Vertebral Artery Mobilization During Transcondylar Extreme Far Lateral Approach for Excision of Large Foramen Magnum Meningioma: 2-Dimensional Operative Video.

Foramen magnum meningiomas are challenging lesions owing to their proximity to the lower brainstem, vertebrobasilar system, and lower cranial nerves.1,2 Tumor size, origin, morphology, relationship to neurovascular structures, and bony anatomy determine the optimal surgical approach.2,3 Classically, far lateral approaches have been the workhorse approach to the foramen magnum. Variations of the far lateral including transcondylar and extended transcondylar (paracondylar), with or without transposition of the vertebral artery, are sometimes used for a more lateral approach to the brainstem and clivus. Here, we present a 60-year-old male patient presenting with a large foramen magnum meningioma. Preoperative workup includes computed tomography and MRI with angiography to assess for posterior circulation dominance, anatomic variants including posterior inferior cerebellar artery origin, venous, and bony anatomy.1,4 An extreme far lateral provides access anterior to the vertebral artery to extend exposure beyond the standard far lateral approach. This comprised transcondylar drilling, bony mobilization of the V3 Vertebral artery from C1 foramen transversarium, and dural mobilization of vertebral artery with a dural cuff at its site of dural entry. The patient tolerated the procedure, gross total resection was achieved, and the patient was discharged home. This video demonstrates in detail the steps of exposure, condylar drilling, vertebral artery transposition, and dural opening. These maneuvers can be difficult to conceptualize yet are key to successful extended transcondylar exposure. The patient gave informed consent for surgery and video recording. Institutional Review Board approval was deemed unnecessary.

Intraoperative and postoperative complications for repeat high-grade glioma resections with concurrent chemotherapy: patient series.

BACKGROUND: High-grade gliomas are aggressive primary brain tumors, the most common of which is glioblastoma multiforme. Despite advances in treatment, the prognosis for these patients remains poor. The most common chemotherapeutic agents used in the treatment of this pathology include temozolomide (TMZ), procarbazine, lomustine, and vincristine. It is unclear whether chemotherapy should be held during resection for high-grade gliomas, because the perioperative risk profile is not clearly defined. OBSERVATIONS: The authors report a case series of 18 surgeries to investigate the effects of concurrent TMZ and lomustine chemotherapy on surgical complications in patients undergoing repeat resection for recurrent high-grade gliomas. The authors found no postoperative infections, self-limiting postoperative complications, or excessive intraoperative blood loss and found one intraoperative complication. LESSONS: There may not be a need to pause TMZ and lomustine chemotherapy during recurrent resections for high-grade gliomas, and continuing these medications throughout the perioperative period may be appropriate. This case series suggests that patients receiving TMZ and lomustine chemotherapy who need a repeat resection for recurrent high-grade gliomas should consider remaining on their chemotherapy regimen because it has been shown in the literature to improve recurrence-free survival time.

Efficacy of Antithrombotic Therapy and Risk of Hemorrhagic Complication in Blunt Cerebrovascular Injury Patients with Concomitant Injury: A Systematic Review.

BACKGROUND: The risk-benefit balance of antithrombotic therapy administration for blunt cerebrovascular injuries (BCVI) patients with concomitant injuries at high risk for bleeding is an ongoing therapeutic conundrum for trauma clinicians. We performed a systematic review to assess the reported efficacy and safety of treatment in this population with respect to prevention of ischemic stroke and risk of hemorrhagic complications. STUDY DESIGN: A systematic electronic literature search of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases was performed from January 1, 1996 to December 31, 2021. Studies were included if they reported treatment-stratified clinical outcomes after antithrombotic therapy in BCVI patients with concomitant injuries at high risk of bleeding into a critical site. Data were extracted from selected studies by two independent reviewers, including the main outcomes of interest were BCVI-related ischemic stroke rates and rates of hemorrhagic complications. RESULTS: Of the 5,999 studies reviewed, 10 reported on the effects of treating BCVI patients with concurrent traumatic injuries and were included for review. In the pooled data, among patients with BCVI and concomitant injury who received any form of antithrombotic therapy, the BCVI-related stroke rate was 7.6%. The subgroup of patients who did not receive therapy had an overall BCVI-related stroke rate of 34%. The total rate of hemorrhagic complications in the treated population was 3.4%. CONCLUSIONS: In BCVI patients with concomitant injuries at high risk for bleeding, antithrombotic use reduces the risk of ischemic strokes with a low reported risk of serious hemorrhagic complications.

