RESUMO
BACKGROUND AND PURPOSE: Ischemic injury triggers multiple pathological responses in the brain tissue, including spreading depolarizations across the cerebral cortex (cortical spreading depolarizations [CSD]). Microglia have been recently shown to play a significant role in the propagation of CSD. However, the intracellular responses of myeloid cells during ischemic stroke have not been investigated. METHODS: We have studied intracellular calcium activity in cortical microglia in the stroke model of the middle cerebral artery occlusion, using the murine Polr2a-based and Cre-dependent GCaMP5 and tdTomato reporter (PC::G5-tdT). High-speed 2-photon microscopy through cranial windows was employed to record signals from genetically encoded indicators of calcium. Inflammatory stimuli and pharmacological inhibition were used to modulate microglial calcium responses in the somatosensory cortex. RESULTS: In vivo imaging revealed periodical calcium activity in microglia during the hyperacute phase of ischemic stroke. This activity was more frequent during the first 6 hours after occlusion, but the amplitudes of calcium transients became larger at later time points. Consistent with CSD nature of these events, we reproducibly triggered comparable calcium transients with microinjections of potassium chloride (KCl) into adjacent cortical areas. Furthermore, lipopolysaccharide-induced peripheral inflammation, mimicking sterile inflammation during ischemic stroke, produced significantly greater microglial calcium transients during CSD. Finally, in vivo pharmacological analysis with CRAC (calcium release-activated channel) inhibitor CM-EX-137 demonstrated that CSD-associated microglial calcium transients after KCl microinjections are mediated at least in part by the CRAC mechanism. CONCLUSIONS: Our findings demonstrate that microglia participate in ischemic brain injury via previously undetected mechanisms, which may provide new avenues for therapeutic interventions.
Assuntos
Sinalização do Cálcio , AVC Isquêmico/fisiopatologia , Microglia , Doença Aguda , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Encefalite/induzido quimicamente , Encefalite/fisiopatologia , Processamento de Imagem Assistida por Computador , Infarto da Artéria Cerebral Média/fisiopatologia , Lipopolissacarídeos , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica , Células Mieloides , Cloreto de Potássio/farmacologia , Córtex Somatossensorial/fisiopatologiaRESUMO
PURPOSE: Primary pituitary abscesses are extraordinarily rare lesions, especially in pediatric populations, with very few cases described in the literature. Here we review this rare condition and discuss its management. METHODS: We report a case of a previously healthy 12-year-old female patient who presented with vomiting and meningismus. We review the literature on pediatric patients presenting with pituitary abscesses and the described treatments. An operative video demonstrating our surgical technique is provided. RESULTS: Magnetic resonance imaging of the brain revealed a rim-enhancing, diffusion-restricting sellar lesion concerning for abscess. No sinus disease or other structural cause of intracranial infection was identified. An endoscopic transsphenoidal approach was used to visualize the endonasal structures, and microscopic guidance was used for evacuation of the abscess. Purulent material was drained immediately upon entry into the lesion. Tissue cultures grew Cutibacterium acnes. Postoperatively, the patient was hypocortisolemic but otherwise endocrinologically normal. She was discharged four days later on oral hydrocortisone and intravenous ceftriaxone without any neurologic deficit. CONCLUSION: To the best of our knowledge, this is the second report in the literature of a primary pituitary abscess due to C. acnes infection.
Assuntos
Abscesso Encefálico , Doenças da Hipófise , Adolescente , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/cirurgia , Criança , Drenagem , Endoscopia , Feminino , Humanos , Imageamento por Ressonância Magnética , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/cirurgiaRESUMO
BACKGROUND: Previous studies have not evaluated the impact of illness severity and postrupture procedures in the cost of care for intracranial aneurysms. We hypothesize that the severity of aneurysm rupture and the aggressiveness of postrupture interventions play a role in cost. METHODS: The Value Driven Outcomes database was used to assess direct patient cost during the treatment of ruptured intracranial aneurysm with clipping, coiling, and Pipeline flow diverters. RESULTS: One hundred ninety-eight patients (mean age 52.8 ± 14.1 years; 40.0% male) underwent craniotomy (64.6%), coiling (26.7%), or flow diversion (8.6%). Coiling was 1.4× more expensive than clipping (p = .005) and flow diversion was 1.7× more expensive than clipping (p < .001). More severe illness as measured by American Society of Anesthesia, Hunt/Hess, and Fisher scales incurred higher costs than less severe illness (p < .05). Use of a lumbar drain protocol to reduce subarachnoid hemorrhage and use of an external ventricular drain to manage intracranial pressure were associated with reduced (p = .05) and increased (p < .001) total costs, respectively. Patients with severe vasospasm (p < .005), those that received shunts (p < .001), and those who had complications (p < .001) had higher costs. Multivariate analysis showed that procedure type, length of stay, number of angiograms, vasospasm severity, disposition, and year of treatment were independent predictors of cost. CONCLUSIONS: These results show for the first time that disease and vasospasm severity and intensity of treatment directly impact the cost of care for patients with aneurysms in the USA. Strategies to alter these variables may prove important for cost reduction.
