RESUMO
BACKGROUND: Spinal cord glioma (SCG) is considered an orphan disease that lacks effective treatment options with margins that are surgically inaccessible and an overall paucity of literature on the topic. The tumor microenvironment is a critical factor to consider in treatment and modeling design, especially with respect to the unresectable tumor edge. Recently, our group developed a high-grade spinal cord glioma (SCG) model in Göttingen minipigs. METHODS: Immunofluorescence and ELISA were performed to explore the microenvironmental features and inflammation cytokines in this minipig SCG model. Protein carbonyl assay and GSH/GSSG assay were analyzed in the core and edge lesions in the minipig SCG model. The primary core and edge cells proliferation rate were shown in vitro, and the xenograft model in vivo. RESULTS: We identified an elevated Ki-67 proliferative index, vascular and pericyte markers, CD31 and desmin in the tumor edge as compared to the tumor core. In addition, we found that the tumor edge demonstrated increased pro-inflammatory and gliomagenic cytokines including TNF-α, IL-1ß, and IL-6. Furthermore, the mediation of oxidative stress is upregulated in the tumor edge. Hypoxic markers had statistically significant increased staining in the tumor core, but were notably still present in the tumor edge. The edge cells cultures derived from SCG biopsy also demonstrated an increased proliferative rate compared to core cell cultures in a xenotransplantation model. CONCLUSIONS: Our study demonstrates heterogeneity in microenvironmental features in our minipig model of high-grade SCG, with a phenotype at the edge showing increased oxidative stress, proliferation, inflammatory cytokines, neovascularization, and decreased but present staining for hypoxic markers. These findings support the utility of this model as a means for investigating therapeutic approaches targeting the more aggressive and surgically unresectable tumor border.
Assuntos
Glioma , Microambiente Tumoral , Animais , Humanos , Suínos , Porco Miniatura , Medula Espinal , Citocinas , Modelos Animais de DoençasRESUMO
This manuscript introduces the latest generation of a patient-mounted platform designed for segmental injections of therapeutics direct into the spinal cord parenchyma. It emphasizes its importance and it presents the rationale for developing this delivery methodology. It compares the newest with the previous generations, detailing how the modifications can streamline transportation, assembly, sterilization, and utilization of the platform by different surgeons. Finally, the illustrations depict the main alterations, as well as a cadaveric assessment of the device prototype in the cervical and thoracolumbar regions.
Assuntos
Medula Espinal , Humanos , Injeções Espinhais , Medula Espinal/cirurgiaRESUMO
Intramedullary spinal cord tumors are a rare and understudied cancer with poor treatment options and prognosis. Our prior study used a combination of PDGF-B, HRAS, and p53 knockdown to induce the development of high-grade glioma in the spinal cords of minipigs. In this study, we evaluate the ability of each vector alone and combinations of vectors to produce high-grade spinal cord gliomas. Eight groups of rats (n = 8/group) underwent thoracolumbar laminectomy and injection of lentiviral vector in the lateral white matter of the spinal cord. Each group received a different combination of lentiviral vectors expressing PDGF-B, a constitutively active HRAS mutant, or shRNA targeting p53, or a control vector. All animals were monitored once per week for clinical deficits for 98 days. Tissues were harvested and analyzed using hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining. Rats injected with PDGF-B+HRAS+sh-p53 (triple cocktail) exhibited statistically significant declines in all behavioral measures (Basso Beattie Bresnahan scoring, Tarlov scoring, weight, and survival rate) over time when compared to the control. Histologically, all groups except the control and those injected with sh-p53 displayed the development of tumors at the injection site, although there were differences in the rate of tumor growth and the histopathological features of the lesions between groups. Examination of immunohistochemistry revealed rats receiving triple cocktail displayed the largest and most significant increase in the Ki67 proliferation index and GFAP positivity than any other group. PDGF-B+HRAS also displayed a significant increase in the Ki67 proliferation index. Rats receiving PDGF-B alone and PDGF-B+ sh-p53 displayed more a significant increase in SOX2-positive staining than in any other group. We found that different vector combinations produced differing high-grade glioma models in rodents. The combination of all three vectors produced a model of high-grade glioma more efficiently and aggressively with respect to behavioral, physiological, and histological characteristics than the rest of the vector combinations. Thus, the present rat model of spinal cord glioma may potentially be used to evaluate therapeutic strategies in the future.
