Positive allosteric modulators of the GABAB receptor: a new class of ligands with therapeutic potential for alcohol use disorder.

BACKGROUND: Positive allosteric modulators (PAMs) of the GABAB receptor constitute a new class of GABAB-receptor ligands. GABAB PAMs reproduce several pharmacological effects of the orthosteric GABAB receptor agonist, baclofen, although displaying a better safety profile. AIMS: This paper reviews the reducing or, frequently, even suppressing effects of all GABAB PAMs tested to date on multiple alcohol-related behaviours in laboratory rodents exposed to validated experimental models of human alcohol use disorder. RESULTS: Acute or repeated treatment with CGP7930, GS39783, BHF177, rac-BHFF, ADX71441, CMPPE, COR659, ASP8062, KK-92A, and ORM-27669 reduced excessive alcohol drinking, relapse- and binge-like drinking, operant alcohol self-administration, reinstatement of alcohol seeking, and alcohol-induced conditioned place preference in rats and mice. CONCLUSIONS: These effects closely mirrored those of baclofen; notably, they were associated to remarkably lower levels of tolerance and toxicity. The recent transition of ASP8062 to clinical testing will soon prove whether these highly consistent preclinical data translate to AUD patients.

Repurposing drugs for treatment of alcohol use disorder.

Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.

Action of GABAB receptor on local network oscillation in somatosensory cortex of oral part: focusing on NMDA receptor.

The balance of activity between glutamatergic and GABAergic networks is particularly important for oscillatory neural activities in the brain. Here, we investigated the roles of GABAB receptors in network oscillation in the oral somatosensory cortex (OSC), focusing on NMDA receptors. Neural oscillation at the frequency of 8-10 Hz was elicited in rat brain slices after caffeine application. Oscillations comprised a non-NMDA receptor-dependent initial phase and a later NMDA receptor-dependent oscillatory phase, with the oscillator located in the upper layer of the OSC. Baclofen was applied to investigate the actions of GABAB receptors. The later NMDA receptor-dependent oscillatory phase completely disappeared, but the initial phase did not. These results suggest that GABAB receptors mainly act on NMDA receptor, in which metabotropic actions of GABAB receptors may contribute to the attenuation of NMDA receptor activities. A regulatory system for network oscillation involving GABAB receptors may be present in the OSC.

Utilizing combination intrathecal baclofen and analgesic medication to manage spasticity and pain in patients with pediatric-onset disability: Case series.

PURPOSE: The use of intrathecal medications for the management of spasticity and various pain syndromes in the adult population has been previously reported. However, no evidence-based guidelines currently exist in the pediatric population. This case series presents patients (n = 8) with pediatric-onset disability who underwent placement of intrathecal baclofen pumps initially for management of severe spasticity. Despite titration of dose and use of oral analgesia, their uncontrolled pain persisted. Each patient was transitioned to a combination of baclofen and analgesic intrathecal therapy. The outcome in pain improvement and quality of life, as reported by patients and/or caregivers, were retrospectively reviewed. METHODS: Retrospective review of the background and decision-making process regarding transition to combination intrathecal therapy identified patient selection characteristics. Each patient and/or their caregivers completed a survey regarding improvements in pain, spasticity, function, and quality of life following initiation of combination intrathecal medications. RESULTS: Survey results revealed improvements in functional and pain assessments after initiation of combination baclofen and analgesic intrathecal medication. Patients and caregivers reported decreases in pain and oral spasticity medications. CONCLUSION: Use of pumps with antispasmodic and analgesic medication for combination intrathecal medication delivery should be considered in the management of patients with childhood-onset disabilities who have both severe spasticity and pain.

