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

We report a patient with severe paraneoplastic encephalomyeloneuritis, occult small-cell carcinoma of the lung, and high titers of circulating antineuronal antibody who died shortly after developing limbic encephalitis. The antibody was of IgG class and reacted specifically with nuclei and cytoplasm of all neurons in the pattern typical for encephalomyelitis and subacute sensory neuropathy associated with small-cell carcinoma (type II, anti-Hu). At autopsy, perivascular inflammatory infiltrates were prominent. All samples of serum, CSF, and postmortem peritoneal and pleural fluid contained high titers of antibody. Direct immunofluorescence of frozen tissue revealed IgG bound to most remaining neurons in multiple brain regions in a pattern similar to indirect immunofluorescence of normal brain tissue. IgG was also bound to tumor. Attempts to elute antibody from tissue decreased background staining but did not remove neuronal immunofluorescence. These results indicate that antibody can access and bind specifically to neuronal antigens in the brain during the course of paraneoplastic disease.
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PMID:Localization of antibody in the central nervous system of a patient with paraneoplastic encephalomyeloneuritis. 165 26

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

The perivascular spaces of the central nervous system are involved in various pathological situations. The aim of this paper is to focus on the histopathological lesions of the perivascular spaces which commonly occur in the infectious (bacterial, viral, parasitic), tumoral (carcinoma, lymphoma, leukemia), demyelinating (multiple sclerosis, allergic encephalomyelitis) and vascular diseases of the brain. According to their apparent function in each of these situations an attempt was made to classify the main physiopathological processes involving the perivascular spaces into 3 distinct groups. The perivascular spaces may be considered as follows: (1) double way route between the parenchyma and the leptomeningeal space (extension to the brain of a meningeal pathological process, drainage of parenchymal wastes); (2) elective location of the inflammatory reaction partly as a result of the presence of connective tissue; (3) site of particular lesions such as dilatation, the pathogenesis of which remains unclear.
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PMID:[Pathology of perivascular spaces in the central nervous system]. 650 82

Hel-N1 is a novel human complementary DNA encoding a neuronal RNA-binding protein which shares considerable sequence homology with the HuD protein, a target of type I anti-neuronal nuclear antibodies in patients with paraneoplastic encephalomyelitis. The aim of the present study was to determine the prevalence of antibodies against the Hel-N1 protein among patients with lung carcinoma, including those with paraneoplastic disorders. Sera from 45 patients with lung cancer (42 with small-cell carcinoma) and from 28 control patients with other neurological diseases were studied by enzyme-linked immunosorbent assay (ELISA) and by immunoblotting with recombinant Hel-N1 protein. Sixteen of the 45 lung cancer patients (14 with small-cell and 2 with undifferentiated carcinoma) had paraneoplastic encephalomyelitis and high-titer type I anti-neuronal nuclear antibodies; sera from each of these 16 patients also showed strong reactivity with Hel-N1 protein. The other 29 lung cancer patients, all of whom had neurological dysfunction and 24 of whom had known or suspected paraneoplastic disorders, lacked the type I antibody by standard testing. The mean anti-Hel-N1 titer (by ELISA) of sera from patients negative for type I anti-neuronal nuclear antibody was significantly less than that of the patients positive for the type I antibody, but exceeded that of the control patients with other neurological diseases (p < 0.001). Fifteen (52%) of the 29 type I antibody-negative patients had positive serum anti-Hel-N1 titers which did not overlap the high anti-Hel-N1 titers of the 16 type I antibody-positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoantibodies against the Hel-N1 RNA-binding protein among patients with lung carcinoma: an association with type I anti-neuronal nuclear antibodies. 805 56

Paraneoplastic encephalomyelitis developed as the presenting feature of small-cell lung carcinoma in 3 patients. Two patients with paraneoplastic encephalomyelitis manifested predominantly as subacute sensory neuronopathy did not improve after prednisone treatment and chemotherapy. The third patient had severe axial and limb rigidity and myoclonus, which partially improved after chemotherapy and treatment with intravenous immunoglobulin and prednisone. Serum from each patient immunocytochemically stained the neuropil and to a lesser degree the neuronal cytoplasm in human cerebral and cerebellar cortex. On immunoblots of human neuronal extracts, each patient's serum contained high-titer IgG antibodies reacting with a protein band of apparent molecular mass 125 kd. This autoantibody pattern is indistinguishable from antibodies recently identified in several women with breast carcinoma and stiff-man syndrome. Screening of a human brain complementary DNA expression library with patient serum yielded clones whose sequence is identical to that of the synaptic vesicle-related protein amphiphysin. Reverse transcriptase-polymerase chain reaction demonstrated expression of amphiphysin in 8 of 10 small-cell lung carcinomas and in 5 of 14 breast carcinomas. These observations highlight the clinical and serological heterogeneity of paraneoplastic central nervous system disorders: Patients with a given clinical syndrome may have different antineuronal antibodies, and patients with a given autoantibody specificity have differing clinical presentations.
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PMID:Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. 861 52

