Response Assessment in Brain Metastases Managed by Stereotactic Radiosurgery: A Reappraisal of the RANO-BM Criteria.

BACKGROUND: Brain metastases (BM) are increasingly being treated using stereotactic radiosurgery (SRS). Standardized response criteria are necessary to improve research and treatment protocols. This study's goal was to validate the RANO-BM criteria thresholds for tumor progression in a cohort of patients with brain metastases managed using SRS. METHODS: We performed a retrospective analysis of patients treated at least twice with SRS for brain metastases. Local progression, as defined by RANO-BM criteria, was compared to our multidisciplinary tumor board's treatment recommendation. A ROC curve was generated using varying diameter thresholds to assess the sensitivity and specificity of current RANO-BM criteria. RESULTS: 249 metastases in 67 patients were included in the analysis. RANO-BM criteria current progression thresholds yielded a sensitivity of 38%, a specificity of 95%, a positive predictive value of 71%, and a negative predictive value of 84% relative to our tumor board's treatment recommendation. Modified RANO-BM criteria using absolute diameter differences of 2.5 mm yielded a sensitivity of 83%, a specificity of 87%, a positive predictive value of 67% and a negative predictive value of 94%. CONCLUSIONS: Current RANO-BM criteria unreliably identifies clinically relevant tumor progression. The use of absolute diameter differences thresholds appears superior in our BM cohort.

Classification of subdural hematomas: proposal for a new system improving the ICD Coding Tools.

Background: The International Statistical Classification of Diseases (ICD) classifies subdural hematoma (SDH) as traumatic or non-traumatic. In clinical settings, however, SDH is typically described as either acute or chronic. Objective: The goal of this study was to assess how the ICD Coding Tools captures the clinical terminology and propose an improved classification that would increase the system's usefulness in administrative, statistical and research applications. Methods: We performed a retrospective analysis of patients who presented to our center with an ICD diagnostic code for either traumatic or non-traumatic SDH. A qualitative analysis of patients' charts was performed to identify elements relevant to management and prognosis, following which a meeting between expert investigators was held to elaborate a new classification of SDH. Imaging from all patients was then reviewed and cases were reclassified according to our proposed system. Results: A total of 277 SDH cases were included. Themes documented in the charts included chronicity, etiology, side, and symptoms. We created a new classification which distinguishes acute SDH (aSDH) from membrane-associated SDH (mSDH). aSDH were further divided into traumatic aSDH (taSDH) and non-traumatic aSDH (ntaSDH), while mSDH were divided into acute on chronic (a/cSDH), subacute (sSDH) and chronic (cSDH) categories. Conclusion: The ICD coding system correctly identifies taSDH and ntaSDH. However, it remains non-specific for mSDH. We propose this new SDH classification system to better capture chronicity and etiology - factors felt to impact management and prognosis.

Work-up and Management of Asymptomatic Extracranial Traumatic Vertebral Artery Injury.

BACKGROUND: Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1-2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains. METHODS: A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics. RESULTS: One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3-6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1-3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3-6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1-3 months. CONCLUSION: This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.

Systemic considerations for the surgical treatment of spinal metastatic disease: a scoping literature review.

Systemic assessment is a pillar in the neurological, oncological, mechanical, and systemic (NOMS) decision-making framework for the treatment of patients with spinal metastatic disease. Despite this importance, emerging evidence relating systemic considerations to clinical outcomes following surgery for spinal metastatic disease has not been comprehensively summarised. We aimed to conduct a scoping literature review of this broad topic. We searched MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL databases from Jan 1, 2000, to July 31, 2021. 61 articles were included, accounting for a total of 22 335 patients. Preoperative systemic variables negatively associated with postoperative clinical outcomes included demographics (eg, older age [>60 years], Black race, male sex, low or elevated body-mass index, and smoking status), medical comorbidities (eg, cardiac, pulmonary, hepatic, renal, endocrine, vascular, and rheumatological), biochemical abnormalities (eg, hypoalbuminaemia, atypical blood cell counts, and elevated C-reactive protein concentration), low muscle mass, generalised motor weakness (American Spinal Cord Injury Association Impairment Scale grade and Frankel grade) and poor ambulation, reduced performance status, and systemic disease burden. This is the first comprehensive scoping review to broadly summarise emerging evidence relevant to the systemic assessment component of the widely used NOMS framework for spinal metastatic disease decision making. Medical, surgical, and radiation oncologists can consider these findings when prognosticating spinal metastatic disease-related surgical outcomes on the basis of patients' systemic condition. These factors might inform a shared decision-making approach with patients and their families.

