Pathogenesis of spinal intramedullary lipomas: two case reports.

BACKGROUND: Spinal lipomas not associated with dysraphism are rare and have an unknown natural history. In this report, we describe two cases; they showed recurrence during long-term follow-up, which makes us doubt a benign malformative etiology. CASE REPORTS: Two patients, a 19-year-old South American woman and a 14-year-old boy with spinal lipomas, underwent surgical resection. The lipomas were not associated with dysraphism and were located in the cervicothoracic and craniocervical junctions. In both cases, we decided to operate due to clinical progression; the former had a progressive natural course, and the latter experienced clinical worsening after recurrence from previous surgeries. The surgery took place with the assistance of neurophysiological monitoring and intraoperative ultrasound; a partial resection and medullary decompression were done, following the more recent recommendations. DISCUSSION: The natural history of these lesions is currently unknown due to their rarity and the heterogeneity in the long-term follow-up of previously reported cases. Although previous reports describe good outcomes after surgical resection, long follow-ups, especially in young subjects, may show differences in these outcomes with progression and recurrence. We contribute to this last piece of evidence by describing two more cases of progression and recurrence. LESSONS: Long-term close follow-up should be done in young subjects with spinal lipomas, as they are more prone to an aggressive course. Metabolism and hormonal changes may be behind this progression. Reoperation must be considered if neurological decline is detected.

Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

BACKGROUND: The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection. METHODS: Patients received trotabresib 30 mg/day on days 1-4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery. Primary endpoints were plasma pharmacokinetics and trotabresib concentrations in resected tissue. Secondary and exploratory endpoints included safety, pharmacodynamics, and antitumor activity. RESULTS: Twenty patients received preoperative trotabresib and underwent resection with no delays or cancelations of surgery; 16 patients received maintenance trotabresib after recovery from surgery. Trotabresib plasma pharmacokinetics were consistent with previous data. Mean trotabresib brain tumor tissue:plasma ratio was 0.84 (estimated unbound partition coefficient [KPUU] 0.37), and modulation of pharmacodynamic markers was observed in blood and brain tumor tissue. Trotabresib was well tolerated; the most frequent grade 3/4 treatment-related adverse event during maintenance treatment was thrombocytopenia (5/16 patients). Six-month progression-free survival was 12%. Two patients remain on treatment with stable disease at cycles 25 and 30. CONCLUSIONS: Trotabresib penetrates the blood-brain-tumor barrier in patients with recurrent high-grade glioma and demonstrates target engagement in resected tumor tissue. Plasma pharmacokinetics, blood pharmacodynamics, and safety were comparable with previous results for trotabresib in patients with advanced solid tumors. Investigation of adjuvant trotabresib + temozolomide and concomitant trotabresib + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma is ongoing (NCT04324840).

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

OBJECTIVES: The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. DESIGN: This was an observational retrospective study. SETTINGS: A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. PARTICIPANTS: A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. RESULTS: More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p<0.001), degenerative spine (OR=0.296, p=0.027) and expedited indications (OR=6.095, p<0.001) were independent factors for being operated on during the pandemic. CONCLUSIONS: Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.

Clinical improvement after cranioplasty and its relation to body position and cerebral hemodynamics.

Cranioplasty after decompressive craniectomy (DC) has been found to improve the neurological condition. The underlying mechanisms are still unknown. The aim of this study is to investigate the roles of the postural changes and atmospheric pressure (AP) in the brain hemodynamics and their relationship with clinical improvement. Seventy-eight patients were studied before and 72 h after cranioplasty with cervical and transcranial color Doppler ultrasound (TCCS) in the sitting and supine positions. Craniectomy size, shape, and force exerted by the AP (torque) were calculated. Neurological condition was assessed with the National Institutes of Health Stroke Scale (NIHSS) and the Barthel index. Twenty-eight patients improved after cranioplasty. Their time elapsed from the DC was shorter (214 vs 324 days), preoperative Barthel was worse (54 vs 77), internal carotid artery (ICA) mean velocity of the defect side was lower while sitting (14.4 vs 20.9 cm/s), and torque over the craniectomy was greater (2480.3 vs 1464.3 N*cm). Multivariate binary logistic regression showed the consistency of these changes. TCCS findings were no longer present postoperatively. Lower ICA (defect side) velocity in the sitting position correlates significantly with clinical improvement. Greater torque exerted by the AP might explain different susceptibilities to postural changes, corrected by cranioplasty.

