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)

The purpose of this investigation was to study the effectiveness of gabapentin in controlling spasticity in persons with spinal cord injury (SCI) using a surface EMG-based quantitative assessment technique called the brain motor control assessment (BMCA). Six men from a Veterans Affairs Medical Center with spasticity due to traumatic SCI were studied as part of a multi-center, placebo-controlled, cross-over, clinical trial of gabapentin. Spasticity was evaluated using multi-channel surface EMG recordings of muscles in the lower extremities, abdomen and low back before and during treatment with oral gabapentin or placebo. Gabapentin or placebo was given orally in doses 400 mg three times daily for 48 h. Following a 10 day wash-out period subjects were crossed-over to receive the medication not received the first time. This was followed by an elective open-label extension. Group results during the controlled trial did not reach statistical significance at the dosage used. One subject demonstrated a dramatic improvement in spasticity that was apparent both clinically and with the BMCA. Other subjects demonstrated modest improvements which were seen in the BMCA but not recognized clinically. During the open label extension, the four subjects who participated experienced important clinical improvements with higher doses (to 3600 mg/day). These improvements were often in components of spasticity in which the BMCA had detected subclinical changes during the cross-over trial. A seventh subject was studied using the BMCA at doses of 1200 mg T.I.D. gabapentin, off gabapentin and 800 mg T.I.D. gabapentin and demonstrated quantitatively a dose-related effect with higher doses of gabapentin which matched clinical observations. Gabapentin at doses of 400 mg T.I.D. may be effective in controlling some features of spasticity in persons with SCI. Higher doses provide greater control of spasticity, and controlled studies using higher doses are needed to evaluate gabapentin's efficacy.
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PMID:Effectiveness of gabapentin in controlling spasticity: a quantitative study. 907 68

The use of a recently released anticonvulsant, gabapentin, in the treatment of spasticity in two patients with multiple sclerosis is reported. Gabapentin was chosen because of its GABA-ergic effect and because previously reported studies have shown that it is well tolerated compared with other GABA-mimetic medication. Satisfactory release of spasticity with significant improvement of functional outcome was noted in both cases. Both patients were first treated with gabapentin for one month at 300 mg per day and then, with no reported side-effects, at 400 mg per day. Before treatment, spasticity (graded with modified Ashworth Scale) in one patient was 3 for left lower and 2 for right lower limbs, and Expanded Disability Status Scale (EDSS) was 7; ambulation was limited to a few steps with a standard walker. After two weeks of treatment, spasticity was 2 and 1 for the left and right lower limbs, respectively. At three-month intervals, spasticity was +1 for left and 1 for right lower limbs, and EDSS was 6; the patient could ambulate 75 to 100 m with a standard walker. In the second patient, spasticity before treatment was 2 for both lower and left upper limbs. EDSS was 5.5, and ambulation was confined to 100 m with a cane. Spasticity improved to +1 in lower and 1 in left upper limbs after two weeks and to 1 and normal after three months. At three months, EDSS was 3 and the patient could ambulate for long distances without an assistive device. We suggest that gabapentin can be used effectively to decrease spasticity without significant side effects in patients with multiple sclerosis.
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PMID:Gabapentin for relief of spasticity associated with multiple sclerosis. 979 39

The paper is a review of current experience with use of gabapentin--a new antiepileptic drug--in neurologic conditions others than epilepsy. Mechanism of action of the drug is not fully elucidated yet. However it proved to be effective in therapy of chronic pain, especially in neuropathic pain, neuralgia, low back pain, reflex sympathetic dystrophy and erythromelalgia. Gabapentin is also effective in pain and spasticity in multiple sclerosis. Clinical studies of gabapentin in movement disorders, such as Parkinson disease, essential tremor and atrophic lateral sclerosis are discussed in the paper. It can be summarized that gabapentin is a valuable medication and the use thereof in neurology is not limited to epilepsy.
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PMID:[GABApentin--new therapeutic possibilities]. 1252 21

Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the CNS. There are currently a number of disease-modifying medications for MS that modulate or suppress the immune system; however, these medications do not directly relieve MS symptoms, which include visual deficits, gait problems, sensory deficits, weakness, tremor, spasticity and pain, among others. Pain is a common symptom in MS which has recently been estimated to be experienced by more than 40% of patients. Nociceptive pain occurs as an appropriate physiological response transmitted to a conscious level when nociceptors in bone, muscle or any body tissue are activated, warning the organism of tissue damage. Neuropathic pain is initiated as a direct consequence of a lesion or disease affecting the somatosensory system, with no physiological advantage. Nociceptive and neuropathic pain in MS may be present concurrently and at different stages of the disease, and may be associated with other symptoms. Central neuropathic pain has been reported to be among the most common pain syndromes in MS. It is described as constant, often spontaneous, burning occurring more frequently in the lower limbs. Treatment typically includes tricyclic antidepressants and antiepileptic medications, although studies have been conducted in relatively small samples and optimal dosing has not been confirmed. Cannabinoids have been among the few treatments studied in well designed, randomized, placebo-controlled trials for central neuropathic pain. In the largest of these trials, which included 630 subjects, a 15-week comparison between Delta9-tetrahydrocannabinol and placebo was performed. More patients receiving active treatment perceived an improvement in pain than those receiving placebo, although approximately 20% of subjects reported worsening of pain while on active treatment. Trigeminal neuralgia, while affecting less than 5% of patients with MS, is the most studied pain syndrome. The pain can be extreme and is typically treated with carbamazepine, although adverse effects can mimic an MS exacerbation. Painful topic spasms occur in approximately 11% of the MS population and are treated with antispasticity medications such as baclofen and benzodiazepines. Gabapentin has also demonstrated efficacy, but all studies have included small sample sizes. In general, evidence for treating pain in MS is limited. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. Treatment is often based on anecdotal reports and clinical experience. We present a review of treatment options for pain in MS, which should serve to update current knowledge, highlight shortcomings in clinical research and provide indications towards achieving evidence-based treatment of pain in MS.
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PMID:Pharmacological management of pain in patients with multiple sclerosis. 2056 32

