Challenges and Opportunities in Awake Craniotomy for Brain Tumor Surgery in Low- and Lower-Middle-Income Countries: A Narrative Review and Perspective.

BACKGROUND: Low-income countries (LICs) and lower-middle-income countries (LMICs) are presented with unique challenges and opportunities when performing awake craniotomy (AC) for brain tumors. These circumstances arise from factors that are financial, infrastructural, educational, personnel, and sociocultural in nature. METHODS: We performed a systematic narrative review of series on AC for intra-axial brain tumors in LICs/LMICs using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, focusing on the challenges and opportunities in these settings. The PubMed, Scopus, and Web of Science databases were searched. RESULTS: After initially identifying 74 studies, inclusion-exclusion criteria were applied, leaving a total of 14 studies included in the review. These involved 409 patients who underwent AC in LICs/LMICs. These series were from India, Ghana, Nigeria, Iran, Pakistan, Morocco, the Philippines, and Egypt. The most common pathology encountered were gliomas (10-70%). Most studies (11/14, 78.5%) reported on their technique of cortical-subcortical mapping. All reported on motor mapping and 8 of these performed language mapping. The most common outcomes reported were seizure and neurologic deficits, and longest follow-up was at 1 year. Challenges noted were lack of equipment and trained personnel, need for validated tests for the local setting, and sociocultural factors. Opportunities identified were volume for training, technique innovation, and international collaboration. CONCLUSIONS: There are numerous challenges and opportunities that arise when performing AC in LICs/LMICs. A collaborative approach toward harnessing the opportunities, and seeking creative solutions to address the challenges, would provide an ideal mechanism toward advancing neurosurgical care and specialty worldwide.

Missed pituitary microadenoma during endoscopic transsphenoidal surgery for short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing with symptom relief: illustrative case.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare headache disorder that has been associated with pituitary adenomas. Resection has been posited to be curative. OBSERVATIONS: A 60-year-old female presented with a 10-year history of SUNCT, which had been medically refractory. Sellar magnetic resonance imaging (MRI) showed a 2 × 2 mm nodule in the right anterolateral aspect of the pituitary. Endoscopic endonasal transsphenoidal resection of the pituitary microadenoma with neuronavigation was performed. The patient felt immediate relief from the headaches. Postoperative MRI showed persistence of the pituitary microadenoma and the resection tract to be inferomedial to the lesion. The right middle and partial superior turbinectomy site was close to the sphenopalatine foramen (SPF). The patient was discharged on postoperative day 1 and remained headache-free without any medications at the 4-month follow-up. LESSONS: Resection of pituitary lesions associated with SUNCT may not necessarily be the cause of SUNCT resolution. Manipulation of the middle and superior turbinate close to the SPF may lead to a pterygopalatine ganglion block. This may be the mechanism of cure for SUNCT in patients with related pituitary lesions who undergo endonasal resection.

Cortical mapping in multilinguals undergoing awake brain surgery for brain tumors: Illustrative cases and systematic review.

BACKGROUND: Awake brain mapping in multilingual patients with brain tumors presents unique challenges to the neurosurgeon. Knowledge of potential eloquent sites is vital to preserve language function. METHODS: We present two cases of pars opercularis glioma and perform a systematic review in accordance with PRISMA guidelines. RESULTS: Our review yielded 7 studies, with a total of 25 multilingual brain tumor patients who underwent awake brain mapping. The age ranged from 25 to 62 years. Majority were female (56.5%). Most (52%) were trilingual, while 20% were quadrilingual and 28% were pentalingual. All tumors were left-sided, mostly in the frontal lobe. These were predominantly gliomas. Extent of resection was gross total in 61%. The brain mapping findings were heterogeneous. Some authors reported a greater number of cortical sites for the first language compared to others. Others found that the first and second languages shared cortical sites whereas the third and subsequent languages were located in distant sites. The peri-Sylvian area was also found to be involved in language that was learned at an earlier age. Subsequent languages thus involved more distant sites. A larger number of cortical areas were also activated for languages that were learned later in life. In terms of language disturbance and recovery, there were mixed results. CONCLUSION: Cortical mapping in multilingual brain tumor patients showed heterogeneity in terms of the location and number of language areas in the face of pathology. These findings may influence neurosurgical and oncological management of tumors in the speech area but emphasize the need to tailor surgical approaches and intraoperative testing to the patient.

