Episode 117: Neuropathy: A Non-motor Symptom of Parkinson’s Disease

Dan Keller 0:02 Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller, at the Parkinson's Foundation. We want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.

According to the Cleveland Clinic, it's estimated that up to 30% of Americans may experience a neuropathy during their lives. These feelings of numbness, tingling, pain, or other abnormal sensations often result from damage or dysfunction of sensory nerves in the periphery. These are the nerves that bring sensations to the brain and spinal cord, which form the central nervous system.

In this episode, Nurse Practitioner Ellen Walter of the Cleveland Clinic gives a brief overview of the various kinds of neuropathies, and then focuses on peripheral neuropathies. She also goes into some detail about the importance of identifying the specific causes of neuropathies, since some can be treated.

Ellen Walter, CNP 1:36 I think this is actually a tough topic to cover, and by tough I mean it's not necessarily straightforward. However, I think that's precisely why people are often interested in hearing about it and learning a little bit about neuropathy. Basically, short and simple, neuropathy is damage to the nerves.

Today, as we talk, I'm mostly going to speak about peripheral neuropathy—meaning damage to the peripheral nerves. This is the part of our nervous system that carries messages to and from the brain and the spinal cord. There are different types of neuropathy or nerve damage, but again, we'll mostly focus on the peripheral system. For example, carpal tunnel syndrome is a type of what is called a focal neuropathy. Another example is an autonomic neuropathy, which involves damage to the nerves that control the automatic functions in our body that we just don't consciously think about, such as heart rate, blood pressure, and digestion. Because it can get a bit complicated, staying a little more focused on peripheral neuropathy will be our main goal today.

Dan Keller 2:33 And those peripheral neuropathies are mostly sensory, or are there motor problems also?

Ellen Walter, CNP 2:40 There can be both. Though I only mentioned a few types of neuropathy earlier, there are so many different classifications, so it really depends on exactly what type of nerve fibers are affected. To keep it simple by lumping the primary symptoms together: someone might feel pain, numbness, or tingling that typically starts in their feet and works its way up. Someone may also become overly sensitive to touch, develop muscle weakness, or experience a loss of coordination. Some individuals might even feel like they have socks or gloves on when they're not actually wearing any.

Dan Keller 3:14 Are people with Parkinson's more likely to get neuropathy? And among this specific population, how common is it?

Ellen Walter, CNP 3:23 The answer to this question historically seems to be a bit controversial. I know that when I first started learning about it and people would ask me that question, I would ask different movement disorder specialists and frequently get conflicting answers. However, when you review the medical literature, there does seem to be a significantly higher incidence of neuropathy in people with Parkinson's as compared to those without.

Approximately 30% of people who have Parkinson's will develop a neuropathy. While it's true that as people age, they naturally have a greater risk for developing neuropathy—and certainly as they develop comorbidities like diabetes—aging alone really does not explain the statistical difference in why people with Parkinson's are uniquely prone to getting it.

Dan Keller 4:04 Besides it being uncomfortable or painful, can it actually be dangerous?

Ellen Walter, CNP 4:10 It can certainly be dangerous if a serious underlying cause is missed. Sometimes, peripheral neuropathy can be a paraneoplastic sign—meaning it can be an early indicator of an underlying cancer. Alternatively, it could be a sign that a patient has diabetes that is not being well managed.

If someone is experiencing symptoms like unexplained bone pain, weakness, frequent infections, or other new symptoms occurring at the same time they are developing peripheral neuropathy, those are major red flags that something else is going on. Regardless of what the root cause is, early diagnosis and treatment are critical to help control the symptoms and hopefully prevent further nerve damage.

A type of neurologist called a neuromuscular specialist can be consulted to verify that a patient truly has a neuropathy, and then help determine its specific severity and cause. Especially if it happens to be related to an underlying malignancy, you want to ensure that gets identified and taken care of right away.

Dan Keller 5:15 If someone has numbness from a peripheral neuropathy affecting their feet, I would imagine they don't sense the ground very well. Can this lead to falls?

Ellen Walter, CNP 5:27 Absolutely, and that is a major clinical concern. People who have Parkinson's disease who have a neuropathy on top of it are at a significantly higher risk for sustaining falls compared to someone who doesn't have that sensory loss. I think it can also become a safety issue with driving if a patient cannot accurately feel the gas and brake pedals. There are definitely several distinct dangers that can result directly from peripheral neuropathy.

