Organelle resolved proteomics uncovers PLA2R1 as a novel cell surface marker required for chordoma growth.

Chordomas are clinically aggressive tumors with a high rate of disease progression despite maximal therapy. Given the limited therapeutic options available, there remains an urgent need for the development of novel therapies to improve clinical outcomes. Cell surface proteins are attractive therapeutic targets yet are challenging to profile with common methods. Four chordoma cell lines were analyzed by quantitative proteomics using a differential ultracentrifugation organellar fractionation approach. A subtractive proteomics strategy was applied to select proteins that are plasma membrane enriched. Systematic data integration prioritized PLA2R1 (secretory phospholipase A2 receptor-PLA2R1) as a chordoma-enriched surface protein. The expression profile of PLA2R1 was validated across chordoma cell lines, patient surgical tissue samples, and normal tissue lysates via immunoblotting. PLA2R1 expression was further validated by immunohistochemical analysis in a richly annotated cohort of 25-patient tissues. Immunohistochemistry analysis revealed that elevated expression of PLA2R1 is correlated with poor prognosis. Using siRNA- and CRISPR/Cas9-mediated knockdown of PLA2R1, we demonstrated significant inhibition of 2D, 3D and in vivo chordoma growth. PLA2R1 depletion resulted in cell cycle defects and metabolic rewiring via the MAPK signaling pathway, suggesting that PLA2R1 plays an essential role in chordoma biology. We have characterized the proteome of four chordoma cell lines and uncovered PLA2R1 as a novel cell-surface protein required for chordoma cell survival and association with patient outcome.

Fractionated radiotherapy for surgically resected intracranial meningiomas: A multicentre retrospective cohort study.

BACKGROUND: Aside from surgical resection, the only standard of care treatment modality for meningiomas is radiotherapy (RT). Despite this, few studies have focused on identifying clinical covariates associated with failure of fractionated RT following surgical resection (fRT), and the timing of fRT following surgery still remains controversial (adjuvant versus salvage fRT). We assessed the outcomes of the largest, multi-institutional cohort of surgically resected meningiomas treated with subsequent adjuvant and salvage fRT to identify factors associated with local freedom from recurrence (LFFR) over 3-10 years post-fRT and to determine the optimal timing of fRT. METHODS: Patients with intracranial meningiomas who underwent surgery and fRT between 1997 and 2018 were included. Primary endpoints were radiographic recurrence/progression and time to progression from the completion of fRT. RESULTS: 404 meningiomas were included for analysis. Of these, 167 (41.3%) recurred post-fRT. Clinical covariates independently associated with worse PFS post-fRT included receipt of previous RT to the meningioma, having a WHO grade 3 meningioma or recurrent meningioma, the meningioma having a higher MIB1-index or brain invasion on pathology, and older patient age at diagnosis. Subgroup analysis identified higher MIB1-index as a histological factor associated with poorer LFFR in WHO grade 2 meningiomas. 179 patients underwent adjuvant RT shortly after surgery whereas 225 patients had delayed, salvage fRT after recurrence/progression. Following propensity score matching, patients that underwent adjuvant fRT had improved LFFR post-fRT compared to those that received salvage fRT. CONCLUSION: There is a paucity of clinical factors that can predict a meningioma's response to fRT following surgery. Adjuvant fRT may be associated with improved PFS post-fRT compared to salvage fRT. Molecular biomarkers of RT-responsiveness are needed to better inform fRT treatment decisions.

Outcomes and predictors of response to fractionated radiotherapy as primary treatment for intracranial meningiomas.

