Normal tissue content impact on the GBM molecular classification.

Molecular classification of glioblastoma has enabled a deeper understanding of the disease. The four-subtype model (including Proneural, Classical, Mesenchymal and Neural) has been replaced by a model that discards the Neural subtype, found to be associated with samples with a high content of normal tissue. These samples can be misclassified preventing biological and clinical insights into the different tumor subtypes from coming to light. In this work, we present a model that tackles both the molecular classification of samples and discrimination of those with a high content of normal cells. We performed a transcriptomic in silico analysis on glioblastoma (GBM) samples (n = 810) and tested different criteria to optimize the number of genes needed for molecular classification. We used gene expression of normal brain samples (n = 555) to design an additional gene signature to detect samples with a high normal tissue content. Microdissection samples of different structures within GBM (n = 122) have been used to validate the final model. Finally, the model was tested in a cohort of 43 patients and confirmed by histology. Based on the expression of 20 genes, our model is able to discriminate samples with a high content of normal tissue and to classify the remaining ones. We have shown that taking into consideration normal cells can prevent errors in the classification and the subsequent misinterpretation of the results. Moreover, considering only samples with a low content of normal cells, we found an association between the complexity of the samples and survival for the three molecular subtypes.

[Incidence and risk factors of 30-day readmission in neurosurgical patients]. / Incidencia y factores de riesgo de reingreso hospitalario a los 30 días en pacientes neuroquirúrgicos.

AIM: The 30-day readmission rate has become an important indicator of health care quality. This study focuses on the incidence of 30-day readmission in neurosurgical patients and related risk factors. MATERIAL AND METHODS: A retrospective review was performed on patients treated in a neurosurgery department between 1 January 2012 and the 31 December 2013. Patients requiring readmission within 30 days of discharge and the readmission diagnosis were identified, and the factors related to their readmission were analysed. RESULTS: A total of 1,854 interventions were carried out on 1,739 patients during the aforementioned (study) period. Of the remaining patients, 174 (10.2%) required readmission within 30 days of discharge. The main causes of readmission were problems related to the surgical wound (21.2% of all readmissions), followed by respiratory processes (18.8%). A total of 73.9% of readmissions occurred in patients who had undergone cranial surgery. Multiple comorbidities estimated by Charlson comorbidity index and length of hospital stay were identified as factors related to a higher readmission rate. CONCLUSIONS: The 30-day readmission rate observed in our series was 10.2%. Multiple comorbidity expressed by the Charlson comorbidity index and length of hospital stay were related to readmission.

[Anterior and anterolateral approach in the treatment of thoracic and lumbar vertebral metastasis causing spinal cord compression]. / Abordaje anterior y anterolateral en el tratamiento de la compresión medular metastásica a nivel torácico y lumbar.

OBJECTIVES: To analyse the results of the anterior and anterolateral approaches in the treatment of thoracic and lumbar spine metastasis. MATERIALS AND METHODS: Patients who underwent surgery between 2003 and 2012 in our institution using an anterior or an anterolateral approach for the treatment of thoracic or lumbar spine metastasis were retrospectively reviewed. RESULTS: Twenty-two patients with median age of 49.5 years (26-73 years) and median follow-up of 9.5 months (0-96 months) were analysed. The most common primary malignancies were renal cell carcinomas and breast adenocarcinomas. Before the intervention, 12 (54.5%) patients were able to walk (Frankel D and E). Preoperative arteriography was performed in 14 (63.6%) patients, and 7 (31.8%) of them underwent tumour embolisation. Medical complications occurred in 5 (22.7%) patients during the immediate postoperative period, 2 (9.1%) of whom died. At the end of follow-up, 16 (72%) of the remaining 20 patients were able to walk (Frankel D and E). Ninety percent of the patients could reduce at least 50% of their analgesic drug requirements. During follow-up 16 patients died, with a median survival of 10 months (range 0-48 months). CONCLUSIONS: Resection of thoracolumbar vertebral metastases by an anterior/anterolateral approach, despite its considerable risk of morbidity and mortality, offers the possibility of significant improvement in the quality of life of the patient; and it does so not only by preserving or restoring their ability to walk but also by ameliorating pain. Preoperative angiography, considering the embolisation of the lesion, is an important tool.

Cerebral salt wasting syndrome: postoperative complication in tumours of the cerebellopontine angle.

Cerebral salt wasting (CSW) is a rare complication in posterior fossa tumour surgery. We present two patients with cerebellopontine angle (CPA) tumours who developed cerebral salt wasting postoperatively. Both patients deteriorated in spite of intensive fluid and salt replacement. On CT scan the patients presented mild to moderate ventricular dilation, which was treated with an external ventricular drainage. After the resolution of hydrocephalus, fluid balance rapidly returned to normal in both patients and the clinical status improved. Identification and treatment of secondary obstructive hydrocephalus may contribute to the management of CSW associated to posterior fossa tumour surgery.

[Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations]. / Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía.

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It́s recommended a one week treatment with antiepileptic drugs in patients who didnt have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient.

DREZotomy in the treatment of deafferentation pain: review of results and analysis of predictive factors for success. / Drezotomía en el tratamiento del dolor por desaferentización: revisión de resultados y análisis de factores predictores de éxito.

BACKGROUND AND OBJECTIVES: The treatment of deafferentation pain by spinal DREZotomy is a proven therapeutic option in the literature. In recent years, use of DREZotomy has been relegated to second place due to the emergence of neuromodulation therapies. The objectives of this study are to demonstrate that DREZotomy continues to be an effective and safe treatment and to analyse predictive factors for success. PATIENTS AND METHODS: A retrospective study was conducted of all patients treated in our department with spinal DREZotomy from 1998 to 2018. Bulbar DREZotomy procedures were excluded. A visual analogue scale (VAS) and the reduction of routine medication were used as outcome variables. Demographic, clinical and operative variables were analysed as predictive factors for success. RESULTS: A total of 27 patients (51.9% female) with a mean age of 53.7 years underwent DREZotomy. The main cause of pain was brachial plexus injury (BPI) (55.6%) followed by neoplasms (18.5%). The mean time of pain evolution was 8.4 years with a mean intensity of 8.7 according to the VAS, even though 63% of the patients had previously received neurostimulation therapy. Favourable outcome (≥50% pain reduction in the VAS) was observed in 77.8% of patients during the postoperative period and remained in 59.3% of patients after 22 months average follow-up (mean reduction of 4.9 points). This allowed for a reduction in routine analgesic treatment in 70.4% of them. DREZotomy in BPI-related pain presented a significantly higher success rate (93%) than the other pathologies (41.7%) (p=.001). No association was observed between outcome and age, gender, DREZ technique, duration of pain or previous neurostimulation therapies. There were six neurological complications, four post-operative transient neurological deficits and two permanent deficits. CONCLUSION: Dorsal root entry zone surgery is effective and safe for treating patients with deafferentation pain, especially after brachial plexus injury. It can be considered an alternative treatment after failed neurostimulation techniques for pain control. However, its indication should be considered as the first therapeutic option after medical therapy failure due to its good long-term results.

Late recurrence of medulloblastoma after 17 years of complete remission.

BACKGROUND: To describe an exceptional case of late recurrence of medulloblastoma after 17 years of complete remission. CASE DESCRIPTION: A 42-year-old male consulted in ER for 10-day occipital headache. He had a previous history of cerebellar medulloblastoma 17 years ago treated with gross total resection, chemotherapy and radiotherapy. During his yearly follow-up he had maintained complete remission. MRi showed a cerebellar mass suggestive of medulloblastoma recurrence vs radio-induced tumor. Craniotomy and complete resection of the tumor was performed. The anatomopathological analysis confirmed the recurrence of medulloblastoma. The patient received high dose of adjuvant chemotherapy and he maintains complete remission after 18 months. CONCLUSION: Recurrence of medulloblastoma may occur despite more than 15 years of complete remission. Because of this fact it is mandatory to continue the follow-up of these patients. Aggressive management of recurrence is recommended in absence of disease dissemination.

Spinal epidural abscess caused by Streptococcus agalactiae in an immunocompetent patient. / Absceso epidural espinal por Streptococcus agalactiae en un paciente inmunocompetente.

BACKGROUND: Streptococcus agalactiae is an uncommon microorganism that causes spinal epidural abscess (SEA) and usually affects individuals with a predisposing condition or potential source of infection. CASE DESCRIPTION: We present the case of an immunocompetent 53-year-old patient with an unremarkable past medical history who developed progressive low extremity weakness, bowel and bladder dysfunction and genital sensory impairment. A neurological exam on admission revealed flaccid proximal paraparesis, T10 sensory level, atonic anal sphincter and normal myotatic reflexes. Urgent neuroimaging showed a large thoracic epidural spinal abscess. Laminectomy and abscess drainage were immediately performed and systemic antibiotic treatment was initiated. Abscess cultures revealed Streptococcus agalactiae. After an exhaustive workup no predisposing factors or local or systemic source for the infection were found. CONCLUSIONS: We report a singular case of spinal epidural abscess caused by Streptococcus agalactiae in a healthy patient with no predisposing factors. This case also highlights the importance of an early diagnosis and treatment to obtain a better neurological outcome.

Comprehensive Characterization of a Porcine Model of The "Small-for-Flow" Syndrome.

