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Glioblastoma (GBM) is a primary CNS tumor that is highly lethal in adults and has limited treatment options. Despite advancements in understanding the GBM biology, the standard treatment for GBM has remained unchanged for more than a decade. Only 6.8% of patients survive beyond five years. Telomerase, particularly the hTERT promoter mutations present in up to 80% of GBM cases, represents a promising therapeutic target due to its role in sustaining telomere length and cancer cell proliferation. This review examines the biology of telomerase in GBM and explores potential telomerase-targeted therapies. We conducted a systematic review following the PRISMA-P guidelines in the MEDLINE/PubMed and Scopus databases, from January 1995 to April 2024. We searched for suitable articles by utilizing the terms "GBM", "high-grade gliomas", "hTERT" and "telomerase". We incorporated studies addressing telomerase-targeted therapies into GBM studies, excluding non-English articles, reviews, and meta-analyses. We evaluated a total of 777 records and 46 full texts, including 36 studies in the final review. Several compounds aimed at inhibiting hTERT transcription demonstrated promising preclinical outcomes; however, they were unsuccessful in clinical trials owing to intricate regulatory pathways and inadequate pharmacokinetics. Direct hTERT inhibitors encountered numerous obstacles, including a prolonged latency for telomere shortening and the activation of the alternative lengthening of telomeres (ALT). The G-quadruplex DNA stabilizers appeared to be potential indirect inhibitors, but further clinical studies are required. Imetelstat, the only telomerase inhibitor that has undergone clinical trials, has demonstrated efficacy in various cancers, but its efficacy in GBM has been limited. Telomerase-targeted therapies in GBM is challenging due to complex hTERT regulation and inadequate inhibitor pharmacokinetics. Our study demonstrates that, despite promising preclinical results, no Telomerase inhibitors have been approved for GBM, and clinical trials have been largely unsuccessful. Future strategies may include Telomerase-based vaccines and multi-target inhibitors, which may provide more effective treatments when combined with a better understanding of telomere dynamics and tumor biology. These treatments have the potential to be integrated with existing ones and to improve the outcomes for patients with GBM.
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Glioblastoma , Telomerasa , Telomerasa/antagonistas & inhibidores , Telomerasa/metabolismo , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Terapia Molecular Dirigida , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Telómero/metabolismo , Telómero/efectos de los fármacos , AnimalesRESUMEN
Secondary adrenal insufficiency (SAI) is an endocrine disorder due to impaired secretion of ACTH resulting from any disease affecting the pituitary gland. Glucocorticoid replacement therapy is mandatory to ensure patient survival, haemodynamic stability, and quality of life. In fact, a correct dose adjustement is mandatory due to the fact that inappropriately low doses expose patients to hypoadrenal crisis, while inappropriately high doses contribute to glucose metabolic and cardiovascular deterioration. This review analyses the current evidence from available publications on the epidemiology and aetiology of SAI and examines the association between glucocorticoid replacement therapy and glucometabolic and cardiovascular effects.
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Transbasal meningiomas1 are a rare group of tumors that grow intracranially, invade the skull base, and propagate extracranially; they are usually located at the level of the olfactory cribra and sphenoid wing.1-4 Transbasal tuberculum sellae meningiomas are a subset of these tumors, which extend into the suprasellar and sphenoid regions. The traditional transcranial approach for some transbasal meningiomas has recently evolved toward the transnasal endoscopic approach, which allows the removal of both the intranasal and intracranial components, reducing the manipulation of the optic nerves and neurovascular structures. Nevertheless, specific anatomical criteria must be present; the knowledge of specific anatomy5,6 and the surgeon's experience are fundamental for reaching the most favorable outcome.7-11 In this video, we present the case of a 50-year-old woman with a history of progressive visual impairment and scotoma in the left inferotemporal quadrant. Radiological examinations suggested a transbasal tuberculum meningioma that extended into the suprasellar region, sphenoid sinus, and optic canals. An endoscopic transtuberculum approach with intraoperative visual-evoked potentials12 was performed, allowing an early devascularization with the preservation of the superior hypophyseal arteries and the removal of the component extending in the medial portion of both optic canals. The postoperative MRI documented a gross total resection without complications. The patient reported an immediate improvement of the visual symptoms. Histopathology documented a meningioma (CNS World Health Organization grade 1) with bone invasion. The patient consented to the procedure and to the publication of her image; Institutional Review Board approval was not required for this single case report.