Dan Keller 6:00 What exactly puts a person with Parkinson's more at risk for neuropathy? You have their underlying disease, you have drugs, and you have aging. How do these factors all intersect?

Ellen Walter, CNP 6:13 There is a distinct biochemical link to the standard Parkinson's medication, levodopa. Most people with Parkinson's end up taking levodopa at some point throughout their journey; it remains the gold standard of treatment. Approximately one-third of those who take oral levodopa develop a peripheral neuropathy.

Even more striking is that among those who use Duopa—which is the carbidopa/levodopa intestinal gel formulation delivered via a pump—over 40% will develop a neuropathy. That particular presentation tends to have a more acute, rapid onset, whereas those who are taking the standard pill form of levodopa experience a more slowly progressive course.

Now, the obvious question is: does this mean we should stop using these medications because they are linked with peripheral neuropathy? Of course not. Levodopa is the gold standard for managing motor symptoms. However, it highlights why routine monitoring of specific lab values associated with neuropathy, such as a vitamin B12 deficiency, is so important.

If you look at the non-medication side, there have also been fascinating studies looking at newly diagnosed Parkinson's patients who have not yet started any medication. When compared to control groups without Parkinson's, these drug-naive patients also exhibit a higher incidence of neuropathy. One study published toward the end of 2020 evaluated 105 individuals with newly diagnosed Parkinson's, and almost a quarter of them were found to have an objective neuropathy before ever starting a single Parkinson's drug. This tells us that it isn't exclusively the medication driving the nerve damage. It is highly complex and we don't know the exact mechanism, but we do know that this drug-naive group had baseline metabolic abnormalities in their blood work. Multiple studies have confirmed similar metabolic shifts alongside deficiencies in key B vitamins, specifically B12, B6, and B9, which is folic acid.

Dan Keller 8:01 Some people experience a transient tingling in their feet at night that eventually goes away. Would that be clinically considered a neuropathy?

Ellen Walter, CNP 8:11 It's hard to know for sure without an evaluation. There is a strong possibility that it isn't a neuropathy at all, but rather restless legs syndrome, or RLS. Many people with Parkinson's suffer from restless legs syndrome, which is characterized by an uncomfortable, deep sensation in the legs that triggers an irresistible urge to move them. Patients will kick their legs or get up and pace around to make the sensation go away.

Because this sensation is described differently by every person—some call it a bug-crawling feeling, others describe it as a tingling or pulling—it can easily mimic what a patient with true neuropathy feels. To complicate matters further, neuropathy pain also characteristically worsens at night, which is exactly when restless legs syndrome peaks. And to make it even more challenging for clinicians, a patient can absolutely have both conditions simultaneously.

Sometimes, patients use the wrong terminology to describe what they are feeling, which places the responsibility on us as healthcare providers to take a meticulous clinical history. I'll be honest, I have been fooled by patients using standard terms incorrectly. They will come in and say, "My restless legs syndrome has really been acting up," so you work on adjusting their treatment for RLS, only to discover later on that it wasn't restless legs syndrome at all. They just thought that's what it was because it sounded like what a friend had, when in reality their symptoms were driven by a neuropathy. We must ensure we are taking an exceptionally thorough history and referring patients for diagnostic testing if there is any clinical suspicion of a neuropathy.

Dan Keller 9:46 How do people know when it's time to see a healthcare provider? Are there specific red flags or symptoms to be particularly concerned about?

Ellen Walter, CNP 9:54 Patients should absolutely see their provider if they notice any sensory changes that could indicate a neuropathy, such as persistent numbness, tingling, or burning pain. I would actually caution people not to adopt the term "neuropathy" in their descriptions until they have been formally diagnosed; it is much more helpful to describe the raw, exact physical sensations they are feeling rather than offering a self-diagnosis.

If we suspect a neuropathy is developing, whether that is identified by their primary care provider or their movement disorder specialist, we can refer them to a neuromuscular specialist for a formal workup. As for red flags indicating a more urgent underlying issue, those include the things I mentioned earlier: unexplained bone pain, the development of acute muscle weakness—which might mean a nerve is severely compressed or impinged somewhere—frequent infections, or any sudden loss of function, like suddenly being unable to use a hand or experiencing weakness in a leg.

Dan Keller 11:01 How extensive is the diagnostic workup when a patient describes these symptoms? Is there a standard algorithm or decision tree you follow?