A nationwide prospective multicenter study of external ventricular drainage: accuracy, safety, and related complications.

OBJECTIVE: External ventricular drainage (EVD) catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH), and suboptimal placement. The aim of this study was to investigate the rates of EVD catheter complications and their associated risk factor profiles in order to optimize the safety and accuracy of catheter insertion. METHODS: A total of 348 patients with urgently placed EVD catheters were included as a part of a prospective multicenter observational cohort. Strict definitions were applied for each complication category. RESULTS: The rates of misplacement, ECI/ventriculitis, and ICH were 38.6%, 12.2%, and 9.2%, respectively. Catheter misplacement was associated with midline shift (p = 0.002), operator experience (p = 0.031), and intracranial length (p < 0.001). Although mostly asymptomatic, ICH occurred more often in patients receiving prophylactic low-molecular-weight heparin (LMWH) (p = 0.002) and those who required catheter replacement (p = 0.026). Infectious complications (ECI/ventriculitis and suspected ECI) occurred more commonly in patients whose catheters were inserted at the bedside (p = 0.004) and those with smaller incisions (≤ 1 cm) (p < 0.001). ECI/ventriculitis was not associated with preinsertion antibiotic prophylaxis (p = 0.421), catheter replacement (p = 0.118), and catheter tunneling length (p = 0.782). CONCLUSIONS: EVD-associated complications are common. These results suggest that the operating room setting can help reduce the risk of infection, but not the use of preoperative antibiotic prophylaxis. Although EVD-related ICH was associated with LMWH prophylaxis for deep vein thrombosis, there were no significant clinical manifestations in the majority of patients. Catheter misplacement was associated with operator level of training and midline shift. Information from this multicenter prospective cohort can be utilized to increase the safety profile of this common neurosurgical procedure.

Minimally Invasive Resection of an S3 Osteoid Osteoma Using an Intraoperative O-Arm: A Technical Note.

Osteoid osteomas are benign primary bone tumors that typically arise in posterior vertebrae of the spine. For patients with severe pain or those poorly controlled with non-steroidal anti-inflammatory drugs, surgical management is the mainstay of treatment. The recommended surgical treatment option is complete open excision, although minimally invasive CT-guided percutaneous excision and CT-guided radiofrequency ablation have been reported. Open resection can result in prolonged hospital stays, activity restrictions, and possible spinal destabilization. We sought to utilize a lateral minimally invasive approach. We highlight the importance of aggressive surgical resection and the utility of using fluoroscopy and O-arm guidance to optimize the extent of resection. We report a pediatric case of a 12-year-old male who presented with an S3 osteoid osteoma. The patient underwent a minimally invasive resection with complete resection and confirmation of the histopathologic diagnosis. Postoperative imaging showed complete resection of the tumor. The patient went home five hours after surgery with return to daily activities; his symptoms resolved completely. However, the patient had symptomatic recurrence and underwent a second more aggressive minimally invasive resection using O-arm guidance. At the current three-month follow-up, the patient is symptom- and tumor-free. The minimally invasive resection of a pediatric sacral osteoid osteoma is a valid alternative to standard open resection and is associated with a decreased blood loss, decreased length of stay in the hospital, and decreased time to full functional recovery. The pitfalls are learning curve and risk of incomplete resection that can be counterbalanced with an intraoperative O-arm to guide resection and confirm complete excision.

Successful Management of Glioblastoma Chemotherapy-Associated Dysgeusia with Gabapentin.

