Clinical meaning
Peripheral neuropathy refers to damage or dysfunction of the peripheral nerves (those outside the brain and spinal cord), resulting in sensory, motor, or autonomic symptoms depending on which nerve fibers are affected. It is extremely common, affecting up to 8% of the general population and up to 50% of patients with diabetes.
Peripheral nerves contain three types of fibers: sensory (carrying touch, pain, temperature, and position information from the body to the brain), motor (carrying movement commands from the brain to muscles), and autonomic (controlling involuntary functions like blood pressure, heart rate, digestion, and sweating). Neuropathy can affect any combination of these fiber types.
The two main patterns of nerve damage are axonal degeneration and demyelination. In axonal degeneration (the most common), the axon itself is damaged, typically starting at the most distal portions (the longest nerves are affected first). This produces the characteristic stocking-glove distribution where symptoms begin in the toes and feet, progress to the ankles and calves, and eventually involve the fingertips and hands. The pathophysiology involves metabolic damage to the axon from hyperglycemia (diabetic neuropathy), toxins (alcohol, chemotherapy), nutritional deficiencies (B12, thiamine), or ischemia.
In demyelinating neuropathy, the myelin sheath is damaged while the axon is preserved initially. This produces motor weakness and areflexia more prominently than sensory symptoms. Guillain-Barre syndrome is the classic acute demyelinating neuropathy.
Diabetic peripheral neuropathy, the most common form, occurs through several mechanisms: hyperglycemia activates the polyol pathway, converting glucose to sorbitol which accumulates in nerve cells and causes osmotic damage. Advanced glycation end-products (AGEs) damage nerve proteins and blood vessel walls. Microvascular disease reduces blood supply to peripheral nerves (vasa nervorum), causing ischemic nerve injury.