Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management.

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.

Tratamiento de la mielopatía cervical mediante abordaje posterior: laminoplastia vs. laminectomía con fijación posterior. ¿Existen diferencias desde el punto de vista clínico y radiológico? / Treatment of cervical myelopathy by posterior approach: Laminoplasty vs. laminectomy with posterior fixation, are there differences from a clinical and radiological point of view?

Introducción La mielopatía cervical degenerativa representa una entidad patológica producida por la estenosis del canal medular cervical, resultando en una compresión crónica de la médula espinal, variable y progresiva. El abordaje quirúrgico de la columna cervical puede realizarse por vía anterior y/o vía posterior. Respecto al abordaje posterior, existen 2 técnicas fundamentales: laminoplastia y laminectomía con fijación posterior (LFP). En la literatura actual existe controversia acerca de cuál de las 2 técnicas permite obtener mejores resultados postoperatorios. El objetivo es el estudio de las diferencias entre laminoplastia y LFP desde el punto de vista clínico y radiológico. Materiales y métodosSe realiza un estudio de una cohorte histórica de 39 pacientes (12 LFP y 27 laminoplastia) intervenidos en un período de 10 años en el Hospital Universitario La Paz con un seguimiento de 12 meses tras la cirugía. Se analizan y comparan los resultados clínicos mediante la escala de Nurick y la Escala Japanese Orthopaedic Association modificada (mJOA) y los resultados radiológicos mediante el ángulo de Cobb, eje sagital vertical, T1 Slope y el alineamiento (medido mediante Cobb-T1 Sloppe). Resultados Se observan diferencias significativas en la mejoría postoperatoria de la escala Nurick (p=0,008) y mJOA (p=0,018) en el grupo de laminoplastia. En LFP se objetiva una tendencia a una mejoría mayor, pero no se alcanza la significación estadística debido al bajo tamaño muestral de este grupo. No se objetivan diferencias estadísticamente significativas en cuanto a la variables radiológicas. Respecto al total de complicaciones, se observó un número mayor en el grupo de laminoplastia (7 casos) frente a LFP (un caso), pero no se vieron diferencias estadísticamente significativas... (AU)

Introduction Cervical degenerative myelopathy is a variable and progressive degenerative disease caused by chronic compression of the spinal cord. Surgical approaches for the cervical spine can be performed anteriorly and/or posteriorly. Regarding the posterior approach, there are 2 fundamental techniques: laminoplasty and laminectomy with posterior fixation (LPF). There is still controversy concerning the technique in terms of outcome and complications. The aim of the present work is to analyze from the clinical and radiological point of view these 2 techniques: laminoplasty and LPF. Materials and methods A historical cohort of 39 patients was reviewed (12 LFP and 27 laminoplasty) including patients operated in a 10 years period at the Hospital Universitario La Paz with a follow-up of 12 months after surgery was carried out. The clinical results were analyzed and compared using the Nurick scale and the modified Japanese Orthopaedic Association Scale (mJOA) and the radiological results using the Cobb angle, Sagittal Vertical Axis, T1 Slope and alignment (measured by Cobb-T1 Sloppe). Results Significant differences were observed in the postoperative improvement of the Nurick scale (P=.008) and mJOA (P=.018) in the laminoplasty group. In LFP there is a tendency to a greater improvement, but statistical significance is not reached due to the low sample size of this group. No statistically significant differences were observed in the radiological variables. Regarding the total number of complications, a higher number was observed in the laminoplasty group (7 cases) versus LFP (one case), but no statistically significant differences were observed. (AU)

Beyond Classic Anastomoses Training Models: Overview of Aneurysm Creation in Rodent Vessel Model.

