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1.
Neurosurg Focus ; 56(6): E12, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38823042

RESUMO

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.


Assuntos
Baclofeno , Bombas de Infusão Implantáveis , Injeções Espinhais , Relaxantes Musculares Centrais , Humanos , Baclofeno/administração & dosagem , Baclofeno/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Fatores de Risco , Bombas de Infusão Implantáveis/efeitos adversos , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/efeitos adversos , Injeções Espinhais/efeitos adversos , Idoso , Adulto Jovem , Espasticidade Muscular/tratamento farmacológico , Falha de Equipamento/estatística & dados numéricos , Adolescente
2.
Neurosurg Focus ; 56(6): E11, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38823047

RESUMO

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.


Assuntos
Baclofeno , Paralisia Cerebral , Bombas de Infusão Implantáveis , Relaxantes Musculares Centrais , Humanos , Baclofeno/administração & dosagem , Baclofeno/efeitos adversos , Masculino , Feminino , Criança , Bombas de Infusão Implantáveis/efeitos adversos , Fatores de Risco , Relaxantes Musculares Centrais/administração & dosagem , Estudos Retrospectivos , Adolescente , Paralisia Cerebral/cirurgia , Paralisia Cerebral/complicações , Pré-Escolar , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Espasticidade Muscular/cirurgia , Reoperação/métodos , Injeções Espinhais/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Falha de Equipamento , Estudos de Coortes
4.
Neurosurg Focus ; 56(6): E14, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38823049

RESUMO

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.


Assuntos
Baclofeno , Injeções Espinhais , Esclerose Múltipla , Relaxantes Musculares Centrais , Espasticidade Muscular , Baclofeno/administração & dosagem , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/complicações , Injeções Espinhais/métodos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Relaxantes Musculares Centrais/administração & dosagem , Resultado do Tratamento
5.
Neurosurg Focus ; 56(6): E13, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38823059

RESUMO

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.


Assuntos
Baclofeno , Injeções Espinhais , Relaxantes Musculares Centrais , Humanos , Baclofeno/administração & dosagem , Feminino , Estudos Retrospectivos , Masculino , Criança , Injeções Espinhais/métodos , Adolescente , Relaxantes Musculares Centrais/administração & dosagem , Resultado do Tratamento , Pré-Escolar , Hipertonia Muscular/tratamento farmacológico , Bombas de Infusão Implantáveis/efeitos adversos , Vértebras Cervicais/cirurgia
6.
J Craniofac Surg ; 35(4): e351-e354, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829149

RESUMO

Malignant hyperthermia (MH) is a fatal hyperthermia with a high mortality, which usually occurs during induction of general anesthesia. Dantrolene sodium is a wonder drug currently used for treating malignant hyperthermia. However, preparing, storing, and maintaining dantrolene sodium are crucially expensive, thus making it financially unsatisfactory and difficult for clinicians to acquire in time. Monitoring patients' condition closely and intervening promptly when early signs of malignant hyperthermia occur can effectively prevent the condition from worsening and win over time for the arrival of dantraline sodium. This article is to report a case in which we successfully rescued a child occurring malignant hyperthermia without using dantrolene sodium.


Assuntos
Anestesia Geral , Dantroleno , Hipertermia Maligna , Relaxantes Musculares Centrais , Humanos , Dantroleno/uso terapêutico , Relaxantes Musculares Centrais/uso terapêutico , Masculino , Feminino , Pré-Escolar
7.
Artigo em Russo | MEDLINE | ID: mdl-38881022

RESUMO

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.


Assuntos
Baclofeno , Injeções Espinhais , Relaxantes Musculares Centrais , Espasticidade Muscular , Baclofeno/administração & dosagem , Baclofeno/uso terapêutico , Humanos , Espasticidade Muscular/tratamento farmacológico , Injeções Espinhais/métodos , Relaxantes Musculares Centrais/administração & dosagem , Bombas de Infusão Implantáveis , Qualidade de Vida
8.
World Neurosurg ; 187: e908-e913, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38734171

RESUMO

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.


Assuntos
Baclofeno , Injeções Espinhais , Relaxantes Musculares Centrais , Espasticidade Muscular , Humanos , Baclofeno/administração & dosagem , Masculino , Feminino , Espasticidade Muscular/tratamento farmacológico , Relaxantes Musculares Centrais/administração & dosagem , Pessoa de Meia-Idade , Injeções Espinhais/métodos , Estudos Retrospectivos , Adulto , Idoso , Resultado do Tratamento , Adulto Jovem
9.
Reg Anesth Pain Med ; 49(7): 540-542, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38724273

