Therapeutic use of medical Cannabis in neurological diseases: a clinical update.

The use of medical Cannabis has increased in recent years due to changing legal circumstances in many countries. Approval exists only for a few neurological conditions such as rare forms of epilepsy or spasticity in multiple sclerosis. Beyond that, however, medical Cannabis is used for a wide range of neurological conditions and symptoms. In Germany, in parallel with new legislation that has simplified the prescription of medical Cannabis, an accompanying survey has been implemented for which initial data are now available. In this context, our review provides an overview of the evidence for the therapeutic use of medical Cannabis in neurology, the potential benefits, and side effects.

Intrathecal baclofen efficacy for managing motor function and spasticity severity in patients with cerebral palsy: a systematic review and meta-analysis.

BACKGROUND: Spasticity can significantly affect a patient's quality of life, caregiver satisfaction, and the financial burden on the healthcare system. Baclofen is one of only a few options for treating spasticity. The purpose of this study is to investigate the impact of intrathecal baclofen (ITB) therapy on severe40.23 spasticity and motor function in patients with cerebral palsy. METHODS: We conducted a systematic review in PubMed, Scopus, Ovid, and the Cochrane Library in accordance with the PRISMA guidelines. We included studies based on eligibility criteria that included desired participants (cerebral palsy patients with spasticity), interventions (intrathecal baclofen), and outcomes (the Ashworth scales and the Gross Motor Function Measure [GMFM]). The within-group Cohen's d standardized mean differences (SMD) were analyzed using the random effect model. RESULTS: We screened 768 papers and included 19 in the severity of spasticity section and 6 in the motor function section. The pre-intervention average spasticity score (SD) was 3.2 (0.78), and the post-intervention average score (SD) was 1.9 (0.72), showing a 40.25% reduction. The SMD for spasticity reduction was - 1.7000 (95% CI [-2.1546; -1.2454], p-value < 0.0001), involving 343 patients with a weighted average age of 15.78 years and a weighted average baclofen dose of 289 µg/day. The SMD for the MAS and Ashworth Scale subgroups were - 1.7845 (95% CI [-2.8704; -0.6986]) and - 1.4837 (95% CI [-1.8585; -1.1088]), respectively. We found no relationship between the participants' mean age, baclofen dose, measurement time, and the results. The pre-intervention average GMFM (SD) was 40.03 (26.01), and the post-intervention average score (SD) was 43.88 (26.18), showing a 9.62% increase. The SMD for motor function using GMFM was 0.1503 (95% CI [0.0784; 0.2223], p-value = 0.0030), involving 117 patients with a weighted average age of 13.63 and a weighted average baclofen dose of 203 µg/day. In 501 ITB implantations, 203 medical complications were reported, including six new-onset seizures (2.96% of medical complications), seven increased seizure frequency (3.45%), 33 infections (16.26%), eight meningitis (3.94%), and 16 cerebrospinal fluid leaks (7.88%). Delivery system complications, including 75 catheter and pump complications, were also reported. CONCLUSION: Despite the risk of complications, ITB has a significant impact on the reduction of spasticity. A small but statistically significant improvement in motor function was also noted in a group of patients.

Outcomes, complications, and dosing of intrathecal baclofen in the treatment of multiple sclerosis: a systematic review.

