Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuron-restricted autoantibodies are important markers of neurological autoimmunity related to cancer. We identified a new paraneoplastic IgG, PCA-2 (Purkinje cell cytoplasmic antibody type 2), in 10 patients. Nine had mixed subacute neurological presentations (5 brainstem or limbic encephalitis, 3 cerebellar ataxia, 2 Lambert-Eaton myasthenic syndrome, 1 autonomic neuropathy, and 1 motor neuropathy). All 9 were smokers, and 8 had definite or probable lung cancer (7 with biopsy-confirmed small cell lung carcinoma [SCLC]; 1 imaged only). One patient had no follow-up information. A 10th patient was among 58 with uncomplicated SCLC. PCA-2 binds to a cytoplasmic antigen in neurons and SCLC cells. Its immunostaining pattern in mouse tissues is distinct from that of the paraneoplastic autoantibodies PCA-1 (anti-Yo, marker of immune response initiated by ovarian or breast carcinoma) and PCA-Tr (anti-Tr, immune response marker of Hodgkin's lymphoma). PCA-2 binds to cerebellar Purkinje somata and dendrites, neurons in internal granular layer and dentate nucleus, and neuronal elements in gut and kidney. Western blots of reduced/denatured cerebellar and SCLC proteins reveal a common antigenic band, of approximately 280 kd. PCA-2 is the seventh IgG neuronal autoantibody marker of paraneoplastic autoimmunity identifiable unambiguously by standardized immunofluorescence criteria.
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PMID:New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. 1071 48

The neuromuscular junction lacks the protection of the blood-nerve barrier and is vulnerable to antibody-mediated disorders. In myasthenia gravis (MG), 85% of patients have IgG antibodies to acetylcholine receptors (AChRs). About half the remaining patients have IgG antibodies to Muscle Specific Kinase (MuSK), an AChR-associated transmembrane post-synaptic protein concerned in AChR aggregation. Bulbar weakness is typically predominant in this form of MG, and females are more often affected. The Lambert-Eaton Myasthenic Syndrome (LEMS) can occur in a paraneoplastic form (P-LEMS) usually with small cell lung cancer, or in a non-paraneoplastic form (NP-LEMS). In both, IgG antibodies to nerve terminal voltage-gated calcium channels (VGCCs), detectable in over 90% of patients, lead to VGCC loss and impaired quantal release of transmitter and may be implicated in the occasionally associated cerebellar ataxia. Neuromyotonia (NMT) and Cramp-Fasciculation syndrome (C-FS) are manifestations of peripheral nerve hyperexcitability and share some clinical and electromyographic features. Antibodies to voltage-gated potassium channels (VGKCs) are present in about 40% of NMT patients, but less frequently in C-FS, and appear to cause loss of functional VGKCs. They may also be implicated in the Maladie de Morvan and limbic encephalitis that can associate with NMT: The antibodies described here provide valuable aids to diagnosis and management. The Congenital Myasthenic Syndromes are a group of genetically determined heterogeneous disorders, usually recessively inherited. The commonest mutation sites appear to be the acetylcholine receptor epsilon-subunit and rapsyn.
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PMID:Neuromuscular junction channelopathies: a brief overview. 1648 66

Thirty years ago, antibodies against the muscle acetylcholine receptor (AChR) were recognized as the cause of myasthenia gravis. Since then, there has been great interest in identifying other neurological disorders associated with autoantibodies. Several other antibody-mediated neuromuscular disorders have been identified, each associated with an antibody against a ligand- or voltage-gated ion channel. The Lambert-Eaton syndrome is caused by antibodies against voltage-gated calcium channels and often occurs in patients with small cell lung cancer. Acquired neuromyotonia is caused by voltage-gated potassium channel antibodies, and autoimmune autonomic ganglionopathy is caused by antibodies against the neuronal AChR in autonomic ganglia. There is good evidence that antibodies in these disorders cause changes in synaptic function or neuronal excitability by directly inhibiting ion channel function. More recently, studies have identified ion channel antibodies in patients with certain CNS disorders, such as steroid-responsive encephalitis and paraneoplastic cerebellar ataxia. It remains unclear if antibodies can gain access to the CNS and directly cause ion channel dysfunction. Treatment of autoimmune channelopathies includes drugs that help restore normal neuronal function and treatments to remove pathogenic antibodies (plasma exchange) or modulate the immune response (steroids or immunosuppressants). These disabling neurological disorders may be dramatically responsive to immunomodulatory therapy. Future studies will likely lead to identification of other ion channel antibodies and other autoimmune channelopathies.
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PMID:Autoimmune and paraneoplastic channelopathies. 1739 41