Ellen Walter, CNP 11:10 It really depends on the clinical situation. If someone presents with localized numbness, tingling, and pain confined to an arm or a leg, a lot of times it is due to a temporary nerve compression or entrapment that may resolve on its own, so conservative monitoring might be appropriate initially. However, if they present with objective muscle weakness, I would never wait and monitor it; I would immediately refer them to a specialist. Depending on where we suspect the issue originates, that might be a neuromuscular specialist or a spine specialist if we suspect radiculopathy coming from the neck or back.

When a patient continues to experience symptoms and sees a neuromuscular specialist, they will typically undergo an electromyogram (EMG) and a nerve conduction study. These diagnostic tools evaluate exactly how electrical signals are traveling through the nerves and can definitively answer whether it is a peripheral neuropathy, a pinched nerve in the neck, or an impingement in the lower back. It can also help identify patterns typical of metabolic causes like diabetes.

Once a neuropathy is confirmed, comprehensive blood work is ordered to screen for underlying causes. This includes checking for the specific B vitamin deficiencies we discussed, evaluating long-term blood sugar control via an HbA1c, and screening for systemic causes like rheumatoid arthritis, kidney disease, or a plethora of other contributing conditions.

My primary philosophy when treating individuals with Parkinson's is that just because you have Parkinson's doesn't mean everything is caused by Parkinson's. If a patient comes in with a neuropathy, I refuse to simply say, "Oh, you're taking levodopa, so it must be the levodopa." We shouldn't blame Parkinson's until we have systematically ruled out everything else, and a neuromuscular specialist will do exactly that—look for every other potential contributing factor.

Dan Keller 13:32 It sounds like managing this condition depends entirely on identifying the root cause—whether it is metabolic, a vitamin deficiency, an impingement syndrome, or related to medication. You really have to establish the cause before you can determine the treatment.

Ellen Walter, CNP 13:48 Absolutely. That is the fundamental first step. Any underlying cause must be identified and directly managed. If a vitamin deficiency is found, it must be aggressively treated. For a patient with diabetes or even pre-diabetes, strict blood sugar control is vital to prevent the neuropathy from worsening, even if diabetes wasn't the initial primary cause; you certainly don't want to compound the damage.

Smoking cessation is crucial because smoking constricts the small blood vessels that deliver oxygen and essential nutrients to the nerves to keep them healthy. Regular exercise is highly beneficial for the exact opposite reason—it increases systemic circulation and enhances nutrient delivery to the peripheral tissues.

For many patients, a significant portion of peripheral neuropathy management is aimed at symptomatic pain control. This often involves oral medications that help quiet overactive pain signals, such as gabapentin, Lyrica, or Cymbalta—names that are likely familiar to many listeners. Topical compounding creams, such as lidocaine patches or capsaicin cream, can also be highly effective for localized pain.

If the neuropathy is driven by physical nerve entrapment, mechanical interventions are required. This might mean surgery for carpal tunnel syndrome or an ulnar neuropathy. For certain autonomic neuropathies or severe nerve damage affecting bladder function, advanced therapies like a peripheral nerve stimulator might be utilized. The treatment roadmap is entirely dictated by what is causing the damage.

Dan Keller 15:32 If I'm understanding you correctly, it sounds like the lifestyle modifications people can make to manage existing neuropathy are the exact same preventative steps people should take to avoid developing it in the first place—such as stopping smoking and managing weight.

Ellen Walter, CNP 15:47 Exactly. Minimizing exposure to known neurotoxins and limiting alcohol intake are key, as chronic alcoholism is a direct cause of toxic neuropathy. Controlling blood sugar and maintaining a regular exercise routine are excellent preventative measures.

Another incredibly painful type of nerve damage occurs as a complication of shingles, known as postherpetic neuralgia. Getting vaccinated against shingles is a highly effective preventative step.

To prevent focal neuropathies like carpal tunnel syndrome, it helps to avoid repetitive ergonomic movements when possible. Of course, that isn't always fully achievable—if someone's job requires them to type for ten hours a day, they can't easily avoid it, but they can integrate ergonomic adjustments, use voice dictation software to break up the repetitive strain, or wear structural wrist splints at night. Sleeping with a supportive brace helps keep the carpal tunnel open and prevents micro-damage while you sleep.