OBJECTIVE: The purpose of this systematic review was to evaluate empirical outcomes of studies in the literature that investigated effectiveness of intrathecal baclofen (ITB) in the treatment of multiple sclerosis (MS)-related spasticity (MSRS) based on various metrics. Since the first description of this route of baclofen delivery for MS patients by Penn and Kroin in 1984, numerous studies have contributed to the medical community's knowledge of this treatment modality. The authors sought to add to the literature a systematic review of studies over the last 2 decades that elucidates the clinical impact of ITB in treating MSRS with the following endpoints: impact on patient-centered outcomes, such as spasticity reduction (primary), complications (secondary), and dosing (secondary). METHODS: The authors queried three databases (PubMed, Scopus, and Cochrane Library) using the following search terms: (intrathecal baclofen) AND (multiple sclerosis). The set inclusion criteria were as follows: 1) original, full-text article; 2) written in the English language; 3) published between and including the years 2000 and 2023; 4) discussion of pre- and post-ITB pump implantation outcomes (e.g., reduction in spasticity and improved comfort) in MSRS patients with long-term ITB treatment; and 5) contained a minimum of 5 MS patients. Data on study type, patient demographics, follow-up periods, primary outcomes, and secondary outcomes were extracted from the included studies. RESULTS: The authors' search yielded 465 studies, of which 17 met inclusion criteria. Overall, they found evidence for the effectiveness of ITB in treating MSRS patients whose condition was refractory to oral medications, with significant reported changes in spasm frequency from pre- to postimplantation. They also found evidence supporting the positive impact of ITB on MSRS patients' quality of life. Moreover, the authors found that most complications were surgical rather than pharmacological. In addition, the average 1-year dose of ITB (reported in 7 of the included studies) was 191.93 µg/day, which is substantially lower than ITB doses reported in the literature for patients with central (non-MS) or spinal origins of spasticity at 1-year follow-up. CONCLUSIONS: The evidence supports ITB as a clinically effective treatment for MSRS, particularly in patients in whom oral antispasmodics and physiotherapy have failed. This systematic review contributes a comprehensive synthesis of clinical benefits, complications, and dosing of ITB reported over the past 2 decades, which furthers an understanding of ITB's clinical utility in practice.

Uncovering the rate and risk factors of intrathecal baclofen pump-associated complications in the adult population.

OBJECTIVE: The aim of this study was 1) to describe the rate of intrathecal baclofen (ITB)-associated complications at a large tertiary center, and 2) to evaluate the impact of patient-related factors on the likelihood of developing such complications. METHODS: A retrospective single-center study was carried out. A total of 301 eligible patients were included in the analysis. Univariate regression models were used to evaluate the impact of age, sex, diagnosis, ambulation status, modified Ashworth scale score, body mass index, diabetes status, and pain level on the likelihood of developing a device-related infection, pump malfunction, catheter malfunction, and other clinically significant complications. RESULTS: Overall, 27% of patients experienced an ITB-related complication. The most common complications included infection (6%, 18/301), pump malfunction (7.3%, 22/301), and catheter malfunction (14%, 42/301). The univariate analyses revealed that the patient's ambulatory status had a significant impact on the likelihood of developing a catheter-related malfunction. Furthermore, a trend toward significance was identified between patients' preoperative body mass index and device-related infection. Finally, the risk of suffering any ITB-related complications was statistically correlated with the number of years that had passed since the initial pump implantation. CONCLUSIONS: The authors' analysis reveals a previously underrecognized association between ambulatory status at the time of ITB pump implantation and the incidence of catheter-related complications, and confirms the impact of time since surgery on the risk of developing any ITB-related complication. The patient's age, sex, diagnosis, diabetes status, or pain level at baseline were not associated with the risk of complications. Collectively, these insights contribute novel information to the existing literature, providing practical value for physicians in guiding patient selection for ITB therapy.

Spinal catheter revision in pediatric intrathecal baclofen pumps: risk factors and postoperative outcomes.

