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, a gamma-aminobutyric acid agonist, acts at the spinal cord level to impede the release of excitatory neurotransmitters that cause spasticity. Oral baclofen improves cerebral spasticity mildly, but its activity is limited because of its poor lipid solubility. Cerebrospinal fluid baclofen levels after intrathecal administration are many times higher than those achieved after oral administration. Continuous intrathecal baclofen infusion has been used to treat cerebral spasticity in two patient groups: in older ambulatory children with inadequate underlying leg strength, and in patients with severe spasticity in both the upper and lower extremities. Responsiveness to intrathecal baclofen is confirmed by test injections before insertion of a programmable subcutaneous pump. Continuous intrathecal baclofen infusion dosages vary from 27 to 800 micrograms/day. Continuous intrathecal baclofen infusion reduces spasticity in the upper and lower extremities, and improves upper extremity function and activities of daily living but has no effect on athetosis in the dosages used to treat spasticity. Complications related to the intrathecal catheter occur in approximately 20% of patients, and infection requiring pump removal occurs in approximately 5%. Preliminary studies indicate that continuous intrathecal baclofen infusion alleviates some forms of generalized dystonia associated with cerebral palsy.
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PMID:Baclofen in the treatment of cerebral palsy. 888 81

Intrathecal baclofen reduces spasticity in individuals with cerebral palsy. Intrathecal doses are far lower than oral doses and the effects are considerably greater, and the side effects are fewer. Response to intrathecal baclofen must be confirmed by a screening trial before implantation of a pump for chronic infusion. Intrathecal baclofen reduces spasticity in the upper and lower extremities and is often associated with improved gait and upper extremity function. Quality of life improves for patients and caregivers. The Medtronic pump has been exceedingly reliable and typically functions for 4 or 5 years. The currently available intrathecal catheter is associated with far fewer complications than the initial catheter. Baclofen overdoses are unusual and are usually caused by pump programming errors rather than pump malfunction. Preliminary studies suggest that continuous intrathecal baclofen infusion reduces generalized dystonia in cerebral palsy. Screening to determine response of dystonia to intrathecal baclofen is by continuous infusion. The doses required to reduce dystonia are higher than those for cerebral spasticity. Additional investigations are underway to quantify the effects of continuous intrathecal baclofen infusion on communication, disability, and dystonia.
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PMID:Intrathecal baclofen in cerebral palsy movement disorders. 895 59

Baclofen is used for the treatment of post-traumatic spasticity. It carries a risk of overdose as well as of an acute withdrawal syndrome. We report two cases of severe hypertonia and hyperthermia (> 42 degrees C), occurring after accidental discontinuation of intrathecal infusion of baclofen. Both hypertonia and hyperthermia ceased when administration of baclofen was resumed. In parallel, the patients developed transient life-threatening alterations of hepatic (cytolysis), haematologic (coagulopathy) and cardiorespiratory functions for some days. It is concluded that the occurrence of such a withdrawal syndrome should be prevented, especially in patients with chronic intrathecal administration and first symptoms should be recognized without delay. Relationships with other malignant hyperthermias are discussed.
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PMID:[Severe hyperthermia caused by sudden withdrawal of continuous intrathecal administration of baclofen]. 903 59

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

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

Baclofen, a water soluble drug advocated for the treatment of spinal spasticity, was microencapsulated, using the oil/water emulsion extraction process in an attempt to identify the appropriate experimental conditions capable of producing microspheres releasing baclofen over 2-4 weeks. Individual microspheres ranging in size from 15 to 30 microns were formed exhibiting smooth surfaces at low drug payload (12.8% w/w), irregular and rough surface at high drug content (33.9% w/w). The microencapsulation yield remained practically unchanged (85-90%) up to theoretical payloads of 37.5% w/w, and decreased markedly to 70% when the initial theoretical payload was 50% w/w. The in vitro release profile of baclofen from the poly(D,L-lactide-co-glycolide) microspheres was biphasic only for the high drug payload microspheres with a rapid release of 70% within 48 h, followed by a slower release rate over at least 25 days. In contrast, the microspheres containing low baclofen contents (12.8% w/w) exhibited a gradual and progressive release rate over the course of the experiment. The baclofen release data did not fit either the general equation which describes the diffusional release of dispersed tiny drug particles from spherical micromatrices, or to the kinetic equations which describe the release of dissolved drug from monolithic microspherical devices. It appears that the release of baclofen from the present microspheres is not governed by a unique mechanism. This should be attributed either to the presence of some uncoated drug particles or to the large size of the embedded drug particles compared with the relatively small size of the spherical micromatices, or to some polymeric erosion occurring after several days incubation in the release medium.
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PMID:The characterization and release kinetics evaluation of baclofen microspheres designed for intrathecal injection. 1020 18

