Effects Of Intrathecal Baclofen Therapy Research Articles

Does Intrathecal Baclofen Therapy Lead to an Improvement in Impairments and Functional Limitations in Patients With Acquired Brain Injury (ABI)? A Retrospective Study

Research Objectives To investigate effects of intrathecal baclofen (ITB) therapy on impairments and functional limitations in the acquired brain injury population(ABI). Design A retrospective study using chart reviews using a standardized data collection form on inpatient brain injury units to collect data on effects of ITB therapy on the ABI population with defined inclusion and exclusion criteria. A standardized data collection form was utilized along with a procedural manual for data abstraction. Setting Specialized acute and sub acute brain injury units. Participants Initially, 59 subjects were considered and a total of 15 medical records had sufficient data to analyze which met our criteria. 12 male patients (80%) and three female patients (20%). The mean age for ITB pump implantation was 35.5 years and the range was 18-67 years of age. Interventions Intrathecal Baclofen Pump Therapy with adjunctive therapies (for example skilled therapy, local Botox injections, serial casting, medication). Main Outcome Measures Modified Ashworth Scores, Passive Range of Motion, Mobility, JFK Coma Recovery Scale- Revised. Results The most significant change was noted with Modified Ashworth Scale (MAS) scores in the proximal hip muscle groups. Modified Ashworth Scale (MAS) scores with high significance (p-values ≤0.05) and large effect size (Cohen's D values >0.8) included right hip flexors, right hip extensors and R hip adductors. No statistically significant findings were found in other muscle groups, functional mobility, PROM and CRS-R (Coma Recovery Scale-Revised©) scales. Conclusions There were no significant changes noted in regards to functional status. However, data reflects improvements in spasticity of proximal hip musculature. This may result in improved positioning in bed or wheelchair as well as ease of hygiene and improved comfort. More research is recommended with a larger sample size and additional focus on pain and caregiver burden. Author(s) Disclosures All authors of this research study have no conflicts to disclose. To investigate effects of intrathecal baclofen (ITB) therapy on impairments and functional limitations in the acquired brain injury population(ABI). A retrospective study using chart reviews using a standardized data collection form on inpatient brain injury units to collect data on effects of ITB therapy on the ABI population with defined inclusion and exclusion criteria. A standardized data collection form was utilized along with a procedural manual for data abstraction. Specialized acute and sub acute brain injury units. Initially, 59 subjects were considered and a total of 15 medical records had sufficient data to analyze which met our criteria. 12 male patients (80%) and three female patients (20%). The mean age for ITB pump implantation was 35.5 years and the range was 18-67 years of age. Intrathecal Baclofen Pump Therapy with adjunctive therapies (for example skilled therapy, local Botox injections, serial casting, medication). Modified Ashworth Scores, Passive Range of Motion, Mobility, JFK Coma Recovery Scale- Revised. The most significant change was noted with Modified Ashworth Scale (MAS) scores in the proximal hip muscle groups. Modified Ashworth Scale (MAS) scores with high significance (p-values ≤0.05) and large effect size (Cohen's D values >0.8) included right hip flexors, right hip extensors and R hip adductors. No statistically significant findings were found in other muscle groups, functional mobility, PROM and CRS-R (Coma Recovery Scale-Revised©) scales. There were no significant changes noted in regards to functional status. However, data reflects improvements in spasticity of proximal hip musculature. This may result in improved positioning in bed or wheelchair as well as ease of hygiene and improved comfort. More research is recommended with a larger sample size and additional focus on pain and caregiver burden.