Patient's expectations of surgery for lumbar degenerative spondylolisthesis: analysis by type of surgery and patient factors from the Canadian Spine Outcomes and Research Network (CSORN).

BACKGROUND CONTEXT: Preoperative expectations influence postoperative outcomes. Patients with lumbar degenerative spondylolisthesis have especially high expectations of pain relief and overall functional well-being compared to patients with lumbar stenosis. PURPOSE: The primary objective was to analyze preoperative expectations of lumbar DS patients with respect to the type of surgery proposed (decompression vs decompression and fusion). Secondarily, we aimed to assess the associations between preoperative expectations and patient and clinical factors as well as postoperative expectations fulfillment. STUDY DESIGN/SETTING: Patients were prospectively enrolled in a multicenter, prospective cohort study evaluating the assessment and management of degenerative spondylolisthesis utilizing the infrastructure of the Canadian Spine Outcomes and Research Network (CSORN) surgical registry. PATIENT SAMPLE: Patients with a diagnosis of degenerative spondylolisthesis with symptoms of neurogenic claudication or radiculopathy with or without back pain, unresponsive to nonoperative management over at least 3 months were included. Patients who underwent decompression, decompression and posterolateral fusion or decompression and interbody fusion at Canadian spine centers between January 2015 and September 2021 were included. OUTCOME MEASURES: The North American Spine Society Lumbar Spine Questionnaire was utilized for expectations measurement. The expectation questionnaire was completed following consent and before surgery and at 1 year. METHODS: Expectations for pain relief and improvements in overall functional well-being were rated on a scale of 0 to 100. Preoperative expectation in terms of pain relief and functional well-being score were calculated. Multivariate linear regression was used to evaluate the association between expected preoperative patient factors and pain relief and functional well-being. The factors associated with the most important expectation were evaluated using multivariable multinomial logistic regression. RESULTS: Three hundred fifty-two patients were included with 100 patients undergoing decompression and 252 patients also undergoing fusion. The seven items of preoperative expectations did not differ between the procedure groups nor did expected change. The mean pain relief and overall functional well-being expectation scores did not significantly differ between procedures. Higher expectations were associated with having more comorbidities [ß=-2.0 (SE 0.8), p=.020], being physically active [ß=8.4 (SE 3.2), p=.010] and having more leg pain [ß=1.6 (SE 0.7), p=.015]. Better perceived physical health measured by SF12 PCS was associated with lower expectation of pain relief [ß= -0.4 (SE 0.2), p=.039] and functional well-being [ß=-0.84 (SE 0.2), p=.001]. Better perceived mental health measured by SF12 MCS was associated with lower expectation of functional well-being [ß=-0.8 (SE 0.2), p=.001]. Postoperative expectations fulfillment did not differ between procedures. CONCLUSION: Preoperative expectations in terms of pain relief and functional well-being were similar between the two most common procedures performed, decompression ± fusion. Secondarily, higher preoperative expectations were associated with greater pain, disability and being physically active. Expectations fulfillment did not differ between procedures.

Survival and Recurrence Outcomes Following Adjuvant Radiotherapy for Grade 2 Intracranial Meningiomas: 13-Year Experience in a Tertiary-Care Center.

