Jodi Knapp

Medications can cause neuropathy through a variety of mechanisms that lead to damage or dysfunction of the peripheral nerves. This condition, known as drug-induced peripheral neuropathy, can arise due to direct toxicity to the nerves, nutrient deficiencies caused by the drug, or interference with metabolic processes essential for nerve function.

Mechanisms by Which Medications Cause Neuropathy:

1. Direct Neurotoxicity: Some drugs can directly damage the nerve fibers (axons) or their protective coverings (myelin), leading to dysfunction in nerve signaling. This damage results in symptoms like pain, numbness, tingling, and muscle weakness. Drugs that commonly cause direct neurotoxicity include:
   • Chemotherapy drugs: Certain cancer treatments, such as platinum-based agents (cisplatin, carboplatin), taxanes (paclitaxel), and vinca alkaloids (vincristine), are notorious for causing neuropathy. These drugs are toxic to rapidly dividing cells, including nerve cells, leading to peripheral neuropathy.
   • Antiretroviral drugs: Used to treat HIV/AIDS, medications such as stavudine and didanosine can cause peripheral neuropathy by directly damaging nerve cells.
   • Amiodarone: A medication used to control abnormal heart rhythms, which can induce neuropathy through long-term exposure.
2. Oxidative Stress: Certain drugs can increase oxidative stress within nerve cells, which leads to cellular damage and disrupts the normal function of the nerves. This oxidative damage can contribute to the development of neuropathy.
   • Chemotherapy agents: Many chemotherapy drugs increase oxidative stress, which not only affects cancer cells but also damages peripheral nerves.
   • Antibiotics: Some antibiotics, particularly fluoroquinolones (e.g., ciprofloxacin), can cause oxidative stress in nerve tissues, leading to sensory and motor neuropathy.
3. Nutritional Deficiencies: Some medications interfere with the absorption or metabolism of essential nutrients required for nerve health, particularly certain B vitamins. Nerve cells rely on a proper supply of these nutrients to maintain their function, and deficiencies can lead to nerve damage.
   • Metformin: Used to manage diabetes, long-term use of metformin can cause vitamin B12 deficiency, which is essential for nerve function. A deficiency in B12 can lead to peripheral neuropathy.
   • Isoniazid: A medication used to treat tuberculosis, isoniazid can cause a deficiency in pyridoxine (vitamin B6), leading to neuropathy if not supplemented appropriately.
   • Alcohol: Though not a “medication” in the traditional sense, chronic alcohol use can cause significant nutrient deficiencies, especially of vitamins B1 (thiamine) and B12, which are crucial for nerve health.
4. Mitochondrial Dysfunction: Some drugs impair the function of mitochondria, the energy-producing structures within cells. Since peripheral nerves have high energy demands, disruptions in mitochondrial function can lead to nerve damage.
   • Antiretroviral drugs: Some HIV medications can cause mitochondrial toxicity, leading to peripheral neuropathy.
   • Chemotherapy agents: Certain chemotherapy drugs may affect mitochondrial function in peripheral nerves.
5. Impaired Nerve Repair Mechanisms: Certain medications can hinder the body’s ability to repair damaged nerves. This is particularly problematic for peripheral nerves, which are more susceptible to injury due to their length and exposure to external stressors.
   • Colchicine: Used for gout treatment, colchicine can interfere with microtubule formation, which is critical for transporting nutrients and other molecules within nerve cells, leading to neuropathy.
   • Phenytoin: An anticonvulsant used to manage seizures, long-term use of phenytoin can impair nerve repair, contributing to peripheral neuropathy in some individuals.
6. Immune-Mediated Neuropathy: Some medications can trigger an immune response that mistakenly attacks peripheral nerves, leading to neuropathy. This is often referred to as drug-induced autoimmune neuropathy.
   • Immune checkpoint inhibitors: Used in cancer immunotherapy, drugs like nivolumab or pembrolizumab can cause autoimmune neuropathy by triggering an immune response against peripheral nerves.