Nowadays, due to the decline in the number of microsurgical clippings for cerebral aneurysms and revascularization procedures, young neurosurgeons have fewer opportunities to participate and train on this type of surgery. Vascular neurosurgery is a demanding subspecialty that requires skills that can only be acquired with technical experience. This background pushes the new generations to be ready for such challenging cases by training hard on different available models, such as synthetic tubes, chicken wings, or placenta vessels. Although many training models for vascular neurosurgery have been described worldwide, one of the best is the rodent vessels model. It offers pulsation, coagulation, and real blood flow conditions in a physiologic atmosphere that mimics perfectly the intracranial human vessels environment, especially in terms of size. However, the current differences in governmental different regulations about the use of living animals in medical experimentation and the social awareness, as well as the lack of financial support, cause more difficulties for neurosurgeons to start with that kind of training. In this review, we describe the tools and techniques as basic steps for vascular microsurgery training by using rodent models, that provide an accurate copy of brain vessels environment under stable conditions. The initial three classical known microanastomoses for neurosurgeons are end-to-end, end-to-side, and side-to-side, but in literature, there have been described other more complex exercises for training and investigation, such as aneurysm models. Although there is still little data available, we aim to summarize and discuss aneurysm's training models and reviewed the current literature on the subject and its applications, including a detailed description of the techniques.

Treatment of cervical myelopathy by posterior approach: Laminoplasty vs. laminectomy with posterior fixation, are there differences from a clinical and radiological point of view?

INTRODUCTION: Cervical degenerative myelopathy is a variable and progressive degenerative disease caused by chronic compression of the spinal cord. Surgical approaches for the cervical spine can be performed anteriorly and/or posteriorly. Regarding the posterior approach, there are 2 fundamental techniques: laminoplasty and laminectomy with posterior fixation (LPF). There is still controversy concerning the technique in terms of outcome and complications. The aim of the present work is to analyze from the clinical and radiological point of view these 2 techniques: laminoplasty and LPF. MATERIALS AND METHODS: A historical cohort of 39 patients was reviewed (12 LFP and 27 laminoplasty) including patients operated in a 10 years period at the Hospital Universitario La Paz with a follow-up of 12 months after surgery was carried out. The clinical results were analyzed and compared using the Nurick scale and the modified Japanese Orthopaedic Association Scale (mJOA) and the radiological results using the Cobb angle, Sagittal Vertical Axis, T1 Slope and alignment (measured by Cobb-T1 Sloppe). RESULTS: Significant differences were observed in the postoperative improvement of the Nurick scale (p = 0.008) and mJOA (p = 0.018) in the laminoplasty group. In LFP there is a tendency to a greater improvement, but statistical significance is not reached due to the low sample size of this group. No statistically significant differences were observed in the radiological variables. Regarding the total number of complications, a higher number was observed in the laminoplasty group (7 cases) versus LFP (one case), but no statistically significant differences were observed. CONCLUSIONS: Laminoplasty and LFP are both safe and effective procedures in the treatment of cervical degenerative myelopathy. The findings of our study demonstrate statistically significant clinical improvement based on the Nurick and mJOA scales with laminoplasty. No significant differences in terms of complications or radiological variables were observed between the 2 techniques.

Case Report: Decompressive Craniectomy for COVID-19 Malignant Cerebral Artery Infarction. Is Surgery a Good Option?

SARS-CoV2 infection can lead to a prothrombotic state. Large vessel occlusion, as well as malignant cerebral stroke have been described in COVID-19 patients. In the following months, given the increase in COVID-19 cases, an increase in malignant cerebral SARS-CoV2 associated strokes are expected. The baseline situation of the patients as well as the risk of evolution to a serious disease due to the virus, depict a unique scenario. Decompressive craniectomy is a life-saving procedure indicated in patients who suffer a malignant cerebral stroke; however, it is unclear whether the same eligibility criteria should be used for patients with COVID-19. To our knowledge seven cases of decompressive craniectomy and malignant cerebral stroke have been described to date. We report on a 39-year-old female with no major risk factors for cerebrovascular disease, apart from oral contraception, and mild COVID-19 symptoms who suffered from left hemispheric syndrome. The patient underwent endovascular treatment with stenting and afterward decompressive craniectomy due to a worsening neurological status with unilateral unreactive mydriasis. We present the case and provide a comprehensive review of the available literature related to the surgical treatment for COVID-19 associated malignant strokes, to establish whether the same eligibility criteria for non-COVID-19 associated strokes should be used. Eight patients, including our case, were surgically managed due to malignant cerebral stroke. Seven of these patients received decompressive craniectomy, and six of them met the eligibility criteria of the current stroke guidelines. The mortality rate was 33%, similar to that described in non-COVID-19 cases. Two patients had a left middle cerebral artery (MCA) and both survived after decompressive craniectomy. Our results support that decompressive craniectomy, using the current stroke guidelines, should be considered an effective life-saving treatment for COVID-19-related malignant cerebral strokes.