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The management of meningioma in elderly patients (MEP) presents a complex and evolving challenge. Data available offer conflicting information on treatment options and complications. This survey aimed to examine the current approach to MEP, comparing the national profile to data in the current literature. A survey addressing the treatments options and management of meningioma in elderly was designed on behalf of SINch® (Società Italiana di Neurochirurgia) and sent via email to all Chiefs of Neurosurgical Departments. The survey remained open for responses from May 5th, 2022, until November 21st, 2022. A search of the literature published between January 2000 and March 2023, in accordance to PRISMA guidelines, was included. A total of 51 Neurosurgical centers participated in the survey. The caseload profile of each center influences the choice of treatment selection (Stereotactic Radiosurgery versus open surgery) (p = 0.01) and the consolidated practice of discussing cases within a multidisciplinary group (p = 0.02). The pooled meta-analysis demonstrated a significant increased risk in the elderly group for permanent deficits (p < 0.00001), postoperative infections (p = 0.0004) and hemorrhage (p = 0.0001), perioperative mortality (p < 0.00001), and medical complications (p < 0.00001) as compared to the young population. This study presents the initial comprehensive analysis of the existing trends in the surgical management of MEP in Italy. The significant variation in practices primarily stems from the absence of standardized guidelines. While most centers have adopted an integrated approach, there is a need to promote a multidisciplinary care model. Prospective studies are needed to gather robust evidence in this clinical setting.
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Neoplasias Meníngeas , Meningioma , Procedimientos Neuroquirúrgicos , Humanos , Meningioma/cirugía , Italia , Procedimientos Neuroquirúrgicos/métodos , Anciano , Neoplasias Meníngeas/cirugía , Neurocirugia , Encuestas y Cuestionarios , Sociedades Médicas , Radiocirugia/métodosRESUMEN
The use of microelectrode recording (MER) during deep brain stimulation (DBS) for Parkinson Disease is controversial. Furthermore, in asleep DBS anesthesia can impair the ability to record single-cell electric activity.The purpose of this study was to describe our surgical and anesthesiologic protocol for MER assessment during asleep subthalamic nucleus (STN) DBS and to put our findings in the context of a systematic review of the literature. Sixty-three STN electrodes were implanted in 32 patients under general anesthesia. A frameless technique using O-Arm scanning was adopted in all cases. Total intravenous anesthesia, monitored with bispectral index, was administered using a target controlled infusion of both propofol and remifentanil. A systematic review of the literature with metanalysis on MER in asleep vs awake STN DBS for Parkinson Disease was performed. In our series, MER could be reliably recorded in all cases, impacting profoundly on electrode positioning: the final position was located within 2 mm from the planned target only in 42.9% cases. Depth modification > 2 mm was necessary in 21 cases (33.3%), while in 15 cases (23.8%) a different track was used. At 1-year follow-up we observed a significant reduction in LEDD, UPDRS Part III score off-medications, and UPDRS Part III score on medications, as compared to baseline. The systematic review of the literature yielded 23 papers; adding the cases here reported, overall 1258 asleep DBS cases using MER are described. This technique was safe and effective: metanalysis showed similar, if not better, outcome of asleep vs awake patients operated using MER. MER are a useful and reliable tool during asleep STN DBS, leading to a fine tuning of electrode position in the majority of cases. Collaboration between neurosurgeon, neurophysiologist and neuroanesthesiologist is crucial, since slight modifications of sedation level can impact profoundly on MER reliability.
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Estimulación Encefálica Profunda , Microelectrodos , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Estimulación Encefálica Profunda/métodos , Enfermedad de Parkinson/terapia , Persona de Mediana Edad , Anciano , Masculino , Femenino , Electrodos Implantados , Monitorización Neurofisiológica Intraoperatoria/métodosRESUMEN
Given that glioma cells tend to infiltrate and migrate along WM tracts, leading to demyelination and axonal injuries, Diffusion Tensor Imaging (DTI) emerged as a promising tool for identifying major "high-risk areas" of recurrence within the peritumoral brain zone (PBZ) or at a distance throughout the adjacents white matter tracts. Of our systematic review is to answer the following research question: In patients with brain tumor, is DTI able to recognizes within the peri-tumoral brain zone (PBZ) areas more prone to local (near the surgical cavity) or remote recurrence compared to the conventional imaging techniques?. We conducted a comprehensive literature search to identify relevant studies in line with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. 15 papers were deemed compatible with our research question and included. To enhance the paper's readability, we have categorized our findings into two distinct groups: the first delves into the role of DTI in detecting PBZ sub-regions of infiltration and local recurrences (n = 8), while the second group explores the feasibility of DTI in detecting white matter tract infiltration and remote recurrences (n = 7). DTI values and, within a broader framework, radiomics investigations can provide precise, voxel-by-voxel insights into the state of PBZ and recurrences. Better defining the regions at risk for potential recurrence within the PBZ and along WM bundles will allow targeted therapy.