RESUMO

INTRODUCTION: This case report presents the management of a 62-year-old woman with generalized grade 4 tetanus, focusing on the innovative use of intrathecal baclofen (ITB) therapy. The patient initially presented with a laceration and subsequently developed severe tetanic spasms, necessitating interventions beyond standard tetanus immunoglobulin and antibiotics due to the condition's progressive and life-threatening nature. The preference for ITB over oral baclofen is highlighted, considering ITB's enhanced bioavailability in the central nervous system and its efficacy in reducing spinal cord reflexes, which is critical for managing severe spasticity.On her return to the emergency department with symptoms of tetanus, the patient received ITB following the failure of oral baclofen to control the spasms. ITB administration necessitated a lumbar drain, which was later substituted with a tunneled intrathecal catheter due to the extended requirement for baclofen infusion and the unavailability of suitable infusion pumps. This scenario represented a significant application of a CADD-Solis external pump for continuous ITB infusion.Transitioning the patient from ITB to oral baclofen was a crucial management step to facilitate discharge and recovery, underscoring the importance of a careful approach to prevent withdrawal symptoms and maintain care continuity. Despite initial complications, including an infection signaled by leucocytosis and confirmed through cerebrospinal fluid culture, the patient was effectively treated and discharged. CONCLUSION: This report contributes to the sparse literature on prolonged ITB use for generalized grade 4 tetanus treatment, underlining the need for interdisciplinary collaboration for the best patient outcomes. It showcases the potential of ITB in spasticity management, in reducing the need for sedation, and in shortening the duration of mechanical ventilation, advocating for a tailored approach that utilizes a full spectrum of pharmacological and supportive therapies.


Assuntos
Baclofeno , Injeções Espinhais , Relaxantes Musculares Centrais , Tétano , Humanos , Baclofeno/administração & dosagem , Feminino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/administração & dosagem , Tétano/tratamento farmacológico , Tétano/diagnóstico , Fatores de Tempo , Resultado do Tratamento
10.
Medicina (Kaunas) ; 60(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38792938

RESUMO

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.


Assuntos
Baclofeno , Vértebras Cervicais , Síndrome de Klippel-Feil , Humanos , Baclofeno/uso terapêutico , Baclofeno/administração & dosagem , Masculino , Síndrome de Klippel-Feil/complicações , Adolescente , Vértebras Cervicais/anormalidades , Vértebras Cervicais/cirurgia , Fusão Vertebral/métodos , Injeções Espinhais/métodos , Relaxantes Musculares Centrais/uso terapêutico , Relaxantes Musculares Centrais/administração & dosagem , Osso Occipital/anormalidades , Osso Occipital/cirurgia , Resultado do Tratamento , Descompressão Cirúrgica/métodos
11.
Mikrochim Acta ; 191(6): 336, 2024 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777836

RESUMO

A nanocomposite of Ce-doped ZnO/r-GO was synthesized using a conventional hydrothermal method. The synthesized nanocomposites were utilized for the purpose of sensitive and selective detection of cyclobenzaprine hydrochloride (CBP). The properties of the composite were extensively analyzed, including its morphology, structure, and electrochemical behavior. This study investigates the application of a modified glassy carbon electrode for the detection of CBP, a muscle relaxant used to treat musculoskeletal diseases that cause muscle spasms. The electrode is modified with Ce-doped ZnO/r-GO. Various detection methods, such as cyclic voltammetric and square wave techniques (SWV), were utilized. The composite material showed high effectiveness as an electron transfer mediator in the oxidation of CBP. The electrode showed a good response for SWV evaluations in CBP identification, with a minimum detection limit of 1.6 × 10-8 M and a wide linear range from 10 × 10-6 M to 0.6 × 10-7 M, under ideal conditions. The rate constant for charge transfer (ks) and the estimation of the electrochemical active surface area were obtained. A developed sensor exhibited desirable selectivity, long-lasting stability, and remarkable reproducibility. A sensor was used to analyze water, human serum, and urine samples, resulting in positive recovery results.


Assuntos
Amitriptilina , Técnicas Eletroquímicas , Eletrodos , Limite de Detecção , Óxido de Zinco , Óxido de Zinco/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Amitriptilina/química , Amitriptilina/urina , Amitriptilina/sangue , Amitriptilina/análogos & derivados , Nanocompostos/química , Humanos , Relaxantes Musculares Centrais/química , Relaxantes Musculares Centrais/urina , Relaxantes Musculares Centrais/sangue , Relaxantes Musculares Centrais/análise , Reprodutibilidade dos Testes
12.
BMC Neurol ; 24(1): 143, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678195

RESUMO

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.


