Intrathecal baclofen for treatment of spasticity of multiple sclerosis patients

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.     

Intrathecal baclofen in the management of spasticity due to cerebral palsy

Intrathecal baclofen is a cornerstone in the treatment of spasticity in children. However, further research is required to set criteria for treatment. This paper offers insight into the national act on baclofen and the experience at the Nottingham University Hospital.     

Intrathecal baclofen therapy to spasticity]

Intrathecal baclofen injection (ITB) has been available since April, 2006 in Japan. According to the clinical trial data, ITB reduced continuously the average Ashworth spasticity score (1 no spasticity-5 completely contracted) from 3.85 to 1.84 or below as well as the average spasm score (0 no spasm-4 more than 10 spasms hour) from 2.56 to 0.75. It also reduced the number of patients with severe pain from 45% to 17% as well as the number of patients with severe compressive sensation from 65% to 11%. The effect was very dramatic and there have been no severe side effect. ITB seems effective and useful to patients suffered from marked spasticity. It appears also safe when appropriate patients are selected and careful procedures are taken. Because ITB needs surgical procedures, neurosurgeon or orthopedic surgeons have been involved so far. We neurologist, however, should at least know about ITB and its powerful effect against severe spasticity while we must be aware of dangerous situation due to overdose and secession of the baclofen.     

Intrathecal baclofen therapy for stroke-related spasticity

Intrathecal baclofen (ITB) therapy is a widely recognized management technique for severe, disabling spasticity in individuals with cerebral palsy and spinal and brain injuries. Its utility in the stroke population has only been recognized recently. Unlike the aforementioned patient populations, many stroke survivors are ambulatory and are able to maintain a certain degree of functional independence through compensatory use of the uninvolved limbs. Clinicians often fail to recognize the potential enhancement in the function of these individuals if they gain better control of their spastic limbs. Other spasticity treatments, such as oral medications and neurolytic procedures, offer the advantage of being nonsurgical; however, not every stroke patient will respond well to them. Some patients may not tolerate the systemic side effects of oral medications, such as drowsiness and sedation. In patients with severe multilimb spasticity, phenol and even high doses of botulinum toxin may not adequately control spasticity. ITB therapy offers the advantage of effectively decreasing severe, diffuse spasticity without causing untoward effects on arousal and cognition. This article will review the efficacy of ITB therapy in treating spasticity and enhancing function in stroke survivors.     

Intrathecal baclofen therapy in children with severe spasticity: Outcome and complications

Objective: To investigate clinical efficacy and incidence of complications regarding intrathecal baclofen (ITB) therapy in children.

Methods: Retrospective medical chart review of 15 paediatric patients with congenital brain injuries who underwent ITB implantation for treatment of severe spasticity between 2003 and 2009.

Results: Compared to the preoperative state, ITB therapy significantly reduced spasticity of lower limbs with corresponding decrease of the modified Ashworth scale (p?p?=?0.001). Cobb angle of patients with scoliosis prior to ITB therapy (n?=?8) increased significantly (p?Conclusion: Intrathecal baclofen is an effective therapy option for paediatric patients to significantly reduce spasticity of lower limbs. The high incidence of complications implicates the need for a close monitoring of the patients especially in the early post-operative period.     

Tizanidine versus baclofen in the treatment of spasticity in multiple sclerosis patients

Sixteen patients suffering from spasticity due to multiple sclerosis were treated with baclofen and tizanidine in a partially blind cross-over study. No significant difference in efficacy was found. The most striking difference was seen in the side-effects: baclofen frequently caused more or less severe muscle weakness and even falling during walking and standing. Treatment with tizanidine produced an apparent improvement of mobility in some patients suffering from moderate or marked paresis associated with a marked spasticity of their legs. Isometric muscle strength did not show any significant changes during either treatment. The different impact of baclofen and tizanidine on mobility and weight support seems to be related to their different site of action in spasticity.     

The use of baclofen in treatment of spasticity in multiple sclerosis.

Baclofen was used in a double-blind crossover placebo-controlled trial to treat spasticity in patients with multiple sclerosis (MS). While on Baclofen, patients obtained a significant (p less than 0.001) reduction in spasticity compared to controls. The drug was particularly effective in alleviating flexor and extensors spasms, as well as their associated pain. Side effects were common in this study, but were usually well tolerated by the patients. The commonest side effects were sedation, nausea and vomiting. There were no changes in hepatic, renal, or hematological function in any patients. Increase weakness due to loss of spasticity for support was also a fairly common complaint. The drug seems best indicated in patients in whom spasticity is not required for support or other activities of daily living. Careful monitoring of the patient is essential for effective use of this drug.     

Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis

Tizanidine (Sirdalud) was compared to baclofen (Lioresal) in a randomized, double-blind, cross-over trial. Each medication was introduced over a three week titration period and then maintained at the highest tolerated dose for five weeks. The two treatment phases were separated by a one week drug withdrawal and a two week washout period. Sixty-six patients entered the trial and forty-eight completed both treatment phases. At the end of the trial, neurologists and physiotherapists thought that baclofen was superior on the basis of perceived efficacy and tolerance (p less than or equal to 0.05). Although the efficacy of tizanidine or baclofen was judged as good to excellent by 24 and 39% of patients respectively, this difference was not statistically significant. Muscle weakness was the most common adverse effect. This was significantly more troublesome in patients treated with baclofen. Somnolence and xerostomia were more common in patients treated with tizanidine. Both baclofen and tizanidine appear to be useful adjuncts in the treatment of spasticity in patients with multiple sclerosis. Preference of either drug is tempered principally by side-effects.     

Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen

In a retrospective study, changes in baclofen dose and complication frequency were recorded in 79 patients with intrathecal baclofen administration and the effect on nightly muscle spasms was measured over a mean observation period of 34 months, during which time an increase in the daily dose of baclofen during the first 1--1-1/2 years is notified. On subsequent pump fillings the daily dose of baclofen remained stable in the group of non-multiple sclerosis patients. In contrast, the group of multiple sclerosis patients showed a steady increase in their daily dose of baclofen. We found a frequency of complications of 0.014 monthly often due to catheter problems. There was a significant decrease in numbers of nightly muscle spasms in an 8 h recording period from 77+/-20 preoperatively and 9+/-3 (P=0.02) 3 months after surgery. The steady increase in the daily dose of baclofen in order to obtain adequate reduction in spasticity and nightly muscle spasms in the first 1--1-1/2 years cannot fully be explained by caution and difficulties in achieving the correct dose, but also indicates that tolerance to baclofen occurs. Complications are often due to infection or catheter problems.     

Intrathecal baclofen alleviates autonomic dysfunction in severe brain injury

Sympathetic storm phenomena are well known therapeutic problems in patients with severe brain injury. We have treated four patients with intrathecal baclofen (ITB) who suffered from severe hypertension, tachycardia and other sympathetic storm phenomena after different primary events. In all patients conventional therapy with sedatives and antiadrenergic medication had been taken to the upper limits before initiating ITB. Autonomic dysfunction immediately improved in three of four patients. In all patients ITB, via lumbar or ventricular route, proved safe and without complications. The anatomical and pharmacological basis of the GABA-B agonist action on such sympathetic storm phenomena are not yet fully understood. However, the positive results observed in three out of four patients are promising and require further investigation. ITB is a new therapeutic approach to control otherwise unresponsive sympathetic storm phenomena in severe brain injury.     

Intrathecal baclofen therapy for severe spasticity: analysis on a series of 112 consecutive patients and future prospectives

Objective

Intrathecal baclofen therapy (ITB) is a well-known treatment for spasticity. Despite this fact, several topics have to be still discussed: new indications and screening tools, appropriate surgical timing and complicance avoidance.

Methods

A total of 112 consecutive patients all with a severe, progressive and refractory to medical therapy spasticity from different causes were treated using ITB, after a bolus test. Every patient was assessed by means of Modified Ashworth Scale (MAS), Penn spasm frequency scale (SFS) and Visual Analog Scale for pain. Since available, a Gait analysis was also performed.

Results

There were 63 males (56%) and 49 females (44%). Seventy-four (66%) had a quadriparesis, 34 (30.4%) had a paraparesis and 4 (3.6%) were hemiplegic. Among these patients 77 (68.7%) were non ambulatory, while 35 (31.3%) were ambulatory. These patients suffered from spasticity due to many different diseases.Mean follow-up was 55 months. The mean Modified Ashworth score decreased from 4.5 ± 0.5 preoperatively to 1.2 ± 0.4 on chronic intrathecal baclofen. Daily baclofen dose varied between 23 and 500 mcg. Drug-induced complications and catheter related problems occurred, respectively in 7 (6.3%) and 10 patients (8.9%).

Conclusions

Although ITB is a well known and good treatment option in the management of severe spasticity, because of the different goals and subgroups of patients treated, a variety of techniques are needed to evaluate the benefits of this therapy. New indications, effects of ITB on central nervous system and cognitive functions needs yet to be fully clarified.     

Intrathecal baclofen for long-term treatment of spasticity: a multi-centre study.

Twenty eight patients with severe, intractable spasticity have been treated by chronic intrathecal administration of baclofen. An implantable programmable drug-administration-device (DAD) was used with a permanent intrathecal catheter. Infusion of 50 to 800 micrograms/day of baclofen completely abolished spasticity. Follow-up was up to two years. Therapeutic effect was documented by clinical assessment of tone, spasms and reflexes and by electrophysiological recordings of mono- and polysynaptic reflex activity. Complications and untoward side-effects of the procedure were few. This procedure is recommended for spasticity of spinal origin refractory to physiotherapy and oral medication. It is a preferable alternative to ablative surgical intervention.     

Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis

Sativex is an endocannabinoid system modulator principally containing Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit.