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Spinal cord injury (SCI) is a devastating condition that can cause significant motor and sensory impairment. Microglia, the central nervous system's immune sentinels, are known to be promising therapeutic targets in both SCI and neurodegenerative diseases. The most effective way to deliver medications and control microglial inflammation is through nanovectors; however, because of the variability in microglial morphology and the lack of standardized techniques, it is still difficult to precisely measure their activation in preclinical models. This problem is especially important in SCI, where the intricacy of the glia response following traumatic events necessitates the use of a sophisticated method to automatically discern between various microglial cell activation states that vary over time and space as the secondary injury progresses. We address this issue by proposing a deep learning-based technique for quantifying microglial activation following drug-loaded nanovector treatment in a preclinical SCI model. Our method uses a convolutional neural network to segment and classify microglia based on morphological characteristics. Our approach's accuracy and efficiency are demonstrated through evaluation on a collection of histology pictures from injured and intact spinal cords. This robust computational technique has potential for analyzing microglial activation across various neuropathologies and demonstrating the usefulness of nanovectors in modifying microglia in SCI and other neurological disorders. It has the ability to speed development in this crucial sector by providing a standardized and objective way to compare therapeutic options.
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Purpose: Glioblastoma is the most common type of primary brain malignancy and has a poor prognosis. The standard treatment strategy is based on maximal safe surgical resection followed by radiotherapy and chemotherapy. Surgical resection can be optimized by using 5-delta-aminolevulinic acid (5-ALA)-induced fluorescence, which is the current mainstay. Although 5-ALA-induced fluorescence has gained general acceptance, it is also limited by inter-observer variability and non-standardized fluorescence parameters. We present a new software for processing images analysis to better recognize the tumor infiltration margins using an intraoperative immediate safety map of 5-ALA-induced fluorescence. We tested this in a brain model using a commercial surgical exoscope. Methods: A dedicated software GLIOVIS (ACQuF-II, Advanced Colorimetry-based Quantification of Fluorescence) was designed for processing analysis of images taken on the Intraoperative Orbital Camera Olympus Orbeye (IOC) to determine the relative quantification of Protoporphyrin IX (5-ALA metabolite) fluorescence. The software allows to superpose the new fluorescence intensity map and the safety margins over the original images. The software was tested on gel-based brain models. Results: Two surrogate models were developed: PpIX agarose gel-integrated in gelatin-based brain model at different scales (1:25 and 1:1). The images taken with the IOC were then processed using GLIOVIS. The intensity map and safety margins could be obtained for all available models. Conclusions: GLIOVIS for 5-ALA-guided surgery image processing was validated on various gelatin-based brain models. Different levels of fluorescence could be qualitatively digitalized using this technique. These results need to be further confirmed and corroborated in vivo and validated clinically in order to define a new standard of care for glioblastoma resection.
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BACKGROUND: To date, no shared algorithms with the aim of guiding surgical strategy in complex cases of degenerative cervical myelopathy (DCM) exist. Our purpose is to present the Cervical Surgical Score (CSS) which could help in identifying complex DCM cases, suggesting a surgical strategy. METHODS: We created the CSS based on multidisciplinary and literature-focused discussions, based on eight parameters including number of levels of cervical pathology and myelopathy, type and predominance of compression and grade of clinical myelopathy. We prospectively enrolled surgical DCM patients in a 15-months period, collecting clinical and radiological data. During outpatient clinic a specific surgical indication was offered to DCM patients. To validate the score, each outpatient clinic surgical indication was compared a posteriori to the one that resulted from multidisciplinary CSS scoring, focusing on patients for which both an anterior and posterior approach were considered suitable. RESULTS: A total of 100 patients operated on for DCM at our Institution between December 2021 and February 2023 were prospectively enrolled. In 53% of patients the pathology was present at more than two levels. According to CSS calculation, 14% of patients resulted in the "grey zone", where both an anterior and posterior approach were deemed feasible. Among them, in 42.8% of cases the CSS allowed a modification of the originally planned surgery. Looking at outcome, an improvement of m-JOA score in 62% of patients was disclosed. CONCLUSIONS: This preliminary study showed the reliability and usefulness of CSS in detecting complex DCM cases, requiring further analysis by expert spine surgeons, suggesting a surgical strategy.