Assuntos
Aneurisma Roto/economia , Craniotomia/economia , Gastos em Saúde/estatística & dados numéricos , Aneurisma Intracraniano/economia , Adulto , Idoso , Aneurisma Roto/patologia , Aneurisma Roto/cirurgia , Craniotomia/efeitos adversos , Feminino , Humanos , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Índice de Gravidade de Doença , Estados UnidosRESUMO
OBJECTIVE With the continuous rise of health care costs, hospitals and health care providers must find ways to reduce costs while maintaining high-quality care. Comparing surgical and endovascular treatment of intracranial aneurysms may offer direction in reducing health care costs. The Value-Driven Outcomes (VDO) database at the University of Utah identifies cost drivers and tracks changes over time. In this study, the authors evaluate specific cost drivers for surgical clipping and endovascular management (i.e., coil embolization and flow diversion) of both ruptured and unruptured intracranial aneurysms using the VDO system. METHODS The authors retrospectively reviewed surgical and endovascular treatment of ruptured and unruptured intracranial aneurysms from July 2011 to January 2017. Total cost (as a percentage of each patient's cost to the system), subcategory costs, and potential cost drivers were evaluated and analyzed. RESULTS A total of 514 aneurysms in 469 patients were treated; 273 aneurysms were surgically clipped, 102 were repaired with coiling, and 139 were addressed with flow diverter placements. Middle cerebral artery aneurysms accounted for the largest portion of cases in the clipping group (29.7%), whereas anterior communicating artery aneurysms were most frequently involved in the coiling group (30.4%) and internal carotid artery aneurysms were the majority in the flow diverter group (63.3%). Coiling (mean total cost 0.25% ± 0.20%) had a higher cost than flow diversion (mean 0.20% ± 0.16%) and clipping (mean 0.17 ± 0.14%; p = 0.0001, 1-way ANOVA). Coiling cases cost 1.5 times as much as clipping and flow diversion costs 1.2 times as much as clipping. Facility costs were the most significant contributor to intracranial clipping costs (60.2%), followed by supplies (18.3%). Supplies were the greatest cost contributor to coiling costs (43.2%), followed by facility (40.0%); similarly, supplies were the greatest portion of costs in flow diversion (57.5%), followed by facility (28.5%). Cost differences for aneurysm location, rupture status, American Society of Anesthesiologists (ASA) grade, and discharge disposition could be identified, with variability depending on surgical procedure. A multivariate analysis showed that rupture status, surgical procedure type, ASA status, discharge disposition, and year of surgery all significantly affected cost (p < 0.0001). CONCLUSIONS Facility utilization and supplies constitute the majority of total costs in aneurysm treatment strategies, but significant variation exists depending on surgical approach, rupture status, and patient discharge disposition. Developing and implementing approaches and protocols to improve resource utilization are important in reducing costs while maintaining high-quality patient care.
Assuntos
Procedimentos Endovasculares/economia , Custos de Cuidados de Saúde , Aneurisma Intracraniano/economia , Aneurisma Intracraniano/cirurgia , Stents Metálicos Autoexpansíveis/economia , Instrumentos Cirúrgicos/economia , Adulto , Idoso , Estudos de Coortes , Procedimentos Endovasculares/tendências , Feminino , Custos de Cuidados de Saúde/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/tendências , Instrumentos Cirúrgicos/tendências , Resultado do TratamentoRESUMO
Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.
