Diagnosing and Managing Peripheral Neuropathy

Clinical Assessment and Diagnosis

The diagnosis of peripheral neuropathy is primarily clinical, based on a detailed history and focused neurological examination, with nerve conduction studies reserved for cases with asymmetric patterns, uncertain diagnosis, or when distinguishing axonal from demyelinating pathology is critical for management, as recommended by the American College of Physicians 1, 2
Large fiber involvement is characterized by numbness, loss of vibration sense, impaired proprioception, and "glove and stocking" distribution of sensory loss, according to the American Academy of Neurology 1, 2
Small fiber neuropathy is characterized by burning feet/hands, lancinating pain, dysesthesia, allodynia, and hyperalgesia, with standard neurophysiology often being completely normal in these cases, as noted by the American Academy of Neurology 2, 4
Motor involvement is characterized by distal weakness, muscle atrophy in feet, reduced/absent deep tendon reflexes, tremor, or cramps, as described by the American College of Physicians 1, 5
Autonomic symptoms include constipation, postural hypotension, bladder dysfunction, delayed gastric emptying, or reduced heart rate variability, according to the American Autonomic Society 2, 4

The American College of Physicians recommends ordering baseline laboratory tests, including fasting blood glucose and hemoglobin A1c, to identify treatable causes of peripheral neuropathy 3
The American Academy of Neurology suggests considering neurophysiology in specific scenarios, such as asymmetric pattern of symptoms, normal clinical examination despite patient complaints, or need to distinguish axonal from demyelinating neuropathy 1, 2, 4
Axonal degeneration is characterized by progressive reduction of sensory nerve action potential amplitude, followed by impaired nerve conduction velocity, as described by the American Academy of Neurology 1, 5
The American Academy of Neurology recommends skin biopsy as the gold standard for diagnosing small fiber neuropathy, demonstrating degeneration of small C and Aδ fibers 2, 5, 4

The American Diabetes Association recommends screening all patients with type 2 diabetes at diagnosis and patients with type 1 diabetes starting 5 years after diagnosis, then annually thereafter, for diabetic neuropathy 6, 3
The American College of Physicians suggests optimizing glucose control to prevent or delay neuropathy development in type 1 diabetes and slow progression in type 2 diabetes 6, 3
The American Academy of Neurology recommends pregabalin, duloxetine, or gabapentin as initial pharmacologic treatments for neuropathic pain, with duloxetine at 60 mg once daily, pregabalin at 300-600 mg/day, and gabapentin at 300-2,400 mg/day 6, 3, 7