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Neoplasias Encefálicas , Imagen de Difusión Tensora , Glioma , Recurrencia Local de Neoplasia , Humanos , Imagen de Difusión Tensora/métodos , Glioma/diagnóstico por imagen , Glioma/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
Background: The treatment of spheno-orbital meningiomas (SOMs) requires extensive bone resections, creating significant defects in a complex geometrical space. Bone reconstruction represents a fundamental step that optimizes long-term aesthetic and functional outcomes. In recent years, 3D printing technology has also been exploited for complex skull base reconstructions, but reports remain scarce. Methods: We retrospectively analyzed four consecutive patients who underwent SOM resection and one-step 3D PEEK customized reconstruction from 2019 to 2023. A systematic review of 3D printing customized implants for SOM was then performed. Results: All patients underwent a frontotemporal craniotomy, removal of SOM, and reconstruction of the superolateral orbital wall and pterional region. The aesthetic outcome was extremely satisfactory in all cases. No orbital implant malposition or infectious complications were documented. Eleven papers were included in the literature review, describing 27 patients. Most (23) patients underwent a single-stage reconstruction; in three cases, the implant was positioned to correct postoperative delayed enophthalmos. Porous titanium was the most used material (16 patients), while PEEK was used in three cases. Prosthesis malposition was described in two (7.4%) patients. Conclusions: Single-step reconstruction with a personalized 3D PEEK prosthesis represents a valid reconstruction technique for the treatment of SOMs with good aesthetic outcomes.
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BACKGROUND: Subcortical brain mapping in awake glioma surgery might optimize the extent of resection while minimizing neurological morbidity, but it requires a correct interpretation of responses evoked during surgery. To define, with a systematic review: 1) a comprehensive 'map' of the principal white matter bundles involved in awake surgery on language-related networks, describing the most employed tests and the expected responses; 2) In linguistics, a false friend is a word in a different language that looks or sounds like a word in given language but differs significantly in meaning. Similarly, our aim is to give the surgeons a comprehensive review of potentially misleading responses, namely "false friends", in subcortical language mapping. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Standardized data extraction was conducted. RESULTS: Out of a total of 224 initial papers, 67 were included for analysis. Expected responses, common tests, and potential "false friends" were recorded for each of the following white matter bundles: frontal aslant tract, superior and inferior longitudinal fascicles, arcuate fascicle, inferior fronto-occipital fascicle, uncinate fascicle. Practical examples are discussed to underline the risk of intraoperative fallouts ("false friends") that might lead to an early interruption (false positive) or a risky surgical removal (false negative). CONCLUSIONS: This paper represents a critical review of the present status of subcortical awake mapping and underlines practical "false-friend" in mapping critical crossroads in language-related networks.
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Aim of the present study was to conduct a comprehensive review of surgical strategies that can be offered to patients with trigeminal neuralgia undergoing microvascular decompression (MVD) surgery and without intraoperative evidence of neurovascular conflict, with a high pre-operative suspicion of conflict lacking intraoperative confirmation, or individuals experiencing recurrence after previous treatment. This systematic review followed established guidelines (PRISMA) to identify and critically appraise relevant studies. The review question was formulated according to the PICO (P: patients; I: intervention; C: comparison; O: outcomes) framework as follows. For patients with trigeminal neuralgia (P) undergoing MVD surgery (I) without demonstrable preoperative neurovascular conflict, high suspicion of conflict but no intraoperative confirmation or recurrence after previous treatment (C), do additional surgical techniques (nerve combing, neurapraxia, arachnoid lysis) (O) improve pain relief outcomes (O)? The search of the literature yielded a total of 221 results. Duplicate records were then removed (n = [76]). A total of 143 papers was screened, and 117 records were excluded via title and abstract screening; 26 studies were found to be relevant to our research question and were assessed for eligibility. Upon full-text review, 17 articles were included in the review, describing the following techniques; (1) internal neurolysis (n = 6) (2) arachnoid lysis/adhesiolysis (n = 2) (3) neurapraxia (n = 3) (4) partial rhizotomy of the sensory root (n = 4) (5) pontine descending tractotomy (n = 2). The risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomized Studies - of Interventions) assessment tool. While the described techniques hold promise, further research is warranted to establish standardized protocols, refine surgical approaches, and comprehensively evaluate long-term outcomes.