Assuntos
Genômica/métodos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirurgia , Meningioma/genética , Meningioma/cirurgia , Neurocirurgiões/educação , Biomarcadores Tumorais/genética , Humanos , Fator 4 Semelhante a Kruppel , Mutação/genética , Neurofibromina 2/genética , Neurocirurgiões/tendências , Receptor Smoothened/genéticaRESUMO
BACKGROUND: Fixation of the electrode during deep brain stimulation (DBS) surgery is an important aspect of the procedure. We have developed an alternative method for securing leads that utilizes a titanium hemoclip and cement. This technique is described, and the rates of complications are compared to conventional methods of securing leads. METHODS: A total of 291 DBS operations performed by a single surgeon were retrospectively analyzed. We reviewed medical records to look for complications. We compared rates of complications based on the technique used. Re sults: 9 patients (3.1%) developed surgical site infections (SSIs), 4 (1.3%) with SSI of the internal pulse generator pocket. Of the 5 SSIs around the leads, none occurred with StimLoc and 5 (1.1%) with the novel technique. Eight patients (2.7%) required surgical readjustment of the DBS leads due to suboptimal clinical benefit; all 8 (1.8%) occurred with the novel technique. Four patients (1.4%) had lead fractures, 2 (2.2%) with StimLoc and 2 (0.5%) with the novel technique. CONCLUSIONS: We described a method for securing DBS leads and showed an acceptable incidence of hardware complications when compared to the conventional method. We feel this technique has improved cosmetic results and should be considered as a method for securing DBS leads.
Assuntos
Estimulação Encefálica Profunda/métodos , Eletrodos Implantados/efeitos adversos , Transtornos dos Movimentos/terapia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Falha de Equipamento , Humanos , Incidência , Estudos RetrospectivosRESUMO
Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.
Assuntos
Tomada de Decisão Clínica/métodos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Adulto JovemRESUMO
Previous human antibody studies have shown that the human VH1-46 antibody variable gene segment encodes much of the naturally occurring human B cell response to rotavirus and is directed to virus protein 6 (VP6). It is currently unknown why some of the VH1-46-encoded human VP6 monoclonal antibodies inhibit viral transcription while others do not. In part, there are affinity differences between antibodies that likely affect inhibitory activity, but we also hypothesize that there are differing modes of binding to VP6 that affect the ability to block the transcriptional pore on double-layered particles. Here, we used a hybrid method approach for antibody epitope mapping, including single-particle cryo-electron microscopy (cryo-EM) and enhanced amide hydrogen-deuterium exchange mass spectrometry (DXMS) to determine the location and mode of binding of a VH1-46-encoded antibody, RV6-25. The structure of the RV6-25 antibody-double-layered particle (DLP) complex indicated a very complex binding pattern that revealed subtle differences in accessibility of the VP6 epitope depending on its position in the type I, II, or III channels. These subtle variations in the presentation or accessibility of the RV VP6 capsid layer led to position-specific differences in occupancy for binding of the RV6-25 antibody. The studies also showed that the location of binding of the noninhibitory antibody RV6-25 on the apical surface of RV VP6 head domain does not obstruct the transcription pore upon antibody binding, in contrast to binding of an inhibitory antibody, RV6-26, deeper in the transcriptional pore.
Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Proteínas do Capsídeo/imunologia , Epitopos/imunologia , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação de Anticorpos , Biopolímeros/imunologia , Microscopia Crioeletrônica , Primers do DNA , Epitopos/química , Espectrometria de Massas , Dados de Sequência MolecularRESUMO
BACKGROUND: Grafts available for posterior fossa dural reconstruction after Chiari decompression surgery include synthetic, xenograft, allograft, and autograft materials. The reported rates of postoperative pseudomeningocele and cerebrospinal fluid leak vary, but so far, no dural patch material or technique has sufficiently eliminated these problems. OBJECTIVE: To compare the incidence of graft-related complications after posterior fossa surgery using AlloDerm alone vs AlloDerm with a DuraGen underlay. METHODS: We performed a retrospective single-center study of a cohort of 106 patients who underwent Chiari decompression surgery by a single surgeon from 2014 through 2021. Age, sex, body mass index, tonsillar descent, syrinx formation, type of dural graft, and follow-up data were analyzed using univariate and χ2 statistical tests. RESULTS: The AlloDerm-only group had a percutaneous cerebrospinal fluid (CSF) leak rate of 8.6% vs a 0% rate in the dual graft group (P = .037). At initial follow-up, there was a 15.5% combined rate of pseudomeningocele formation plus CSF leak in the AlloDerm-only group vs 18.8% in the AlloDerm + DuraGen group (P = .659). However, the pseudomeningoceles were larger in the AlloDerm-only cohort (45.5 vs 22.4 mm anteroposterior plane, P = .004), and 5 patients in this group required operative repair (56%). All pseudomeningoceles resolved without reoperation in the AlloDerm + DuraGen group (P = .003). CONCLUSION: The use of a DuraGen underlay with a sutured AlloDerm dural patch resulted in significantly fewer CSF-related complications and eliminated the need for reoperation compared with AlloDerm alone. This single-center study provides evidence that buttressing posterior fossa dural grafts with a DuraGen underlay may decrease the risk of postoperative complications.
