Effects of Baclofen on Central Paroxysmal Positional Downbeat Nystagmus.

Paroxysmal positional nystagmus frequently occurs in lesions involving the cerebellum, and has been ascribed to disinhibition and enhanced canal signals during positioning due to cerebellar dysfunction. This study aims to elucidate the mechanism of central positional nystagmus (CPN) by determining the effects of baclofen on the intensity of paroxysmal positional downbeat nystagmus due to central lesions. Fifteen patients with paroxysmal downbeat CPN were subjected to manual straight head-hanging before administration of baclofen, while taking baclofen 30 mg per day for at least one week, and two weeks after discontinuation of baclofen. The maximum slow phase velocity (SPV) and time constant (TC) of the induced paroxysmal downbeat CPN were analyzed. The positional vertigo was evaluated using an 11-point numerical rating scale (0 to 10) in 9 patients. After treatment with baclofen, the median of the maximum SPV of paroxysmal downbeat CPN decreased from 30.1°/s [interquartile range (IQR) = 19.6-39.0°/s] to 15.2°/s (IQR = 11.2-22.0°/s, Wilcoxon signed rank test, p < 0.001) with the median decrement ratio at 40.2% (IQR = 28.2-50.6%). After discontinuation of baclofen, the maximum SPV re-increased to 24.6°/s (IQR = 13.1-34.4°/s, Wilcoxon signed rank test, p = 0.001) with the median increment ratio at 23.5% (IQR = 5.2-87.9%). In contrast, the TCs of paroxysmal downbeat CPN remained unchanged at approximately 3.0 s throughout the evaluation. The positional vertigo also decreased with the medication (Wilcoxon signed rank test, p = 0.020), and remained unchanged even after discontinuation of medication (Wilcoxon signed rank test, p = 0.737). The results of this study support the prior presumption that paroxysmal CPN is caused by enhanced responses of the semicircular canals during positioning due to cerebellar disinhibition. Baclofen may be tried in symptomatic patients with paroxysmal CPN.

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.

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.

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.

Safety and efficacy of continuous intrathecal baclofen via cervical catheter tip: a retrospective case series.

OBJECTIVE: Intrathecal baclofen (ITB) is an effective treatment for hypertonia in children involving the implantation of a pump and catheter system. The highest concentration of ITB is at the catheter tip. The catheter tip location is most commonly within the lumbar or thoracic spine. The cervical tip location has traditionally been avoided because of concerns of hypoventilation and pneumonia; however, these complications in cervical compared with thoracic or lumbar placement have not been reliably proven. Some studies have suggested that cervical ITB location better treats upper-extremity hypertonia. There are limited data describing the safety and efficacy of cervical ITB on hypertonia. The authors present a single-institution retrospective case series highlighting the safety and efficacy of using cervical ITB location for the treatment of hypertonia. METHODS: Retrospective data analysis was performed for children who underwent continuous dosing cervical ITB between April 2022 and October 2023. Nonmodifiable risk factors, clinical variables, operative characteristics, and adverse outcomes were collected. RESULTS: This study included 25 patients (8 female). The mean age at implantation was 12.4 years, and the mean operative duration was 90 minutes. The mean Barry-Albright Dystonia Scale score decreased by 9.5 points (p = 0.01). The mean aggregated modified Ashworth scale score in the upper extremities decreased by 2.14 points (p = 0.04), and that in the lower extremities decreased by 4.98 points (p < 0.01). One patient each (4%) had infection and baclofen toxicity. Two patients (8%) had respiratory depression requiring continuous positive airway pressure. There was no incidence of pneumonia or wound dehiscence. CONCLUSIONS: The cervical catheter tip location for ITB is safe, is effective to control tone, and should be considered for the treatment of hypertonia. Larger studies with longer follow-up are necessary to further determine upper-limit dosing safety along with long-term functional benefits in these patients.

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.