Meningiomas Associated with Subdural Hematomas: A Systematic Review of Clinical Features and Outcomes.

BACKGROUND: Meningiomas associated with subdural hematomas (SDHs) are exceedingly rare. As such, the clinical features, optimal medical and surgical management, and outcomes of treatment for these lesions remain unknown. METHODS: We performed a systematic review of the PubMed and Scopus databases for case reports and case series of patients with presumptive clinical or definitive diagnoses of meningiomas presenting with SDH on computed tomography scan or magnetic resonance imaging. Data on demographics, clinical manifestations, surgical management, adjuvant treatment, and outcome on last follow-up were collected. RESULTS: Inclusion criteria were met by 59 cases, including a case described in the current study. Mean age of patients was 62 years (range: 5-85 years), with a slight female predilection (1.3:1). The most common clinical symptom and sign were headache and focal weakness, respectively. All except 2 patients underwent surgery, either a single or staged procedure, for evacuation of hematoma and/or excision of tumor. Treatment for meningioma in patients who presented with SDH was associated with a mortality rate of 12% (6/51) at a median follow-up of 3 months. Complete neurologic recovery was reported in 71% of patients. CONCLUSIONS: SDHs are rare manifestations of intracranial meningiomas. Current management is largely surgical for immediate relief of mass effect and oncologic control. Most reported patients survived with complete neurologic recovery.

Good Visual Outcomes After Pituitary Tumor Surgery Are Associated With Increased Visual Cortex Functional Connectivity.

BACKGROUND: Patients presenting with visual impairment secondary to pituitary macroadenomas often experience variable recovery after surgery. Several factors may impact visual outcomes including the extent of neuroaxonal damage in the afferent visual pathway and cortical plasticity. Optical coherence tomography (OCT) measures of retinal structure and resting-state functional MRI (rsfMRI) can be used to evaluate the impact of neuroaxonal injury and cortical adaptive processes, respectively. The purpose of this study was to determine whether rsfMRI patterns of functional connectivity (FC) distinguish patients with good vs poor visual outcomes after surgical decompression of pituitary adenomas. METHODS: In this retrospective cohort study, we compared FC patterns between patients who manifested good (GO) vs poor (PO) visual outcomes after pituitary tumor surgery. Patients (n = 21) underwent postoperative rsfMRI a minimum of 1 year after tumor surgery. Seed-based connectivity of the visual cortex (primary [V1], prestriate [V2], and extrastriate [V5]) was compared between GO and PO patients and between patients and healthy controls (HCs) (n = 19). Demographics, visual function, and OCT data were compared preoperatively and postoperatively between patient groups. The threshold for GO was visual field mean deviation equal or less than -5.00 dB and/or visual acuity equal to or better than 20/40. RESULTS: Increased postoperative FC of the visual system was noted for GO relative to PO patients. Specifically, good visual outcomes were associated with increased connectivity of right V5 to the bilateral frontal cortices. Compared with HCs, GO patients showed increased connectivity of V1 and left V2 to sensorimotor cortex, increased connectivity of right and left V2 to medial prefrontal cortex, and increased connectivity of right V5 the right temporal and frontal cortices. CONCLUSIONS: Increased visual cortex connectivity is associated with good visual outcomes in patients with pituitary tumor, at late phase of recovery. Our findings suggest that rsfMRI does distinguish GO and PO patients after pituitary tumor surgery. This imaging modality may have a future role in characterizing the impact of cortical adaptation on visual recovery.