Common Medications That Can Cause Neuropathy:

1. Chemotherapy Drugs:
   • Platinum compounds: Cisplatin, carboplatin, and oxaliplatin.
   • Taxanes: Paclitaxel, docetaxel.
   • Vinca alkaloids: Vincristine, vinblastine.
2. Antibiotics:
   • Fluoroquinolones: Ciprofloxacin, levofloxacin.
   • Nitrofurantoin: Used to treat urinary tract infections, which can cause peripheral neuropathy, especially with long-term use.
3. Antiretroviral Drugs:
   • Stavudine and didanosine (HIV medications) are known for their potential to cause nerve damage.
4. Anticonvulsants:
   • Phenytoin: An older anticonvulsant that can cause neuropathy with chronic use.
5. Cardiovascular Drugs:
   • Amiodarone: Used for arrhythmias, can cause neuropathy, particularly in patients on long-term treatment.
6. Statins:
   • Though rare, some patients taking statins (used to lower cholesterol) may develop peripheral neuropathy.
7. Alcohol:
   • Chronic alcohol consumption can cause alcoholic neuropathy, leading to nerve damage due to both direct toxicity and nutrient deficiencies (especially B vitamins).

Management of Drug-Induced Neuropathy:

1. Discontinuing the Medication: The first step in managing drug-induced neuropathy is often stopping or reducing the dosage of the offending drug if possible. In cases where this is not possible, close monitoring is required.
2. Symptom Management:
   • Medications: Pain associated with neuropathy can be managed with drugs such as gabapentin, pregabalin, or duloxetine.
   • Topical treatments: Capsaicin cream or lidocaine patches may help with localized nerve pain.
3. Nutritional Support: For medications that cause neuropathy through nutrient deficiencies, supplementation with vitamins (especially B12, B6, and folate) can be helpful.
4. Physical Therapy: To improve balance, strength, and mobility in patients with neuropathy.
5. Prevention: Regular monitoring of nerve function during treatment with high-risk medications can help detect neuropathy early. For example, doctors may periodically check vitamin levels in patients on medications like metformin or isoniazid.

In summary, medications can cause neuropathy through various mechanisms, including direct neurotoxicity, mitochondrial damage, nutrient deficiencies, and immune responses. Early detection and intervention are critical to preventing irreversible nerve damage.

Traumatic injuries can have a significant impact on the development of neuropathy by causing direct damage to the peripheral nerves. When nerves are injured or compressed as a result of trauma, their ability to transmit signals between the brain, spinal cord, and muscles or sensory organs can be compromised, leading to a range of neuropathic symptoms. Depending on the severity and location of the trauma, the neuropathy can be temporary or permanent, and the symptoms can vary from mild to debilitating.

How Traumatic Injuries Cause Neuropathy:

1. Nerve Compression or Crushing:
   • Trauma can compress or crush peripheral nerves, leading to neuropathy. For example, in accidents where the limbs are subjected to high pressure (like car accidents or falls), the nerves may be squeezed, disrupting signal transmission. This can cause compression neuropathies such as:
     • Carpal tunnel syndrome: From pressure on the median nerve in the wrist.
     • Ulnar neuropathy: From compression of the ulnar nerve, often at the elbow.
     • Radial nerve palsy: From compression of the radial nerve in the upper arm (often referred to as “Saturday night palsy”).
2. Nerve Laceration or Severing:
   • When a nerve is cut or severed, as in deep lacerations or traumatic amputations, the connection between the nerve endings and the muscles or skin is lost, leading to severe neuropathy. This may result in complete loss of sensation and paralysis in the affected area.
     • Example: A hand injury that severs the median nerve can cause loss of sensation and function in the thumb, index, and middle fingers.
3. Stretch or Tension Injuries:
   • Nerves are sensitive to being stretched or pulled beyond their normal range. Traumatic events such as dislocations, fractures, or forceful impacts can overstretch or tear nerves, leading to neuropathy. Nerves that are stretched may not immediately tear but can suffer from long-term dysfunction due to internal damage.
     • Brachial plexus injuries: Often seen in motorcycle accidents, these injuries involve damage to the network of nerves controlling the arms and hands. This can lead to weakness, paralysis, or numbness in the arm.
4. Blunt Force Trauma:
   • Even without cutting or severing the nerves, blunt trauma (like hitting or being struck by an object) can cause damage to the nerve fibers. Swelling or bruising after an injury can compress nearby nerves, leading to temporary or permanent neuropathy.
     • Foot drop: A condition that can result from blunt force trauma to the peroneal nerve, causing weakness or paralysis in the muscles responsible for lifting the foot.
5. Bone Fractures:
   • A bone fracture can impinge on nearby nerves, leading to neuropathy. This is especially true in fractures near the long bones of the limbs (e.g., humerus, femur), where nerves may be closely associated with the bone.
     • Radial nerve palsy can occur with fractures of the humerus bone in the arm, leading to weakness or loss of function in the wrist and fingers.
6. Whiplash and Spinal Injuries:
   • Trauma to the spine, such as whiplash or fractures of the vertebrae, can compress or damage the spinal nerves or nerve roots as they exit the spinal cord. This can cause neuropathy that radiates down the limbs, leading to pain, weakness, or numbness.
     • Cervical radiculopathy: Results from nerve root compression in the neck, causing pain, tingling, and weakness that radiates into the arms.
     • Lumbar radiculopathy (sciatica): Compression of the sciatic nerve root due to trauma in the lower back, resulting in pain, numbness, and weakness down the leg.
7. Nerve Entrapment Syndromes:
   • Trauma can lead to scarring, inflammation, or misalignment of tissues, which may trap or pinch nerves, causing long-term neuropathy.
     • Tarsal tunnel syndrome: Trauma to the ankle or foot can lead to compression of the tibial nerve, causing neuropathy in the foot.

