The effect of baclofen on the transmission in spinal pathways in spastic multiple sclerosis patients (original) (raw)
Related papers
Neurological Research, 2013
Objective: The aim of this study was to compare the relative efficacy of baclofen and self-applied transcutaneous electrical nerve stimulation (TENS) for the treatment of spasticity in the lower extremities in multiple sclerosis (MS). Methods: A randomized controlled clinical trial was conducted from September 2010 to June 2011. Fiftytwo patients with MS presenting muscle spasm in the leg at 20-50 years of age were randomly allocated to receive a four-week treatment course of either baclofen (10 mg twice daily, increasing over three weeks to 25 mg) or self-applied TENS. Response to treatment was assessed at four weeks after commencement of the intervention by modified Ashworth scale (MAS). Results: Spasticity decreased in both groups. Of the 26 people treated with TENS, the mean (standard deviation (SD)) MAS decreased from 1.77 (0.29) at baseline to 0.73 (0.70) at the four-week follow-up (P , 0.001). Correspondingly, in the 26 people treated with baclofen, the mean (SD) MAS decreased from 1.73 (0.38) to 1.15 (0.63) (P , 0.001). The mean difference in MAS score at the four-week follow-up was significantly lower in the TENS group than the baclofen group (mean difference 20.42; 95% CI, 20.79, 20.05; P , 0.05). Discussion: This study demonstrates that both baclofen and TENS can be effective in reducing MS-related spasticity. The mean MAS score was significantly lower in the TENS group. However given the side-effect profile of baclofen, TENS may have some benefits over baclofen.
A Double-Blind Trial with Baclofen (Lioresal�) and Diazepam in Spasticity Due to Multiple Sclerosis
Acta Neurol Scand, 2009
In 17 in-patients suffering from spasticity due to multiple sclerosis, the effect and tolerability of baclofen (Lioresal @) and diazepam were studied in a double-blind, within patient trial with random allocation and flexible dose. The treatment periods wcre 4 weeks each. As to efficacy, the variables : spasticity, clonus, flexor spasms, gait and bladder function wcre evaluated clinically. No significant difference was found between the two drugs. As f a r as side-effects are concerned, scdation was specifically inquired about. Apart from that, spontaneously reported side-effects were recorded. Sedation was more often seen during treatment with diazepam, while the side-effects during baclofen treatment were more varied. The total number and severity of sideeffects wcre equal in the two treatment groups. A preference for one of the two treatment periods was stated by the investigator before the code was broken. A significant difference (P < 0.001) in favour of LioresaIB was found. This is discussed in the light of the fact that no significant difference was found for the individual symptoms o r side-effects. Patients with spasticity present considerable problems with regard to both preservation of skills and, in more serious cases, nursing. We therefore thought it worthwhile to carry out a closer study of a new antispastic agent, baclofen (Lioresal @), which in controlled trials (Hudgson & Weightman 1971, Jerusalem 1968, Pedersen et al. 1970) has proved effective in the treatment of spasticity. Baclofen is a derivative of gamma-amino-butyric acid (Figure 1). The theoretical basis for the synthesis of baclofen is that gammaamino-butyric acid has been proved to be a naturally occurring inhibitory transmitter in the CNS (Bazernore et al. 1957). However, this transmitter, being a strongly polar and hydrophilic substance, cannot penetrate the blood-brain barrier and therefore cannot be used in therapy. By substituting a lipophilic group (parachlorophenyl) it has
Annals of Rehabilitation Medicine
Objective To investigate dosage changes in intrathecal baclofen during long-term treatment of patients with severe leg spasticity. Methods We performed a retrospective chart review of 49 patients treated with an intrathecal baclofen pump (ITB) because of severe leg spasticity, for a minimum of 7 years. Eight patients were excluded due to catheter/pump failure or factors aggravating spasticity. Of the remaining 41 patients, 19 had spinal cord injury (SCI) and 22 were diagnosed with multiple sclerosis (MS). Among the SCI patients, 15 had cervical and 4 thoracic SCI, with 7 patients showing the American Spinal Injury Association impairment scale (AIS) A and 12 patients with AIS B-D. The dose was regulated by discussion among the patients and their physicians, usually 4-10 times annually, to reduce leg spasticity and also avoid leg/trunk weakness. Results After 1 year patients on ITB needed a median dose of 168 mg/24 hr (range, 30-725 mg) for an optimal effect. After 7 to 10 years the dosage needed to reduce leg spasticity in the MS patients was significantly increased compared with the initial dose (mean 157%, n=22 and mean 194%, n=18). In contrast, the SCI patients needed only a modest increase (mean 113% and 121%). The difference between MS and SCI patients was significant (t-test p=0.006 and p=0.004). Conclusion The increased dosage in MS patients compared with patients diagnosed with SCI probably reflects the progressive disease course. The need for a large dosage increase in patients with SCI suggests possible pump failure, triggering factors for spasticity or progressive spinal disease.
