Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paraneoplastic neurological syndromes are mostly associated with small cell lung cancer. Lambert-Eaton myasthenic syndrome appears to be caused by anti-presynaptic calcium channel antibodies. Calcium channels are also present in the cell membrane of small cell lung cancer, which may trigger the formation of anti-calcium channel antibodies. It is the most convincing argument in support of the auto-immune paraneoplastic theory, which refers to cross-antigenicity. Serum of patients with small cell carcinoma and cancer-associated retinopathy contains immunoglobulins against several antigens in the retinal and tumor cells. Patients with chronic intestinal pseudoobstruction (gastrointestinal neuropathy) associated with small cell lung cancer displayed circulating IgG antibodies reactive with neurons of myenteric plexus (anti-enteric neuronal antibodies). On the other hand, high levels of anti-neuronal antibodies (anti-Hu) have been found in the serum and cerebrospinal fluid of patients suffering from subacute encephalomyelitis (limbic encephalitis, cerebellar degeneration, sensory neuronopathy) associated with small cell lung cancer. The pathogenic role of the anti-neuronal antibody is not well established. Nevertheless, the finding of high titer antineuronal antibody in patients with a suggestive clinical syndrome is of great interest since it confirms the paraneoplastic syndrome and suggests the location of the primary tumor when the cancer is unknown.
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PMID:[Autoimmunity and cancer: paraneoplastic neurological syndromes associated with small cell cancer]. 133 87

Paraneoplastic neurological syndromes are of two types: some are more often seen without than with cancers and may therefore be called "occasionally para neoplastic" (e.g. chronic sensorimotor polyneuropathy and polymyositis), while others are fairly regularly associated with cancers, and particularly with small cell lung carcinoma. In this category falls subacute encephalomyelitis, an entity of broad anatomico-clinical spectrum including limbic encephalitis and subacute sensory neuronopathy; the patient's serum and cerebrospinal fluid may contain neuronal antinuclear antibodies. One type of subacute cerebellar degeneration is characterized by the presence of antibodies specifically directed against Purkinje cell cytoplasmic antigens, and it is associated with ovarian and mammary cancers. The other type shows no antibodies or different antibodies and sometimes neuronal antinuclear antibodies; the latter case may represent the cerebellar form of subacute encephalopathy. Because it may be either a true autoimmune disease or a true paraneoplastic syndrome, Lambert-Eaton myasthenic syndrome, caused by autoantibodies that block the voltage-dependent calcium channels, stands out as the most convincing argument in support of the autoimmune paraneoplastic syndrome theory. The theory, which refers to cross-antigenicity, cannot be extended to the other syndromes without reservation: there is no evidence that autoantibodies are neurotoxic, and specific autoantibodies in high levels are sometimes detected in patients with cancer but without any neurological symptom. Nevertheless, the finding of circulating antineuronal antibodies in patients with a suggestive clinical syndrome should prompt investigations for cancer perhaps at an early stage.
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PMID:[Paraneoplastic neurologic syndromes]. 182 23

We studied the nervous systems and tumors of five patients with anti-Hu-positive paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/PSN) to determine if the autoantibody found in the serum and CSF was also present in those tissues. Immunohistochemical studies of the nervous system revealed the presence of IgG bound predominantly to the nuclei of most of the neurons and the cytoplasm of some glial cells. IgG was also present to a lesser degree in the neuropil. In brains of patients who died of cancer without the paraneoplastic syndrome, IgG was present in the immediate perivascular areas and to a very limited degree in the neuropil. There was no IgG in neurons, and in only some of the controls a few glial cells showed IgG immunoreactivity in the cytoplasm. The amount of anti-Hu IgG relative to total IgG in various brain regions and tumor was determined by quantitative Western blot analysis. The proportion of anti-Hu IgG was greater in some areas of the brain and tumor than in serum and CSF. Control brains did not contain anti-Hu IgG. There was a limited correlation among (1) the principal clinical symptoms, (2) regions of major tissue injury, and (3) the quantitative anti-Hu IgG distribution. We conclude that although the role of the antibody in the pathogenesis of the disease is still uncertain, its specific localization in the nervous system and tumor suggests an immunologic etiology of this paraneoplastic syndrome.
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PMID:Detection of the anti-Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuronopathy. 194 5

