More Neuropathy in Levodopa-Treated Parkinson's Patients

Allison Shelley

November 04, 2011

November 4, 2011 — New evidence suggests that clinical testing for neuropathy in patients with Parkinson's disease receiving long-term levodopa therapy may be advisable.

New findings show that neuropathy is more prevalent in 'patients with Parkinson's disease, and point to a potential link with vitamin B12 deficiency and cumulative levodopa exposure.

"The description of the increased prevalence of neuropathy in Parkinson's disease is recent and remains controversial," acknowledge the investigators led by Yusuf Rajabally, MD, from the University Hospitals of Leicester in the United Kingdom. "Precise underlying pathophysiologic mechanisms implicated also remain debated as are the etiologies and consequences of neuropathy in this population."

These new results support an increased neuropathy prevalence in Parkinson's and "suggest the practical value of measuring vitamin B12 levels in levodopa-treated patients with PD, for whom serial clinical assessments for neuropathy appear justified. Trials of prophylactic replacement therapy may now require consideration."

The results were published online November 2 in Neurology.

Is it conceivable that for 40 years we have overlooked an insidious long-term levodopa treatment adverse effect?

In an accompanying editorial, François Tison, MD, and Gwendal Le Masson, MD, from Bordeaux University in France, ask, "Is it conceivable that for 40 years we have overlooked an insidious long-term levodopa treatment adverse effect, such as neuropathy, in idiopathic Parkinson's disease?"

They say the role remains hypothetical, but "the clinical relevance is evident, as sensory neuropathy may contribute to impaired balance and neuropathic pain."

In this cross-sectional study of 37 patients with Parkinson's disease and 37 age- and sex-matched controls, investigators evaluated the prevalence of neuropathy using the Utah Early Neuropathy Scale, a sensitive and validated scale.

The odds ratio for neuropathy was 6.9, with a 95% confidence interval of 1.78 to 26.73.

Patients With Neuropathy

Outcome Patients with Parkinson's, n (%) Control Subjects, n (%) P Value
Neuropathy 14 (37.8) 3 (8.1) .005

Investigators found that vitamin B12 deficiency was a significantly more common cause of neuropathy (P = .024), and vitamin B12 levels were also significantly lower in patients with Parkinson's disease and neuropathy than in control patients with neuropathy and no Parkinson's (P =.002).

They also found that cumulative levodopa exposure correlated with Parkinson's duration (P =.001) and vitamin B12 levels (P =.044).

"Our results support the possibility that genetically predisposed patients with Parkinson's disease may develop levodopa-induced vitamin B12 deficiency with subsequent neurotoxic methylmalonic acid accumulation," the authors report.

"In view of these data," the editorialists add, "we now need well-designed unselected population-based investigations and at best prospective epidemiologic studies, as well as experimental and clinical/electrophysiologic studies either demonstrating or refuting a direct causative link between levodopa exposure in idiopathic Parkinson's disease, neuropathy, and vitamin B12 deficiency or increased homocysteine and methylmalonic acid."

Meanwhile, what should be done for patients with Parkinson's disease?

The investigators call for clinical assessment of neuropathy in patients treated with levodopa on a long-term basis. They also recommend a classic workup including vitamin B12, homocysteine, methylmalonic acid levels in patients with confirmed neuropathy.

Finally, they suggest possible systematic B12 or folate supplementation.

This study was funded by the Leicestershire Neurological Trust, a Registered Charitable Organization in the United Kingdom. Dr. Yusuf Rajabally received an educational grant, unrelated to this study, from UCB. Jean Martey, BSc, received a grant from GlaxoSmithKline and speaker honoraria from Abbott and UCB.

Neurology. 2011;77:1947-1950. Abstract

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