Paraproteinemic Neuropathy: A Practical Review

Richard A. Rison; Said R. Beydoun

Disclosures

BMC Neurol. 2016;16(13) 

In This Article

Symptomatic Treatment Strategy

Symptomatic treatment of the neuropathy itself usually involves membrane stabilizers, tricyclic anti-depressants, and/or serotonin-norepinephrine reuptake inhibitors. Guidelines from the American Academy of Neurology summarize evidence-based information on pharmacologic and nonpharmacologic treatments for painful neuropathy.[59]

Gabapentin

A structural analogue of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), gabapentin is a first line treatment for neuropathic pain and is effective for a variety of neuropathic pain conditions. It exerts its anti-nociceptive effect by binding the alpha-2 delta calcium channel in the dorsal horn of the spinal cord. It should be used with caution in renal insufficiency; the dose must be adjusted.

Pregabalin

Designed as a more potent successor to gabapentin, pregabalin is effective for a variety of neuropathic conditions. It should be used with caution in renal insufficiency; the dose must be adjusted.

Valproate

Valproate agent should be used with caution in hepatic impairment; dose reduction is required. The US FDA requires a boxed warning to advise of hepatic failure resulting in fatalities and to advise of teratogenic effects, such as neural tube defects, when used in pregnancy.

Dextromethorphan

N-methyl-d-aspartate (NMDA) antagonists such as dextromethorphan block the activation of NMDA receptors, which is contributory to development of central sensitization resulting in hyperalgesia, hyperpathia, allodynia, and reduced functionality of opioid receptors. Side effects may include light-headedness, drowsiness, visual disturbances, and hot flushes; the agent should be used with caution in patients who are sedated or debilitated.[60]

Tramadol

The mixed opioid, mu agonist and inhibitor of uptake of serotonin and norepinephrine, should be used with caution in renal and hepatic impairment; dose reduction is required. In rare instances anaphylactic reactions have been reported. The agent may cause CNS depression, which may impair physical or mental abilities.

Duloxetine

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) used for symptomatic treatment for peripheral neuropathy. It is FDA approved for the treatment of diabetic peripheral neuropathic pain (DPNP). The US FDA requires a boxed warning to advise of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders.

Amitriptyline

Amitriptyline is the most widely used tricyclic antidepressant (TCA), and is used off-label for symptomatic treatment of peripheral neuropathy. The US FDA requires a boxed warning to advise of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder and other psychiatric disorders.

Venlafaxine

The serotonin/norepinephrine reuptake inhibitor (SNRI) venlafaxine is used off-label for symptomatic treatment of peripheral neuropathy. The US FDA requires a boxed warning to advise of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder and other psychiatric disorders. In patients with renal impairment (GFR 10–70 ml/min), reduce total daily dose by 25 to 50 %. In patients with mild to moderate hepatic impairment, reduce total daily dose by 50 %.

Autologous Peripheral Stem Cell Transplantation

As a first line treatment for POEMS syndrome and alternative treatment (in combination with melphalan) for AL, autologous peripheral stem cell transplantation entails administration of myeloablative doses of chemotherapy and/or radiation therapy followed by infusion of peripheral blood stem cells.[61,62]

Granulocyte colony stimulating factor (G-CSF) is given to stimulate peripheral blood stem cells followed by hematopoietic stem cell mobilization four to six days later. Peripheral blood progenitor cells (PBPCs) are mobilized using a variety of techniques. Following initiation of a mobilization regimen, patients are monitored by peripheral blood CD34 counts. Apheresis begins when the peripheral CD34+ counts have reached a target level (i.e., 10 CD34 cells/μl). After completion of the preparative chemotherapy, PBPCs are reinfused. A period of pancytopenia follows and red blood cell and platelet transfusions are administered as necessary while G-CSF is used to speed neutrophil engraftment. Lifelong follow up is necessary to monitor for complications and recurrence. Patients are at risk for bacterial, viral, and fungal infections. Early adverse effects include nausea, vomiting, diarrhea, and mouth sores; later adverse effects include cataracts, sterility, and increased risk of other neoplasias.

Efficacy of the procedure for peripheral neuropathy symptom improvement is based on small case series, and data suggest that most patients achieve at least some neurologic improvement. A small study of 9 patients with POEMS syndrome evaluated the extent and time course of neurologic improvement after autologous peripheral blood stem cell transplantation. Within 3 months, neurologic improvement began, and all the patients showed substantial neurologic recovery during the next 3 months. At the end of follow-up periods (8 to 49 months, median 20 months), neuropathy was still improving and no patients had recurrence of symptoms (level of evidence: 3).[62]

Radiation Therapy

Radiation therapy as a first line treatment for dominant sclerotic plasmacytoma in POEMS syndrome is delivered to osteosclerotic lesions in doses of 40–50 Gy. More than 50 % of patients treated with radiation show improvement of the neuropathy, but improvement in some patients may be delayed, occurring after six months or longer.[31]

Physical, Occupational, Speech, Recreational, and Rehabilitative Therapies

For training in performance of activities of daily living, physical therapy that focuses on compensatory strategies to accommodate for limbs with a loss of sensation and weakness is often done by patients with peripheral neuropathies. Amyloidosis as a paraprotein can cause gastroparesis/dysphagia, which is also seen in CANOMAD and can result from medication toxicity. Speech therapy focused on training in swallowing may attenuate symptoms in patients suffering gastroparesis or dysphagia.[63,64] Recreational therapy helps patients recover basic motor functioning, to build confidence and socialize more effectively. Treatments may incorporate arts and crafts, sports, games, dance, drama, and/or music. Patients with chronic disease, especially the elderly, who are isolated and at risk for depression, may benefit from these therapies, which can improve socialization and diminish isolation.

Orthotics

For the prevention of foot ulcers and infections, orthotics are molded cushion inserts for the foot that distribute pressures, reduce high stress areas, and provide shock absorption.

Acupuncture

A method of Chinese medicine aims to produce analgesia by insertion of sharp, thin needles into the body at very specific points. Acupuncture has produced improvement in both subjective symptoms and objective nerve conduction study findings.[65]

Transcutaneous Electrical Nerve Stimulation (TENS)

TENS is a form of electroanalgesia that reduces pain through nociceptive inhibition at the presynaptic level in the dorsal horn of the spinal cord. A TENS unit consists of 1 or more electrical-signal generators, a battery, and a set of electrodes. The TENS unit is small and programmable, and the generators can deliver trains of stimuli with variable current strengths, pulse rates, and pulse widths. Patients may experience skin irritation due to drying out of the electrode gel. TENS is contraindicated in patients with a demand-type pacemaker.

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