Paraneoplastic syndromes affecting the nervous system are rare and their diagnosis is often difficult when the original cancer is unknown. Recently, high levels of antineuronal antibodies (AB) have been found in serum and CSF of some patients with paraneoplastic syndromes. The anti-Yo AB recognizes 2 proteins of 34 and 62 kd in the cytoplasm of Purkinje cells and in malignant cells of patients suffering from paraneoplastic cerebellar degeneration associated with ovarian and breast cancer. The anti-Hu AB recognizes a 37-40 kd protein in nuclei of neurons and in tumor cells of patients suffering from subacute sensory neuronopathy and encephalomyelitis associated with small cell lung cancer. Other antineuronal AB have been more rarely identified. The presence of high titer of one of these AB in a patient with suspected paraneoplastic syndrome is of great practical interest since it confirms the neurological diagnosis and strongly suggests the location of the primary tumor when the malignancy is unknown. The pathogenetic role of the antineuronal AB is unknown but it is likely that some paraneoplastic syndromes affecting the nervous system are due to an immune reaction against antigens shared by the tumor and the nervous system. To date, no efficient treatment has been found.
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PMID:[Autoimmunity and paraneoplastic neurologic syndromes]. 196 63

We looked for the presence of the anti-Hu antibody in the sera from 50 normal subjects; 44 patients with small cell lung cancer, not associated with paraneoplastic disease; and 25 patients with small cell lung cancer associated with paraneoplastic sensory neuropathy, encephalomyelitis, or both. Using the avidin-biotin immunoperoxidase method and a highly sensitive quantitative Western blot analysis, the anti-Hu antibody was not detected in the 50 normal human sera. Seven of the 44 patients with small cell lung cancer but no paraneoplastic syndrome had detectable levels (average titer, 76 U/ml) of anti-Hu antibody on Western blot. These levels are significantly lower than the average titer of the 25 patients who had small cell lung cancer and paraneoplastic sensory neuropathy or encephalomyelitis (average titer, 4,592 U/ml). In the group with nonparaneoplastic small cell lung cancer (low anti-Hu titer) there was a predominance of women (5 women: 2 men), and all patients had "limited" disease when diagnosed. In the antibody-negative group the sex ratio was 16 women to 21 men and 51% of the patients had "extensive" disease. None of the 7 patients with a low-titer anti-Hu antibody developed a paraneoplastic syndrome by the time of writing. The anti-Hu antibody appears, when present, to be a good marker for small cell lung cancer and, when present at high titer, for small cell lung cancer associated with a paraneoplastic syndrome.
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PMID:Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer--a quantitative western blot analysis. 216 35

"Remote effects" of cancer on the nervous system (paraneoplastic syndromes) are disorders of the nervous system of unknown cause that occur almost exclusively, or with greatly increased frequency, in patients with identifiable or occult cancer. There are several hypotheses concerning the pathogenesis of these rare disorders. One hypothesis is that the underlying tumor and portions of the nervous system share antigens and that an autoimmune response generated against the tumor causes the nervous system disorder. Evidence supporting this hypothesis includes the ability to transmit the Lambert-Eaton Syndrome (a paraneoplastic syndrome involving the neuromuscular junction) to experimental animals by infusing IgG from patients with the disorder, the presence of autoantibodies against Purkinje cell neurons in some patients with paraneoplastic cerebellar degeneration, and the presence of autoantibodies against many neurons in patients with sensory neuronopathy and encephalomyelitis. Other evidence supporting the hypothesis is presented in this review.
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PMID:Autoimmune pathogenesis of paraneoplastic neurological syndromes. 331 39

The authors report a case of hypertonia, the clinical and electrophysiological features of which were identical to those of the Stiff-man syndrome first described by Moersch and Woltman in 1956. This and the five other previously reported cases can be attributed to encephalomyelitis of the anterior horns of the spinal cord. All of these cases had severe but partial involvement of the anterior horns and the probable physiopathological mechanism of the resulting contractures was elective destruction of the small inhibitory neurones. In the present case, the association of a limbic encephalitis and secondary exteriorization of a carcinoma of the pharynx, strongly suggested a paraneoplasic encephalomyelitis. This is the first report indicating an association between the Stiff man syndrome and a paraneoplastic syndrome. Another point of interest was the spectacular response of the hypertonia to steroid therapy suggesting a central neuropharmacological effect quite apart from the non specific anti-inflammatory action on the encephalomyelitis.
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PMID:[Amnesia and stiff-man syndrome. Manifestations disclosing paraneoplastic encephalomyelitis]. 343 72