Assuntos
Malformação de Arnold-Chiari , Rinorreia de Líquido Cefalorraquidiano , Procedimentos de Cirurgia Plástica , Humanos , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Estudos Retrospectivos , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Vazamento de Líquido Cefalorraquidiano/complicações , Rinorreia de Líquido Cefalorraquidiano/etiologia , Malformação de Arnold-Chiari/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
Smooth symmetric facial muscle function is important for social interactions. When lesions of the facial nerve occur, achieving complete restoration of balanced and spontaneous facial function can be challenging. In this video, the authors demonstrate the surgical details and long-term follow-up of a masseter-to-facial nerve transfer in a 3-year-old girl who had insidious onset of a left facial palsy due to a facial nerve schwannoma. After resection, she underwent distal nerve repair with a masseter-to-zygomatic branch transfer. She demonstrated decreased lagophthalmos and good activation and excursion on the left side with near symmetry to the right side, but lacked left frontalis function. The video can be found here: https://stream.cadmore.media/r10.3171/2022.9.FOCVID22107.
RESUMO
OBJECTIVE: Minimally invasive surgery (MIS) techniques have advanced the treatment of metastatic diseases to the spine. The objective of this review is to describe clinical outcomes, benefits, and complications of these techniques. METHODS: All relevant clinical studies describing the role of MIS, computer-assisted navigation (CAN), robot-assisted (RA) procedures, and laser interstitial thermal therapy (LITT) in the treatment of metastatic spine diseases were identified from PubMed, MEDLINE, and relevant article bibliographies. RESULTS: For MIS articles, we filtered 1480 results and identified 26 studies. For CAN, we searched 464 articles to identify 18 articles for review. For RA, we searched 321 results to identify 7 studies for review. For LITT, we identified 21 articles for review. CONCLUSIONS: MIS for the treatment of spine metastasis has significant potential benefits in reducing surgical site infections, hospital stay, and blood loss without compromising instrument accuracy or overall outcomes. Overall, MIS and its adjuncts have the potential to reduce the risks involved in the treatment of patients with metastatic disease to the spinal column without compromising the benefits of decompression and stabilization of the spine.
Assuntos
Fusão Vertebral , Neoplasias da Coluna Vertebral , Humanos , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Fusão Vertebral/métodos , Neoplasias da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia , Resultado do TratamentoRESUMO
Traumatic spinal cord injury is a common neurologic insult worldwide that can result in severe disability. Early stabilization of the patient's airway, breathing, and circulation as well as cervical and thoracolumbar spinal immobilization is necessary to prevent additional injury and optimize outcomes. Computed tomography (CT) scan and magnetic resonance imaging (MRI) of the spinal column can assist with determining the extent of bony and ligamentous injury, which will guide surgical management. With or without surgical intervention, patients with spinal cord injury require intensive care unit management and close observation to monitor for potential complications.