OBJECTIVE: We sought to evaluate overall survival (OS) and local recurrence (LR) in patients with grade 2 meningiomas treated with adjuvant radiotherapy compared to surgery alone at time of diagnosis. METHODS: All patients at the authors' institution between 2007 and 2020 were retrospectively reviewed. OS, LR, and treatment toxicities were assessed. Sensitivity analyses were performed for patients with initial gross total resection (GTR) and subtotal resection (STR). Kaplan-Meier analyses and log-rank test for significance were used to compare surgery alone and adjuvant radiotherapy groups. RESULTS: We included 189 patients with mean age 57.4 ± 14.6 years. Patients were 64% female, and median follow-up was 64 (interquartile range: 20-96) months. At initial treatment, 21 patients received adjuvant radiotherapy and 168 received surgery alone. There was no significant difference for OS (hazard ratio = 1.3 [95% confidence interval 0.4-4.5], P = 0.92) overall or when limited to GTR (P = 0.38) or STR (P = 0.85). There was no significant difference in LR overall (P = 0.75) or when restricted to GTR (P = 0.77) or STR (P = 0.20). No patient had radiotherapy stopped or altered because of side effects; however, 71.4% reported tolerable side effects during the treatment period and 14.3% reported chronic side effects persisting longer than 12 months post treatment. CONCLUSIONS: In a large retrospective cohort, we found no survival or local recurrence benefit to adjuvant radiotherapy in treatment of grade 2 meningiomas. Sensitivity analysis limited to initial GTR and STR also failed to demonstrate any OS or LR benefit with adjuvant radiotherapy. In our experience, there is limited utility to upfront adjuvant radiotherapy following initial surgical resection in the treatment of grade 2 meningiomas.

The impact of brain invasion criteria on the incidence and distribution of WHO grade 1, 2, and 3 meningiomas.

BACKGROUND: In 2016 brain invasion was added as a standalone diagnostic criterion for Grade 2 meningiomas in the WHO Classification of Brain Tumors. The aim of this study was to compare the incidence and distribution of meningiomas, and agreement, between the 2007 and 2016 WHO criteria. METHODS: All cases of intracranial meningiomas diagnosed between 2007 and 2020 at a tertiary care academic hospital were identified. The incidence of each meningioma grade in the WHO 2007 and WHO 2016 cohorts were compared. Additionally, each case in the 2007 cohort was re-graded according to the WHO 2016 criteria to determine the intra-class correlation (ICC) between criteria. RESULTS: Of 814 cases, 532 (65.4%) were in the 2007 WHO cohort and 282 (34.6%) were in the 2016 WHO cohort. There were no differences in the distribution of meningioma grades between cohorts (P = .11). Incidence rates were: 75.0% vs. 75.2% for Grade 1, 22.7% vs. 24.5% for Grade 2, and 2.3% vs. 0.4% for Grade 3, for the 2007 and 2016 cohorts, respectively. Upon re-grading, 21 cases (3.9%) were changed. ICC between original and revised grade was 0.92 (95% CI: 0.91-0.93). Amongst Grade 2 meningiomas with brain invasion, 75.8% had three or more atypical histologic features or an elevated mitotic index. CONCLUSIONS: Including brain invasion as a standalone diagnostic criterion for Grade 2 meningiomas had minimal impact on the incidence of specific meningioma grade tumors. There is strong agreement between the 2007 and 2016 WHO criteria, likely due to cosegregation of grade elevating features.

Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity.

Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision-making. Drug-associated cues have long been known to facilitate habitual drug-seeking, and the salient audiovisual cues embedded within modern gambling products may likewise encourage problem gambling. The dopamine neurons of the ventral tegmental area (VTA) are exquisitely sensitive to drugs of abuse, uncertain rewards, and reward-paired cues and may therefore be the common neural substrate mediating synergistic features of both disorders. To test this hypothesis, we first gained specific inhibitory control over VTA dopamine neurons by transducing a floxed inhibitory DREADD (AAV5-hSyn-DIO-hM4D(Gi)-mCherry) in rats expressing Cre recombinase in tyrosine hydroxylase neurons. We then trained rats in our cued rat gambling task (crGT), inhibiting dopamine neurons throughout task acquisition and performance, before allowing them to self-administer cocaine in the same diurnal period as crGT sessions. The trajectories of addiction differ in women and men, and the dopamine system may differ functionally across the sexes; therefore, we used male and female rats here. We found that inhibition of VTA dopamine neurons decreased cue-induced risky choice and reduced motor impulsivity in males, but surprisingly, enhanced risky decision making in females. Inhibiting VTA dopamine neurons also prevented cocaine-induced changes in decision making in both sexes, but nevertheless drove all animals to consume more cocaine. These findings show that chronic dampening of dopamine signalling can have both protective and deleterious effects on addiction-relevant behaviours, depending on biological sex and dependent variable of interest.