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Cirugía para Descompresión Microvascular , Neuralgia del Trigémino , Neuralgia del Trigémino/cirugía , Humanos , Cirugía para Descompresión Microvascular/métodos , Resultado del TratamientoRESUMEN
Background/Objectives: Lumbar disc herniation, a complex challenge in spinal health, significantly impacts individuals across diverse age groups. This article delves into the intricacies of this condition, emphasising the pivotal role of anatomical considerations in its understanding and management. Additionally, lumbar discectomy might be considered an "easy" surgery; nevertheless, it carries significant risks. The aim of the study was to present a groundbreaking "three-step approach" with some anatomical insight derived from our comprehensive clinical experiences, designed to systematise the surgical approach and optimise the outcomes, especially for young spine surgeons. We highlighted the purpose of the study and introduced our research question(s) and the context surrounding them. Methods: This retrospective study involved patients treated for lumbar disc herniation at a single institution. The patient demographics, surgical details, and postoperative assessments were meticulously recorded. All surgeries were performed by a consistent surgical team. Results: A total of 847 patients of the 998 patients initially included completed the follow-up period. A three-step approach was performed for every patient. The recurrence rate was 1.89%. Furthermore, the incidence of lumbar instability and the need for reoperation were carefully examined, presenting a holistic view of the outcomes. Conclusions: The three-step approach emerged as a robust and effective strategy for addressing lumbar disc herniation. This structured approach ensures a safe and educational experience for young spinal surgeons.
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BACKGROUND: In accordance with technique advancement and minimal invasiveness surgical approaches, the minipterional has progressively replaced the standard pterional approach for treatment of unruptured middle cerebral artery (MCA) aneurysms. Nowadays, multimodal intraoperative resources including microDoppler and microflow probes, indocyanine green videoangiography, and neurophysiologic monitoring constitute a fundamental prerequisite for increasing the safety of the clipping procedure. Our study investigated and compared in a single-center experience the effect of the evolution of a minimally invasive and multimodal approach in unruptured MCA aneurysm surgery by measuring postoperative complication rate, recovery time, and long-term neuropsychological and functional outcomes. METHODS: One hundred and thirty-one patients who underwent surgical treatment for unruptured MCA aneurysms at our institution were evaluated retrospectively. Patients' clinical, radiologic, and surgical reports were collected. Cognitive evaluation and quality of life were assessed through validated tests in telephone interviews. Patients who met the inclusion criteria were divided into 2 groups: "PT (pterional)" and "MPT (minipterional)." RESULTS: Ninety-two patients were included in the analysis. A significant reduction of postoperative complication rates and new-onset postoperative seizures was recorded in the MPT group (P value = 0.006). Severe cognitive deficits were lower in the MPT group, although without a clear statistical correlation. CONCLUSIONS: Decreased complication rates, faster recovery time, and a trend toward better cognitive and functional performances were documented for the MPT group of patients. In our experience, the minipterional approach with multimodality-assisted microsurgery reduced neurologic complications and recovery time and improved long-term cognitive outcome and quality of life.
