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1.
Br Med Bull ; 151(1): 49-68, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39222962

RESUMO

INTRODUCTION: Spinal cord injury (SCI) may bring lifelong consequences for affected patients and a high financial burden to the health care system. SOURCE OF DATA: Published peer-reviewed scientific articles identified from EMBASE, Google Scholar, PubMed and Scopus. AREAS OF AGREEMENT: Surgery and blood pressure management are the main targets in acute SCI to avoid secondary damage. AREAS OF CONTROVERSY: The management of secondary chronic SCI is challenging, with unpredictable outcomes. GROWING POINTS: Given the lack of consensus on pharmacological therapy for acute and secondary chronic SCI, the present study analyses the currently available drugs and treatment options to manage secondary chronic SCI. AREAS TIMELY FOR DEVELOPING RESEARCH: Different approaches exist for the pharmacological management of secondary chronic SCI. One of the most investigated drugs, 4-aminopyridine, improves central motor conduction and shows improvement in neurological signs. Positive results in different areas have been observed in patients receiving the anti-spastic drugs tizanidine and baclofen or Granulocyte colony-stimulating factor. Growth hormone showed only minimal or no significant effects, and the therapy of secondary chronic SCI with riluzole has been poorly researched to date.


Assuntos
Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Humanos , Doença Crônica , Riluzol/uso terapêutico , 4-Aminopiridina/uso terapêutico , Clonidina/uso terapêutico , Clonidina/análogos & derivados , Baclofeno/uso terapêutico
2.
A A Pract ; 18(9): e01851, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39311454

RESUMO

The off-label use of an intravenous dexmedetomidine infusion is an option for refractory symptoms in pediatric palliative care with a few published cases of in-home use, most limited to end-of-life care. After an intrathecal baclofen pump malfunction with meningitis and medication withdrawal, a 17-year-old adolescent with quadriparetic cerebral palsy and paroxysmal autonomic instability experienced relief of refractory pain and dystonia with an in-home intravenous dexmedetomidine infusion. His interdisciplinary care team collaborated to establish safety measures and adjust his home medication regimen to further improve quality of life well before his end of life.


Assuntos
Paralisia Cerebral , Dexmedetomidina , Distonia , Humanos , Dexmedetomidina/administração & dosagem , Adolescente , Masculino , Distonia/tratamento farmacológico , Infusões Intravenosas , Paralisia Cerebral/tratamento farmacológico , Paralisia Cerebral/complicações , Baclofeno/administração & dosagem , Terapia por Infusões no Domicílio , Cuidados Paliativos
3.
Acta Neurochir (Wien) ; 166(1): 308, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39078485

RESUMO

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.


Assuntos
Paralisia Cerebral , Espasticidade Muscular , Rizotomia , Raízes Nervosas Espinhais , Paralisia Cerebral/cirurgia , Humanos , Rizotomia/métodos , Masculino , Raízes Nervosas Espinhais/cirurgia , Criança , Feminino , Espasticidade Muscular/cirurgia , Espasticidade Muscular/tratamento farmacológico , Resultado do Tratamento , Adolescente , Baclofeno/administração & dosagem , Baclofeno/uso terapêutico , Pré-Escolar , Relaxantes Musculares Centrais/uso terapêutico , Relaxantes Musculares Centrais/administração & dosagem
4.
Eur J Pharmacol ; 979: 176768, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39002637

RESUMO

Previous studies from our laboratory have shown sex differences in the behavioral, molecular, and neurochemical manifestations of morphine withdrawal and they were related to an increased sensitivity to morphine effects in males. In addition, we observed an interaction between the GABAergic and opioid systems that could also be sex-dependent. Baclofen, a GABAB receptor agonist, prevented the somatic expression and the molecular and neurochemical changes induced by morphine withdrawal syndrome in mice. On the contrary, little is known about baclofen effects in the rewarding properties of morphine in male and female mice. The present study aimed to explore the effect of baclofen (1, 2 and 3 mg/kg, i.p.) pretreatment in the rewarding effects induced by morphine (7 mg/kg, s.c.) and its effect on c-Fos and brain-derived neurotrophic factor (BDNF) expression induced by the rewarding properties of morphine in prepubertal male and female mice. Baclofen (2 mg/kg) pretreatment prevented the rewarding effects of morphine only in male mice, while baclofen (3 mg/kg) reduced these effects in both sexes. Moreover, the rewarding effects of morphine were associated with a decrease of BDNF and c-Fos expression cingulate cortex, nucleus accumbens shell, cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) areas of the hippocampus only in male mice. In addition, baclofen pretreatment prevented these changes in BDNF, but not in c-Fos expression. In conclusion, our results show that GABAB receptors have a regulatory role in the rewarding effects of morphine that could be of interest for a potential future therapeutic application in opioid use disorders.