Real-world evidence on spinal cord neuromodulation and pain: Long-term effectiveness analysis in a single-center cohort.

Introduction: Chronic pain inflicts damage in multiple spheres of patient's life and remains a challenge for health care providers. Real-world evidence derived from outcome registries represents a key aspect of the ongoing systematic assessment and future development of neurostimulation devices. Research question: The objective of the present study was to assess the long-term effectiveness of neurostimulation as a treatment for spinal chronic pain. Material and methods: The patients analyzed in the present study represent a singlecenter cohort of 52 individuals. Primary outcome measures included numeric pain rating scale, Beck depression index II and Oswestry disability index variation from baseline to 36-month visits. Secondary outcomes included its evaluation at 6-month, 12-month and 24-month visits. Results: A significant improvement in targeted pain, depression and disability values were observed at 36-month follow-up (P â€‹< â€‹0.001, P â€‹= â€‹0.009 and P â€‹< â€‹0.001 respectively). Those results were consistent in the leg and back pain subgroup but not in the neck, chest and arm pain subgroup. The decrease in pain, depression and disability values happened progressively through time, with the exception of the 12-month visit, where a mild stagnation was observed. Discussion and conclusion: Our results suggest that spinal cord stimulation is an effective long-term treatment for spinal chronic pain in real-world conditions when applied to a variety of patients and conditions usually seen in routine practice. Nevertheless, some fluctuations may occur during treatment so prolonged follow-up periods should be considered before rendering an unsuccessful therapy diagnosis.

Assessment of Pre-operative Measurements of Tumor Size by MRI Methods as Survival Predictors in Wild Type IDH Glioblastoma.

Objective: We evaluate the performance of three MRI methods to determine non-invasively tumor size, as overall survival (OS) and Progression Free Survival (PFS) predictors, in a cohort of wild type, IDH negative, glioblastoma patients. Investigated protocols included bidimensional (2D) diameter measurements, and three-dimensional (3D) estimations by the ellipsoid or semi-automatic segmentation methods. Methods: We investigated OS in a cohort of 44 patients diagnosed with wild type IDH glioblastoma (58.2 ± 11.4 years, 1.9/1 male/female) treated with neurosurgical resection followed by adjuvant chemo and radiotherapy. Pre-operative MRI images were evaluated to determine tumor mass area and volume, gadolinium enhancement volume, necrosis volume, and FLAIR-T2 hyper-intensity area and volume. We implemented then multivariate Cox statistical analysis to select optimal predictors for OS and PFS. Results: Median OS was 16 months (1-42 months), ranging from 9 ± 2.4 months in patients over 65 years, to 18 ± 1.6 months in younger ones. Patients with tumors carrying O6-methylguanin-DNA-methyltransferase (MGMT) methylation survived 30 ± 5.2 vs. 13 ± 2.5 months in non-methylated. Our study evidenced high and positive correlations among the results of the three methods to determine tumor size. FLAIR-T2 hyper-intensity areas (2D) and volumes (3D) were also similar as determined by the three methods. Cox proportional hazards analysis with the 2D and 3D methods indicated that OS was associated to age ≥ 65 years (HR 2.70, 2.94, and 3.16), MGMT methylation (HR 2.98, 3.07, and 2.90), and FLAIR-T2 ≥ 2,000 mm2 or ≥60 cm3 (HR 4.16, 3.93, and 3.72), respectively. Other variables including necrosis, tumor mass, necrosis/tumor ratio, and FLAIR/tumor ratio were not significantly correlated with OS. Conclusion: Our results reveal a high correlation among measurements of tumor size performed with the three methods. Pre-operative FLAIR-T2 hyperintensity area and volumes provided, independently of the measurement method, the optimal neuroimaging features predicting OS in primary glioblastoma patients, followed by age ≥ 65 years and MGMT methylation.

