Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hashimoto's encephalopathy (HE) has been described as an encephalopathy, with acute or subacute onset, accompanied by seizures, tremor, myoclonus, ataxia, psychosis, and stroke-like episodes, with a relapsing/remitting or progressive course. HE patients have positive antithyroid antibodies, are usually in a subclinical hypothyroid state, have elevated cerebral spinal fluid (CSF) protein, and have nonspecific electroencephalogram (EEG) and imaging abnormalities in the absence of CNS infection, tumor, or stroke. The authors present two cases of HE, demonstrating an excellent response to high dose steroids acutely followed by long-term treatment with steroids and other immunomodulatory agents. A review of the literature is also provided.
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PMID:Long-term treatment of Hashimoto's encephalopathy. 1652 66

Paraneoplastic Neurologic Diseases (PND) are remote complications of certain neoplastic diseases characterized by distinct neurological deficits in the central as well as the peripheral nervous system. The neurological disorders are usually clinically evident before the cancer is identified. PND are rare syndromes believed to have an immunological link where antibodies or activated T cells are acting against self antigens shared by the tumor cells and neurons. Most of these onconeural antigens are located in the cytoplasm-nuclear compartment of the cell, whereas others are located at the membrane and act as receptors or ion channels. This short review discusses the autoimmune mechanisms involved in PND in general and in opsoclonus-myoclonus-ataxia in particular. The article attempts to clarify why in most PND the immune effector mechanisms against onconeural antigens detected in sera of patients may not be the direct cause of the neurological deficit. We elaborate on the difference between the immune response against cytoplasmic-nuclear antigens as opposed to membranal antigens with regard to the fact that: a) the nervous system is considered immune privileged; b) neither the tumors nor the neurons have an optimal expression of MHC class I antigens and onconeural epitopes on the membrane. The availability of onconeural antigens to the immune effectors mechanisms is probably the main reason why there are few animal models for PND.
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PMID:[Autoimmune mechanisms in paraneoplastic neurological diseases: the paradigm of opsoclonus myoclonus ataxia syndrome]. 1664 34

Epilepsy of progressive myoclonus type 2 gene A (EPM2A) encodes a dual specificity protein phosphatase called Laforin. Laforin is also a tumor suppressor that dephosphorylates GSK3beta at the critical Ser9 position and regulates Wnt signaling. The epilepsy-causing mutations have a deleterious effect on phosphatase activity, regardless of whether they locate in the carbohydrate-binding domain (CBD) at the N terminus or the dual specificity phosphatase domain (DSPD) at the C terminus. How mutations outside the DSPD reduce the phosphatase activity of Laforin remains unexplained. Here we report that Laforin expressed in mammalian cells forms dimers that are highly resistant to SDS treatment. Deleting CBD completely abolished the dimerization and phosphatase activity of Laforin. Moreover, all of the naturally occurring Laforin mutations tested impaired laforin GSK3beta dephosphorylation at Ser9 dimerization, and beta-catenin accumulation in nucleus. Our results demonstrate a critical role of dimerization in Laforin function and suggest an important new dimension in protein phosphatase function and in molecular pathogenesis of Lafora's disease.
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PMID:Dimerization of Laforin is required for its optimal phosphatase activity, regulation of GSK3beta phosphorylation, and Wnt signaling. 1697 87

Opsoclonus-myoclonus syndrome (OMS) in children is a rare neurological condition with opsoclonus, myoclonus, ataxia and irritability in the first 2 years of life. It can be idiopathic, parainfectious, or paraneoplastic with tumours of the neural crest. Few studies of long-term follow-up after OMS have been published. We investigated the motor, cognitive and behavioural outcome of ten patients (eight girls and two boys) seen between 1987 and 2002. We reviewed the records and reassessed the patients. A ganglioneuroma was found in one patient and a neuroblastoma in another. Tumour resection did not influence the OMS. The age at diagnosis was 10-24 months and the follow-up period 1-17 years (average 6.5 years). The interval between the first signs and symptoms and starting treatment was 2-12 weeks: treatment consisted of different immunosupressants. Remission was achieved within 5 months in seven, and relapses were present in seven of ten. At follow-up, only one child had mild ataxia. IQ testing was performed in nine with scores below 75 in four and above 85 in four. Attention deficit and visuomotor difficulties led to school problems with special needs, also in those three children with normal IQs. Only two children were attending regular schools. Behavioural problems were reported in seven, and speech difficulties were present in five. In conclusion, the long-term outcome in our patients with OMS was dominated by cognitive and behavioural problems and not by ataxia. Compared with previous reports, our patients were treated earlier. Larger studies and uniform treatment protocols are needed to demonstrate whether early and prolonged immunosupressant therapy has a favourable influence on outcome.
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PMID:Long-term outcome of ten children with opsoclonus-myoclonus syndrome. 1708 89

