Definition of Chemotherapy-Induced Peripheral Neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is defined as somatic or autonomic signs or symptoms resulting from damage to the peripheral nervous system (PNS) or autonomic nervous system (ANS) caused by chemotherapeutic agents.² CIPN tends to be worse in patients with pre-existing nerve entrapments or neuropathies.³ It has been reported that 30% to 40% of patients receiving chemotherapy experience CIPN, and as more aggressive pharmacological agents are developed and survival rates increase in the future, this number is projected to grow.

Quality of life is adversely affected by CIPN, and symptoms can interfere with treatment resulting in a reduction of dosage or even discontinuation of life-sustaining medications.⁴ This is called a dose limiting factor. Currently there are no proven methods to treat CIPN.

Anatomy and Physiology Related to Chemotherapy-Induced Peripheral Neuropathy

Peripheral nerves are comprised of nerve fibers with varied myelination, morphology, functions, and chemical features. These differing fibers vary in their resistance to and response to the toxicity of chemotherapy drugs. Most nutritional, metabolic, and toxic neuropathies are axonopathies, meaning the pathology is axonal. The axon or the Schwann cell is typically the site of lesion.²

Any portion of the PNS or the central nervous system (CNS) or even muscle can be injured by anticancer drugs. Symmetrical distal polyneuropathy is the most common pattern of symptoms. Other patterns of peripheral nerve disease in CIPN are radiculopathy, plexopathy, polyradiculoneuropathy, mononeuropathy, and multiple mononeuropathy (also known as mononeuritis multiplex).

Symptoms

In CIPN, allodynia (experiencing pain with stimuli that is not typically painful) occurs especially in response to hot or cold. Motor impairment occurs less frequently and usually has a later onset. Purely autonomic symptoms are uncommon, but some autonomic involvement combined with PNS involvement is common.

Fine motor skills are affected, impairing activities, such as buttoning, donning earrings, doing clasps, and handling or manipulating small objects. Sensory ataxia is more severe when the eyes are closed or the lighting is low. Proprioceptive sensory disturbances also occur, as demonstrated by Romberg sign, which is a loss of balance that occurs when the patient stands with the eyes closed. Motor neuropathy presents with signs of weakness, cramps, atrophy, and fasciculation. Like sensory symptoms, the onset is typically distal. Findings of proximal weakness may be indicative of another condition, so be sure to mention this finding to the referring provider.

Nociceptive pain is defined as pain that is caused by structural dysfunction, such as a fracture. Neuropathic pain is defined as pain that is caused by peripheral nerve dysfunction and is typically sensory pain. This type of pain is difficult for patients to describe in words.

Small Fiber Neuropathy

Most CIPNs are described as mixed fiber neuropathies because there is involvement of both large and small fibers. Small fiber neuropathy is a result of damage to A-delta and C fibers, which are the smallest unmyelinated fibers. These fibers carry sensations of temperature and dull pain. Patients with small fiber neuropathy have intense neuropathic pain that is worse than those with large fiber neuropathy. They also demonstrate autonomic symptoms because autonomic fibers are small non-myelinated fibers. It is harder to clinically diagnose small fiber neuropathy than large fiber neuropathy in part because nerve conduction studies examine only large fibers that are myelinated and fast conducting.

Chemotherapy-Induced Peripheral Neuropathy Symptom Timeline

Symptoms of CIPN may disappear when the chemotherapeutic agents are discontinued, but some symptoms may persist even after the medications have been stopped. This is called the coasting phenomenon, which is a result of slow physiopathology or slow drug clearance.

Chemotherapeutic Agents Involved in Chemotherapy-Induced Peripheral Neuropathy

Certain chemotherapeutic agents have been identified as drugs that contribute to CIPN. At the time of this writing, they include microtubule-stabilizing agents (MTSAs), platinum compounds, cisplatin, oxaliplatin, carboplatin, vinca alkaloids, proteasome inhibitors, thalidomide, and lenalidomide.

Diagnosis of Chemotherapy-Induced Peripheral Neuropathy

Simple clinical assessments are usually sufficient to diagnose CIPN. As noted earlier, nerve conduction studies are useful in identifying large myelinated fast conduction nerve involvement, but they do not identify small fiber dysfunction. In the oncology literature, scales of symptom severity describe levels of impact on ADLs. One such scale is the National Cancer Institute Grading: Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 that scores neuropathic pain with grades 1-4.⁶ Another scale is the Total Neuropathy Scores (TNS) that reflects sensory, motor, autonomic, and strength symptoms with grades 1-4.² The National Cancer Institute Common Toxicity Criteria–Version 3 scores motor and sensory symptoms with grades 1-5.¹

Neuroplasticity

Hand therapists are experts on sensory reeducation and desensitization. These treatment programs are based on concepts of neuroplasticity, which refers to the fact that our brains can be reorganized neuronally in response to stimuli. Neuroplasticity involves learning, habituation, memory, and cellular recovery.7,8 Key concepts of neuroplasticity are:

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