OBJECTIVE: Intrathecal baclofen (ITB) pumps are commonly used in pediatric patients with cerebral palsy (CP) and medically refractory spasticity. However, catheter malfunction and associated risk factors are not well understood. The aim of this study was to examine potential risk factors for spinal catheter malfunction and characterize postoperative follow-up to understand the clinical consequences. METHODS: Patients who received ITB pump replacement or revision at Boston Children's Hospital between 2010 and 2023 were retrospectively reviewed. The spinal catheter revision cohort (SCRC) included patients whose spinal catheter was occluded requiring lumbar catheter revision. The second cohort included abdominal pump replacements only (APRC). Between-group comparisons and multivariable regression identified factors associated with catheter revision and postoperative outcomes. RESULTS: Forty-one (33.6%) patients underwent spinal catheter revision and were compared with 81 patients (66.4%) who underwent abdominal pump replacement only. Younger age at surgery and an elevated preoperative lower-extremity modified Ashworth scale grade were associated with spinal catheter revision (p < 0.05). Catheter model type, tip location, and history of spinal fusion were not associated with obstruction. Postoperatively, SCRC patients experienced a higher rate of infection (17.1%) relative to APRC patients (0%) within 30 days from their ITB pump replacement procedure (p < 0.05) and greater likelihood of subsequent ITB system removal compared with the APRC (24.4% vs 7.4%, p < 0.05). Although not differing preoperatively, SCRC patients had lower postoperative ITB doses when compared with the APRC group (median dose 143 vs 350 µg/day, p < 0.05) at hospital discharge and remained statistically different at the 6-month and 1-year follow-ups (p < 0.05). There were no postoperative differences in baclofen overdose, withdrawal, or median number of hospital readmissions within 30 days. Overall, 31.7% of spinal catheter revisions were unanticipated by the clinical team at time of surgery. CONCLUSIONS: Younger age at surgery and increased preoperative lower-extremity tone may be risk factors for catheter obstruction, resulting in a higher rate of postoperative infection and subsequent ITB pump removal compared with pump replacement alone. Spinal catheter occlusion can complicate revision or replacement procedures, especially when unanticipated. Routine clinical assessment may be inadequate for diagnosing insidious catheter malfunction. Catheter occlusion deserves further study, and routine assessment of catheter patency may be warranted to prevent suboptimal tone therapy.

[Intrathecal baclofen therapy: a 30-year experience]. / Intratekal'naya baklofenovaya terapiya: 30 let primeneniya.

BACKGROUND: The first pump for intrathecal administration of baclofen was implanted in 1984. Over thirty years, intrathecal prolonged infusion of muscle relaxants has occupied a worthy niche among all methods for correction of non-focal drug-resistant disabling muscle spasticity. However, this method has not become routine despite high awareness of specialists in Russia and abroad, as well as undeniable advantages for restoring the daily activity, improving the walking pattern and providing care and quality of life in people with limited mobility. This is due to scrupulous analysis of adverse events and accurate attitude towards its use.The purpose of this review was to systematize data on indications, selection criteria, pump implantation technique, subsequent patient management and treatment outcomes over a 30-year history. METHOD: A review of national and foreign literature was performed. RESULTS AND CONCLUSION: Prolonged intrathecal baclofen therapy is perspective for long-term treatment of severe spasticity interfering with quality of life and self-care if oral muscle relaxants are contraindicated or ineffective. This procedure is effective for impaired articulation, chewing and spastic pain syndrome. One can reduce the incidence of side effects via correct dosage of the drug, and tolerance to therapy can be reduced by timely elimination of problems with catheter.

Spasticity treatment patterns among people with multiple sclerosis: a Swedish cohort study.

BACKGROUND: Spasticity is common among people with multiple sclerosis (MS), but there are few studies of spasticity treatment patterns. We aim to describe associations with spasticity treatment measured primarily by oral baclofen use. METHODS: This cohort study using Swedish registers included 1826 and 3519 people with incident and prevalent MS (pwIMS, pwPMS) respectively, followed from 2005 to 2014. Cox regression assessed factors associated with new baclofen prescriptions and its discontinuation. RESULTS: A total of 10% of pwIMS and 19% of pwPMS received baclofen, a drug prescribed specifically for spasticity in Sweden, of which many patients had relapsing-remitting course. Prescriptions occurred soon after MS diagnosis: pwIMS received baclofen typically within 6 months of diagnosis, and pwPMS within 3 years. Younger patients compared with older patients were three times more likely to receive baclofen with similar disability level measured using Expanded Disability Severity Scores (EDSS). Patients aged 18-44 years with EDSS 3.0-5.0 have an HR for baclofen use of 5.62 (95% CI 2.91 to 10.85) and EDSS 6+ have an HR of 15.41 (95% CI 7.07 to 33.58) compared with individuals with EDSS 0-2.5. In comparison, patients aged 45+ years with EDSS 3.0-5.0 have an HR of 2.05 (95% CI 1.10 to 3.82) and EDSS 6+ an HR of 4.26 (95% CI 1.96 to 9.17). Baclofen discontinuation was high: 49% (95% CI 0.42 to 0.57) of pwIMS discontinued within 150 days of dispensation, 90% discontinued within 2 years including patients with progressive course or higher EDSS. Associations among pwPMS and sensitivity analyses including additional treatments were similar. CONCLUSIONS: Younger patients with MS are more likely to receive baclofen compared with older patients with MS. High rates of baclofen discontinuation highlight the need for more tolerable and efficacious spasticity treatments and monitoring of spasticity among people with MS.

