Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Baclofen is a central nervous system agent that is commonly used for the treatment of muscle spasticity in spinal cord injury patients. Acute withdrawal of this medication can induce the development of neurological symptoms, including seizure disorder, psychosis, hallucinations and visual disturbances. We report 3 cases of acute central nervous system symptoms that developed in spinal cord injury patients. Each patient had been chronically maintained on a baclofen regimen to control muscle spasticity. Symptoms developed shortly after baclofen therapy was interrupted following genitourinary surgery. It is important that urologists become familiar with the symptomatology of baclofen withdrawal, the methods of its prevention and the appropriate therapy should the syndrome develop.
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PMID:Neurological manifestations of baclofen withdrawal. 823 May 32

Glutamate is the major excitatory neurotransmitter of the central nervous system. Besides its importance in many physiological processes, increased glutamate release and subsequent excessive stimulation of the various glutamate receptors are thought to play critical roles in the pathophysiological mechanisms underlying many neurologic diseases. Experimental data suggest that blockade of glutamate receptors or inhibition of glutamate release has positive effects in many disease models. Glutamate antagonists are already in clinical use for the treatment of Parkinson's disease, epilepsy, spasticity, and neuropathic pain. Overall, glutamate antagonists have not been found clinically effective for neuroprotective treatment of cerebral ischemia or chronic neurodegenerative diseases, with one exception. Side effects of glutamate antagonists can be mainly attributed to central mechanisms and include psychosis, agitation, and disorientation. It is to be hoped that further development of new glutamate antagonists that block disease-relevant subtypes of glutamate receptors will lead to more effective drugs with fewer side effects.
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PMID:[Glutamate antagonists in neurology]. 1143 98

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury. The UK Government stated that it would be willing to amend the Misuse of Drugs Act 1971 to permit the introduction of a cannabis-based medicine. GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing High THC in more than 100 patients with cancer pain in the UK. Also included is a phase III trial of THC:CBD (narrow ratio) being conducted in patients with severe pain due to brachial plexus injury, as are two more phase III trials of THC:CBD (narrow ratio) targeting spasticity and bladder dysfunction in multiple sclerosis patients. Another phase III trial of THC:CBD (narrow ratio) in patients with spinal cord injury is also being conducted. Results from the trials are expected during 2003. Three additional trials are also in the early stages of planning. These trials include a phase I trial of THC:CBD (broad ratio) in patients with inflammatory bowel disease, a phase I trial of High CBD in patients with psychotic disorders such as schizophrenia, and a preclinical trial of High CBD in various CNS disorders (including epilepsy, stroke and head injury). GW Pharmaceuticals submitted an application for approval of cannabis-based medicines to UK regulatory authorities in March 2003. Originally GW hoped to market cannabis-based prescription medicines by 2004, but is now planning for a launch in the UK towards the end of 2003. Several trials for GW's cannabis derivatives have also been completed, including four randomised, double-blind, placebo-controlled phase III clinical trials conducted in the UK. The trials were initiated by GW in April 2002, to investigate the use of a sublingual spray containing THC:CBD (narrow ratio) in the following medical conditions: pain in spinal cord injury, pain and sleep in MS and spinal cord injury, neuropathic pain in MS and general neuropathic pain (presented as allodynia). Results from these trials show that THC:CBD (narrow ratio) caused statistically significant reductions in neuropathic pain in patients with MS and other conditions. In addition, improvements in other MS symptoms were observed as well. Phase II studies of THC:CBD (narrow ratio) have also been completed in patients with MS, spinal cord injury, neuropathic pain and a small number of patients with peripheral neuropathy secondary to diabetes mellitus or AIDS. A phase II trial of THC:CBD (broad ratio) has also been completed in a small number of patients with rheumatoid arthritis, as has a trial of High CBD in patients with neurogenic symptoms. A phase II trial has also been evaluated with High THC in small numbers of patients for the treatment of perioperative pain. The phase II trials provided positive results and confirmed an excellent safety profile for cannabis-based medicines. GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury in 2002. Following meetings with the US FDA, Drug Enforcement Agency (DEA), the Office for National Drug Control Policy, and National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the US. Preclinical research with these extracts in the US is ongoing.
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PMID:Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD. 1295