History and evolution of surgical treatment for spasticity: a journey from neurotomy to selective dorsal rhizotomy.

The evolution of neurosurgical approaches to spasticity spans centuries, marked by key milestones and innovative practitioners. Probable ancient descriptions of spasmodic conditions were first classified as spasticity in the 19th century through the interventions of Dr. William John Little on patients with cerebral palsy. The late 19th century witnessed pioneering efforts by surgeons such as Dr. Charles Loomis Dana, who explored neurotomies, and Dr. Charles Sherrington, who proposed dorsal rhizotomy to address spasticity. Dorsal rhizotomy rose to prominence under the expertise of Dr. Otfrid Foerster but saw a decline in the 1920s due to emerging alternative procedures and associated complications. The mid-20th century saw a shift toward myelotomy but the revival of dorsal rhizotomy under Dr. Claude Gros' selective approach and Dr. Marc Sindou's dorsal root entry zone (DREZ) lesioning. In the late 1970s, Dr. Victor Fasano introduced functional dorsal rhizotomy, incorporating electrophysiological evaluations. Dr. Warwick Peacock and Dr. Leila Arens further modified selective dorsal rhizotomy, focusing on approaches at the cauda equina level. Later, baclofen delivered intrathecally via an implanted programmable pump emerged as a promising alternative around the late 1980s, pioneered by Richard Penn and Jeffrey Kroin and then led by A. Leland Albright. Moreover, intraventricular baclofen has also been tried in this matter. The evolution of these neurosurgical interventions highlights the dynamic nature of medical progress, with each era building upon and refining the work of significant individuals, ultimately contributing to successful outcomes in the management of spasticity.

Postoperative outcomes and stimulation responses for sectioned nerve roots during selective dorsal rhizotomy in cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is the most cause of motor dysfunction in children. Selective dorsal rhizotomy (SDR) plays a major role in long term spasticity control. However, limited data exists on the effect of SDR on postoperative spasticity treatment requirements and supraspinal effects, and the stimulation responses of dorsal nerve roots in those with CP. METHODS: The current study included the outcome for 35 individuals undergoing SDR for motor functional outcome, spasticity, baclofen dose changes, botulinum toxin injection frequency, and spasticity related orthopedic procedures. We also report on the stimulation responses in 112 individuals who underwent SDR at our institution. RESULTS: There was a significant difference in gross motor function measures (GMFM)-66 scores at last follow up that remained present when considering only ambulatory children but not with non-ambulatory children. Ashworth scores were significantly decreased for both upper and lower extremities after SDR at all follow up points. There was a significant decrease in Baclofen dose and botulinum toxin injections requirements after SDR, but no significant difference in the need for orthopedic intervention. A total of 5502 dorsal nerve roots were tested showing a decrease in stimulation intensity and increase in grade on the right side and for descending lumbosacral levels. CONCLUSIONS: SDR improves gross motor scores during short term follow up but has additional benefits in decreasing baclofen dosing and botulinum toxin injections requirements after surgery. They stimulation responses of sectioned dorsal nerve roots adds to the limited available data and our understanding of the pathological changes that occur in CP.

Posterior Occipitocervical Fixation and Intrathecal Baclofen Therapy for the Treatment of Basilar Invagination with Klippel-Feil Syndrome: A Case Report.

Klippel-Feil syndrome (KFS) is characterized by the congenital fusion of the cervical vertebrae and is sometimes accompanied by anomalies in the craniocervical junction. In basilar invagination (BI), which is a dislocation of the dens in an upper direction, compression of the brainstem and cervical cord results in neurological defects and surgery is required. A 16-year-old boy diagnosed with KFS and severe BI presented with spastic tetraplegia, opisthotonus and dyspnea. CT scans showed basilar impression, occipitalization of C1 and fusion of C2/C3. MRI showed ventral compression of the medullocervical junction. Posterior occipitocervical reduction and fusion along with decompression were performed. Paralysis gradually improved postoperatively over 3 weeks. However, severe spasticity and opisthotonus persisted and intrathecal baclofen (ITB) therapy was initiated. Following this, opisthotonus disappeared and spasticity of the extremities improved. Rehabilitation therapy continued by controlling the dose of ITB. Five years after the surgery, self-propelled wheelchair driving was achieved and activities of daily life improved. The treatment strategy for patients with BI and congenital anomalies remains controversial. Posterior reduction and internal fixation using instrumentation were effective techniques in this case. Spasticity control achieved through a combination of surgery and ITB treatment enabled the amelioration of therapeutic efficacy of rehabilitation and the improvement of ADL.

