Managing Peripheral Neuropathy

Assistant professor of neurology at the University of Michigan Health System in Ann Arbor, Michigan

How does peripheral neuropathy manifest?

Peripheral neuropathy usually causes numbness, tingling, pain, and weakness that starts in the toes and rises to the level of the knees, before starting in the hands. Atypical neuropathies can be asymmetric, motor-predominant, start in the hands and feet at the same time, and cause autonomic symptoms. Symptoms and clinical presentation of treatment-emergent peripheral neuropathy can also differ based on the type of treatment.

Do you treat many patients experiencing peripheral neuropathy who also have hematologic disease?

We do see many patients with peripheral neuropathy as a result of hematologic diseases or the treatments for these conditions. As hematologists/oncologists very well know, many chemotherapeutic agents can cause neuropathy; chemotherapy-induced peripheral neuropathy is the most common scenario in which patients with hematologic malignancies develop this condition.

Peripheral neuropathy is also a frequent complication of plasma-cell disorders, such as multiple myeloma, amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, and Waldenström macroglobulinemia. In these cases, the peripheral nerves are one of many involved sites of the disease. The hematologic condition most commonly associated with peripheral neuropathy is monoclonal gammopathy of unknown significance (MGUS).

Patients with peripheral neuropathy have a high prevalence of monoclonal proteins; therefore, guidelines from the American Academy of Neurology recommend routine serum protein electrophoresis (SPEP) testing with immunofixation in these patients.

Peripheral neuropathy is a common complication of hematologic disease – is there a causal relationship?

The current understanding is that the proteins associated with the hematologic diseases noted previously are directly pathologic to the nerves. We are in need of better information about factors that predispose patients to peripheral neuropathy. However, there are several known variables and comorbidities also associated with its development: the presence of diabetes mellitus, alcohol abuse, vitamin deficiencies, and viral infections.

What do hematologists need to know about preventing peripheral neuropathy?

Prevention of peripheral neuropathy is essential for maintaining the patient’s quality of life and functional ability. Because peripheral neuropathy is a frequent and dose-limiting side effect of anti-cancer treatment, preventing this complication is important to preserve treatment efficacy.

The key to preventing peripheral neuropathy is understanding the risks of chemotherapy known to cause this common condition, and using the lowest dose possible that will still provide clinical benefit.

Prevention of treatment-emergent peripheral neuropathy requires close and frequent monitoring. If treatment-emergent peripheral neuropathy occurs, there are two things that a hematologist can do to limit nerve injury with chemotherapy or anti-cancer drug: lower the dose of the drug or stop treatment.

Standard of care includes using specific algorithms to modify the drug dose and dosing schedule among patients who have developed peripheral neuropathy.

Identifying peripheral neuropathy early is important to the risk/benefit calculation of whether to continue the chemotherapy. Early detection of treatment-related peripheral neuropathy is required for timely and appropriate intervention. Hematologists/oncologists are likely familiar with patient-focused screening and grading tools, such as the Functional Assessment of Cancer Therapy Neurotoxicity, the National Cancer Institute’s common terminology criteria for neuropathy, and the reduced Total Neuropathy Score to monitor patient symptoms, but in addition, hematologists should perform regular examinations to monitor for any neuropathic symptoms, evaluating sensation (touch, pain, temperature, etc.), distal muscle strength, and reflexes in their patients.

Certain algorithms also call for assessing symptoms with electrophysiologic measurements (such as nerve-conduction studies and needle electromyography) to detect neurologic damage and quantify the severity of neuropathy.

All patients should be evaluated for clinical signs and symptoms of peripheral neuropathy before they receive any neurotoxic drug. If a patient does develop peripheral neuropathy, close and frequent monitoring is even more important; these patients are at risk for developing more severe peripheral neuropathy with anti-cancer treatment.

How can hematologists help patients manage treatment-emergent peripheral neuropathy?

Treatment of peripheral neuropathy is focused on managing neuropathic pain, including pharmacologic pain management and supportive care. The treating physician, nursing staff, and the neurologist should work together to manage the pain.

Patients with severe peripheral neuropathy may also experience difficulties with daily tasks and may benefit from physical exercise or physiotherapy.

Pharmacologic options include six medications with high-level evidence to support their use in this setting, including anti-convulsants (gabapentin and pregabalin) and anti-depressants (amitriptyline, nortriptyline, venlafaxine, and duloxetine). Gabapentin and pregabalin are the most commonly prescribed first-line treatment; they are well-tolerated and have demonstrated efficacy in managing painful diabetic neuropathy, as well. However, treatment choice is dependent on patient age, drug interactions, and patient comorbidities. In patients with coexisting depression, for instance, anti-depressants may be the first drug of choice.

Opioids are also commonly used to help patients maintain or regain function and minimize pain.

When should the hematologist refer to the neurologist? And vice versa?

Hematologists should refer to neurologists when neuropathic pain is hard to control with the medications listed above.

When a patient is experiencing neuropathy that is not typical for the type of medication, dose, or underlying disorder, he or she should also be referred to the neurologist (for instance, when neuropathy progresses months after the cessation of chemotherapy).

Other reasons for referral are when patients have atypical features such as asymmetry, motor predominance, non-length dependence, and autonomic symptoms.

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