Clinical efficacy of ultrasound-guided stellate ganglion block combined with extracorporeal shock wave therapy on limb spasticity in patients with ischemic stroke.

INTRODUCTION: To observe the clinical efficacy of ultrasound-guided stellate ganglion block (SGB) + extracorporeal shock wave therapy (ESWT) for limb spasticity in patients with ischemic stroke. METHODS: A total of 60 patients with post-stroke limb spasticity in our hospital were selected and randomly divided into four groups (n = 15). In the control group, patients received routine rehabilitation training. Based on routine rehabilitation training, SGB group patients underwent ultrasound-guided SGB, ESWT group patients received ESWT, and SGB + ESWT group patients received ultrasound-guided SGB combined with ESWT. The total treatment course was one month. The Modified Barthel Index (MBI) score, Fugl-Meyer Assessment and upper limb rehabilitation training system were applied to evaluate the activities of daily living, upper limb motor function and upper limb performance before and after treatment. Finally, the improvement after treatment was compared among different groups. RESULTS: After treatment, compared with the control group, the MBI score and the upper limb score based on Fugl-Meyer Assessment in the SGB, ESWT, and SGB + ESWT groups were significantly increased (P < 0.05). Furthermore, compared with the SGB and ESWT groups, SGB + ESWT exhibited a higher upper limb function score (P < 0.05), while the MBI score was not significantly different (P > 0.05). In terms of upper limb performance ability, patients in the SGB, ESWT and SGB + ESWT groups had better fitting degree, participation and exertion of exercise than those in the control group, and the SGB + ESWT group patients had the same movement trajectory as robots. CONCLUSION: Ultrasound-guided SGB and ESWT can reduce the muscle tension of patients, alleviate spasticity, promote the motor function of the upper limb, and improve the working performance of patients. However, the effect of SGB combined with ESWT is better.

Resting-state functional connectivity in multiple sclerosis patients receiving nabiximols for spasticity.

BACKGROUND: Nabiximols (Sativex®) is a cannabinoid approved for multiple sclerosis (MS)-related spasticity. Its mechanism of action is partially understood, and efficacy is variable. OBJECTIVE: To conduct an exploratory analysis of brain networks connectivity changes on resting state (RS) functional MRI (fMRI) of MS patients treated with nabiximols. METHODS: We identified a group of MS patients treated with Sativex® at Verona University Hospital, who underwent RS brain fMRI in the 4 weeks before (T0) and 4-8 weeks after (T1) treatment start. Sativex® response was defined as ≥ 20% spasticity Numerical Rating Scale score reduction at T1 vs. T0. Connectivity changes on fMRI were compared between T0 and T1 in the whole group and according to response status. ROI-to-ROI and seed-to-voxel connectivity were evaluated. RESULTS: Twelve MS patients (7 males) were eligible for the study. Seven patients (58.3%) resulted Sativex® responders at T1. On fMRI analysis, Sativex® exposure was associated with global brain connectivity increase (particularly in responders), decreased connectivity of motor areas, and bidirectional connectivity changes of the left cerebellum with a number of cortical areas. CONCLUSIONS: Nabiximols administration is associated with brain connectivity increase of MS patients with spasticity. Modulation of sensorimotor cortical areas and cerebellum connectivity could play a role in nabiximols effect.

Cannabis and Cannabinoids in Multiple Sclerosis: From Experimental Models to Clinical Practice-A Review.

