Peripheral Nerve Disease

Peripheral nerve disorders are common conditions affecting approximately 2.4% of the population

Prevalence increases with age to up to 8% of the population

Altered sensation including numbness, pain, and paresthesia if a sensory nerve is involved

Weakness (distal more than proximal) if a motor nerve is involved

Altered pain and temperature sensation if small fibers are primarily affected

Autonomic dysfunction such as orthostatic hypotension may ensue if autonomic nerves are involved

When large fibers are the main target of the disease process, there is loss of tendon reflexes, touch and pressure sensation, proprioception, and weakness

Clinical patterns of neuropathy

• Mononeuropathy—only one nerve involved in the disease process

• Mononeuritis multiplex—multiple randomly distributed nerves involved in the disease process

• Polyneuropathy—multiple nerves involved with symmetrical, distal greater than proximal distribution

• Radiculopathy—nerve root involvement with a dermatomal distribution of dysfunction

Electrodiagnostic studies are useful to define the distribution and pattern of peripheral nerve involvement and to characterize the underlying pathologic process into axonal (low action potential amplitudes) versus demyelinating (slow conduction velocity or conduction block)

Depends on the specific disease process

There are no specific imaging findings that help with the diagnosis of neuropathy

Demyelination and remyelination

• Schwann cell dysfunction or damage to the myelin sheath results in loss of myelin along one or more segments of the nerve fiber

• Myelin debris is initially engulfed by Schwann cells and later by macrophages

• The unaffected denuded axon provides a stimulus for recovery

• The initial step in remyelination involves Schwann cell proliferation and spread along the denuded axon

• Remyelinated internodes are shorter than normal

• The new myelin sheath is thin in proportion to the diameter of the axon

• Repetitive episodes of demyelination/remyelination result in “onion bulbs,” which represent concentric deposition of Schwann cell cytoplasm and redundant basement membrane around a thinly myelinated axon

• Chronic demyelinating neuropathies eventually lead to some degree of axonal damage

Axonal degeneration and regeneration including Wallerian degeneration

• Axonal injury may result from a focal event (e.g., trauma or ischemia) affecting a specific nerve or from a generalized process affecting the neuron cell body (neuronopathy) or its axon (axonopathy)

• When axonal damage results from a focal insult to the nerve, the distal portion undergoes Wallerian degeneration with all the involved nerve fibers undergoing degradation simultaneously

• In axonopathies, axonal degeneration occurs in a retrograde (“dying back”) direction and reflects the accumulated effect on individual fibers randomly over time

• With primary injury to the axon, there is secondary degradation of myelin; myelin ovoids represent compartments within the Schwann cell cytoplasm containing fragments of axons and myelin

• Later macrophages also participate in phagocytosis of axonal and myelin debris

• Axonal regeneration is accompanied by extensive Schwann cell proliferation

• Regenerative clusters are groups of closely aggregated, thinly myelinated, small diameter axons that sprout from the regenerating axon

• In chronic axonal neuropathies, there is little evidence of axonal regeneration with associated marked loss of large myelinated fibers and fibrosis

• Abundant collagen pockets are seen when there is prominent loss of small unmyelinated fibers

Prominent inflammation occurs in inflammatory demyelinating neuropathies or vasculitic neuropathies

Immunostudies for subtyping and characterization of the inflammatory infiltrate if present

Toluidine blue–stained, resin-embedded thin sections allow for better evaluation of the myelin sheath and axonal changes than hematoxylin and eosin (H&E)–stained paraffin-embedded sections

Electron microscopy is necessary for evaluation of the small unmyelinated fiber system

Amyloid stains (Congo red) for amyloid neuropathy

Neuropathies can be classified based on the main pathologic process into axonal neuropathies, demyelinating neuropathies, or mixed neuropathies

• Examples of axonopathies include vasculitis; trauma; diabetic neuropathy; drug toxicity; alcoholic neuropathy; amyloid neuropathy; hypothyroidism; polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS); and hereditary axonal neuropathies such as Charcot-Marie-Tooth disease type 2

• Examples of demyelinating neuropathies include autoimmune demyelination (Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy), hereditary demyelinating neuropathies such as Charcot-Marie-Tooth disease type 1, paraproteinemic neuropathy, and diphtheric neuropathy

The pathologic changes described here are nonspecific and may be seen in neuropathies of varied etiologies

Only a small group of peripheral neuropathies show disease-specific pathologic features including vasculitis, amyloid neuropathy, leprosy, sarcoid, hereditary motor and sensory neuropathies, and neuropathy associated with neoplasms