Polyneuropathy

Polyneuropathy is a condition where multiple peripheral nerves throughout the body become damaged at the same time, causing problems with sensation, movement, or other body functions. It affects between 1% and 7% of people in the United States, with higher rates among those over 50 years of age.

Table of contents

• What is Polyneuropathy?
• Types of Polyneuropathy
• Causes and Risk Factors
• Symptoms
• Diagnosis
• Treatment
• Living with Polyneuropathy

What is Polyneuropathy?

Polyneuropathy is damage or disease affecting peripheral nerves (nerves located outside the brain and spinal cord) in roughly the same areas on both sides of the body^[1]. These peripheral nerves are responsible for sending information between the central nervous system (the brain and spinal cord) and the rest of your body^[2].

The word “polyneuropathy” comes from Greek: “poly” means “many,” “neuro” means “nerve,” and “pathy” means “sickness” or “affliction”^[3]. This differs from mononeuropathy, where just one nerve is affected^[1].

Polyneuropathy can affect different types of nerves. Sensory nerves receive sensations like temperature, pain, vibration, or touch from the skin. Motor nerves control muscle movement. Some forms affect both feeling and movement, called sensorimotor neuropathy. The condition may also affect autonomic nerves, which control involuntary functions such as digestion, bladder control, blood pressure, and heart rate^[2][4].

peripheral neuropathy

Types of Polyneuropathy

There are more than 100 types of peripheral neuropathy, and most of them are polyneuropathies^[1]. Each type is classified according to the type of nerve damage, the underlying cause, and the symptoms it produces.

Polyneuropathy can be divided into two major categories based on how quickly symptoms develop^[7]:

Acute polyneuropathy occurs when symptoms develop suddenly and severely. This type is common when you have an autoimmune reaction or infection causing nerve damage. The most common cause of acute symmetrical peripheral neuropathy is Guillain-Barré syndrome, a condition that can be fatal^[1][4]. Acute cases can often be treated successfully in a short time^[7].

Chronic polyneuropathy develops gradually, often over months or years^[4]. When symptoms last a long time and cannot be treated quickly, the cause is often an underlying condition such as diabetes or kidney failure. Most polyneuropathies are chronic and develop over many months^[1]. Some neuropathies can take years to develop^[1].

Polyneuropathies may also be classified by which part of the nerve cell is affected^[3]:

• Distal axonopathy: The most common response of neurons to metabolic or toxic disturbances. The most distal portions of nerve fibers usually degenerate first, and the damage advances slowly toward the nerve’s cell body.
• Myelinopathy: Due to loss of myelin (the protective sheath around nerves) or damage to Schwann cells. This slows down or completely blocks nerve signals.
• Neuronopathy: Results from issues in the peripheral nervous system neurons themselves.

Causes and Risk Factors

Several medical conditions and other factors can cause polyneuropathy. In Europe and North America, diabetes mellitus is the most common cause^[6]. A 2023 study of 25,710 people in China with type 2 diabetes found that 20% to 80% had diabetic peripheral neuropathy, with some variations according to geographical location^[1].

Alcohol misuse is another significant cause. Alcohol can damage nerve tissue, and alcohol use disorder is often associated with nutritional deficiencies that contribute to neuropathy. Alcohol-associated polyneuropathy has a prevalence of 22% to 66% among persons with chronic alcoholism^[1][6].

Other common causes include^[1][4][6]:

• Autoimmune conditions: The immune system attacks the body, causing damage to nerves. Conditions include Sjögren disease, celiac disease, Guillain-Barré syndrome, rheumatoid arthritis, lupus, and chronic inflammatory demyelinating polyneuropathy.
• Bacterial or viral infections: Certain infections, including Lyme disease, shingles, hepatitis B, hepatitis C, and HIV, can lead to neuropathy.
• Chemotherapy medications: Because of the increasing prevalence of cancer and use of new chemotherapeutic drugs, chemotherapy-induced neuropathies have gained clinical importance. Their prevalence is often stated to be 30% to 40%, with high variation depending on the drug and treatment regimen used.
• Vitamin deficiencies: Particularly vitamin B12 deficiency, which can also cause other spinal cord conditions. Other nutritional deficiencies such as thiamin deficiency are uncommon in the United States except among people with alcohol use disorder who are malnourished.
• Other medications: Including the antiseizure medication phenytoin, some antibiotics (such as chloramphenicol, nitrofurantoin, and sulfonamides), and some chemotherapy medications (such as vinblastine and vincristine).
• Toxic substances: Including heavy metals such as arsenic, lead, and mercury.
• Hereditary conditions: Such as Charcot-Marie-Tooth disease.
• Thyroid problems: An underactive thyroid gland (hypothyroidism).
• Kidney failure
• Cancer: Such as multiple myeloma, which damages nerves by directly invading or putting pressure on them.

Certain factors increase the risk of developing polyneuropathy^[1][5]:

• Advanced age
• A family history of neuropathy
• Malnourishment
• Excessive use of alcohol
• Preexisting medical conditions such as diabetes or thyroid dysfunction

Peripheral neuropathy is very common with some age-related diseases, which means the risk of developing peripheral neuropathy increases as you get older^[5]. About 2.4% of people globally have a form of peripheral neuropathy. Among people 45 and older, that percentage rises to between 5% and 7%^[5].

The cause of chronic polyneuropathy is often unknown^[4]. About half of all cases of polyneuropathy have no clear identifiable cause^[6].

Symptoms

Symptoms of polyneuropathy may appear suddenly (acute) or develop slowly over time (chronic), depending on the cause^[4]. The condition usually begins in the hands and feet and may progress to the arms and legs^[1]. Polyneuropathy tends to develop in the longest, most distal parts of the nerves, and is most often first felt in the feet. It begins with strange sensory symptoms or even pain in the balls of the feet that eventually spreads to the entire sole, wraps over the top of the foot, and eventually moves upward the legs^[23].

Common symptoms include^[2][4][7]:

• Gradual onset of numbness, prickling, or tingling in your feet or hands. These sensations can spread upward into your legs and arms.
• Sharp, jabbing, throbbing, or burning pain
• Random, odd sensations, known as paresthesias
• Extreme sensitivity to touch, known as allodynia
• Pain during activities that shouldn’t cause pain
• Feeling weak in your legs or arms (sometimes due to weak or atrophied muscles)
• Inability to walk straight, leading to stumbling or falling
• Loss of balance, particularly in the dark
• Reduced coordination
• Muscle cramps and loss of muscle mass
• Dizziness, especially when getting up from a bed or a chair
• Loss of reflexes
• Clumsiness
• Sexual dysfunction

People with peripheral neuropathy usually describe the pain as stabbing, burning, or tingling^[2]. About half of all cases of polyneuropathy are associated with pain^[6]. Many patients struggle with nighttime symptoms that can cause insomnia and impact daytime activities because of disrupted sleep^[23].

Acute polyneuropathies often begin suddenly in both legs and progress rapidly upward to the arms. Symptoms include weakness and a pins-and-needles sensation or loss of sensation. The muscles that control breathing may be affected, resulting in respiratory failure^[4].

Many chronic polyneuropathies affect sensation primarily. Usually, the feet are affected first, but sometimes the hands are affected at the same time^[4].

Diagnosis

To diagnose polyneuropathy, healthcare providers begin with a thorough history of your symptoms and a physical examination^[4][8]. They will ask about your medical history, including your symptoms, lifestyle, exposure to toxins, drinking habits, and family history of nervous system diseases^[8].

A neurological examination checks your tendon reflexes, muscle strength and tone, ability to feel certain sensations, and balance and coordination^[8][14].