Using Normalization Process Theory to Evaluate the Implementation of Montessori-Based Volunteer Visits Within a Canadian Long-Term Care Home.

BACKGROUND AND OBJECTIVES: Montessori-based interventions (MBIs) have potential to improve the life quality of long-term care residents with dementia. In this study, we aimed to understand the processes by which staff integrated a volunteer-led MBI into practice within a special dementia care unit, and to explore staff members ' perceptions of associated strengths and limitations. RESEARCH DESIGN AND METHODS: This study relied on a qualitative descriptive design. Following a 3-month period of volunteer involvement, we conducted 21 interviews with staff members to document perceptions of the new program and subjected interview transcripts to qualitative content analysis, guided by normalization process theory. RESULTS: During the implementation of the volunteer-led MBI, staff members developed a shared understanding of the intervention, a sense of commitment, practical ways to support the intervention, and opinions about the value of the residents. Overall, we found that the volunteer-led MBI was quickly and successfully integrated into practice and was perceived to support both residents and staff members in meaningful ways. Nevertheless, some limitations were also identified. DISCUSSION AND IMPLICATIONS: Volunteer-delivered MBIs are a useful adjunct to practice within a special dementia care unit. This article raises attention to some strengths and limitations associated with this approach.

Prior Exposure to Salient Win-Paired Cues in a Rat Gambling Task Increases Sensitivity to Cocaine Self-Administration and Suppresses Dopamine Efflux in Nucleus Accumbens: Support for the Reward Deficiency Hypothesis of Addiction.

Rats trained to perform a version of the rat gambling task (rGT) in which salient audiovisual cues accompany reward delivery, similar to commercial gambling products, show greater preference for risky options. Given previous demonstrations that probabilistic reinforcement schedules can enhance psychostimulant-induced increases in accumbal DA and locomotor activity, we theorized that performing this cued task could perpetuate a proaddiction phenotype. Significantly more rats developed a preference for the risky options in the cued versus uncued rGT at baseline, and this bias was further exacerbated by cocaine self-administration, whereas the choice pattern of optimal decision-makers was unaffected. The addition of reward-paired cues therefore increased the proportion of rats exhibiting a maladaptive cognitive response to cocaine self-administration. Risky choice was not associated with responding for conditioned reinforcement or a marker of goal/sign-tracking, suggesting that reward-concurrent cues precipitate maladaptive choice via a unique mechanism unrelated to simple approach toward, or responding for, conditioned stimuli. Although "protected" from any resulting decision-making impairment, optimal decision-makers trained on the cued rGT nevertheless self-administered more cocaine than those trained on the uncued task. Collectively, these data suggest that repeated engagement with heavily cued probabilistic reward schedules can drive addiction vulnerability through multiple behavioral mechanisms. Rats trained on the cued rGT also exhibited blunted locomotor sensitization and lower basal accumbal DA levels, yet greater cocaine-induced increases in accumbal DA efflux. Gambling in the presence of salient cues may therefore result in an adaptive downregulation of the mesolimbic DA system, rendering individuals more sensitive to the deleterious effects of taking cocaine.SIGNIFICANCE STATEMENT Impaired cost/benefit decision making, exemplified by preference for the risky, disadvantageous options on the Iowa Gambling Task, is associated with greater risk of relapse and treatment failure in substance use disorder. Understanding factors that enhance preference for risk may help elucidate the neurobiological mechanisms underlying maladaptive decision making in addiction, thereby improving treatment outcomes. Problem gambling is also highly comorbid with substance use disorder, and many commercial gambling products incorporate salient win-paired cues. Here we show that adding reward-concurrent cues to a rat analog of the IGT precipitates a hypodopaminergic state, characterized by blunted accumbal DA efflux and attenuated locomotor sensitization, which may contribute to the enhanced responsivity to uncertain rewards or the reinforcing effects of cocaine we observed.