A small, prospective study has revealed both clinical symptoms of peripheral neuropathy and pathological evidence of small nerve fiber damage after initiation of levodopa/carbidopa intestinal gel (LCIG) infusion in patients with advanced Parkinson’s disease.1
Parkinson’s disease (PD) is characterized by a degeneration of dopamine terminals, which leads to dyskinesias. Oral levodopa/carbidopa has a half-life of only about 90 minutes; however LCIG, delivered by continuous infusion via percutaneous endoscopic gastrostomy (PEG) tube, allows for continuous dopamine administration and is associated with improvements in both motor and nonmotor symptoms of PD.2
LCIG infusion is typically reserved for patients with advanced PD who demonstrate fluctuating symptoms refractory to oral treatments. However, LCIG infusion has recently been tied to peripheral neuropathy ranging from pain and sensory disturbances to Guillain-Barre-type polyneuropathy. The mechanism of this adverse effect is not fully understood, but B12 deficiency and increases in homocysteine have been suggested as a cause.1
In the current study, Grazia Devigili, MD, PhD, of the University-Hospital S. Maria della Misericordia in Udine, Italy and colleagues sought to find evidence of small nerve fiber damage after LCIG infusion.
Study participants were clinically evaluated and assessed using the Quantitative Sensory Testing battery, nerve conduction studies, and baseline and serial intraepidermal nerve fiber density testing.
The study included 6 patients in the PD treatment naïve group, 6 patients in the L-dopa group, and 5 patients in the LCIG group (mean age 67, 67, and 68 years, respectively). There were no differences between the groups at baseline for signs of clinical neuropathy, skin innervation, or thermal thresholds. At month 3, the LCIG group demonstrated decreases in epidermal innervation (P< .002) and increased thermal thresholds. At month 6, 4 participants in the LCIG group demonstrated increases in the Douleur Neuropathique 4 (DN4) (P< .01) and Inflammatory Neuropathy Cause and Treatment-Sensory Sum Score (INCAT-SSS) (P< .002) questionnaires. Further, participants had increased thermal thresholds, reports of burning pain, and skin denervation (P< .004), which required treatment for neuropathic pain in 2 participants. At the completion of the study at 12 months, 1 patient demonstrated mild large fiber axonal sensory peripheral neuropathy.
Notably, participants in the LCIG group demonstrated improved PD symptoms and quality of life compared to the other groups (P= .009 and P= .002).
“Our findings lead us to consider possible damage to small nerve fibers” the authors wrote. “This can lead to development of pain or sensory discomforts, thus skin biopsy should be considered to be a potential outcome measure for LCIG treatment.”
The findings, if confirmed in a larger cohort, pose a significant cost-benefit challenge for treatment of advanced PD, as the authors noted that patients in the study treated with LCIG infusion saw significant improvements in motor complications and clinical global status despite the highlighted adverse effects.
The authors report no relevant disclosures.
- Devigili G, Tch SR, Lettieri C, Eleopra R. Levodopa/carbidopa intestinal gel (LCIG) therapy for advanced Parkinson’s Disease: An early toxic effect for small nerve fibers?. Muscle Nerve. 2016 Sept 26; doi:10.1002/mus.25377. [Epub ahead of print]
- Pedersen SW, Clausen J, Gregerslund MM. Practical guidance on how to handle levodopa/carbidopa intestinal gel therapy of advanced PD in a movement disorder clinic. Open Neurol J. 2012;6:37-50.