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Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase (MGMT)-methylated GBM cases. However, approximately 20% of patients with MGMT-unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients' clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.
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Glioblastoma , MicroRNAs , Humanos , Glioblastoma/metabolismo , MicroRNAs/metabolismo , Dacarbazina/uso terapêutico , Relevância Clínica , Temozolomida/farmacologia , Temozolomida/uso terapêuticoRESUMO
Anterior Visual Pathway (aVP) damage may be linked to diverse inflammatory, degenerative and/or vascular conditions. Currently however, a standardized methodological framework for extracting MRI biomarkers of the aVP is not available. We used high-resolution, 3-D MRI data to generate a probabilistic anatomical atlas of the normal aVP and its intraorbital (iOrb), intracanalicular (iCan), intracranial (iCran), optic chiasm (OC), and tract (OT) subdivisions. We acquired 0.6 mm3 steady-state free-precession images from 24 healthy participants using a 3 T scanner. aVP masks were obtained by manual segmentation of each aVP subdivision. Mask straightening and normalization with cross-sectional area (CSA) preservation were obtained using scripts developed in-house. A probabilistic atlas ("aVP-24") was generated by averaging left and right sides of all subjects. Leave-one-out cross-validation with respect to interindividual variability was performed employing the Dice Similarity Index (DSI). Spatially normalized representations of the aVP subdivisions were generated. Overlapping CSA values before and after normalization demonstrate preservation of the aVP cross-section. Volume, length, CSA, and ellipticity index (ε) biometrics were extracted. The aVP-24 morphology followed previous descriptions from the gross anatomy. Atlas spatial validation DSI scores of 0.85 in 50% and 0.77 in 95% of participants indicated good generalizability across the subjects. The proposed MRI standardization framework allows for previously unavailable, geometrically unbiased biometric data of the entire aVP and provides the base for future spatial-resolved, group-level investigations.
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Doenças Vasculares , Vias Visuais , Humanos , Imageamento por Ressonância Magnética/métodos , Quiasma Óptico , Biometria , Processamento de Imagem Assistida por Computador/métodosRESUMO
Listeria monocytogenes is a Gram-positive pathogenic bacterium which can be found in soil or water. Infection with the microorganism can occur after ingestion of contaminated food products. Small and large outbreaks of listeriosis have been described in the past. L. monocytogenes can cause a number of different clinical syndromes, most frequently sepsis, meningitis, and rhombencephalitis, particularly in immunocompromised hosts. L. monocytogenes systemic infections can develop following tissue penetration across the gastrointestinal tract or to hematogenous spread to sterile sites, possibly evolving towards bacteremia. L. monocytogenes only rarely causes bone or joint infections, usually in the context of prosthetic material that can provide a site for bacterial seeding. We describe here the clinical findings of invasive listeriosis, mainly focusing on the diagnosis, clinical management, and treatment of bone and vertebral infections occurring in the context of invasive listeriosis.
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INTRODUCTION: In recent years, introduction of the exoscope system has been responsible for a new era of optics in surgery. Such a system has started to be widely used in neurosurgery. More recently, the exoscope has also been increasingly used for spinal procedures. Thus, we aimed to explore the potential for exoscope-assisted spinal procedures and define the advantages and drawbacks of implementing the system into our daily routine. METHODS: To achieve the aim of the study, we retrospectively reviewed the case series of patients treated by a senior surgeon and analyzed the results, complications, and operative time. The operating times were compared between the exoscope-assisted procedures and microscope-assisted procedures. RESULTS: A total of 24 spinal procedure were performed with the exoscope in a 2-month period. In this first patient series performed by a single surgeon without experience with the exoscope, the learning curve seemed to be relatively low, with mastery of the instrument achieved after the performance of only a few cases. Comparing the cases after the plateau of the learning curve had been reached with those performed during the still active phase of the learning curve, a significant difference was found in the operative times. No statistically significant difference was detected in terms of blood loss or intraoperative complications. CONCLUSIONS: Based on our first experience, use of the exoscope shows promising potential for opening up new frontiers in spinal microsurgery. In addition, it has a low learning curve for experienced surgeons.