[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.

[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.

Management of an intrathecal baclofen pump pocket empyema caused by a proximal vesicocutaneous fistula: A case report.

Background: Intrathecal baclofen infusing pumps are nowadays commonly implanted in patients suffering from severe, intractable spasticity with a background of multiple sclerosis. Although intrathecal baclofen therapy is considered a safe therapeutic modality, complications are unavoidable and broadly categorized as mechanical and infectious. In the instance of a pump pocket infection, a surgical explanation of the pump is often necessary to treat the infection. Case Description: We present the rare case of a 60-year-old woman who was admitted emergently to our clinic with a subcutaneous pump pocket empyema caused by proximal vesicocutaneous fistulas. The patient underwent explantation of the pump and otherwise had an uncomplicated perioperative course. Conclusion: The surgical explanation of the baclofen pump and antibiotic treatment were sufficient to treat the pump pocket empyema in this instance. To the best of our knowledge, this is the first report of a pump pocket empyema formed in the proximity of a vesicocutaneous fistula.

Intrathecal Baclofen Injection Efficacy for Spasticity Management in Patients With Stroke: A Meta-Analysis.

Although intrathecal baclofen injections have been used for spasticity management regarding stroke, spinal cord injury, and central nervous system diseases, their relative efficacy is controversial. This systematic review scoured 3 multinational electronic databases (Cochrane Library, MEDLINE, and Embase) to isolate relevant studies. We analyzed non-randomized studies and randomized control trials (RCTs) with direct comparisons against other spasticity management interventions for adult stroke patients. Risk of Bias (RoB) and the Risk of Bias Assessment tool for Non-randomized Studies evaluations were implemented with Cochrane's RoB tool. Meta-analysis was performed with Revman 5.4, and evidence validity was assessed with the Grading of Recommendations, Assessment, Development, and Evaluations method. Lastly, the intrathecal baclofen injection meta-analysis included 2 RCTs and 7 non-RCTs for assessing spasticity and 4 non-RCTs to measure gait velocity. Based on this data, intrathecal baclofen injection significantly impacted spasticity and gait speed. Thus, intrathecal baclofen injection can potentially treat severe spasticity unresponsive to conventional spasticity therapy. Furthermore, clinicians must consider individual patient characteristics and conditions when contemplating intrathecal baclofen injection for spasticity intervention.

GABA/baclofen stabilizes PD-L1 and enhances immunotherapy of breast cancer.

The programmed death-ligand 1 (PD-L1) on the surface of tumor cells binds to the receptor programmed cell death protein 1 (PD-1) on effector T cells, thereby inhibiting the anti-tumor immune response. Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has been approved for the treatment of human cancers with lasting clinical benefit. However, many cancer patients did not respond to anti-PD-1/PD-L1 antibody blocking therapy or drugs targeting PD-1/PD-L1. Recent studies have shown that the response to PD-1/PD-L1 blockade may be related to the PD-L1 abundance of tumor cells. Therefore, it is of crucial significance to find drugs to regulate the expression of PD-L1, which can provide new strategies to improve the response rate and efficacy of PD-1/PD-L1 blocking in cancer treatment. Here, we found that GABA and baclofen, upregulates the protein level of PD-L1 by reducing the mRNA and protein levels of STUB1, a E3 ubiquitin ligase, thereby decreasing the interaction between STUB1 and PD-L1, and ultimately stabilizing PD-L1. Notably, GABA and baclofen did not affect cell proliferation in vitro, while in the treatment of breast cancer in mice, the therapeutic effect of baclofen combined with anti-PD-L1 antibody is significantly better than that of using anti-PD-L1 antibody alone by stimulating tumor infiltration of CD8+ T cells and antitumor immunity. Taken together, we unveiled a previously unappreciated role of GABA/baclofen in stabilizing PD-L1 and enhancing the immunotherapy of breast cancer.