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Aneurisma Intracraneal , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Aneurisma Intracraneal/cirugía , Resultado del Tratamiento , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos Neuroquirúrgicos/métodos , Adulto , Pruebas Neuropsicológicas , Calidad de Vida , Microcirugia/métodosRESUMEN
BACKGROUND: Spontaneous non-traumatic subarachnoid hemorrhage (sSAH) is a severe brain vascular accident. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) can be theoretically assayed to predict a patient's progression, picturing different aspects of clinical failure after sSAH. The study aims to: a) explore the correlation between sSAH blood volume and biomarkers variation; b) evaluate if these can be predictive of the neurogenic response after sSAH and be prognostic of patient outcome; c) establish eventual threshold levels of biomarkers to define patients' clinical outcome. METHODS: Blood volumetry at CT scan upon admission, GFAP and UCH-L1 were collected at 24 h, at 72 h, and after 7 days from hemorrhage. Trends and cut-off serum sampling were determined. Clinical outcome was assessed with mRS scale at 14 days. RESULTS: A strong correlation between GFAP and UCH-L1 and blood diffusion volume in all explored serum intervals related to unfavorable outcome. GFAP and UCH-L1 were very early predictors of unfavorable outcomes at 24 h from sSAH (p = 0.002 and 0.011 respectively). Threshold levels of UCH-L1 apparently revealed a very early, early and late predictor of unfavorable outcomes. CONCLUSION: GFAP and UCH-L1 represent a potential tool for prompt monitoring and customization of therapies in neurosurgical patients.
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Biomarcadores , Proteína Ácida Fibrilar de la Glía , Hemorragia Subaracnoidea , Ubiquitina Tiolesterasa , Humanos , Ubiquitina Tiolesterasa/sangre , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/complicaciones , Proteína Ácida Fibrilar de la Glía/sangre , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Pronóstico , Anciano , Adulto , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The potential advantages of exoscopy have been discussed theoretically for a long time. Such a concept holds significance, especially in the specific setting of the posterior cranial fossa (PCF), characterized by complex anatomy and long and narrow surgical corridors with relatively extreme working angles. We aimed to: 1) analyze the institutional preliminary case-based data on the use of the Robotic 3D Exoscope AEOS Aesculap in three different PCF approaches: retrosigmoid (RSA), midline suboccipital (MSA), and supracerebellar infratentorial via feedbacks was collected using a 20-point questionnaire, and 2) perform a comprehensive review of the literature concerning the use of EX in PCF surgery. RESULTS: A total of 38 patients with neurosurgical pathologies underwent a neurosurgical procedure using the EX (Robotic 3D exoscope AEOS Aesculap) at our institution between January and March 2022. 21 surgeons were involved in the abovementioned PCF surgeries and answered the questionnaire. The main perceived advantages were in terms of ergonomics (67%), magnification (52%), and visualization of extreme angles. The main reported disadvantage was color vision (16, 76%), followed by manual mobility (24%). Concerning the review, the search of the literature yielded a total of 177 results. Upon full-text review, 17 articles were included, including 153 patients. CONCLUSIONS: In conclusion, our study provides a comprehensive evaluation of the advantages and challenges associated with using the exoscope in posterior fossa surgery, setting a precedent as the first to report on a questionnaire-based analysis of exoscope utilization in this specific domain.
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BACKGROUND: The balance between comprehensive intraoperative neurophysiological monitoring (IONM) for both upper and lower limbs while ensuring the reliability of motor evoked potentials (MEPs) is paramount in motor area surgery. It is commonly difficult to obtain good simultaneous stimulation of both upper and lower limbs. A series of factors can bias MEP accuracy, and inappropriate stimulation intensity can result in unreliable monitoring. The presented IONM technique is based on the concurrent use of both transcranial and cortical strip electrodes to facilitate simultaneous monitoring of both upper and lower limbs at optimized stimulation intensities to increase IONM accuracy during motor area surgery. METHODS: Ten nonconsecutive motor area tumors were studied. Good visualization of both limbs was observed in the series at a low amperage (1.2 mA from the strip electrode and 165.3 mA from the transcranial electrode). RESULTS: Our analysis confirms concordance between the IONM data and postoperative outcomes. An MEP reduction >20% and >50% correlated with postoperative modified Rankin scale score changes without false-negative IONM findings. CONCLUSIONS: The technique was demonstrated to be accurate in providing a good simultaneous neurophysiological evaluation of both upper and lower limbs with an optimized and stimulation amplitude. The technique results in a low encumbrance of electrodes in the surgical field. Our results have confirmed the "proof of concept," its reliability and feasibility.
