Peripheral neuropathy is nerve damage that can cause tingling toes, numb feet, or trouble with balance. It can have many possible causes. Monoclonal gammopathy of undetermined significance (MGUS) and peripheral neuropathy can occur together. But having both conditions doesn’t automatically mean MGUS caused the nerve damage.

MGUS is a condition that can sometimes progress to myeloma or other blood cell cancers. MGUS itself usually doesn’t cause symptoms. But in some people, the abnormal protein made by the condition may affect the nerves.

This article will explain how MGUS and peripheral neuropathy may be connected, what symptoms can occur, how doctors look for the cause, and how neuropathy may be treated and managed.

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Symptoms of MGUS Neuropathy

Peripheral neuropathy symptoms depend on which nerves are damaged. Symptoms often start in the feet or hands and may gradually spread farther up the legs or arms.

MGUS neuropathy symptoms may include:

• Numbness — You may have less feeling in your feet, toes, hands, or fingers.
• Tingling — Some people describe pins and needles, prickling, or buzzing sensations.
• Pain — Nerve pain may feel burning, stabbing, throbbing, or electric.
• Changes in sensation — Touch, temperature, or vibration may feel different from usual.
• Balance problems — Reduced sensation in the feet can contribute to unsteadiness or falls.
• Muscle weakness — Damage to nerves that control movement can make certain muscles weaker.

Symptoms can range from mild changes in sensation to problems that interfere with walking or everyday activities, although severe symptoms are rare.

“My first symptom of MGUS was numbness in my toes. My neuropathy spread from my feet to the top of my hips,” one MyMyelomaTeam member said, describing a very rare reaction. “I was so weak I ended up in a wheelchair. I walked with a walker or a cane for several years.”

Tell your healthcare team about new or worsening numbness, weakness, pain, or balance problems, particularly if the symptoms are spreading or changing over time.

How Doctors Diagnose MGUS Neuropathy

Finding the cause of neuropathy can take time, particularly when MGUS, myeloma, myeloma treatments, and other health conditions could all play a role.

There isn’t one test that can prove MGUS is responsible for peripheral neuropathy. Healthcare providers may consider the pattern of nerve symptoms and the type of monoclonal protein. They may also do neurologic testing and look at other possible causes.

Testing for Other Causes

There are other blood disorders that can affect nerves. Depending on your symptoms and test results, the evaluation may look for conditions such as:

• AL amyloidosis
• POEMS syndrome
• Waldenström macroglobulinemia
• Active myeloma

Distinguishing among these conditions is an important part of evaluating neuropathy in someone with a monoclonal protein. When the connection between MGUS and neuropathy isn’t clear, a hematologist and neurologist may work together.

Keep your hematology and neurology teams updated about when symptoms began and how they’re changing. This can help them determine which tests and treatments make the most sense for you.

Blood Tests

Blood testing is commonly part of the diagnostic evaluation for peripheral neuropathy. It can provide more information about MGUS and other possible causes of neuropathy.

Blood tests may also check for other conditions that can contribute to neuropathy, such as diabetes or low vitamin levels, especially vitamin B12 deficiency.

If your doctor thinks you may have an IgM-related neuropathy, your care team may test for anti-MAG antibodies. Doctors interpret anti-MAG antibody results together with a person’s symptoms and nerve-testing results rather than relying on the antibody test alone.

Neurologic Testing

Depending on your symptoms, neurologic testing may include:

• Neurologic exam — Checks reflexes, muscle strength, coordination, balance, and the ability to feel different sensations.
• Nerve conduction studies — Measure how fast and how strongly electrical signals travel through peripheral nerves.
• Electromyography — Uses a thin needle electrode in a muscle to measure its electrical activity.

These tests may also show whether the main problem involves the nerve fibers themselves or their protective covering, called myelin. IgM-related neuropathies such as anti-MAG neuropathy often produce a pattern of myelin damage.

MGUS Neuropathy Treatment and Management

Most people with MGUS don’t need treatment for MGUS itself. Instead, doctors usually monitor the condition over time with follow-up visits and laboratory testing.

When MGUS Neuropathy May Be Treated

For IgM-associated neuropathy, treatment may be considered when symptoms are progressing or interfering with everyday function. The goal may be to slow or prevent additional nerve damage and, when possible, improve function.

Neurologic improvement may take months or even years after treatment because nerves recover slowly.

Treatment depends on the type of monoclonal protein and the specific neuropathy. Some IgM-related neuropathies may be treated with therapies that target the abnormal B cells producing IgM.

Rituximab is one treatment that has been studied for anti-MAG neuropathy, but clinical trials have produced mixed results.

If doctors find that another condition is causing your neuropathy, treatment is aimed at that condition instead.

Symptom Management

Even when the underlying nerve damage can’t be reversed, treatment may help you manage symptoms and stay active. Medicines used for nerve pain and physical therapy may help with movement, weakness, and balance problems.

Reduced sensation can make it harder to notice an injury, particularly on the feet. Make sure to protect areas that have reduced sensation and take steps to reduce the risk of accidents.

Practical steps that may help you manage peripheral neuropathy and stay safe include:

• Check numb areas regularly — Look for cuts, blisters, burns, sores, or other injuries that you may not have felt.
• Protect your feet — Wear comfortable, well-fitting shoes and take care of your skin and toenails.
• Protect your hands — Wear gloves when doing tasks that could cause cuts or burns, and take extra care with knives, scissors, and other sharp objects.
• Be careful with extreme temperatures — Reduced sensation can make it harder to tell when something is hot enough to burn you or cold enough to damage your skin.
• Reduce your risk of falls — Improve lighting, remove loose rugs and clutter, install handrails where needed, and use nonslip mats in the bathroom.
• Use mobility support when needed — A cane, walker, brace, or other aid may make it easier and safer to get around.
• Stay active when it’s safe — Exercise may help maintain muscle strength and balance. If you have myeloma, ask your healthcare team which activities are safe for you, especially if you have bone problems, pain, or significant neuropathy.
• Ask about physical or occupational therapy — A physical therapist can help with strength, balance, and walking, while an occupational therapist can suggest safer ways to handle everyday activities.
• Manage other health conditions — Keeping conditions such as diabetes under control may help prevent further nerve damage.
• Report changes promptly — Tell your healthcare team if numbness, weakness, pain, balance problems, or trouble using your hands or feet is getting worse.