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

Anti-Ri antibodies most often occur in patients with breast cancer and typically are associated with the paraneoplastic syndrome of opsoclonus-myoclonus-ataxia. This study reports a patient with diplopia and ophthalmoplegia. She had anti-Ri antibodies, and despite an exhaustive search for malignancy at presentation, breast cancer was not detected for six months.
 ...
PMID:Ophthalmoplegia associated with the anti-Ri antibody. 1060 78

The structure of a Nova protein K homology (KH) domain recognizing single-stranded RNA has been determined at 2.4 A resolution. Mammalian Nova antigens (1 and 2) constitute an important family of regulators of RNA metabolism in neurons, first identified using sera from cancer patients with the autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia (POMA). The structure of the third KH domain (KH3) of Nova-2 bound to a stem loop RNA resembles a molecular vise, with 5'-Ura-Cyt-Ade-Cyt-3' pinioned between an invariant Gly-X-X-Gly motif and the variable loop. Tetranucleotide recognition is supported by an aliphatic alpha helix/beta sheet RNA-binding platform, which mimics 5'-Ura-Gua-3' by making Watson-Crick-like hydrogen bonds with 5'-Cyt-Ade-3'. Sequence conservation suggests that fragile X mental retardation results from perturbation of RNA binding by the FMR1 protein.
 ...
PMID:Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome. 1067 14

1. Morphine is recommended by the World Health Organization as the drug of choice for the management of moderate to severe cancer pain. 2. Education of health professionals in the past decade has resulted in a large increase in the prescribing of opioids, such as morphine, and in the magnitude of the doses administered, resulting in an improvement in the quality of pain relief available for many cancer patients. 3. However, the reported incidence of neuroexcitatory side effects (allodynia, myoclonus, seizures) in patients administered large doses of systemic morphine or its structural analogue, hydromorphone (HMOR), has also increased. 4. Clinically, increasing the magnitude of the morphine or HMOR dose administered to patients already exhibiting neuroexcitatory opioid related side effects, results in an exacerbation rather than an attenuation of the excitatory behaviours. 5. In contrast, cessation of the opioid or rotation to a structurally dissimilar opioid (e.g. from morphine/HMOR to methadone or fentanyl), usually results in a restoration of analgesia and resolution of the neuroexcitatory opioid side effects over a period of hours to days. 6. To explain the clinical success of 'opioid rotation', it is essential to understand the in vivo metabolic fate of morphine and HMOR. 7. Following systemic administration, morphine and HMOR are metabolized primarily to the corresponding 3-glucuronide metabolites, morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G), which are not only devoid of analgesic activity but evoke a range of dose-dependent excitatory behaviours, including allodynia, myoclonus and seizures, following intracerebroventricular (i.c.v.) administration to rats. 8. Several studies have shown that, following chronic oral or subcutaneous morphine administration to patients with cancer pain, the cerebrospinal fluid (CSF) concentrations of M3G exceed those of morphine and morphine-6-glucuronide (analgesically active morphine metabolite) by approximately two- and five-fold, respectively. 9. These findings suggest that when the M3G concentration (or H3G by analogy) in the CSF exceeds the neuroexcitatory threshold, excitatory behaviours will be evoked in patients. 10. Thus, rotation of the opioid from morphine/HMOR to a structurally dissimilar opioid, such as methadone or fentanyl, will allow clearance of M3G/H3G from the patient central nervous system over hours to days, thereby producing a time-dependent resolution of the neuroexcitatory behaviours while maintaining analgesia with methadone or fentanyl.
 ...
PMID:Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. 1087 11

The optimal management of opioid-related side effects is hampered by a lack of comparative studies of management strategies. The prevalence of such side effects is influenced by the extent of disease, the patient's age, the presence of coexistent renal and hepatic disease, pulmonary disease, and cognitive dysfunction, a prior opioid history, use of polypharmacy, dose of opioid drug being administered, and the route of administration. The most common opioid-related side effects are constipation, sedation, nausea, vomiting, and cognitive disturbance. Less frequent side effects include urinary retention, perceptual distortion, respiratory depression, and myoclonus. In an era emphasizing quality of life in cancer care, clinicians need to be aware of (1) factors that influence the prevalence of opioid-related side effects, (2) effective management strategies, and (3) how to recognize when symptoms are opioid related as opposed to caused by other etiologies, such as the patient's disease process or treatment approaches. The use of validated instruments and repeated assessment enhances such an evaluation and subsequent treatment. This article delineates the current optimal management of opioid-related nausea and vomiting, constipation, cognitive side effects, myoclonus, and respiratory depression.
 ...
PMID:Current management of opioid-related side effects. 1127 83

Paraneoplastic syndromes are disorders associated with cancer but without a direct effect of the tumor mass or its metastases on the nervous system. Small cell carcinoma of lung associated with paraneoplastic sensory neuronopathy and/or paraneoplastic encephalomyelitis with the presence of anti-Hu antibodies has been termed "anti-Hu syndrome." Anti-Hu associated PSN-PEM is an immune disorder in which both cell-mediated and humoral mechanisms are involved. Patients are considered affected by Anti-Hu associated PSN-PEM when they develop clinical signs and symptoms of CNS dysfunction and/or sensory neuropathy not caused by metastases or other disorders, and serum or cerebrospinal fluid is positive for Hu abs. SCLC is found in more than 90% of patients with cancer and positive Hu abs. Individual patients with Hu abs associated to SCLC may suffer PSN-PEM, limbic encephalitis, brainstem encephalopathy, opsoclonus-myoclonus, paraneoplastic cerebellar degeneration or myelopathy. Hu abs have a specificity of 99% and sensitivity of 82% in detecting paraneoplastic neurological syndromes. There are two types of treatment: the first is to treat the cancer, the second is to suppress the immune reaction with the use of corticosteroids, cyclophosphamide, azathioprine, plasma exchange, intravenous immunoglobulin and immunoadsorption; however, treatment of paraneoplastic syndromes is generally unsatisfactory.
 ...
PMID:Paraneoplastic syndromes associated with anti-Hu antibodies. 1134 32