The use of transcranial motor-evoked potentials, somatosensory-evoked potentials and free-run electromyography for proper placement of paddle leads in chronic pain.

Introduction: As an alternative to those patients who cannot be performed an awake spinal cord stimulation (SCS) or had been percutaneously implanted with poor pain relief outcomes, neurophysiological monitoring through transcranial motor evoked potentials (MEPs), somatosensory-evoked potentials (SSEPs) and free-run electromyography (EMG) under general anesthesia allows the correct placement of surgical leads and provide objective responses.Methods: An initial series of 15 patients undergoing SCS implantation for chronic pain. Physiologic midline was determined with 32-channel NIM-Eclipse System equipment. During neurophysiological monitoring, MEPs, SSEPs, EMG and CMAPs were recorded.Results: MEPs, SSEPs, and EMG were able to target spinal cord physiological midline during SCS to all patients. Physiologic midline was deviated in 53% patients. No warning events in SSEPs, MEPs, or EMG were recorded in any patient.Conclusions: Bilateral CMAPs recording allows placement of paddle leads in physiological midline, obtaining an accurate coverage, pain relief and avoid unpleasant or ineffective stimulation postoperatively. While these neurophysiological techniques are generally used to provide information on the state of the nervous system and prevent neurological injury risks during SCS, our work has shown that can accurate direct lead placement.

Llamada para participar en el estudio internacional de resultados del traumatismo craneoencefálico (Global Neurotrauma Outcomes Study) / Call to participate in the international study of traumatic brain injury results (Global Neurotrauma Outcomes Study)

El traumatismo craneoencefálico (TCE) representa una cantidad significativa de muertes y discapacidad a nivel mundial, afectando la mayor parte de esta carga a los países con ingresos medios y bajos. El estudio GNOS es un estudio internacional multicéntrico de cohorte prospectiva. Es el primer estudio neuroquirúrgico global que tiene como objetivo proporcionar una imagen completa del manejo y los resultados de los pacientes que han sido tratados mediante cirugía urgente por TCE a nivel mundial

Traumatic brain injury (TBI) accounts for a significant amount of death and disability worldwide and the majority of this burden affects individuals in low-and-middle income countries. The GNOS is a multi-centre international, prospective cohort study. This study is the first global neurosurgical study that aims to provide a comprehensive picture of the management and outcomes of patients undergoing emergency surgery for TBI worldwide

Call to participate in the international study of traumatic brain injury results (Global Neurotrauma Outcomes Study). / Llamada para participar en el estudio internacional de resultados del traumatismo craneoencefálico (Global Neurotrauma Outcomes Study).

Traumatic brain injury (TBI) accounts for a significant amount of death and disability worldwide and the majority of this burden affects individuals in low-and-middle income countries. The GNOS is a multi-centre international, prospective cohort study. This study is the first global neurosurgical study that aims to provide a comprehensive picture of the management and outcomes of patients undergoing emergency surgery for TBI worldwide.