Opsoclonus-myoclonus-ataxia-syndrome (OMS) represents a rare neuroblastoma-associated paraneoplastic syndrome that commonly results in neurologic deficits despite tumor resection and immunosuppressive therapy. We describe the response of five such children to high-dose dexamethasone pulses including two patients in whom previous glucocorticoids, rituximab, and cytostatic drugs were not successful. All patients had MYCN non-amplified tumors that were detected 1 to 7 months after the onset of the OMS or ataxia. This treatment resulted in a good partial response in three and in complete remission in two patients. Our results show that dexamethasone pulses are likely to be useful for both, first-line- and salvage-therapy for OMS-patients.
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PMID:Treatment of neuroblastoma-related opsoclonus-myoclonus-ataxia syndrome with high-dose dexamethasone pulses. 1722 43

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

We report an autopsy case of paraneoplastic opsoclonus-myoclonus-ataxia syndrome associated with small cell carcinoma of the lung. Chemotherapy and lung lobectomy resulted in complete tumor remission and disappearance of myoclonus. However, emotional and behavioral disturbances relapsed and remitted associated with exacerbation of truncal ataxia and ocular flutter, which responded favorably to prednisolone. At autopsy, after 2 years and 11 months of illness, there was no recurrence of cancer. Neuropathologically, only the cerebellum was affected, with diffuse loss of Purkinje cells and dentate neurons, suggesting that the paraneoplastic cerebellar involvement may be responsible for the cognitive affective symptoms in our patient.
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PMID:Autopsy case of opsoclonus-myoclonus-ataxia and cerebellar cognitive affective syndrome associated with small cell carcinoma of the lung. 1753 81

Paraneoplastic neurological syndromes (PNS) are remote effects of cancer, which are not caused by invasion of the tumour or its metastasis, but presumably immunologic mediated. They developed in less than 1% of patients with systemic cancers, most Limbic encephalitis (LE) is the most common clinical paraneoplastic syndrome attainting the CNS (Central Nervous System), and it is characterized by involvement of hippocampus and amygdala; LE is also the only one with clearly defined imaging features. We report a 64 year old man, former smoker, which presented multiple paraneoplastic syndromes, namely LE, opsoclonus-myoclonus, subacute cerebellar degeneration, brainstem encephalitis, sensory-motor neuropathy and inappropriate antidiuretic hormone secretion syndrome (SIADH); these syndromes were identifiable in the clinical and imaging examination, confirmed by the neuro-pathological study. Magnetic Resonance Imaging disclosed on T2 weighted images bilateral hyperintensity within medial temporal lobes, hypothalamus, thalamus, brain stem, upper and medium cerebellar peduncles and upper cervical spinal cord. The underlying tumour was not found in imaging studies or in the autopsy examination. A mediastinal adenopathy depicted a metastasis from low differentiated neoplasm cells, with some signs of neuroendocrine differentiation. With this case we provide a comprehensive illustration of the PNS, from a clinical, imaging and pathological point of view. This report also emphasises the importance of a diagnosis based on early clinical and imaging findings, given that, in most cases the cancer is not apparent.
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PMID:[Multiple paraneoplastic syndromes occurring in the same patient: clinical, imaging and neuro-pathological documentation]. 1758 9

We describe a man of 59 years old, a smoker (20 cigarettes per day), without any pathologic background, with epilepsia partialis continua, with a relatively sudden appearance in the last 6 weeks. We wanted to find the cause of these prolonged focal seizures. The initial diagnosis of emergency was that of right side hemiballismus. The initial diagnosis on admission was prolonged right brachial myoclonus. Initially I was thinking of primary tumor or secondary one but paraclinic examinations excluded this diagnosis. After 5 months I repeated cerebral MRI scan which revealed left neoplasm of cavum. After another 6 months head and neck MRI described left rhinopharyngeal neoplasm with laterocervical adenopathies, cerebral metastases secondary to bronchopulmonary cancer with mediastinal invasion. The epilepsia partialis continua preceded by one year the primary neoplastic process.
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PMID:[Paraneoplastic syndrome presenting as epilepsia partialis continua]. 1829 93

Opsoclonus-myoclonus-ataxia syndrome (OMS) is a rare neurological disorder of probably autoimmune origin. Most cases are associated with a remote neoplasm or a viral infection; however in some instances no underlying aetiology can be demonstrated. We report the presence of anti-glutamic acid decarboxylase antibodies (anti-GAD Abs) in the serum and CSF of a patient with idiopathic OMS. Treatment with intravenous immunoglobulin led to a remarkable clinical improvement with parallel reduction of anti-GAD titers. Anti-GAD Abs have been associated with several neurological syndromes. They could also be responsible for the clinical triad of OMS, by impairing GABAergic transmission in specific brainstem and cerebellar circuits. We propose that testing for anti-GAD Abs should be performed in OMS, especially when no other aetiological association can be demonstrated.
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PMID:Opsoclonus-myoclonus-ataxia syndrome with autoantibodies to glutamic acid decarboxylase. 1843 86


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