Background: Surgery is the primary treatment for most meningiomas. However, primary fractionated radiotherapy (fRT) remains an option for patients with larger meningiomas in challenging anatomic locations or patients at prohibitively high surgical risk. Outcome prediction for these patients is uncertain and cannot be guided by histopathology without available tumor tissue from surgery. Therefore, we aimed to assess the clinical factors that contribute to treatment failure in a large cohort of meningiomas consecutively treated with fRT as primary therapy, with the goal of identifying predictors of response. Methods: Patients treated with primary fRT for intracranial meningiomas from 1998 to 2017 were reviewed. Those who received primary surgical resection, radiosurgery, previous fRT, or had <6 months of clinical follow-up were excluded. We applied logistic regression and Cox regression modeling to ascertain key predictors of treatment failure, progression-free survival (PFS), and adverse events (AE) following fRT. Results: Our cohort included 137 meningiomas, 21 of which progressed after fRT (median PFS 3.45 years). Progressive meningiomas had a larger median gross tumor volume (GTV) compared to those that remained stable (19.1 cm3 vs 9.6 cm3, p = 2.86 × 10-2). GTV > 11.27 cm3 was independently predictive of progression and larger GTV was associated with higher risk of significant (grades 3/4) AE following fRT. Cavernous sinus and optic nerve sheath meningiomas had overall excellent outcomes post-fRT. Conclusions: We present a large cohort of meningiomas treated with primary fRT and find GTV and anatomic location to be key predictors of outcome, adding to the complex treatment considerations for this heterogeneous disease.

Cerebrospinal fluid methylome-based liquid biopsies for accurate malignant brain neoplasm classification.

BACKGROUND: Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for the clinical management of the main three intra-axial brain tumor types. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. This study aimed to utilize methylomes from cerebrospinal fluid (CSF), a biofluid proximal to brain tumors, for reliable non-invasive classification that addresses limitations associated with low target abundance in existing approaches. METHODS: Binomial GLMnet classifiers of tumor type were built, in fifty iterations of 80% discovery sets, using CSF methylomes obtained from 57 BM, GBM, CNSL, and non-neoplastic control patients. Publicly-available tissue methylation profiles (N = 197) on these entities and normal brain parenchyma were used for validation and model optimization. RESULTS: Models reliably distinguished between BM (area under receiver operating characteristic curve [AUROC] = 0.93, 95% confidence interval [CI]: 0.71-1.0), GBM (AUROC = 0.83, 95% CI: 0.63-1.0), and CNSL (AUROC = 0.91, 95% CI: 0.66-1.0) in independent 20% validation sets. For validation, CSF-based methylome signatures reliably distinguished between tumor types within external tissue samples and tumors from non-neoplastic controls in CSF and tissue. CSF methylome signals were observed to align closely with tissue signatures for each entity. An additional set of optimized CSF-based models, built using tumor-specific features present in tissue data, showed enhanced classification accuracy. CONCLUSIONS: CSF methylomes are reliable for liquid biopsy-based classification of the major three malignant brain tumor types. We discuss how liquid biopsies may impact brain cancer management in the future by avoiding surgical risks, classifying unbiopsiable tumors, and guiding surgical planning when resection is indicated.

Surgery for Recurrent Glioblastoma Multiforme: A Retrospective Case Control Study.

OBJECTIVE: The role of surgery in recurrent glioblastoma multiforme (GBM) remains a controversial topic. The goal of this study was to perform a case control analysis including time to tumor recurrence as an additional prognostic factor in order to determine which patients benefit most from repeat surgery. METHODS: Our brain tumor database was reviewed over a 10-year period for all adult (≥18 years old) patients with primary isocitrate dehydrogenase wildtype GBM who received surgery for recurrent disease. These patients were then age, sex, and treatment matched to case controls from our institution who received medical therapy for recurrent disease. RESULTS: A total of 174 adult patients with GBM were included in the study, 87 patients who received surgery for recurrent GBM (surgery cohort) and 87 patients who did not receive surgery for recurrent GBM (nonsurgery cohort). The surgery cohort had longer overall survival (P = 0.0003) and postrecurrence survival (P = 0.001) than the nonsurgery cohort. When the surgery cohort was split into 2 groups on the basis of time to tumor recurrence, the long time to recurrence group (>6 months) demonstrated significantly increased survival compared with the short time to recurrence group (P < 0.0001). Multivariate analysis of both cohorts demonstrated surgery for recurrent GBM was independently significant after adjusting for age, Karnofsky Performance Scale, and time to tumor recurrence (P < 0.0001). CONCLUSIONS: Surgery for recurrent GBM leads to improved survival independent of age, Karnofsky Performance Scale, and time to tumor recurrence. Patients with time to tumor recurrence >6 months benefit most from additional surgery.