Hemorrhagic Intracranial Cavernoma Presenting as a Homonymous Horizontal Sectoranopia.

ABSTRACT: Hemorrhagic lateral geniculate nucleus (LGN) insults are rare but have been reported in association with tumors, vascular malformations, and trauma. The localization of LGN lesions is facilitated by recognition of pathognomonic visual field defects. A 21-year old woman developed a sudden onset painless left homonymous horizontal sectoranopia. Magnetic resonance imaging revealed a hemorrhagic cavernous malformation of the right temporal lobe. Optical coherence tomography (OCT) and Humphrey perimetry findings localized the lesion to the right LGN. Specifically, OCT testing revealed a right homonymous sectoranopia pattern of hemi-retinal macular ganglion layer-inner plexiform layer (mGCIPL) thinning contralateral to the left sided visual field defect. The OCT pattern reflected retrograde neuroaxonal degeneration from the right LGN lesion. This case highlights a unique pattern of mGCIPL thinning characteristic for a posterior lateral choroidal artery injury, affecting the LGN. These findings illustrate how functional eloquence correlates with topographical elegance in the afferent visual pathway.

Desmoplastic myxoid tumor of pineal region, SMARCB1-mutant, in young adult.

We present a young adult woman who developed a myxoid tumor of the pineal region having a SMARCB1 mutation, which was phenotypically similar to the recently described desmoplastic myxoid, SMARCB1-mutant tumor of the pineal region (DMT-SMARCB1). The 24-year-old woman presented with headaches, nausea, and emesis. Neuroimaging identified a hypodense lesion in CT scans that was T1-hypointense, hyperintense in both T2-weighted and FLAIR MRI scans, and displayed gadolinium enhancement. The resected tumor had an abundant, Alcian-blue positive myxoid matrix with interspersed, non-neoplastic neuropil-glial-vascular elements. It immunoreacted with CD34 and individual cells for EMA. Immunohistochemistry revealed loss of nuclear INI1 expression by the myxoid component but its retention in the vascular elements. Molecular analyses identified a SMARCB1 deletion and DNA methylation studies showed that this tumor grouped together with the recently described DMT-SMARCB1. A cerebrospinal fluid cytologic preparation had several cells morphologically similar to those in routine and electron microscopy. We briefly discuss the correlation of the pathology with the radiology and how this tumor compares with other SMARCB1-mutant tumors of the nervous system.

Tactics: an open-source platform for planning, simulating and validating stereotactic surgery.

Frame-based stereotaxy is widely used for planning and implanting deep-brain electrodes. In 2013, as part of a clinical study on deep-brain stimulation for treatment-resistant depression, our group identified a need for software to simulate and plan stereotactic procedures. Shortcomings in extant commercial systems encouraged us to develop Tactics. Tactics is purpose-designed for frame-based stereotactic placement of electrodes. The workflow is far simpler than commercial systems. By simulating specific electrode placement, immediate in-context view of each electrode contact, and the cortical entry site are available within seconds. Post implantation, electrode placement is verified by linearly registering post-operative images. Tactics has been particularly helpful for invasive electroencephalography electrodes where as many as 20 electrodes are planned and placed within minutes. Currently, no commercial system has a workflow supporting the efficient placement of this many electrodes. Tactics includes a novel implementation of automated frame localization and a user-extensible mechanism for importing electrode specifications for visualization of individual electrode contacts. The system was systematically validated, through comparison against gold-standard techniques and quantitative analysis of targeting accuracy using a purpose-built imaging phantom mountable by a stereotactic frame. Internal to our research group, Tactics has been used to plan over 300 depth-electrode targets and trajectories in over 50 surgical cases, and to plan dozens of stereotactic biopsies. Source code and pre-built binaries for Tactics are public and open-source, enabling use and contribution by the extended community.

Cost-effectiveness of the endoscopic versus microscopic approach for pituitary adenoma resection.