Chronic opioid medication has been found to cause myoclonus in patients taking it for cancer pain. Gabapentin seemed a likely candidate for the treatment of this myoclonus and has indeed proved useful, as illustrated in this paper by two case histories.
Support Care Cancer 2001 May
PMID:Gabapentin for opiod-related myoclonus in cancer patients. 1140 Nov 5

Opsoclonus is a rare but distinctive disorder of ocular motility, characterized by irregular, continual and conjugated chaotic saccades of the eyes. It is increased with eye closure and fixation, and it persists during sleep. Opsoclonus appears more commonly in children and in half of such cases in association with neuroblastoma. In adults the most frequent causes are idiopathic (50%) and paraneoplastic (20%). Among the second group, different types of tumors involving a wide variety of organs have been reported. Opsoclonus when accompanied by other symptoms of central nervous system involvement (head, appendicular myoclonus and truncal ataxia) constitutes a clinical picture, known as opsoclonus-myoclonus syndrome. We report the case of a young patient affected by renal cell carcinoma associated with opsoclonus-myoclonus syndrome which did not respond to medical therapy but dramatically improved after cancer ablation.
 ...
PMID:Opsoclonus-myoclonus syndrome as a paraneoplastic manifestation of renal cell carcinoma. a case report and review of the literature. 1191 72

The review presents an overview on the pathogenesis of paraneoplastic neurological disorders (PNDs) and the current therapeutic immunosuppressive or immunomodulatory strategies used in these patients. PNDs are disturbances in the functioning of the nervous system in cancer patients, where the disturbances are not due to a local effect of the tumour or its metastases. Most of these clinically, well-defined syndromes in adults are associated with lung cancer (especially small cell lung cancer), lymphomas and gynaecological tumours. Since autoantibodies directed against proteins expressed in neurons and tumour cells have been found, PNDs are suspected to be autoimmune. In neuromuscular PND, immunosuppressive therapies, plasmapheresis and intravenous immunoglobulins are effective treatments. In contrast, central nervous system PNDs seen in adults are by far the most problematic group to treat. With exception of the stiff-man syndrome, immunosuppression appears to have little effect on these neurological disorders. Tumour therapy stabilises PNDs but does not cause improvement. Plasmapheresis reduces the autoantibody titre in the sera of these patients but, like tumour therapy, does not lead to a clinical improvement. In children with paraneoplastic opsoclonus-myoclonus syndrome, steroids and intravenous immunoglobulins may lead to a complete or partial remission of PNDs.
 ...
PMID:Immunotherapeutic approaches to paraneoplastic neurological disorders. 1195 79

Mental status changes are second only to headaches as a cause of neurologic consultation in children with systemic cancer, but the literature on these patients is sparse. This study consisted of a review of the consultations because of changes in mental status in patients with pediatric cancer, with analysis of clinical presentation, etiology, underlying cancer, and neuroradiologic findings. Hematologic cancers were the underlying disorder in slightly more than one half of the patients. The majority of children suffered from iatrogenically induced encephalopathy, predominantly opioid-related. Several drugs were associated with depressed sensorium, but a pure metabolic deficit was rare. One third of the patients had multiple causative factors. Neuroimaging studies were particularly helpful in children with unexplained somnolence but were less useful if the patient had hallucinations. The absence of localizing signs in children with unexplained somnolence or stupor did not exclude the presence of structural disease. Altered mental status is frequently observed in children being actively treated for systemic cancer. The majority of children suffer from iatrogenically induced encephalopathy, predominantly opioid-related. The presence of hallucinations favors a toxic-metabolic dysfunction, especially if associated with myoclonus. Under those circumstances a neuroimaging study is usually unrewarding. If the main complaint is unexplained somnolence without hallucinations or delusions, the performance of a brain imaging study is mandatory, even in the absence of localizing signs.
 ...
PMID:Mental status changes in children with systemic cancer. 1216 Sep 72

The study objective was to determine whether switching patients from morphine to transdermal fentanyl resulted in a reduction of morphine-associated side effects, and an improvement in cognitive function and patients' well being while maintaining adequate pain and symptom control. Nineteen patients aged 42-86 with terminal cancer, maintained on morphine for pain and distressed as a result of morphine toxicity, were given the dose of fentanyl corresponding to their current morphine dose. Pain control was then maintained (mostly fentanyl 50-100 microg/h) over the 14-day study period. Throughout the study, patients' global assessment of well being (primary efficacy variable) was statistically significantly improved. Sleepiness and drowsiness were significantly less of a problem. There was a trend towards improvement in attention span/concentration, and in the power and quality of concentration. Cognitive function tests also revealed a significant improvement in working (short term) and speed of memory although not in secondary (long term) memory. Patients did not experience hallucinations or delusions and there was no change in levels of anxiety or depression (Hospital Anxiety Depression Scale). The incidence of dizziness was significantly reduced, and there was a nonsignificant decrease in number of patients who suffered myoclonus and in the severity of this condition over the 14 days. The investigator's overall impression of treatment with transdermal fentanyl was 'fair', which was not in agreement with the positive impression expressed by patients (score 74, range: 0 worst, 100 best). Further work is required to determine if the improvement in patients' well being and cognitive function is achieved in larger study populations.
 ...
PMID:Opioid switching from morphine to transdermal fentanyl for toxicity reduction in palliative care. 1238 Jun 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>