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Levodopa‐Induced Neuropathy: A Systematic Review
Author(s) -
Romagnolo Alberto,
Merola Aristide,
Artusi Carlo Alberto,
Rizzone Mario Giorgio,
Zibetti Maurizio,
Lopiano Leonardo
Publication year - 2019
Publication title -
movement disorders clinical practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 18
ISSN - 2330-1619
DOI - 10.1002/mdc3.12688
Subject(s) - medicine , carbidopa , levodopa , methylmalonic acid , neurology , parkinson's disease , peripheral neuropathy , gastroenterology , pathological , clinical trial , disease , vitamin b12 , vitamin e , endocrinology , diabetes mellitus , psychiatry , biochemistry , chemistry , antioxidant
Background Clinical, neurophysiological, and pathological evidence suggest an association between Parkinson's disease (PD) and peripheral neuropathy (PNP), with a possible causative role of levodopa metabolic products, such as homocysteine and methylmalonic acid. Methods We conducted a systematic review of studies reporting cases of PNP in l ‐dopa‐treated PD patients indexed in PubMed between January 1990 and March 2018. Results We identified 38 articles reporting cases of PNP in PD patients treated with oral l ‐dopa or with l ‐dopa/carbidopa intestinal gel infusion (LCIG). Prevalence of PNP was 30.2% in the former group and 42.1% in the latter. Oral l ‐dopa was mostly associated with slowly progressive PNP, whereas LCIG showed an acute or subacute onset in 35.7% of cases. In both groups, there was an association between PNP and higher l ‐dopa doses, as well as with the following biochemical alterations: increased homocysteine; reduced vitamin B12; increased methylmalonic acid; and reduced vitamin B6. A skin biopsy was performed in 181 patients, showing signs of small fibers neuropathy in 169 (93.4%). Positive, yet preliminary, results were observed in patients receiving periodic vitamin supplementation. Conclusions Over one third of PD patients in treatment with l ‐dopa may develop PNP, with a significantly higher prevalence of acute and subacute forms in those receiving LCIG. Pathogenic mechanisms remain unclear, but possibly related to a complex interplay between peripheral neurodegenerative processes and l ‐dopa neurotoxic metabolites. Prospective, randomized, clinical trials are required to identify factors associated with the onset and progression of PD‐associated PNP and clarify the protective role of B‐group vitamin supplementation.