Assuntos
Baclofeno , Fator Neurotrófico Derivado do Encéfalo , Morfina , Proteínas Proto-Oncogênicas c-fos , Recompensa , Animais , Baclofeno/farmacologia , Masculino , Feminino , Morfina/farmacologia , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Agonistas dos Receptores de GABA-B/farmacologia , Caracteres Sexuais , Comportamento Animal/efeitos dos fármacos , Fatores Sexuais
5.
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
6.
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
7.
J Chin Med Assoc ; 87(8): 754-764, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38860774

RESUMO

BACKGROUND: Drug addiction is a social and medical problem that must be urgently addressed. The nucleus accumbens (NAc) is closely related to addiction-related learning memory, and γ-aminobutyric acid type B receptor (GABA B R) is a potential target for the treatment of drug addiction. However, the role of GABA B R activity levels in the NAc in cocaine addiction is unclear. METHODS: In this study, we established an animal model of cocaine dependence, modulated the level of GABA B R activity, applied a conditioned place preference assay (CPP) to assess the role of the NAc in reconsolidation of addiction memory, evaluated learning and memory functions by behavioral experiments, examined the expression of GB1, GB2, cyclic adenosine monophosphate response element binding protein (CREB), p-CREB, protein kinase A (PKA), protein kinase (ERK), and Brain-derived neurotrophic factor (BDNF) in the NAc by molecular biology experiments, and screened differentially significantly expressed genes by transcriptome sequencing. RESULTS: Our study showed that the GABA B receptor agonist baclofen (BLF) had a significant effect on locomotor distance in rats, promoted an increase in GABA levels and significantly inhibited the PKA and ERK1/2/CREB/BDNF signaling pathways. Moreover, transcriptome sequencing showed that GABA B R antagonist intervention identified a total of 21 upregulated mRNAs and 21 downregulated mRNAs. The differentially expressed (DE) mRNA genes were mainly enriched in tyrosine metabolism; however, further study is needed. CONCLUSION: GABA B R activity in the NAc is involved in the regulation of cocaine addiction and may play an important role through key mRNA pathways.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Núcleo Accumbens , RNA Mensageiro , Ratos Sprague-Dawley , Receptores de GABA-B , Animais , Ratos , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Masculino , Receptores de GABA-B/genética , RNA Mensageiro/análise , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Baclofeno/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
8.
Brain Res ; 1841: 149086, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38876319

RESUMO

Alcohol use disorder (AUD) remains a critical public health issue worldwide, characterized by high relapse rates often triggered by contextual cues. This research investigates the neural mechanisms behind context-induced reinstatement of alcohol-seeking behavior, focusing on the nucleus accumbens and its interactions with the prelimbic cortex, employing Male Long-Evans rats in an ABA renewal model. In our experimental setup, rats were trained to self-administer 10 % ethanol in Context A, followed by extinction of lever pressing in the presence of discrete cues in Context B. The context-induced reinstatement of ethanol-seeking was then assessed by re-exposing rats to Context A or B under extinction conditions, aiming to simulate the environmental cues' influence on relapse behaviors. Three experiments were conducted: Experiment 1 utilized Fos-immunohistochemistry to examine neuronal activation in the nucleus accumbens; Experiment 2 applied the baclofen + muscimol inactivation technique to probe the functional importance of the nucleus accumbens core; Experiment 3 used Fos-immunofluorescence along with Retrobeads injection to investigate activation of neurons projecting from the prelimbic cortex to the nucleus accumbens core. Our findings revealed significant increases in Fos-immunoreactive nuclei within the nucleus accumbens core and shell during the reinstatement phase in Context A, underscoring the environment's potent effect on ethanol-seeking behavior. Additionally, inactivation of the nucleus accumbens core markedly reduced reinstatement, and there was a notable activation of neurons from the prelimbic cortex to the nucleus accumbens core in the ethanol-associated context. These results highlight the critical role of the nucleus accumbens core and its corticostriatal projections in the neural circuitry underlying context-driven ethanol seeking.


