Sensory Neuropathy and Malignancy
ABSTRACT & COMMENTARY
Source: Camerlingo M, et al. Malignancy and sensory neuropathy of unexplained cause. Arch Neurol 1998;55:981-984.
Among 363 patients with peripheral sensory neuropathy prospectively observed over a seven- year period, no cause could be identified in 53. Two patients refused further follow-up, but the remaining 51 patients, 42 men and nine women with a mean age of 64.5 years, were followed at six-month intervals for a mean of 51.4 months. Patients initially underwent extensive evaluations including cerebrospinal fluid examination, sural nerve biopsy, search for humoral markers of neoplasms (carcinoembryonic antigen, alpha-feto-protein, prostatic specific antigen) and circulating antibodies (anti-Hu, anti-Yo, and anti-Ri antibodies), chest radiograph, total body CT, gastroscopy, and rectal examination for occult blood. At six-month intervals, the search for cancer was repeated with routine blood tests, ultrasound examination of the abdomen, pelvis, and thyroid gland, chest radiograph, and stool specimens for occult blood.
Cancer was found in 18 patients (35.3%) within 3-72 months (mean, 27.9 months) of onset of the neuropathy and included non-Hodgkin lymphoma (n = 3), sarcoma (n = 1), and cancer of the liver (n = 4), bladder (n = 3), lung (small cell), prostate (2 each), breast, pancreas, or sublingual gland (1 each). Four patients improved neurologically following treatment of their cancer (1 each with lung, liver, bladder, and sublingual gland cancer), and three did so within weeks-the bladder cancer patient showing a slower improvement. An additional patient developed prostate cancer subsequent to acceptance of the manuscript for publication. Heightened vigilance for occult neoplasms is warranted in patients with undiagnosed sensory neuropathy.
COMMENTARY
Cancer affects the neuromuscular system either directly, by compression or infiltration, or indirectly, by paraneoplastic effect. The latter are rare and present in less than 1% of cancer patients, but they capture clinical attention out of proportion to their incidence due to their unique serologic and often striking clinical phenomenology.
Cancer does not occur more frequently in patients with typical amyotrophic lateral sclerosis, despite the plethora of case reports suggesting otherwise.1 However, particularly young (< 30 years) or old (older than 70 years) patients should be evaluated for malignancy, and patients with paraproteinemia and elevated cerebrospinal fluid (CSF) protein should be screened for lymphoma.2 Subacute motor neuronopathy is an accepted paraneoplastic effect of Hodgkin's disease and lymphoma, occurring most often while the patient is in remission, but it is rarely debilitating and tends to stabilize or improve with time.3
Leptomeningeal neoplastic polyradiculopathy demonstrates typical radicular symptoms and signs. F-wave electrodiagnostic studies may provide an early clue to compression,4 and CSF analysis is almost always abnormal.5
Subacute sensory neuronopathy is most often seen with small cell lung cancer. Differentiation from idiopathic sensory neuropathy is indicated by finding CSF pleocytosis and elevated protein or associated paraneoplastic encephalomyelitis (in 70%), and anti-Hu antibodies, a complement-binding IgG antibody in serum and CSF that reacts with a tumor antigen and an identical brain nuclear protein. Unfortunately, treatment of the underlying cancer is of no benefit.
Curiously, among patients with idiopathic sensory neuropathy and no evidence of cancer, the incidence of circulating dominant clones of T cells, the T-cell counterpart of monoclonal gammopathy of undetermined significance (MGUS), is strikingly high.6 Eighty percent of patients with chronic idiopathic axonal neuropathy (12/15) or chronic idiopathic ataxic neuropathy (4/5) demonstrated these clones, as compared to 20% of normal controls (2/10), elderly patients with degenerative neurologic disease, including Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis (2/10), or elderly patients with chronic inflammatory demyelinating polyneuropathy (2/10). The relevance of these clones to the underlying neuropathy is unknown but supports the notion that autoimmunity may be causative. The finding suggests the potential for future therapeutic trials using traditional immunosuppressive agents or high-dose intravenous immune globulin. -mr
References
1. Rosenfeld MR, Posner JB. Paraneoplastic motor neuron disease. Adv Neurol 1991;56:445-459.
2. Younger DS, et al. Lymphoma, motor neuron diseases, and amyotrophic lateral sclerosis. Ann Neurol 1991; 29:78-86.
3. Schold SC, et al. Subacute motor neuronopathy: A remote effect of lymphoma. Ann Neurol 1979;5: 271-287.
4. Argov Z, Siegal T. Leptomeningeal metastases: Peripheral nerve and root involvement-clinical and electrophysiological study. Ann Neurol 1985;17:593-596.
5. Olson ME, et al. Infiltration of the leptomeninges by systemic cancer. A clinical and pathologic study. Arch Neurol 1974;30:122-137.
6. Gherardi RK, et al. Dominant T-cell clones of unknown significance in patients with idiopathic sensory neuropathies. Neurology 1998;51:384-389.
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