The evidence for the therapeutic efficacy of cannabinoids in the treatment of multiple sclerosis (MS) is increasing but is not as yet convincing. Although several trials have reported no significant effect, the majority of the evidence which supports a beneficial effect on spasticity and pain is based on subjective measurements in trials where unblinding was likely to be a problem. The available clinical trial data suggest that the adverse side effects associated with using cannabis-based medicinal extracts (CBMEs) are generally mild, such as dry mouth, dizziness, somnolence, nausea and intoxication, and in no case did toxicity develop. However, most of these trials were run over a period of months and it is possible that other adverse side effects, not seen in these short-term studies, could develop with long-term use. Despite the evidence that cannabinoids can disrupt cognitive function and promote depression, on the basis of current data, such adverse effects seem unlikely to be associated with the use of CBMEs. Likewise, there is no evidence to suggest that their effects on balance and motor control, or immune function, may be clinically significant. There is, however, reason to be concerned about the use of therapeutic cannabinoids by people predisposed to psychosis and by pregnant women, given the increasing evidence of their adverse effects on the fetus. In conclusion, given the modest therapeutic effects of cannabinoids demonstrated so far, and the risk of long-term adverse side effects, there is reason to be cautious about their use in the treatment of MS.
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PMID:The safety of cannabinoids for the treatment of multiple sclerosis. 1593 52

Hereditary spastic paraparesis (HSP) is characterized by progressive spasticity and weakness of the legs with or without additional abnormalities. Reports of psychiatric disorders in patients with HSP are limited to mood disturbances rather than to psychosis. We had noted significant psychotic illness in several patients recruited to a survey of HSP in Ireland and therefore set about examining the frequency and nature of psychosis in our patients with HSP. Cases with HSP and psychotic illness were identified from a nationwide epidemiological and clinical study. Psychiatric case notes were reviewed and Operational Diagnostic Criteria Checklist (OPCRIT) applied. Six patients from four families with HSP had evidence of psychosis in addition to paraparesis. OPCRIT diagnoses were 'narrow schizophrenia' (n = 2), 'broad schizophrenia' (n = 2) and 'schizo-affective/manic disorder' (n = 2). Patients were from families with Kjellin's syndrome and SPG4-HSP but not other kindreds and psychosis was not evident in family members without HSP. We found a higher than expected rate of psychosis in the Irish HSP population. Two groups of HSP patients may have increased risk of developing psychosis: those with Kjellin's syndrome and those with SPG4-HSP.
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PMID:Hereditary spastic paraparesis and psychosis. 1687 99

Mitochondrial disorders, in particular respiratory chain diseases (RCDs), present either as single organ problem or as multi-system disease. One of the most frequently affected organs in RCDs, in addition to the skeletal muscle, is the central nervous system (CNS). CNS manifestations of RCDs include epilepsy, stroke-like episodes, migraine-like headache, ataxia, spasticity, movement disorders, psychosis, demyelination, calcification, but also dementia. Cognitive impairment may be a feature of syndromic as well as non-syndromic RCDs. Syndromic RCDs associated with cognitive impairment include MELAS, KSS, Leigh syndrome, and many others. RCDs with cognitive decline not only result from mtDNA mutations but also from mutations in nuclear genes. At onset there is often no general intellectual deterioration in these patients but specific cognitive deficits, particularly in the visual construction, attention, abstraction, or flexibility. Diagnosis of cognitive impairment from RCDs is based on neuropsychological testing, imaging studies, including MRI, PET, SPECT, or MR-spectroscopy, CSF investigations, or electroencephalography. Therapeutic strategies for dementia in RCDs rely on symptomatic measures. Only single patients may profit from cholinesterase inhibitors or memantine, antioxidants, vitamins, or other substitutes. Overall, cognitive decline in RCDs (mitochondrial dementia) needs to be included in the differentials of dementia.
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PMID:Cognitive decline as a manifestation of mitochondrial disorders (mitochondrial dementia). 1857 95

