Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six patients with small cell lung cancer developed a slowly progressive neurologic syndrome characterized by apathy, abulia, memory loss, gait ataxia, and corticospinal tract signs 26 to 50 months (mean, 35.2 months) after prophylactic cranial irradiation and systemic chemotherapy. In each case this was accompanied by CT and/or MRI evidence of changes in the periventricular white matter. These patients are long-term survivors (41 to 69 months) and do not have CNS metastases.
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PMID:Delayed leukoencephalopathy in survivors with small cell lung cancer. 303 38

We reported a case of opsoclonus-myoclonus syndrome. A 63-year-old man was admitted to Kenwakai Hospital with rapidly progressing symptoms, including lumbago, whole body pain, vertigo, nausea, and anorexia. He became bed-ridden because of severe vertigo and truncal ataxia. Five days after admission, he developed opsoclonus followed by myoclonus and mild disturbance of consciousness, but he showed no appendicular ataxia or pyramidal tract sign. He was treated with prednisolone, 40 mg/day, which was effective for disturbance of consciousness, but opsoclonus and myoclonus persisted. He died of liver dysfunction and ventricular fibrillation 3 weeks after onset. Blood examination revealed high LDH (1,106 IU/l), Al-P, and gamma-GTP titers. Tumor markers were normal except for increase NSE activity (129 ng/ml). The cerebrospinal fluid showed normal cell count, 63.9 mg/dl of protein, 7.3 mg/dl of IgG, and normal glucose. A cranial CT scan showed an old lacune only. Chest rentgenogram and CT scan revealed mediastinal and hilar lymph node enlargement. An abdominal CT scan showed multiple low density masses in the liver. Small cell lung cancer associated with opsoclonus-myoclonus syndrome was suspected. Western blot analysis revealed that his serum reacted with protein in the cerebellum, cerebrum, and dorsal root ganglion with a molecular weight of 77 kDa. This is the first time such an antibody was ever been detected in patients with opsoclonus-myoclonus syndrome. The molecular weights of the antigens previously found by the serum of patients with this syndrome, were 55 kDa and 80 kDa in patients with breast cancer, and 210 kDa in patients with neuroblastoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of opsoclonus-myoclonus syndrome associated with anti-central nervous system antibody]. 782 Sep 64

We report a patient with small cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar degeneration (SCD). The patient was a 71-year-old man suffering from weakness of the limbs and a gait disturbance who developed limb ataxia and dysarthria one month after admission. Electrophysiologic studies confirmed the diagnosis of Lambert-Eaton myasthenic syndrome. Chest X-rays 2 months after admission revealed an abnormal shadow, and small cell lung cancer was diagnosed on the basis of biopsy specimens. Anti-voltage-gated calcium channel antibody was positive. Anti-Yo and -Hu antibodies were negative. The patient was treated by plasmapheresis and chemotherapy, which resulted in a transient improvement in the LEMS symptoms but not in the SCD. Fifteen cases of LEMS associated with SCD have been reported in the Japanese literature, and all were accompanied by small cell lung cancer. We discuss the frequency of association with LEMS and SCD and the effects of plasmapheresis and chemotherapy in both diseases.
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PMID:[Report of a case of small cell lung cancer associated with Lambert-Eaton myasthenic syndrome and subacute cerebellar degeneration--with a review of the Japanese literature]. 819 44

A phase I dose-escalation study of multicyclic, ifosfamide, carboplatin, and etoposide (ICE) with sequential reinfusion of peripheral blood stem cells (PBSCs) was conducted to determine the maximum-tolerated dose (MTD) of ICE. Twenty-four patients with SCLC (LD: 6, ED: 18) were treated with ifosfamide (3000-9000 mg/m2, 24-h infusion), carboplatin (300-400 mg/m2), and etoposide (300 mg/m2) followed by subcutaneous filgrastim (75 microg/day) from day 4 to the day of PBSC collection. PBSC were harvested when the WBC count reached >/=5 x 109/l. The leukapheresis product was cryopreserved and reinfused on day 4 of the next cycle, which was started 48 h after the last PBSC collection. The ifosfamide dose was escalated as follows: 3000 mg/m2 (level 1), 5000 mg/m2 (level 2), 7000 mg/m2 (level 3), 9000 mg/m2 (level 4). Patients with LD were treated with concurrent radiotherapy at 1.5 Gy twice daily for the initial 3 weeks to a total dose of 45 Gy and MTD, defined separately. Patients were evaluated for hematologic and non-hematologic toxicity, actual dose intensities, as well as response to therapy. The maximum-tolerated dose (MTD) was defined as the dose level at which more than 5 days of grade 4 myelo- suppression or non-hematologic toxicity greater than grade 3 developed in two thirds of the patients. For ED cases, MTD was level 4 and the recommended dose of ifosfamide was 7000 mg/m2. For LD cases, the recommended dose of ifosfamide was 5000 mg/m2. The dose limiting toxicity of multicyclic ICE was hemato- logic toxicity and CNS toxicity which manifested as ataxia. Tumor responses were seen in all patients, with 14 patients showing a complete response. The actual total dose-intensity at the recommended dose level was 2.2 and 1.74, for ED and LD, respectively, compared with previously reported ICE regimens. PBSC support for dose-intensive ICE regimen permitted dose escalation of ifosfamide with a mean interval of 16-17 days. We conclude that this regimen is well tolerated, with acceptable hematological and non-hematological toxicity. Bone Marrow Transplantation (2000) 25, 5-11.
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PMID:A phase I dose escalation study of multicyclic, dose-intensive chemotherapy with peripheral blood stem cell support for small cell lung cancer. 1065 7