Assuntos
Glioma/etiologia , Lentivirus/genética , Neoplasias da Medula Espinal/etiologia , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Vetores Genéticos , Glioma/patologia , Glioma/fisiopatologia , Mutação , Neoplasias Experimentais/etiologia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/fisiopatologia , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/fisiopatologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
Brachial plexus palsy is a surgically manageable condition. Re-animating the shoulder is a high priority for restoring upper extremity function. Methods for reinnervating injured nerves include the transfer of a healthy nerve or fascicle distal to the site of injury, or grafting a healthy sensory nerve to restore motor function. Studies aiming to compare these two techniques for restoring shoulder abduction have yielded conflicting results. We conducted a systematic review and meta-analysis following the PRISMA guidelines. We reviewed the PubMed database for studies comparing nerve transfer and nerve grafting for shoulder abduction published by December 2018. Outcomes using the Medical Research Scale (MRC) for muscle strength were assessed using a random effects model meta-analysis. Five studies comprising a total of 212 patients (n = 158, nerve transfer; n = 54, nerve grafts) were used for the analysis. The rate of functional recovery of shoulder function was slightly better for nerve transfer (n = 114/158, 72%) than for nerve graft patients (n = 36/54, 67%). However, this was not statistically significant (OR 1.34, 95% CI 0.27-6.72, I2 = 62.9%). Nerve transfer and grafting are similarly effective in terms of shoulder abduction. Future prospective studies are needed to validate our results and identify the optimal shoulder re-animation strategy in patients with brachial plexus injuries.
Assuntos
Neuropatias do Plexo Braquial/complicações , Neuropatias do Plexo Braquial/cirurgia , Transferência de Nervo/métodos , Procedimentos Neurocirúrgicos/métodos , Ombro/fisiopatologia , Neuropatias do Plexo Braquial/fisiopatologia , Humanos , Recuperação de Função Fisiológica , Resultado do Tratamento , Extremidade Superior/fisiopatologiaRESUMO
Malignant peripheral nerve sheath tumors (MPNST) are a rare and aggressive group of tumors that are challenging to treat. Neurofibromatosis type 1 (NF-1)-associated MPNSTs have been associated with poorer clinical outcomes. The treatment options for NF-1-associated MPNSTs broadly include surgery (SG), chemotherapy (CT), and adjuvant radiotherapy (RT). Overall, the role and efficacy of CT and RT are unclear. Examination of existing literature for studies reporting on NF-1-associated MPNSTs and respective treatment-related outcomes was conducted. We conducted a systematic review according to PRISMA guidelines in PubMed/Medline and Cochrane databases of studies which reported treatment-specific outcomes in NF-1-associated MPNSTs. The literature search found 444 records after removal of duplicates. The present study included 50 patients across 12 observational studies. All of the included studies reported data on overall survival (OS 52%, n = 26/50) but mean follow-up in months among the studies and among patients varied widely, between 10.85 (SD, ± 10.38) and 192 (SD, ± 98.22). From the included studies, patients underwent either SG alone (n = 21), SG + CT (n = 10), SG + RT (n = 7), or SG + CT + RT (n = 12). The quality of evidence in the literature regarding optimal treatment options for NF-1-associated MPNSTs remains tenuous. Future retrospective and prospective comparative trials should consider adherence to a set of reporting guidelines to improve the quality of evidence in the literature with respect to individual treatment-related outcomes. The need for prospective multi-institutional efforts cannot be overstated.
