If you’ve been dealing with unexplained nerve pain, weakness, or numbness, you may have come across the term polyneuropathy. It’s a broad category. One rare form, called transthyretin amyloid polyneuropathy (ATTR-PN), has a very specific cause — it’s often genetic.

This may feel overwhelming at first. But understanding your symptoms is a powerful first step. It helps you manage your health and get the right care. This article will help you understand polyneuropathy. It’ll also explain the specific causes of ATTR polyneuropathy.

What Is Polyneuropathy?

Your nervous system is like a network of “wires.” These wires are your nerve cells. They connect your brain and spinal cord (the central nervous system) to the rest of your body (the peripheral nervous system). These two systems talk to each other through electrical signals. This allows you to move and think.

The peripheral network is vast and delicate, making it vulnerable to damage from various health issues. When this damage is widespread, affecting multiple nerves at the same time, it’s called polyneuropathy.

Polyneuropathy is a disease. It happens when the connection between your nerve cells is broken. The word seems complicated, but it has just two parts:

• Poly — Many
• Neuropathy — Nerve damage in the peripheral nervous system

So polyneuropathy means that many nerves are damaged in the peripheral nervous system. When these nerves are damaged, it causes weakness, pain, and numbness. This usually happens in the feet and hands — body parts connected to the peripheral nervous system.

How Is Polyneuropathy Different From Other Nerve Damage?

Some people have other types of nerve damage. These conditions have different causes:

• Mononeuropathy — Nerve damage occurs in a single nerve (for example, carpal tunnel syndrome is damage to just the median nerve in the wrist)
• Radiculopathy — Nerve damage occurs where the peripheral nerve connects to the spine (for example, a pinched nerve in the neck or back)

The symptoms of pain and numbness are similar with mononeuropathy, radiculopathy, and polyneuropathy. However, mononeuropathy and radiculopathy are often caused by injury or pressure on a nerve. Polyneuropathy is caused by several factors, including genetics, infections, substance use disorder, or diseases like diabetes.

What Causes Polyneuropathy?

The exact causes of polyneuropathy are often unknown, but some risk factors are known. These include:

• Diabetes (the most common cause)
• Alcohol use disorder
• Vitamin B12 deficiency
• Autoimmune diseases (Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, lupus)
• Medications (some antibiotics and chemotherapy medications)
• Kidney failure
• Toxic substances (lead, mercury, arsenic)
• Infections (hepatitis C, human immunodeficiency virus, Lyme disease)
• Genetics

The progression of polyneuropathy can be slow and gradual, developing over many months or even years. In other cases, it may appear more suddenly. The specific pattern of symptoms and their rate of progression often provide important clues for doctors, helping them identify the underlying cause.

What Does Polyneuropathy Feel Like?

The symptoms of polyneuropathy can vary, but they often follow a predictable pattern of starting in the feet and moving upward. There are three main types of symptoms: sensory, motor, and autonomic.

Sensory Symptoms

Sensory symptoms are the most common and cause unique changes to sensation in the hands and feet. These sensations can be constant or may come and go intermittently, sometimes flaring up more noticeably at night and disturbing your sleep. Sensory symptoms include:

• Numbness and loss of sensation — Feeling like you’re walking on cotton or wearing socks when you’re not
• Tingling — A prickling or “pins and needles” sensation
• Pain — A feeling of burning, sharpness, stabbing, jolting, or electric-like sensation
• Touch sensitivity — Even touch from a light bedsheet can feel painful or uncomfortable

Motor Symptoms

Motor symptoms mainly include changes in movement and can significantly impact someone’s mobility. These include:

• Muscle weakness (especially in the feet, ankles, and hands)
• Muscle cramps and twitching
• Loss of coordination and balance

Autonomic Symptoms

The autonomic nerves control involuntary functions like your heartbeat, blood pressure, and digestion. If the autonomic nerves are damaged, it can cause problems with these involuntary functions. Autonomic symptoms include:

• Dizziness or fainting
• Diarrhea or constipation
• Nausea
• Bladder problems
• Sexual dysfunction
• Unintentional weight loss

What Is ATTR Amyloidosis Polyneuropathy?

For some people with polyneuropathy, the cause is a specific inherited or age-related condition known as ATTR amyloidosis.

Polyneuropathy means that many nerves are damaged in the peripheral nervous system. When these nerves are damaged, it causes weakness, pain, and numbness.

Amyloidosis is a disease where proteins aren’t folded correctly and end up accumulating in the body. These misfolded proteins build up in organs and prevent them from working properly.

In people with ATTR amyloidosis, a protein called transthyretin (TTR) is misfolded. These misfolded proteins build up and create stiff fibers called amyloids. Amyloid fibers that build up around nerves press on the cells and damage them. This causes the symptoms of polyneuropathy.

What Causes ATTR Amyloidosis Polyneuropathy?

ATTR amyloidosis polyneuropathy most often has genetic or age-related causes.

• Hereditary ATTR (hATTR) — Caused by a genetic mutation (change) that you inherit
• Wild-type ATTR (ATTRwt) — Caused by age-related mistakes in how proteins fold

What To Do if You Experience Polyneuropathy Symptoms

If you’re experiencing symptoms of polyneuropathy, don’t panic, but be proactive. It’s important to take early action if you suspect you’re experiencing early signs and symptoms so you can get the help you need quickly.

• Document your symptoms — Keep a symptom journal and take notes on what sensations you feel in addition to when, where, and to what severity you feel them. This will help your doctor.
• Schedule an appointment with your doctor — Start with your primary care physician. Tell them you are concerned about polyneuropathy.
• Seek out a specialist — You may be referred to a neurologist or an amyloidosis center for comprehensive care.

What To Expect During the Diagnosis Process

There are many causes of polyneuropathy, so your doctor will need to rule out potential causes. Here are some elements of the diagnosis process you may experience:

• A detailed history and physical exam, including reflex tests and sensory checks
• Blood tests and urine tests to rule out other common causes for neuropathy, like diabetes and vitamin deficiencies
• Nerve and muscle function tests
• Specific tests for ATTR, like genetic testing for hATTR or tissue biopsies to look for amyloid deposits, if indicated

How Is Polyneuropathy Managed and Treated?

The goal after diagnosis is to shift to managing your disease. Management differs depending on the underlying cause. Several treatment avenues exist to help people with ATTR amyloidosis and polyneuropathy. There isn’t a cure yet, but the treatment options have changed dramatically and can be helpful to many.

• Disease-modifying therapies — There are treatments specifically for ATTR that slow or halt disease progression
• Symptom management — There are medications to manage neuropathic pain and autonomic symptoms
• Physical therapy — Working with a physical therapist can help maintain muscle strength and mobility

In addition to medical treatments, lifestyle adjustments play a crucial role in improving your day-to-day life. These can include meticulous foot care to prevent injuries you might not feel or using assistive devices like a cane for stability. Managing underlying conditions, such as controlling blood sugar if you have diabetes, is also critical.

Polyneuropathy is caused by several factors, including genetics, infections, substance use disorder, or diseases like diabetes.

It’s important to have a team of healthcare professionals who work together to make a care plan for you.

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