Role of GABAB receptors in cognition and EEG activity in aged APP and PS1 transgenic mice.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Recent evidence suggests that gamma-aminobutyric acid B (GABAB) receptor-mediated inhibition is a major contributor to AD pathobiology, and GABAB receptors have been hypothesized to be a potential target for AD treatment. The aim of this study is to determine how GABAB regulation alters cognitive function and brain activity in an AD mouse model. Early, middle and late stage (8-23 months) amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice were used for the study. The GABAB agonist baclofen (1 and 2.5 mg/kg, i. p.) and the antagonist phaclofen (0.5 mg/kg, i. p.) were used. Primarily, we found that GABAB activation was able to improve spatial and/or working memory performance in early and late stage AD animals. In addition, GABAB activation and inhibition could regulate global and local EEG oscillations in AD animals, with activation mainly regulating low-frequency activity (delta-theta bands) and inhibition mainly regulating mid- and high-frequency activity (alpha-gamma bands), although the regulated magnitude at some frequencies was reduced in AD. The cognitive improvements in AD animals may be explained by the reduced EEG activity in the theta frequency band (2-4 Hz). This study provides evidence for a potential therapeutic effect of baclofen in the elderly AD brain and for GABAB receptor-mediated inhibition as a potential therapeutic target for AD.

Symptomatic Treatment of Myelopathy.

OBJECTIVE: This article discusses the effects of myelopathy on multiple organ systems and reviews the treatment and management of some of these effects. LATEST DEVELOPMENTS: Recent advances in functional electrical stimulation, epidural spinal cord stimulation, robotics, and surgical techniques such as nerve transfer show promise in improving function in patients with myelopathy. Ongoing research in stem cell therapy and neurotherapeutic drugs may provide further therapeutic avenues in the future. ESSENTIAL POINTS: Treatment for symptoms of spinal cord injury should be targeted toward patient goals. If nerve transfer for upper extremity function is considered, the patient should be evaluated at around 6 months from injury to assess for lower motor neuron involvement and possible time limitations of surgery. A patient with injury at or above the T6 level is at risk for autonomic dysreflexia, a life-threatening condition that presents with elevated blood pressure and can lead to emergent hypertensive crisis. Baclofen withdrawal due to baclofen pump failure or programming errors may also be life-threatening. Proper management of symptoms may help avoid complications such as autonomic dysreflexia, renal failure, heterotopic ossification, and fractures.

[Features of lung damage in baclofen poisoning]. / Osobennosti povrezhdeniya legkikh pri otravlenii baklofenom.

OBJECTIVE: To reveal pathological lung changes in baclofen poisoning and to assess their dynamics. MATERIAL AND METHODS: The experiment included 20 mature (at age 20 weeks) male rats of Wistar line weighing 290-350 gr. The animals were divided into 3 study groups (5 rats in each) depending on experiment's duration after 85 mg/kg baclofen administration: 3, 4.5 and 24 h in the 1st, 2nd and 3rd groups, respectively. Control group consisted of 5 animals without baclofen administration. RESULTS: A number of pathological reactions, including circulatory disorder (venular and capillary congestion, hemorrhage in interalveolar septa, alveoli, sludge) and the appearance of emphysema loci (interalveolar septa at emphysema loci are thinned), alternating with atelectases and dystelectases. The area taken up by vessels after 4.5 h. baclofen administration was statistically significantly higher than in control group, and after 24 h. - statistically significantly higher than in 4.5 h. The area with white blood cells and WBC/IAP ratio after 4.5 h of baclofen administration were statistically significantly higher than in control group after 3 and 24 h of administration. The number of white blood cells, giving PAS positive reaction, increases during baclofen administration. The complex of pathological lung changes, revealed by ourselves, has a certain dynamics. CONCLUSION: The data on morphological lung changes combined with results of chemical examination can be used to diagnose baclofen poisoning and to determine the time elapsed since this medicine administration.

A case report of integrating Chinese and Western medicine: A new era in the treatment of stiff person syndrome.