Late-onset Tay-Sachs (LOTS) disease is a chronic, progressive, lysosomal storage disorder caused by a partial deficiency of beta-hexosaminidase A (HEXA) activity. Deficient levels of HEXA result in the intracellular accumulation of GM2-ganglioside, resulting in toxicity to nerve cells. Clinical manifestations primarily involve the central nervous system (CNS) and lower motor neurons, and include ataxia, weakness, spasticity, dysarthria, dysphagia, dystonia, seizures, psychosis, mania, depression, and cognitive decline. The prevalence of peripheral nervous system (PNS) involvement in LOTS has not been well documented, but it has traditionally been thought to be very low. We examined a cohort of 30 patients with LOTS who underwent clinical and electrophysiologic examination, and found evidence of a predominantly axon loss polyneuropathy affecting distal nerve segments in the lower and upper extremities in eight patients (27%).
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PMID:Late-onset Tay-Sachs disease: the spectrum of peripheral neuropathy in 30 affected patients. 1864 77

A novel X-chromosome linked phenotype is reported. Three affected males had learning disability in early childhood and subsequently developed progressive ataxia, dystonia, and spasticity with death at ages 9, 14 and 19 years. Two female obligate carriers had learning difficulties with psychosis in one case. A third, possible carrier had learning difficulties and epilepsy. A family study indicates that this inherited syndrome is most likely due to an unreported MECP2 variant, p.V122A, located in the methyl binding domain of the MECP2 protein. The clinical features are similar to those present in the newly reported MECP2 duplication syndrome. Non-progressive neuropsychiatric symptoms in female relatives of a male child with learning disability, ataxia and progressive spasticity may constitute a clue to inherited, MECP2 pathogenesis.
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PMID:Semi-dominant X-chromosome linked learning disability with progressive ataxia, spasticity and dystonia associated with the novel MECP2 variant p.V122A: akin to the new MECP2 duplication syndrome? 1959 82

The total anterior tenoarthrolysis (TATA) allows tenolysis, arthrolysis and skin repair in the same operation, avoiding combined different surgical procedures. The authors present a series of personal and original indications and propose a partial anterior tenoarthrolysis (PATA) for the treatment of isolated stiffness of the proximal interphalangeal joint or in the presence of less severe flexion contractures. The etiology was wide various, and the TATA revealed to be extremely useful also in tetraplegia or spasticity, permitting respectively the following tendon transfer and the hygienic improvement, and in the presence of global stiffness following complex lesions, reflex sympathetic algodystrophy or psychotic contracture. The performed additional procedures, at the skin and tendon level, further expanded the inclusion criteria. In the presence of appropriate indications, the TATA is a very useful tool with excellent outcome and represents a salvage procedure in the more severe deformities, avoiding joint fusion, with shortage of the digit, or amputation.
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PMID:The total anterior tenoarthrolysis in the treatment of the stiffness in flexion of the fingers. 1977 78

Cannabinoids such as Cannabis-based medicinal extracts (CBMEs) are increasingly being used in the treatment of spasticity associated with multiple sclerosis (MS). They have been shown to have a beneficial effect on spasticity; however, this evidence is largely based on subjective rating scales. Objective measurements using the Ashworth scale have tended to show no significant effect; however, the validity of this scale has been questioned. The available clinical trial data suggest that the adverse side effects associated with using CBMEs are generally mild, such as dry mouth, dizziness, somnolence, nausea and intoxication. However, most of these trials were run over a period of months and it is possible that other adverse side effects could develop with long-term use. There may be reason to be concerned about the use of therapeutic cannabinoids by adolescents, people predisposed to psychosis and pregnant women.
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PMID:New approaches in the management of spasticity in multiple sclerosis patients: role of cannabinoids. 2023 85


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