Paraneoplastic neurological syndromes (PNS) can be defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or metabolic disruptions. PNS are rare, affecting less than 1/10,000 patients with cancer. Only the Lambert-Eaton myasthenic syndrome is relatively frequent, occurring in about 1% of patients with small cell lung cancer. PNS can affect any part of the central and peripheral nervous system, the neuromuscular junction, and muscle. They can be isolated or occur in association. In most patients, the neurological disorder develops before the cancer becomes clinically overt and the patient is referred to the neurologist who has the charge of identifying a neurological disorder as paraneoplastic. PNS are usually severely disabling. The most common PNS are Lambert-Eaton myasthenic syndrome (LEMS), subacute cerebellar ataxia, limbic encephalitis (LE), opsoclonus-myoclonus (OM), retinopathies (cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), Stiff-Person syndrome (SPS), chronic gastrointestinal pseudoobstruction (CGP), sensory neuronopathy (SSN), encephalomyelitis (EM) and dermatomyositis. PNS are caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and the nervous system, designated as onconeural antigens. Due to their high specificity (> 90%), the best way to diagnose a neurological disorder as paraneoplastic is to identify one of the well-characterized anti-onconeural protein antibodies in the patient's serum. In addition, as these antibodies are associated with a restricted range of cancers, they can guide the search for the underlying tumor at a stage when it is frequently not clinically overt. This is a critical point as, to date, the best way to stabilize PNS is to treat the cancer as soon as possible. Unfortunately, about one-third of patients do not have detectable antibodies and 5% to 10% have an atypical antibody that is not well-characterized. As PNS are believed to be immune-mediated, suppression of the immune response represents another treatment approach.
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PMID:Paraneoplastic neurological syndromes. 1748 Feb 25

Opsoclonus myoclonus syndrome, one of the paraneoplastic neurological syndromes involving several neurological symptoms that result from "remote effects" of cancer, is a rare disease characterized by opsoclonus, cerebellar ataxia and myoclonus of the trunk and extremities. A 53-year-old man was admitted with dizziness and difficulty walking. Medical examinations led to a diagnosis of opsoclonus myoclonus syndrome. CT scans showed mediastinal and cervical lymphadenopathy, and a diagnosis of small cell lung cancer was made. Steroid therapy and chemotherapy (carboplatin + etoposide) produced significant improvement in the neurological symptoms.
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PMID:[Small cell lung cancer complicated by opsoclonus myoclonus syndrome]. 1999 3

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disorder in which autoantibodies inhibit the presynaptic release of acetylcholine. Autoantibodies against P/Q-type voltage-gated calcium channels (VGCC) are detected in 85% of patients with LEMS. In addition, autoantibodies to synaptotagmin, an M1-type muscarinic acetylcholine receptor and SOX1 are also found in the sera of patients with LEMS. LEMS is closely associated with small cell lung cancer (SCLC) in 50-60% of patients. Patients with SCLC who have anti-VGCC antibodies have been reported to have a favorable prognosis. In contrast to paraneoplatic LEMS, other forms of LEMS may have an autoimmune aspect because of the established association between human leukocyte antigen and a family history of other autoimmune disorders in this condition. The clinical features of LEMS include proximal weakness, areflexia, ptosis, cerebellar ataxia and autonomic dysfunction. The findings of electrophysiological examination show that LEMS is characterized by compound muscle action potential potentials with a low amplitude and increment upon repetitive nerve stimulation at a high rate. Tumor removal is the primary treatment of LEMS. The efficacy of 3,4-diaminopyridine for the treatment of LEMS has also been established. Patients with LEMS require the immunotherapies such as plasma exchange and the administration of high doses of immunoglobulin and prednisolone.
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PMID:[Lambert-Eaton myasthenic syndrome (LEMS)]. 2042 Jan 83