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Neoplasias Encefálicas , Potenciales Evocados Motores , Monitorización Neurofisiológica Intraoperatoria , Corteza Motora , Humanos , Potenciales Evocados Motores/fisiología , Femenino , Masculino , Corteza Motora/fisiopatología , Corteza Motora/cirugía , Neoplasias Encefálicas/cirugía , Monitorización Neurofisiológica Intraoperatoria/métodos , Persona de Mediana Edad , Adulto , Anciano , Técnicas Estereotáxicas , Reproducibilidad de los Resultados , Procedimientos Neuroquirúrgicos/métodosRESUMEN
BACKGROUND: Interruption of the fistulous point is the goal of treatment of spinal dural arteriovenous fistulas (dAVFs). Microsurgery remains a highly efficient treatment in terms of complete occlusion with the lowest risk of recurrence rate. It is reported that the hardest step involves finding the fistulous site itself, potentially extending surgical access and time and increasing potential postoperative surgical-related complications. The accurate preoperative detection of the shunt and spinal level together is crucial for guiding optimal, fast, and safe microsurgical treatment. METHODS: We describe a preoperative angiographic protocol for achieving a safe and simple resection of spinal dural arteriovenous fistulas based on a 6-year institutional experience of 42 patients who underwent minimally invasive procedures. Two illustrative cases are included to support the technical descriptions. RESULTS: The suspected artery associated with the vascular malformation of interest is studied in our angiographic protocol through nonsubtracted selective acquisitions in lateral projection. The resulting frames are reconstructed with three-dimensional rotational angiography. The implementation of the preoperative angiographic protocol allowed 100% of intraoperative identification of the fistulous point in all cases with the use of a minimally invasive approach. CONCLUSIONS: Nowadays, neurosurgeons advocate for minimally invasive procedures and procedures with low morbidity risk for treatment of spinal dural arteriovenous fistulas. Our preoperative approach for accurate angiographic localization of the fistulous point through nonsubtracted and three-dimensional reconstructed angiography allowed us to achieve safe and definitive occlusion of the shunt.
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Malformaciones Vasculares del Sistema Nervioso Central , Procedimientos Quirúrgicos Mínimamente Invasivos , Cuidados Preoperatorios , Humanos , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Femenino , Anciano , Cuidados Preoperatorios/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Adulto , Procedimientos Neuroquirúrgicos/métodos , Angiografía/métodos , Microcirugia/métodos , Médula Espinal/diagnóstico por imagen , Médula Espinal/irrigación sanguínea , Médula Espinal/cirugíaRESUMEN
OBJECTIVE: To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases. METHODS: This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases. RESULTS: Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated (BRCAm), 54 BRCA wild-type (BRCAwt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCAm, 11 BRCAwt) and 12 after (8 BRCAm, 4 BRCAwt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCAm group (median post-brain metastasis survival: BRCAm 23 months vs BRCAwt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCAm 8 months vs BRCAwt 8 months, p=0.31). In the BRCAm group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line. CONCLUSIONS: BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis.
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Neoplasias Encefálicas , Carcinoma Epitelial de Ovario , Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/mortalidad , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/cirugía , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/secundario , Carcinoma Epitelial de Ovario/patología , Anciano , Adulto , Proteína BRCA2/genética , Proteína BRCA1/genéticaRESUMEN
Background: Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3K27M mutations. According to the WHO (2021), SpDGs are included in diffuse midline H3K27-altered gliomas, which occur more frequently in adults and show unusual clinical presentation, neuroradiological features, and clinical behavior, which differ from H3 G34-mutant diffuse hemispheric glioma. Currently, homogeneous adult-only case series of SpDG, with complete data and adequate follow-up, are still lacking. Methods: We conducted a qualitative systematic review, focusing exclusively on adult and young adult patients, encompassing all studies reporting cases of primitive, non-metastatic SpDG with H3K27 mutation. We analyzed the type of treatment administered, survival, follow-up duration, and outcomes. Results: We identified 30 eligible articles published between 1990 and 2023, which collectively reported on 62 adult and young adult patients with primitive SpDG. Postoperative outcomes were assessed based on the duration of follow-up, with outcomes categorized as either survival or mortality. Patients who underwent surgery were followed up for a mean duration of 17.37 months, while those who underwent biopsy had a mean follow-up period of 14.65 months. Among patients who were still alive, the mean follow-up duration was 18.77 months. The radiological presentation of SpDG varies widely, indicating its lack of uniformity. Conclusion: Therefore, we presented a descriptive scenario where SpDG was initially suspected to be a meningioma, but was later revealed to be a malignant SpDG with H3K27M mutation.
