Today I will address the potential link between Parkinson’s disease and a common neurologic condition called peripheral neuropathy. This topic was submitted via the Suggest a Topic portal. I am grateful for your suggestions so please continue to let us know what you’d like to learn more about!

In order to understand what peripheral neuropathy is and what symptoms it can cause, we will briefly review the components of the nervous system.

Central nervous system vs. peripheral nervous system

Neurologic control of the body is very broadly divided into two systems – the central nervous system which consists of the brain and the spinal cord – and the peripheral nervous system which consists of the network of nerves that are outside the brain and spinal cord, and innervate the limbs and the organs of the body.

The peripheral nervous system is composed of three types of nerves: autonomic nerves, sensory nerves and motor nerves. Different types of nerves have varying diameters and are generally divided into those that are small and those that are large.

• Autonomic nerves exert control over functions that are not under conscious direction such as respiration, heart function, blood pressure, digestion, urination, sexual function, pupillary response, and much more. This information is conveyed on small fibers.
• Motor nerves carry information on limb movement from the brain and spinal cord to the limbs. This information is conveyed on large fibers.
• Sensory nerves carry information on the various sensations felt by the limb to the brain and spinal cord. There are two main types of sensory nerves:
  • Pain and temperature fibers which are small fibers
  • Vibration and joint position sense fibers which are large fibers

The peripheral nervous system and Parkinson’s disease

It is well-established that the autonomic nervous system can be significantly affected in PD causing symptoms such as constipation, urinary dysfunction and orthostatic hypotension. The autonomic nerves that bring signals to the gut for example, can be directly affected by Lewy body-like accumulations and neurodegeneration. (This is not the only way that automatic functions of the body are affected in PD however. There can also be Lewy bodies and neurodegeneration in the parts of the brain that control these functions.)

What remains unclear is if motor and sensory nerves are also affected in PD.

What is peripheral neuropathy?

Peripheral neuropathy (PN) is a condition in which there is damage to peripheral nerves. Symptoms depend on which type of nerves are affected and can result in:

• Weakness
• Imbalance with walking
• Numbness
• Pain or paresthesias (sensations such as burning or tingling) in the limbs

The legs are more commonly affected than the arms because the nerves to the legs are longer than the arms and therefore more prone to damage.

Symptoms of peripheral neuropathy

The symptoms of PN can be non-specific, and a person therefore may not be able to distinguish on their own whether his/her symptoms are due to PN or another condition. PN, however, often results in specific findings on a neurologic exam, such as decreased sensation to pin prick or vibration or the lack of ability to discern which way a toe is being pointed without looking. Other tests such as Electromyogram (EMG) and Nerve conduction studies (NCS) may be necessary to confirm the diagnosis. Small fiber neuropathy which typically causes pain, burning, tingling and/or numbness in the feet, may have normal EMG and NCS and a skin biopsy may be necessary to confirm the diagnosis. With the appropriate examination and supportive tests however, a neurologist should be able to distinguish the symptoms of peripheral neuropathy from other conditions, including PD, that may cause similar symptoms.

There are many known causes of PN including diabetes, vitamin deficiencies, certain infections, and autoimmune diseases. Many of these causes can be treated, so it is important to know if you do have PN and what the cause is. There are those people; however, who have the signs and symptoms of PN, but no known cause can be identified.

Peripheral neuropathy and Parkinson’s disease

A number of studies have tried to determine if PN is more common among people with PD as opposed to people without PD. PN is a relatively common condition in the general population, which makes it difficult to ascertain whether or not it is even more common among people with PD.

The available studies have varying results and are difficult to compare with each other as they:

• Include different types of populations of people with PD (e.g. some studies excluded people with PD who also had diabetes, a very common cause of PN; other studies included those with diabetes)
• Assess peripheral neuropathy differently (different studies based the prevalence of PN among people with PD in different ways – symptom questionnaires or checklists, clinical exam or EMG/NCS)
• Assess for causes of peripheral neuropathy differently (some studies performed comprehensive testing for many causes of PN; others only checked for a few of the most common causes of PN)

A recent review looked at all the available data and determined that large fiber neuropathy was present in 16% of patients with PD, about double the prevalence of this condition in the general population. Skin biopsy-proven small fiber neuropathy (which includes autonomic neuropathy) was present in over 50% of people with PD, although this result was based on a small sample of patients.

The use of levodopa and peripheral neuropathy

There are reports in the literature that levodopa use may increase the risk of peripheral neuropathy, although other studies suggest that this is not the case. There are studies that demonstrate for example, that cumulative Levodopa exposure correlates to prevalence of PN in people with PD. Other studies however, demonstrate no difference in the prevalence of PN whether the person was treated with Levodopa or not, suggesting that Levodopa treatment does not play a role in development of PN.

Another area of research that emerges from the literature is the potential role of Vitamin B6 and Vitamin B12 deficiency in the development of PN in those with PD. Some studies suggest that Vitamin B6 and Vitamin B12 deficiency (or both) are more common causes of PN among those with PD than those with PN who do not have PD.

There is also research that suggests that levodopa treatment may contribute to PN through impairment of Vitamin B6 and Vitamin B12 metabolism, leading to deficiency. Taking COMT inhibitors such as Entacapone may protect against this complication.

Regardless, if PN is diagnosed in anyone, whether they have PD or not, and whether they take Levodopa or not, Vitamin B6, Vitamin B12 and various other markers of their metabolism (including homocysteine levels and methylmalonic acid) should be tested. If levels are low or even low-normal, a person should take supplementation, which may help with the symptoms of PN. Other causes of PN, many of which can be checked with various blood tests, should be investigated as well.

Levodopa-carbidopa intestinal gel (LCIG) and peripheral neuropathy

There have been a number of reports in the literature that use of Levodopa-carbidopa intestinal gel (LCIG) may uncommonly cause a more sub-acute and more severe form of PN than seen in the general PD population, potentially due to vitamin deficiency. Other reports however, do not support this claim. Based on the available studies, it would be particularly prudent that those on LCIG treatment have their Vitamin B6 and B12 levels checked, and receive supplementation if necessary.

More research needs to be done to fully understand the relationship between PN and PD. What we do know is that if you are experiencing new or more intense neurologic symptoms such as weakness, numbness, or burning/tingling sensation in your limbs, talk with your neurologist. These symptoms may not be directly related to PD and may be due to PN. If you do have PN, then your neurologist can check for various causes of PN – many of which can be treated.

Tips and takeaways

• Peripheral neuropathy is a condition in which there is damage to the peripheral nervous system, the system of nerve fibers that innervates the organs and limbs.
• Peripheral neuropathy may cause weakness, imbalance with walking, numbness, pain or paresthesias (abnormal sensation such as tingling or burning), usually in the feet (but sometimes in the hands as well).
• There is a higher rate of peripheral neuropathy among people with PD as compared to those without PD, although the nature of this relationship is unclear.
• Levodopa treatment may contribute to lower Vitamin B6 and Vitamin B12 levels which may contribute to peripheral neuropathy.
• Anyone with PN should consult their doctor to try to determine the cause of the PN.
• Speak with your doctor about any concerns you may have about potential PN symptoms.