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Glioma is one of the most common central nervous system (CNS) cancers that can be found within the brain and the spinal cord. One of the pressing issues plaguing the development of therapeutics for glioma originates from the selective and semipermeable CNS membranes: the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). It is difficult to bypass these membranes and target the desired cancerous tissue because the purpose of the BBB and BSCB is to filter toxins and foreign material from invading CNS spaces. There are currently four varieties of Food and Drug Administration (FDA)-approved drug treatment for glioma; yet these therapies have limitations including, but not limited to, relatively low transmission through the BBB/BSCB, despite pharmacokinetic characteristics that allow them to cross the barriers. Steps must be taken to improve the development of novel and repurposed glioma treatments through the consideration of pharmacological profiles and innovative drug delivery techniques. This review addresses current FDA-approved glioma treatments' gaps, shortcomings, and challenges. We then outline how incorporating computational BBB/BSCB models and innovative drug delivery mechanisms will help motivate clinical advancements in glioma drug delivery. Ultimately, considering these attributes will improve the process of novel and repurposed drug development in glioma and the efficacy of glioma treatment.
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Antineoplásicos , Barrera Hematoencefálica , Neoplasias Encefálicas , Sistemas de Liberación de Medicamentos , Desarrollo de Medicamentos , Glioma , Glioma/tratamiento farmacológico , Humanos , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patologíaRESUMEN
Membrane remodeling drives a broad spectrum of cellular functions, and it is regulated through mechanical forces exerted on the membrane by cytoplasmic complexes. Here, we investigate how actin filaments dynamically tune their structure to control the active transfer of membranes between cellular compartments with distinct compositions and biophysical properties. Using intravital subcellular microscopy in live rodents we show that a lattice composed of linear filaments stabilizes the granule membrane after fusion with the plasma membrane and a network of branched filaments linked to the membranes by Ezrin, a regulator of membrane tension, initiates and drives to completion the integration step. Our results highlight how the actin cytoskeleton tunes its structure to adapt to dynamic changes in the biophysical properties of membranes.
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Citoesqueleto de Actina , Actinas , Membrana Celular , Animales , Citoesqueleto de Actina/metabolismo , Membrana Celular/metabolismo , Actinas/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/genética , Ratas , Ratones , Fusión de MembranaRESUMEN
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.
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Glioma , Microambiente Tumoral , Animales , Humanos , Porcinos , Porcinos Enanos , Médula Espinal , Citocinas , Modelos Animales de EnfermedadRESUMEN
Membrane remodeling drives a broad spectrum of cellular functions, and it is regulated through mechanical forces exerted on the membrane by cytoplasmic complexes. Here, we investigate how actin filaments dynamically tune their structure to control the active transfer of membranes between cellular compartments with distinct compositions and biophysical properties. Using intravital subcellular microscopy in live rodents we show that: a lattice composed of linear filaments stabilizes the granule membrane after fusion with the plasma membrane; and a network of branched filaments linked to the membranes by Ezrin, a regulator of membrane tension, initiates and drives to completion the integration step. Our results highlight how the actin cytoskeleton tunes its structure to adapt to dynamic changes in the biophysical properties of membranes.
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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.
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Glioma/etiología , Lentivirus/genética , Neoplasias de la Médula Espinal/etiología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Vectores Genéticos , Glioma/patología , Glioma/fisiopatología , Mutación , Neoplasias Experimentales/etiología , Neoplasias Experimentales/patología , Neoplasias Experimentales/fisiopatología , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Ratas , Ratas Sprague-Dawley , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/fisiopatología , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
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.
