Q 2.6. Polyneuritis and Polyneuropathies. Toxic and Deficiency Neuropathies.

1. Polyneuritis and Polyneuropathies: An Overview

• • Polyneuropathy refers to a diffuse peripheral nerve disorder that affects multiple nerves, typically in a symmetrical and bilateral manner. 
  • Electrodiagnostic tests play a crucial role in classifying the nerve structures involved, determining distribution, and assessing the severity of the disorder to identify the underlying cause.
  • Treatment aims at addressing the specific cause.

 

2. Polyneuropathies can be classified into two main types: primarily demyelinating or axonal. 

Demyelinating Polyneuropathies:

• In these conditions, the myelin sheath (the protective covering around nerve fibers) is damaged or lost.
• Clinical features may include acute-to-subacute onset, asymmetry, non-length dependence, motor-predominant signs, and associated systemic features.
• Nerve conduction studies and electromyography help categorize the polyneuropathy as primarily demyelinating.
• Examples of demyelinating polyneuropathies include chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other immune-mediated neuropathies.

 

Axonal Polyneuropathies:

• In these conditions, the nerve fibers themselves (axons) are damaged or degenerate.
• Axonal polyneuropathies can be motor or sensory predominant, and sometimes a mixed pattern is observed.
• Electrodiagnostic testing often reveals axonal degeneration with secondary demyelination in motor nerves more than sensory nerves.
• Examples of axonal polyneuropathies include diabetic polyneuropathy (which can have both demyelinating and axonal components) and other acquired or hereditary neuropathies.
  •  

3. Classification Based on Area of Dysfunction

Motor Fiber-Affected Polyneuropathies:

• Immune-Mediated Disorders: Examples include Guillain-Barré syndrome and multifocal motor neuropathy with conduction block.
• Lead Toxicity: Exposure to lead can lead to motor nerve dysfunction.
• Tick Bite: Certain tick-borne infections can affect motor fibers.
• Porphyria: A group of rare genetic disorders that can impact motor nerves.
• Spinal Muscular Atrophy: Although primarily a motor neuron disorder, it can mimic motor polyneuropathy.
  •  

Sensory Fiber-Affected Polyneuropathies:

• Dorsal Root Ganglionitis of Cancer: Cancer-related inflammation affecting sensory nerves.
• Leprosy: A chronic infectious disease that damages sensory nerves.
• AIDS: Human immunodeficiency virus (HIV) infection can lead to sensory neuropathy.
• Diabetes Mellitus: Chronic high blood sugar levels can cause sensory polyneuropathy.
• Chronic Pyridoxine Intoxication: Excessive vitamin B6 intake can harm sensory nerves.
  •  

Polyneuropathies Affecting Cranial Nerves:

• Guillain-Barré Syndrome, Lyme Disease, and Diabetes can involve cranial nerves.
• Diphtheria is another infectious cause affecting both peripheral and cranial nerves.
  •  

 

4. Toxin neuropathies result from exposure to various toxic substances that damage peripheral nerves. These toxins can affect nerve function, leading to sensory, motor, or autonomic symptoms.

Common Toxins and Their Mechanisms:

 

• Heavy Metals (e.g., lead, mercury, arsenic):
  • Lead neuropathy: Inhibits enzymes involved in myelin synthesis, causing demyelination.
  • Mercury: Damages axons and Schwann cells.
  • Arsenic: Causes axonal degeneration.
• Organophosphates (e.g., pesticides):
  • Inhibit acetylcholinesterase, leading to excessive acetylcholine at neuromuscular junctions.
  • Symptoms: Weakness, fasciculations, and respiratory failure.
• Alcohol:
  • Alcoholic neuropathy: Axonal degeneration due to direct toxicity and nutritional deficiencies.
  • Vitamin B12 deficiency (common in alcoholics) exacerbates neuropathy.

• Chemotherapy Drugs:
  • Platinum compounds, taxanes, and vinca alkaloids can cause neuropathy.
  • Mechanisms: Axonal degeneration, mitochondrial dysfunction, and oxidative stress.
• Industrial Solvents (e.g., hexane, n-hexane):
  • Distal symmetric polyneuropathy due to axonal damage.
• Snake Venom:
  • Neurotoxic snake bites can cause rapid paralysis by blocking neurotransmitter release.

     

 

Clinical Presentation:

• Symptoms: Vary based on the toxin and affected nerve fibers.
  • • • Sensory neuropathy: Numbness, tingling, burning pain.
      • Motor neuropathy: Weakness, muscle atrophy.
      • Autonomic neuropathy: Orthostatic hypotension, gastroparesis.
• Physical Examination:
• • • • Loss of deep tendon reflexes (demyelinating neuropathy).
      • Distal muscle weakness (axonal neuropathy).

Diagnosis:

• Detailed History: Exposure to toxins, occupational history, alcohol use.
• Nerve Conduction Studies (NCS):
  • • Demyelinating neuropathy: Prolonged distal latencies, slowed conduction velocities.
    • Axonal neuropathy: Reduced compound muscle action potentials (CMAPs).
• Electromyography (EMG): Detects denervation and assesses muscle activity.

 

Management:

• • Remove Exposure: Identify and eliminate the toxin source.
  • Supportive Care: Pain management, physical therapy.
  • Vitamin Supplementation (e.g., B vitamins for alcohol-related neuropathy).
  • Antioxidants (e.g., alpha-lipoic acid) may help in some cases.

 

5. Deficiency neuropathies result from inadequate levels of essential nutrients, particularly vitamins and minerals. These deficiencies impair nerve function, leading to various neurological symptoms.

Types of Deficiency Neuropathies:

• Vitamin B1 (Thiamine) Deficiency:
  • • Beriberi syndrome: Presents as a progressive axonal sensorimotor peripheral neuropathy.
    • Skin changes (atrophy) are also common.
• Vitamin B12 Deficiency:
  • • Causes a demyelinating neuropathy.
    • Associated with pernicious anemia.
• Vitamin B6 (Pyridoxine) Deficiency:
• • • Can lead to sensory neuropathy.
    • Often seen in alcoholics.

• Vitamin E Deficiency:

• • • Causes a demyelinating neuropathy.
    • Rare but important to recognize.
• Vitamin D Deficiency:

• • • May contribute to neuropathic symptoms.
• Mineral Deficiencies:

• • • Copper deficiency: Associated with axonal neuropathy.
    • Zinc deficiency: Can cause sensory neuropathy.

Clinical Presentation:

• Symptoms:
  • • Weakness, numbness, and pain (usually in hands and feet).
    • Digestive and urinary disturbances.
• Physical Examination:
• • • Loss of deep tendon reflexes (demyelinating neuropathy).
    • Distal muscle weakness (axonal neuropathy).

Diagnosis:

• Detailed History:

• • • Explore dietary habits, alcohol use, and underlying conditions.
• Laboratory Tests:

• • • Measure vitamin and mineral levels.
    • Serum B12, folate, and vitamin D assays.
    • Nerve Conduction Studies (NCS) and Electromyography (EMG).

Treatment:

• Address the Underlying Deficiency:
  • • Supplement the deficient nutrient (e.g., B vitamins, vitamin D).
    • Modify diet to include rich sources of essential nutrients.
• Monitor Progress:
• • • Regular follow-up to assess improvement.

Remember, accurate diagnosis and understanding the underlying cause are essential for effective management.

 

References:

1 msdmanuals.com

2 healthline.com

3 pn.bmj.com

4 uptodate.com