Assuntos
Neoplasias de Bainha Neural/etiologia , Neoplasias de Bainha Neural/terapia , Neurofibromatose 1/complicações , Neurofibromatose 1/terapia , Humanos , Neoplasias de Bainha Neural/cirurgia , Procedimentos NeurocirúrgicosRESUMO
Restoration of elbow flexion is the priority in traumatic brachial plexus injuries. Surgical approaches commonly include nerve transfers and nerve grafting. Our objective was to evaluate the safety and efficacy profile of nerve transfers versus grafting for traumatic nonobstetric brachial plexus injuries. METHODS: This systematic literature review was performed according to the PRISMA guidelines. A random-effects model meta-analysis was conducted, and the I-square was used to assess heterogeneity. The Medical Research Scale (MRC) score was used to assess the efficacy of the procedures. RESULTS: Nine studies comprising 490 patients overall were identified. In the pooled analysis, functional recovery of elbow flexion defined as MRC ≥ M3, was superior in the transfer (N = 272/350, 77.7%) compared to the graft group (N = 99/140, 70.7%); however statistical significance was not reached (OR: 1.95; 95%CI: 0.79-4.83; I2 : 58.8%). However, the odds for successful restoration of elbow flexion (MRC≥M3) were significantly higher when the ulnar (OR:12.20; 95%CI:3.05-48.80; I2 :0%) or pectoral nerves (OR: 9.69; 95% CI: 1.83-51.25; I2 : 0%) were used as healthy donors for the transfer compared to the graft procedures. Results between the two groups were similar when the intercostal, spinal accessory, thoracodorsal, contralateral C7 and phrenic nerves were used as donors for the transfer procedures. CONCLUSIONS: The ulnar or pectoral nerve transfer to musculocutaneous is associated with statistically significant superior rates of elbow flexion recovery as compared to graft. No differences were identified in the pooled analysis or the subgroups of other donors used in nerve transfers. Future randomized studies or prospective cohorts are needed to validate our results.
Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Transferência de Nervo , Plexo Braquial/cirurgia , Neuropatias do Plexo Braquial/cirurgia , Cotovelo , Humanos , Estudos Prospectivos , Amplitude de Movimento ArticularRESUMO
BACKGROUND/AIMS: Postherpetic neuralgia (PHN) can be refractory to both medical and minimally invasive treatments. Its complex pathophysiology explains the numerous neurosurgical procedures that have been implemented through the years. Our objective was to summarize all available neurosurgical strategies for the management of resistant PHN and evaluate their respective safety and efficacy outcomes. METHODS: A comprehensive systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 38 studies comprising 811 patients with refractory PHN were included. The safety and efficacy of the following procedures were investigated: spinal cord stimulation (SCS), dorsal root entry zone (DREZ) lesioning, intrathecal drug delivery, caudalis DREZ lesioning, dorsal root ganglion (DRG) radiofrequency lesioning, peripheral nerve stimulation, gamma knife surgery, deep brain stimulation, cordotomy, percutaneous radiofrequency rhizotomy and Gasserian ganglion stimulation. CONCLUSIONS: There are several available neurosurgical approaches for recalcitrant PHN including neuromodulatory and ablative procedures. It is suggested that patients with resistant PHN undergo minimally invasive procedures first, including SCS, peripheral nerve stimulation or DRG radiofrequency lesioning. More invasive procedures should be reserved for refractory cases. Comparative studies are needed in order to construct a PHN neurosurgical management algorithm.
Assuntos
Neuralgia Pós-Herpética/cirurgia , Neurocirurgiões/tendências , Procedimentos Neurocirúrgicos/tendências , Cordotomia/métodos , Cordotomia/tendências , Humanos , Neuralgia Pós-Herpética/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Rizotomia/métodos , Rizotomia/tendências , Estimulação da Medula Espinal/métodos , Estimulação da Medula Espinal/tendênciasRESUMO
BACKGROUND: Stereotactic targeting techniques in nonhuman primate (NHP) models are often utilized in the preclinical investigation of new drug therapies with the goal of demonstrating accurate and reliable delivery of a therapy to the target tissue. However, targeting certain neuroanatomical structures can be challenging. The deep cerebellar nuclei, specifically the dentate nucleus, are potential stereotactic targets for the treatment of certain ataxias. Currently, there are no detailed techniques describing frameless targeting of these structures in a NHP model. A well-defined, accurate, and reliable stereotactic surgical approach to the dentate in these animal models is critical to prove the feasibility and safety of drug delivery in order to develop clinical protocols. METHODS: Frameless stereotactic neuronavigation was employed to target the bilateral dentate nuclei of the cerebellum in four healthy juvenile Cynomolgus monkeys via a suboccipital, transcerebellar approach. The precision and accuracy of the targeting were evaluated radiologically and histologically. RESULTS: Using the described surgical methodology, we were successful in hitting the target deep cerebellar nuclei seven out of eight times. CONCLUSION: Frameless stereotactic targeting of the cerebellar dentate nuclei in NHPs for future investigational drug delivery is feasible, safe, and accurate as described by this report. Potential areas for improving the technique are discussed.
