Peripheral Neuropathy

Peripheral neuropathy is the term used to describe damage to the peripheral nerve cells. It may be a complication of the myeloma or a result of the side effect of anti-myeloma treatments. Nurses play a key role in the prevention, assessment and management of myeloma patients with peripheral neuropathy and patient education is crucial. Peripheral neuropathy is a serious and potentially debilitating complication and side effect of treatment which if not managed correctly, can lead to a significant decrease in patients’ quality of life and interruption in their treatment. Regular assessment by nurses is important to reduce the risk of permanent neurological damage through timely intervention such as dose reduction or treatment pause/change.

Approximately 15% of patients are estimated to have symptoms of peripheral neuropathy at the time of diagnosis but a further 80% develop some degree of this potentially debilitating condition at some point during the course of their myeloma. Risk factors include duration and dose of certain treatments, comorbidities such as diabetes, alcoholism, nutritional deficiency, HIV or pre-existing neuropathy.

The exact cause of myeloma-related neuropathy is not known but may be due to the toxic actions of paraproteins causing inflammation, injury or degeneration of the peripheral nerve fibre. It may also result from the compression of the spinal cord or nerve roots by a plasmacytoma. In some patients, hyperviscosity caused by excessive paraprotein levels in the blood may also lead to symptoms of neuropathy.

For the majority of myeloma patients, their treatment, particularly ixazomib, thalidomide and bortezomib, is the main cause of peripheral neuropathy. Evidence indicates that such treatment-induced neuropathy is dose-related. Therefore, modifying the dose and/or schedule as early as possible can, in most cases, reduce symptoms and reverse damage.

The symptoms of peripheral neuropathy vary depending on the type of nerve that is affected. The clinical consequences of peripheral neuropathy involving the major nerve types are:

Sensory neuropathy

• Paraesthesia symptoms
• Tingling, numbness, burning, sensitivity to touch
• Pain
• Impaired muscle tone
• Poor coordination and position sense
• Hearing loss, tinnitus

Motor neuropathy

• Muscle cramps
• Muscle tremors, poor coordination
• Muscle weakness, mobility changes

Autonomic neuropathy

• Bradycardia
• Orthostatic/postural hypotension
• Constipation
• Urinary bladder dysfunction
• Erectile dysfunction

Assessment of peripheral neuropathy

Patients should undergo an accurate neurological assessment at baseline before the start of treatment and then at regular intervals during treatment.

The initial assessment should identify patients at an increased risk of, or who already have pre-existing neuropathy caused by the myeloma itself or other comorbidities. It is important then to repeat assessment preferably before the start of each new treatment cycle so that any new or worsening neuropathy can be detected as early as possible. Assessments should also be continued even after treatment has stopped, particularly if the last treatment was thalidomide.

Several general neurotoxicity assessment tools are available but no standardised measure of peripheral neuropathy exists. Grading the severity of symptoms is considered to be the most important criteria for an objective assessment to be made, and several tools have been designed for this particular purpose, such as the Functional Assessment of Cancer Therapy/Gynaecology Oncology Group Neurotoxicity Questionnaire (FACT/GOG-Ntx) and the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5 (Table 8). This allows different members of the multidisciplinary team to assess the same patient accurately. Note, events greater > grade 2 must be referred to the medical team.

Nurses are ideally placed to engage in dialogue with their patients about any signs or symptoms they might have. It is important to note that some patients may be hesitant to report their symptoms out of fear that their treatment may be stopped or modified. Nurses must reassure their patients that dose-modifications do not necessarily compromise treatment effectiveness and explain that unreported symptoms will greatly increase the likelihood that the neuropathy may progressively worsen. Read more about how to assess and manage this complication in our Myeloma Nurse Guide: Peripheral Neuropathy.

Table 8: Grading of peripheral neuropathy, NCI CTCAE (5.0)

Management of peripheral neuropathy

There is no treatment as such for peripheral neuropathy but symptoms should improve with ongoing conventional anti-myeloma treatment if it is related to the myeloma.

If the neuropathy is caused by anti-myeloma treatment, then prompt action is essential. The severity, based on the NCI CTCAE grading system, should be established and one of the following carried out:

• Dose reduction
• Schedule modification
• Temporary suspension of treatment until < grade 1 severity reached, or discontinued
• Change from intravenous to subcutaneous route of administration (Bortezomib)

For many patients, neuropathy can cause varying degrees of pain. However, it is well recognised that neuropathic pain responds poorly to standard analgesics. Opioids can be effective but at high doses, are associated with significant side effects. Pain-modulating treatments (gabapentin, pregabalin) or antidepressants (amitryptiline, duloxetine) are more effective in relieving neuropathic pain. Topical treatments (e.g. lidocaine cream, capsaicin- or menthol-based creams) can be effective for painful skin areas.

Patients who do not respond well to their prescribed pain relief should be referred to the pain specialist/palliative care team.

Some patients may also benefit from non-pharmacological approaches to relieve the symptoms of peripheral neuropathy. Based upon anecdotal evidence, the following are considered to be effective which nurses can recommend to their patients:

• Daily vitamin and nutritional supplements e.g. multi-B complex vitamins, folic acid, vitamin E, a-lipoic acid
• Quinine tablets or tonic water for cramp
• Emollient creams e.g. cocoa butter, eucalyptus-based creams (apply to affected area twice/day with gentle massage)
• Transcutaneous electrical nerve stimulation (TENS) machines to help reduce pain
• Complementary therapies such as acupuncture, reflexology and gentle massage

Nurses play a central role in educating patients and their families about the possible risks of peripheral neuropathy when they start specific treatments. Patients must be informed of the signs and symptoms and know how, when and to whom they should report them to.

Patients should be encouraged to describe their symptoms as accurately as possible and to speak up about the level of pain they have and the impact the neuropathy is having on their quality of life. Where appropriate, nurses should establish whether it is affecting the patients’ ability to perform activities of daily living (dressing, feeding, washing), provide patients with self-care measures, and if necessary make referrals to occupational therapy and/or physiotherapy.

Nurses should be aware they may be required to counsel those patients whose treatment has been suspended. Sometimes patients find it difficult to understand the need to do this particularly if they are responding well to it. It is important patients are assured that a dose reduction or temporary halt to treatment will not cause their myeloma to progress. If treatment is to be discontinued, then patients should be informed of alternative options.

By implementing appropriate timely management, nurses can help maintain quality of life and outcomes for patients.

Watch a video clip of Prof Sam Ahmedzai describing how to manage peripheral neuropathy in myeloma patients:

Further reading

Snowden et al., (2017) Guidelines for screening and management of late and long-term consequences of myeloma and its treatment. B J Haem. 176 (6) 888-907.