Dysgeusia is a frequent, yet underreported side effect of chemotherapy for cancer. We report here the first use of gabapentin in two glioblastoma patients who developed dysgeusia following intra-arterial administration of carboplatin or oral administration of lomustine, respectively. Treatment initiation was followed by resolution of taste alteration within weeks. Both patients reported significant improvement in their quality of life and regained weight, allowing further chemotherapy cycles. We hypothesized that in these two cases, chemotherapy impeded gustatory cells turnover and function, resulting in a gustatory "deafferentation-like" syndrome which was successfully addressed by the medication.

Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study.

Importance: Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited. Objective: To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT. Design, Setting, and Participants: FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019. Interventions: SRS and WBRT for small cell lung cancer brain metastases. Main Outcomes and Measures: Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses. Results: In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results. Conclusions and Relevance: Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.

Stereotactic radiosurgery for central neurocytomas: an international multicenter retrospective cohort study.

OBJECTIVE: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors. METHODS: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated. RESULTS: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022). CONCLUSIONS: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

Gender differences in the surgical management of lumbar degenerative disease: a scoping review.

OBJECTIVE: Despite efforts toward achieving gender equality in clinical trial enrollment, females are often underrepresented, and gender-specific data analysis is often unavailable. Identifying and reducing gender bias in medical decision-making and outcome reporting may facilitate equitable healthcare delivery. Gender disparity in the utilization of surgical therapy has been exemplified in the orthopedic literature through studies of total joint arthroplasty. A paucity of literature is available to guide the management of lumbar degenerative disease, which stratifies on the basis of demographic factors. The objective of this study was to systematically map and synthesize the adult surgical literature regarding gender differences in pre- and postoperative patient-reported clinical assessment scores for patients with lumbar degenerative disease (disc degeneration, disc herniation, spondylolisthesis, and spinal canal stenosis). METHODS: A systematic scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. MEDLINE, Embase, and the Cochrane Registry of Controlled Trials were searched from inception to September 2018. Study characteristics including patient demographics, diagnoses, procedures, and pre- and postoperative clinical assessment scores (pain, disability, and health-related quality of life [HRQoL]) were collected. RESULTS: Thirty articles were identified, accounting for 32,951 patients. Six studies accounted for 84% of patients; 5 of the 6 studies were published by European groups. The most common lumbar degenerative conditions were disc herniation (59.0%), disc degeneration (20.3%), and spinal canal stenosis (15.9%). The majority of studies reported worse preoperative pain (93.3%), disability (81.3%), and HRQoL (75%) among females. The remainder reported equivalent preoperative scores between males and females. The majority of studies (63.3%) did not report preoperative duration of symptoms, and this represents a limitation of the data. Eighty percent of studies found that females had worse absolute postoperative scores in at least one outcome category (pain, disability, or HRQoL). The remainder reported equivalent absolute postoperative scores between males and females. Seventy-three percent of studies reported either an equivalent or greater interval change for females. CONCLUSIONS: Female patients undergoing surgery for lumbar degenerative disease (disc degeneration, disc herniation, spondylolisthesis, and spinal canal stenosis) have worse absolute preoperative pain, disability, and HRQoL. Following surgery, females have worse absolute pain, disability, and HRQoL, but demonstrate an equal or greater interval change compared to males. Further studies should examine gender differences in preoperative workup and clinical course.

Neuronavigation-Guided Endoscopic Endonasal Drainage of Pediatric Anterior Cranial Base Epidural and Subdural Empyema.

In children, epidural and/or subdural intracranial empyema can complicate frontal sinusitis or pansinusitis. The standard transcranial approach used to treat epidural or subdural empyema has many drawbacks, but these can be avoided with an endoscopic expanded endonasal approach (EEA). To support the feasibility and advantages of this approach, we report the successful drainage through endoscopic EEA of a bifrontal empyema caused by an intracranial extension of pansinusitis. Our case and the ones previously reported in the literature establish well that endoscopic EEA offers several advantages over the standard craniotomy. Hence, EEA should be considered as an alternative to the transcranial approach when surgically draining anterior skull base empyema resulting from pansinusitis in children.

Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF).

BACKGROUND: Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. OBJECTIVE: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). METHODS: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. RESULTS: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005). CONCLUSION: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Repeat stereotactic radiosurgery for the management of locally recurrent brain metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is a well-established treatment option for brain metastases (BM). Repeat SRS for progressive BM is an increasingly used paradigm, although little data is available to support this practice. The goal of this study was to assess the safety and efficacy of a second SRS procedure on a previously treated BM. METHODS: We performed a retrospective metastasis-level analysis of patients who underwent two SRS procedures on the same lesion and for whom at least 6 months of radiological follow-up was available. The data collected included patient characteristics, clinical symptoms at time of treatment, SRS parameters, radiological response per RANO-BM criteria, clinical evolution and survival. RESULTS: Seventy-five BM in 56 patients were included in the analysis. Most frequent primary histologies were non-small-cell lung cancer (59%) and breast cancer (19%). At the second SRS, median treatment volume was 1.19 cc (range 0.07-20.6) treated with a median margin dose of 18 Gy (range 12-20) at the 50% isodose line (range 30-80%). Median follow-up was 11 months. Progression per RANO-BM criteria occurred in 31%, yielding actuarial local control at 1, 2, and 5 years of 68%, 54% and 54% respectively. At last follow-up, 10 patients (18%) had improved relative to the initial presentation, while 21 (38%) were stable and 25 (44%) were deteriorated. Radiation-induced edema and radionecrosis occurred in 8.3% and 5% respectively. The median survival from the diagnosis of BM was 30 months. CONCLUSION: Repeat SRS is a safe and effective novel therapeutic approach to consider in carefully selected patients.

Embolization of the Middle meningeal artery in chronic subdural hematoma - A systematic review.

Chronic subdural hematomas (cSDH) are one of the most frequent reasons for consultation in neurosurgery. Multiple authors have proposed middle meningeal artery embolization (MMAE) as an option in cSDH patients to manage recurrence or avoid surgery altogether. Although many articles have been published on the matter, the current body of evidence still has to be evaluated before MMAE is integrated into clinical practice. The goal of this study was to review the evidence on MMAE in cSDH to assess its safety, feasibility, indications and efficacy. We performed a systematic review of the literature according to PRISMA guidelines using multiple electronic databases. Our search yielded a total of 18 original articles from which data were extracted. A total of 190 patients underwent MMAE from which 81.3% were symptomatic cSDH. Over half (52.3%) of the described population were undergoing antithrombotic therapy. Most (83%) procedures used polyvinyl alcohol (PVA) particles and no complications were reported regarding the embolization procedures. Although the definition of resolution varied among authors, cSDH resolution was reported in 96.8% of cases. MMAE is a feasible technique for cSDH, but the current body of evidence does not yet support its use as a standard treatment. Further studies with a higher level of evidence are necessary before MMAE can be formally recommended.

Mobile Applications in Neurosurgery: A Systematic Review, Quality Audit, and Survey of Canadian Neurosurgery Residents.

BACKGROUND: In the past decade, smartphone applications (Apps) have experienced remarkable development across all fields of medicine, including neurosurgery. However, owing to a lack of regulatory oversight and peer review, a clear need exists for a comprehensive review and audit of the existing available Apps. In the present study, we systematically reviewed the existing mobile Apps in neurosurgery, evaluated their clinical use by neurosurgery residents in Canada, and performed a quality audit of the most popular Apps. METHODS: Indexed Apps were identified from either the Google Play Store or the iOS App Store using a comprehensive list of keywords related to neurosurgery. A subsequent cross-sectional survey of 76 Canadian neurosurgery residents was conducted, including a section on smartphone App use. We next evaluated the most popular Apps among the residents using the Healthcare Smartphone App Evaluation Tool and performed a quality audit of their content using established medical references. RESULTS: The survey identified 118 mobile Apps related to neurosurgery. The 3 most used Apps used by the current cohort of Canadian neurosurgery residents were Neurosurgery Survival Guide, Neuromind, and the Journal of Neurosurgery App. Each of these 3 Apps received an excellent score on the Healthcare Smartphone App Evaluation Tool. A quality audit of 30 pages of the Neurosurgery Survival Guide and 40 clinical scores of the Neuromind App, performed by 10 neurosurgery residents, failed to reveal inaccurate or false statements. CONCLUSION: The present study has highlighted the current landscape of neurosurgery mobile Apps and their use among neurosurgery residents.