Depending on your history and examination, healthcare providers may order several tests^[8]:

• Blood tests: These can detect low levels of vitamins, diabetes, signs of inflammation, or metabolic issues that can cause peripheral neuropathy.
• Electromyography (EMG): Measures and records electrical activity in your muscles to find nerve damage. A thin needle is inserted into the muscle to measure electrical activity as you contract the muscle.
• Nerve conduction studies: Usually done during an EMG. Flat electrodes are placed on the skin and a low electric current stimulates the nerves. The healthcare professional records how the nerves respond to the electric current.
• Imaging tests: CT or MRI scans can look for problems affecting the blood vessels and bones, such as herniated disks or pinched nerves.
• Nerve biopsy: Involves removing a small piece of nerve tissue for examination.
• Skin biopsy: Can help diagnose certain types of neuropathy.
• Autonomic reflex screen: Records how the autonomic nerve fibers work.
• Other tests: Include sweat tests that measure your body’s ability to sweat and sensory tests that record how you feel touch, vibration, cooling, and heat.
• Urine tests
• Genetic testing: For hereditary forms of polyneuropathy.

A timely diagnosis of the cause of polyneuropathy is a prerequisite for the initiation of appropriate specific treatment. Patients with severe neuropathy of unidentified cause should be referred to a specialized center for a thorough diagnostic evaluation^[6].

Treatment

Treatment for peripheral neuropathy may include treating any underlying cause or managing symptoms^[10]. The options for treatment depend on the cause, which should be identified as precisely as possible^[6]. Since everyone experiences neuropathy differently, treatment plans are tailored to meet unique individual needs^[14].

Treating the Underlying Cause

Treatment may be more successful for certain underlying causes. For example^[10]:

• Ensuring diabetes is well controlled may help improve neuropathy or at least stop it getting worse
• Vitamin B12 deficiency can be treated with B12 injections or tablets
• Peripheral neuropathy caused by a medicine you’re taking may improve if the medicine is stopped
• Treating infections, managing thyroid problems, or addressing nutritional deficiencies

Pharmacologic treatment of peripheral neuropathy hinges upon treating the underlying cause when known. Treatment of reversible causes during the acute stage may aid in nerve regeneration and remyelination^[15]. However, the underlying cause may not always be treatable^[10].

Some less common types of peripheral neuropathy may be treated with medicines such as steroids (powerful anti-inflammatory medicines), immunosuppressants (medicines that reduce the activity of the immune system), or injections of immunoglobulin (a mixture of blood proteins called antibodies made by the immune system)^[10].

Managing Pain

Unlike most other types of pain, neuropathic pain does not usually get better with common painkillers such as paracetamol and ibuprofen^[10]. Neuropathic pain can be treated symptomatically with medication^[6]. Treatment approaches follow a tiered system^[13]:

First-line therapies include^[13]:

• Gabapentinoids (such as gabapentin and pregabalin), which target voltage-gated calcium channels
• Tricyclic antidepressants (such as amitriptyline and nortriptyline)
• Serotonin-norepinephrine reuptake inhibitors such as duloxetine

Second-line options include^[13]:

• Topical agents such as 5% lidocaine and 8% capsaicin patches. Capsaicin is the substance that makes chili peppers hot and is thought to work by stopping the nerves from sending pain messages to the brain^[10].
• Opioid-like medications such as tramadol and tapentadol. Tramadol is a powerful painkiller that can be used to treat neuropathic pain that does not respond to other treatments. It is usually only prescribed for a short time^[10].

Third-line treatments for refractory cases include NMDA receptor antagonists (such as ketamine and dextromethorphan), cannabinoids, and botulinum toxin type A, though these have more limited clinical evidence^[13].

These medicines should usually be started at the minimum dose, with the dose gradually increased until you notice an effect. Higher doses may be better at managing pain but are also more likely to cause side effects^[10].

Other Treatment Options

Additional treatment and management approaches include^[6][12][14]:

• Physical therapy: Can help strengthen muscles and improve coordination. Exercise, physiotherapy, and ergotherapy can be beneficial depending on symptoms and functional deficits.
• Occupational therapy: Helps adjust to changes in your body and helps you move more comfortably.
• Transcutaneous electrical nerve stimulation (TENS): A method of therapy that works by inhibiting pain signals from reaching the brain. It places very small electrical impulses on specific nerve paths through electrodes placed on the skin.
• Spinal cord stimulation: For cases where pharmacological approaches fail.
• Assistive devices: From specialized footwear to electrical nerve stimulation devices. Technologies offer hope for the future.
• Splints: To support weak ankles or walking aids to help you get around.

