Motor neuron syndromes in cancer patients

Abstract

Previous reports indicate that motor neuron disease (MND) may rarely be associated with systemic cancer. We have encountered 14 patients with MND and cancer who formed three distinct groups. Group 1: Three patients developed a rapidly progressive MND, less prominent symptoms of involvement of other areas of the nervous system, and anti-Hu antibodies. Group 2: Five women developed signs of upper motor neuron (UMN) disease, initially resembling primary lateral sclerosis (PLS), and breast cancer. In 4, symptoms of UMN occurred within 3 months of cancer diagnosis or tumor recurrence. They had no metastases or spinal cord compression. Serum anti-neuronal antibodies were negative. Three patients are alive (follow-up of 156, 15, and 12 months), and 2 remain without lower motor neuron signs. Group 3: Six patients developed MND resembling amyotrophic lateral sclerosis between 47 months before and 48 months after their cancer diagnosis. In group 1, the MND associated with the anti-Hu antibody is unequivocally paraneoplastic. In group 2, the proximate onset of MND with the diagnosis of cancer or its recurrence, its pure or long-lasting UMN signs, and its association with breast cancer, suggest that the disorder may be paraneoplastic. Although for most cancer patients who develop MND the occurrence of both disorders is probably coincidental, in some patients with MND a careful search for an underlying cancer is warranted (ie, patients in groups 1 and 2).

Clinical Features in Association with Neurodegenerative Diseases and Malignancies

“…Meanwhile, malignancies preceding ALS were cancers of the oral cavity, thyroid, breast, colon, testicle, and ovary, Hodgkin's disease, and melanoma, and colon cancers were found most frequently (3 out of 11 cases) in the USA [13,14]. In our case series, cancers developed at various sites of the body in the ALS group, similar to previous reports.…”

“…Although patients with Alzheimer's disease have a low risk of cancer, the epidemiological association between cancer and other neurodegenerative diseases has not been well established [12,13,14,15,16]. It remains controversial whether patients with ALS have a risk of developing cancer, except for melanoma [12,13,14,17]. Patients with PD have a low risk of developing many cancers; however, the incidence of some types of cancer is higher (e.g.…”

“…Malignancies with ALS have been reported as follows: cancers of the hypopharynx, thymus, lung, breast, colon, skin, kidney, testicle, prostate, and uterus, astrocytoma, liposarcoma, lymphosarcoma, leukemia, and lymphoma [12,13,14,24,25,26,27]. Meanwhile, malignancies preceding ALS were cancers of the oral cavity, thyroid, breast, colon, testicle, and ovary, Hodgkin's disease, and melanoma, and colon cancers were found most frequently (3 out of 11 cases) in the USA [13,14].…”

Brachial Diparesis due to Motor Neuronopathy as One of the Predominant Presenting Signs of Occult Small Cell Lung Carcinoma

“…In PNS, the symptoms usually consist of malignant inflammatory sensory polyganglioneuropathy, gastrointestinal dysmotility, autonomic neuropathy and limbic encephalitis (2). A motor neuron dysfunction is extremely rare as a PNS sign and has been reported in several patients with PNS and anti-Hu antibodies (4), two patients with SCLC and anti-neuronal antibodies (5) and three patients with motor neuron disease and other cancers (6) in three different studies. Apart from these series, two relevant reports of cases with lower motor neuron disease and antiHu antibodies have been published (7,8).…”

“…They cross-react with the nervous system tissues, leading to a humoral and T-cell-mediated immune response (9). Postmortem examinations of the spinal cord in three patients in the aforementioned studies revealed the marked depletion of anterior horn cells (6,8), with inflammatory infiltrates (6). Although anti-Hu antibodies stain the nuclei of all neurons of the brain, spinal cord and dorsal root ganglia in a diffuse homogeneous manner (8), it is not clear why sensory polyganglioneuropathy predominates over motor neuronopathy.…”