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Curva de Aprendizado , Procedimentos Neurocirúrgicos , Humanos , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/métodos , Coluna Vertebral/cirurgia , Microscopia , Microcirurgia/métodosRESUMO
OBJECTIVE: Among the already difficult management of neuro-oncological patients, the elderly population remains vulnerable. Because of the pathology and the comorbidities, they present a significantly higher rate of medical issues related to surgical management. Despite this, the surgical option, if feasible, remains the gold standard in these patients, and an Enhanced Recovery After Surgery (ERAS) protocol could improve the postoperative safety of the patients. With this purpose, we prepared this study with the aim of defining the postoperative hospital length of stay (LOS), but also of evaluating the postoperative morbidity, perioperative complications, and postoperative pain scores. METHODS: This was a retrospective, single-cohort study performed at an academic hospital (Department of Neurosurgery, Neurocenter of South Switzerland, Switzerland) on elderly patients who underwent craniotomy for glioblastoma. Patients were enrolled in a novel ERAS protocol from January 2022 to December 2022. Since this is a feasibility study and a direct comparison was not possible, we used a historical cohort of elderly patients who had undergone elective craniotomy surgery for glioblastoma as a control group. RESULTS: A total of 19 patients treated in our center for glioblastoma multiforme (GBM) who were aged over 75 years were included in this study. Among those, seven were newly recruited patients included in the ERAS protocol, while the remaining twelve were part of a historical cohort of previously treated patients. From a statistical point of view, the two cohorts were comparable in terms of baseline demographics. In the follow-up, it was shown that in the ERAS group, there was a reduction in the use of opioids after the surgical procedures that could be seen at 30 days (36.2% vs. 71.7%, p < 0.001), but also at 3 months, after surgery (33.0% vs. 80.0%, p < 0.001). A significant difference has also been documented in terms of mobilization and ambulation: compared to the historical cohort, in the ERAS group, there was a higher rate of mobilization (60.0% vs. 10.0%, p < 0.001), but also of ambulation (36.1% vs. 10.0%, p < 0.001). CONCLUSIONS: The ERAS protocol for the management of glioblastoma in elderly patients seems to be an effective option for reducing LOS in the hospital, as well as for reducing the number of days spent in the ICU, improving the general recovery of the patient, and reducing the costs associated with hospitalization.
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Introduction: Intracranial aneurysms occur in 3%-5% of the general population. While the precise biological mechanisms underlying the formation, growth, and sudden rupture of intracranial aneurysms remain partially unknown, recent research has shed light on the potential role of inflammation in aneurysm development and rupture. In addition, there are ongoing investigations exploring the feasibility of employing new drug therapies for controlling the risk factors associated with aneurysms. CD68, a glycosylated glycoprotein and the human homolog of macrosialin, is prominently expressed in monocyte/macrophages within inflamed tissues and has shown potential application in oncology. An observational study was conducted with the aim of comparing the histological characteristics of aneurysm walls with preoperative MRI scans, specifically focusing on CD68 activity. Method: An observational pilot study was conducted to investigate the histological characteristics of the aneurysm wall that could be potentially associated with aneurysm growth and rupture. A total of 22 patients diagnosed with ruptured and unruptured intracranial aneurysms who had undergone conventional clipping between January 2017 and December 2022 were included in the study. Results: A histopathological analysis of the aneurysm wall was performed in all patients, particularly focusing on the presence of CD68. A preoperative MRI with gadolinium was conducted in 10 patients with unruptured aneurysms and six patients with ruptured aneurysms. An emergency clipping was performed in the remaining six patients. The results showed that CD68 positivity and wall enhancement were significantly associated with intracranial aneurysm wall degeneration, growth, and rupture. Conclusion: The histological and radiological inflammatory findings observed in the wall of cerebral aneurysms, as well as the CD68 positivity, are significantly associated with the risk of intracranial aneurysm growth and rupture. This study highlights the crucial importance of considering clinical and medical data when making treatment decisions for intracranial aneurysms. Furthermore, it emphasizes the relevance of evaluating wall enhancement in MRI scans as part of the diagnostic and prognostic process.