Effects of intrathecal baclofen therapy in subjects with disorders of consciousness: a reappraisal

Baclofen is a structural analogue of gamma-amino-butyric acid (GABA), which reduces spastic hypertonia of striated muscle due to a mechanism of GABAB-ergic inhibition of mono- and polysynaptic reflexes at the spinal level. There are reports of patients with severe disorders of consciousness that presented a substantial improvement following intrathecal baclofen (ITB) administration for severe spasticity. The neural mechanisms underlying the clinical recovery after ITB have not yet been clarified. Baclofen could modulate sleep-wake cycles that may be dysregulated and thus interfere with alertness and awareness. The diminished proprioceptive and nociceptive sensory inputs may relieve thalamo-cortical neural networks involved in maintaining the consciousness of the self and the world. ITB treatment might also promote the recovery of an impaired GABAergic cortical tone, restoring the balance between excitatory and inhibitory cortical activity. Furthermore, glutamatergic synapses are directly or indirectly modulated by GABAB-ergic receptors. Neurophysiological techniques (such as transcranial magnetic stimulation, electroencephalography, or the combination of both) can be helpful to explore the effects of intrathecal or oral baclofen on the modulation of neural cortical circuits in humans with disorders of consciousness.

The Impact of Intrathecal Baclofen Therapy on Health-related Quality of Life for Children with Marked Hypertonia

ABSTRACT Purpose: To investigate the effects of intrathecal baclofen therapy (ITB) on health-related quality of life for children with cerebral palsy and neurological conditions. Method: This study is part of a longitudinal, multicentre audit. The primary outcome measure, the Caregiver Priorities and Child Health Index of Life with Disabilities, was completed at baseline, 6 and 12 months post ITB implant. Results: Forty subjects with cerebral palsy and other neurological conditions demonstrated significant improvement in aspects of health-related quality of life following ITB therapy, mean change 42.3 (SD 14.9) at baseline to 53.3 (SD 14.7) at 12 months (p< .001). Conclusion: Evidence to demonstrate the utility of ITB in pediatric populations beyond spasticity and dystonia reduction is limited. Our findings suggest that ITB improves aspects of quality of life, comfort, and ease of caregiving in children with cerebral palsy and other neurological conditions.

Molecular mechanisms of the antispasticity effects of baclofen on spinal ventral horn neurons.

Baclofen is a lipophilic γ-aminobutyric acid (GABA) derivative that exhibits strong intrinsic activity and a high affinity for GABAB receptors. Intrathecal baclofen therapy has been used as an antispasticity and muscle relaxant drug in the clinical treatment of patients with severe spasticity. However, the cellular mechanisms of the antispasticity effects of baclofen on the ventral horn neurons of the spinal cord are unknown. We examined the action of baclofen on excitatory synaptic transmission in ventral horn neurons in the rat spinal cord by whole-cell patch-clamp recordings. Baclofen significantly reduced the frequency and amplitude of miniature excitatory postsynaptic currents. The reduction in miniature excitatory postsynaptic current frequency was particularly strong, indicating presynaptic inhibition by baclofen. Moreover, baclofen-induced outward currents in all neurons tested. The baclofen-induced outward currents persisted in the presence of tetrodotoxin and glutamate receptor antagonists and were diminished in the presence of the postsynaptic intracellular K channel blocker cesium sulfate and the G-protein inhibitor guanosine 5'-(β-thio)diphosphate trilithium salt. These results indicate direct postsynaptic depression mediated by G-protein-activated K channels by GABAB receptors on ventral horn neurons. The baclofen-induced outward currents and the inhibitory effects on spontaneous excitatory postsynaptic currents were blocked by the selective GABAB receptor antagonist CGP35348. Baclofen may have both presynaptic and postsynaptic capacity to inhibit synaptic transmission in ventral horn neurons by GABAB receptors. These cellular mechanisms may induce the antispasticity effects of intrathecal baclofen therapy in the spinal cord.

Intrathecal Baclofen Therapy Prior to Spinal Fusion for Patients With Gross Motor Function Classification System IV-V Cerebral Palsy.