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: a nationwide study in Spain.

OBJECTIVE: To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. SETTINGS: The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. PARTICIPANTS: This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. INTERVENTIONS: An exploratory factorial analysis was performed to select the most relevant variables of the sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. RESULTS: Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/105 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. CONCLUSIONS: Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105 people/week) was a statistically independent predictor of mortality. TRIAL REGISTRATION NUMBER: CEIM 20/217.

Reduction in the infection rate of cranioplasty with a tailored antibiotic prophylaxis: a nonrandomized study.

BACKGROUND: Cranioplasty carries a high risk of surgical site infections (SSIs) for a scheduled procedure, particularly with antibiotic-resistant bacteria. METHODS: The goal of this retrospective study was to measure the effect of tailored antibiotic prophylaxis on SSIs resulting from cranioplasties. The authors collected a prospective database of cranioplasties from 2009 to 2018. Risk factors for SSI were registered, as well as infection occurring during the first year postoperatively. A new protocol was initiated in 2016 consisting of antibiotic prophylaxis tailored to the colonizing flora of the skin of the scalp and decolonization of patients who were nasal carriers of methicillin-resistant S. aureus (MRSA); infection rates were compared. RESULTS: One hundred nine cranioplasties were identified, 64 in the old protocol and 45 in the new protocol. Of the 109 cranioplasties, 16 (14.7%) suffered an infection, 14 (21.9%) in the old protocol group and 2 (4.4%) in the new protocol group (OR for the new protocol 0.166, 95% CI 0.036-0.772). Multiple surgeries (OR 3.44), Barthel ≤ 70 (OR 3.53), and previous infection (OR 3.9) were risk factors for SSI. Of the bacteria identified in the skin of the scalp, 22.2% were resistant to routine prophylaxis (cefazoline). Only one patient was identified as a nasal carrier of MRSA and was decolonized. CONCLUSIONS: A high percentage of bacteria resistant to routine prophylaxis (cefazoline) was identified in the skin of these patients' scalps. The use of tailored antibiotic prophylaxis reduced significantly the infection rate in this particular set of patients.

Neuropsychological management of the awake patient surgery: A protocol based on 3-year experience with glial tumors. / Protocolo de intervención neuropsicológica en la cirugía del paciente despierto: experiencia de 3 años con tumores gliales.

INTRODUCTION: Glial brain tumours usually require neurosurgical treatment and they are associated with cognitive, emotional and behavioural impairments. Awake intraoperative brain mapping is the gold standard technique used to optimize the onco-functional balance. Neuropsychological assessment and intervention have relevance in this type of procedures. Currently, there is a lack of protocolled structure for the neuropsychological intervention being able to satisfy patient needs. METHOD: A retrospective descriptive study of 52 patients was performed, all of them with a diagnosis of glial tumour. The structure of the protocol developed in our centre is reported, also data of neuropsychological evaluation, comparing baseline performance with both immediate posterior performance, and long term performance. RESULTS: We describe our experience in each step of the intervention, highlighting the development of eight neurocognitive protocols for intraoperative brain mapping. The results of the neuropsychological examination objectify deficits in the immediate after surgery assessment which are reduced in the long-term assessment. CONCLUSIONS: We emphasize the need of providing and structuring the cognitive and emotional aspects of patients suffering from any pathology that entails acquired brain damage in hospital environment. This type of approach is aimed at increasing the quality of life of cancer patients by structuring and optimizing tasks during their surgical intervention and attending to the neuropsychological difficulties they suffer.

Venous angioma associated with atypical ophthalmoplegic migraine.

BACKGROUND: Ophthalmoplegic migraine is a rare syndrome in which episodic headaches are associated with ophthalmoplegia. Several recent reports emphasize the possibility, especially in atypical cases, of a heterogeneous type of ophthalmoplegic migraine. METHODS: We describe the case of an 18-year-old woman with recurrent episodic headache accompanied by binocular diplopia due to left third cranial nerve palsy. The symptoms resolve in hours. A diagnosis of atypical ophthalmoplegic migraine was established. RESULTS: Digital angiography revealed a venous angioma draining into the left cavernous sinus. CONCLUSIONS: This case reveals the importance of differential diagnosis in atypical migraine in which the symptomatology could be secondary to intracranial lesions. We propose venous stasis as a cause of symptoms.