Chronic intrathecal baclofen administration for control of severe spasticity
Journal of Neurosurgery, 1990
✓ Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cas...
Intrathecal Baclofen for the Treatment of Spasticity of Cerebral Origin
Journal for Specialists in Pediatric Nursing, 2003
We conducted a retrospective study of the case files of 64 multiple sclerosis (MS) patients presenting severe spasticity, who had received intrathecal (IT) baclofen test injections between 1992 and 2004 in a rehabilitation unit. In almost all cases of our series, IT baclofen was proposed to patients who were no longer able to walk. IT baclofen is a safe and effective treatment to reduce spasticity in MS patients. Despite an advanced stage of the disease at the time of pump placement, the complication rate was low and the efficacy of this treatment was maintained over time. Multiple Sclerosis 2006; 12: 101 Á/103. www.multiplesclerosisjournal.com
International Journal of MS Care, 2001
The effectiveness of intrathecal baclofen therapy (ITB) in the management of severe spasticity in people with multiple sclerosis (MS) was reviewed retrospectively. The multidisciplinary team reviewed the medical, therapy, and nursing notes of 19 people with MS who were treated with ITB. The audited information included surgical procedures, postoperative complications, medical side effects, dose requirements, and multidisciplinary input. Seventeen people were included in the audit. A total of 23 problems and 34 functional goals as objects for ITB treatment were recorded. Eighty-seven percent of the patients had sustained improvement in at least one problem, and 79% in at least one goal. Only two patients had no sustained improvement in any problem or goal. These results suggest that ITB can be an effective intervention in people with severe spasticity in MS. However, this approach requires careful patient selection, a dynamic goal-oriented approach, expert implantation, and ongoing e...
Acta Neurologica Scandinavica, 1987
The anti-spastic effect of a new drug, tizanidine, was compared with that of baclofen in a double-blind clinical trial; 40 seriously handicapped patients with multiple sclerosis (MS) were randomly allocated treatment with one or the other drug for a 6-week period. The antispastic effect was evaluated by clinical criteria. The optimal daily dose of both drugs varied considerably from patient to patient, and was on the average 23 mg for Tizanidin and 59 mg for baclofen. To the extent an antispastic effect was observed, the 2 drugs appeared to be equally effective when given at a 1:2 ratio (mg tizanidine: mg baclofen). Side effects of both drugs were sleepiness, muscular weakness and dry mouth. Tizanidine had a mild depressive effect on blood pressure. Sudden withdrawal of both drugs was accompanied by a transient relative increase of spasticity in approximately half the patients. There were no other changes suggesting physical or psychological dependence. The present study underscores that neither baclofen nor tizanidine are ideal antispastic drugs, and emphasize the need for further research.
Experimental Brain Research, 1985
Intravenous baclofen (1–6.25 mg kg-1) substantially reduced the monosynaptic excitation of neurones in the intermediate nucleus of the cat spinal cord by impulses in group I extensor muscle primary afferent fibres, but had little or no effect on excitation by stimulating fibres of the ipsilateral dorsolateral funiculus or the contralateral red nucleus. Relatively low concentrations of baclofen thus appear not to influence the release of excitatory transmitter from the terminals of rubrospinal, corticospinal and long descending propriospinal fibres, in contrast to the reduction of the release of primary afferent transmitters.
Intraspinal baclofen in the treatment of severe spasticity and spasms
Acta Neurochirurgica, 1991
Ten patients with severe spasticity were evaluated according to a standardized protocol in order to be treated by intraspinal baclofen. Entry criteria in the protocol were the following: 1) Stable central nervous system lesion, 2) Severe spasticity and/or fiexo-extensor spasms not controllable by oral treatment, 3) Normal CSF circulation and 4) Informed consent. All patients received a test dose of twenty-five micrograms of baclofen injected intrathecally. At intervals of at least one day, doses were increased in 10-25 microgram steps until total abolition of spontaneous spasms was achieved in complete spinal cord lesions. In patients with residual motor function, doses were titrated until the optimal dose was found that reduced spasms and enabled performance of maximum daily life activities according to the patient's neurological level.