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Subarachnoid hemorrhage (SAH) represents a severe acute event with high morbidity and mortality due to the development of early brain injury (EBI), secondary delayed cerebral ischemia (DCI), and shunt-related hydrocephalus. Secondary events (SSE) such as neuroinflammation, vasospasm, excitotoxicity, blood-brain barrier disruption, oxidative cascade, and neuronal apoptosis are related to DCI. Despite improvement in management strategies and therapeutic protocols, surviving patients frequently present neurological deficits with neurocognitive impairment. The aim of this paper is to offer to clinicians a practical review of the actually documented pathophysiological events following subarachnoid hemorrhage. To reach our goal we performed a literature review analyzing reported studies regarding the mediators involved in the pathophysiological events following SAH occurring in the cerebrospinal fluid (CSF) (hemoglobin degradation products, platelets, complement, cytokines, chemokines, leucocytes, endothelin-1, NO-synthase, osteopontin, matricellular proteins, blood-brain barrier disruption, microglia polarization). The cascade of pathophysiological events secondary to SAH is very complex and involves several interconnected, but also distinct pathways. The identification of single therapeutical targets or specific pharmacological agents may be a limited strategy able to block only selective pathophysiological paths, but not the global evolution of SAH-related events. We report furthermore on the role of heparin in SAH management and discuss the rationale for use of intrathecal heparin as a pleiotropic therapeutical agent. The combination of the anticoagulant effect and the ability to interfere with SSE theoretically make heparin a very interesting molecule for SAH management.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Heparina/uso terapêutico , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/complicações , Infarto Cerebral/complicações , Isquemia Encefálica/complicaçõesRESUMO
Glioblastoma multiforme (GBM) remains one of the tumors with the worst prognosis. In recent years, a better overall survival (OS) has been described in cases subjected to Gross Total Resection (GTR) that were presenting hypermethylation of Methylguanine-DNA methyltransferase (MGMT) promoter. Recently, also the expression of specific miRNAs involved in MGMT silencing has been related to survival. In this study, we evaluate MGMT expression by immunohistochemistry (IHC), MGMT promoter methylation and miRNA expression in 112 GBMs and correlate the data to patients' clinical outcomes. Statistical analyses demonstrate a significant association between positive MGMT IHC and the expression of miR-181c, miR-195, miR-648 and miR-767.3p between unmethylated cases and the low expression of miR-181d and miR-648 and between methylated cases and the low expression of miR-196b. Addressing the concerns of clinical associations, a better OS has been described in presence of negative MGMT IHC, in methylated patients and in the cases with miR-21, miR-196b overexpression or miR-767.3 downregulation. In addition, a better progression-free survival (PFS) is associated with MGMT methylation and GTR but not with MGMT IHC and miRNA expression. In conclusion, our data reinforce the clinical relevance of miRNA expression as an additional marker to predict efficacy of chemoradiation in GBM.
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BACKGROUND: In the last years, laser interstitial thermal therapy (LITT) has started to be used also in neurosurgical setting. Its efficacy for intracranial pathologies, namely, tumors and epilepsy, has been widely demonstrated. However, the literature evidences about the use of LITT for spinal lesions are recent, and it is still a topic of discussion regarding its efficacy. Here, the authors sought to present a systematic review of the literature investigating the utility of LITT for spinal lesions. METHODS: Using PubMed, Scopus, and the Cochrane Library, the authors performed a systematic review of the literature focused on the use of spinal laser interstitial thermal therapy (sLITT). Included in the search were randomized controlled trials, cohort studies, and clinical series. Two independent reviewers conducted the study appraisal, data abstraction, and quality assessments of the studies. RESULTS: Out of the initial 134 studies, 6 met the inclusion criteria for the systematic review, resulting in a total of 206 patients. All the patients have been treated with sLITT for compressive spinal metastases. Most of the lesions were thoracic (88.8%). All the studies reported an effective local control of the disease with a reduction of epidural compression at 30 days. Complication rate was 12.6%, but most of them were transient conditions, and only 3.4% patients needed a revision surgery. CONCLUSION: sLITT is safe and provides effective local control for epidural compression from metastases, particularly in the thoracic spine. The authors propose considering sLITT as an alternative to open surgery in selected patients with spinal metastases.