Assuntos
Traumatismos da Medula Espinal , Humanos , Masculino , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapiaRESUMO
STUDY DESIGN: Review article. OBJECTIVES: There have been substantial increases in the utilization of complex spinal surgery in the last 20 years. Spinal instrumented surgery is associated with high costs as well as significant variation in approach and care. The objective of this manuscript is to identify and review drivers of instrumented spine surgery cost and explain how surgeons can reduce costs without compromising outcome. METHODS: A literature search was conducted using PubMed. The literature review returned 217 citations. 27 publications were found to meet the inclusion criteria. The relevant literature on drivers of spine instrumented surgery cost is reviewed. RESULTS: The drivers of cost in instrumented spine surgery are varied and include implant costs, complications, readmissions, facility-based costs, surgeon-driven preferences, and patient comorbidities. Each major cost driver represents an opportunity for potential reductions in cost. With high resource utilization and often uncertain outcomes, spinal surgery has been heavily scrutinized by payers and hospital systems, with efforts to reduce costs and standardize surgical approach and care pathways. CONCLUSIONS: Education about cost and commitment to standardization would be useful strategies to reduce cost without compromising patient-reported outcomes after instrumented spinal fusion.
RESUMO
Introduction Anterior cervical discectomy and fusions (ACDFs) are generally limited to the levels causing neurological symptoms, but whether adjacent asymptomatic levels should be included if they demonstrate severe radiographic degeneration is a matter of controversy. We evaluated whether asymptomatic preoperative magnetic resonance imaging (MRI) abnormalities at adjacent levels were predictive of reoperation for symptomatic adjacent-segment degeneration (ASD) after the initial ACDF. Methods We reviewed patients treated with ACDF in 2000-2010 who had MRIs preoperatively and again ≥3 years after the index surgery to evaluate new neurological symptoms. Patients were stratified by ASD severity score, calculated based on MRI features. The associations between preoperative ASD severity score and reoperation for ASD were evaluated with logistic and Cox regressions after adjusting for covariates. Results Of 1038 patients who underwent ACDF, 96 (9%) had MRI evaluation ≥3 years postoperatively (mean follow-up 78 months). Of the 195 adjacent segments evaluated, 14 (7%) were included in subsequent fusion procedures. The 10-year surgery-free survival estimate was 82.7% (73.4-93.2%). After adjusting for covariates, ASD severity scores were predictive of reoperation only for patients with the highest score (hazard ratio [HR] 4.5 [1.0-19.8]) and those with foraminal stenosis (HR 4.2 [.4-12.7]). However, the prevalence of reoperation for ASD in these groups was only 16% and 15%, respectively. Conclusion The prevalence of reoperation for ASD was low for patients who presented with new symptoms ≥3 years after the index ACDF. Our findings do not support including asymptomatic levels in an anterior fusion construct, even if severe MRI abnormalities are present preoperatively.
RESUMO
BACKGROUND: Adjacent-segment disease (ASD) is a well-described long-term complication after lumbar fusion. There is a lack of consensus about the risk factors for development of ASD, but identifying them could improve surgical outcomes. Our goal was to analyze the effect of patient characteristics and radiographic parameters on the development of symptomatic ASD requiring revision surgery after posterior lumbar fusion. METHODS: In this retrospective cohort study, we identified patients who underwent lumbar fusion surgery and revision surgery from May 2012 to November 2018 using an institutional lumbar fusion registry. Patients having both pre- and post-operative upright radiographs were included in the study. Revision surgeries for which the index operation was performed at an outside hospital were excluded from analysis. Univariate analysis was conducted on candidate variables, and variables with P< 0.2 were selected for multivariate logistic regression. RESULTS: Of the 106 patients identified, 21 required reoperation (29 months average follow-up). Age >65 years (OR 4.14, 95% CI 1.46-11.76, P= 0.008), body mass index (BMI) >34 (OR 1.13, 95% CI 1.04-1.23, P = 0.004), and osteoporosis (OR 14, 95% CI 1.38-142.42, P = 0.03) were independent predictors of reoperation in the multivariate analysis. Increased facet diastasis at fusion levels (OR 0.60, 95% CI 0.42-0.85, P = 0.004) was associated with reduced reoperation rates. Change in segmental LL at the index operation level, rostral and caudal facet diastasis, vacuum discs, and T2 hyperintensity in the facets were not predictors of reoperation. CONCLUSION: Age >65, BMI >34, and osteoporosis were independent predictors of adjacent-segment reoperation after lumbar spinal fusion.