A case of severe and prolonged γ-hydroxybutyrate (GHB) withdrawal syndrome successfully managed with a slow benzodiazepine and baclofen taper.

INTRODUCTION: γ-hydroxybutyrate (GHB) is a GABA-B agonist that rapidly produces effects that are likened to both alcohol and MDMA/ecstasy. GHB use can lead to neuroadaptation with a characteristic withdrawal syndrome. There is currently a paucity of data on the progression of GHB withdrawal, however, due to the drug's short half-life it is generally considered to be typically 5-7 days, although some cases can be severe and complicated by life threatening delirium. Here, we present a case of severe GHB withdrawal, which recurred on multiple occasions over 56 days, despite initial clinical stabilisation on each occasion and toxicological evidence of abstinence from GHB between episodes. CASE PRESENTATION: A male patient in his 30s presented with agitated delirium on a background of severe GHB use disorder with a 15-year history of daily high dose GHB use. Following 3 hospital admissions over 8 weeks, all requiring intravenous sedation and tracheal intubation, the patient's withdrawal delirium was successfully treated with a slow benzodiazepine and baclofen wean over a period of 6 months. Relapse to GHB use between hospitalisations was excluded toxicologically via blood analysis performed at an institute of forensic pathology. DISCUSSION AND CONCLUSIONS: This case highlights that GHB withdrawal can be more prolonged than previously reported in the literature and in some cases may require slow and prolonged tapering of treatment to prevent re-emergence of delirium. Similar to previous case reports, benzodiazepines and GABA-B receptor agonists appear to be appropriate drug classes to manage GHB withdrawal.

Intrathecal Baclofen Therapy for Refractory Spasticity: A Case Series.

BACKGROUND: Management of refractory spasticity symptoms remains a challenging task for clinicians. Intrathecal baclofen (ITB) therapy has emerged as a promising option for treating this condition. This study evaluates the effectiveness of ITB therapy in managing refractory spasticity symptoms. METHODS: A retrospective chart review was conducted on 34 patients with refractory spasticity symptoms who underwent ITB therapy at a single institution. The patients' demographics, clinical characteristics, and dosages were recorded. The primary outcome measures were the reduction in pain, improvement in mobility, decrease in spasm frequency, and alleviation of spasticity. RESULTS: ITB therapy successfully reduced pain, improved mobility, decreased spasm frequency, and alleviated spasticity. The mean daily administered dose was 245 µg (range: 88-510 µg, standard deviation:104). However, it was observed that the appropriate dosage of ITB therapy was patient-specific and time-sensitive. Moreover, side effects were observed when an incorrect dose was administered. CONCLUSIONS: ITB therapy is an effective and safe option for managing refractory spasticity symptoms. However, the appropriate dosage should be individualized and monitored closely to avoid side effects. This study highlights the importance of carefully considering the potential risks and benefits of ITB therapy for each patient.

Case report: Intrathecal baclofen therapy improved gait pattern in a stroke patient with spastic dystonia.