Editor's Choice - Peri-Operative Outcomes of Carotid Endarterectomy are Not Improved on Dual Antiplatelet Therapy vs. Aspirin Monotherapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis of the peri-operative outcomes of carotid endarterectomy (CEA) on dual antiplatelet therapy (DAPT) vs. aspirin monotherapy was carried out, to determine optimal peri-operative management with these antiplatelet agents. DATA SOURCES: The Web of Science, Pubmed, and Embase databases were searched from inception to July 2021. The corresponding authors of excluded articles were contacted to obtain additional data for possible inclusion. REVIEW METHODS: The main outcomes included ischaemic complications (stroke, transient ischaemic attack [TIA], and transcranial Doppler [TCD] measured micro-emboli), haemorrhagic complications (haemorrhagic stroke, neck haematoma, and re-operation for bleeding), and composite outcomes. Pooled estimates using odds ratios (ORs) were combined using a random or fixed effects model based on the results of the chi square test and calculation of I2. RESULTS: In total, 47 411 patients were included in 11 studies, with 14 345 (30.2%) receiving DAPT and 33 066 (69.7%) receiving aspirin only. There was no significant difference in the rates of peri-operative stroke (OR 0.87, 95% confidence interval [CI] 0.72 - 1.05) and TIA (OR 0.78, 95% CI 0.52 - 1.17) despite a significant reduction in TCD measured micro-emboli (OR 0.19, 95% CI 0.10 - 0.35) in the DAPT compared with the aspirin monotherapy group. Subgroup analysis did not reveal any significant difference in ischaemic stroke risk between patients with asymptomatic and symptomatic carotid artery stenosis. DAPT was associated with an increased risk of neck haematoma (OR 2.79, 95% CI 1.87 - 4.18) and re-operation for bleeding (OR 1.98, 95% CI 1.77 - 2.23) vs. aspirin. Haemorrhagic stroke was an under reported outcome in the literature. CONCLUSION: This meta-analysis found that CEA while on DAPT increased the risk of haemorrhagic complications, with similar rates of ischaemic complications, vs. aspirin monotherapy. This suggests that the risks of performing CEA on DAPT outweigh the benefits, even in patients with symptomatic carotid stenosis. The overall quality of studies was low, and improved reporting of CEA outcomes in the literature is necessary.

DNA methylation-based prognostic subtypes of chordoma tumors in tissue and plasma.

BACKGROUND: Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic chordoma subtypes that are detected noninvasively using plasma methylomes. METHODS: Methylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available. RESULTS: Consensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1-94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poor-performing "Immune-infiltrated" subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing "Cellular" subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versus-other binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52-1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data. CONCLUSIONS: Here, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome-based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.

Central Nervous System Metastases.

The proportion of patients developing central nervous system (CNS) metastasis is increasing. Most are identified once symptomatic. Surgical resection is indicated for solitary or symptomatic brain metastases, separation surgery for compressive radioresistant spinal metastases, and instrumentation for unstable spinal lesions. Surgical biopsies are performed when histological diagnoses are required. Stereotactic radiosurgery is an option for limited small brain metastases and radioresistant spinal metastases. Whole-brain radiotherapy is reserved for extensive brain metastases and leptomeningeal disease with approaches to reduce cognitive side effects. Radiosensitive and inoperable spinal metastases typically receive external beam radiotherapy. Systemic therapy is increasingly being utilized for CNS metastases.

Resection and radiotherapy for intracranial ependymoma: a multiinstitutional 50-year experience.