In the last decade, anti-neurons autoantibodies have been found in serum and cerebro spinal fluid of patients suffering from neurological paraneoplastic syndrome. This discovery has made possible to improve the knowledge of these syndromes as well as to characterize some proteins specific to the nervous system, unknown until now. Paraneoplastic encephalomyelitis can manifest together with an ataxic sensitive neuropathy, a limbic encephalitis, a brainstem or cerebellum syndrome. This encephalomyelitis is almost always associated with a small cells lung cancer and auto-antibodies, called anti-Hu, which recognize all the neurons of the nervous system. Patients with paraneoplastic cerebellar degeneration present an antibody, called anti-Yo, directed against Purkinje cells. In this case, the tumor is a gynecologic cancer. Patients presenting with an opso-myoclonus and a breast cancer have an antineurons anti-body, called anti-Ri, which is absent when the opso-myoclonus is associated with a lung cancer or a neuroblastoma. These three antibodies are the most frequently found and the best studied, but others, rarer, have been described. The genes coding for the proteins recognized by these three antibodies have been cloned. These proteins seem to play a major role in the neuronal maturation and homeostasis. These antibodies prove to be irreplaceable tools to study the phenomenons subtending the neuronal degeneration and the cellular proliferation.
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PMID:[Value of the detection of anti-nervous system autoantibodies in neurologic paraneoplastic syndromes]. 805 19

Small cell lung cancer (SCLC) is known to express the HuD protein, the neuronal antigen homologous to Drosophila Elav and Sxl genes involved in neuronal and sex development. HuD is the target of an immune response including high titered antibodies causing paraneoplastic encephalomyelitis and sensory neuropathy. Because the p53 recessive oncogene is mutated and anti-p53 antibodies frequently occur in cancer patients, we wondered if the development of anti-HuD antibodies signaled the presence of HuD mutations in lung cancer. The HuD gene was mapped to chromosome region 1p using a human-mouse hybrid cell panel. We confirmed that 26 of 46 cancer (43 lung cancer and 3 mesothelioma) cell lines expressed HuD mRNA and that this expression, as well as protein expression by Western blot, correlated strongly with the SCLC neuroendocrine phenotype. Southern blot and single-strand conformation polymorphism analyses showed that HuD was not mutated in 78 lung cancers, including patients with the severe paraneoplastic syndrome. Northern blot analysis showed that lung cancer cell lines expressed two major mRNAs (4.3 and 4.0 kilobases) of HuD. We found the three previously described alternative spliced mRNA forms (HuDpro, HuD, and HuDmex). In addition, we also found HuD mRNA had an alternative splicing form in its 5'-coding region. This alternative splice introduced 87 base pairs of sequence and a termination codon resulting in a predicted small, truncated protein (11 amino acids) reminiscent of the male-specific truncated protein in the Sex-lethal (Sxl) gene of Drosophila. However, mRNAs encoding both full-length and truncated proteins were expressed in all SCLCs. These results show that the HuD gene is not mutated in lung cancer, including tumors from patients producing anti-HuD antibodies, but HuD expression is an independent marker or determinant of the neuroendocrine differentiation seen in SCLC.
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PMID:Molecular analysis of the HuD gene encoding a paraneoplastic encephalomyelitis antigen in human lung cancer cell lines. 806 66

A neurologic paraneoplastic syndrome may be the first sign of an occult and treatable cancer. Some syndromes are associated with autoantibodies against neuronal antigens. Patients with cerebellar degeneration and ovarian or breast cancer have antibodies against 34 and 62 kilodalton (kDa) proteins in Purkinje cell cytoplasm: anti-Yo antibodies. Patients with encephalomyelitis or sensory neuronopathy and small cell lung cancer have antibodies against 35-40 kDa neuronal nuclear proteins: anti-Hu antibodies. Patients with opsoclonus-myoclonus and breast cancer have antibodies against 55 and 80 kDa neuronal nuclear proteins: anti-Ri antibodies. Patients with Lambert-Eaton myasthenic syndrome and small cell lung cancer have antibodies against voltage-gated calcium channels (anti-VGCC) in motor nerve terminals. The presence of anti-neuronal antibodies strongly indicates that a neurological syndrome is paraneoplastic, and often identify the site of an occult neoplasm. However, the absence of detectable antibodies does not rule out the presence of an underlying tumour.
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PMID:[Neurologic paraneoplastic syndromes and anti-neuronal antibodies]. 863 63


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