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Large Fiber Neuropathy: Symptoms, Causes, and Treatment Options

Large fiber neuropathy is a type of peripheral neuropathy that primarily affects the sensory nerves. These large fiber nerves are responsible for sensations like proprioception (the awareness of self-movement and force) and vibration. The condition can often lead to a range of symptoms, making it essential to understand and identify the signs and the potential avenues for treatment.

Damage to large sensory fibers can impair an individual's ability to feel vibrations and touch, particularly in the hands and feet. It might lead to the sensation of wearing gloves and stockings when not actually wearing them. This damage can also contribute to the loss of reflexes, which could impact motor nerve function as well. It is crucial to recognize large fiber neuropathy in its early stages, as this can enable patients to pursue appropriate therapies and prevent further progression of the condition.

Many factors can contribute to the development of large fiber neuropathy, such as underlying medical conditions, injuries, or exposure to toxins. In the coming sections, we will explore the various causes, symptoms, and treatment options available for managing large fiber neuropathy, providing valuable information for patients and healthcare professionals alike.

Large Fiber Neuropathy Overview

Peripheral Neuropathy

Large fiber neuropathy is a subgroup of peripheral neuropathies affecting the sensory nerves. These nerves are responsible for a broad range of sensations such as proprioception (the sensation of self-movement and force) and vibration. Damage to large sensory fibers can result in the loss of reflexes and an altered sense of touch, particularly in the hands and feet. Patients may experience sensations similar to wearing gloves and stockings when they are not.

Central Nervous System

The central nervous system (CNS) consists of the brain and spinal cord. CNS is responsible for processing information from the peripheral nervous system and controlling the body's responses. While large fiber neuropathy predominantly affects the peripheral nervous system, its symptoms can have an indirect impact on the CNS's ability to process sensory information properly. For instance, loss of proprioception can lead to balance and coordination issues, necessitating the brain to work harder in compensating for the missing sensory input.

Peripheral Nervous System

The peripheral nervous system (PNS) is composed of nerves that transmit information between the CNS and the rest of the body. Polyneuropathy is a peripheral nerve disorder that affects multiple nerves and typically presents as symmetrical, bilateral dysfunction. Large fiber neuropathy, a type of polyneuropathy, primarily targets the large fiber sensory nerves within the PNS. In rare cases, it can selectively affect the large fibers or their cell bodies as seen in some very rare conditions.

In managing large fiber neuropathy symptoms, treatments may include medications such as amitriptyline or gabapentin, as noted in a Mayo Clinic Connect discussion. Physical therapy, lifestyle modifications, and addressing underlying conditions may also be helpful.

Causes of Large Fiber Neuropathy


Diabetes is the primary cause of peripheral neuropathy in the United States, with about 50% of diabetics experiencing it in their lifetime. High blood sugar levels can damage large nerves, leading to large fiber neuropathy.


Physical injury, such as trauma from car accidents, falls, sports, or medical procedures, can cause large fiber neuropathy. These injuries can compress, stretch, or crush nerves, impacting their function.

Infections and Autoimmune Diseases

Some infections, like leprosy and human immunodeficiency virus (HIV), can contribute to large fiber neuropathy. Additionally, autoimmune diseases like Guillain-Barré syndrome and vasculitis can cause this condition by damaging or inflaming nerve tissues.

Nutritional Deficiencies and Metabolic Disorders

Large fiber neuropathy can result from nutritional deficiencies, such as a lack of vitamin B12 or Vitamin E, as well as metabolic disorders like hypothyroidism. These conditions can interfere with nerve function and lead to neuropathy.

Hereditary and Genetic Factors

Certain hereditary and genetic factors can cause large fiber neuropathy, such as Charcot-Marie-Tooth disease, which is a group of inherited disorders affecting nerve fibers. These genetic factors contribute to the development or severity of neuropathy.

Toxic Exposures

Long-term exposure to toxins like alcohol can cause large fiber neuropathy. Alcoholism, for example, can lead to neuropathy due to nerve damage caused by excessive alcohol consumption. Some medications and environmental toxins may also contribute to large fiber neuropathy.

Symptoms and Signs of Large Fiber Neuropathy

Large fiber neuropathy affects the sensory and motor nerves, as well as the autonomic nerves. The symptoms vary depending on the nerves involved and can manifest in different ways. This section will cover the sensory, motor, and autonomic symptoms associated with large fiber neuropathy.