Assuntos
Comportamento de Procura de Droga , Etanol , Extinção Psicológica , Núcleo Accumbens , Ratos Long-Evans , Animais , Núcleo Accumbens/efeitos dos fármacos , Masculino , Etanol/administração & dosagem , Etanol/farmacologia , Comportamento de Procura de Droga/fisiologia , Ratos , Extinção Psicológica/fisiologia , Extinção Psicológica/efeitos dos fármacos , Autoadministração , Vias Neurais/fisiologia , Alcoolismo , Sinais (Psicologia) , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Baclofeno/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Muscimol/farmacologia
9.
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
10.
Int Rev Neurobiol ; 175: 153-185, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38555115

RESUMO

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.


Assuntos
Alcoolismo , Oxibato de Sódio , Síndrome de Abstinência a Substâncias , Humanos , Alcoolismo/tratamento farmacológico , Acamprosato/uso terapêutico , Naltrexona/uso terapêutico , Dissulfiram/uso terapêutico , Oxibato de Sódio/uso terapêutico , Baclofeno/uso terapêutico , Reposicionamento de Medicamentos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Consumo de Bebidas Alcoólicas
11.
Oper Neurosurg (Hagerstown) ; 27(4): 415-423, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38531088

RESUMO

BACKGROUND AND OBJECTIVES: Intrathecal baclofen (ITB) for severe spasticity can encounter complications such as wound dehiscence and ulcers because of elevated intracompartmental pressure within the abdominal subcutaneous and subfascial pocket housing the pump. We propose an innovative technique to manage ITB wound ulcers. METHODS: Resecting the umbilicus create a more spacious and less tension-prone pocket for the ITB pump. RESULTS: Between 2015 and 2023, we implanted ITB pumps in 65 patients. Among them, 5 patients presented with skin ulcer or dehiscence underwent surgery using the novel technique. Postoperative follow-up revealed successful wound healing, with no further wound-related complications. CONCLUSION: The proposed technique provides effective and practical solution to wound and skin complications related to ITB pump. Moreover, it may serve as a viable preemptive strategy during the initial implantation of the ITB pump in selected patients.


Assuntos
Baclofeno , Bombas de Infusão Implantáveis , Injeções Espinhais , Relaxantes Musculares Centrais , Umbigo , Humanos , Umbigo/cirurgia , Baclofeno/administração & dosagem , Masculino , Feminino , Adulto , Injeções Espinhais/métodos , Relaxantes Musculares Centrais/administração & dosagem , Pessoa de Meia-Idade , Espasticidade Muscular/cirurgia , Espasticidade Muscular/tratamento farmacológico
12.
Continuum (Minneap Minn) ; 30(1): 224-242, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38330480

RESUMO

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.


Assuntos
Disreflexia Autonômica , Doenças do Sistema Nervoso Autônomo , Hipertensão , Traumatismos da Medula Espinal , Humanos , Disreflexia Autonômica/diagnóstico , Disreflexia Autonômica/etiologia , Disreflexia Autonômica/terapia , Baclofeno/uso terapêutico , Traumatismos da Medula Espinal/complicações , Doenças do Sistema Nervoso Autônomo/complicações , Hipertensão/complicações
13.
Sleep ; 47(8)2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-38334297

RESUMO

Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.