RESUMO
BACKGROUND: Sedating antispastic medications and focal therapies like botulinum toxin are the most common therapies for spasticity but are temporary and must be performed continuously for a principally static neurological insult. Alternatively, highly selective partial neurectomies (HSPNs) may reduce focal spasticity more permanently. OBJECTIVE: To quantify the change in spasticity after HSPN and assess patient satisfaction. METHODS: We retrospectively reviewed the records of patients with upper- and/or lower-extremity spasticity treated with HSPN from 2014 to 2018. Only cases with a modified Ashworth scale (MAS) score independently determined by a physical therapist were included. Pre- and postoperative MAS, complications, and patient satisfaction were evaluated. RESULTS: The 38 patients identified (24 male, 14 female; mean age 49 yr) underwent a total of 88 procedures for focal spasticity (73% upper extremity, 27% lower extremity). MAS scores were adjusted to a 6-point scale for evaluation. The mean preoperative and final postoperative follow-up adjusted MAS scores were 3.6 and 1.7, respectively (P < .001), which represents average MAS less than 1+. Positive, neutral, and worse results were described by 91%, 6%, and 3% of patients, respectively. Four patients requested revision surgery. No perioperative complications were encountered. CONCLUSION: This is the first North American series to analyze HSPN for spasticity and the only series based on independent evaluation results. HSPN surgery demonstrated objective short- and long-term reduction in spasticity with minimal morbidity and excellent patient satisfaction.
Assuntos
Toxinas Botulínicas Tipo A , Acidente Vascular Cerebral , Denervação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Helicobacter pylori VacA is a pore-forming toxin that causes multiple alterations in human cells and contributes to the pathogenesis of peptic ulcer disease and gastric cancer. The toxin is secreted by H. pylori as an 88 kDa monomer (p88) consisting of two domains (p33 and p55). While an X-ray crystal structure for p55 exists and p88 oligomers have been visualized by cryo-electron microscopy, a detailed analysis of p33 has been hindered by an inability to purify this domain in an active form. In this study, we expressed and purified a recombinant form of p33 under denaturing conditions and optimized conditions for the refolding of the soluble protein. We show that refolded p33 can be added to purified p55 in trans to cause vacuolation of HeLa cells and inhibition of IL-2 production by Jurkat cells, effects identical to those produced by the p88 toxin from H. pylori. The p33 protein markedly enhances the cell binding properties of p55. Size exclusion chromatography experiments suggest that p33 and p55 assemble into a complex consistent with the size of a p88 monomer. Electron microscopy of these p33/p55 complexes reveals small rod-shaped structures that can convert to oligomeric flower-shaped structures in the presence of detergent. We propose that the oligomerization observed in these experiments mimics the process by which VacA oligomerizes when in contact with membranes of host cells.
Assuntos
Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica , Microscopia Crioeletrônica , Ciclofosfamida , Dactinomicina , Doxorrubicina , Células HeLa , Humanos , Interleucina-2/genética , Interleucina-2/metabolismo , Toxinas Biológicas/genética , Toxinas Biológicas/metabolismo , Vincristina , Raios XRESUMO
OBJECTIVE: Traditional animal models of nerve injury use controlled crush or transection injuries to investigate nerve regeneration; however, a more common and challenging clinical problem involves closed traction nerve injuries. The authors have produced a precise traction injury model and sought to examine how the pathophysiology of stretch injuries compares with that of crush and transection injuries. METHODS: Ninety-five late-adolescent (8-week-old) male mice underwent 1 of 7 injury grades or a sham injury (n > 10 per group): elastic stretch, inelastic stretch, stretch rupture, crush, primary coaptation, secondary coaptation, and critical gap. Animals underwent serial neurological assessment with sciatic function index, tapered beam, and von Frey monofilament testing for 48 days after injury, followed by trichrome and immunofluorescent nerve histology and muscle weight evaluation. RESULTS: The in-continuity injuries, crush and elastic stretch, demonstrated different recovery profiles, with more severe functional deficits after crush injury than after elastic stretch immediately following injury (p < 0.05). However, animals with either injury type returned to baseline performance in all neurological assessments, accompanied by minimal change in nerve histology. Inelastic stretch, a partial discontinuity injury, produced more severe neurological deficits, incomplete return of function, 47% ± 9.1% (mean ± SD) reduction of axon counts (p < 0.001), and partial neuroma formation within the nerve. Discontinuity injuries, including immediate and delayed nerve repair, stretch rupture, and critical gap, manifested severe, long-term neurological deficits and profound axonal loss, coupled with intraneural scar formation. Although repaired nerves demonstrated axon regeneration across the gap, rupture and critical gap injuries demonstrated negligible axon crossing, despite rupture injuries having healed into continuity. CONCLUSIONS: Stretch-injured nerves present unique pathology and functional deficits compared with traditional nerve injury models. Because of the profound neuroma formation, stretch injuries represent an opportunity to study the pathophysiology associated with clinical injury mechanisms. Further validation for comparison with human injuries will require evaluation in a large-animal model.