A 57-year-old man was admitted to our hospital in November 1997 because of dysarthria, progressive ataxia, generalized weakness, and incoordination in both hands. He had been aware of the dysarthria 6 months earlier. Chest roentgenograms and computed tomographic films disclosed a 5 cm x 6 cm mass in the left S3b. The patient was given a diagnosis of small cell lung cancer (T3N2M0, stage IIIA) associated with paraneoplastic cerebellar degeneration (PCD). Three courses of chemotherapy (carboplatin and etoposide) eliminated the tumor and slightly alleviated the PCD symptoms. In March 1998, electromyograms revealed a fall in the single-stimulated M wave and a waxing phenomenon that had not been observed on admission. Anti-P/Q type voltage gated calcium channel antibody was detected in serum samples obtained on admission and after chemotherapy. These findings confirmed an association with Lambert-Eaton myasthenic syndrome. No relapse of the tumor has been observed 15 months after the last course of chemotherapy.
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PMID:[Small cell lung cancer associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome]. 1070 41

A 55-year-old man presenting with 4 weeks of progressive dysarthria, gait ataxia and vertigo was admitted to our hospital. Chest X-ray films revealed a mass shadow in the right upper lobe of the lung, and transbronchial brushing specimens showed small-cell carcinoma. Extensive examination revealed metastatic lesions in the mediastinal lymph nodes and liver, but brain MRI showed no findings suggestive of metastasis or atrophy. A diagnosis of PCD associated with SCLC was made, and the patient had a high titer of anti-P/Q-type VGCC antibody. He was treated by chemotherapy and radiation therapy, which resulted in a transient improvement in the PCD symptoms.
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PMID:[A case of small cell lung cancer with paraneoplastic cerebellar degeneration and anti-voltage-gated calcium channel antibody]. 1129 85

Paraneoplastic neurological syndromes are frequently associated in patients with small cell lung cancer (SCLC) and antineuronal antibodies are involved in the autoimmune mechanism. Multiple syndromes are sometimes complicated in a single patient with SCLC. However, little is known about non-SCLC-associated neurological manifestations. We report two patients with complicated paraneoplastic neurological syndromes. Patient 1 showed paraneoplastic limbic encephalitis (PLE), paraneoplastic sensory neuropathy (PSN) and Lambert-Eaton myasthenic syndrome (LEMS) associated with SCLC. Patient 2 developed opsoclonus-ataxia and probable PLE associated with non-SCLC. Analysis of various antineuronal antibodies revealed that anti-Hu and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in Patient 1 but any antibodies were not in Patient 2. Brain MRI demonstrated high intensity signals in temporal lobes particularly on fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted images. These findings suggest that complicated paraneoplastic neurological syndromes occur in non-SCLC as well as SCLC and that unidentified antineuronal autoantibodies may underlie the pathophysiology.
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PMID:Complicated paraneoplastic neurological syndromes: a report of two patients with small cell or non-small cell lung cancer. 1464 18