Sensory Symptoms

Damage to large sensory fibers can result in a variety of symptoms, including:

  • Numbness or tingling, especially in the hands and feet
  • Loss of feeling of vibration and touch
  • Feeling as if you are wearing socks or gloves when you are not
  • Difficulty with proprioception, or your sense of your body's position in space

Additionally, sensory nerve damage can cause allodynia, or pain from normally non-painful stimuli, such as light touch, and pain from temperature changes.

Motor Symptoms

When motor fibers are affected by large fiber neuropathy, symptoms may include:

  • Muscle weakness, which can be greater than expected for the degree of muscle atrophy
  • Fasciculations, or involuntary muscle twitching
  • Difficulty with balance and coordination

For more severe cases, the motor symptoms can progress to the point of impaired mobility or even paralysis.

Autonomic Symptoms

Autonomic nerve dysfunction is a component of large fiber neuropathy and can lead to various symptoms, such as:

  • Heat intolerance, or difficulty regulating body temperature
  • Loss of control over functions, such as bladder and bowel control
  • Dizziness upon standing, caused by poor control of blood pressure

In cases where large fiber neuropathy impacts autonomic nerves, patients may require additional treatments to manage these symptoms, on top of interventions to address the sensory and motor symptoms.

Diagnosis and Evaluation

Patient History

When diagnosing large fiber neuropathy, obtaining a detailed patient history is crucial. It is important to ask about any family history of neurological disorders, systemic diseases (e.g., diabetes), or exposure to neurotoxic agents.

Physical Examination

During the physical examination, the evaluation should focus on assessing the patient's:

  • Reflexes: Testing deep tendon reflexes can indicate abnormalities in the large sensory and motor nerve fibers.
  • Light touch: Testing for light touch sensation can help identify sensory deficits.

Additionally, a thorough examination of the cranial nerves and assessment of muscle strength, muscle tone, and coordination should be performed.

Laboratory and Imaging Studies

Depending on the suspected underlying cause, several laboratory tests and imaging studies may be ordered to aid in the diagnosis. These can include:

  • Blood tests: To assess for metabolic or immune-mediated causes.
  • Lumbar puncture: For cerebrospinal fluid analysis in cases with suspected inflammatory etiology.
  • Imaging studies: Such as MRI or CT scans, which may be helpful if the neuropathy is related to a structural lesion or mass.

Electrophysiological Testing

Electrophysiological testing plays a vital role in the evaluation of large fiber neuropathy. The most commonly used tests are:

  1. Nerve Conduction Studies (NCS): These assess the function of large myelinated fibers and can identify abnormalities in nerve conduction velocity, amplitude, and latency. However, NCS may be normal in cases with primarily small fiber dysfunction.

  2. Electromyography (EMG): This test evaluates the electrical activity of muscles and can identify abnormalities in the motor unit, which may be indicative of large fiber neuropathy.

  3. Autonomic Testing: While less specific for large fiber neuropathy, autonomic testing can be helpful in detecting autonomic nerve dysfunction.

If the initial evaluation does not provide a definitive diagnosis, a referral to a neurologist may be necessary for further testing, such as skin biopsies or specialized nerve conduction studies. Overall, a multidisciplinary approach involving various diagnostic modalities is essential in the identification and management of large fiber neuropathies.

Treatment and Management

Medications and Pharmacotherapy

Various medications can be used to manage large fiber neuropathy symptoms. For neuropathic pain, gabapentin and pregabalin are commonly prescribed. These medications help in reducing pain and improving nerve function. Additionally, antidepressants such as tricyclics and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) can also be used for pain management.

For patients experiencing problems with blood pressure and heartbeat, medications may be prescribed to alleviate lightheadedness and maintain stability.

Non-pharmacological Interventions

Non-pharmacological interventions like physical therapy and Transcutaneous Nerve Stimulation (TENS) can complement medication in the treatment of large fiber neuropathy. TENS uses a gentle electric current to stimulate damaged nerve cells, providing relief from pain and improving overall nerve function. In some severe cases, surgery may be necessary.