Resultados quirúrgicos de fracturas cervicales traumáticas en pacientes con espondilitis anquilosante / Surgical outcomes of traumatic cervical fractures in patients with ankylosing spondylitis

Objetivo: La espondilitis anquilosante es una enfermedad reumática inflamatoria que afecta principalmente al esqueleto axial. La columna vertebral rígida puede secundariamente desarrollar osteoporosis, lo que aumenta aún más el riesgo de fractura vertebral. En este estudio, hemos revisado las fracturas en pacientes con espondilitis anquilosante que habían sido diagnosticados clínicamente para definir mejor el mecanismo de la lesión, déficit neurológico asociado y las estrategias de tratamiento. Métodos: Entre enero del 2004 y diciembre del 2014, 6 pacientes fueron revisados con espondilitis anquilosante y con complicaciones neurológicas después de caídas. El estudio de neuroimagen se obtuvo en todos los pacientes mediante el uso de la radiografía simple, TC y RM. La discapacidad se valoró según la escala de ASIA, se utilizó con el fin de evaluar el estado neurológico de los pacientes. La decisión quirúrgica se basó en relación con la afectación neurológica y la inestabilidad espinal. Resultados: Se identificaron un total de 6 lesiones cervicales en pacientes con espondilitis anquilosante: 2 presentaron fracturas por mecanismos de extensión y 4 por mecanismos de flexión. Todos los casos fueron intervenidos quirúrgicamente. Los 6 pacientes presentaron déficit neurológico postraumático y en 4 de ellos se observó mejoría neurológica tras la cirugía. Dos casos no mejoraron tras la cirugía. Uno de ellos presentó un grado de ASIA A y el otro paciente, que mejoró inicialmente con la cirugía, falleció por neumonía en el postoperatorio dos meses después. Conclusiones: Los pacientes con espondilitis anquilosante son altamente susceptibles a la fractura vertebral y lesiones de la médula espinal, incluso después de traumatismos leves. Se recomienda la TC inicial o la RM de toda la columna vertebral, incluso si los síntomas del paciente son leves. El paciente también debe tener la estabilización quirúrgica temprana para corregir la deformidad espinal y evitar el empeoramiento del estado neurológico del paciente

Objective: Ankylosing spondylitis is an inflammatory rheumatic disease mainly affecting the axial skeleton. The rigid spine may secondarily develop osteoporosis, further increasing the risk of spinal fracture. In this study, we reviewed fractures in patients with ankylosing spondylitis that had been clinically diagnosed to better define the mechanism of injury, associated neurological deficit, predisposing factors, and management strategies. Methods: Between January 2004 and December 2014, 6 patients with ankylosing spondylitis and neurological complications after injuries were treated. Neuroimaging evaluation was obtained in all patients by using plain radiography, CT scan, and MR imaging. The ASIA Impairment Scale was used in order to evaluate the neurologic status of the patients. Surgical decision was based on relationship of neurological involvement and spinal instability. Results: A total of 6 cervical injuries were identified in a review of patients in whom ankylosing spondylitis had been diagnosed. Of these, 2 patients were associated with a hyperextension mechanism and 4 cases by flexion mechanism. Posttraumatic neurological deficits were demonstrated in all 6 cases and neurological improvement after surgery was observed in 4 of these cases. The two cases were not improved by the surgery was on a case by presenting a degree of Asia A and another patient who initially improved with surgery but died of pneumonia in the postoperative. Conclusions: Patients with ankylosing spondylitis are highly susceptible to spinal fracture and spinal cord injury even after only mild trauma. Initial CT or MR imaging of the whole spine is recommended even if the patient's symptoms are mild. The patient should also have early surgical stabilization to correct spinal deformity and avoid worsening of the patient's neurological status

Surgical outcomes of traumatic cervical fractures in patients with ankylosing spondylitis. / Resultados quirúrgicos de fracturas cervicales traumáticas en pacientes con espondilitis anquilosante.

