Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial

Intrathecal baclofen infusion has demonstrated effectiveness in decreasing spasticity of spinal origin. Oral antispasticity medication is minimally effective or not well tolerated in cerebral palsy. This study assessed the effectiveness of intrathecal baclofen in reducing spasticity in cerebral palsy. Candidates were screened by randomized, double-blind, intrathecal injections of baclofen and placebo. Responders were defined as those who experienced an average reduction of 1.0 in the lower extremities on the Ashworth Scale for spasticity. Responders received intrathecal baclofen via the SynchroMed System and were followed for up to 43 months. Fifty-one patients completed screening and 44 entered open-label trials. Lower-extremity spasticity decreased from an average baseline score of 3.64 to 1.90 at 39 months. A decrease in upper extremity spasticity was evidenced over the same study period. Forty-two patients reported adverse events. Most common reports were hypotonia, seizures (no new onset), somnolence, and nausea or vomiting. Fifty-nine percent of the patients experienced procedural or system-related events. Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen. Adverse events, although common, were manageable.     

Time course of the effect of a bolus dose of intrathecal baclofen on severe cerebral spasticity

Abstract. Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using clinical scales such as the Modified Ashworth Scale (MAS). In the literature, the time and period of maximum effect of a bolus dose of intrathecally administered baclofen in patients with cerebral spasticity is variously reported. The aim of the study was, therefore, to reveal the time course of the effect of a BBT on severe cerebral spasticity by the use of a recently described spasticity measurement method.Spasticity in knee joints of 13 patients with severe cerebral spasticity was repeatedly assessed using the MAS and also continuously recorded by the measurement of force under circular fibreglass casts. Force was recorded as nettorque by multiplying the force by the distance between sensor and joint axis, thus allowing inter-individual comparison. Half-hour time integrals (TI) of net-torque were determined 9 hours before and 22 hours after intrathecal baclofen administration. Post-BBT half-hour time integrals (TI₊₀, TI_+0.5, to TI₊₂₂) were compared with the mean of 17 pre-BBT half-hour time integrals .Significantly lower post-BBT half-hour time integrals compared with were found between TI₊₂ and TI₊₈ (Dunnett adjusted p < 0.05). The median lowest TI after BBT of the 13 patients was TI₊₄. The lowest mean MAS scores were found 4 hours after BBT. The findings suggest that the greatest effect of BBT on cerebral spasticity occurs between 2 and 8.5 hours, with a maximal effect at 4 hours after intrathecal baclofen injection. Clinical scales used to determine the effect of BBT should thus be carried out during this period—ideally at 4 hours after baclofen injection.     

Epilepsy and intrathecal baclofen therapy in children with cerebral palsy

The objective of this study was to analyze the relationship between epilepsy and intrathecal baclofen by investigating a consecutive sample of 150 children with cerebral palsy or spasticity of cerebral origin who underwent intrathecal baclofen. The medical charts of the 150 children were retrospectively reviewed. A series of 100 children with cerebral palsy, operated on other procedures, was reviewed as a control group. Forty percent of the 150 children had epilepsy before intrathecal baclofen pump implantation; 13.3% had a decrease in seizure frequency after intrathecal baclofen, while two children worsened and one child had seizures ex novo. We conclude that in children with spasticity of cerebral origin, intrathecal baclofen does not seem to aggravate or induce seizure activity.     

Optimierte Therapie des spastischen Syndroms durch Kombination von intrathekalem Baclofen mit Botulinumtoxin

Intrathecal administration of baclofen has proved to be an effective treatment of spasticity related to CNS damage. Especially patients with spinal spasticity due to traumatic spinal cord injury or transverse myelitis showed a dramatic reduction of spasticity and improvement of their Ashworth scores. The results are, however, often disappointing in patients with muscular hypertension of the extensor muscles, which is frequently found in patients with multiple sclerosis or cerebral hypoxia. In the latter, using intrathecal baclofen may be restricted by serious side effects. Botulinumtoxin A is widely used in patients with various forms of dystonia. It has also been studied in spastic disorders, where local injections were valuable in relieving focal spasticity in hemiparetic patients and in infantile cerebral palsy. It is used only cautiously in severe paraspasticity. The case reports of 4 patients with incomplete and complete paraparesis due to spinal cord injury, neurodegenerative pyramidal disorder, and cerebral hypoxia demonstrate that a combination of intrathecal baclofen and botulinumtoxin A can improve clinical benefits and reduce side effects.     