RATIONALE: At present, there are limitations to the treatment of stiff person syndrome (SPS). Current treatments are still ineffective or financially burdensome for some patients, so it is imperative to explore more appropriate treatments for patients. This is a case report of a SPS with a more significant effect of combined Chinese and Western medicine, which may provide new treatment ideas for other patients. PATIENT CONCERNS: This patient presented with episodes of stiffness and pain in the lower back and lower extremities. His electromyography shows continued activation of normal motor units in the paraspinal and abdominal muscles. However, relevant laboratory tests including glutamic acid decarboxylase antibody and Amphiphysin antibody were negative. After a period of treatment including clonazepam, baclofen, prednisone and intravenous immunoglobulin, this patient experiences a shortened maintenance period of medication, accompanied by symptoms such as emotional anxiety and cognitive decline, which severely affects his life. DIAGNOSES: This patient was diagnosed with SPS. INTERVENTIONS: In May 2022 the patient decided to combine Chinese medicine for simultaneous treatment. OUTCOMES: During the period of simultaneous treatment with Chinese and Western medicine, the patient experienced remission of clinical symptoms, reduction of concomitant symptoms and improved quality of life. CONCLUSION: A combination of Western and Chinese medicine was effective in relieving this patient pain and stiffness and reducing the patient anxiety. Combined Chinese and Western medicine treatment may be able to bring better results to more patients with stiff person syndrome.

Baclofen in the treatment of alcohol use disorder: tailored doses matter.

AIMS: To address the question of tailored baclofen prescribing in alcohol use disorder (AUD) in relation to dose-dependent efficacy and the potential danger of high doses and to provide suggestions for the use of high doses of baclofen in the treatment of AUD. The context is the approvement in France of baclofen in the treatment of AUD without dose limitation, making French physicians, who usually prescribe baclofen in a tailored manner, often use high or very high doses. METHODS: A narrative review of the results of randomized controlled trials (RCTs) and observational studies that used tailored baclofen prescribing and of the severe adverse effects of baclofen that have been reported in the literature. RESULTS: The results show that RCTs using tailored doses of baclofen in AUD are not completely demonstrative, though they are encouraging according to certain meta-analyses, while observational studies that used tailored doses constantly show a good effectiveness of baclofen treatment. The results suggest that many severe adverse effects of baclofen could be related to a nonrespect by physicians of prescription rules and appropriate treatment monitoring. CONCLUSIONS: The use of tailored doses shows that the dose required to suppress cravings is highly variable, low or high, depending on each case. Analysis of the circumstances in which severe adverse effects occur suggest that a careful monitoring of baclofen prescribing might prevent a large majority of severe adverse effects. We propose that the education of the patients and the prescription skills, seriousness, and availability of the prescribing physicians are of major importance in the managing of tailored baclofen treatment of AUD.

Efficacy and safety of alcohol reduction pharmacotherapy according to treatment duration in patients with alcohol dependence or alcohol use disorder: A systematic review and network meta-analysis.

BACKGROUND AND AIMS: Relapse is common in alcohol dependence (AD) and alcohol use disorder (AUD), so alcohol reduction therapy should be measured over as long a period as possible; however, existing reviews do not consider the duration of treatment and therefore alcohol reduction therapy may not have been appropriately evaluated. This review evaluated the efficacy and safety of alcohol reduction pharmacotherapy in patients with AD or AUD according to the duration of treatment. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that assessed 15 pharmacological agents. MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov and the International Clinical Trials Registry Platform were searched for eligible trials through to May 2021. Outcomes were heavy drinking days (HDD), total alcohol consumption (TAC), any adverse event and days without drinking. RESULTS: Fifty-five RCTs (n = 8891) were included. Nalmefene was superior to placebo for reducing HDD (standard mean difference [SMD] -0.28, 95% confidence interval [CI] -0.37, -0.18) and TAC (SMD -0.25, 95% CI -0.35, -0.16) in the long-term, but not in the short-term. Topiramate was superior to placebo for reducing HDD (SMD -0.35, 95% CI -0.59, -0.12) and days without drinking (SMD 0.46, 95% CI 0.11, 0.82), and baclofen was superior for reducing TAC (SMD -0.70, 95% CI -1.29, -0.11), in the short-term. The frequency of adverse events was higher with nalmefene and topiramate than with placebo. CONCLUSION: Nalmefene, topiramate and baclofen may be effective as alcohol reduction pharmacotherapy; however, only nalmefene has demonstrated long-term efficacy, and nalmefene and topiramate have a significantly higher frequency of adverse events compared with placebo.