Assuntos
Núcleos Cerebelares/diagnóstico por imagem , Núcleos Cerebelares/cirurgia , Terapia Genética/métodos , Neuronavegação/métodos , Técnicas Estereotáxicas , Animais , Feminino , Imageamento Tridimensional/métodos , Macaca fascicularis , Masculino , Neuronavegação/instrumentação , PrimatasRESUMO
BACKGROUND: Optimized management of pediatric hydrocephalus remains the subject of debate. Ventriculoperitoneal shunt is largely considered the standard of care. However, the advancements and introduction of new cerebrospinal fluid (CSF) diversion approaches including the use of endoscopic third ventriculostomy (ETV) offer appealing alternatives that have been reported in numerous observational series. OBJECTIVE: To evaluate the comparative safety and efficacy of shunting and ETV in pediatric hydrocephalus cases. METHODS: This systematic literature review was performed according to the PRISMA guidelines. Eligible studies were identified through a search of PubMed (Medline) and Cochrane until October 2018. A random effects model meta-analysis was conducted and the I-square was used to assess heterogeneity. The ROBINS-1 tool and Cochrane tool were used to assess risk of bias in the observational and randomized studies, respectively. RESULTS: Fourteen studies including 8419 patients were identified. Patients in the ETV group had a statistically significant lower risk of infection compared to shunt (OR: 0.19; 95% CI: 0.07-0.53; I2: 0%). All-cause mortality (OR: 0.77; 95% CI: 0.35-1.68; I2: 0%), post-operative CSF leak (OR: 1.53; 95% CI: 0.37-6.31; I2: 0%), and reoperation rates were similar between the two study groups (OR: 0.72; 95% CI: 0.39-1.32; I2: 93.5%). Subgroup analyses for re-operation demonstrated that ETV in Africa (OR: 0.13; 95% CI: 0.03-0.48; I2: 0%) and Europe (OR: 0.39; 95% CI: 0.30-0.52; I2:1.4%) was associated with significantly lower odds of re-operation compared to shunt, but not in USA/Canada (OR: 1.49; 95% CI: 0.85-2.63; I2:86.2%). Meta-regression analyses of age and duration of follow-up did not affect re-operation rates. CONCLUSIONS: ETV was associated with a statistically significant lower risk of procedure-related infection compared to shunt. All-cause mortality, CSF leak, and re-operation rates were similar between the study groups. Subgroup analysis based on the geographic region showed that ETV is associated with statistically significant lower odds for re-operation in Europe and Africa, but not in USA/Canada. Future RCTs are needed to validate the results of this study and elucidate the cause of this heterogeneity.
Assuntos
Hidrocefalia/cirurgia , Derivação Ventriculoperitoneal/métodos , Ventriculostomia/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neuroendoscopia/métodos , Terceiro Ventrículo/cirurgia , Derivação Ventriculoperitoneal/efeitos adversos , Ventriculostomia/efeitos adversosRESUMO
BACKGROUND: Functional elbow flexion recovery is one of the main goals of neonatal brachial plexus palsy (NBPP) reconstruction. The current neurosurgical treatment options include nerve grafting and nerve transfer. OBJECTIVE: The present study sought to examine the literature for comparison of functional elbow flexion recovery in NBPP following nerve grafting or nerve transfer. We conducted a systematic literature review and meta-analysis according to PRISMA guidelines. A search was conducted on Pubmed/Medline and Cochrane for eligible studies published until November of 2018. Odd ratios (OR) and 95% confidence intervals (CI) were calculated to compare functional elbow flexion outcomes between nerve graft and nerve transfer. A random effects model meta-analysis was conducted. A Medical Research Council (MRC) score ≥ 3 or Active Movement Scale (AMS) ≥ 5 was considered a functional recovery of elbow flexion. RESULTS: The present study included 194 patients from 1990 to 2015 across five observational trials. Only pediatric patients with obstetric brachial plexus injury were included. The mean patient age at surgery varied between studies from 5.7 months to 11.9 months and mean follow-up from 12 to 70 months. No complications or cases of donor site morbidity were reported. From the included studies, 118 patients were reported with MRC or AMS scoring usable for odd ratio comparison. Functional recovery occurred with nerve transfer in 95.2% of patients (n = 59/62) and with nerve grafting in 96.4% of patients (n = 54/56). Overall, the outcomes for elbow flexion between the groups appeared similar (OR 1.15, 95% CI 0.19-7.08, I2 2.9%). CONCLUSION: Comparing nerve grafting and nerve transfer for NBPP, there is no statistically significant difference in functional elbow flexion recovery.