OBJECTIVE: Maximal safe resection is the standard-of-care treatment for adults with intracranial ependymoma. The value of adjuvant radiotherapy remains unclear as these tumors are rare and current data are limited to a few retrospective cohort studies. In this study, the authors assembled a cohort of patients across multiple international institutions to assess the utility of adjuvant radiotherapy in this patient population. METHODS: Adults with intracranial ependymoma managed surgically at the University Health Network in Toronto, Canada, the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma, and The Ottawa Hospital in Ottawa, Canada, were included in this study. The primary end points were progression-free survival (PFS) and overall survival (OS). Clinicopathological variables were assessed in univariate and multivariate Cox proportional hazard models for prognostic significance of PFS and OS. RESULTS: A total of 122 patients diagnosed between 1968 and 2019 were identified for inclusion. The majority of patients had grade II ependymomas on histopathology (78%) that were infratentorially located (71%), underwent gross-total (GTR) or near-total resection (NTR; 55%), and were treated with adjuvant radiotherapy (67%). A volumetric analysis of the extent of resection in 49 patients with available tumor volume data supported the accuracy of the categorical GTR, NTR, and subtotal resection (STR) groups utilized. Independent statistically significant predictors of poorer PFS in the multivariate analysis included STR or biopsy (vs GTR/NTR; HR 5.4, 95% confidence interval [CI] 2.4-11.0, p < 0.0001) and not receiving adjuvant radiotherapy; cranial (HR 0.5, 95% CI 0.2-1.1) and craniospinal (HR 0.2, 95% CI 0.04-0.5) adjuvant radiotherapy regimens improved PFS (p = 0.0147). Predictors of poorer OS in the multivariate analysis were grade III histopathology (vs grade II: HR 5.7, 95% CI 1.6-20.2, p = 0.0064) and undergoing a biopsy/STR (vs GTR/NTR: HR 9.8, 95% CI 3.2-30.1, p = 0.0001). CONCLUSIONS: The results of this 50-year experience in treating adult intracranial ependymomas confirm an important role for maximal safe resection (ideally GTR or NTR) and demonstrate that adjuvant radiotherapy improves PFS. This work will guide future studies as testing for molecular ependymoma alterations become incorporated into routine clinical practice.

Liquid Biomarkers for Improved Diagnosis and Classification of CNS Tumors.

Liquid biopsy, as a non-invasive technique for cancer diagnosis, has emerged as a major step forward in conquering tumors. Current practice in diagnosis of central nervous system (CNS) tumors involves invasive acquisition of tumor biopsy upon detection of tumor on neuroimaging. Liquid biopsy enables non-invasive, rapid, precise and, in particular, real-time cancer detection, prognosis and treatment monitoring, especially for CNS tumors. This approach can also uncover the heterogeneity of these tumors and will likely replace tissue biopsy in the future. Key components of liquid biopsy mainly include circulating tumor cells (CTC), circulating tumor nucleic acids (ctDNA, miRNA) and exosomes and samples can be obtained from the cerebrospinal fluid, plasma and serum of patients with CNS malignancies. This review covers current progress in application of liquid biopsies for diagnosis and monitoring of CNS malignancies.

A case series of pediatric survivors of anaplastic pleomorphic xanthoastrocytoma.

BACKGROUND: Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists regarding the optimal therapy. Here, we report on 3 pediatric cases of APXA. METHODS: Our institutional database was queried for cases of APXA and 3 cases were identified. Surgical samples were processed for methylation profiling and chromosomal microarray analysis. Methylation data were uploaded to the online CNS tumor classifier to determine methylation-based diagnoses to determine copy number variations (CNVs). RESULTS: Two patients were male, 1 female, and all were aged 12 years at diagnosis. All underwent a gross total resection (GTR) and were diagnosed with an APXA. Immunohistochemical analysis demonstrated that 2 cases were BRAF V600E positive. Methylation-based tumor classification supported the APXA diagnosis in all cases. CNV analyses revealed homozygous CKDN2A deletions in all and chromosome 9p loss in 2 cases. All patients received radiation therapy (54 Gy in 30 fractions) with concurrent temozolomide. Two patients received maintenance chemotherapy with temozolomide and lomustine for 6 cycles as per the Children's Oncology Group ACNS0423. The third patient recurred and went on to receive a second GTR and 6 cycles of lomustine, vincristine, and procarbazine. All are alive with no evidence of disease >4 years post-treatment completion (overall survival = 100%, event free survival = 67%). CONCLUSIONS: The natural history and optimal treatment of this rare pediatric tumor are not well understood. This case series supports the use of adjuvant chemoradiotherapy in the treatment of APXA. The genetic landscape may be informative for optimizing treatment and prognosis.

