the United States in 2015 for the treatment of refractory motor fluctuations in individuals with Parkinson disease (PD). Many neurologists in the United States have not had personal experience with implementation and management of the unique delivery system for this treatment. Methods and Findings This educational review was developed to provide practitioners with an understanding of LCIG use from the clinician's point of view. Practical recommendations for the use of LCIG from the early planning stages through long‐term patient management were compiled from the published literature, regulatory guidance, and clinical experience. Among the topics reviewed were: assembling a multidisciplinary treatment team, identifying treatment candidates, patient/care partner education, procedural considerations, post‐procedural care, LCIG initiation and titration, troubleshooting issues, and ongoing monitoring. For most of these steps, a considerable amount of individualization is possible, which allows clinicians to tailor protocols based on the needs of their teams, the healthcare system, and the patient and care partner. Although clinical practices are heterogeneous, themes of early planning, ongoing education, and a team‐based approach to management are universal. Conclusions By using established protocols and insights gleaned from experienced practitioners, clinicians who are unfamiliar with LCIG can more feasibly incorporate this treatment option into their armamentarium for treating PD motor fluctuations.

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Peripheral neuropathy associated with levodopa–carbidopa intestinal infusion: a long‐term prospective assessment

Cited by 66 publications

References 27 publications

Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy

Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy

Proposition of zinc supplementation during levodopa–carbidopa intestinal gel treatment

Implementing Levodopa‐Carbidopa Intestinal Gel for Parkinson Disease: Insights from US Practitioners

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