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1.
Surg Neurol Int ; 15: 343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39373004

RESUMO

Background: Spinal arteriovenous fistulas (SAVFs) are direct communication between arteries and veins without intervening abnormal vessel nidus, which often results in venous congestion and spinal cord dysfunction. Ventrally located SAVF can be challenging to treat through traditional open or endovascular approaches. Case Description: We describe a hybrid (open/endovascular) procedure in a 72-year-old male with a Takai Type IVb SAVF presenting with paraparesis and sphincter dysfunction. Imaging revealed a conus medullaris SAVF in which the main fistulous connection was located ventrally. The conventional endovascular approach was deemed risky, and open surgery failed in the first attempt. The SAVF was resolved using a hybrid approach: under direct visualization, an engorged dorsal vein was punctured with an Angiocath, and a fluoroscopy-guided microcatheter was advanced through it to reach and embolize the ventral perimedullary fistulous connection. After surgery, his progressive neurological decline stabilized, radiographic spinal cord edema improved, and follow-up angiography confirmed obliteration of the fistula. Neurological function remained at the preoperative baseline. Conclusion: This approach may be a treatment for selected cases of type IVb SAVF. Easily accessible feeding vessels are coagulated and cut; the inaccessible ones can be embolized endovascularly during the same procedure.

2.
J Neurooncol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325339

RESUMO

PURPOSE: Spinal laser interstitial thermal therapy (sLITT) is a less invasive alternative to surgery for metastatic epidural spinal cord compression. Here, we analyze outcomes of patients treated with sLITT either in conjunction with radiotherapy or as a standalone salvage therapy. METHODS: We included patients with thoracic vertebral metastatic cord compression treated with sLITT. Outcomes included freedom from local failure (FFLF) and overall survival (OS). Factors associated with FFLF were identified with univariable and multivariable analyses via a Cox proportional hazards model. RESULTS: Between 2013-2022, 129 patients received sLITT to 144 vertebral segments; 69% were radiotherapy naïve, 81% were radioresistant histologies, and 74% were centered in the vertebral body. Median age was 61 years. Pre-sLITT Bilsky score was 3 in 28%, 2 in 33%, and 1c in 37%. Radiotherapy was delivered in conjunction with sLITT for 80% of cases, including 68% that received stereotactic radiotherapy, at a median of 5 days after sLITT. Median follow-up was 9.1 months. One-year FFLF and OS was 80% and 78%, respectively. On multivariable analysis, variables independently associated with adverse FFLF included paraspinal/foraminal disease location (p = 0.001), and post-sLITT imaging Bilsky score of 2 (p = 0.073) or 3 (p = 0.011). Prior radiotherapy, technique of radiotherapy, and time between radiotherapy and sLITT were not associated with FFLF. CONCLUSION: sLITT with radiotherapy is an effective minimally invasive treatment approach for thoracic metastatic epidural spinal cord compression. Early treatment response may serve as a prognostic imaging biomarker.

3.
Pain Manag ; 14(7): 347-353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39269163

RESUMO

Aim: Chronic shoulder pain due to iatrogenic spinal accessory nerve (SAN) injury continues to be under-recognized, resulting in delayed time-to-diagnosis and poorer outcomes. Solutions are needed to improve the management of this condition, which can be challenging as care needs to be coordinated across pain management, neurophysiology, rehabilitation and reconstructive surgery.Cases: We present a series of six patients with shoulder pain refractory to conservative pain treatments to highlight how SAN injuries continued to be missed and treatment delayed, even at advanced care centers. The time to diagnosis of SAN palsy took an average of 21 months and treatment was inconsistent for all patients.Discussion: None of the six cases had initial suspicion of SAN palsy and only one patient received targeted SAN injury care. SAN treatment should be started as early as possible so that patients can be referred for prompt surgical evaluation if they fail conservative management. Integrated care pathways may be a solution for formalizing multidisciplinary team involvement and improving SAN injury outcomes.Conclusion: Systemic processes, such as integrated care pathways, are needed to optimize early recognition and targeted treatment of SAN injury and may be beneficial for other underdiagnosed and undertreated neuropathic pain conditions.


Neck dissection surgeries, which are done to treat various head and neck cancers, can often lead to shoulder pain. This pain commonly involves damage to a nerve called the spinal accessory nerve (SAN). Even though this nerve injury has been well-described by experts, many patients continue to experience delays in getting a correct diagnosis and treatment for this pain.This study describes six cases from a large cancer center where patients developed chronic shoulder pain after neck dissection. These patients waited an average of 21 months to reach a correct diagnosis of SAN injury. The pain and symptoms were often mistaken for other conditions. In one case, a patient received delayed treatment from a coordinated team of medical specialists, leading to improvements in her pain and shoulder function.The delay in diagnosing SAN injuries is likely due to two main challenges: a lack of awareness among providers and a tendency for healthcare to focus on specific areas rather than a team-based approach. Early diagnosis is crucial to prevent and minimize long-term pain and muscle loss.To improve patient care, this study suggests using an integrated care pathway approach and gives an example of how providers can adopt this approach. This method involves coordinating various medical specialists to ensure prompt diagnosis and treatment. By improving how SAN injuries are managed, patients can receive better care and avoid chronic pain and disability.


Assuntos
Dor Crônica , Dor de Ombro , Humanos , Dor de Ombro/terapia , Dor de Ombro/etiologia , Dor Crônica/terapia , Dor Crônica/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Traumatismos do Nervo Acessório , Manejo da Dor/métodos , Idoso , Nervo Acessório
4.
Global Spine J ; : 21925682241278323, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39166967

RESUMO

STUDY DESIGN: Survey study. OBJECTIVES: The purpose of this study was to characterize the utility of 3D printed patient specific anatomic models for the planning of complex primary spine tumor surgeries. METHODS: A survey of individual members of an international study group of spinal oncology surgeons was performed. Participants were provided a clinical vignette, pathologic diagnosis, and pre-operative imaging for three primary spinal oncology cases. Study participants provided a free text surgical plan for resection and were then presented an associated 3D printed model for each case and asked to re-evaluate their surgical plan. RESULTS: Ten spinal oncology surgeons participated in the study, representing nine institutions across five countries. Four of the surgeons (40%) made significant changes to their surgical plan after reviewing the 3D models, including sacrifice of an additional nerve root to obtain negative margins, sparing an SI joint that was originally planned for inclusion in the en bloc resection, adjusting the location of osteotomy cuts, changes to the number of surgical stages and/or staging order, and preservation of neurology that was originally planned for sacrifice. The overall impression of the 3D models was positive, with 90% of the participants stating they found the 3D model useful in developing a surgical plan. CONCLUSIONS: Surgical planning for resection of primary spinal column tumors is challenging and time intensive. 3D printed patient specific surgical models may be an additional tool that can augment surgical planning and execution by improving the chance of accomplishing surgical resection goals and minimizing morbidity.

5.
J Neurosurg Case Lessons ; 8(4)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39038367

RESUMO

BACKGROUND: Paget's disease of bone (PDB) is a common bone metabolic pathology in older adults, characterized by mixed osteolytic, osteoblastic, and quiescent periods. Surgical guidelines for PDB involving the spine are not well-defined and are reserved for cases refractory to medical treatments, typically bisphosphonates like zoledronic acid. This case study describes a 52-year-old male with PDB who presented with rapidly progressing myelopathy symptoms refractory to standard medical treatment, warranting surgical decompression. OBSERVATIONS: Surgical decompression and fusion, involving laminectomy with partial facetectomies, placement of pedicle screw instrumentation, and posterolateral arthrodesis spanning beyond the pathological segment, was performed. Follow-up visits indicated progressive improvement in symptoms and mobility, and imaging showed stable postsurgical changes with increased sclerosis in the affected vertebrae on a 2-year postsurgical course. LESSONS: This case underscores that PDB of the spine can transition from asymptomatic to significant impairment and demonstrates that surgical intervention can provide effective symptomatic relief in myelopathy secondary to PDB. The case contributes to the growing evidence of the effectiveness of surgical decompression in PDB involving the spine. https://thejns.org/doi/10.3171/CASE24203.

6.
Brain ; 147(9): 2991-2997, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39046204

RESUMO

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. Tomivosertib treatment also decreased action potential amplitude and produced alterations in the magnitude of after hyperpolarizing currents, suggesting modification of Na+ and K+ channel activity as a consequence of drug treatment. Parallel to the effects on electrophysiology, eFT508 treatment led to a profound loss of eIF4E serine 209 phosphorylation in primary sensory neurons, a specific substrate of MNK, within 2 min of drug treatment. Our results create a compelling case for the future testing of MNK inhibitors in clinical trials for neuropathic pain.


Assuntos
Potenciais de Ação , Gânglios Espinais , Radiculopatia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Humanos , Masculino , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Radiculopatia/tratamento farmacológico , Células Cultivadas , Pessoa de Meia-Idade , Feminino , Idoso , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Sulfonas/farmacologia , Sulfonas/uso terapêutico , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo
7.
J Neurosurg Spine ; 41(3): 436-444, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38875722

RESUMO

OBJECTIVE: Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases. METHODS: Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence. RESULTS: A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear. CONCLUSIONS: High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.


Assuntos
Recidiva Local de Neoplasia , Neoplasias da Próstata , Radiocirurgia , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Masculino , Radiocirurgia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Idoso , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Resultado do Tratamento , Estudos Retrospectivos , Seguimentos
8.
Cancers (Basel) ; 16(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38893133

RESUMO

(1) Background: Myxopapillary ependymoma (MPE) is a rare tumor of the spine, typically slow-growing and low-grade. Optimal management strategies remain unclear due to limited evidence given the low incidence of the disease. (2) Methods: We analyzed data from 1197 patients with spinal MPE from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2020). Patient demographics, treatment modalities, and survival outcomes were examined using statistical analyses. (3) Results: Most patients were White (89.9%) with a median age at diagnosis of 42 years. Surgical resection was performed in 95% of cases. The estimated 10-year overall survival was 91.4%. Younger age (hazard ratio (HR) = 1.09, p < 0.001) and receipt of surgery (HR = 0.43, p = 0.007) were associated with improved survival. Surprisingly, male sex was associated with worse survival (HR = 1.86, p = 0.008) and a younger age at diagnosis compared to females. (4) Conclusions: This study, the largest of its kind, underscores the importance of surgical resection in managing spinal MPE. The unexpected association between male sex and worse survival warrants further investigation into potential sex-specific pathophysiological factors influencing prognosis. Despite limitations, our findings contribute valuable insights for guiding clinical management strategies for spinal MPE.

9.
J Neurosurg Pediatr ; 33(5): 484-495, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428008

RESUMO

OBJECTIVE: Thoracic outlet syndrome (TOS) is a complex disorder affecting the neurovascular structures of the upper extremity as they traverse from the neck and thorax to the upper extremity. This systematic review and meta-analysis focuses on pediatric TOS, offering insights into its clinical presentation, etiology, treatment modalities, and outcomes in contrast to those reported in adult TOS. METHODS: A comprehensive search for pediatric TOS in the PubMed database using PRISMA guidelines identified 6 relevant studies published between 2008 and 2022. In total, 227 pediatric TOS cases in 216 patients were analyzed. Data categories explored for TOS in pediatric patients included study design, number of patients included, mean age and sex of patients, TOS type, laterality, bony abnormalities, time to surgery, symptoms, treatment modalities, initial surgical technique, surgical complications, percent lost to follow-up, mean follow-up period, and treatment outcome. RESULTS: The results from the 6 studies of 216 patients show a distinct pattern in pediatric TOS, with a 1.84:1 female-to-male ratio, a mean age of 15.49 years, and a lower prevalence of neurogenic TOS (75%, 95% CI 0.41-0.93; I2 = 86%, p < 0.01) compared with the prevailing literature on adults (87.5%-99%). Venous and arterial TOS accounted for a higher proportion of cases in pediatric patients than in adults, challenging the traditional adult-oriented perspective. Right-sided presentations were more common, reflecting right-arm dominance in most individuals. Additionally, bony abnormalities were more common in adults (30%) than in children (10.65%). Treatments involved mixed methods, predominantly using combinations of muscle resection (95.26%), neurolysis (78.02%), and bone resection (72.41%). Patients had high rates of symptom improvement (89%, 95% CI 0.67-0.97; I2 = 85%, p < 0.01) following surgery, with improvement of symptoms ranging from slight to complete relief. Complications were infrequent (5.66%), and most patients reported positive outcomes. The limitations of this analysis include subjective diagnostic and reporting criteria for TOS given its broad range of presentations. CONCLUSIONS: This systematic review and meta-analysis brings to light the distinctive characteristics of pediatric TOS and underscores the importance of recognizing these differences to ensure accurate diagnosis and effective treatment in this patient population. Further research is needed to understand the predictive value of conservative treatments, especially in pediatric TOS cases.


Assuntos
Síndrome do Desfiladeiro Torácico , Humanos , Síndrome do Desfiladeiro Torácico/cirurgia , Criança , Adolescente , Feminino , Masculino , Resultado do Tratamento
10.
JCI Insight ; 9(9)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512420

RESUMO

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts and exposed to TTFields. Following TTFields exposure, the bioluminescence imaging (BLI) signal decreased to 10%-80% of baseline, while control cultures displayed a 4.48- to 9.36-fold increase in signal. Lastly, TTFields were applied in an orthotopic murine model of spinal metastasis. After 21 days of treatment, control mice demonstrated a 5-fold increase in BLI signal compared with TTFields-treated mice. TTFields similarly prevented tumor invasion into the spinal canal and development of neurologic symptoms. Our data suggest that TTFields can be leveraged as a local therapy within minimally conductive bone of spinal metastases. This provides the groundwork for future studies investigating TTFields for patients with treatment-refractory spinal metastases.


Assuntos
Neoplasias da Coluna Vertebral , Animais , Humanos , Camundongos , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapia , Linhagem Celular Tumoral , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Proliferação de Células , Modelos Animais de Doenças , Osteossarcoma/patologia , Osteossarcoma/terapia , Feminino , Células A549 , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Radiother Oncol ; 193: 110119, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311030

RESUMO

INTRODUCTION: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). RESULTS: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5-32) and 52.7 cm3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/ß = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). CONCLUSION: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.


Assuntos
Fraturas por Compressão , Segunda Neoplasia Primária , Radiocirurgia , Sarcoma , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Fraturas da Coluna Vertebral/etiologia , Fraturas por Compressão/etiologia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Recidiva Local de Neoplasia/cirurgia , Sarcoma/radioterapia , Sarcoma/cirurgia , Estudos Retrospectivos , Segunda Neoplasia Primária/etiologia
13.
Pract Radiat Oncol ; 14(2): 103-111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37914081

RESUMO

PURPOSE: Carbon fiber reinforced polyetheretherketone (CFRP) is a nonmetallic material that is a subject of growing interest in the field of spinal instrumentation manufacturing. The radiolucency and low magnetic susceptibility of CFRP has potential to create less interference with diagnostic imaging compared with titanium implants. However, an objective comparison of the image artifact produced by titanium and CFRP implants has not been described. Spinal oncology, particularly after resection of spinal tumors and at the time of spinal stereotactic radiosurgery planning, relies heavily on imaging interpretation for evaluating resection, adjuvant treatment planning, and surveillance. We present a study comparing measurements of postoperative magnetic resonance imaging artifacts between titanium and CFRP pedicle screw constructs in the setting of separation surgery for metastatic disease. METHODS AND MATERIALS: The diameter of the signal drop around the screws (pedicle screw artifact) and the diameter of the spinal canal free from artifacts (canal visualization) were measured in consecutive patients who had spinal instrumentation followed by spinal stereotactic radiosurgery in the June 2019 to May 2022 timeframe. The spinal cord presented a shift at the screw level in sagittal images which was also measured (Sagittal Distortion, SagD). RESULTS: Fifty patients, corresponding to 356 screws and 183 vertebral levels, were evaluated overall. CFRP produced less artifacts in all the 3 parameters compared with titanium: mean pedicle screw artifact (CFRP = 5.8 mm, Ti = 13.2 mm), canal visualization (CFRP = 19.2 mm, Ti = 15.5 mm), and SagD (CFRP = .5 mm, Ti = 1.9 mm), all P < .001. In practice, these findings translate into better-quality magnetic resonance imaging. CONCLUSIONS: The initial perceived advantages are easier evaluation of postoperative imaging, facilitating radiation treatment planning, recurrence detection, and avoidance in repeating a suboptimal computed tomography myelogram. Further clinical studies analyzing long-term outcomes of patients treated with CFRP implants are necessary.


Assuntos
Benzofenonas , Parafusos Pediculares , Plásticos , Polímeros , Radiocirurgia , Fusão Vertebral , Humanos , Fibra de Carbono , Artefatos , Titânio , Fusão Vertebral/métodos , Polietilenoglicóis , Cetonas , Imageamento por Ressonância Magnética/métodos
14.
J Neurooncol ; 164(2): 377-386, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37667065

RESUMO

PURPOSE: The management of chordoma or chondrosarcoma involving the spine is often challenging due to adjacent critical structures and tumor radioresistance. Spine stereotactic radiosurgery (SSRS) has radiobiologic advantages compared with conventional radiotherapy, though there is limited evidence on SSRS in this population. We sought to characterize the long-term local control (LC) of patients treated with SSRS. METHODS: We retrospectively reviewed patients with chordoma or chondrosarcoma treated with dose-escalated SSRS, defined as 24 Gy in 1 fraction to the gross tumor volume. Overall survival (OS) was calculated by Kaplan-Meier functions. Competing risk analysis using the cause-specific hazard function estimated LC time. RESULTS: Fifteen patients, including 12 with chordoma and 3 with chondrosarcoma, with 22 lesions were included. SSRS intent was definitive, single-modality in 95% of cases (N = 21) and post-operative in 1 case (5%). After a median censored follow-up time of 5 years (IQR 4 to 8 years), median LC time was not reached (IQR 8 years to not reached), with LC rates of 100%, 100%, and 90% at 1 year, 2 years, and 5 years. The median OS was 8 years (IQR 3 years to not reached). Late grade 3 toxicity occurred after 23% of treatments (N = 5, fracture), all of which were managed successfully with stabilization. CONCLUSION: Definitive dose-escalated SSRS to 24 Gy in 1 fraction appears to be a safe and effective treatment for achieving durable local control in chordoma or chondrosarcoma involving the spine, and may hold particular importance as a low-morbidity alternative to surgery in selected cases.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Cordoma , Radiocirurgia , Neoplasias da Coluna Vertebral , Humanos , Radiocirurgia/efeitos adversos , Cordoma/radioterapia , Cordoma/cirurgia , Cordoma/patologia , Estudos Retrospectivos , Resultado do Tratamento , Condrossarcoma/radioterapia , Condrossarcoma/cirurgia , Condrossarcoma/patologia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia
15.
bioRxiv ; 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37398249

RESUMO

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in preclinical models and in patients suffering from this largely untreated disease. While many intracellular signaling mechanisms have been examined in preclinical models that drive this spontaneous activity (SA), none of these have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we show that inhibition of mitogen activated protein kinase interacting kinase (MNK) with eFT508 (25 nM) reverses SA in human sensory neurons associated with painful dermatomes. MNK inhibition in spontaneously active nociceptors decreased action potential amplitude and produced alterations in the magnitude of afterhyperpolarizing currents suggesting modification of Na+ and K+ channel activity downstream of MNK inhibition. The effects of MNK inhibition on SA took minutes to emerge and were reversible over time with eFT508 washout. MNK inhibition with eFT508 led to a profound loss of eIF4E Serine 209 phosphorylation, a specific target of the kinase, within 2 min of drug treatment, consistent with the rapid action of the drug on SA in electrophysiology experiments. Our results create a compelling case for the future testing of MNK inhibitors in clinical trials for neuropathic pain.

16.
J Neurosurg Spine ; 39(5): 611-617, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37060308

RESUMO

OBJECTIVE: The purpose of this study was to analyze risk factors for sacral fracture following noninstrumented partial sacral amputation for en bloc chordoma resection. METHODS: A multicenter retrospective chart review identified patients who underwent noninstrumented partial sacral amputation for en bloc chordoma resection with pre- and postoperative imaging. Hounsfield units (HU) were measured in the S1 level. Sacral amputation level nomenclature was based on the highest sacral level with bone removed (e.g., S1 foramen amputation at the S1-2 vestigial disc is an S2 sacral amputation). Variables collected included basic demographics, patient comorbidities, surgical approach, preoperative radiographic details, neoadjuvant and adjuvant radiation therapy, and postoperative sacral fracture data. RESULTS: A total of 101 patients (60 men, 41 women) were included; they had an average age of 69 years, BMI of 29 kg/m2, and follow-up of 60 months. The sacral amputation level was S1 (2%), S2 (37%), S3 (44%), S4 (9%), and S5 (9%). Patients had a posterior-only approach (77%) or a combined anterior-posterior approach (23%), with 10 patients (10%) having partial sacroiliac (SI) joint resection. Twenty-seven patients (27%) suffered a postoperative sacral fracture, all occurring between 1 and 7 months after the index surgery. Multivariable logistic regression analysis demonstrated S1 or S2 sacral amputation level (p = 0.001), combined anterior-posterior approach (p = 0.0064), and low superior S1 HU (p = 0.027) to be independent predictors of sacral fracture. The fracture rate for patients with superior S1 HU < 225, 225-300, and > 300 was 38%, 15%, and 9%, respectively. An optimal superior S1 HU cutoff of 300 was found to maximize sensitivity (89%) and specificity (42%) in predicting postamputation sacral fracture. In addition, the fracture rate for patients who underwent partial SI joint resection was 100%. CONCLUSIONS: Patients with S1 or S2 partial sacral amputations, a combined anterior-posterior surgical approach, low superior S1 HU, and partial SI joint resection are at higher risk for postoperative sacral fracture following en bloc chordoma resection and should be considered for spinopelvic instrumentation at the index procedure.


Assuntos
Cordoma , Fraturas Ósseas , Lesões do Pescoço , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Masculino , Humanos , Feminino , Idoso , Cordoma/diagnóstico por imagem , Cordoma/cirurgia , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/efeitos adversos , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Fraturas Ósseas/cirurgia , Lesões do Pescoço/cirurgia , Sacro/diagnóstico por imagem , Sacro/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Resultado do Tratamento
17.
Neurospine ; 20(1): 317-326, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37016879

RESUMO

PURPOSE: Carbon-fiber reinforced polyetheretherketone (CFRP)-based spinal implants are an alternative to titanium, offering less image artifact as their metallic counterparts while maintaining similar biomechanical and biocompatibility properties. Its use in the management of spinal tumors has been reported, however the perceived advantages related to improved imaging quality, radiation treatment planning, and detection of tumor recurrence have not been fully assessed. METHODS: We performed a retrospective review of medical records amongst oncologic patients treated at MD Anderson Cancer Center with CFRP implants. Histology, tumor location, construct features, time of follow-up, adjuvant radiation, recurrences, overall survival, and hardware-related complications were recorded. RESULTS: Sixty-nine consecutive patients were assessed (22 primary tumors, 47 metastases) and the median time for follow-up was 5.4 months. Amongst the cohort, a total of 491 CFRP pedicle screws were implanted. Hardware complications were observed in 5 cases (7.04%). Adjuvant radiation was completed in 8 patients with primary tumors and 29 patients with spinal metastases. A total of 28 patients (40.5%) from the combined primary and metastatic cohorts experienced systemic disease progression, with 12 patients (17.3%) demonstrating local recurrences. Amongst primary and metastatic tumors, overall survival (p = 0.363) and rate of local recurrence (p = 0.112) were similar. CONCLUSION: This largest series of CFRP implants demonstrates safe and effective spinal stabilization for patients with both primary and metastatic tumors. Enhanced postoperative imaging led to minimal imaging artifacts which facilitated postoperative radiation planning and the ability to detect local recurrence.

18.
Neurosurg Focus Video ; 8(1): V9, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36628102

RESUMO

Transfer of the ulnar fascicle to the biceps branch of the musculocutaneous nerve, or Oberlin transfer, has been widely used for the treatment of elbow flexion weakness in the setting of upper trunk brachial plexus palsy. The authors present a modified application of this technique for restoration of functional elbow flexion in a 30-year-old woman with a history of recurrent upper cervical spinal cord pilocytic astrocytoma, complex spinal deformity, and radiation-induced lower motor neuron disease. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2299.

19.
Brain ; 146(2): 749-766, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-35867896

RESUMO

Neuropathic pain is a leading cause of high-impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the dorsal root ganglia is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human dorsal root ganglia from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain-associated dorsal root ganglia. We sequenced 70 human dorsal root ganglia, and among these 50 met inclusion criteria for sufficient neuronal mRNA signal for downstream analysis. Our expression analysis revealed profound sex differences in differentially expressed genes including increase of IL1B, TNF, CXCL14 and OSM in male and CCL1, CCL21, PENK and TLR3 in female dorsal root ganglia associated with neuropathic pain. Coexpression modules revealed enrichment in members of JUN-FOS signalling in males and centromere protein coding genes in females. Neuro-immune signalling pathways revealed distinct cytokine signalling pathways associated with neuropathic pain in males (OSM, LIF, SOCS1) and females (CCL1, CCL19, CCL21). We validated cellular expression profiles of a subset of these findings using RNAscope in situ hybridization. Our findings give direct support for sex differences in underlying mechanisms of neuropathic pain in patient populations.


Assuntos
Neuralgia , RNA , Feminino , Humanos , Masculino , Gânglios Espinais/metabolismo , Neuralgia/genética , Neuralgia/metabolismo , RNA/metabolismo , Transcriptoma , Fatores Sexuais
20.
Br J Radiol ; 96(1141): 20220267, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35946551

RESUMO

Spine is the most frequently involved site of osseous metastases. With improved disease-specific survival in patients with Stage IV cancer, durability of local disease control has become an important goal for treatment of spinal metastases. Herein, we review the multidisciplinary management of spine metastases, including conventional external beam radiation therapy, spine stereotactic radiosurgery, and minimally invasive and open surgical treatment options. We also present a simplified framework for management of spinal metastases used at The University of Texas MD Anderson Cancer Center, focusing on the important decision points where the radiologist can contribute.


Assuntos
Radiocirurgia , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/radioterapia , Radiologistas , Resultado do Tratamento
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