Dysphagia rates in single- and multiple-level anterior cervical discectomy and fusion surgery: a meta-analysis.

BACKGROUND: To conduct a meta-analysis to assess dysphagia complicating single-level and multiple-level (≥2) anterior cervical discectomy and fusion (ACDF) surgery. METHODS: Electronic searches were performed using four electronic databases from their inception to December 2017. Relevant studies reporting the rate of dysphagia as an endpoint for patients undergoing ACDF for degenerative disease, myelopathy, cervical canal stenosis or ossification of the posterior longitudinal ligament were identified according to prior inclusion and exclusion criteria. Statistical analysis was performed using a fixed effect model. P-scores were used to rank the levels of ACDF based on the rate of dysphagia. I2 was used to explore heterogeneity. RESULTS: Ten studies were identified and included in the systematic review and meta-analysis, with a total of 4,018 patients identified; 2,362 patients underwent single-level ACDF, while 1,656 underwent multiple level (≥2 ACDF). The mean age ranged from 49.45 to 57.77 years. Mean follow-up time ranged from 2 days to 27.3 months. Overall, meta-analysis demonstrated a statistically significant higher dysphagia rate for multiple-level ACDF (6.6%) than for single-level ACDF (4%) (P heterogeneity =0.151, OR =1.42, 95% CI: 1.05-1.91, I2=32%). CONCLUSIONS: Dysphagia is a relatively common complication in the early postoperative period following ACDF and may cause patients significant discomfort and distress. This meta-analysis demonstrates a higher rate of dysphagia with multiple-level ACDF than with single-level ACDF at a period of 12-24 months.

Highlights of the 2019 Society for Neuro-Oncology Inaugural Brain Metastases Conference: establishing a dedicated meeting to address an unmet need in the field.

Brain metastases comprise the majority of central nervous tumors in adults and confer poorer survival for patients with primary cancer. Systemic disease control is improving with advances in treatment for primary tumors and the complexity of brain metastases management is increasing with multimodality approaches incorporating combinations of surgery, radiotherapy, chemotherapy, targeted therapies, and immunotherapy. Accordingly, the Society for Neuro-Oncology established an annual brain metastases conference to unite colleagues from multiple disciplines with content spanning a range of timely topics relevant to improving our understanding of brain metastases and how they are optimally treated. The inaugural meeting on August 16-17, 2019 was very successful with 163 impactful presentations being delivered to a large multidisciplinary audience on current research advances in the field of neuro-oncology. This review summarizes the major themes of the meeting and highlights the main findings presented.

Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes.

Definitive diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Noninvasive diagnostic approaches provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. In the present study, we show that DNA-methylation profiles from plasma reveal highly specific signatures to detect and accurately discriminate common primary intracranial tumors that share cell-of-origin lineages and can be challenging to distinguish using standard-of-care imaging.

The central nervous system tumor methylation classifier changes neuro-oncology practice for challenging brain tumor diagnoses and directly impacts patient care.

BACKGROUND: Molecular signatures are being increasingly incorporated into cancer classification systems. DNA methylation-based central nervous system (CNS) tumor classification is being recognized as having the potential to aid in cases of difficult histopathological diagnoses. Here, we present our institutional clinical experience in integrating a DNA-methylation-based classifier into clinical practice and report its impact on CNS tumor patient diagnosis and treatment. METHODS: Prospective case review was undertaken at CNS tumor board discussions over a 3-year period and 55 tumors with a diagnosis that was not certain to two senior neuropathologists were recommended for methylation profiling based on diagnostic needs. Tumor classification, calibrated scores, and copy number variant (CNV) plots were obtained for all 55 cases. These results were integrated with histopathological findings to reach a final diagnosis. We retrospectively reviewed each patient's clinical course to determine final neuro-pathology diagnoses and the impact of methylation profiling on their clinical management, with a focus on changes that were made to treatment decisions. RESULTS: Following methylation profiling, 46 of the 55 (84%) challenging cases received a clinically relevant diagnostic alteration, with two-thirds having a change in the histopathological diagnosis and the other one-third obtaining clinically important molecular diagnostic or subtyping alterations. WHO grading changed by 27% with two-thirds receiving a higher grade. Patient care was directly changed in 15% of all cases with major changes in clinical decision-making being made for these patients to avoid unnecessary or insufficient treatment. CONCLUSIONS: The integration of methylation-based CNS tumor classification into diagnostics has a substantial clinical benefit for patients with challenging CNS tumors while also avoiding unnecessary health care costs. The clinical impact shown here may prompt the expanded use of DNA methylation profiling for CNS tumor diagnostics within prominent neuro-oncology centers globally.