We report a 63-year-old man with progressive gait disturbance and dysarthria. The patient was apparently well until the age of 62 (February, 1990) when he noted unsteadiness of gait. Two months later, dysarthria appeared. He was admitted to Juntendo Izunagaoka Hospital on April 23, 1990. Neurologic examination revealed a mentally sound man with normal higher cerebral functions. Cranial nerves were unremarkable except for scanning speech. His gait was ataxic with positive Romberg sign. No motor weakness was noted, however, he had hypotonia and cerebellar ataxia. Deep tendon reflexes were retained and the plantar response was flexor. Pain, touch and vibration senses were diminished in the distal parts of the lower extremities. Laboratory examination revealed a 2.5 cm mass in the left lung field. Cranial MRI revealed a small T1-low and T2-high signal intensity lesion in the left temporal lobe. Abdominal CT scan revealed multiple low density lesions in the liver. His subsequent course was complicated by progressive deterioration in his gait and loss of deep tendon reflexes. He expired on November 24, 1990. The patient was discussed in the neurological CPC and the chief discussant arrived at the conclusion that the patient had anti-Hu associated paraneoplastic encephalomyelitis and sensory neuropathy. Some other participants thought that the patient had carcinomatous cerebellar degeneration. Postmortem examination revealed a 4x4 cm mass lesion involving the left S4-S5 segments. Histologic examination of the tumor was small cell carcinoma. Many metastatic foci were found in the liver. The cerebral hemispheres were unremarkable except for a small wedge-shaped tissue defect in the left temporal lobe which appeared to have been caused by old head trauma which the patient had received. The cerebellar vermis showed slight enlargement of cortical sulci, however, the cerebellar hemispheres appeared unremarkable. Upon histologic examination, marked loss of Purkinje cells was noted, particularly in the cerebellar anterior lobe. The dentate nucleus showed slight cell loss with increase in fat granule cells. The inferior olive was normal. The histologic characteristics were consistent with the pathologic diagnosis of carcinomatous cerebellar degeneration. No evidence of limbic encephalitis was seen. The peripheral nerve was not examined.
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PMID:[A 63 year-old man with progressive gait disturbance and dysarthria]. 888 38

The presence of specific antineuronal antibodies in some patients with paraneoplastic central nervous system (CNS) disorders supports the theory that these syndromes have an autoimmune etiology. The anti-Purkinje cell antibodies (APCAs) in some patients with paraneoplastic cerebellar degeneration and ovarian or breast carcinomas stain the cytoplasm of Purkinje cells. APCAs react with several distinct neuronal protein autoantigens, including proteins featuring a "leucine zipper" sequence motif, which suggests that they function in regulating DNA transcription. Type 1 anti-neuronal nuclear antibodies (ANNA-1) associated with paraneoplastic encephalomyelitis and small-cell lung carcinoma stain the nucleus and cytoplasm of all neurons, and react with a group of 35- to 40-kd proteins in neuronal immunoblots. The protein targets of ANNA-1 belong to a family of RNA-binding proteins that probably regulate posttranscriptional processing of RNA. Type 2 anti-neuronal nuclear antibodies (ANNA-2) associated with paraneoplastic opsoclonus-ataxia and breast carcinoma also produce a panneuronal immunocytochemical staining pattern, but react with a group of higher-molecular-mass proteins (53-61 kd and 79-84 kd); these autoantigens probably also function as RNA-binding proteins. Several patients with paraneoplastic stiff-man syndrome have antibodies against a 128-kd synaptic protein. These antineuronal antibodies are highly specific (but not infallible) diagnostic markers for the presence of a neoplasm in patients who present with neurological dysfunction. The actual role of these autoantibodies in the pathogenesis of neuronal damage and clinical disease remains to be determined. Current management options for patients with CNS neurological paraneoplastic syndromes are very limited. Only a small minority of patients with paraneoplastic cerebellar degeneration or encephalomyelitis show significant neurological improvement after successful tumor treatment and/or immunosuppressive treatments, while patients with paraneoplastic opsoclonus or stiff-man syndrome have a somewhat better outlook.
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PMID:Autoimmune central nervous system paraneoplastic disorders: mechanisms, diagnosis, and therapeutic options. 896 21