Lifestyle and Self-Care

Adopting a healthy lifestyle plays a significant role in managing large fiber neuropathy symptoms. Some important self-care measures include:

  • Regular exercise: Walking, yoga, and tai chi can improve muscle strength, reduce neuropathy pain, and help in maintaining proper blood sugar levels.
  • Healthy diet: Eating a balanced diet, ensuring adequate vitamin intake, and maintaining proper weight can help in preventing the worsening of neuropathy symptoms.
  • Quit smoking: Cigarette smoking can affect circulation, leading to increased risk of foot problems and other neuropathy complications.
  • Proper foot care: Maintaining foot hygiene, wearing appropriate footwear, and seeking prompt medical care for foot injuries is crucial for patients with lower extremity neuropathy.

Incorporating these lifestyle changes, along with prescribed medications and non-pharmacological interventions, can greatly help in the treatment and management of large fiber neuropathy.

Types and Patterns of Large Fiber Neuropathy

Large fiber neuropathy is a condition affecting the peripheral nervous system, specifically the large sensory nerves that control vibration and proprioception. Symptoms may include loss of feeling of vibration and touch, especially in the hands and feet. This section covers the different types and patterns of large fiber neuropathy, such as focal and multifocal neuropathies, mononeuropathy and multiple mononeuropathies, and polyneuropathies.

Focal and Multifocal Neuropathies

Focal neuropathies involve damage to a single nerve, while multifocal neuropathies affect multiple nerves in different regions. These types of neuropathy may present with motor nerve symptoms or a combination of sensory and motor nerve dysfunction. Focal neuropathy commonly affects nerves in the face, causing facial weakness or paralysis.

Mononeuropathy and Multiple Mononeuropathies

Mononeuropathy refers to the involvement of a single nerve, while multiple mononeuropathy involves several nerves. These neuropathies usually have a sudden onset and can manifest as severe pain, loss of feeling, or muscle weakness. Common causes of mononeuropathy and multiple mononeuropathy may include trauma, entrapment (e.g., carpal tunnel syndrome), or inflammation.


Polyneuropathy involves the simultaneous damage to multiple peripheral nerves throughout the body. The predominant pattern of polyneuropathy is length-dependent, where the longest nerves are most affected. This typically leads to distal involvement, commonly seen in the feet and hands. Diabetic neuropathy is an example of a length-dependent polyneuropathy, as it usually affects the sensory nerves in a distal, symmetric pattern.

In addition to diabetic neuropathy, other common causes of polyneuropathy include:

  • Nutritional deficiencies
  • Chronic kidney disease
  • Infections (e.g., Lyme disease, HIV)

Of the different types of neuropathies, polyneuropathy is the most frequently encountered in clinical settings, often requiring a comprehensive evaluation and differential diagnosis to determine the underlying cause. Treatment options vary based on the cause, but may include addressing the underlying condition, managing symptoms, and implementing physical therapy to manage functional deficits.

Additional Considerations

Peripheral neuropathy is a condition that affects the peripheral nerves, which are responsible for transmitting sensory information and controlling motor functions. Among the various types of neuropathies, large fiber neuropathy is particularly significant due to its impact on large-diameter nerve fibers. These nerve fibers have a myelin sheath that increases the speed of nerve signal transmission and affects sensations such as vibration and proprioception.

Damage to the nerve fibers, cell body, or myelin sheath in large fiber neuropathy can lead to sensory loss, reduced reflexes, and muscle atrophy. The pathophysiology of large fiber neuropathy encompasses injury to these various components, often resulting in a combination of symptoms. A comprehensive neurological examination is crucial to identify the underlying cause and formulate an appropriate treatment plan.

Important factors in the evaluation of a patient with large fiber neuropathy include:

  • Differential diagnosis: Large fiber neuropathy may be caused by various factors, such as demyelinating neuropathies, ischemic events, exposure to chemotherapy drugs, alcohol use, or idiopathic reasons. A thorough differential diagnosis is essential to determine the specific cause and tailor the treatment accordingly.
  • Sensory information: Patients with large fiber neuropathy may experience distorted sensory information, difficulty in recognizing touch or vibration, and a feeling of wearing gloves or stockings when not. Evaluating the patient's sensory system helps identify abnormalities and assess the extent of nerve damage.
  • Motor function: Large fiber neuropathy can lead to weakened reflexes, muscle weakness, and atrophy. Assessing the patient's motor function helps to determine the severity of the condition and the effectiveness of potential treatments.

Due to the wide range of possible causes and symptoms, large fiber neuropathy must be approached with a comprehensive evaluation and individualized treatment strategy. Monitoring factors such as the patient's medical history, responsiveness to treatments, and any potential comorbidities is critical in managing this condition effectively.