Though in the last few decades only a few new drugs have come available for the treatment of spasticity, new insights may revise the role and individual value of several pharmacological treatments. Diazepam, baclofen and tizanidine are the most prescribed drugs for the treatment of spasticity. Intrathecal baclofen and local infiltration of botulin toxin are added values in selective patients. Gabapentin is a novelty, and the working mechanism of cannabis has been elucidated. Dantrolene sodium appears to owe its selectivity from the recently discovered ryanodine receptor, with a peripheral effect in muscles. In this review the pathophysiology and epidemiology of spasticity, pharmacology, clinical efficacy and unwanted effects of the different drugs for spasticity are updated.
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PMID:Spasticity: revisiting the role and the individual value of several pharmacological treatments. 2087 Nov 49

We recently reported that the neuropathic pain medication, gabapentin (GBP; Neurontin), significantly attenuated both noxious colorectal distension (CRD)-induced autonomic dysreflexia (AD) and tail pinch-induced spasticity compared to saline-treated cohorts 2-3 weeks after complete high thoracic (T4) spinal cord injury (SCI). Here we employed long-term blood pressure telemetry to test, firstly, the efficacy of daily versus acute GBP treatment in modulating AD and tail spasticity in response to noxious stimuli at 2 and 3 weeks post-injury. Secondly, we determined whether daily GBP alters baseline cardiovascular parameters, as well as spontaneous AD events detected using a novel algorithm based on blood pressure telemetry data. At both 14 and 21 days after SCI, irrespective of daily treatment, acute GBP given 1 h prior to stimulus significantly attenuated CRD-induced AD and pinch-evoked tail spasticity; conversely, acute saline had no such effects. Moreover, daily GBP did not alter 24 h mean arterial pressure (MAP) or heart rate (HR) values compared to saline treatment, nor did it reduce the incidence of spontaneous AD events compared to saline over the three week assessment period. Power spectral density (PSD) analysis of the MAP signals demonstrated relative power losses in mid frequency ranges (0.2-0.8 Hz) for all injured animals relative to low frequency MAP power (0.02-0.08 Hz). However, there was no significant difference between groups over time post-injury; hence, GBP had no effect on the persistent loss of MAP fluctuations in the mid frequency range after injury. In summary, the mechanism(s) by which acute GBP treatment mitigate aberrant somatosensory and cardiophysiological responses to noxious stimuli after SCI remain unclear. Nevertheless, with further refinements in defining the dynamics associated with AD events, such as eliminating requisite concomitant bradycardia, the objective repeatability of automatic detection of hypertensive crises provides a potentially useful tool for assessing autonomic function pre- and post-SCI, in conjunction with experimental pharmacotherapeutics for neuropathic pain, such as GBP.
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PMID:Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury. 2293 77

The term hereditary spastic paraplegia (HSP) embraces a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. There currently exist no specific therapies for HSP, and treatment is exclusively symptomatic, aimed at reducing muscle spasticity, and improving strength and gait. The authors set out to perform a comprehensive systematic review of the available scientific literature on the treatment of HSP, applying Cochrane Collaboration methods. The Google Scholar, PubMed and Scopus electronic databases were searched to find relevant randomized control trials (RCTs) and open-label interventional studies, prospective, and retrospective observational studies of supplements, medications, and physical therapy, as well as case reports and case series. Two authors independently analyzed 27 articles selected on the basis of a series of inclusion criteria. Applying a best-evidence synthesis approach, they evaluated these articles for methodological quality. A standardized scoring system was used to obtain interrater assessments. Disagreements were resolved by discussion. The 27 articles focused on pharmacological treatment (n = 17 articles), physical therapy (n = 5), surgical treatment (n = 5). The drugs used in the 17 articles on pharmacological therapy were: gabapentin, progabide, dalfampridine, botulinum toxin, L-Dopa, cholesterol-lowering drugs, betaine, and folinic acid. Gabapentin, progabide, dalfampridine, and botulinum toxin were used as antispastic agents; the study evaluating gabapentin efficacy was well-designed, but failed to demonstrate any significant improvement. L-Dopa, cholesterol-lowering drugs, betaine, and folinic acid were only used in specific HSP subtypes. Two of the three studies evaluating cholesterol-lowering drugs (in SPG5 patients) were well-designed and showed a significant reduction of specific serum biomarkers (oxysterols), but clinical outcomes were not evaluated. The articles focusing on physical treatment and surgical therapy were found to be of low/medium quality and, accordingly, failed to clarify the role of these approaches in HSP. Despite recent advances in understanding of the pathogenesis of HSP and the possibility, in several centers, of obtaining more precise and rapid molecular diagnoses, there is still no adequate evidence base for recommending the various published therapies. Well-designed RCTs are needed to evaluate the efficacy of both symptomatic and pathogenetic treatments.
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PMID:Management of Hereditary Spastic Paraplegia: A Systematic Review of the Literature. 3072 48