Cranioplasties following craniectomies in children-a multicenter, retrospective cohort study.

OBJECTIVE: Complications following pediatric cranioplasty after craniectomy with either autologous bone flaps or cranial implants are reported to be common, particularly bone flap resorption. However, only sparse data are available regarding cranioplasty strategies, complications, and outcomes. This manuscript describes a Canadian-Dutch multicenter pediatric cohort study with autografts and cranial implant cranioplasties following craniectomies for a variety of indications. METHODS: The study included all children (< 18 years) who underwent craniectomy and subsequent cranioplasty surgeries from 2008 to 2014 (with a minimum of 1-year follow-up) at four academic hospitals with a dedicated pediatric neurosurgical service. Data were collected regarding initial diagnosis, age, time interval between craniectomy and cranioplasty, bone flap storage method, type of cranioplasty for initial procedure (and redo if applicable), and the postoperative outcome including surgical site infection, wound breakdowns, bone flap resorption, and inadequate fit/disfigurement. RESULTS: Sixty-four patients (46 males, average age 9.7 ± 5.5 years) were eligible for inclusion, with mean follow-up of 82.3 ± 31.2 months after craniectomy. Forty cranioplasties (62.5%) used autologous bone re-implant, 23 (57.5%) of which showed resorption. On average, resorption was documented at 434 days (range 62-2796 days) after reimplantation. In 20 cases, a revision cranioplasty was needed. In 24 of the post-craniectomy cases (37.5%), a cranial implant was used with one of ten different implant types. Implant loosening prompted a complete revision cranioplasty in 2 cases (8.3%). Cranial implants were associated with low morbidity and lower reoperation dates compared to the autologous cranioplasties. CONCLUSION: The most prominent finding in this multicenter cohort study was that bone flap resorption in children remains a common and widespread problem following craniectomy. Cranioplasty strategies varied between centers and evolved over time within centers. Cranial implants were associated with low morbidity and low reoperation rates. Still, longer term and prospective multicenter cohort studies are needed to optimize cranioplasty strategies in children after craniectomies.

Chronic Subdural Hematoma: Toward a New Management Paradigm for an Increasingly Complex Population.

Chronic subdural hematoma (cSDH) is a frequent yet poorly studied entity. Patients with cSDH are increasingly using antithrombotic medication, are now older, and present with a variety of clinical symptoms, including incidental discoveries. Despite this increasing complexity, management has remained roughly unchanged since the late 1990s. We review here the state of cSDH research under way at Université de Sherbrooke and around the world with a focus on studies addressing specific gaps in the current evidence base. We show that evidence is lacking at many decision points in the typical cSDH patient treatment algorithm. No definition of cSDH is universally accepted, and a formal definition project, along with suggested common data elements to be reported in future trials (CODE-CSDH: formal cSDH definition project) is ongoing. An amendment to International Statistical Classification of Diseases and Related Health Problems (ICD-11) has also been proposed to improve classification and registry research. Within the cSDH clinical assessment, evidence for the occurrence of nonepileptic, stereotypical, and intermittent symptoms (NESIS) is emerging. The GENESIS study (Generation Evidence on the etiology and management of NESIS) will test etiological and therapeutic hypotheses for this patient subpopulation. For patients at high risk of recurrence, the TRACS (TXA for cSDH) and EMMACS studies (Embolization of the Middle Meningeal Artery in Chronic Subdural Hematoma study) are, respectively, assessing the use of tranexamic acid and meningeal artery embolization. The overarching vision is that patients with cSDH might be stratified for operative versus conservative treatment based on the need for mass effect removal, then be offered adjuvant therapies based on their risk of recurrence and thrombotic complications. We believe that such tailoring of therapy to each individual should help improve outcomes.

