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Neuropathy refers to damage or malfunction of the nerves in the arms and legs (called the peripheral nerves). There are many causes of neuropathy, most of them unrelated with cancer, and therefore non paraneoplastic. For example, there are many neuropathies that are inherited. Diseases of the kidney, liver, gastrointestinal tract, and common diseases like diabetes can all cause neuropathy.
In patients with cancer, peripheral neuropathy may occur as a PND but more frequently it is a result of other complications of cancer, or from side effects cancer treatment, such as chemotherapy or radiation. Patients who receive transplants of organs, bone marrow, or hematopoietic stem-cells may also develop peripheral neuropathies that are not paraneoplastic. Medications used to prevent rejection of transplanted organs or bone marrow, frequently cause neuropathy.
Before deciding that a neuropathy is paraneoplastic, these other more common causes of neuropathy need to be considered. One may think that finding paraneoplastic antibodies in the patients blood will help to clarify whether a neuropathy is paraneoplastic or not, but only a small number of patients (~ about 1 to 2 out of 10) with true paraneoplastic neuropathies have antibodies that are actually useful. The two most useful antibodies are anti-Hu and anti-CV2/CRMP5.
There are two main types of peripheral nerves: motor nerves and sensory nerves. Motor nerves make the muscles move and are important in keeping muscles strong. Sensory nerves allow us to feel different sensation such as touch, pain, vibration, hot and cold. All neuropathies, whether paraneoplastic or not, are classified by the type of nerves affected.
- A neuropathy can affect only motor nerves in which case it is called a motor neuropathy. Patients with motor neuropathies develop weakness of the affected muscles.
- When only the sensory nerves are affected it is called a sensory neuropathy. In this case patients can lose the ability to tell hot from cold and can easily burn themselves in the bath. They can develop numbness and tingling and uncomfortable sensations.
- When both types of nerves are affected, called a sensorimotor neuropathy, patients will have a combination of weakness and sensory problems.
Most neuropathies affect both sides of the body equally and the worse symptoms are in the hands and feet rather than in the hip or shoulders.
It is also important to consider the part of the nerve that is affected. Nerves are like wires with insulation. The wire part is called the axon and the insulation is called myelin. Neuropathies can be axonal when the axon is predominantly affected, or demyelinating when the myelin is predominantly affected. In many types of neuropathies, both the axons and myelin are affected. The main tests that help to assess whether a neuropathy is axonal or demyelinating are the EMG/ nerve conduction velocities and biopsy of the nerve (which is not a routine test). Neuropathies that affect the axon tend to be more severe and difficult to treat than neuropathies that affect the myelin.
In general the treatment for paraneoplastic neuropathies is to treat the tumor and sometimes, give immunotherapy. Immunotherapies may include, corticosteroids, plasma exchange, IVIg.
Patients with diseases of the blood cells such as lymphoma, myeloma (osteolytic or osteosclerotic), and Waldënstrons macroglobulinemia among others often develop a paraneoplastic neuropathy (Table). The treatment and prognosis of the paraneoplastic neuropathies related to these diseases depends on the main disorder (e.g., myeloma, lymphoma, or other) and type of neuropathy (i.e., predominantly axonal or demyelinating). For example, the neuropathy associated with osteosclerotic myeloma is very responsive to treatment of the tumor, while the neuropathy associated with multiple myeloma usually does not respond to treatment.
Table: Disorders of the blood, bone marrow or lymph nodes that associate with neuropathies
Chronic lymphocytic leukemia
Several types of neuropathy
B cell lymphoma
Several types of neuropathy
Patients may develop cryoglobulin-related neuropathy
Several types of neuropathy; may include deposits of amyloid
Neuropathy resembling: chronic inflammatory demyelinating neuropathy.
Frequent association with POEMS syndrome (Polyneuropathy, Organomegaly, Edocrinopathy, M protein, Skin changes)
Predominant distal sensory neuropathy with motor weakness. Tremor and gait problems are often associated.
Patients may develop antibodies against MAG (myelin-associated glycoprotein) or several gangliosides
Castleman´s disease (also called angiofollicular lymph node hyperplasia)
Frequent association with HIV infection, Kaposis sarcoma.
Several types of neuropathy.
May associate with POEMS syndrome (see above)
There are no specific antibody markers that indicate that a neuropathy associated with any of these diseases is paraneoplastic or is related to another problem (for example a side effect of chemotherapy). Some patients with neuropathies that are predominantly demyelinating or associate with antibodies that react with the peripheral nerve (anti-MAG, or anti-gangliosides) may improve significantly after treating the tumor and immunotherapy. A drug called rituximab can be useful for some of these neuropathies.