Assuntos
Apneia do Sono Tipo Central , Humanos , Apneia do Sono Tipo Central/induzido quimicamente , Apneia do Sono Tipo Central/fisiopatologia , Analgésicos Opioides/efeitos adversos , Ticagrelor/efeitos adversos , Oxibato de Sódio/efeitos adversos , Baclofeno/efeitos adversos , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico , Adenosina/efeitos adversos , Gabapentina/efeitos adversos , Polissonografia/efeitos dos fármacos
14.
No Shinkei Geka ; 52(1): 63-69, 2024 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-38246671

RESUMO

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.


Assuntos
Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/tratamento farmacológico , Lamotrigina , Carbamazepina , Baclofeno , Gabapentina
15.
Child Care Health Dev ; 50(1): e13169, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658639

RESUMO

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.


Assuntos
Baclofeno , Paralisia Cerebral , Criança , Humanos , Hipertonia Muscular , Gabapentina , Canadá
16.
Childs Nerv Syst ; 40(3): 855-861, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37783799

RESUMO

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.


Assuntos
Paralisia Cerebral , Paraplegia Espástica Hereditária , Criança , Humanos , Adolescente , Pré-Escolar , Estudos Retrospectivos , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/cirurgia , Paraplegia Espástica Hereditária/complicações , Paralisia Cerebral/complicações , Espasticidade Muscular/genética , Espasticidade Muscular/cirurgia , Baclofeno/uso terapêutico , Rizotomia/métodos , Resultado do Tratamento , Espastina
17.
Spine Deform ; 12(2): 473-480, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38006455

RESUMO

PURPOSE: To assess the complication risks associated with intrathecal baclofen (ITB) pumps in cerebral palsy (CP) patients undergoing posterior spinal fusion (PSF) and to determine if timing of pump implantation before or during PSF impacts the risk of complications. METHODS: A prospectively collected multicenter database was retrospectively reviewed to identify CP patients undergoing PSF from 2008 to 2023. Patients were divided into 2 cohorts: those with an ITB pump (ITB cohort) and those without (non-ITB cohort). The ITB cohort was further categorized by placement of the pump prior to or during PSF. Cohorts were then compared in terms of postoperative complications, perioperative complications, and need for revision surgery. RESULTS: Four hundred six patients (ITB n = 79 [53 prior to, 26 during PSF], non-ITB n = 326) were included in this analysis. At an average follow-up of 4.0 years (range 2-10 years), there were no significant differences between the ITB and non-ITB cohorts in the rate of perioperative complications (5.0% vs 6.5%, p = 0.80), revision surgeries (2.5% vs 4.6%, p = 0.54), or any complication type, regardless of whether pumps were placed prior to or during PSF, aside from longer surgical times in the latter group. CONCLUSION: Complication rates are similar for ITBs placed prior to and during PSF. Patients with spastic CP may safely be treated with ITB pumps without increased risks of complication or further reoperation/revision following PSF. LEVEL OF EVIDENCE: Level III.


Assuntos
Paralisia Cerebral , Relaxantes Musculares Centrais , Escoliose , Fusão Vertebral , Humanos , Baclofeno/efeitos adversos , Relaxantes Musculares Centrais/efeitos adversos , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Bombas de Infusão Implantáveis/efeitos adversos , Escoliose/complicações , Paralisia Cerebral/tratamento farmacológico , Paralisia Cerebral/complicações
18.
BMJ Support Palliat Care ; 13(e3): e1405-e1408, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36787986

RESUMO

OBJECTIVE: Hiccups can be bothersome and spawn morbidity. Although oral baclofen is perhaps the most prescribed agent for hiccups, a paucity of data supports its use. METHODS: This multisite, single institution study examined the medical records of patients who had hiccups and had been prescribed baclofenas noted in a clinical encounter. Mixed methods were used to assess baclofen's palliative efficacy. In view of the sometimes transient nature of hiccups and other such factors, cessation or palliation of hiccups in 75% of patients was sought to indicate true palliation. RESULTS: A total of 301 patients with a median age of 61 years (range 20-87 years) and a male predominance are the focus of this report. Baclofen was most often prescribed at 10 mg orally three times a day. Only 105 patients (35%) (95% CI: 30% to 41%) acquired hiccup palliation. Corroborative medical record quotations included, 'Still has hiccups.'Quotations such as, 'Responding to baclofen this AM', were also recorded. Baclofen appeared more likely to benefit patients with hiccups of >48 hours (chronic) duration in univariable analyses (OR for benefit: 0.51 (95% CI: 0.29 to 0.91; p=0.02) with similar conclusions drawn from multivariable analyses. Adverse events occurred in 15 patients with drowsiness the most common. CONCLUSIONS: Baclofen did not meet this study's a priori threshold for successful hiccup palliation, but further study is indicated to learn whether baclofen might help patients with chronic hiccups.