GABAB receptor-mediated modulation in the developing dorsal nucleus of the lateral lemniscus.

The dorsal nucleus of the lateral lemniscus (DNLL) is a GABAergic, reciprocally connected auditory brainstem structure that continues to develop postnatally in rodents. One key feature of the DNLL is the generation of a strong, prolonged, ionotropic, GABAA receptor-mediated inhibition. Possible GABAB receptor-mediated signalling is unexplored in the DNLL. Here, we used Mongolian gerbils of either sex to describe GABAB receptor-mediated modulation of postsynaptic potassium currents and synaptic inputs in postnatal (P) animals of days 10/11 and 23-28. Throughout development, we observed the presence of a Baclofen-activated GABAB receptor-enhanced potassium outward conductance that is capable of suppressing action potential generation. In P10/11, old gerbils GABAB receptor activation enhances glutamatergic and suppresses ionotropic GABAergic synaptic transmission. During development, this differential modulation becomes less distinct, because in P22-28, old animals Baclofen-activated GABAB receptors rather enhance ionotropic GABAergic synaptic transmission, whereas glutamatergic transmission is both enhanced and suppressed. Blocking GABAB receptors causes an increase in ionotropic GABAergic transmission in P10/11 old gerbils that was independent on stimulation frequency but depended on the type of short-term plasticity. Together with the lack of Baclofen-induced changes in the synaptic paired-pulse ratio of either input type, we suggest that GABAB receptor-mediated modulation is predominantly postsynaptic and activates different signalling cascades. Thus, we argue that in DNLL neurons, the GABAB receptor is a post-synaptically located signalling hub that alters signalling cascades during development for distinct targets.

[Pharmacological Treatment of Trigeminal Neuralgia].

Although carbamazepine is the first-line treatment option for trigeminal neuralgia, it may not be sustained long-term. The benefits of carbamazepine are offset by adverse effects that lead to its withdrawal. The alternatives to carbamazepine include gabapentin, pregabalin, and microgabalin. Although used off-label in Japan, baclofen, lamotrigine, intravenous lidocaine, and botulinum toxin type A are also effective. Clinical experience has shown that alternative treatments are less effective than carbamazepine. Therefore, they can be used instead of or in addition to carbamazepine. The adverse effects of drugs include drowsiness, dizziness, rash, bone marrow suppression, and liver dysfunction. Carbamazepine and lamotrigine are particularly likely to cause severe drug eruptions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Low-dose titration is important to avoid the development of rashes and adverse effects.

Intrathecal baclofen for the management of hereditary spastic paraparesis: a systematic review.

This systematic review aims to evaluate the use of intrathecal baclofen (ITB) for hereditary spastic paraparesis (HSP) treatment. An extensive search in two electronical databases was performed. We identified articles published between 1990 and 2022 (PubMed, Scopus), and applied the following inclusion criteria: diagnosis of HSP at the time of the intervention, either familial or sporadic; report on the effect of ITB in patients with HSP; test trial via either bolus injections or continuous infusion tests; and ITB pump implantation. A data extraction sheet based on the Cochrane Consumers and Communication Review Group's data extraction template was created and adapted to collect relevant data. A qualitative analysis was performed to present the results in narrative summary fashion. A total of 6 studies met our inclusion criteria. 51 patients with HSP had a pre-implantation ITB trial. The time since the diagnosis until the pump implantation ranged from 5 to 30 years. The initial bolus ranged from 20 to 50 µg and the mean doses used at steady state ranged from 65 to 705 µg. An improvement in spasticity was observed on the modified Ashworth Scale in patients treated with ITB. Although all studies reported a subjective gait improvement, not all found an objective improvement in gait. The most common side effect reported was catheter-related problems. The findings of this review support the use of ITB as an effective and a viable option for the treatment of spasticity in HSP refractory to conservative therapies.