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Neoplasias Encefálicas , Terapia a Laser , Compressão da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/complicações , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Coluna Vertebral , Lasers , Neoplasias Encefálicas/complicaçõesRESUMO
INTRODUCTION: Neurosurgery is one of the fields in which intraoperative imaging is paramount. One of these main imaging tools that have been acquiring the interest of the neurosurgical community is Ultrasound elastography (USE), which is an imaging technology sensitive to tissue stiffness. Here we present a systematic review of the use of USE in neurosurgery. EVIDENCE ACQUISITION: A systematic review of the literature has been performed, according to the PRISMA guideline, for the last 30 years on 3 different databases (MEDLINE, Scopus, and Cochrane), to gather all the studies on the use of ultrasound elastography for neurosurgical pathologies, including both clinical and laboratory studies. EVIDENCE SYNTHESIS: A total of 15 articles met the inclusion criteria. USE has widely and safely been used especially for oncological lesions (meningiomas and gliomas) and focal cortical dysplasia. However, there are also encouraging laboratory studies about its application for the management of traumatic brain injury, and ischemic stroke. CONCLUSIONS: This systematic review showed that, despite the lack of strong evidence, USE is a valid intraoperative tool, especially in oncological neurosurgery.
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Lesões Encefálicas Traumáticas , Técnicas de Imagem por Elasticidade , Glioma , Neurocirurgia , Humanos , Procedimentos Neurocirúrgicos/métodos , Glioma/cirurgia , Lesões Encefálicas Traumáticas/cirurgiaRESUMO
OBJECTIVE: The aim of our study is to report a multicenter experience in the treatment of IV and V grade arteriovenous malformations (AVMs) and to apply commonly used grading scales for surgical risk assessment for these vascular high-grade lesions. METHODS: Between January 2015 and December 2019, a retrospective study was conducted to identify patients undergoing microsurgical intervention for cAVMs at two Italian centers specialized in the treatment of vascular pathologies. Data on patients with Spetzler-Martin IV and V and with a score equal or more than 7 according to Lawton-Young classification were collected. Ruptured AVMs at admission were subsequently classified according to the new proposed AVICH classification. RESULTS: A total of 20 patients with high grade (IV and V) cAVMs were enrolled in the study and the average follow-up was 36.45 months. The outcome based on mRS was favorable in 65 % of cases. The pre-operative mRS was a factor influencing clinical outcome, as well as the number of bleedings preceding the treatment, age, and nidus characteristics. S-M IV, L-Y 3 and S-M supp 7 scores were associated with good outcome. Based on the AVICH classification, for ruptured cAVMs, having a score of 9 ore less was correlated to a postoperative mRS fewer or equal than 2. CONCLUSIONS: Surgical management for high-grade AVMs should be considered in highly selected patients with repeated bleeding or disabling symptoms. Classification systems provide an aid in selecting patients for surgery, also in grade IV and V. It is essential to establish common registers for the management of these complex vascular malformations.
