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9 Articles in Volume 13, Issue #3
Comprehensive Rehabilitation of the Cancer Pain Patient
Neuropathy in the Cancer Patient: Causes and Cures
The Basics of Breakthrough Pain: Transmucosal Fentanyl
The Use of Botulinum Toxin in Migraines: A Review
Complex Regional Pain Syndrome: Systemic Complications
Diagnostic Ultrasound in Carpal Tunnel Syndrome: A Helpful Additional Tool
The Homebound Adolescent Headache Patient
Editor's Memo: Neurosteroids—Gaining Ground In Pain Management Research
Ask the Expert: Monitoring Liver Function

Neuropathy in the Cancer Patient: Causes and Cures

Identifying the causes of neuropathy in cancer patients can be difficult. This review looks at the common causes of neuropathy in cancer patients, as well as effective therapies—and even preventions.
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Neuropathic pain is often defined as pain caused by a lesion or disease of the somatosensory nervous system. Peripheral neuropathies arise from disorders associated specifically outside the central nervous system (CNS) and within the peripheral nervous system.1 Symptoms of peripheral neuropathy include numbness, tingling, paresthesia (pins and needles sensations), sensitivity to touch, or muscle weakness. In patients with extreme symptoms, they may present with burning pain, muscle wasting, paralysis, or organ dysfunction.1

There are multiple causes of peripheral neuropathy, and in the cancer patient, identifying the culprit may be complicated by a plethora of etiologies. This review will focus on potential origins of neuropathic pain in the cancer patient, including both disease- and drug-induced peripheral neuropathy; current treatment modalities of cancer-induced peripheral neuropathy (CIPN); and how to prevent the development of peripheral neuropathy in cancer patients. According to the American Cancer Society, about 11.9 million Americans suffer from cancer pain, but it remains unclear what portion of that pain is specifically neuropathic versus somatic, visceral, or a combination. It also is equally unclear what percentage of these cases is due to disease, treatments, or both.2

Cancer-induced Peripheral Neuropathy

By virtue of the nature of the disease, cancer alone can cause neuropathy. Certain neuropathies can develop due to remote or paraneoplastic effect; invasion of the cancer or compression of the nerves; or as a side effect secondary to treatment.3 The cancers commonly associated with neuropathies are listed in Table 1. This section focuses on the role of CIPN in the cancer patient.

Paraneoplastic encephalomyelitis/sensory neuronopathy (PEN/SN) is a type of neuropathy most commonly associated with lung cancer, typically small-cell lung cancer. Unlike other types of pain syndromes, PEN/SN is not due to the effects of the tumor itself, metastasis, treatment, infection, or metabolic abnormalities. Rather, it is thought to be a result of "remote effects" of the cancer that lead to the production of antibodies or inflammatory cells against any neural antigens that the tumor may express.4 The symptoms can be acute or progressive. Patients typically present with numbness and parasthesias in the distal extremities, usually unilaterally. Eventually, this type of neuropathy may result in loss of proprioception and sensory ataxia. Oftentimes, these patients develop confusion, memory loss, depression, hallucinations, seizures, and/or cerebellar ataxia. Treating the underlying cancer does not always affect the clinical course of PEN/SN. Some patients may occasionally improve after the tumor has been treated. Other treatments such as plasmapheresis, intravenous immunoglobulin, and immunosuppressive agents have not shown any greater benefit.3,4

Tumor Infiltration
Peripheral neuropathy may develop secondary to tumor infiltration. Leukemia and lymphoma cells can infiltrate the cranial and peripheral nerves; the result can be mononeuropathy, mononeuropathy multiplex, polyradiculopathy, or plexopathy as a complication. This neuropathy is generally painful and may be an indication of newly diagnosed cancer and/or disease progression. The symptoms can be managed by treating the underlying hematological malignancy or by initiating glucocorticoids if not contraindicated.3

Lymphoma most often causes neuropathy either by infiltration or direct compression of nerves, or by a paraneoplastic process.3 Most peripheral complications are due to non-Hodgkin's lymphoma (NHL).5 Hodgkin's lymphoma, on the other hand, rarely causes neuropathy; it generally causes immunological disorders of the peripheral nervous system such as inflammatory plexopathy or Guillain-Barré syndrome.5 Although the NHL neuropathy may manifest as a sensory or motor symptom, it is commonly seen as a sensorimotor neuropathy. The course of the neuropathy may be acute, gradually progressive, or relapsing and remitting. The neuropathy may respond to the treatment of the underlying lymphoma.5

Multiple Myeloma
Multiple myeloma (MM) is a common hematologic malignancy associated with monoclonal gammapathy. About 40% of patients with MM develop some type of peripheral neuropathy. Patients may develop painful paresthesia and loss of differentiating between pinprick and temperature sensations. The mechanism of the neuropathy is primarily due to amyloidosis with infiltration of the nerves. It is also thought to be due to the metabolic or toxic effects of the systemic consequences of renal failure.3,5

Waldenström's Macroglobulinemia
Waldenström's macroglobulinemia is a cancer of the B lymphocytes. It is caused by a malignant proliferation of lymphoplasmacytoid cells, which produces an overabundance of immunoglobulin M monoclonal proteins with a κ light chain—causing the blood to become hyperviscous. The mechanism of neuropathy is unknown, but it's thought to be related to myelin-associated glycoprotein antibodies. However, a causal relationship has not been confirmed.6

Solid Tumors
The most common solid tumors associated with peripheral neuropathy include breast cancer and lung cancer as reported in case reports and in a prospective, multicenter study in radiotherapy oncology units.7,8

Bone Marrow Transplantation
Although not a neoplasm, bone marrow transplantation (BMT) is a treatment for certain malignancies, which may cause neuropathy. Peripheral neuropathy associated with BMT usually occurs concurrently with chronic graft-versus-host disease (GVHD). Chronic GVHD is a clinical syndrome that occurs in approximately 60% to 80% of long-term survivors of allogeneic hematopoietic stem cell transplantation.3 Chronic GVHD is defined as an autoimmune disorder that occurs 100 days after the allogeneic transplant. Symptoms of chronic GVHD usually include oral ulcerations; keratoconjunctivitis; xerophthalmia; hepatic failure; obstructive lung disease; involvement of the skin and soft tissues; and involvement of the neuromuscular system, CNS, and the gastrointestinal tract.9 These features are shared with a variety of autoimmune disorders, and it is possible that the etiology of this peripheral neuropathy is an immune-mediated response directed against the peripheral nerves. Patients may develop cranial neuropathies, sensorimotor polyneuropathies, multiple mononeuropathies, and severe generalized neuropathies. Symptoms may improve when the intensity of the immunosuppressive therapy for GVHD is increased.3

Last updated on: October 28, 2014

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