BACKGROUND: As far as 80% of people diagnosed with multiple sclerosis (MS) experience disabling symptoms in the course of the disease, such as spasticity and neuropathic pain. As first-line symptomatic therapy is associated with important adverse reactions, cannabinoids have become increasingly popular among patients with MS. This review intends to provide an overview of the evidence of the role of cannabinoids in treating symptoms related to MS and to encourage further research on this matter. AREAS OF UNCERTAINTY: To date, the evidence supporting the role of cannabis and its derivatives in alleviating the MS-related symptoms comes only from studies on experimental models of demyelination. To the best of our knowledge, relatively few clinical trials inquired about the therapeutic effects of cannabinoids on patients with MS, with variable results. DATA SOURCES: We conducted a literature search through PubMed and Google Scholar from the beginning until 2022. We included articles in English describing the latest findings regarding the endocannabinoid system, the pharmacology of cannabinoids, and their therapeutic purpose in MS. RESULTS: Evidence from preclinical studies showed that cannabinoids can limit the demyelination process, promote remyelination, and have anti-inflammatory properties by reducing immune cell infiltration of the central nervous system in mice with experimental autoimmune encephalomyelitis. Moreover, it has been established that experimental autoimmune encephalomyelitis mice treated with cannabinoids experienced a significant reduction of symptoms and slowing of the disease progression. Given the complexity of human immune and nervous systems, cannabinoids did not have the anticipated effects on human subjects. However, data obtained from clinical trials showed some beneficial results of cannabinoids as a single or as add-on therapy in reducing the spasticity and pain related to MS. CONCLUSION: Considering their various mechanisms of action and good tolerability, cannabinoids remain an interesting therapy for spasticity and chronic pain related to MS.

Does intrathecal baclofen therapy decrease the progression of hip displacement in young patients with cerebral palsy?

AIM: To evaluate the effects of intrathecal baclofen pump (ITBP) therapy on hip dysplasia in young patients with cerebral palsy (CP). METHOD: This was a retrospective cohort series of prospectively collected data. Inclusion criteria were all patients with CP in Gross Motor Function Classification System (GMFCS) levels IV or V who underwent ITBP placement under 8 years old with at least 5 years of follow-up. Thirty-four patients were matched to a control group of 71 patients based on GMFCS level, motor type, medical comorbidities, worst hip migration percentage at ITBP placement, age, and Modified Ashworth scale scores. Patients were followed for at least 5 years or until they had hip reconstructive surgery. The primary outcome was the development of hip displacement as measured by the migration percentage at the latest follow-up or the preoperative migration percentage before hip reconstruction. RESULTS: The migration percentage at last follow-up was not statistically different between groups (ITBP: 36.2%, non-ITBP: 44.4%, p = 0.14). The rates of future preventative, reconstructive, and recurrent hip surgery were not different between groups. INTERPRETATION: The use of ITBP as an early treatment of spasticity did not alter the natural history of progressive hip displacement in non-ambulatory patients with CP and hip displacement is likely multifactorial, not solely due to spasticity.

Botulinum toxin in clinical practice: state of the art of administration provisions in Italy.

Botulinum neurotoxin type A is a remarkable therapeutic approach for muscle hyperactivity syndromes, pain, and related disorders. Despite its wide application in neurology, there is a poor knowledge on delivery protocols and dispatch from the healthcare providers. In this study, we reported the result of a 2020 survey about the administration provisions of botulinum neurotoxin type A in Italy. Seven questions including information on characteristics of botulinum neurotoxin facilities, prescription, reimbursement, and execution modalities were adopted. Sixty participants answered the survey. Despite the wide availability of dedicated centers all over the national territory, there was a surprising lack of standardized and shared administration provisions. Most of the Italian medical structures delivered botulinum neurotoxin through outpatient clinics located in public hospital facilities, through the "F file" reimbursement modality. However, there was no agreement on the reimbursement request modality, creating differences in public costs relative to the botulinum toxin consumption across Italy.

Change in upper limb function in people with multiple sclerosis treated with nabiximols: a quantitative kinematic pilot study.