Surgical treatment options for spasticity in children and adolescents with hereditary spastic paraplegia.

PURPOSE: To provide an overview of outcome and complications of selective dorsal rhizotomy (SDR) and intrathecal baclofen pump implantation (ITB) for spasticity treatment in children with hereditary spastic paraplegia (HSP). METHODS: Retrospective study including children with HSP and SDR or ITB. Gross motor function measure (GMFM-66) scores and level of spasticity were assessed. RESULTS: Ten patients were included (most had mutations in ATL1 (n = 4) or SPAST (n = 3) genes). Four walked without and two with walking aids, four were non-walking children. Six patients underwent SDR, three patients ITB, and one both. Mean age at surgery was 8.9 ± 4.5 years with a mean follow-up of 3.4 ± 2.2 years. Five of the SDR patients were walking. Postoperatively spasticity in the legs was reduced in all patients. The change in GMFM-66 score was + 8.0 (0-19.7 min-max). The three ITB patients treated (SPAST (n = 2) and PNPLA6 (n = 1) gene mutation) were children with a progressive disease course. No complications of surgery occurred. CONCLUSIONS: SDR is a feasible treatment option in carefully selected children with HSP, especially in walking patients. The majority of patients benefit with respect to gross motor function, complication risk is low. ITB was used in children with severe and progressive disease.

Intraventricular baclofen for palliative management of acquired generalized dystonia in pediatric patients: a case series and literature review.

Dystonia represents a significant source of disability in children. Generalized dystonia, which involves multiple body regions, leads to impaired mobility and motor function, resulting in substantial challenges in daily activities. Surgical treatments are used when medical treatments fail. Intrathecal baclofen (ITB) or deep brain stimulations (DBS) are the most employed surgical therapies. When these options are not feasible or ineffective, some authors have explored the use of intraventricular baclofen (IVB). In this report, we present four cases of pediatric patients with generalized dystonia who underwent treatment with IVB, resulting in notable improvements. To further explore the potential of this treatment modality, we conducted a comprehensive literature review. The findings from our study provide a comprehensive overview that can guide palliative management in similar cases.

Baclofen and the risk of fall and fracture in older adults: A real-world cohort study.

BACKGROUND: The growth of oral muscle relaxant prescriptions among older adults in the United States is concerning due to the drugs' adverse sedative effects. Baclofen is a gamma-aminobutyric acid agonist muscle relaxant that is associated with encephalopathy. We characterized the risk of fall and fracture associated with oral baclofen against other muscle relaxants (tizanidine or cyclobenzaprine) in older adults. METHODS: We designed a new-user, active-comparator study using tertiary health system data from Geisinger Health, Pennsylvania (January 2005 through December 2018). Older adults (aged ≥65 years) newly treated with baclofen, tizanidine, or cyclobenzaprine were included. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the treatment groups on 58 baseline characteristics. Fine-Gray competing risk regression was used to estimate the risk of fall and fracture. RESULTS: The study cohort comprised of 2205 new baclofen users, 1103 new tizanidine users, and 9708 new cyclobenzaprine users. During a median follow-up of 100 days, baclofen was associated with a higher risk of fall compared to tizanidine (IPTW incidence rate, 108.4 vs. 61.9 per 1000 person-years; subdistribution hazard ratio [SHR], 1.68 [95% CI, 1.20-2.36]). The risk of fall associated with baclofen was comparable to cyclobenzaprine (SHR, 1.17 [95% CI, 0.93-1.47]) with a median follow-up of 106 days. The risk of fracture was similar among patients treated with baclofen versus tizanidine (SHR, 0.85 [95% CI, 0.63-1.14]) or cyclobenzaprine (SHR, 0.85 [95% CI, 0.67-1.07]). CONCLUSIONS: The risk of fall associated with baclofen was greater than tizanidine, but not compared to cyclobenzaprine in older adults. The risk of fracture was comparable among the older users of baclofen, tizanidine, and cyclobenzaprine. Our findings may inform risk-benefit considerations in the increasingly common clinical encounters where oral muscle relaxants are prescribed.