Baclofen, an analog of the putative inhibitory neurotransmitter gamma-aminobutyric acid is capable of crossing the blood-brain barrier. The drug has been shown to have an antinociceptive action and is used effectively in the management of spasticity. Baclofen was first used in the treatment of trigeminal neuralgia in 1980 and is currently used in the management of various types of neuropathic pain. The effect of baclofen on migraine has not been previously studied. The aim of the present open pilot study was to evaluate the efficacy of baclofen in patients with migraine. Fifty-four patients with migraine with and without aura who experienced 4-8 migraine attacks during a 4-week baseline were included. Baclofen, 15-40 mgs, was given in three divided doses for 12 weeks. Headache frequency and severity were recorded. Fifty-one patients completed the trial. Baclofen was found to be effective in 86.2% with > or = 50% headache reduction from baseline. Three patients could not tolerate the drug due to adverse events. In this open study, baclofen was found to be effective for prophylactic treatment of migraine.
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PMID:Baclofen for prevention of migraine. 1044 46

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

The effect of baclofen on walking performance was examined in nine spastic multiple sclerosis patients. In addition, nine healthy subjects were tested as controls. The modulation of the short latency soleus stretch reflex was closer to normal with baclofen compared to the recordings without baclofen, the modulation index being 74% (range: 60 - 100) with baclofen and 62% (range: 20 - 100) without baclofen, P=0.03. In healthy subjects the modulation index was 100% (range: 52 - 100). In the early swing phase the threshold of the soleus stretch reflex was significantly higher during baclofen medication being 139 deg/s (range: 63 - 302) compared with 93 deg/s (range: 37 - 187) without baclofen, P=0.004. The relation between the stretch velocity (input) and the amplitude of the stretch reflex (output) in early swing phase was unchanged being 0. 27 microVs/deg (range: 0.1 - 1.51) in patients with baclofen and 0. 24 microVs/deg (range: 0.08 - 0.79) without baclofen, P=0.25. Baclofen induced no change in input - output properties of the stretch reflex during walking compared with findings in a sitting position at matched EMG activity. There was a significant correlation between clinical spasticity score and stretch reflex threshold in the early swing phase (rho=-0.61, P=0.04) and between clinical spasticity score and the slope of the best linear fit in the early swing phase (rho=0.72, P=0.009).
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PMID:Baclofen increases the soleus stretch reflex threshold in the early swing phase during walking in spastic multiple sclerosis patients. 1077 56

Spasticity is a common and disabling symptom for many patients with upper motor neuron dysfunction. It results from interruption of inhibitory descending spinal motor pathways, and although the pathophysiology of spasticity is poorly understood, the final common pathway is overactivity of the alpha motor neuron. Therapy for spasticity is symptomatic with the aim of increasing functional capacity and relieving discomfort. Any approach to treatment should be multidisciplinary, including physical therapy, and possibly surgery, as well as pharmacotherapy. It is important that treatment be tailored to the individual patient, and that both patient and care giver have realistic expectations. Pharmacotherapy is generally initiated at low dosages and then gradually increased in an attempt to avoid adverse effects. Optimal therapy is the lowest effective dosage. Baclofen, diazepam, tizanidine and dantrolene are currently approved for use in patients with spasticity. In addition, clonidine (usually as combination therapy), gabapentin and botulinum toxin have shown efficacy, however, more studies are required to confirm their place in therapy. Intrathecal baclofen, via a surgically implanted pump and reservoir, may provide relief in patients with refractory severe spasticity.
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PMID:Drugs used to treat spasticity. 1077 31


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