Continuous infusion of intrathecal baclofen: long-term effects on spasticity in spinal cord injury

The effects of intrathecal baclofen infusion were studied in 9 spinal cord injury patients whose spasticity had been refractory to oral medications. In a two stage, placebo controlled trial, baclofen was administered into the lumbar intrathecal space and subsequent clinical and neurophysiologic changes were assessed. In stage 1, 9 patients underwent a 5 day percutaneous infusion of baclofen and placebo via an external pump. Ashworth and reflex scores were assessed at time of enrollment, after infusion of that amount of baclofen which provided optimal spasticity control and after intrathecal infusion of placebo. The mean Ashworth grade decreased from 3.78 +/- 1.34 to 1.16 +/- 0.48 (p less than 0.001) while mean reflex score decreased from 3.57 +/- 1.05 to 0.64 +/- 0.87 (p less than 0.001). These values differed significantly from those associated with placebo therapy (Ashworth grade--2.54 +/- 1.04, p less than 0.001; reflex score--2.56 +/- 1.04, p less than 0.01). Objective improvements in functional abilities and independence were noted in 8 patients, while somatosensory and brainstem auditory evoked potentials were unchanged in all patients. Urodynamic evaluation revealed increased bladder capacity in 3 patients, while in 4 no change was observed. In Stage 2, permanent programmable infusion pumps were implanted in 7 patients who demonstrated a good response during Stage 1. In this group, mean Ashworth score decreased from 3.79 +/- 0.69 to 2 +/- 0.96 (p less than 0.001) and mean reflex score decreased from 3.85 +/- 0.62 to 2.18 +/- 0.43 (p less than 0.001). Baclofen dosage increased from 182 +/- 135 to 528 +/- 266 mcg/day over the 3-22 month follow-up period. Most of the dosage increase occurred within the initial 12 months following infusion pump implantation and tended to plateau thereafter. Minor complications such as catheter dislodgement/kinking and nausea occurred infrequently while no device related infections were observed. There was no clinical evidence of any significant baclofen neurotoxicity either in Stage 1 or 2. The only ambulatory patient developed marked lower extremity weakness during Stage 1 intrathecal baclofen infusion and was temporarily unable to walk. We conclude that continuous administration of intrathecal baclofen is an effective and safe modality for spasticity control in patients who are refractory to oral medications.     

Functional outcome of intrathecal baclofen administration for severe spasticity

PURPOSE: To estimate the functional benefit in patients with severe spasticity treated with intrathecal baclofen infusion through an implantable pump and to stress the need for functional assessment of these patients with a functional scale. PATIENTS AND METHODS: Between 1999 and 2003, 22 patients with a long history of severe and disabling pharmaceutically intractable spasticity, underwent implantation of a pump for continuous intrathecal baclofen infusion. The patients were subdivided into two categories according to the aetiology of spasticity: 15 had Multiple Sclerosis and seven had suffered a Spinal Cord Injury at different levels (from C4 to T11). Clinical status was assessed with the Ashworth and Penn spasm scales. Functional benefits were evaluated with the Barthel index score and pain relief with a self-reported visual analogue pain scale. RESULTS: Postoperatively, all patients presented improvement in spasticity, reduction of spasm frequency, significant improvement in functional status, enhancement of life comfort and reduction of pain. CONCLUSION: Reduction of spasticity and spasms achieved with intrathecally delivered baclofen, leads to functional improvement and pain relief.     

Clinimetric issues of screening for responsiveness to intrathecal baclofen in dystonia

OBJECTIVES: In this study we address clinimetric issues that pertain to the screening of responsiveness to intrathecal baclofen (ITB) in dystonia. METHODS: Eight patients with severe dystonia, who did not respond to oral medication, were evaluated in a double-blind placebo controlled ascending dose screening procedure, which included a randomised sequence of injections of 25, 50 and 75 microg baclofen and placebo. Self-assessments of dystonia severity on a visual analogue scale (VAS) and the Dyskinesia Rating Scale (DRS) were carried out at baseline 1, 4 and 8 hours after a bolus injection. RESULTS: Compared to the VAS, the DRS lacked responsiveness in all patients. Baseline scores of the VAS scores varied considerably between and within patients and underscore the need to express response scores in relation to the baseline. After placebo administration some patients showed a persistent improvement of about 30% across the day, while at some assessments improvements of >50% were noted. Based on the aforementioned findings, a responsiveness coefficient was used which relates the baclofen effect size to the non-specific score changes that may occur as a placebo effect or as random fluctuations in dystonia. Four patients with a responsiveness coefficient >2 received pump implantation and did well on continuous infusion of ITB. Several side effects occurred during the screening procedure, but none interfered with the execution of the screening procedure. CONCLUSIONS: This study demonstrates important clinimetric issues that need to be taken into account when screening for responsiveness to ITB.     