Symptoms of Neuropathy from Trauma:

The symptoms of traumatic neuropathy depend on the type and location of the injury but often include:

• Pain: A burning, tingling, or stabbing sensation.
• Numbness: Loss of sensation in the affected area.
• Weakness or Paralysis: Difficulty moving the affected limb or muscles.
• Tingling or “Pins and Needles”: An abnormal sensation, often described as tingling or prickling, in the hands, feet, or other affected areas.
• Muscle Atrophy: Loss of muscle mass over time if the nerves are severely damaged and unable to control the muscles.

Types of Traumatic Neuropathy:

• Acute Neuropathy: Develops shortly after the injury due to direct damage to the nerves.
• Chronic Neuropathy: Can develop over time if the nerves are subjected to ongoing compression or if healing from trauma is incomplete, leading to long-term dysfunction.

Recovery and Treatment of Traumatic Neuropathy:

1. Rest and Immobilization: After nerve injury, rest and immobilization of the affected limb can help prevent further damage and promote healing. This is particularly important in cases where nerves are compressed or mildly stretched.
2. Surgical Repair: In cases of nerve laceration or severe damage, surgery may be necessary to repair the nerve or to relieve compression. Surgeons may:
   • Reconnect severed nerves through microsurgery.
   • Remove scar tissue or release trapped nerves (e.g., carpal tunnel release).
   • Repair fractures that are impinging on nerves.
3. Physical Therapy: Rehabilitation plays a crucial role in the recovery of traumatic neuropathy. Physical therapy helps improve strength, flexibility, and function, and can prevent muscle atrophy due to nerve damage.
4. Pain Management: Neuropathic pain from traumatic injuries can be managed with medications such as:
   • Anticonvulsants (e.g., gabapentin, pregabalin).
   • Antidepressants (e.g., amitriptyline, duloxetine).
   • Opioids: In severe cases, though they are usually not a first-line treatment for neuropathy.
   • Topical treatments: Like capsaicin cream or lidocaine patches.
5. Nerve Regeneration Therapies: In some cases, nerve regeneration may be possible. Certain supplements, such as vitamin B12 or other B-complex vitamins, can support nerve health. Experimental treatments, like nerve growth factors or electrical stimulation, may also be explored in specific cases.
6. Orthotic Devices: Braces or splints may be used to support weakened limbs and improve mobility in cases of foot drop or wrist drop due to nerve damage.

Prognosis:

The prognosis for traumatic neuropathy varies depending on the severity and type of nerve injury:

• Mild cases of nerve compression or stretch injuries may resolve over weeks to months with proper care.
• Severe cases involving nerve laceration or prolonged compression may result in long-term or permanent damage, though surgical repair and rehabilitation can improve outcomes.
• In some cases, nerves can regenerate, but the process is slow, with recovery often taking months or even years.

In summary, traumatic injuries can cause neuropathy through direct damage to peripheral nerves, compression, laceration, or stretching. The impact of traumatic neuropathy varies in severity, but treatment options such as surgery, physical therapy, and pain management can significantly improve outcomes.