OBJECTIVES: Nabiximols represents an increasingly employed add-on treatment option for spasticity in people with multiple sclerosis (PwMS) who either were unresponsive or reported excessive adverse reactions to other therapies. While several studies performed in the last decade demonstrated its effectiveness, safety, and tolerability, few quantitative data are available on the impact on motor dysfunctions. In this open-label, not concurrently controlled study, we aimed to assess the impact of a 4-week treatment with nabiximols on upper limb functionality. METHODS: Thirteen PwMS (9 female, 4 male) with moderate-severe spasticity underwent a combination of clinical tests (i.e., Box and Block, BBT and Nine-Hole Peg test, 9HPT) and instrumental kinematic analysis of the "hand to mouth" (HTM) movement by means of optical motion capture system. RESULTS: After the treatment, improvements in gross and fine dexterity were found (BBT + 3 blocks/min, 9HPT - 2.9 s, p < 0.05 for both cases). The kinematic analysis indicated that HTM movement was faster (1.69 vs. 1.83 s, p = 0.05), smoother, and more stable. A significant reduction of the severity of spasticity, as indicated by the 0-10 numerical rating scale (4.2 vs. 6.3, p < 0.001), was also observed. CONCLUSION: The findings from the present pilot study suggest that a 4-week treatment with nabiximols ameliorates the spasticity symptoms and the overall motor function of upper limb in PwMS with moderate-severe spasticity. The use of quantitative techniques for human movement analysis may provide valuable information about changes originated by the treatment in realistic upper limb motor tasks involved in activities of daily living.

Daily Vibrotactile Stimulation Exhibits Equal or Greater Spasticity Relief Than Botulinum Toxin in Stroke.

OBJECTIVE: To test the feasibility and efficacy of the VibroTactile Stimulation (VTS) Glove, a wearable device that provides VTS to the impaired limb to reduce spastic hypertonia. DESIGN: Prospective 2-arm intervention study-including 1 group of patients who use Botulinum toxin (BTX-A) for spasticity and 1 group of patients who do not use BTX-A. SETTING: Participants were recruited through rehabilitation and neurology clinics. PARTICIPANTS: Patients with chronic stroke (N=20; mean age=54 years, mean time since stroke=6.9 years). Patients who were previously receiving the standard of care (BTX-A injection) were eligible to participate and started the intervention 12 weeks after their last injection. INTERVENTION: Participants were instructed to use the VTS Glove for 3 hours daily, at home or during everyday activities, for 8 weeks. MAIN OUTCOME MEASURES: Spasticity was assessed with the Modified Ashworth Scale and the Modified Tardieu Scale at baseline and then at 2-week intervals for 12 weeks. Primary outcomes were the difference from baseline and at week 8 (end of VTS Glove use) and week 12 (4 weeks after stopping VTS Glove use). Patients who were receiving BTX-A were also assessed during the 12 weeks preceding the start of VTS Glove use to monitor the effect of BTX-A on spastic hypertonia. Range of motion and participant feedback were also studied. RESULTS: A clinically meaningful difference in spastic hypertonia was found during and after daily VTS Glove use. Modified Ashworth and Modified Tardieu scores were reduced by an average of 0.9 (P=.0014) and 0.7 (P=.0003), respectively, at week 8 of daily VTS Glove use, and by 1.1 (P=.00025) and 0.9 (P=.0001), respectively, 1 month after stopping VTS Glove use. For participants who used BTX-A, 6 out of 11 showed greater change in Modified Ashworth ratings during VTS Glove use (mean=-1.8 vs mean=-1.6 with BTX-A) and 8 out of 11 showed their lowest level of symptoms during VTS Glove use (vs BTX-A). CONCLUSIONS: Daily stimulation from the VTS Glove provides relief of spasticity and hypertonia. For more than half of the participants who had regularly used BTX-A, the VTS Glove provided equal or greater symptom relief.

Intrathecal and Oral Baclofen Use in Adults With Spinal Cord Injury: A Systematic Review of Efficacy in Spasticity Reduction, Functional Changes, Dosing, and Adverse Events.

