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)

We studied the effects of intrathecal baclofen upon voluntary movements. Eleven patients with spasticity of different etiology and one patient with idiopathic dystonia were studied. Six patients participated in a double-blind trial. Kinematic/dynamic and electromyographic (EMG) patterns were recorded during attempts at single-joint elbow or ankle voluntary movements and isometric contractions. Reflex responses were also recorded. Baclofen suppressed spastic signs in 10 patients: it eliminated clonus and decreased the co-contraction of antagonist and distant muscle groups. Baclofen could induce weakness, particularly in patients with cerebral palsy (CP). Patients with hemi-syndromes did not notice any effects of baclofen in their 'unaffected' limbs. Intrathecal baclofen could improve voluntary movements in some patients with spasticity resulting in better walking and usage of arms. We hypothesize that spasticity induces an adaptive reaction at a segmental level that includes an increase in the number and/or affinity of GABA-sensitive receptors.
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PMID:Changes in voluntary motor control induced by intrathecal baclofen in patients with spasticity of different etiology. 923 40

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

Clonidine, a noradrenergic agonist, and cyproheptadine, a serotonergic antagonist, have each been associated with improved walking in SCI subjects. Baclofen, a GABA agonist, is frequently prescribed for spasticity but its effects on walking have not been well quantified. The objective of this study was to compare the effects of clonidine, cyproheptadine and baclofen on walking in SCI subjects with incomplete injuries. A motorized treadmill was used and harness support provided when necessary. A repeated single-subject design was employed for the twelve subjects. The greatest effects were found in more severely disabled subjects. Cyproheptadine was associated with greatly reduced need for assistance, increases in maximum treadmill speed (MTS) and reduced clonus. Clonidine was associated with increases in MTS and a generally more upright posture. Baclofen was associated with minor changes in walking. In many cases of drug effects, MTS increases and other changes were retained following washout of drugs. The significance and implications of the drug effects and the retention of effects during washout periods are discussed. It is concluded that clonidine and cyproheptadine have different effects but both appear useful for severely disabled SCI subjects. The effects of baclofen on walking after spinal cord injury remains unclear.
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PMID:Effects of drugs on walking after spinal cord injury. 980 Feb 74

Systemic pharmacologic treatments may be indicated in conditions in which the distribution of muscle overactivity is diffuse. Antispastic drugs act in the CNS either by suppression of excitation (glutamate) enhancement of inhibition (GABA, glycine), or a combination of the two. Only four drugs are currently approved by the US FDA as antispactic agents: baclofen, diazepam, dantrolene sodium, and tizanidine. However, there are a number of other drugs available with proven antispastic action. This chapter reviews the pharmacology, physiology of action, dosage, and results from controlled clinical trials on side effects, efficacy, and indications for 21 drugs in several categories. Categories reviewed include agents acting through the GABAergic system (baclofen, benzodiazepines, piracetam, progabide); drugs affecting ion flux (dantrolene sodium, lamotrigine, riluzole; drugs acting on monoamines (tizanidine, clonidine, thymoxamine, beta blockers, and cyproheptadine); drugs acting on excitatory amino acids (orphenadrine citrate); cannabinoids; inhibitory neuromediators; and other miscellaneous agents. The technique, advantages and limitations of intrathecal administration of baclofen, morphine, and midazolam are reviewed. Two consistent limitations appear throughout the controlled studies reviewed: the lack of quantitative and sensitive functional assessment and the lack of comparative trials between different agents. In the majority of trials in which meaningful functional assessment was included, the study drug failed to improve function, even though the antispastic action was significant. Placebo-controlled trials of virtually all major centrally acting antispastic agents have shown that sedation, reduction of global performance, and muscle weakness are frequent side effects. It appears preferable to use centrally acting drugs such as baclofen, tizanidine, and diazepam in spasticity of spinal origin (spinal cord injury and multiple sclerosis), whereas dantrolene sodium, due to its primarily peripheral mechanism of action, may be preferable in spasticity of cerebral origin (stroke and traumatic brain injury) where sensitivity to sedating effects is generally higher. Intrathecal administration of antispastic drugs has been used mainly in cases of muscle overactivity occurring primarily in the lower limbs in nonambulatory, severely disabled patients but new indications may emerge in spasticity of cerebral origin. Intrathecal therapy is an invasive procedure involving long-term implantation of a foreign device, and the potential disadvantages must be weighed against the level of disability in each patient and the resistance to other forms of antispastic therapy. In all forms of treatment of muscle overactivity, one must distinguish between two different goals of therapy: improvement of active function and improvement of hygiene and comfort. The risk of global performance reduction associated with general or regional administration of antispastic drugs may be more acceptable when the primary goal of therapy is hygiene and comfort than when active function is a priority.
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PMID:Traditional pharmacological treatments for spasticity. Part II: General and regional treatments. 982 84