Background: Intrathecal baclofen (ITB) therapy, a viable alternative for unsuitable candidates of conventional spasticity medications, is a preferred method of administration over the oral route. Owing to its enhanced bioavailability, ITB ensures a more effective delivery at the target site. Objective: There is a lack of conclusive evidence regarding the use of ITB treatment in managing ambulatory patients with spastic dystonia. Before ITB pump implantation, patients commonly undergo an ITB bolus injection trial to rule out potential adverse reactions and verify the therapeutic effects on hypertonic issues. In this report, we highlight a case of spastic dystonia, particularly focusing on an ambulatory patient who demonstrated significant improvement in both the modified Ashworth scale (MAS) score and gait pattern following the ITB injection trial. Case report: This case report outlines the medical history of a 67-year-old male diagnosed with left-side hemiplegia and spastic dystonia, resulting from his second episode of intracranial hemorrhage in the right thalamus. An ITB injection trial was initiated because the patient was not suitable for continued botulinum toxin injections and oral medications. This was due to the persistent occurrence of spastic dystonia in both the upper and lower extremities. The patient underwent a four-day ITB injection trial with progressively increasing doses, resulting in improved MAS scores and gait parameters, including cadence, step length, step time, stride length, and stride time were increased. Particularly, kinematic gait analysis demonstrates a substantial improvement of increased knee flexion in the swing phase in stiff knee gait pattern. These findings indicated a gradual reduction in spasticity-related symptoms, signifying the positive effect of the ITB injection trial. The patient eventually received an ITB pump implantation. Conclusion: In this post-stroke patient with spastic dystonia, ITB therapy has demonstrated effective and substantial management of spasticity, along with improvement in gait patterns.

An Uncommon Side Effect of Baclofen Withdrawal in End Stage Renal Disease.

Baclofen is a commonly prescribed muscle relaxant that functions to reduce spasticity associated with a variety of musculoskeletal and neurological conditions. Patients with decreased renal function, however, are at an increased risk of suffering from baclofen withdrawal symptoms. We discuss the case of a 77-year-old male who presented to the emergency room with altered mental status and was admitted for acute metabolic encephalopathy found to be from abrupt cessation of baclofen. The presence of kidney disease in this patient further increased his susceptibility to the withdrawal symptoms that began after cessation of the normal medication regimen. This case further illustrates the importance of both comprehensive history and a high index of suspicion when it comes to patient presentation of baclofen withdrawal.

Long-term use of intrathecal baclofen reduces neuropathic pain and its interference with general activity in spinal cord injury individuals.

INTRODUCTION: Long-term analgesic effect of intrathecal baclofen was reported in individuals with spinal cord injury. We conducted a prospective study to evaluate the effect of intrathecal baclofen on subtypes of neuropathic pain and its interference with general activity. MATERIALS AND METHODS: Nine spinal cord injury individuals who presented with severe spasticity and moderate to severe neuropathic pain received intrathecal baclofen via an implanted pump. We applied the ASIA Impairment Scale to assess spinal cord injury severity. Neuropathic pain was evaluated by numerical rating scale, Neuropathic Pain Symptom Inventory, and Brief Pain Inventory. Evaluations were performed at baseline and after at least 6 months of continuous intrathecal baclofen treatment. RESULTS: Intrathecal baclofen led to significant pain reduction as measured by numerical rating scale, Neuropathic Pain Symptom Inventory, and Brief Pain Inventory (p < 0.05). Improvements were significant for paroxysmal pain and dysesthesia and for pain interference with general activity, as assessed by the Brief Pain Inventory (p < 0.05). There was a significant relationship between the time since spinal cord injury and changes in paroxysmal pain as well as in the total Neuropathic Pain Symptom Inventory score (p < 0.05). The baclofen dose correlated also to the percentage changes in neuropathic pain improvement and sleep (p < 0.003). CONCLUSIONS: The present results provide evidence that intrathecal baclofen effectively reduces neuropathic pain, particularly paroxysmal pain and dysesthesia, and improves pain interference and overall well-being in individuals with spinal cord injury. Clinicians should be aware of this less well-known beneficial effect of intrathecal baclofen and should consider such a treatment option for better control of neuropathic pain in individuals with spinal cord injury.