Patients with Gross Motor Function Classification System (GMFCS) IV-V cerebral palsy (CP) have significant spasticity and frequently develop scoliosis. Intrathecal baclofen (ITB) pumps are effective in managing spasticity. The effect of ITB therapy on the postoperative course following spinal fusion in patients with GMFCS IV-V CP has not been described. This study sought to compare postoperative recovery, including complications, in patients using ITB therapy with those with no ITB therapy. Evaluate the effect of ITB on the postoperative recovery for patients with GMFCS IV-V CP who undergo spinal fusion for scoliosis. Health records for patients with GMFCS IV-V CP who underwent a spinal fusion for scoliosis at a major quaternary-care children's hospital from January 2009 to October 2015 were reviewed and relevant data were abstracted. Descriptive statistics and regression models were used to compare patients. Sixty-nine patients were included-19 ITB therapy and 50 no ITB therapy. Demographic and operative characteristics were similar across groups. The mean length of stay for patients in the ITB therapy group was 11.2 days and 14.3 days for the no ITB therapy group, with no difference between groups (p = .12). Pain scores in both groups decreased at the same rate, with scores in the ITB therapy group averaging one-half point lower (p = .32). The average amount of morphine equivalents (p = .71) and benzodiazepine equivalents (p = .53) used were similar between groups. Complication rates were significantly different between groups. Four (21%) of the ITB therapy patients had 1 or more complications whereas 28 (56%, p = .01) in the no ITB therapy group had 1 or more complications. The average number of complications per patient in the ITB therapy group was 0.3 (SD: 0.075, range: 0-3) and the no ITB therapy group was 1.1 (SD: 1.1, range: 0-6, p = .01). There was no significant difference in length of stay, pain scores, or pain/spasticity medication use between groups after spinal fusion, but there was a significantly lower incidence of complications in the ITB therapy group.

Respiratory Function Under Intrathecal Baclofen Therapy in Patients With Spastic Tetraplegia

Intrathecal baclofen (ITB) therapy is an effective treatment for patients with severe spasticity. However, the effect of ITB therapy on respiratory function has not been reported in detail. In this study we quantitatively analyzed the effects of ITB on the respiratory function of patients with spastic tetraplegia. We retrospectively reviewed 23 patients who were administrated ITB therapy from January 2009 to December 2012. Six of these 23 patients, who had spastic tetraplegia and were able to undergo spirometric testing, were included this study. The spasticity derived from cervical spinal cord injury in four patients and cerebral palsy (CP) in two patients. Patients' Ashworth Scale scores and spirometer measurements obtained before and 1-6 months after the start of ITB therapy were evaluated and compared. Before ITB therapy, %FVC of all six patients was below 80%, and a restrictive respiratory disorder was diagnosed in five patients and a combined respiratory disorder in one patient. Ashworth Scale scores for both the lower and upper extremities improved significantly with ITB therapy. Forced vital capacity (FVC), %FVC, and forced expiratory volume at one sec also improved significantly with ITB therapy. Respiratory disorders were indeed present in our SCI and CP patients with spastic tetraplegia, and the respiratory function of these patients improved with ITB therapy. Our results suggest that ITB therapy is safe and efficacious in patients with spastic tetraplegia and respiratory dysfunction.

Long-term effects of intrathecal baclofen in multiple sclerosis

ObjectivesSpasticity is associated with various neurological conditions. In this study the authors analyzed the long term effects of intrathecal baclofen therapy in multiple sclerosis and evalued the benefits of the treatment on spasticity, disability, pain, spasm frequency and rated the incidence of side effects. Patients and methodsA records of 123 patients, with a severe, progressive and refractory to medical therapy spasticity from different causes, underwent baclofen pump placement, after a bolus test, from 2000 to 2012,under Department of Neurosurgery at the Second University of Naples/Italy. We present our experience in treating 28 subjects that was affected by multiple sclerosis. For all patients we reviewed long-term response to therapy, surgical technique, surgery- and pump-related complications. Every patients were evaluated by means of the Modified Ashworth Scale (MAS), Penn Spasm Frequency Scale (SFS), Visual analogue Scale For Pain (VAS), Barthel index (BI) and Self Rating Depression Scale (SDS) ResultsDuring follow up the mean MAS score for upper and lower extremities decrease significantly. Also SFS's decrease was statistically significant. This resulted in a dramatic improvement of BI. Furthermore, we observed a marked improvement in VAS and SDS. ConclusionsIntrathecal baclofen provides effective long-term treatment of spasticity multiple sclerosis related. ITB therapy increases the quality of lifestyle and functional independence in appropriately selected cases.

