Parkinson’s disease (PD) is a progressive movement disorder resulting from the loss of dopamine-producing cells deep within the brain, leading to characteristic symptoms like tremor, rigidity, and slowed movement. Peripheral neuropathy (PN) is a separate condition involving damage to the nerves outside the brain and spinal cord, which typically causes sensations like numbness, tingling, or pain in the hands and feet. Accumulating evidence reveals a significant connection between PD and PN. Recognizing and addressing neuropathy in individuals with PD can substantially improve their quality of life.
Defining Peripheral Neuropathy in Parkinson’s Disease
Peripheral neuropathy is much more prevalent in the Parkinson’s disease population than in the general public. Research suggests the rate of neuropathy in people with PD may be as high as 40% to 55%, compared to an estimated 8% to 9% in similarly aged individuals without the condition.
The peripheral nervous system includes all the motor and sensory nerves that extend from the central nervous system to the rest of the body. When these nerves are damaged, it is termed peripheral neuropathy, and the symptoms depend on the type of nerve fiber affected. In the context of PD, a specific type of nerve damage known as Small Fiber Neuropathy (SFN) appears to be the most common presentation.
SFN affects the small, unmyelinated nerve fibers responsible for transmitting pain, temperature, and autonomic information. Patients with PD who have SFN often experience burning or pins-and-needles sensations in their feet, which can contribute to problems with balance and gait. This sensory disturbance can easily be misattributed to other PD-related motor symptoms. Neuropathy significantly increases disability, leading to a higher risk of falls and reduced functional mobility.
Pathological Basis of the Neuropathy Link
One theory for the connection is that peripheral neuropathy is an inherent, non-motor feature of Parkinson’s disease progression itself, rather than a side effect of medication or other factors. This hypothesis focuses on the hallmark pathology of PD: the abnormal accumulation of a protein called alpha-synuclein. These misfolded protein aggregates form structures known as Lewy bodies, which cause damage to nerve cells.
While Lewy bodies are most recognized for destroying dopamine-producing neurons in the brain, they are not confined to the central nervous system. Alpha-synuclein aggregates have also been detected in the peripheral nerves, including those found in the skin and the gut, long before motor symptoms appear.
The presence of alpha-synuclein deposits in peripheral nerve fibers is strongly correlated with small-fiber neuropathy, indicating a direct role in nerve damage. Researchers have found these pathological deposits in skin biopsies from individuals with PD, sometimes even in the absence of other known causes for neuropathy. The pathology in peripheral nerves may also explain some of the non-motor symptoms of PD, such as constipation and orthostatic hypotension, which are mediated by the autonomic nervous system.
Secondary Causes and Clinical Identification
Beyond the intrinsic pathology of Parkinson’s disease, several extrinsic factors common in PD patients can contribute to or worsen peripheral neuropathy. The most significant of these involves the long-term use of levodopa, the most effective medication for managing PD motor symptoms. Levodopa, which is converted to dopamine in the brain, has been shown to interfere with the metabolism of certain B vitamins, particularly Vitamin B6 (pyridoxine) and Vitamin B12 (cobalamin).
These B vitamins, along with folate, are essential cofactors for healthy nerve function, and a deficiency can directly cause peripheral neuropathy. Levodopa’s metabolism can lead to a depletion of these vitamins, or an increase in homocysteine levels, a byproduct linked to nerve and vascular damage. This risk may be particularly pronounced with high doses of oral levodopa or with continuous infusion formulations, such as Levodopa/Carbidopa Intestinal Gel (LCIG).
Clinical identification of neuropathy begins with a careful review of symptoms, as the signs can overlap with PD-related issues. Patients should report any new or worsening sensations such as burning, tingling, numbness, or shooting pain, especially in the feet and lower legs. A neurologist will then typically perform a physical examination to check for decreased sensation to pinprick or vibration, which are signs of nerve damage.
Diagnostic testing often includes blood work to specifically check for deficiencies in Vitamin B12, B6, and folate, as well as checking homocysteine levels. If a vitamin deficiency is not found, the neurologist may order a nerve conduction study (NCS) and electromyography (EMG) to assess the function of the larger nerve fibers. If those tests are normal but symptoms remain, a skin biopsy may be considered to confirm small fiber neuropathy, which is often missed by standard nerve conduction tests.
Managing Neuropathy Alongside Parkinson’s Treatment
Effective management of neuropathy requires a dual approach that addresses both the underlying causes and the symptoms. Addressing secondary causes, particularly potential vitamin deficiencies related to levodopa therapy, is necessary. Regular monitoring of Vitamin B12 and B6 levels through blood tests is recommended for individuals on long-term or high-dose levodopa.
If a deficiency is detected, supplementation with the appropriate B vitamin is often initiated, which can stabilize or improve neuropathy symptoms and prevent further nerve damage. In some cases, a movement disorder specialist may need to consider adjusting the levodopa dosage or switching to an alternative formulation to mitigate vitamin depletion. Collaboration between the PD specialist and a neurologist is important to ensure that adjustments to PD medication do not compromise motor control.
For symptomatic relief of nerve pain, several medications can be used, including certain anti-seizure drugs like gabapentin or pregabalin, or specific types of anti-depressants such as duloxetine. Topical treatments like lidocaine cream or capsaicin patches can also provide localized relief for burning or tingling sensations. The management strategy is always individualized, focusing on minimizing discomfort while maintaining optimal control over the motor symptoms of Parkinson’s disease.