Comparison of the effects of EPA and DHA alone or in combination in a murine model of myocardial infarction.

The aim of this project was to investigate the impact of two dietary omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alone or in combination, on infarct size. Adult, male Sprague-Dawley rats were fed for 14 days with different omega-3 diets. The animals were subjected to ischemia for 40min followed by reperfusion. Infarct size, Akt (protein kinase B) activation level, caspase-3 activity and mitochondrial permeability transition pore (mPTP) opening were measured. The results indicate that EPA or DHA alone significantly reduced infarct size compared to the other diets. Akt activity was increased in the group fed EPA or DHA alone, whereas no significant activation was observed in the other groups compared to no omega-3 PUFA. DHA alone reduced caspase-3 activity and conferred resistance to mPTP opening. In conclusion, our results demonstrate that EPA and DHA are individually effective in diminishing infarct size in our experimental model while their combination is not.

Linoleic acid attenuates cardioprotection induced by resolvin D1.

We previously observed that resolvin D1 (RvD1), a metabolite of the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid, reduces infarct size by a mechanism involving the PI3-K/Akt pathway. In parallel, the beneficial effect of a high omega-3 PUFA diet on infarct size can be attenuated by increased omega-6 PUFA consumption. The present study was designed to determine if augmented linoleic acid (LA), an omega-6 PUFA administered at the same time, attenuates the cardioprotective action of RvD1. Male Sprague-Dawley rats received 0.1µg RvD1 alone or with one of three LA doses (1, 5 or 10µg) directly into the left ventricle chamber 5min before ischemia. The animals underwent 40min of ischemia by occlusion of the left descending coronary artery followed by 30min or 24h of reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion, while caspase-3, -8 and -9 and Akt activities were assessed at 30min of reperfusion. LA attenuated cardioprotection afforded by RvD1, resulting in significantly increased infarct size. Neutrophil accumulation and Akt activity were similar between groups. Caspase activities, especially caspase-9, which could be activated by ischemia, were stimulated in the presence of LA, suggesting that this omega-6 PUFA accentuates ischemia intensity. The present results indicate that LA significantly attenuates the beneficial effect of RvD1 on infarct size. Therefore, reduction of omega-6 intake should be considered to maintain the protection afforded by RvD1.

Metabolites derived from omega-3 polyunsaturated fatty acids are important for cardioprotection.

Although controversial, some data suggest that omega-3 polyunsaturated fatty acids (PUFA) are beneficial to cardiovascular diseases, and could reduce infarct size. In parallel, we have reported that the administration of Resolvin D1 (RvD1), a metabolite of docosahexaenoic acid, an omega-3 PUFA, can reduce infarct size. The present study was designed to determine if the inhibition of two important enzymes involved in the formation of RvD1 from omega-3 PUFA could reduce the cardioprotective effect of omega-3 PUFA. Sprague-Dawley rats were fed with a diet rich in omega-3 PUFA during 10 days before myocardial infarction (MI). Two days before MI, rats received a daily dose of Meloxicam, an inhibitor of cyclooxygenase-2, PD146176, an inhibitor of 15-lipoxygenase, both inhibitors or vehicle. MI was induced by the occlusion of the left coronary artery for 40min followed by reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion while caspase-3, -8 and Akt activities were assessed at 30min of reperfusion. Rats receiving inhibitors, alone or in combination, showed a larger infarct size than those receiving omega-3 PUFA alone. Caspase-3 and -8 activities are higher in ischemic areas with inhibitors while Akt activity is diminished in groups treated with inhibitors. Moreover, the study showed that RvD1 restores cardioprotection when added to the inhibitors. Results from this study indicate that the inhibition of the metabolism of Omega-3 PUFA attenuate their cardioprotective properties. Then, resolvins seem to be an important mediator in the cardioprotection conferred by omega-3 PUFA in our experimental model of MI.