OBJECTIVE: Ankylosing spondylitis is an inflammatory rheumatic disease mainly affecting the axial skeleton. The rigid spine may secondarily develop osteoporosis, further increasing the risk of spinal fracture. In this study, we reviewed fractures in patients with ankylosing spondylitis that had been clinically diagnosed to better define the mechanism of injury, associated neurological deficit, predisposing factors, and management strategies. METHODS: Between January 2004 and December 2014, 6 patients with ankylosing spondylitis and neurological complications after injuries were treated. Neuroimaging evaluation was obtained in all patients by using plain radiography, CT scan, and MR imaging. The ASIA Impairment Scale was used in order to evaluate the neurologic status of the patients. Surgical decision was based on relationship of neurological involvement and spinal instability. RESULTS: A total of 6 cervical injuries were identified in a review of patients in whom ankylosing spondylitis had been diagnosed. Of these, 2 patients were associated with a hyperextension mechanism and 4 cases by flexion mechanism. Posttraumatic neurological deficits were demonstrated in all 6 cases and neurological improvement after surgery was observed in 4 of these cases. The two cases were not improved by the surgery was on a case by presenting a degree of Asia A and another patient who initially improved with surgery but died of pneumonia in the postoperative. CONCLUSIONS: Patients with ankylosing spondylitis are highly susceptible to spinal fracture and spinal cord injury even after only mild trauma. Initial CT or MR imaging of the whole spine is recommended even if the patient's symptoms are mild. The patient should also have early surgical stabilization to correct spinal deformity and avoid worsening of the patient's neurological status.

Jugulotympanic paragangliomas treated with Gamma Knife radiosurgery: a single-center review of 58 cases.

OBJECT: Jugulotympanic paragangliomas (JTPs) are rare benign tumors whose surgical treatment is usually associated with partial resection of the lesion, high morbidity, and even death. Gamma Knife radiosurgery (GKRS) has been reported as a useful treatment option. The goal of this retrospective study is to analyze the role of GKRS in tumor volume control and clinical outcomes of these patients. METHODS: A total of 75 patients with JTPs were treated with GKRS at the authors' center from 1995 to 2012. The authors analyzed those treated during this period to allow for a minimal observation time of 2 years. The MR images and clinical reports of these patients were reviewed to assess clinical and volumetric outcomes of the tumors. The radiological and clinical assessments, along with a group of prognostic factors measured, were analyzed using descriptive methods. The time to volumetric and clinical progression was analyzed using the Kaplan-Meier method. Prognostic factors were identified using log-rank statistics and multivariate Cox regression models. RESULTS: The mean follow-up was 86.4 months. The authors observed volumetric tumor control in 94.8% of cases. In 67.2% of cases, tumor volume decreased by a mean of 40.1% from the original size. Of patients with previous tinnitus, 54% reported complete recovery. Improvement of other symptoms was observed in 34.5% of cases. Overall, clinical control was achieved in 91.4% of cases. Previous embolization and familial history of paraganglioma were selected as significant prognostic factors for volumetric response to GKRS treatment in the univariate analysis. In multivariate analysis, no factors were significantly correlated with progression-free survival. No patient died of side effects related to GKRS treatment or tumor progression. CONCLUSIONS: Gamma Knife radiosurgery is an effective, safe, and efficient therapeutic option for the treatment of these tumors as a first-line treatment or in conjunction with traditional surgery, endovascular treatment, or conventional fractionated radiotherapy.

Rheumatoid meningitis mimicking progressive supranuclear palsy.

INTRODUCTION: Rheumatoid meningitis is an uncommon manifestation of longstanding rheumatoid arthritis and few cases have been described. The clinical presentation is extremely variable as reported in medical literature. CASE REPORT: We report a 71-year-old woman with 15 years of seropositive rheumatoid arthritis who developed neurological complications: cognitive deterioration; hypomimia; limitation on vertical gaze; and axial stiffness, resembling progressive supranuclear palsy and seizures. Brain magnetic resonance imaging showed a diffuse dural plaque on both frontal and temporal lobes exhibiting homogeneous gadolinium enhancement. There was diffuse leptomeningeal enhancement and hyperintense white matter lesions. The final diagnosis made by image-guided biopsy showed rheumatoid pachymeningitis. After the definitive diagnosis, high doses of corticosteroids and immunosuppressive treatment were started. CONCLUSIONS: We emphasize the diagnostic importance of the biopsy in cases of chronic pachymeningitis and stress that diverse entities can cause progressive supranuclear palsy-like phenotypes.