OBJECTIVE: To examine the efficacy, dosing, and safety profiles of intrathecal and oral baclofen in treating spasticity after spinal cord injury (SCI). DATA SOURCES: PubMed and Cochrane Databases were searched from 1970-2018 with keywords baclofen, spinal cord injury, and efficacy. STUDY SELECTION: The database search yielded 588 sources and 10 additional relevant publications. After removal of duplicates, 398 publications were screened. DATA EXTRACTION: Data were extracted using the following population, intervention, comparator, outcomes, and study designs criteria: studies including adult patients with SCI with spasticity; the intervention could be oral or intrathecal administration of baclofen; selection was inclusive for control groups, surgical management, rehabilitation, and alternative pharmaceutical agents; outcomes were efficacy, dosing, and adverse events. Randomized controlled trials, observational studies, and case reports were included. Meta-analyses and systematic reviews were excluded. DATA SYNTHESIS: A total of 98 studies were included with 1943 patients. Only 4 randomized, double-blinded, and placebo-controlled trials were reported. Thirty-nine studies examined changes in the Modified Ashworth Scale (MAS; 34 studies) and Penn Spasm scores (Penn Spasm Frequency; 19 studies), with average reductions of 1.7±1.3 and 1.6±1.4 in individuals with SCI, respectively. Of these data, a total of 6 of the 34 studies (MAS) and 2 of the 19 studies (Penn Spasm Frequency) analyzed oral baclofen. Forty-three studies addressed adverse events with muscle weakness and fatigue frequently reported. CONCLUSIONS: Baclofen is the most commonly-prescribed antispasmodic after SCI. Surprisingly, there remains a significant lack of large, placebo-controlled, double-blinded clinical trials, with most efficacy data arising from small studies examining treatment across different etiologies. In the studies reviewed, baclofen effectively improved spasticity outcome measures, with increased efficacy through intrathecal administration. Few studies assessed how reduced neural excitability affected residual motor function and activities of daily living. A host of adverse events were reported that may negatively affect quality of life. Comparative randomized controlled trials of baclofen and alternative treatments are warranted because these have demonstrated promise in relieving spasticity with reduced adverse events and without negatively affecting residual motor function.

The impact of intrathecal baclofen on the ability to walk: A systematic review.

OBJECTIVE: Intrathecal baclofen (ITB) is an effective treatment for lower limb spasticity. In ambulatory patients with spasticity, there is a justifiable concern that ITB treatment may compromise ambulatory function by reducing the heightened muscle tone, thereby unmasking underlying muscle weakness. ITB is hence offered with reservation in ambulant patients. In this article, we review the literature surrounding the effect of ITB therapy on ambulatory function in patients with concurrent spasticity and discuss the key findings. DATA SOURCES: A literature search of ProQuest Medline and EBSCO CINAHL databases was performed. REVIEW METHOD: Inclusion criteria included (a) studies reporting the effect of ITB in adult ambulatory patients; (b) studies with an intervention of screening test trial via either bolus injections or continuous infusion tests; and (c) studies with an intervention of ITB pump implantation. Seventeen eligible studies were identified and two authors independently assessed the study quality using the risk of bias in nonrandomised studies of interventions tool (ROBINS-I). RESULTS: Seventeen studies were included, with a total of 534 participants. Most of the patients remain ambulatory after ITB treatment, accompanied by improvements in gait speed and reduction in spasticity. CONCLUSION: ITB therapy when administered in carefully selected ambulatory patients with spasticity is not associated with loss of ambulatory function.

Brief pump externalization without ITB wean to treat a probable pocket infection.

BACKGROUND AND IMPORTANCE: Intrathecal baclofen (ITB) pumps are an effective management tool for spasticity and dystonia. In the pediatric population, ITB complications including infection are common, and strategies to minimize their impact are important. Current standard of care for pump infection involves a wean of the ITB therapy followed by explantation of the hardware, which can be a three to 6-month process. CLINICAL PRESENTATION: We present a 20-year-old female who developed an pump pocket infection after revision. The pump was removed from the body but left connected. The pocket was debrided, thoroughly washed, and packed with multiple microbicidal agents. Nine days later, a new pump and proximal catheter was re-implanted without complications or interruption of medication administered intrathecally. One year later, the patient is doing well without any infectious problems. CONCLUSION: To our knowledge, this is the first report of an externalized pump and expedited reimplantation without a break in ITB therapy. Further studies are required in order to best characterize this technique as a potential alternative for infected baclofen pump pockets.

