Peripheral Neuropathy Can Be Evident, Levodopa Link Possible

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by Steve Bryson, PhD |

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Damage to certain nerve fibers in the extremities, known as peripheral neuropathy, was evident in some people with Parkinson’s disease, including those at early disease stages, a study reported.

Findings in this work, which used a sensitive electrophysiological device to examine nerves, also suggested that peripheral neuropathy was related to both Parkinson’s itself as well as to long-term use of levodopa, a standard disease treatment.

Likewise, tests revealed that high blood levels of homocysteine were independent risk factor for peripheral neuropathy in these patients, and may associate with levodopa treatment over time. Homocysteine is a type of amino acid, the building blocks of proteins.

The study, “Fiber selectivity of peripheral neuropathy in patients with Parkinson’s disease,” was published in the journal Acta Neurologica Scandinavica.

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Peripheral neuropathy, or damage to the nerves outside of the brain and spinal cord, often leads to weakness, numbness, and pain, usually in the hands and feet, resulting in problems with balance and mobility.

While some studies suggest peripheral neuropathy is a feature of Parkinson’s, others indicate that the use of levodopa could aggravate neuropathy.

Most of this research used traditional electrophysiological testing methods that can only measure damage to large nerve fibers responsible for detecting vibrations and sensing movement, but not damage to small nerve fibers, which relay information about pain and temperature.

The Neurometer is a more sensitive and non-invasive neurodiagnostic device that evaluates the function of more than 90% of sensory nerve fiber types, including large myelinated fibers, medium-size myelinated fibers, and small unmyelinated fibers. Of note, myelin is a fat-rich material that surrounds nerve fibers to increase the speed of electrical signals.

Researchers at the Second Affiliated Hospital of Soochow University in China applied the Neurometer to determine the functional status of each type of peripheral nerve fiber in a group of Parkinson’s patients. They investigated both peripheral neuropathy and the potential the impact of levodopa therapy.

The study included 20 people recently diagnosed with Parkinson’s on no disease treatment (median disease duration of two years; a treatment-naïve group), 20 patients with three or fewer years of levodopa exposure (median disease duration of three years), and 20 people treated with levodopa for more than three years (median disease duration of eight years). Their average ages ranged from about 61 to 68, but age differences between the groups were not statically significant.

All patients were evaluated using the unified Parkinson’s disease rating scale (UPDRS) and the Hoehn and Yahr (H&Y) scale, two standard assessment methods. Motor function, as assessed by the UPDRS part 3, and H&Y stage measuring disease progression, were both significantly worse in those with longer disease duration and treatment use.

A group of 22 age-matched healthy adults was assessed as a control group for comparison. Blood levels of vitamin B12, folic acid, and homocysteine were measured in all participants.

Nerve function was examined through Neurometer measures of the current perception threshold (CPT), in which three different impulse frequencies are used to determine a person’s ability to detect an electrical stimulus applied to both middle fingers. The 2000 Hz frequency stimulated large nerve fibers, the 250 Hz frequency activated medium-sized fibers, and the 5 Hz frequency stimulated small fibers. Higher CPT values indicate peripheral neuropathy.

Analysis showed that CPT values at 250 Hz and 5 Hz were significantly higher in those exposed to levodopa for more than three years than in the two other patient groups and the control group.

In comparison, CPT values at 5 Hz were lower for the treatment-naïve patients than for controls, indicating that “small-fiber lesions presenting as [increased sensitivity] is an intrinsic feature of PD [Parkinson’s disease] itself, which can occur in the early stage of PD,” the team wrote. No other significant differences in CPT in patients at 5 Hz were found.

No relationship was evident between UPDRS part 3 scores and CPT values across all frequencies. But higher CPT values at 5 Hz on the more affected side of the body correlated with a higher (worse) H&Y stage, “suggesting that peripheral nerve involvement mirrors [brain and spinal cord] degeneration,” the researchers noted.

Based on CPT measures, 16 patients were determined to have peripheral neuropathy, with a prevalence of 26.7%. Among them, 13 had used levodopa for more than three years, one for three years or less, and two were treatment naïve.

Higher homocysteine levels in the bloodstream alone were determined to be an independent risk factor for peripheral nerve damage in Parkinson’s. Further analysis showed higher homocysteine levels correlated positively with higher daily doses of levodopa and levodopa-equivalent medicines, and more prolonged levodopa exposure.

Our findings, the researchers wrote, suggest Parkinson’s patients “with more longer [levodopa] exposure duration had more serious peripheral nerve damage.”

Homocysteine is usually broken down by different vitamins, such as vitamin B12 or B6, and transformed into other substances that the body needs. Higher blood levels of homocysteine could indicate vitamin deficiency or other disorders.

“In summary, [peripheral neuropathy] in PD patients can occur in the early stage of PD and is fiber-selective, especially for [medium] and [small] nerve fibers,” the scientists wrote. “[Peripheral neuropathy] in PD patients is related to PD itself and long-term [levodopa] exposure.”

Elevated blood levels of homocysteine “is a risk factor” for peripheral neuropathy in these patients, the researchers added. “Therefore, we  speculate that for patients with PD appropriate supplementation of  ‘functional’ vitamin B12 and folic acid deficiency to decrease [homocysteine] may be helpful in preventing or reducing” peripheral neuropathy, especially for those on levodopa treatment.