Assuntos
Paralisia do Plexo Braquial Neonatal/cirurgia , Transferência de Nervo/métodos , Nervos Periféricos/transplante , Articulação do Cotovelo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Amplitude de Movimento Articular , Recuperação de Função FisiológicaRESUMO
BACKGROUND: Cranioplasty (CP) following decompressive craniectomy (DC) is a common neurosurgical procedure for cranial cosmesis and protection. There is uncertainty regarding the complication rates and potential benefits related to the timing of CP. OBJECTIVE: To investigate the impact of the timing of CP on complication rates for different etiologies of DC. METHODS: A retrospective chart review was performed of all CP cases between 2004 and 2018 for traumatic and nontraumatic indications of DC. Demographics, clinical characteristics, and complications were collected. Early and late CP were defined as replacement of the bone flap at ≤90 and >90 d following DC, respectively. RESULTS: A total of 278 patients were included, receiving 81 early and 197 late CPs. When analyzing all patients, early CP was associated with a statistically significant higher odds of any complication (odds ratio [OR]: 3.25, P < .001), reoperation (OR: 2.57, P = .019), hydrocephalus (OR: 6.03, P = .003), and symptomatic extra-axial collections (OR: 9.22, P = .003). Subgroup analysis demonstrated statistically significant higher odds of these complications only for the CP trauma subgroup, but not the nontrauma subgroup. The odds of complications postCP demonstrated a statistically significant decrease of 4.4% for each week after DC (Unit Odds Ratio [U-OR]: 0.956, P = .0363). CONCLUSION: In our retrospective series, early CP was associated with higher odds of postoperative complications compared to late CP in the trauma subgroup. Greater care should be taken in preoperative planning and increased vigilance postoperatively for complications with this potentially more vulnerable subpopulation. Future prospective controlled trials are needed to elucidate optimal timing for CP.
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Craniectomia Descompressiva , Procedimentos de Cirurgia Plástica , Craniectomia Descompressiva/efeitos adversos , Humanos , Estudos Retrospectivos , Crânio/cirurgia , Retalhos CirúrgicosRESUMO
The thoracic sympathetic chain is implicated in several disease processes including palmar hyperhidrosis and complex regional pain syndrome. These diseases are often medically refractory and require surgical treatments including sympathectomies and ganglion blocks. The use of chemogenetic or optogenetic technologies to modulate sympathetic chain activity may be a potential treatment for these diseases. However, there is no established thoracoscopic surgical approach to deliver viral vectors into the thoracic sympathetic chain and ganglia. Our objective was to evaluate the feasibility of thoracoscopic injection of the swine sympathetic chain. Two Landrace farm pigs underwent a novel procedure for thoracoscopic sympathetic chain injections. One was non-survival and one was a five-day survival surgery. Both procedures successfully delivered methylene blue in the thoracic sympathetic chain. Over the five-day postoperative period, the animal displayed stable vital signs. Thoracoscopic targeted injections of the sympathetic chain is a feasible approach to deliver therapeutics in swine. Future studies should investigate the use of transgene expression as a potential means to control sympathetic output for the development of novel therapies for palmar or axillary hyperhidrosis, thoracic neuropathic pain syndromes and select peripheral vascular diseases.
Assuntos
Gânglios Simpáticos/cirurgia , Toracoscopia/métodos , Animais , Vias Autônomas , Feminino , Optogenética/métodos , SuínosRESUMO
BACKGROUND: Facial pain syndromes can be refractory to medical management and often need neurosurgical interventions. Neuromodulation techniques, including percutaneous trigeminal ganglion (TG) stimulation, are reversible and have emerged as alternative treatment options for intractable facial pain. OBJECTIVE: To report the complication rates and analgesic effects associated with TG stimulation and identify potential predictors for these outcomes. METHODS: A retrospective chart review of 59 patients with refractory facial pain who underwent TG stimulation was conducted. Outcomes following trial period and permanent stimulation were analyzed. Patients with >50% pain relief during trial stimulation received permanent implantation of the stimulation system. RESULTS: Successful trial stimulation was endorsed by 71.2% of patients. During the trial period, 1 TG lead erosion was identified. History of trauma (facial/head trauma and oral surgery) was the only predictor of a failed trial compared to pain of idiopathic etiology (odds ratio: 0.15; 95% CI: 0.03-0.66). Following permanent implantation, approximately 29.6% and 26.5% of patients were diagnosed with lead erosion and infection of the hardware, respectively. TG lead migrations occurred in 11.7% of the patients. The numeric rating scale score showed a statistically significant reduction of 2.49 (95% CI: 1.37-3.61; P = .0001) at an average of 10.8 mo following permanent implantation. CONCLUSION: TG stimulation is a feasible neuromodulatory approach for the treatment of intractable facial pain. Facial/head trauma and oral surgery may predict a nonsuccessful trial stimulation. Future development of specifically designed electrodes for stimulation of the TG, and solutions to reduce lead contamination are needed to mitigate the relatively high complication rate.