Intracerebroventricular baclofen therapy improves function and quality of life in a child with severe cerebral palsy.

Limited therapies are available for severe cerebral palsy children (CP) with complex movement disorders, especially when both dystonia and spasticity are present. In this publication, we present the improvement of a child with severe CP after intracerebroventricular baclofen therapy. The treatment can impact not just the movement disorders but also on the quality of life of the child and caregivers. Global functional improvements can be observed on the 6-month follow-up.

Distribution of the intramuscular innervation of the triceps brachii: Clinical importance in the treatment of spasticity with botulinum neurotoxin.

This study aimed to identify ideal sites for botulinum toxin injection by analyzing the intramuscular nerve patterns of the triceps brachii muscles. A modified Sihler's method was applied to the triceps brachii muscle (15 specimens), with long, medial, and lateral heads. The intramuscular arborization areas of the long, medial, and lateral heads of the triceps brachii muscle were measured as a percentage of the total distance from the midpoint of the olecranon (0%) to the anteroinferior point of the acromion (100%), by dividing the medial and lateral parts based on the line connecting the midpoint of the olecranon and the anteroinferior point of the acromion. Intramuscular arborization patterns were observed at the long head at two medial regions, proximally 30%-50% and distally 60%-70%; medial head of 30%-40%; and lateral head of 30%-60%. These results suggest that the treatment of spasticity of the triceps brachii muscles involves botulinum toxin injections in specific areas. The areas corresponding to the areas of maximum arborization are recommended as the most effective and safe points for botulinum toxin injection.

Assessment of Health Care Costs and Total Baclofen Use Associated With Targeted Drug Delivery for Spasticity.

BACKGROUND: Chronic spasticity causes significant impairment and financial burden. Oral baclofen, the first-line therapy, can have intolerable, dose-dependent side effects. Targeted drug delivery (TDD) through intrathecal baclofen delivers smaller amounts of baclofen into the thecal sac via an implanted infusion system. However, the health care resource utilization of patients with spasticity receiving TDD has not been studied extensively. MATERIALS AND METHODS: Adult patients who received TDD for spasticity between 2009 and 2017 were identified using the IBM MarketScan® data bases. Patients' use of oral baclofen and health care costs were examined at baseline (one year before implantation) and three years after implantation. A multivariable regression model using the generalized estimating equations method and a log link function was used to compare postimplantation costs with those at baseline. RESULTS: The study identified 771 patients with TDD for medication analysis and 576 for cost analysis. At baseline, the median costs were $39,326 (interquartile range [IQR]: $19,526-$80,679), which increased to $75,728 (IQR: $44,199-$122,676) in year 1, decreased to $27,160 (IQR: $11,896-$62,427) in year 2, and increased slightly to $28,008 (IQR: $11,771-$61,885) in year 3. In multivariable analysis, the cost was 47% higher than at baseline (cost ratio [CR] 1.47, 95% CI: 1.32-1.63) in year 1 but was 25% lower (CR 0.75, 95% CI: 0.66-0.86) in year 2 and 32% lower (CR 0.68, 95% CI: 0.59-0.79) in year 3. Before implant, 58% of patients took oral baclofen, which decreased to 24% by year 3. The median daily baclofen dose decreased from 61.8 mg (IQR: 40-86.4) before TDD to 32.8 mg (IQR: 30-65.7) three years later. CONCLUSIONS: Our findings indicate that patients who undergo TDD use less oral baclofen, potentially reducing the risk of side effects. Although total health care costs increased immediately after TDD, most likely owing to device and implantation costs, they decreased below baseline after one year. The costs of TDD reach cost neutrality approximately three years after implant, indicating its potential for long-term cost savings.