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INTRODUCTION: Skeletal fragility is a clinically relevant and not-reversible complication of acromegaly, involving around 30-40% of patients since the disease diagnosis. Few studies have investigated the effects on skeletal health of medical therapies for acromegaly. In this retrospective longitudinal monocentre study, we investigated the outcome of skeletal fragility in patients treated with Pasireotide Lar in combination with Pegvisomant (Pasi-Lar + Peg-V), also comparing those observed in patients treated with conventional therapies. RESULTS: We included 6 patients treated with Pasi-Lar + Peg-V, 5 patients treated with Peg-V in monotherapy (m-Peg-V), 16 patients treated with Peg-V plus first-generation somatostatin receptor ligands (fg-SRLs + Peg-V), 9 patients treated with Pasi-Lar. None of the patients treated with Pasi-Lar + Peg-V experienced worsening of spine and femoral bone mineral density (BMD) and incident vertebral fractures (i-VFs). Eight patients experienced i-VFs. The frequency of i-VFs was significantly lower in patients treated with the Pasi-Lar + Peg-V (0/8; 0%), as compared to those observed in m-Peg-V treated patients (4/8; 50%, p = 0.02). The frequency of i-VFs was slightly but not significantly higher in Pasi-Lar treated patients (1/8; 12.5% p = 0.6) and in fg-SRLs + Peg-V treated patients (3/8; 37.5% p = 0.364), concerning those treated with Pasi-Lar + Peg-V (0/8; 0%). I-VFs occurred more frequently in patients with higher GH levels at acromegaly diagnosis (p < 0.001), and in patients who experienced a BMD worsening (p = 0.005). CONCLUSION: Our preliminary data suggested that in conventional and multi-drug resistant acromegaly, the combination therapy Pasi-Lar + Peg-V may prevent the worsening of BMD and the occurrence of i-VFs. Prospective and translational studies should further validate these results and ascertain underlying physiopathology mechanisms.
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Acromegalia , Densidad Ósea , Hormona de Crecimiento Humana , Somatostatina , Humanos , Acromegalia/tratamiento farmacológico , Densidad Ósea/efectos de los fármacos , Persona de Mediana Edad , Femenino , Masculino , Estudios Retrospectivos , Adulto , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Hormona de Crecimiento Humana/análogos & derivados , Proyectos Piloto , Anciano , Estudios LongitudinalesRESUMEN
STUDY DESIGN: Prospective study. OBJECTIVE: To evaluate the influence of preoperatively assessed psychosomatic traits on postoperative pain, disability, and quality of life outcomes. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion (ACDF) is a widely employed surgical procedure for treating cervical spondylosis. Despite its effectiveness, various studies have reported non-success rates in terms of alleviating disability and pain. Psychological factors have become increasingly recognized as critical determinants of surgical outcomes in various medical disciplines. The full extent of their impact within the context of ACDF remains insufficiently explored. This case series aims to assess the influence of preoperative psychological profiling on long-term pain, disability and quality of life outcomes. METHODS: We conducted a prospective cohort study of prospectively collected data from 76 consecutive patients who underwent ACDF with PEEK inter-fixed cages from July 2019 to November 2021. The preoperative psychological traits were assessed using the Symptom Checklist 90 (SCL-90) questionnaire. The Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), Neck Disability index (NDI), EuroQol-5D (EQ-5D), and Short Form-36 (SF-36) were collected preoperatively, one month postoperatively, and at least one year after the surgical procedure. RESULTS: The correlation analyses revealed associations between psychosomatic traits and multiple preoperative and postoperative outcome measures. The univariate analyses and linear regression analyses demonstrated the influence of the Global Severity Index (GSI) over the final follow-up scores for the ODI, VAS, NDI, EQ-5D, and SF-36. The GSI consistently exhibited a stronger correlation with the final follow-up pain, disability, and quality of life outcomes with respect to the correspondent preoperative values. CONCLUSION: This study highlights the importance of psychosomatic traits as predictive factors for ACDF outcomes and emphasizes their relevance in preoperative assessment for informing patients about realistic expectations. The findings underscore the need to consider psychological profiles in the preoperative workup, opening avenues for research into medications and psychological therapies. Recognizing the influence of psychosocial elements informs treatment strategies, fostering tailored surgical approaches and patient care.
RESUMEN
BACKGROUND: Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here. METHODS: A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024. RESULTS: A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black-reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role. CASE PRESENTATION: A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black-tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse. CONCLUSIONS: This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.