Assuntos
Terapia por Estimulação Elétrica/métodos , Manejo da Dor/métodos , Neuralgia do Trigêmeo/terapia , Adulto , Idoso , Dor Facial/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Intratável/terapia , Estudos Retrospectivos , Neuralgia do Trigêmeo/complicaçõesRESUMO
BACKGROUND: Neurodegenerative diseases and spinal cord injury can affect respiratory function often through motor neuron loss innervating the diaphragm. To reinnervate this muscle, new motor neurons could be transplanted into the phrenic nerve (PN), allowing them to extend axons to the diaphragm. These neurons could then be driven by an optogenetics approach to regulate breathing. This type of approach has already been demonstrated in the peripheral nerves of mice. However, there is no established thoracoscopic approach to PN injection. Also, there is currently a lack of preclinical large animal models of diaphragmatic dysfunction in order to evaluate the efficacy of potential treatments. OBJECTIVE: To evaluate the feasibility of thoracoscopic drug delivery into the PN and to assess the viability of hemidiaphragmatic paralysis in a porcine model. METHODS: Two Landrace farm pigs underwent a novel procedure for thoracoscopic PN injections, including 1 nonsurvival and 1 survival surgery. Nonsurvival surgery involved bilateral PN injections and ligation. Survival surgery included a right PN injection and transection proximal to the injection site to induce hemidiaphragmatic paralysis. RESULTS: PN injections were successfully performed in both procedures. The animal that underwent survival surgery recovered postoperatively with an established right hemidiaphragmatic paralysis. Over the 5-d postoperative period, the animal displayed stable vital signs and oxygenation saturation on room air with voluntary breathing. CONCLUSION: Thoracoscopic targeting of the porcine PN is a feasible approach to administer therapeutic agents. A swine model of hemidiaphragmatic paralysis induced by unilateral PN ligation or transection may be potentially used to study diaphragmatic reinnervation following delivery of therapeutics.
Assuntos
Diafragma/inervação , Modelos Animais de Doenças , Nervo Frênico/cirurgia , Toracoscopia/métodos , Animais , Diafragma/patologia , Diafragma/fisiopatologia , Feminino , Projetos Piloto , Paralisia Respiratória/etiologia , Traumatismos da Medula Espinal/complicações , SuínosRESUMO
BACKGROUND: Dural arteriovenous fistulae (dAVFs) can sporadically compress the root entry zone of the trigeminal nerve or the Gasserian ganglion and therefore be a rare cause of isolated or complicated trigeminal neuralgia (TN). CASE DESCRIPTION: We describe 2 cases of TN related to dAVF treated similarly with transarterial embolization but with divergent outcomes. Further, we completed a comprehensive literature review of previously reported cases to date. A sparse but growing literature with regards to this specific and rare but salient cause of TN was noted. The type of dAVF most commonly found to cause TN was that of a tentorial nidus, a lesion generally accepted to be at high risk of hemorrhage and in need of urgent treatment. This warrants imaging for new TN presentations to ensure that a dangerous lesion does not represent the underlying cause, especially when the TN symptoms are comorbid with other symptoms such as a bruit. Treatments pursued span the range of open surgery, endovascular treatment, and radiosurgery with great success in treating both the TN symptoms, as well as the rupture risk of the dAVF itself in most cases. Indeed, endovascular approaches are becoming more widely employed for these cases over time, often resolving the abnormality on first treatment attempt. Other cases reach resolution after employing a combination of treatment modalities. CONCLUSIONS: This work highlights that dAVFs, particularly the tentorial type, are capable of causing TN symptomatically identical to that of other etiologies and that treatment of the dAVF itself is often sufficient.
