Chapter 19: Neuropathies Associated with Malignancy

INTRODUCTION

Patients with malignancy can develop peripheral neuropathies as the result of (1) a direct effect of the cancer by invasion or compression of the nerves, (2) a remote or paraneoplastic effect including vasculitis, (3) a direct toxic effect of treatment, or (4) an alteration of immune status caused by immunosuppression (Table 19-1).^1,2 It is difficult to estimate the frequency of polyneuropathy in patients with cancer because it is dependent on a number of factors including the type, stage, and location of the malignancy, as well as confounding variables such as malnutrition, the toxic effects of therapy, and the background incidence of neuropathy in this frequently older population. Nevertheless, some series indicate that 1.7–5.5% of patients with cancer have clinical symptoms or signs of a peripheral neuropathy, while neurophysiologic testing (quantitative sensory testing and nerve conduction studies [NCS]) demonstrates evidence of peripheral neuropathy in as many as 30–40% of patients with cancer.³ The most common associated malignancy is lung cancer, but neuropathies also complicate carcinoma of the breast, ovaries, stomach, colon, rectum, and other organs including the lymphoproliferative system.

PARANEOPLASTIC NEUROPATHIES

Neuropathies related to remote effects of carcinoma or the so-called paraneoplastic syndromes are quite interesting but quite rare.^1,2,4

PARANEOPLASTIC SENSORY NEURONOPATHY/GANGLIONOPATHY

In 1948, Denny-Brown reported two patients with small-cell lung cancer (SCLC) and sensory neuronopathy (SN).⁵ Autopsies revealed dorsal root ganglionitis with degeneration of the posterior columns as well as peripheral sensory axons. Subsequently, there have been many reports of patients presenting with paraneoplastic encephalomyelitis (PEM) and/or SN.^3,5–31 SCLC is the most common malignancy associated with PEM/SN, but cases of carcinoma of the esophagus, breast, ovaries, kidney, and lymphoma have also been reported.^3,5,6 Approximately 13% of patients with SCLC have another type of concomitant malignancy.³ Therefore, finding a malignancy other than SCLC in a patient with PEM/SN does not obviate the need to look for concurrent lung cancer.

Clinical Features

PEM/SN most commonly develops in the sixth or seventh decade.^3,5,6,32 The disease is more common in women than in men (up to a 2:1 ratio). The neurologic symptoms usually precede the diagnosis of cancer. Most malignancies are detected within 4–12 months, although there are reports of cancer being diagnosed 8 years ...