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Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Hemorragia/cirurgia , Humanos , Malformações Arteriovenosas Intracranianas/cirurgia , Microcirurgia , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
PURPOSE: CT-guided percutaneous procedures involving the skull base and atlanto-axial cervical spine pose particular challenges due to high density of vital vascular and nervous structures and because the ideal needle trajectory often has a cranio-caudal obliquity different from the axial scan plane. We describe how the variable CT gantry tilt, combined with gantry-needle-target alignment technique, is used to obtain precise and safe needle placement in conventional and non-conventional approaches to the skull base and the atlanto-axial spine. METHODS: We retrospectively analyzed consecutive CT-guided needle accesses to the skull base and atlanto-axial spine performed for tissue sampling through fine-needle aspirates and core biopsies, cementoplasty of neoplastic lytic lesions of atlanto-axial spine, pain management injections, and dural puncture for cerebro-spinal fluid sampling. All the accesses were performed with the gantry-needle-target alignment technique. Procedural complications were recorded. RESULTS: Thirty-nine CT-guided procedures were analyzed. Paramaxillary approach was used in 15 cases, postero-lateral in 11, subzygomatic in 3. Nine non-conventional approach were performed: submastoid in 3 cases, suprazygomatic in 2, trans-nasal in 2, trans-mastoid in 1, and trans-auricular in 1. Two peri-procedural complications occurred: one asymptomatic and one resolved within 24 h. All the procedures were successfully completed with successful needle access to the target. CONCLUSION: The gantry tilt and gantry-needle-target alignment technique allows to obtain double-oblique needle accesses for CT-guided procedures involving the skull base and atlanto-axial cervical spine, minimizing uncertainty of needle trajectory and obtaining safe needle placement in conventional and non-conventional approaches.
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Vértebras Cervicais , Tomografia Computadorizada por Raios X , Vértebras Cervicais/diagnóstico por imagem , Cabeça , Humanos , Estudos Retrospectivos , Base do Crânio , Tomografia Computadorizada por Raios X/métodosRESUMO
INTRODUCTION: Cranial reconstruction (CR) is a neurosurgical procedure performed to restore the cranial vault after a decompressive craniectomy. There are contrasting reports from the literature about the complications related to the use of heterologous materials for CR in the pediatric population. In this study, the authors try to better define such a rate of adverse events for autologous and heterologous materials. MATERIALS AND METHODS: A systematic review of articles published up to December 2021 was performed. Studies were included if they reported the specific use of cranioplasty materials following craniectomy in patients younger than 18 years of age and had a minimum follow-up of at least 1 year. RESULTS: A total of 20 studies were selected. A total of 544 cases were included, of which 422 (77.6%) were with heterologous materials and 122 (22.4%) with autologous bone. The mean average age was 9.5 years. Polyetheretherketone and polymethylmethacrylate reported 29% and 33.3%, respectively, of complications, but only 3% and 5.6% of surgical revision. PHA reported a rate of 11.9%. Titanium reported 9.2% of complications and 4.1% of surgical revisions. Porous polyethylene had a complication rate of 36.4% and a revision rate of 0%. CONCLUSION: There is still no perfect material for CR. It seems that heterologous materials are superior to autologous bone for CR in children, and we may consider, whenever economic conditions will allow it, to use alloplastic material as first-line in small children.
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Craniectomia Descompressiva , Procedimentos de Cirurgia Plástica , Criança , Craniotomia/efeitos adversos , Craniectomia Descompressiva/efeitos adversos , Humanos , Complicações Pós-Operatórias/etiologia , Prevalência , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Crânio/cirurgiaRESUMO
Decompressive craniectomy is one of the most common neurosurgical procedures, usually performed after neuropathological disorders, such as traumatic brain injury (TBI), but also vascular accidents (strokes), erosive tumours, infections and other congenital abnormalities. This procedure is usually followed by the reconstruction of the cranial vault, which is also known as cranioplasty (CP). The gold-standard material for the reconstruction process is the autologous bone of the patient. However, this is not always a feasible option for all patients. Several heterologous materials have been created in the last decades to overcome such limitation. One of the most prominent materials that started to be used in CP is porous hydroxyapatite. PHA is a bioceramic material from the calcium phosphate family. It is already widely used in other medical specialties and only recently in neurosurgery. In this narrative review of the literature, we summarize the evidence on the use of PHA for cranial reconstruction, highlighting the clinical properties and limitations. We also explain how this material contributed to changing the concept of cranial reconstruction from reparative to regenerative surgery.