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.
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PMID:The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain. 1075 9

A specific microdialysis probe combined with high performance liquid chromatography analysis was used to compare the basal levels of extracellular amino acids (AAs) in the dorsal horn (DH) between two groups of patients undergoing spinal surgery for the treatment of peripheral neuropathic pain (n = 5) or disabling spasticity (n = 5). A stabilized concentration was reached in the dialysates 45 min after probe implantation for excitatory AAs (glutamate and aspartate) and inhibitory AAs (GABA and glycine). A significant increase in the ratios aspartate/GABA and aspartate/glycine was found in the group of patients suffering from neuropathic pain. This study shows the feasibility of a microdialysis investigation in the DH of patients during a neurosurgical operation and supports in humans the hypothesis of an imbalance between excitatory AAs and inhibitory AAs within the DH in neuropathic pain states, as suggested by previous animal studies.
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PMID:Amino acids in spinal dorsal horn of patients during surgery for neuropathic pain or spasticity. 1085 47

The recent cloning of two GABA(B) receptor subunits, GABA(B1) and GABA(B2), has raised the possibility that differences in GABA(B) receptor subunit composition may give rise to pharmacologically or functionally distinct receptors. If present, such molecular diversity could permit the selective targeting of GABA(B) receptor subtypes specifically involved in pathologies such as drug addiction, spasticity, pain, and epilepsy. To address these issues we have developed a GABA(B1) subunit knockout mouse using gene targeting techniques. In the brains of GABA(B1) null mice, all pre- and postsynaptic GABA(B) receptor function was absent demonstrating that the GABA(B1) subunit is essential for all GABA(B) receptor-mediated mechanisms. Despite this, GABA(B1) null mice appeared normal at birth, although by postnatal week four their growth was retarded and they developed a generalized epilepsy that resulted in premature death. In addition, GABA(B1) heterozygote animals showed enhanced prepulse inhibition responses compared to littermate controls, suggesting that GABA(B1) deficient mice exhibit increased sensorimotor gating mechanisms. These data suggest that GABA(B) receptor antagonists may be of benefit in the treatment of psychiatric and neurological disorders in which attentional processing is impaired.
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PMID:Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. 1141 94

Spasticity is a result of an imbalance between the afferent excitatory and descending inhibitory pathways after central nervous system damage. Its pharmacologic control is believed to result from the antagonism of inhibitory mechanisms (gamma-aminobutyric acid [GABA] or glycine-mediated antagonism of excitatory mechanisms), or both. Because GABA receptor sites are widely present in the central nervous system, it is amenable to pharmacologic manipulation.
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PMID:GABA agonists and gabapentin for spastic hypertonia. 1172 68

When spasticity produces a clinical disability by interfering with posture, motor capacity, nursing or daily living activities, medical treatment is recommended. It is mainly indicated when the muscle overactivity is diffusely distributed and should be implemented early, to prevent permanent musculoskeletal deformities or contractures. A pharmacological approach relies on the use of drugs which modulate neurotransmitters acting at the cortico-spinal level (GABA, glycine, glutamate, noradrenaline, serotonin). The aim of this treatment is to decrease spinal reflex excitability by reducing the release of excitatory neurotransmitters, or by potentiating the activity of inhibitory inputs. Evaluation of the efficacy of these drugs is determined by the therapeutic objectives which may be biomechanical, or functional. Diazepam increases presynaptic inhibition by stimulating GABA(A) receptors in the brainstem and spinal cord. In double-blind studies of patients with spinal cord lesions, antispastic efficacy has been shown, but side-effects are common. Baclofen stimulates GABA(B) receptors inducing a suppression of excitatory neurotransmitter release. Antispastic efficacy is sufficiently documented, but no definite effects on ambulation or activities of daily living have been proved. Tizanidine has an alpha2-agonist activity (at spinal and supraspinal level) and decreases the presynaptic activity of excitatory interneurones. The main clinical effects are a reduction in tonic stretch, polysynaptic reflexes, and co-contraction, with fewer side-effects but no definite functional change. The efficacy of several other antispastic drugs is documented in a few controlled studies, but the majority of information arises from open trials or anecdotal observations.
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PMID:The medical management of spasticity. 1191 47

Intrathecal baclofen is used as a muscle relaxant and antispasmodic in cases of spasticity resulting from central nervous system trauma. The baclofen withdrawal syndrome may include hyperthermia, tachycardia, hypertension, seizures, altered mental status, and psychomotor agitation. We report a case in which the removal of a baclofen pump lead tothe development of severe withdrawal symptoms despite oral baclofen replacement therapy. In order to avoid the development of withdrawal, adequate doses of GABA agonist agents should be administered immediately prior to, and following, baclofen pump removal.
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PMID:Baclofen withdrawal following removal of an intrathecal baclofen pump despite oral baclofen replacement. 1470 58


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