Assuntos
Baclofeno , Paralisia Cerebral , Injeções Espinhais , Relaxantes Musculares Centrais , Espasticidade Muscular , Baclofeno/administração & dosagem , Humanos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Paralisia Cerebral/tratamento farmacológico , Paralisia Cerebral/complicações , Injeções Espinhais/métodos , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/uso terapêutico , Resultado do Tratamento , Índice de Gravidade de Doença , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia
13.
Biochem Pharmacol ; 224: 116244, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38685280

RESUMO

Traumatic brain injury (TBI) triggers a bevy of changes including mitochondrial dysfunction, apoptosis, oxidative stress, neurobehavioural impairment, and neuroinflammation, among others. Dantrolene (DNT), a muscle relaxant which inhibits intracellular Ca2+ signaling from the ER, has been repurposed as a potential neuroprotective agent in various neurological diseases. However, there have been limited studies on whether it can mitigate TBI-induced deficits and restore impaired mitochondrial dynamics. This study sought to evaluate whether Dantrolene can potentially provide neuroprotection in an in vivo model of TBI. Male wistar rats subjected to TBI were treated with DNT (10 mg/kg) 1 h and 12 h post surgery. Animals were assessed 24 h post-TBI to evaluate neurobehavioural deficits and cerebral edema. We evaluated the protein expressions of apoptotic, autophagic, and neuroinflammatory markers by immunoblotting, as well as Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) via Flow Cytometry to ascertain the effects of DNT on TBI. We further analysed immunofluorescence staining with Glial Fibrillary Acidic Protein (GFAP) and immunohistochemistry with NF-κß to investigate neuroinflammation. H&E staining was also performed post-TBI. Our findings revealed DNT administration inhibits mitochondria-mediated apoptotis and reduces heightened oxidative stress. DNT treatment was also found to reverse neurobehavioural impairments and offer neuroprotection by preserving neuronal architechture. We also demonstrated that DNT inhibits neuronal autophagy and alleviates neuroinflammation following TBI by modulating the NF-κß/Akt signaling pathway. Thus, our results suggest a novel application of DNT in ameliorating the multitude of deficits induced by TBI, thereby conferring neuroprotection.


Assuntos
Lesões Encefálicas Traumáticas , Dantroleno , Mitocôndrias , NF-kappa B , Doenças Neuroinflamatórias , Proteínas Proto-Oncogênicas c-akt , Ratos Wistar , Animais , Dantroleno/farmacologia , Dantroleno/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Masculino , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , NF-kappa B/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Relaxantes Musculares Centrais/farmacologia , Relaxantes Musculares Centrais/uso terapêutico
14.
Acta Anaesthesiol Scand ; 68(6): 788-793, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38566397

RESUMO

BACKGROUND: Malignant hyperthermia (MH) is a rare pharmacogenetic disorder that can lead to a life-threatening reaction during general anaesthesia with triggering agents. Prompt life-saving treatment includes the immediate administration of the antidote dantrolene. This study investigated Swedish healthcare providers' awareness and adherence to guidelines and recommendations with respect to MH and whether adherence to safe MH-praxis varies with hospital care-complexity level and private versus public management form. METHOD: Agreements and procurement specifications between all 21 Swedish County Councils and privately run surgical care providers were reviewed alongside with questionnaire-aided collection of information from 62 publicly funded health care providers (both privately and publicly run). RESULTS: No procurement requirement specification or contract contained requirements on anaesthesia or aspects of MH. All publicly run hospitals stocked dantrolene and 28 out of 52 (54%) stocked the recommended amount. Seven out of nine (78%) of the privately run institutions stocked dantrolene, and one stocked the recommended amount. Publicly run hospitals adhered to recommendations to a greater extent than privately run institutions, both with respect to stocking of dantrolene (p = .02) and to stocking the recommended amount (p = .03). CONCLUSIONS: Contracts between Swedish county councils and private surgical care subcontractors rarely outline expectations of standards for the safe practice of anaesthesia such as preparedness to handle a life-threatening MH reaction. Among Swedish publicly funded anaesthesia providers there is room for improvement in adherence to the EMHG guideline on dantrolene availability. Publicly run hospitals seem to have better compliance with these recommendations than privately run institutions. Raising awareness about current guidelines is important to improve safety for known and unknown MH-susceptible individuals.


Assuntos
Dantroleno , Fidelidade a Diretrizes , Hipertermia Maligna , Humanos , Suécia , Dantroleno/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Inquéritos e Questionários , Relaxantes Musculares Centrais
16.
J Pediatr Rehabil Med ; 17(1): 57-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38552121

RESUMO

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.


Assuntos
Baclofeno , Relaxantes Musculares Centrais , Adulto , Humanos , Criança , Baclofeno/uso terapêutico , Relaxantes Musculares Centrais/uso terapêutico , Estudos Retrospectivos , Qualidade de Vida , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Dor , Analgésicos/uso terapêutico , Bombas de Infusão Implantáveis
17.
Chem Pharm Bull (Tokyo) ; 72(3): 345-348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556262

RESUMO

Eperisone Hydrochloride was launched in Japan in 1983 and has been used to improve muscle tone and treat spastic paralysis (Originator: Eisai Co., Ltd.). However, its biochemical mechanism of action is unknown. SB Drug Discovery was used to evaluate purinergic P2X (P2X) receptor antagonism using fluorescence. In this study, we discovered that its target protein is the P2X7 receptor. Also, P2X receptor subtype selectivity was high. This finding demonstrates the (Eperisone-P2X7-pain linkage), the validity of P2X7 as a drug target, and the possibility of drug repositioning of Eperisone Hydrochloride.