Cardiovascular alterations heralded by intrathecal baclofen bolus

We describe two patients in whom serious bradycardia and arterial hypotension occurred after a small intrathecal baclofen (ITB) test bolus. Both patients suffered from severe spasticity (one due to brain injury, one due to spinal cord injury). Medical history and diagnostic examinations revealed no previous cardiological problems. Ten minutes following a 50 μg ITB bolus, patient 1 developed bradycardia (58 bpm) and incomplete right branch block, lasting for 3 hours. In patient 2, a 20 μg ITB bolus was followed after 5 minutes by severe bradycardia (30 bpm) and hypotension (60/30 mmHg), without loss of consciousness, lasting for 10 minutes. Exaggerated muscle tone was alleviated in both patients after 2 hours by the applied doses. Neither patient underwent implantation of a permanent pump system, both were continued on oral baclofen. Despite numerous unremarkable repeat cardiological exams, both patients suffered fatal cardiac arrest one and two months later, respectively. Our observations suggest that ITB may herald cardiovascular dysfunction in predisposed patients. Careful cardiological examination before ITB treatment, and close monitoring during ITB testing in particular, is advised.     

Clonazepam, baclofen and placebo in the treatment of spasticity.

25 patients with multiple sclerosis (MS) and other spastic disorders, 33 MS patients and 10 control patients with MS were given clonazepam, baclofen or placebo over a period of 5 days to 20 weeks. Both clonazepam and baclofen were significantly more effective than placebo in the treatment of spasticity (p less than 0.005 or p less than 0.01). A clinical trial of clonazepam versus baclofen was carried out and this showed no significant difference between the two drugs. However, there was indication that clonazepam influenced with better improvement in patients with slight muscle hypertonia mainly of cerebral origin. Patients with more severe forms, mainly of spinal spasticity, benefited rather from baclofen treatment (Fisher's test, p = 0.003). There was suggestion that combination of the two drugs may be more effective in some patients than than clonazepam or baclofen alone.     

Lasting reduction of severe spasticity after ending chronic treatment with intrathecal baclofen.

OBJECTIVE--To investigate whether the dose of intrathecal baclofen necessary for a sufficient reduction of muscle tone and spasms changes during treatment of severe spasticity. METHODS--A group of 27 patients received intrathecal baclofen for 61 (SD 18) months. RESULTS--Spasticity remained absent or strongly reduced after stopping the intrathecal baclofen infusion in seven patients. The dose of baclofen could be reduced to 40% of that dose which was originally necessary in 10 patients. The dose remained the same or increased slightly in 10 patients. Possible reasons for the continuing reduction of spasticity after terminating long term intrathecal baclofen infusion in some patients could be: lasting morphological changes in spinal cord neurons by second messenger controlled modulation of gene expression, a toxic effect of baclofen on spinal neurons, muscular atrophy, inflammation due to the catheter, or progression of multiple sclerosis. CONCLUSIONS--A higher initial daily dose of intrathecal baclofen might lead to a faster, lasting suppression of spasticity and the development of spastic symptoms might even be prevented by pre-emptive treatment with baclofen in patients with newly acquired lesions of the spinal cord.     

Measurement of the effect of a bolus dose of intrathecal baclofen by a repetitive movement test

We assessed the repetitive movement (RM) test for measuring the effect of a trial bolus dose of intrathecal baclofen on spasticity. The RM test measures passive range of motion (ROM) by electrogoniometry and stretch reflex activity (SRA) of the flexors and extensors of the knee and ankle by surface electromyography. The SRA has a dynamic component (dynamic stretch reflex, DSR) and a tonic component (tonic stretch reflex, TSR). Four hypotheses were formulated: (a) RM results show a negative relationship between SRA and ROM; (b) values on the RM test are correlated with clinical scores of tonus and spasticity; (c) RM results show a reduction in SRA after administration of the clinically optimal dose of baclofen; and (d) RM results show a dose-dependent effect of intrathecal baclofen on SRA. Twenty-four patients were selected because they had impairments and disabilities caused by intractable spasticity. A bolus of baclofen was administered with incremental doses (25–150 μg) until an optimal effect or no effect was obtained. The main outcome measures were RM test and clinical assessments of the Ashworth and spasm score. The results were (a) For the ankle a negative correlation was found between ROM and TSR of the flexor and extensors; for the knee a significant negative correlation was found only with the DSR of the biceps femoris. (b) A positive correlation was found between the Ashworth score and TSR of the extensors and between the spasm score and DSR and TSR of the gastrocnemius muscle. (c) Significant differences were found between baseline measurements and the optimal dose of baclofen for all measures. (d) A significant dose-dependent effect of intrathecal baclofen on the level of SRA was observed. The RM test is thus a useful clinical tool for objectively measuring the effect of intrathecal baclofen administration on spasticity in patients with an upper motor neuron syndrome. Received: 11 December 1998 Received in revised form: 6 May 1999 Accepted: 20 May 1999     