RESUMO
Background D-dimers are serum acute-phase proteins with a role in mediating inflammation that may be used as biomarkers for the prediction of deep vein thrombosis. Recent studies have shown that D-dimers can be used to predict prognosis and stratify risk in neurosurgical patients; however, a comparative analysis across diagnostic subtypes has yet to be performed. Methods A bioinformatics analysis evaluated neurosurgical patients with admission D-dimer levels between 2008 and 2017. Nonroutine disposition (e.g., skilled nursing facility, rehabilitation, other hospital, mortality) was primarily evaluated. Results A total of 1,854 patients (mean age 55.1±18.2 years, 55.4% male; mean admission D-dimer 4.83±7.78 µg/ml) were identified. Patient diagnoses included vascular (27.1%), trauma (16.4%), multiple diagnoses (15.7%), spine (15.6%), tumor (13.0%), and other (12.2%) causes. Univariate analysis showed that older age (p=0.0001), higher American Society of Anesthesiologists (ASA) score (p=0.0001), lower Glasgow Coma Scale (GCS) score (p=0.0001), diagnosis type (p=0.0001), longer length of stay (LOS) (p=0.0001), higher infection rate (p=0.0001), surgery in the past year (p=0.02), and higher D-dimer levels (3.4±4.9 vs. 5.4±8.7 µg/ml, p=0.0001) were associated with nonroutine disposition. Multivariate logistic regression showed that elevated D-dimers were independently associated with a greater relative risk of nonroutine disposition (relative risk [RR] 1.026, 95% CI 1.02-1.033, p=0.0001). Conclusions Elevated admission D-dimer values were independently associated with a 3% increased risk of nonroutine disposition per D-dimer unit after accounting for other factors. These results suggest that D-dimer values may help in stratifying patient risk models despite clinical heterogeneity. Further refinement of neurosurgical patient risk models using clinical variables and biomarkers may aid in resource allocation and early warning.
RESUMO
BACKGROUND: Occipitocervical instability may result from transcondylar resection of the occipital condyle. Initially, patients may be able to maintain a neutral alignment but severe occipitoatlantal subluxation may subsequently occur, with cranial settling, spinal cord kinking, and neurological injury. OBJECTIVE: To evaluate the ability of posterior fixation constructs to prevent progression to severe deformity after radical unilateral condylectomy. METHODS: Eight human cadaveric specimens (Oc-C2) underwent biomechanical testing to compare stiffness under physiological loads (1.5 N m). A complete unilateral condylectomy was performed to destabilize one Oc-C1 joint, and the contralateral joint was left intact. Unilateral Oc-C1 or Oc-C2 constructs on the resected side and bilateral Oc-C1 or Oc-C2 constructs were tested. RESULTS: The bilateral Oc-C2 construct provided the greatest stiffness, but the difference was only statistically significant in certain planes of motion. The unilateral constructs had similar stiffness in lateral bending, but the unilateral Oc-C1 construct was less stiff in axial rotation and flexion-extension than the unilateral Oc-C2 construct. The bilateral Oc-C2 construct was stiffer than the unilateral Oc-C2 construct in axial rotation and lateral bending, but there was no difference between these constructs in flexion-extension. CONCLUSION: Patients who undergo a complete unilateral condylectomy require close surveillance for occipitocervical instability. A bilateral Oc-C2 construct provides suitable biomechanical strength, which is superior to other constructs. A unilateral construct decreases abnormal motion but lacks the stiffness of a bilateral construct. However, given that most patients undergo a partial condylectomy and only a small proportion of patients develop instability, there may be scenarios in which a unilateral construct may be appropriate, such as for temporary internal stabilization.