Timing of intrathecal baclofen therapy in persons with acquired brain injury: Influence on outcome

Objective: Evaluation of the effects of intrathecal baclofen therapy (ITB) delivered by a pump implanted at a very early stage in acquired brain injury (ABI).Study design: This investigation was a longitudinal prospective observational study, including a series of 13 ABI implanted within 6 months of the acute events.Main outcome measure: The Modified Ashworth Scale (MAS) and Spasms Frequency Score (SFS) have been used as a primary outcome measure. The Disability Rating Scale (DRS) and Level of Cognitive Functioning (LCF) scores have been computed in order to verify possible interferences of baclofen therapy at an early stage on a global outcome. An intrathecal bolus test was not performed. Drug tolerability was tested by oral administration of baclofen 100 mg.Results: Reduction of spasticity and spasms frequency were measured 3 months after patients received the implant and at the 1-year follow-up. There was no difference found for global outcome measure between the group of patients who received the implant earlier (within 3 months) compared to the group who received it later (between 3–6 months).Conclusion: ITB therapy in ABI should be considered as early as possible. The implants are safe and effective in reducing spasticity. An intrathecal bolus test was not compulsory in ABI.

Effects of intrathecal baclofen therapy on motor and cognitive functions in a rat model of cerebral palsy

Cerebral palsy (CP) arises in the early stages of brain development and manifests as spastic paresis that is often associated with cognitive dysfunction. Available CP treatments are aimed at the management of spasticity and include botulinum toxin administration, selective dorsal rhizotomy, and intrathecal baclofen (ITB). In this study, the authors investigated whether the management of spasticity with ITB therapy affected motor function and whether the release of spasticity was associated with an improvement in intellectual function. Newborn Sprague-Dawley rats were divided into the following groups: control, CP model, and CP model with ITB therapy. For the CP model, postnatal Day 7 (P7) rats were exposed to hypoxic conditions (8% O(2)) for 150 minutes after ligation of the right common carotid artery. In the groups receiving ITB therapy, a spinal catheter was connected to an osmotic pump filled with baclofen and placed in the spinal subarachnoid space on P21 in the early group and on P35 in the late group. A daily dose of 12 μg of baclofen was continuously administered until P49, resulting in 28 days of therapy in the early group and 14 days in the late group. Changes in spasticity in the CP and CP with ITB treatment groups were confirmed by assessing the motor evoked potential in the plantar muscle. In the CP group, the time required to complete a beam-walking test on P49 was significantly longer than that in the control and ITB treatment groups (4.15 ± 0.60 vs 2.10 ± 0.18 and 2.22 ± 0.22 seconds, respectively). Results of the beam-walking test are expressed as the mean ± SD. Radial arm maze performance on P49 indicated that spatial reference memory had significantly deteriorated in the CP group compared with controls (2.33 ± 0.87 vs 0.86 ± 0.90 points); moreover, working memory was also negatively affected by CP (0.78 ± 1.09 vs 0.14 ± 0.38 points). Results of the memory tests are expressed as the mean ± SE. These memory functions did not recover after ITB treatment. Management of spasticity with ITB therapy improved the walking ability in the rat CP model. Intrathecal baclofen therapy-which reduces harmful sensory and motor stimulations caused by spasticity to more optimal levels-contributed to motor function recovery; however, it had no effect on intellectual recovery as assessed by memory performance in the rat CP model.