Tone management: An environmental scan of current management practices across Canada.

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Publication Trends of Research on Intrathecal Baclofen Therapy: A Bibliometric Analysis of the Literature.

OBJECTIVE: The objective of this study was to analyze the trends in publications on intrathecal baclofen (ITB) therapy. METHODS: We searched Elsevier's Scopus database in February 2022 to find articles focused on ITB therapy. Data extracted included citation count, publication year, author's country and income category, journal and its 5-year impact factor, research type, disease requiring ITB, and target population. RESULTS: The analysis covered 615 articles from 1985 to 2022. The average citation count per article was 27.47 (95% confidence interval 23.75-31.18) and the mean impact factor was 4.54 (95% confidence interval 3.84-5.24). The majority (76.42%) were primary research, with 8.1% being interventional and 91.9% observational. Even so, one half of the top ten most cited were interventional. Secondary research and case reports made up 12.68% and 10.73% respectively, with narrative reviews making up most of the secondary research (79.48%). Only 1 study conducted a meta-analysis. The United States was the most prolific country. High-income countries published 96.42% of articles. CONCLUSIONS: The rising number of ITB articles and citations indicates growing interest and expanding knowledge in this field. However, there's a notable scarcity of research from low- and middle-income countries, particularly those with high prevalence of ITB-treatable diseases. The need for more evidence to overcome potential barriers to ITB implementation is emphasized. Despite an increasing number of publications, a large proportion presented low levels of evidence, such as case reports and narrative reviews, highlighting the need for more rigorous research methods to solidify the evidence base for ITB therapy.

Safety and efficacy of intrathecal baclofen trials for the treatment of hypertonia: a retrospective cohort study.

OBJECTIVE: Intrathecal baclofen (ITB) is an effective treatment for refractory hypertonia in children. ITB has long been effective for the treatment of spasticity, and indications have naturally evolved to include dystonia and mixed pediatric movement disorders (PMDs). The established uses for ITB trials are insurance prerequisite, mixed tone, and family request. Despite agreement for ITB therapy by a multidisciplinary group of subspecialists in a complex PMD program, insurance companies often require an ITB trial be performed. A longitudinal cohort was identified to determine the safety and efficacy of ITB trials and to determine the utility of test dosing in this population. METHODS: Retrospective data analysis was performed for patients with hypertonia who underwent ITB bolus trials at the authors' institution between 2021 and 2023. Nonmodifiable risk factors and clinical variables were collected. RESULTS: Thirty-one patients (11 female) underwent 32 ITB trials. Of these patients, 67.7% had a diagnosis of mixed hypertonia, 32.3% pure spasticity, and 9.1% secondary dystonia. The mean age at test dose was 12.8 years, and 58.1% of patients were born premature. The mode Gross Motor Function Classification System score was 5. The mean difference in Barry-Albright Dystonia Scale (BADS) scores was -7.33 points (p = 0.01) at 2.5 hours postoperatively. The mean difference in upper-extremity modified Ashworth Scale (mAS) scores was -5.36 points (p = 0.003), and that for lower-extremity mAS scores was -6.61 (p < 0.001). In total, 21.9% of patients developed a post-dural puncture headache. Conversion to a permanent baclofen pump was performed in 22/32 (68.8%) patients. Of those who did not pursue pump placement, 1 patient had high surgical risk, 1 had an ineffective response, 1 had a bad reaction to the test dose and cited both regression and increased discomfort, and 2 declined despite an effective trial owing to family preferences. CONCLUSIONS: ITB trials require hospitalization in some form and carry risks of procedural complications. The decision to pursue a trial should be made on a case-by-case basis by clinicians and should not be determined by insurance companies. The complication rate of ITB trials is high, and a test dose is unnecessary in this fragile population.