We report a 76-year-old man who developed blurred vision and dementia. He was apparently well until April 4, 1990 (70-year-old at that time) when he had a sudden onset of bilateral loss of vision. Corrected vision was 0.1 (right) and 0.09 (left). He was admitted to the ophthalmology service of our hospital on April 9, 1990, and neurological consultation was asked on April 11. Neurologic examination revealed alert and oriented man without dementia. Higher cerebral functions were intact. He had bilateral large visual field defects with loss of vision; he was only able to count the digit number with his right eye and to recognize hand movement with his left eye. Otherwise neurologic examination was unremarkable. General physical examination was also unremarkable; he had no hypertension. Cranial CT scan was normal on April 11; lumber spinal fluid contained 1 cell/microliter, 63 mg/dl of sugar, and 97 mg/dl of protein; myelin basic protein was detected, however, oligoclonal bands were absent. He was treated with methylprednisolone pulse therapy and oral steroid, however, no improvement was noted in his vision. He started to show gaze paresis to left, ideomotor apraxia, agnosia of the body, and dementia. Cranial CT scan on June 11 revealed a low density area in the deep left parietal white matter facing the trigonal area of the lateral ventricle. He was discharged on July 2, 1990. Hasegawa dementia scale was 2/32.5 upon discharge. In the subsequent course, he showed improvement in his mental capacity and Hasegawa dementia scale was 22.5/32.5 in 1991, however, no improvement was noted in his vision. In 1994, he started to show mental decline in that he became disoriented, and showed delusional ideation of self persecution and depersonalization with occasional confusional state. He also showed unsteady gait. Cranial MRI on February 13, 1996 revealed a T2-high signal intensity lesion on each side of the parietal deep white matter more on the left and another T2-high signal intensity lesion in the left pons as well as in the right thalamus. He complained of right hypochondrial pain and was admitted to another hospital on April 22, 1996. He was markedly confused and demented. He continued to show bilateral loss of vision, but no motor palsy was noted. Cranial CT scan on April 23, 1996 revealed diffuse cortical atrophy and ventricular dilatation in addition to the low density areas in both parietal deep white matter. He developed jaundice in the middle of May. Abdominal CT scan revealed multiple low-to iso-density areas in the liver and marked iso-to high-density swelling of the right kidney. The patient expired on June 9th, 1996. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had had a carcinomatous limbic encephalitis with optic neuropathy and a choleduct carcinoma. Other opinions entertained included acute disseminated encephalomyelitis with optic neuritis, and granulomatous angiitis of the central nervous system. Some participants thought the primary site of the carcinoma was the right kidney with metastasis to the liver. Post mortem examination revealed a mixed type carcinoma in the right kidney with liver metastases. Neuropathologic examination revealed an incomplete softening in the optic chiasm and the left optic nerve, and in the left parieto-occipital areas. (The right hemisphere was frozen for future biochemical assay.) One of the adjacent cortical arteries had an organized thrombus. Other arteries and arterioles also showed sclerotic changes. Some of the leptomeningeal arteries were positive for Congored staining as well as for beta-amyloid immunostaining. Many senile plaques were seen diffusely in the cerebral cortex and neurofibrillary tangles were seen in the CA1 area and the parahippocampal gylus. No cellular infiltrations or demyelinated foci were seen. The neuropathologic features were consistent with circulatory disturbance based on the amyloid angiopa
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PMID:[A 76-year-old man with loss of vision and dementia]. 928 74

Inhibition of experimental tumor growth, life-span, mitotic activity and cytologic damage have been studied in cells of ascitic and solid carcinoma of Ehrlich in the course of biotherapy with vaccines of Venezuelan encephalomyelitis virus, mumps and influenza viruses. Summing up, it is concluded that the vaccine of Venezuelan encephalomyelitis virus looks most promising as far as further research in development of an antitumor viral drug is concerned.
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PMID:[Biotherapy of experimental tumors with vaccines of Venezuelan encephalomyelitis virus, parotitis and influenza viruses and cytologic evaluation of effectiveness]. 1253 Feb 70


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