Assuntos
Baclofeno , Soluço , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Baclofeno/uso terapêutico , Soluço/tratamento farmacológico
19.
Nervenarzt ; 94(12): 1116-1122, 2023 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-37955654

RESUMO

BACKGROUND: The causes of spasticity are various and include cerebral palsy, spinal cord injury, stroke, multiple sclerosis or other congenital or acquired lesions of the central nervous system (CNS). While there is often a partial functional component, spasticity also results in varying degrees of impairment of the quality of life. OBJECTIVE: A review of surgical treatment options for spasticity. MATERIAL AND METHODS: A systematic PubMed review of the literature on epidemiology and treatment options with a focus on neurosurgical interventions for spasticity and developments in the last 20 years as well as inclusion of still valid older landmark papers was carried out. Illustration of indications, technique, follow-up, and possible pitfalls of the different methods for the surgical treatment of spasticity. RESULTS: Depending on the affected region, the number of muscle groups, and the extent of spasticity, focal (selective peripheral neurotomy, nerve transfer), regional (selective dorsal rhizotomy), or generalized (baclofen pump) procedures can be performed. The indications are usually established by an interdisciplinary team. Conservative (physiotherapy, oral medications) and focally invasive (botulinum toxin injections) methods should be performed in advance. In cases of insufficient response to treatment or only short-term relief, surgical methods can be evaluated. These are usually preceded by test phases with, for example, trial injections. CONCLUSION: Surgical methods are a useful adjunct in cases of insufficient response to conservative treatment in children and adults with spasticity.


Assuntos
Paralisia Cerebral , Qualidade de Vida , Criança , Humanos , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/cirurgia , Baclofeno/uso terapêutico , Rizotomia/efeitos adversos , Rizotomia/métodos
20.
Int Rev Neurobiol ; 172: 79-99, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37833019

RESUMO

RATIONALE: Spasticity develops in 80% of spinal cord injury cases and negatively affects the patents' quality of life. The most common method of surgical treatment for severe spasticity is a long-term intrathecal baclofen therapy (ITB). Long-term spinal cord stimulation is another possible treatment technique. This paper aims to evaluate the changes in quality of life for patients with spasticity who have been treated with neuromodulation (SCS or ITB) in 12 months after the surgery, as well to compare the changes in quality of life for patients who have been treated with spinal cord stimulation and those who received long-term intrathecal baclofen therapy. MATERIALS AND METHODS: The influence of spasticity, experienced by the patients with a spinal cord injury, on their quality of life was analyzed before the surgery and 12 months after it. The severity of the spinal cord damage was determined with the scale of the American Spinal Injury Association (ASIA); spasticity was evaluated with the modified Ashworth scale, Penn Spasm Frequency Scale; pain levels were determined with visual analogue scale (VAS), anxiety and depression levels - with HADS. Functional activity of the patients was evaluated with the help of the Functional Independence Measure (FIM). RESULTS: The treatment results for 33 patients (25 men and 8 women), aged from 18 to 62, are presented. After the trial stimulation, the patients were randomly assigned to either SCS or ITB group (18 and 15 people respectively). The decrease of spasticity in both experimental groups caused lower levels of pain, less functional dependency on other people, lower stress and depression rates and, as a consequence, better quality of life and social adaptation. The obtained results for SCS and ITB groups are statistically similar.


Assuntos
Relaxantes Musculares Centrais , Traumatismos da Medula Espinal , Masculino , Humanos , Feminino , Baclofeno/uso terapêutico , Qualidade de Vida , Espasticidade Muscular/terapia , Espasticidade Muscular/complicações , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/terapia , Dor
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