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Médula Espinal , Humanos , Inyecciones Espinales , Médula Espinal/cirugíaRESUMEN
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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Craniectomía Descompresiva , Procedimientos de Cirugía Plástica , Craniectomía Descompresiva/efectos adversos , Humanos , Estudios Retrospectivos , Cráneo/cirugía , Colgajos QuirúrgicosRESUMEN
The loss of salivary gland function caused by radiation therapy of the head and neck or autoimmune disease such as Sjögren's syndrome is a serious condition that affects a patient's quality of life. Due to the combined exocrine and endocrine functions of the salivary gland, gene transfer to the salivary glands holds the potential for developing therapies for disorders of the salivary gland and the expression of therapeutic proteins via the exocrine pathway to the mouth, upper gastrointestinal tract, or endocrine pathway, systemically, into the blood. Recent clinical success with viral vector-mediated gene transfer for the treatment of irradiation-induced damage to the salivary glands has highlighted the need for the development of novel vectors with acinar cell tropism able to result in stable long-term transduction. Previous studies with adeno-associated virus (AAV) focused on the submandibular gland and reported mostly ductal cell transduction. In this study, we have screened AAV vectors for acinar cell tropism in the parotid gland utilizing membrane-tomato floxed membrane-GFP transgenic mice to screen CRE recombinase encoding AAV vectors of different clades to rapidly identify capsid isolates able to transduce salivary gland acinar cells. We determined that AAVRh10 and a novel isolate found as a contaminant of a laboratory stock of simian adenovirus SV15, AAV44.9, are both able to transduce parotid and sublingual acinar cells. Persistence and localization of transduction of these AAVs were tested using vectors encoding firefly luciferase, which was detected 6 months after vector administration. Most luciferase expression was localized to the salivary gland compared to that of distal organs. Transduction resulted in robust secretion of recombinant protein in both blood and saliva. Transduction was species specific, with AAVRh10 having stronger transduction activity in rats compared with AAV44.9 or AAV2 but weaker in human primary salivary gland cells. This work demonstrates efficient transduction of parotid acinar cells by AAV that resulted in secretion of recombinant protein in both serum and saliva.
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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.
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Terapia por Estimulación Eléctrica/métodos , Manejo del Dolor/métodos , Neuralgia del Trigémino/terapia , Adulto , Anciano , Dolor Facial/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Intratable/terapia , Estudios Retrospectivos , Neuralgia del Trigémino/complicacionesRESUMEN
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.
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Ganglios Simpáticos/cirugía , Toracoscopía/métodos , Animales , Vías Autónomas , Femenino , Optogenética/métodos , PorcinosRESUMEN
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.
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Terapia por Estimulación Eléctrica/métodos , Dolor Facial/cirugía , Dolor Facial/terapia , Nervio Trigémino , Adulto , Anciano , Anciano de 80 o más Años , Terapia por Estimulación Eléctrica/efectos adversos , Electrodos Implantados/efectos adversos , Traumatismos del Nervio Facial/complicaciones , Traumatismos del Nervio Facial/terapia , Femenino , Estudios de Seguimiento , Migración de Cuerpo Extraño/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neuralgia Posherpética/terapia , Procedimientos Neuroquirúrgicos/métodos , Dimensión del Dolor , Dolor Intratable , Nervios Periféricos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
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Modelos Animales de Enfermedad , Vectores Genéticos/administración & dosificación , Glioma/patología , Lentivirus/genética , Trastornos Motores/patología , Neoplasias de la Médula Espinal/patología , Animales , Femenino , Vectores Genéticos/genética , Glioma/genética , Humanos , Masculino , Trastornos Motores/genética , Clasificación del Tumor , Neoplasias de la Médula Espinal/genética , Porcinos , Porcinos EnanosRESUMEN
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.
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Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Embolización Terapéutica/métodos , Neuralgia del Trigémino/etiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
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Neuropatías del Plexo Braquial , Plexo Braquial , Transferencia de Nervios , Plexo Braquial/cirugía , Neuropatías del Plexo Braquial/cirugía , Codo , Humanos , Estudios Prospectivos , Rango del Movimiento ArticularRESUMEN
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.
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Diafragma/inervación , Modelos Animales de Enfermedad , Nervio Frénico/cirugía , Toracoscopía/métodos , Animales , Diafragma/patología , Diafragma/fisiopatología , Femenino , Proyectos Piloto , Parálisis Respiratoria/etiología , Traumatismos de la Médula Espinal/complicaciones , PorcinosRESUMEN
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.
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Neoplasias de la Vaina del Nervio/etiología , Neoplasias de la Vaina del Nervio/terapia , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/terapia , Humanos , Neoplasias de la Vaina del Nervio/cirugía , Procedimientos NeuroquirúrgicosRESUMEN
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.
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Neuropatías del Plexo Braquial/complicaciones , Neuropatías del Plexo Braquial/cirugía , Transferencia de Nervios/métodos , Procedimientos Neuroquirúrgicos/métodos , Hombro/fisiopatología , Neuropatías del Plexo Braquial/fisiopatología , Humanos , Recuperación de la Función , Resultado del Tratamiento , Extremidad Superior/fisiopatologíaRESUMEN
BACKGROUND: Occipital neuralgia (ON) is defined as paroxysmal pain in the distribution of the greater, lesser, and/or third occipital nerves. ON can be refractory to conservative management and minimally invasive interventions. Neuromodulatory procedures can potentially treat refractory ON and include occipital nerve stimulation and the sparsely reported high cervical spinal cord stimulation (SCS). OBJECTIVE: To report our experience and conduct a systematic literature review of studies evaluating the effect of high cervical SCS as a treatment modality for refractory ON. METHODS: A retrospective review of patients with refractory ON who underwent high cervical SCS was conducted. In addition, a systematic literature review was performed according to the PRISMA guidelines. RESULTS: Five patients with refractory ON were treated with high cervical (C1-C3) SCS in our institution. Two out of five (40%) patients reported a successful trial stimulation (>50% pain reduction) and received permanent implantation. During the follow-up, the visual analog scale score decreased from 7.5 to 4 and from 6.5 to 5 in these patients. No complications were reported for any of the patients. The systematic literature review, identified two eligible studies, comprising 18 patients overall who underwent cervicomedullary junction SCS. Nine out of 18 patients (50%) had a successful trial and received permanent implantation. CONCLUSION: High cervical or cervicomedullary junction SCS is associated with a 40-50% successful trial rate in refractory ON. No major complications were noted during the follow-up. Future studies are needed to compare the different neurosurgical options, in order to identify the optimal treatment strategy for refractory ON.
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Background Cubital tunnel syndrome (CuTS) is the second most common peripheral neuropathy in the United States. All three current surgical treatment approaches, consisting of in situ decompression, medial epicondylectomy, and transposition, require large curvilinear incisions and dissections that cross the medial epicondyle. However, the use of a large curvilinear incision may not be necessary for in situ decompression and may be achieved with small incisions proximal and distal to the medial epicondyle. This may limit the risk of peri-incisional pain and numbness, similar to the benefits provided by endoscopy. Objective The aim of this study is to evaluate a minimally invasive tunneling approach for in situ ulnar nerve decompression utilizing 2 cm incisions proximal and distal to the medial epicondyle. Methods A retrospective chart review was performed for patients at Emory University Hospital with CuTS who underwent minimally invasive tunneling for in situ decompression. Seven cases were identified. Patient demographics and data on post-operative complications were collected. Pre-operative severity was graded as a Modified McGowan severity. The primary outcome was evaluated using the post-surgical Messina Criterion. Secondary outcomes were reports of peri-incisional pain or numbness evaluated at follow-up. Descriptive statistics are presented. Results Pre-operatively, one of the seven cases was Grade I McGowan and the remaining six were Grade 2a or 2b. Post-operatively, on the Messina Criterion, four of seven patients were rated as having "Good" outcomes, two of seven had "Fair", while one of seven had "Poor." There was one post-operative surgical site infection. Among the other six cases, there were no reports of peri-incisional pain or numbness. Conclusions The use of less-invasive tunneling approach to in situ decompression yielded positive outcomes in this case series with no reports of peri-incisional pain or numbness. A prospective trial may be useful to explore the theoretical benefits of this novel tunneling approach.
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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.