In the nervous system, voltage-gated Ca2+ channels regulate numerous processes critical to neuronal function including secretion of neurotransmitters, initiation of action potentials in dendritic regions of some neurons, growth cone elongation, and gene expression. Because of the critical role which Ca2+ channels play in signaling processes within the nervous system, disruption of their function will lead to profound disturbances in neuronal function. Voltage-gated Ca2+ channels are the targets of several relatively rare neurological or neuromuscular diseases resulting from spontaneously-occurring mutations in genes encoding for parts of the channel proteins, or from autoimmune attack on the channel protein responses. Mutations in CACNAIA, which encodes for the alpha1A subunit of P/Q-type Ca2+ channels, lead to symptoms seen in familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6. Conversely, autoimmune attack on Ca2+ channels at motor axon terminals causes peripheral cholinergic nerve dysfunction observed in Lambert-Eaton Myasthenic Syndrome (LEMS), the best studied of the disorders targeting voltage-gated Ca2+ channels. LEMS is characterized by decreased evoked quantal release of acetylcholine (ACh) and disruption of the presynaptic active zones, the sites at which ACh is thought to be released. LEMS is generally believed to be due to circulating antibodies directed specifically at the Ca2+ channels located at or near the active zone of motor nerve terminals (P/Q-type) and hence involved in the release of ACh. However, other presynaptic proteins have also been postulated to be targets of the autoantibodies. LEMS has a high degree of coincidence (approximately 60%) with small cell lung cancer; the remaining 40% of patients with LEMS have no detectable tumor. Diagnosis of LEMS relies on characteristic patterns of electromyographic changes; these changes are observable at neuromuscular junctions of muscle biopsies from patients with LEMS. In the majority of LEMS patients, those having detectable tumor, the disease is thought to occur as a result of immune response directed initially against voltage-gated Ca2+ channels found on the lung tumor cells. In these patients, effective treatment of the underlying tumor generally causes marked improvement of the symptoms of LEMS as well. Animal models of LEMS can be generated by chronic administration of plasma, serum or immunoglobulin G to mice. These models have helped dramatically in our understanding of the pathogenesis of LEMS. This "passive transfer" model mimics the electrophysiological and ultrastructural findings seen in muscle biopsies of patients with LEMS. In this model, we have shown that the reduction in amplitude of Ca2+ currents through P/Q-type channels is followed by "unmasking" of an L-type Ca2+ current not normally found at the motor nerve terminal which participates in release of ACh from terminals of mice treated with plasma from patients with LEMS. It is unclear what mechanisms underlie the development of this novel L-type Ca2+ current involved in release of ACh at motor nerve terminals during passive transfer of LEMS.
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PMID:Ca2+ channels as targets of neurological disease: Lambert-Eaton Syndrome and other Ca2+ channelopathies. 1500 May 29

Spontaneous remission (SR) of cancer, especially of lung tumor, is a rare biological event. Only seven cases in which small cell lung cancer (SCLC) regressed spontaneously had been previously reported. We report here a rare case of complete SR of SCLC in an 86-year-old man. Paraneoplastic sensory neuronopathy (PSN) is a rare syndrome, which is associated with malignancy such as SCLC and starts with dysesthetic pain and numbness in the distal extremities, then spreading all four limbs and trunk causing severe sensory ataxia. In the previous reports, SR of SCLC is suggested to result from surgical trauma or PSN, which may be able to enhance anti-tumoral immunity. Our report is the case of SR of SCLC, without any therapies nor any invasive examinations. Although the reason of SR of SCLC in the present case is unknown, PSN could be one of the diagnosis by exclusion.
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PMID:Spontaneous remission of small cell lung cancer: a case report and review in the literature. 1679 Feb 92

Paraneoplastic cerebellar degeneration (PCD) can present as a severe and (sub)acute cerebellar syndrome. PCD can accompany different kinds of neoplasms including small cell lung cancer, adenocarcinoma of the breast and ovary, and Hodgkin's lymphoma. A 34-year-old patient is described with acute dysarthria, gait ataxia and diplopia. Despite extensive laboratory and radiological evaluations in this patient with rapidly deteriorating cerebellar syndrome, the diagnosis of a paraneoplastic syndrome was only made after several months, when an anti-Tr antibody was detected in his serum. The search for Hodgkin's disease as concomitant disorder was then started and resulted in stage II B disease. The patient was successively treated with six courses of etoposide, bleomycin, vinblastine and dexamethasone and radiotherapy, which resulted in a complete remission of the Hodgkin's disease. After starting therapy the cerebellar degeneration stabilised. The pathogenesis of neuronal damage in central nervous system paraneoplastic disorders such as the one we describe is not completely understood. Antitumour therapy is assumed to be the important cornerstone in stabilising the neurological condition. Improvement of the cerebellar syndrome in anti-Tr autoantibody paraneoplastic disease is a rare achievement. Early recognition of the concomitant disorders (anti-Tr autoantibody disease and Hodgkin's lymphoma) is of crucial importance.
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PMID:Paraneoplastic cerebellar degeneration preceding the diagnosis of Hodgkin's lymphoma. 1692 86


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