Safety and Efficacy of Intrathecal Baclofen Infusion by Implantable Pump for the Treatment of Severe Spinal Spasticity: A Spanish Multicenter Study

Objective. To assess long‐term efficacy, safety and functional benefit of intrathecal baclofen for severe spinal spasticity. Materials and Methods. This prospective multicenter study was performed in two stages: the first one consisted of an intrathecal bolus injection of baclofen, and the second of a continuous intrathecal baclofen infusion by means of an implantable pump. The sample consisted of 72 adult patients with severe spinal spasticity. Sixty‐four were implanted and followed for 36 months. Muscular tone, spasms, and functional scales were evaluated before and periodically after administration of the drug, with a follow‐up period of 36 months. Results. A very significant decrease in tone and spasms was observed in all cases (p < 0.001). Tolerance appeared during the first 12 months, increasing doses from a mean initial dose of 83.2 μg (range 25–200 μg) to a mean final dose of 270 μg (range 25–800 μg). Later on, efficacy remained stable, except in cases of mechanical problems of the infusion system.     

Guided intrathecal baclofen administration by using soleus stretch reflex in moderate-severe spastic multiple sclerosis patients with implanted pump

We tested the hypothesis that changes in soleus stretch reflex was correlated to changes in intrathecal baclofen dose in 12 multiple sclerosis patients with moderate-severe spasticity treated with intrathecal baclofen pump. Twice patients were evaluated clinically and biomechanically. The short-latency soleus stretch reflex was elicited by rotating the ankle joint 4 degrees with a velocity from 3.1 to 180 degrees/s. There was a strong correlation between changes in intrathecal baclofen dose and amplitude of the short-latency stretch reflex (r=-0.88, P<0.001), which means that with an increase in baclofen dose there is a decrease in the amplitude. In contrast, no correlation exists between changes in intrathecal baclofen dose and clinical assessment of spasticity by using the Ashworth scale. The amplitude of the stretch reflex was very small (5 microV) compared with previous findings (>50 microV), which indicates an effective antispastic effect of intrathecal baclofen. We suggest that clinical evaluation of spasticity using Ashworth scale is insensitive to detect minor changes in moderate-severe spasticity and consequently might not be very useful in evaluating spasticity in relation to ambulatory filling of baclofen pumps. The soleus stretch reflex might be useful in situations when there is doubt about the effect of intrathecally administered baclofen.     

Measurement of the effect of a bolus dose of intrathecal baclofen by continuous measurement of force under fibreglass casts

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using the modified Ashworth Scale (MAS) and Penn Spasm Frequency Scales (SFS). The result of a BBT may be difficult to interpret in patients with reduced joint mobility caused by contractures. The aim of this study was to apply a new spasticity measurement which would quantify and visualise the effect of a BBT in 10 patients with severe cerebral spasticity and contractures. Spasticity was recorded continuously by the measurement of force under circular fibreglass casts in 10 knee joint contractures. Force was recorded as net-torque by multiplying the force and distance between sensor and joint axis, thus allowing inter-individual comparison. MAS, SFS, and two three-hour time integrals of net-torque were determined before and after intrathecally administered baclofen. No significant changes in MAS (p = 0.1) and SFS (p = 0.07) were observed; however, a significant reduction of time integrals of net-torque after baclofen administration (p = 0.005) was found. The present study shows that the antispastic effect of intrathecally administered BBT can be quantitatively assessed and visualised using the described method. It also suggests that this method can be helpful in the assessment of the effectiveness of the BBT in patients with severe spasticity of cerebral origin and contractures. Received: 17 October 2001, Received in revised form: 15 March 2002, Accepted: 18 March 2002     

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 X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy is a progressive neurodegenerative disorder involving the destruction of white matter in the brain and adrenocortical hormone deficiency. Clinical symptoms first appear between 4 and 8 years of age and include spasticity, visual loss, dysphagia, and seizures. In this report, continuous infusion of intrathecal baclofen was used to treat the severe spasticity of an 8-year-old patient with X-linked adrenoleukodystrophy. The improvement in this patient's quality of life, including the elimination of pain and the increased ease of care, suggests that intrathecal baclofen should be considered as part of the treatment strategy for spasticity associated with X-linked adrenoleukodystrophy and other neurodegenerative disorders in children and adults.     