Assuntos
Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/terapia , Embolização Terapêutica/métodos , Neuralgia do Trigêmeo/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Facial pain refractory to medical treatments may benefit from neurosurgical interventions. Only a few studies have reported on the efficacy of peripheral trigeminal stimulation and more specifically supraorbital nerve (SON) and infraorbital nerve (ION) stimulation for the treatment of facial pain. PATIENTS AND METHODS: In the present study, we identified all patients at our institution who underwent SON and/or ION stimulation for treatment of facial pain due to post-herpetic, traumatic or idiopathic etiology. Relevant pre and post-operative outcomes were analyzed. RESULTS: We identified 15 patients who underwent SON and/or ION stimulation. Among them, 12 (80 %) endorsed >50 % pain relief during the trial stimulation period. After a median follow-up of 5.8 months with permanent implantation, 1 patient (8.3 %) was diagnosed with lead erosion and IPG migration, two patients had lead infections (16.7 %) and one (8.3 %) had wound dehiscence. No lead migrations were identified during the long-term follow-up. The VAS score showed a statistically significant reduction from a median pre-operative score of 7 to a post-operative score of 1.8 (pâ¯=â¯0.011), which corresponded to a 74.3 % average pain reduction. CONCLUSION: SON and/or ION stimulation can be an effective treatment for intractable facial pain due to post-herpetic, traumatic or idiopathic etiology; however the complication rate is relatively high. Future prospective studies with longer follow-up periods are warranted.
Assuntos
Terapia por Estimulação Elétrica/métodos , Dor Facial/cirurgia , Dor Facial/terapia , Nervo Trigêmeo , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia por Estimulação Elétrica/efeitos adversos , Eletrodos Implantados/efeitos adversos , Traumatismos do Nervo Facial/complicações , Traumatismos do Nervo Facial/terapia , Feminino , Seguimentos , Migração de Corpo Estranho/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/terapia , Procedimentos Neurocirúrgicos/métodos , Medição da Dor , Dor Intratável , Nervos Periféricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Prior studies have applied driver mutations targeting the RTK/RAS/PI3K and p53 pathways to induce the formation of high-grade gliomas in rodent models. In the present study, we report the production of a high-grade spinal cord glioma model in pigs using lentiviral gene transfer. METHODS: Six Gottingen Minipigs received thoracolumbar (T14-L1) lateral white matter injections of a combination of lentiviral vectors, expressing platelet-derived growth factor beta (PDGF-B), constitutive HRAS, and shRNA-p53 respectively. All animals received injection of control vectors into the contralateral cord. Animals underwent baseline and endpoint magnetic resonance imaging (MRI) and were evaluated daily for clinical deficits. Hematoxylin and eosin (H&E) and immunohistochemical analysis was conducted. Data are presented using descriptive statistics including relative frequencies, mean, standard deviation, and range. RESULTS: 100% of animals (n = 6/6) developed clinical motor deficits ipsilateral to the oncogenic lentiviral injections by a three-week endpoint. MRI scans at endpoint demonstrated contrast enhancing mass lesions at the site of oncogenic lentiviral injection and not at the site of control injections. Immunohistochemistry demonstrated positive staining for GFAP, Olig2, and a high Ki-67 proliferative index. Histopathologic features demonstrate consistent and reproducible growth of a high-grade glioma in all animals. CONCLUSIONS: Lentiviral gene transfer represents a feasible pathway to glioma modeling in higher order species. The present model is the first lentiviral vector induced pig model of high-grade spinal cord glioma and may potentially be used in preclinical therapeutic development programs.
Assuntos
Modelos Animais de Doenças , Vetores Genéticos/administração & dosagem , Glioma/patologia , Lentivirus/genética , Transtornos Motores/patologia , Neoplasias da Medula Espinal/patologia , Animais , Feminino , Vetores Genéticos/genética , Glioma/genética , Humanos , Masculino , Transtornos Motores/genética , Gradação de Tumores , Neoplasias da Medula Espinal/genética , Suínos , Porco MiniaturaRESUMO
BACKGROUND: The restoration of shoulder function after brachial plexus injury is a high priority. Shoulder abduction and stabilization can be achieved by nerve transfer procedures including spinal accessory nerve (SAN) to suprascapular nerve (SSN) and radial to axillary nerve transfer. The objective of this study is to compare functional outcomes after SAN to SSN transfer versus the combined radial to axillary and SA to SSN transfer. METHODS: This retrospective chart review included 14 consecutive patients with brachial plexus injury who underwent SAN to SSN transfer, 4 of whom had both SA to SSN and radial to axillary nerve transfer. RESULTS: SAN to SSN transfer achieved successful shoulder abduction (≥M3) in 64.3% of this cohort (9/14). During the long-term follow-up, patients achieved an average increase of 67.5° in shoulder abduction. There was no association between motor recovery and time from injury to surgery, age, body mass index (BMI), sex, or smoking status. The 4 patients who had SAN to SSN combined with radial to axillary nerve transfer demonstrated a statistically significant increase in the range of abduction (median, 90° vs. 42.5°, respectively; P = 0.022) compared with those who had SAN to SSN transfer alone; however, the difference in Medical Research Council (MRC) grades (MRC > M3) did not reach statistical significance (P = 0.07). CONCLUSIONS: Patients with brachial plexus injury and an intact C7 root could benefit from radial to axillary transfer in addition to SAN to SSN transfer. There was no association between recovery of shoulder abduction and time interval from injury to surgery, age, sex, smoking, and BMI.
Assuntos
Nervo Acessório/transplante , Neuropatias do Plexo Braquial/cirurgia , Transferência de Nervo/métodos , Nervo Radial/transplante , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Estudos Retrospectivos , Ombro/inervação , Ombro/cirurgia , Adulto JovemRESUMO
BACKGROUND: Intercostal-to-musculocutaneous nerve transfer is commonly performed in patients with brachial plexus avulsion injuries. As techniques have improved since its inception in 1963, most patients now experience some level of motor function improvement of their affected arm. While motor outcomes are well described, there is a paucity of literature describing sensory outcomes. It is thus difficult to gauge surgical success with respect to sensory function, and there is a necessity to share clear expectations with patients regarding intended or unintended postoperative sensation. CASE DESCRIPTION: In this case report, we describe an unintended sensory outcome of this procedure. Three years after the operation, our patient experiences a "phantom sensation" on his chest when he is touched on the lateral forearm in the distribution of the lateral antebrachial cutaneous nerve. This outcome can be explained with review of the anatomy before and after the operation. The persistence of this adverse outcome suggests limitations in sensory cortical neuroplasticity. CONCLUSIONS: It is important to be aware of potential sensory complications in intercostal-to-musculocutaneous nerve transfer. Although this complication is known, it is often overlooked and underreported. Complications such as this should be emphasized in order to set expectations for patients and guide evaluation of sensory outcomes in a future study.
Assuntos
Plexo Braquial/lesões , Nervos Intercostais/transplante , Nervo Musculocutâneo/transplante , Transferência de Nervo/efeitos adversos , Transtornos de Sensação/etiologia , Adulto , Neuropatias do Plexo Braquial/etiologia , Humanos , Masculino , Complicações Pós-Operatórias/etiologiaRESUMO
Background Restriction of elbow flexion significantly limits upper extremity function following brachial plexus injuries. In recent years, the double fascicular nerve transfer procedure utilizing ulnar and median nerve transfer to musculocutaneous branches has shown promising functional outcomes. Objective To evaluate restoration of elbow flexion following a double fascicular transfer in patients with brachial plexus injuries and identify predictors of poor outcomes. Methods This retrospective review included 10 consecutive patients with brachial plexus injuries involving C5-C6 root avulsions who underwent the double nerve transfer procedure. The mean follow-up was 12 months and the primary outcome was assessment of elbow flexion with the use of the Medical Research Council (MRC) scale. Results This procedure achieved elbow flexion of MRC grade M3 or higher in 50% of our cohort. Time interval from injury to surgery showed a statistically significant inverse association with functional recovery (r = -0.73, p = 0.016). Patients who had the surgery within six months of the injury, demonstrated higher MRC grades during the follow-up (p = 0.048). There was no association between elbow flexion recovery and age, body mass index (BMI), gender, hypertension, diabetes or smoking status. Conclusions The double fascicular transfer to musculocutaneous may be a safe and effective treatment for restoration of elbow flexion. The procedure is associated with superior functional outcomes when performed within the first six months from the injury.