Pain, Tingling, and Numbness in the Extremities With Foot Drop and Progressive Weakening of the Legs

Sumaira Nabi, MBBS; Rao Suhail, MBBS, FCPS Neurology; Shahzad Ahmed, MBBS


May 19, 2014

These neuropathies most often affect men over age 50 years. Patients usually present with sensory symptoms such as numbness, paresthesia, dysesthesia, and aching or lancinating pain, with these predominantly involving the lower extremities. Touch, joint position, and vibratory sensation are mostly affected. Gait difficulties, imbalance, and ataxia progress over a period of months.[19,20] Weakness of the distal leg muscles with variable atrophy occurs as the disease progresses. A pure motor disorder simulating motor neuron disease is seen in a very small number of patients.[21]

The literature shows that peripheral neuropathy associated with IgM monoclonal gammopathy presents mainly as a chronic demyelinating sensory polyneuropathy, with predominant tremor, sensory loss, and ataxia. Polyneuropathies reported in association with multiple myeloma or with IgG or IgA monoclonal gammopathy are more heterogeneous (mainly axonal or mixed).[22,23,24]

The study of MGUS neuropathy has been confounded by its relation to chronic inflammatory demyelinating polyneuropathy (CIDP), with about one quarter of patients with CIDP also having a paraproteinemia. However, the meaning of this association is unclear. Conduction blocks, which are the cardinal electromyographic feature of CIDP, sometimes occur in MGUS as well,[19,20] and the CSF protein level is usually elevated in both conditions. Moreover, both neuropathies respond to immunomodulating treatments. However, IgM paraproteinemic neuropathies are more refractory to therapy. In some cases, monoclonal gammopathy is a coincidental finding and is unrelated to a patient’s neuropathy.

The optimal therapy for MGUS neuropathies has not been established. About one third of patients with IgG or IgA MGUS improve symptomatically within days or weeks of the administration of high-dose intravenous immunoglobulin (IVIG; 0.4 g/kg of body weight daily for 5 days), plasma exchange (a total of 220 mL/kg, given in 4 or 5 treatments), or therapy with corticosteroids, often in combination with immunosuppressants.[25] However, only the benefit of plasma exchange has been confirmed in a controlled clinical trial.[26,27]

Although the IgM neuropathies tend to be the most refractory to therapy, some improvement can be expected with the same regimens used for the IgG and IgA neuropathies, particularly if cyclophosphamide or chlorambucil is added in doses sufficient to reduce the amount of M-protein.[28,29]

An alternative treatment in paraproteinemic neuropathies is immunoadsorption, but its role has not been fully substantiated through trials.[30] Interferon alfa was beneficial in one trial.[31] However, these treatments generally produce only transient improvement and require repetition every several months, depending on the patient’s response and general condition.