Long term effect (more than five years) of intrathecal baclofen on impairment, disability, and quality of life in patients with severe spasticity of spinal origin

OBJECTIVES: To evaluate long term change in impairment, disability, and health related functional status in patients with severe spasticity who received intrathecal baclofen. METHODS: A long term (more than five years) observational longitudinal follow up study assessing 21 patients who received intrathecal baclofen given by programmable pump. Patients had chronic disabling spasticity which did not respond to oral antispasmolytic agents. Clinical efficacy was assessed by the Ashworth scale and spasm score; disability by the expanded disability status scale (EDSS), ambulation index (AI), and incapacity status scale (ISS); and health related quality of life by the sickness impact profile (SIP) and the Hopkins symptom checklist (HSCL). RESULTS: Compared with pretreatment values, there was a significant improvement in clinical efficacy (Ashworth scale and spasm score, p<0.05) but a small but significant worsening of disability (EDSS, AI, and ISS, p<0.05). Comparing pretreatment with 26 weeks after pump implantation, a worsening was observed in disability (EDSS and ISS, p<0.05) and perceived health status (SIP, psychosocial dimension, p<0.05). CONCLUSIONS: Long term administration of intrathecal baclofen delivered by an implanted programmable pump resulted in improved clinical efficacy but not in improvement in disability or perceived health status.     

Electrophysiological assessment of the effect of intrathecal baclofen in spastic children.

OBJECTIVES: To evaluate the effect of intrathecal baclofen in a group of spastic children using electrophysiological procedures described in adults. METHODS: Six children (aged 1-14 years) with severe spasticity of various aetiologies underwent transcranial magnetic stimulation, H reflex and flexor reflex studies before and after intrathecal injection of baclofen. Ashworth scale was used for clinical evaluation of spasticity. RESULTS: Motor evoked potentials, present in two patients before baclofen, were preserved after injection. Before baclofen, H reflex was present in 5 patients (H(max)/M(max) from 0.23 to 0.84) and absent in one who had infantile neuroaxonal dystrophy. After baclofen, it was absent in 4 patients and markedly reduced in one. Surface of flexor reflex significantly decreased after baclofen (P=0.01), while threshold significantly increased (P=0.003). CONCLUSIONS: In spastic children, the action of baclofen on spinal pathways may be quantified by the same electrophysiological procedures as in adults. This approach may contribute to select optimal dosage.     

Intrathecal baclofen withdrawal: a case report and review of the literature

INTRODUCTION: Spasticity is an endpoint of a variety of neurologic disorders with upper motor neuron damage. There have been several studies demonstrating improvement in spasticity through administration of intrathecal baclofen. Withdrawal from oral baclofen has been well described. Intrathecal baclofen withdrawal has been less frequently reported. We present a case of withdrawal after intrathecal baclofen pump catheter failure. PATIENT: A 14-year-old boy presented with fevers, which were thought to be related to recent spine surgery and possible pneumonia. Eventual workup revealed evidence of intrathecal baclofen withdrawal owing to pump catheter failure. His fevers, with temperatures of up to 40 degrees C, and painful muscle spasms resolved and his clinical condition improved after pump exploration and resumption of intrathecal delivery. CONCLUSIONS: Intrathecal baclofen withdrawal can be life threatening. Prompt recognition and restoration of an adequate intrathecal baclofen dose is essential for recovery.     

Functional improvement in patients with severe spinal spasticity treated with chronic intrathecal baclofen infusion

In this retrospective study we evaluated the efficacy and functional benefits of chronic intrathecal baclofen infusion in severe spinal spasticity. Twenty patients with a diagnosis of severe intractable spinal spasticity were evaluated prior to implantation of a programmable pump for chronic intrathecal baclofen therapy and at follow up, which ranged from 12 to 36 months (mean 22.4 months). The mean age of the patients was 39.1 years. The prevailing pathology was multiple sclerosis. All were unable to walk. Patient assessment was based on the Ashworth Scale, the Spasms Frequency Scale, self-reported pain and Functional Independence Measure (FIM) scores. The Wilcoxon test was used for statistical analysis. A statistically significant decrease in muscle tone, spasms and pain was observed in all the patients. The Ashworth score decreased from 4.4 to 1.8, the spasms frequency score from 2.5 to 0.5 and the self-reported pain score from 5.5 to 2.3. The FIM score also showed a statistically significant change (increasing from a mean of 33.8 to 58.7). Two patients in employment were able to return to work. No severe side effects were observed. Chronic intrathecal baclofen infusion was seen to produce a functional improvement in patients with severe spinal spasticity, particularly as regards bathing, comfortable wheelchair sitting and mobility.