Eating a nutrient-dense diet is important to prevent vitamin deficiencies. However, vitamin B12 can be tricky; many people actually ingest an adequate amount in their diet, but their gastrointestinal tract fails to absorb it properly due to aging or medication interactions. In those cases, oral supplements may not suffice, and patients might require regular B12 injections to bypass the gut and ensure proper absorption. Ultimately, it comes down to open communication with your healthcare team to ensure you are routinely monitored for these deficiencies, especially if you take medications known to cause them.

Dan Keller 17:15 Are there any final takeaways or key points you would like to emphasize?

Ellen Walter, CNP 17:21 The single most important takeaway is simply: do not blame every new symptom on Parkinson's. Never hesitate to ask your provider to look into a new symptom, whether that is your primary care provider or your movement disorder specialist.

In my own clinical practice, I try to be very diligent about screening for B12 deficiencies and other metabolic markers. However, clinical reality means that sometimes a provider walks into an office visit with a specific agenda, but the patient arrives with entirely different, pressing concerns. The visit naturally pivots in a completely different direction, and perhaps a routine lab check gets deferred. Patients should never feel afraid to proactively ask for these labs.

Monitoring B12 is incredibly important for the Parkinson's population due to the biochemical impact of levodopa. It's also worth noting that there are other incredibly common medications that can contribute to a B12 deficiency. A prime example is metformin, the first-line medication for type 2 diabetes. Because many of our Parkinson's patients also manage diabetes, they are often taking both levodopa and metformin simultaneously. That means they have two distinct pharmaceutical factors working against them regarding their risk for a profound B12 deficiency.

Dan Keller 18:32 Wonderful. This has been an incredible amount of practical, highly valuable information, and I know our listeners will deeply appreciate it. Thank you, Ellen.

To read more about today's topic, you can search for "neuropathy" directly on our website at parkinson.org. There you will find dedicated articles discussing neuropathy in people with Parkinson's, alongside related resources on fatigue and gastrointestinal management.

As Ellen emphasized, not all neuropathies experienced by individuals with PD are a direct consequence of the disease itself. The foundation's articles outline a wide array of alternative causes, ranging from medication side effects to normal aging, and it is highly recommended to review these resources to cross-reference your current medications. While certain medications are highly effective at alleviating neuropathic pain, it is important to remember they manage the sensory symptoms rather than halting the underlying nerve damage itself.

It is also worth noting for individuals who have undergone deep brain stimulation (DBS) that an improper setting on the neurostimulator can occasionally induce a persistent tingling sensation that can easily be mistaken for a new neuropathy; often, a precise programming adjustment by your movement disorder specialist can completely eliminate this side effect.

If you search parkinson.org for "Ellen Walter," you can access an even more comprehensive, deep-dive presentation on this topic via the archived expert briefing she co-presented with clinical pharmacist Steven Swank. You can also access our specialized Pain in Parkinson's fact sheet by visiting parkinson.org/library.

If you need personalized guidance or have further questions, our toll-free Helpline is always available. Our compassionate information specialists provide expert answers and resources in both English and Spanish, and can be reached directly at 1-800-4PD-INFO. To stay updated on future educational webinars, foundation events, and community resources, you can easily join our email list at the bottom of our homepage.

If you would like to leave feedback regarding this podcast or suggest future topics, please visit parkinson.org/feedback. If you enjoyed this episode, please subscribe, rate, and review the series on Apple Podcasts or your preferred podcast platform.

At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we will continue bringing you a new episode in this podcast series every two weeks. Until next time, for additional information and resources, please visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, which is 1-800-473-4636. Thank you for listening.

Ellen Walter is an Acute Care Nurse Practitioner at the Cleveland Clinic in the Center for Neurological Restoration. She graduated Summa Cum Laude from Kent State University with a BSN and received her MSN from Case Western Reserve University Frances Payne Bolton School of Nursing.

She has worked for the last 23 years in neuroscience nursing in neurology and neurosurgery practices including caring for individuals who have had deep brain stimulation surgery for the treatment of their movement disorder. She works with a team of specialists in the Movement Disorders section of the Center for Neurological Restoration at the Cleveland Clinic.

Her position there, in addition to caring for those who have had DBS, involves a comprehensive approach caring for persons with Parkinson’s disease, dystonia, essential tremor and other movement disorders.

She has a special interest in exercise and community outreach for Parkinson’s disease as well as creating programs for the care partners.