Poster 383 Urologic Adverse Effects of Intrathecal Baclofen Therapy in a Pediatric Population: Review of Case Series

Poster 383 Urologic Adverse Effects of Intrathecal Baclofen Therapy in a Pediatric Population: Review of Case Series

Treatment of spasticity related to multiple sclerosis with intrathecal baclofen: A long-term follow-up

Spasticity is a frequent disabling symptom in patients with multiple sclerosis, which contributes to functional deterioration. To evaluate the long-term effect of intrathecal baclofen therapy in multiple sclerosis-related spasticity and to evaluate the side-effects of long-term therapy, and the doses of baclofen required. Fourteen patients with multiple sclerosis were followed up clinically for a mean of 62 months (range 19-137 months). Clinical evaluation was made using individual goals, modified Ashworth scale, and Kurtzke Expanded Disability Status Scale. Spasticity, measured with the modified Ashworth score, decreased in all patients by a mean of 1 point. The score on the Expanded Disability Status Scale improved in 2 cases. Prior to implantation, 10 patients (72%) reported severe pain. After implantation 3 improved and 7 became pain-free. The daily doses needed for treatment were highly individual. The effect of intrathecal baclofen on spasticity lasted observation time. One patient experienced progressive cognitive impairment as a side-effect of baclofen. Intrathecal baclofen is well-tolerated and the effect lasts for up to 12 years. A thorough continuous clinical assessment is required because the differentiation between symptoms of multiple sclerosis progression and side-effects of baclofen may be difficult. Intrathecal baclofen should be considered as an option for long-term treatment of patients with advanced spasticity. Pain control can also be achieved by optimized intrathecal baclofen treatment.

Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury

For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threatening withdrawal syndrome present serious problems for its management. Now, in an experimental model of spinal cord injury spasticity, AMPA receptor blockade with NGX424(Tezampanel) has been shown to reduce stretch reflex activity alone and during tolerance to intrathecal baclofen therapy.These results stem from the observation that GluA1 receptors are overexpressed on reactive astrocytes following experimental ischaemic spinal cord injury. Although further validation is required, the appropriate choice of AMPA receptor antagonists for treatment of stretch hyperreflexia based on our recent understanding of reactive astrocyte neurobiology following spinal cord injury may lead to the development of a better adjunct clinical therapy for spasticity without the side effects of intrathecal baclofen therapy.

Continuous intrathecal baclofen therapy in children with cerebral palsy – when does improvement emerge?

The aim of the study was to explore the timing of effects of intrathecal baclofen therapy in children with cerebral palsy. Thirty five children with severe disabilities with cerebral palsy who started continuous intrathecal baclofen therapy (CITB) were followed for 18 months. Pain, number of awakenings during night, spasticity, GMFM-66 scores and PEDI scores were recorded the day before pump implantation and after 6 and 18 months of treatment respectively. Introduction of CITB was associated with changes across all ICF dimensions. Reduced pain and improved sleep occurred within 6 months of treatment. Social function improved within 6 months and continued to improve until 18 months of CITB. Mobility also improved, but with a latency. There seems to be a sequence of changes after introduction of continuous intrathecal baclofen in a child with cerebral palsy that may guide the multidisciplinary team in their timing of therapy during post-surgical follow-up.

Poster 59: Effect of Intrathecal Baclofen Therapy on Gait Performance in Ambulatory Multiple Sclerosis Patients

Objective: To evaluate changes in gait performance after implantation of a baclofen pump in patients with multiple sclerosis (MS). Design: Pre-post intervention study with prospective data collection up to 24±4 weeks. Setting: Spasticity clinic within a large outpatient MS center. Participants: Ambulatory patients with definite MS and severe spasticity refractory to oral medications. Interventions: Surgical implantation of a programmable intrathecal baclofen (ITB) infusion system. Main Outcome Measures: Rivermead Visual Gait Analysis Scale (RVGA), timed 25-foot walk (T25FW), and walking distance.