Assuntos
Relaxantes Musculares Centrais , Propiofenonas , Relaxantes Musculares Centrais/farmacologia , Relaxantes Musculares Centrais/uso terapêutico , Antagonistas do Receptor Purinérgico P2X/farmacologia , Propiofenonas/farmacologia , Propiofenonas/uso terapêutico , Músculos
18.
J Child Neurol ; 39(3-4): 98-103, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38419482

RESUMO

Aims: Post-lumbar puncture headache occurs in 5% to 12% of children. The purpose of this study was to determine the frequency and predictors of post-lumbar puncture headache in children with hypertonia undergoing lumbar puncture for intrathecal baclofen trial. Methods: This was a retrospective single-center review of all 43 children (<18 years) with hypertonia and/or dyskinesia undergoing intrathecal baclofen trial from 2013-2022. Predictors of post-lumbar puncture headache were evaluated via 2-way paired t test and Fisher exact test. Results: Seven subjects (16.3%) developed post-lumbar puncture headache. Of patients who developed post-lumbar puncture headache, 3 required emergency care or hospitalization. One was misdiagnosed with constipation. The 16 patients without opening pressure measured were excluded from subsequent analyses. Of the 27 patients with documented opening pressure, the mean opening pressure was 24.0 cm H2O (SD 6.5) and 5 (18.5%) had elevated opening pressure (>28 cm H2O). Mean opening pressure was higher for those with post-lumbar puncture headache (28.6 vs 22.4 cm H2O, P = .014). Sixty percent of patients with elevated opening pressure developed post-lumbar puncture headache. Baclofen pumps were placed in 4 (80%) patients with elevated opening pressure and 6 (85.7%) with post-lumbar puncture headaches without complications. Interpretation: The risk of post-lumbar puncture headache after intrathecal baclofen trial was higher than reported in the literature, likely because of greater rates of elevated opening pressure. Physicians may use opening pressure to predict risk for post-lumbar puncture headache and should educate families about symptoms. Elevated opening pressure or post-lumbar puncture headache may not preclude baclofen pump placement.


Assuntos
Baclofeno , Injeções Espinhais , Relaxantes Musculares Centrais , Cefaleia Pós-Punção Dural , Humanos , Baclofeno/administração & dosagem , Baclofeno/efeitos adversos , Masculino , Feminino , Criança , Estudos Retrospectivos , Injeções Espinhais/métodos , Adolescente , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/efeitos adversos , Cefaleia Pós-Punção Dural/etiologia , Pré-Escolar , Punção Espinal/efeitos adversos , Hipertonia Muscular/tratamento farmacológico , Hipertonia Muscular/etiologia
20.
Am J Phys Med Rehabil ; 103(6): 510-517, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38261785

RESUMO

OBJECTIVE: This study compared the effectiveness of traditional lectures and microvideos in teaching baclofen pump programming and refilling to physicians who have completed less than 10 refills for the previous 2 yrs. DESIGN: A mixed-method approach was used with 60 participating physicians specializing in physical medicine and rehabilitation or pain management. Preintervention and postintervention assessments were conducted using a rubric, and the participants' perceptions and preferences were gathered through focus group sessions. RESULTS: Two thirds of the participants specialized in physical medicine and rehabilitation. No significant differences in the preintervention, postintervention, or knowledge retention scores were found between the traditional lecture and microvideo groups. Both methods demonstrated comparable effectiveness in improving the baclofen pump refilling and programming skills. Qualitatively, participants perceived both approaches as equally helpful, but those in the microvideo group raised concerns because of instructors' unavailability and online platform navigation. Nevertheless, they preferred the convenience, accessibility, and time efficiency of the microvideos. CONCLUSIONS: The study concluded that microvideos are an effective alternative to traditional lectures for acquiring knowledge on baclofen pump programming and refilling. Further research should consider learners' characteristics and investigate the benefits of blended learning in medical education.


Assuntos
Baclofeno , Relaxantes Musculares Centrais , Humanos , Baclofeno/administração & dosagem , Relaxantes Musculares Centrais/administração & dosagem , Feminino , Masculino , Medicina Física e Reabilitação/educação , Ensino , Adulto , Grupos Focais , Pessoa de Meia-Idade , Gravação em Vídeo , Bombas de Infusão Implantáveis , Educação Médica Continuada/métodos , Espasticidade Muscular/tratamento farmacológico
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