Novel Statistical Analyses to Assess Hearing Outcomes After ABI Implantation in NF2 Patients: Systematic Review and Individualized Patient Data Analysis.

BACKGROUND: Patients with neurofibromatosis type 2 develop bilateral vestibular schwannomas with progressive hearing loss. Auditory brainstem implants (ABIs) stimulate hearing in the cochlear nuclei and show promise in improving hearing. Here, we assess the impact of ABI on hearing over time by systematically reviewing the literature and re-analyzing available individual patient data. METHODS: A multidatabase search identified 3 studies with individual patient data of longitudinal hearing outcomes after ABI insertion in adults. Data were collected on hearing outcomes of different sound complexities from sound to speech using an ABI ± lip reading ability plus demographic data. Because of heterogeneity each study was analyzed separately using random effects multilevel mixed linear modeling. RESULTS: Across all 3 studies (n = 111 total) there were significant improvements in hearing over time from ABI placement (P < 0.000 in all). Improvements in comprehension of sounds, words, sentences, and speech occurred over time with ABI use + lip reading but lip reading ability did not improve over time. All categories of hearing complexity had over 50% comprehension after over 1 year of ABI use and some subsets had over 75% or near 100% comprehension. Vowel comprehension was greater than consonant, and word comprehension was greater than sentence comprehension (P < 0.0001 in both). Age and sex did not predict outcomes. CONCLUSIONS: ABIs improve hearing beyond lip reading alone, which represents baseline patient function prior to treatment, and the benefits continue to improve with time. These findings may be used to guide patient counseling regarding ABI insertion, rehabilitation course after insertion, and future studies.

Use of Antiepileptic Drugs in Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Controversy exists in antiepileptic drug (AED) prophylaxis prescribing in patients with aneurysmal subarachnoid hemorrhage (SAH). We undertook the Use of Antiepileptic Drugs in Aneurysmal Subarachnoid Hemorrhage (ALIBI) study to identify factors associated with prescribing practices. METHODS: A retrospective chart review of all consecutive patients requiring Level 1 care with aneurysmal SAH admitted between 2012 and 2014 to the intensive care unit at Toronto Western Hospital, Ontario, Canada, was conducted. Data were collected on clinical and imaging characteristics. Primary and secondary outcomes were AED prophylaxis and clinical seizure activity during hospitalization. Data were compared using chi-square or Mann-Whitney U-tests. Those variables found to be significant, or trending toward significance, on univariate analysis were fitted to multivariate regression. RESULTS: Sixty-eight patients were included. Mean age was 62 ± 12.2, and 42.6% of patients were male. Of these, 21 patients (30.9%) received AED prophylactically, while 18 (26.5%) had reported seizures at some point during hospitalization. Female gender and presence of midline shift (MLS) were significantly associated or approached significance with AED prophylaxis in univariate analysis (p = 0.036 and p = 0.062, respectively). In multivariate analysis, only MLS was an independent predictor (odds ratio 5.09, p = 0.04). CONCLUSION: The presence of MLS was an independent predictor of seizure activity in patients with aneurysmal SAH. AED prophylaxis prescribing patterns seemed arbitrary and was not informed by identifiable clinical factors or true risk factors for seizure. A current lack of evidence guiding AED prescribing practice highlights the need for larger studies in this patient population.