Paraneoplastic cerebellar degeneration (PCD) is a rare disorder presenting typically with acute or subacute severe cerebellar ataxia. PCD is most commonly associated with small cell lung cancer followed by adenocarcinoma of breast and ovary, and Hogdkin's lymphoma. We report a case of a 54-year-old male with acute-onset pancerebellar syndrome with underlying Hodgkin's lymphoma. A high index of suspicion of PCD resulted in arriving at an early diagnosis of underlying Hodgkin's disease. The patient was managed with six cycles of chemotherapy, which resulted in clinical stabilization and reversal of magnetic resonance imaging abnormalities. Antitumor therapy appears to have a significant impact on reversing PCD and hence early diagnosis and intervention for the primary remains the corner stone in stabilizing the neurological condition.
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PMID:Paraneoplastic cerebellar degeneration in Hodgkin's lymphoma. 2291 95

A 62-year-old man who had suffered from instability of gait and double vision for two months was admitted to our hospital because of weakness of the extremities and ataxia of the extremities and trunk. Chest X-rays and CT scans showed enlargement of the left hilar lymph nodes and a nodular shadow in the left lung. Transbronchial biopsy revealed small cell lung cancer. We diagnosed the patient with two conditions: paraneoplastic cerebellar degeneration (PCD), based on cerebellar ataxia, the presence of Hu antineuronal antibodies, and the absence of cerebellar atrophy and malignancy; and Lambert-Eaton myasthenic syndrome (LEMS), based on weakness of the extremities, the presence of P/Q-type voltage-gated calcium channel antibodies, and waxing in the evoked electromyogram. Anticancer chemoradiation therapy that was started within three months of symptom onset resulted in reductions in size of the hilar lymph nodes and the nodule. Concurrently, cerebellar ataxia, weakness of the extremities, and double vision all disappeared. Anticancer chemotherapy is effective against LEMS while usually less effective against PCD. Early commencement of anticancer chemotherapy is recommended for the treatment of PCD with LEMS.
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PMID:[Synchronous appearance and improvement with anticancer chemotherapy of paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome complicated with small cell lung cancer]. 2347 Aug 89

Paraneoplastic cerebellar degeneration (PCD) can occur severely and appear as subacute cerebellar syndrome. PCD may be associated with small cell lung cancer, adenocarcinoma, breast cancer, ovarian carcinoma, and Hodgkin's lymphoma. An 11-year-old male was admitted with acute cerebellar ataxia, dysarthria, and diplopia. Mediastinal conglomerated lymph nodes were depicted in a chest computed tomography (CT) examination, and diagnosis of stage IV Hodgkin's lymphoma was obtained after a lymph node biopsy. The antibodies against Purkinje cells (anti-Tr antibody) were positive immunohistochemically. Thus, paraneoplastic cerebellar degeneration depending on Hodgkin's disease was diagnosed. Despite the completion of chemotherapy, neurological recovery was not observed in the patient and plasmapheresis with immunoadsorption, and intravenous immunoglobulin (IVIG) was performed. Truncal ataxia, gait disturbance, and tremors decreased. Consequently, we thought that plasmapheresis with the immunoadsorption method and IVIG therapy might be a treatment option for cerebellar ataxia caused by a mechanism of immune ancestry.
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PMID:Hodgkin's lymphoma associated with paraneoplastic cerebellar degeneration in children: a case report and review of the literature. 2844 49

Paraneoplastic cerebellar ataxia (PCA) is most frequently observed in gynaecological cancers, small cell lung cancer, breast cancer, Hodgkin's lymphoma, cancer testis or malignant thymoma. In the literature, there is no data related to the effects of PCA during pregnancy or reports on the effects of anaesthesia in patients with PCA. We present management of a pregnant woman with PCA who was suddenly unable to walk with PCA and for whom effective spinal anaesthesia was performed for an elective caesarean section with no complications.
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PMID:Spinal anaesthesia for a caesarean section in a patient with paraneoplastic cerebellar ataxia. 2851 24


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