Tomaculous Neuropathy - Causes, Symptoms, Diagnosis, and Treatment

What Is Tomaculous Neuropathy?

Tomaculous neuropathy is known as hereditary neuropathy with pressure palsies (HNPP). It is an inherited condition that causes recurrent episodes of tingling, numbness, and muscle weakness in the limbs. It is a disorder that affects peripheral nerves. These nerves connect the brain and spinal cord to the sensory cells in the muscles, which detect pain, touch, and temperature.

The unusual sensitivity can happen with the slightest pressure, such as the one that occurs when carrying grocery bags, leaning on the elbow, sitting without changing position, etc. Symptoms usually start in the third decade and can affect anyone.

It is caused by the deletion of one copy of the PMP22 gene, reducing the amount of respective protein produced. It is a rare condition that affects two to five individuals for every 100000 individuals. It is transmitted from one generation to the next through autosomal dominant inheritance, which means one copy of the altered gene is sufficient to cause the disorder.

Diagnosis can be made with clinical findings and electrophysiologic studies, and treatment mainly involves symptomatic relief.

What Causes Tomaculous Neuropathy or Hereditary Neuropathy With Pressure Palsies (HNPP)?

The peripheral nervous system (part of the nervous system that lies outside the brain and the spinal cord) has specialized cells called the Schwan cells. These cells contain a specific PMP22 gene that provides instructions to make a protein called the peripheral myelin protein 22 (PMP22). It is one of the components of the myelin sheath, the protective covering around the nerves that promotes the efficient transmission of electrical impulses.

When physical pressure is applied to the peripheral nerves get compressed and lose their structure; the PMP22 protein restores this lost structure and protects them from the pressure. It also plays an important role in developing and maintaining the myelin sheath.

In HNPP patients, one copy of the PMP22 genes gets deleted due to genetic mutations (alterations). This condition is known as deletion mutation. Deletion mutations are thought to occur when the enzyme (polymerase) that synthesizes new genetic material (during cell division) slips, effectively missing a part of the gene.

Deleting one copy of the PMP22 gene reduces the amount of PMP22 protein in half; this shortage affects the structure of the myelin sheath. Consequently nerve impulse transmission is impaired. Along with this, the recovery capacity of the nerves from physical pressure also gets reduced, leading to symptoms of HNPP.

What Are the Symptoms of Tomaculous Neuropathy or Hereditary Neuropathy With Pressure Palsies (HNPP)?

Symptoms associated with HNPP occur in episodes due to pressure on a single nerve that runs close to the body’s surface near a bone. Some of the frequently affected nerves are the peroneal nerve near the knee, the ulnar nerve in the elbow, and the median nerve in the wrist.

The typical symptoms of HNPP are:

• Numbness.

• Tingling.

• Weakness.

• Muscle cramps.

• Leg and ankle swelling.

• Reduced ankle reflexes.

• Loss of muscle function (palsy).

• Pain in the limbs (especially in the hands).

• Food drops make it hard to walk, climb stairs, drive, etc.

• Recurrent focal compression neuropathies caused by compression are characteristic features of HNPP. The best example of this neuropathy is carpal tunnel syndrome which is caused due to compression of the median nerve leading to the impairment in the ability to use the wrist, fingers, and hands.

An episode of symptoms associated with HNPP lasts for a few minutes to several months, most people completely recover after an episode, but repeated episodes can cause muscle weakness and loss of sensation.

How Is Tomaculous Neuropathy or Hereditary Neuropathy With Pressure Palsies (HNPP) Diagnosed?

Diagnosis is based on the symptoms, electromagnetic testing, imaging, and genetic testing.

1. Electrodiagnostic Testing: The process of measuring the speed and degree of electrical activity in the muscles and nerves. The commonly used tests are the EMG (electromyography) and NCS (nerve conduction studies), the former being the most popular.Patients with HNPP will exhibit latency (delay) in relation to the corresponding nerve. Some of the commonly seen nerve latencies are distal nerve conduction latency, medial nerve motor, and sensory latency, and reduced sural responses.

2. Imaging: This includes ultrasonography, which will show a multifocal increase in the cross-section of the corresponding nerve and an MRI (magnetic resonance imaging), which will show asymmetric swelling and increased nerve caliber at the entrapment site.

3. Genetic Testing: This can be done by testing only the suspected gene (as seen in single genome testing), or it can be done by including PMP22 genes with other genes (as seen in a neuropathy multigene pool and comprehensive genome testing).

A few other investigations which also assist in the diagnosis are the nerve conduction velocity test, nerve biopsy, and neurological evaluation.

Attention should be paid while diagnosing HNPP because it is often under-diagnosed due to its similar clinical features with other medical conditions like Charcot-Marie-tooth disease, diabetes mellitus, chronic inflammatory demyelinating polyneuropathy (CIDP), hereditary peripheral neuropathies, etc.

How Is Tomaculous Neuropathy or Hereditary Neuropathy With Pressure Palsies (HNPP) Treated?

Treatment primarily focuses on relieving the symptoms. This includes:

1. Medication: These can be over-the-counter medication (for mild pain) or prescription drugs like Pregabalin, Duloxetine, etc. (for severe pain).

2. Transient Bracing: This can be done with an ankle-foot orthosis (AFO) or a wrist splint; shoes with ankle support are also helpful.

3. Protective Pads: Protective pads prevent trauma and pressure on the local nerves.

4. Physical Therapy And Occupational Therapy: Gross motor and fine motor issues can be addressed with these therapies, and they also help with daily activities.

5. Genetic Counseling: It is defined as providing information about the inheritance pattern and associated complications of genetically transmitted conditions to the affected individual and their families. This helps to effectively manage the condition and prevent it from spreading to future generations with the help of prenatal testing.

Apart from these, management of HNPP also includes avoiding and modifying positions that might trigger the episodes and taking safety measures to compensate for the loss of sensation.

Conclusion

Tomaculous neuropathy or HNPP is a genetic condition characterized by deletion mutation of the PMP22 gene. Symptoms are similar to hereditary neuropathies and are hard to diagnose. While the long-term outlook regarding the quality of life depends on the frequency and severity of the episodes, HNPP does not affect life expectancy.