Despite advances in treatment options, many patients remain undertreated, highlighting the need for individualized, multimodal approaches^[13].

Recovery and Outlook

The good news for those living with neuropathy is that it is sometimes reversible. Peripheral nerves do regenerate. Simply by addressing contributing causes such as underlying infections, exposure to toxins, or vitamin and hormonal deficiencies, neuropathy symptoms frequently resolve themselves^[20].

The peripheral nerves have a great ability to heal. Even though it may take months, recovery can occur. However, in some situations, symptoms of neuropathy may lessen but not completely go away. For example, nerve injury caused by radiation often does not recover well. Neuropathy caused by chemotherapy is also difficult to cure, and recovery may take 18 months to five years or longer. During recovery of platinum-induced neuropathy, patients may suffer increased symptoms^[15].

In most cases, however, neuropathy is not curable, and the focus for treatment is managing symptoms^[20].

Living with Polyneuropathy

Living with chronic pain or disability presents daily challenges. Effective self-care and coping skills can help manage the condition^[18].

Lifestyle Changes

Several lifestyle changes can help prevent symptoms or slow progression^[19][20]:

• Modify daily routines: Repetitive and recurring movements and motions, or sitting for extended periods with improper posture, can lead to nerve damage. By stopping or correcting the form with which you perform movements, you can eliminate some of the risks.
• Eliminate alcohol and tobacco: Excessive consumption of alcohol and tobacco may worsen your condition.
• Control blood sugar levels: For those with diabetes, strict glucose control is imperative to prevent progression.
• Maintain a healthy weight
• Exercise regularly: Even exercising three times a week for 30 to 60 minutes can benefit your health and act as a preventative measure. Routine exercise trains your respiratory, cardiovascular, circulatory, and nervous systems.

Dietary Considerations

Eating a healthy diet with foods that support the health of your nervous system can help. You should follow nutrition plans that are high in vitamin B-12, which can include a healthy variety of fruits, vegetables, and lean forms of omega-rich protein such as fish or eggs. Good nutrition including foods rich in thiamine, protein, and antioxidants may help recovery^[15][19].

Coping Strategies

Effective coping skills include^[18]:

• Set priorities: Decide which tasks you need to do on a given day and which can wait until another time.
• Stay active, but don’t overdo
• Accept and acknowledge: Accept the negative aspects of the illness, but then move forward to become more positive to find what works best for you.
• Get out of the house: Visit a friend, go to a movie, or take a walk instead of focusing on pain.
• Get moving: Develop an exercise program that works for you to maintain optimum fitness.
• Seek and accept support: Consider joining a chronic pain support group. Support groups can be good places to hear about coping techniques or treatments that have worked for others.

What predicts depression and anxiety among people with neuropathy is not necessarily the severity of symptoms but psychological and social variables. These include how you feel (hopeless, optimistic, anxious) and whether you are active and have support. All of these variables can be changed^[18].

Managing Symptoms

In addition to treating pain, you may require treatment to help manage other symptoms. For example^[10]:

• If you have muscle weakness, you may need physiotherapy to learn exercises to improve muscle strength
• Medicines for erectile dysfunction, constipation, or slow movement of food through your stomach
• Safety measures to prevent falls due to balance problems

It’s important to be aware of factors that can aggravate symptoms. Common neuropathy triggers include poorly controlled (or untreated) diabetes, drinking alcohol, vitamin B12 deficiency, vitamin B6 imbalance (too little or too much), and certain infections^[23].

If you notice symptoms of neuropathy, it is important to discuss this with your healthcare team as soon as possible. Symptoms are often ignored by both patients and healthcare professionals^[22].