OBJECTIVES/HYPOTHESIS: To evaluate the cost-effectiveness of an endoscopic versus microscopic approach to pituitary adenoma resection. STUDY DESIGN: Markov decision tree economic evaluation. METHODS: An economic evaluation using a Markov decision tree model was performed. The economic perspective was that of the healthcare third-party payer. Effectiveness and probability data were obtained from a single meta-analysis of 38 studies. Costs were obtained from the Healthcare Cost and Utilization Project database and wholesale pharmaceutical pricing. Multiple sensitivity analyses were performed including a probabilistic sensitivity analysis. Comparative treatment groups were: 1) endoscopic approach and 2) microscopic approach to pituitary adenoma resection. The primary outcome was cost per quality-adjusted life year (QALY). The time horizon was 25 years, and costs were discounted at a rate of 3.5%. RESULTS: The endoscopic approach cost a total of $17,244.63 and produced a total of 24.30 QALYs. The microscopic approach cost a total of $23,756.60 and produced a total of 24.20 QALYs. In the reference case, the endoscopic approach was a dominant intervention (both less costly and more effective); therefore, an incremental cost-effectiveness ratio was not calculated. The sensitivity analysis demonstrated 79% certainty that the endoscopic approach is the cost-effective decision, at a willingness to pay threshold of $50,000 per QALY. CONCLUSIONS: This economic evaluation suggests that the endoscopic approach is the more cost-effective intervention compared to the microscopic approach for patients requiring a pituitary adenoma resection.

Population based analysis ependymoma patients in Alberta from 1975 to 2007.

BACKGROUND: Ependymomas are rare tumors of the central nervous system whose management is controversial. This population-based study of adults and children with ependymoma aims to (1) identify clinical and treatment-related factors that impact survival and (2) determine if postoperative radiotherapy (RT) can improve survival of patients with subtotal resection (STR) to levels similar to patients who had gross total resection (GTR). METHODS: This retrospective population-based study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in Alberta, Canada. RESULTS: Younger patients (<7 years of age) were more likely to be diagnosed with grade III tumors compared with adults in whom grade I tumors were more common (p=0.003). Adults were more likely to have spinally located tumors compared to young children whose tumors were typically found in the brain. Overall, young children with ependymoma were more likely to die than older children or adults (p=0.001). An equivalent number of patients underwent GTR as compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor location, lower grade, and GTR were associated with improved progression free survival but only GTR was associated with significant improvement in overall survival. Median survival after STR and RT was 82 months compared with 122 months in patients who had GTR (p=0.0022). CONCLUSIONS: This is the first Canadian population-based analysis of patients with ependymoma including adults and children. Extent of resection appears to be the most important factor determining overall survival. Importantly, the addition of RT to patients initially treated with STR does not improve survival to levels similar to patients receiving GTR.

Three-dimensional database of subcortical electrophysiology for image-guided stereotactic functional neurosurgery.

We present a method of constructing a database of intraoperatively observed human subcortical electrophysiology. In this approach, patient electrophysiological data are standardized using a multiparameter coding system, annotated to their respective magnetic resonance images (MRIs), and nonlinearly registered to a high-resolution MRI reference brain. Once registered, we are able to demonstrate clustering of like interpatient physiologic responses within the thalamus, globus pallidus, subthalamic nucleus, and adjacent structures. These data may in turn be registered to a three-dimensional patient MRI within our image-guided visualization program enabling prior to surgery the delineation of surgical targets, anatomy with high probability of containing specific cell types, and functional borders. The functional data were obtained from 88 patients (106 procedures) via microelectrode recording and electrical stimulation performed during stereotactic neurosurgery at the London Health Sciences Centre. Advantages of this method include the use of nonlinear registration to accommodate for interpatient anatomical variability and the avoidance of digitized versions of printed atlases of anatomy as a common database coordinate system. The resulting database is expandable, easily searched using a graphical user interface, and provides a visual representation of functional organization within the deep brain.