Lymphoma, motor neuron diseases, and amyotrophic lateral sclerosis

Abstract

We studied 9 patients with motor neuron disease and lymphoma. The following several observations have not been recognized in the past: (1) Motor neuron syndromes are associated with either Hodgkin's disease or non-Hodgkin's lymphoma. (2) The syndromes are not restricted to lower motor neuron disorders; 8 of 9 patients had definite or probable upper motor neuron signs as well, qualifying for the diagnosis of amyotrophic lateral sclerosis. Corticospinal tracts were affected in both postmortem examinations. (3) The combination of motor neuron disease and lymphoma is often accompanied by paraproteinemia (3 of 7 patients studied), increased cerebrospinal fluid protein content (6 of 9 patients), and cerebrospinal fluid oligoclonal bands (3 of 9 patients). (4) In 2 patients, asymptomatic non-Hodgkin's lymphoma was found only because the discovery of paraproteinemia gave impetus to examine the bone marrow. (5) Patients with both upper and lower motor neuron signs (amyotrophic lateral sclerosis) may show physiological evidence of conduction block in peripheral nerves or autopsy abnormalities in peripheral nerves. The cause of this syndrome is not known. Both lymphoma and motor neuron disease could have a common cause, possibly a retroviral infection. The frequency of paraproteinemia suggests that an immunological disorder may play a role in the pathogenesis of the neurological disorder.

Lymphoma and peripheral neuropathy: A clinical review

“…34,43,84,109 -111,113,151-153 In addition to typical cases of amyotrophic lateral sclerosis, patients with subacute and chronic motor nerve disease have been described. [151][152][153] There have also been reports of multifocal motor neuropathy with antibodies directed at nerve gangliosides in patients with lymphoma, 96 and autopsy-proven amyotrophic lateral sclerosis with Waldenström's macroglobulinemia and antibodies to sulfated glucuronic acid paragloboside. 110 Among patients with HL or NHL and either classic amyotrophic lateral sclerosis or progressive spinal muscular atrophy, 94,111,[151][152][153] some have paraproteinemia and abnormally increased cerebrospinal fluid protein levels with oligoclonal bands.…”

New Insights into the Viral Theory of Amyotrophic Lateral Sclerosis: Study on the Possible Role of Kaposi’s Sarcoma-Associated Virus/Human Herpesvirus 8

“…Activated T lymphocytes, deposits of immunoglobulin [42]and antibodies that alter the calcium channel function [43]have been found in the anterior horn cells and in the motor cortex of patients. Moreover, an association between lymphoma and gammopathies has been reported in 5–10% of MND cases [7, 44]. …”

Paraneoplastic motor neuron disease with type 1 Purkinje cell antibodies

“…Most reported cases of paraneoplastic ALS have been associated with either a primary lung carcinoma or a lymphoproliferative disorder. 18 Recently, an ALSlike motor neuron syndrome has been observed in a patient with small cell lung carcinoma associated with ANNA-1/anti-Hu antibody. 17 Our patient is distinguished by having high-grade ovarian adenocarcinoma and a high serum titer of PCA-1 antibodies.…”

“…15,18 It usually has a benign course. Neurological deficits are rarely disabling, and spontaneous improvement has been reported after months or years.…”