Neuropathy in Parkinson’s Disease Patients with Intestinal Levodopa Infusion versus Oral Drugs

Abstract

BackgroundSevere polyneuropathy has been observed in a number of patients treated for Parkinson’s disease with Levodopa/Carbidopa intestinal gel infusion. This may reflect a rare individual complication or a systematic side effect.ObjectiveTo investigate whether peripheral nerve function differed between patients with oral treatment versus Levodopa/Carbidopa intestinal gel infusion.MethodsIn an observational design, data from median, tibial, and peroneal neurography were prospectively assessed and compared between patients with conventional drug treatment (n = 15) and with Levodopa/Carbidopa intestinal gel infusion (n = 15). The groups were matched for age and disease duration. In view of the medical risk profile for polyneuropathy, comorbidity and basic serological parameters were assessed.ResultsAxonal neuropathy was common in both patient groups. However, although group differences in risk factors for polyneuropathy were not evident, neurographic abnormalities were more severe in the patients treated with Levodopa/Carbidopa intestinal gel infusion than in the orally treated patients. In the group with Levodopa/Carbidopa intestinal gel infusion, the degree of neuropathic change correlated with weight lost since therapy initiation and with the drug dose. In contrast to the axonal abnormalities, conduction velocity was found normal in both groups.ConclusionThe results are compatible with the promotion of axonal neuropathy by Levodopa/Carbidopa intestinal gel infusion. This could be due to the intrinsically high levodopa doses associated with the therapy and/or malnutritional effects from intestinal drug application. The results should be corroborated by a larger longitudinal and controlled trial.

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

“…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).…”

“…A possible dose dependency is also supported by our observation that patients with LCIG had more severe axonal loss and more nerves affected than the oral group. This finding is exactly the same described in another study examining neuropathy in LCIG treated in comparison to orally treated patients (Jugel et al., 2013). …”

“…Why is this probably a dose‐dependent phenomenon, and why is it so obvious in LCIG? It has been speculated that something in LCIG might be the cause; for example, the methylcellulose gel could hamper jejunal membrane functions (Jugel et al., 2013). We hypothesize that the reason might be the action of carbidopa in LCIG: Carbidopa is widely known as the decarboxylase inhibitor that inevitably comes along in LCIG and most oral levodopa formulations.…”

“…Also folate deficiency (Rajabally & Martey, 2013) and levodopa itself, especially LCIG and its ingredients or its way of resorption (Jugel et al., 2013), have been suspected to be involved in the development of neuropathy in IPD.…”

Peripheral nervous system involvement in Parkinson's disease: Evidence and controversies

“…Indeed, studies showed higher PN risk in CLDII patients compared to DA patients, whereas there was no statistically significant difference between CLDII and oral LD patients [25,35]. Nonetheless, Jugel et al reported more severe neurographic abnormalities in CLDII compared to oral LD patients [48] ( Table 2). The mechanism underlying PN in oral LD and CLDII patients is likely to be similar: a correlation between LD daily dose and PN occurrence has been observed in CLDII patients too [25,35] (Table 2).…”