Utiliser des médicaments antiépileptiques dans des cas d'hémorragie sous-arachnoïdienne anévrismale. Introduction: Dans les cas de patients victimes d'hémorragie sous-arachnoïdienne anévrismale, il faut savoir qu'un traitement prophylactique au moyen de médicaments antiépileptiques demeure controversé. Dans cette étude, nous avons donc entrepris d'identifier les facteurs associés aux pratiques de prescription de ces médicaments lorsque survient ce type d'hémorragie. Méthodes: Pour ce faire, nous avons passé en revue les dossiers de tous les patients vus consécutivement et ayant nécessité, après avoir été admis entre 2012 et 2014 à l'unité des soins intensifs du Toronto Western Hospital (Ontario, Canada), des soins de niveau 1 à la suite d'une hémorragie sous-arachnoïdienne anévrismale. Nous avons collecté nos données en nous basant sur des aspects cliniques et sur d'autres aspects liés à des examens d'IRM. Notre principal résultat mesuré a été l'efficacité d'un traitement prophylactique au moyen de médicaments antiépileptiques; dans un deuxième temps, nous avons aussi cherché à mesurer l'activité convulsive clinique en cours d'hospitalisation. Nous avons ensuite comparé nos données en utilisant les tests du X2 ou de U Mann-Whitney. Les variables apparues significatives ou tendant à être significatives dans le cadre d'une analyse univariée ont été ajustées pour une régression multivariée. Résultats: 68 patients ont été inclus dans cette étude. Leur âge moyen était de 62 ± 12,2; 42,6% d'entre eux étaient des hommes. De ce nombre, 21 patients (30,9%) ont alors suivi un traitement prophylactique au moyen de médicaments antiépileptiques tandis que 18 (26,5%) ont fait état de crises convulsives à un moment ou un autre de leur séjour à l'hôpital. Dans le cadre d'une analyse univariée, le fait d'être une femme et la présence d'une déviation de la ligne médiane (midline shift) ont été par ailleurs nettement associés ou en grande partie associés à un traitement prophylactique au moyen de médicaments antiépileptiques (respectivement p = 0,036 et p = 0,062). Dans le cadre d'une analyse multivariée, seule la déviation de la ligne médiane s'est avérée un facteur prédicteur indépendant (rapport des cotes de 5,09; P = 0,04). Conclusion: La présence de déviation de la ligne médiane constitue un facteur prédictif indépendant d'activité convulsive chez des patients victimes d'hémorragie sous-arachnoïdienne anévrismale. De plus, les tendances en matière de prescription de médicaments antiépileptiques apparaissent arbitraires et ne reposent pas sur des facteurs cliniques identifiables ou sur de véritables facteurs de risque liés aux convulsions. Le manque actuel de preuves pouvant orienter les pratiques de prescription de ces médicaments met en lumière la nécessité d'effectuer de plus amples études au sein de cette population de patients.

The importance of preoperative tissue sampling for mobile spine chordomas: literature review and report of two cases.

INTRODUCTION: Pre-operative biopsy and diagnosis of chordomas of the mobile spine is indicated as en bloc resections improve outcomes. This review of the management of mobile spine chordomas includes two cases of unexpected mobile spine chordomas where a preoperative tissue diagnosis was decided against and may have altered surgical decision-making. CASE PRESENTATION: Two lumbar spine chordomas thought to be metastatic and primary bony lesions preoperatively were not biopsied before surgery and eventual pathology revealed chordoma. Preoperative diagnoses were questioned during surgery after an intraoperative tissue diagnosis of chordoma in one case and unclear pathology with non-characteristic tumor morphology in the other. The surgical plan was altered in these cases to maximize resection as en bloc resection reduces the risk of local recurrence in chordoma. DISCUSSION: Mobile spine chordomas are rare and en bloc resection is recommended, contrary to the usual approach to more common spine tumors. Since en bloc resection of spine chordomas improves disease free survival, it has been recommended that tissue diagnosis be obtained preoperatively when chordoma is considered in the differential diagnosis, in order to guide surgical planning. We present two cases where a preoperative biopsy was considered but not obtained after neuroradiology consultation and imaging review, which may have been managed differently if the diagnosis of spine chordomas were known pre-operatively.