INTRODUCTION: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome. METHODS: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment. RESULTS: All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2-11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h. CONCLUSION: The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the "Small-for-Flow" syndrome.

Hypoglossal nerve paresis secondary to anterior approach of upper cervical spine followed by spontaneous recovery.

We describe an exceptional complication of cervical spine surgery in a 63-year-old male. He suffered the impact of a beam to the top of his head. During evaluation in the emergency room he reported intense neck pain with no other neurological symptoms or findings on physical examination. Spine computed tomography (CT) showed C3 vertebral body fracture that required surgical stabilization. A right side anterior approach to upper cervical spine with C3 corpectomy and placement of iliac bone autograft was performed. After surgery the patient presented dysphagia, dysarthria and limitation tongue mobility to the right side. These findings were consistent with hypoglossal neuropraxia probably related to soft tissue traction generated by the upper part of the self-retaining retractor. After discharge the patient experienced spontaneous improvement of hypoglossal paresis.

Angiocentric Glioma in an Elderly Patient: Case Report and Review of the Literature.

BACKGROUND: Angiocentric glioma is a very uncommon low-grade tumor, predominantly occurring in pediatric patients, that was first described in 2005 and was codified 2 years later as a new central nervous system primary tumor. We herein report an exceptionally rare case of an elderly patient with angiocentric glioma. Only one additional case of angiocentric glioma in a patient older than 65 years has been hitherto reported. CASE DESCRIPTION: An 83-year-old male patient presented at our institution complaining of a 1-month history of progressive weakness of his right hand and difficulty performing fine movements. Magnetic resonance imaging of the brain was performed, and fluid-attenuated inversion recovery and T2-hyperintense diffuse cortico-subcortical lesion were reported. A neuronavigation-guided frontal craniotomy was performed to expose the premotor cortex, motor cortex, Rolandic sulcus, and postcentral gyrus. Intraoperative mapping showed that the tumor was close to the shoulder area. Therefore, only partial resection was safely feasible. Pathology report described astrocytic neoplastic cells affecting mainly the cortex and piamater with the classic finding of subpial palisading, with no endothelial invasion or atypia. Neoplastic cells were positive for glial fibrillary acidic protein, epithelial membrane antigen, Wilms tumor protein-1, P16, and P53. Low proliferative activity was seen (Ki-67 < 2%). Abundant gliovascular structures were also reported. CONCLUSIONS: Considering the morphologic and immunohistochemical data, the final pathologic diagnosis was angiocentric glioma. Furthermore, a thorough review of the literature was performed with the purpose of updating and summarizing the main clinical, radiologic, and pathologic features of this rare tumor.

DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients.

Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs-apoptotic bodies, shedding microvesicles and exosomes-cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF). Furthermore, these EVs can be readily distinguished from total murine EVs, since they carry human-specific DNA sequences relevant for GBM biology. In a small cohort of glioma patients, we finally demonstrated that peripheral blood EVs cargo can be successfully used to detect the presence of IDH1G395A, an essential biomarker in the current management of human glioma.

Long-term Thalamic Deep Brain Stimulation for Essential Tremor: Clinical Outcome and Stimulation Parameters.

BACKGROUND: The reasons underlying the loss of efficacy of deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius (VIM-DBS) over time in patients with essential tremor are not well understood. METHODS: Long-term clinical outcome and stimulation parameters were evaluated in 14 patients with essential tremor who underwent VIM-DBS. The mean ± standard deviation postoperative follow-up was 7.7 ± 3.8 years. At each visit (every 3-6 months), tremor was assessed using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and stimulation parameters were recorded (contacts, voltage, frequency, pulse width, and total electrical energy delivered by the internal generator [TEED 1sec]). RESULTS: The mean reduction in FTM-TRS score was 73.4% at 6 months after VIM-DBS surgery (P < 0.001) and 50.1% at the last visit (P < 0.001). The gradual worsening of FTM-TRS scores over time fit a linear regression model (coefficient of determination [R2] = 0.887; P < 0.001). Stimulation adjustments to optimize tremor control required a statistically significant increase in voltage (P = 0.01), pulse width (P = 0.01), frequency (P = 0.02), and TEED 1sec (P = 0.008). TEED 1sec fit a third-order polynomial curve model throughout the follow-up period (R2 = 0.966; P < 0.001). The initial exponential increase (first 4 years of VIM-DBS) was followed by a plateau and a further increase from the seventh year onward. CONCLUSIONS: The current findings suggest that the waning effect of VIM-DBS over time in patients with essential tremor may be the consequence of a combination of factors. Superimposed on the progression of the disease, tolerance can occur during the early years of stimulation.