Moyamoya disease (MMD) is characterized by progressive occlusion of the intracranial internal carotid arteries, leading to ischemic and hemorrhagic events. Significant clinical differences exist between ischemic and hemorrhagic MMD. To understand the molecular profiles in the cerebrospinal fluid (CSF) of MMD patients, we investigated 62 secreted factors in both MMD subtypes (ischemic and hemorrhagic) and examined their relationship with preoperative perfusion status, the extent of postoperative angiographic revascularization, and functional outcomes. Intraoperative CSF was collected from 32 control and 71 MMD patients (37 ischemic and 34 hemorrhagic). Multiplex Luminex assay analysis showed that 41 molecules were significantly elevated in both MMD subtypes when compared to controls, including platelet-derived growth factor-BB (PDGF-BB), plasminogen activator inhibitor 1 (PAI-1), and intercellular adhesion molecule 1 (ICAM1) ( p < 0.001). Many of these secreted proteins have not been previously reported in MMD, including interleukins (IL-2, IL-4, IL-5, IL-7, IL-8, IL-9, IL-17, IL-18, IL-22, and IL-23) and C-X-C motif chemokines (CXCL1 and CXCL9). Pathway analysis indicated that both MMD subtypes exhibited similar cellular/molecular functions and pathways, including cellular activation, migration, and inflammatory response. While neuroinflammation and dendritic cell pathways were activated in MMD patients, lipid signaling pathways involving nuclear receptors, peroxisome proliferator-activated receptor (PPAR), and liver X receptors (LXR)/retinoid X receptors (RXR) signaling were inhibited. IL-13 and IL-2 were negatively correlated with preoperative cerebral perfusion status, while 7 factors were positively correlated with the extent of postoperative revascularization. These elevated cytokines, chemokines, and growth factors in CSF may contribute to the pathogenesis of MMD and represent potential future therapeutic targets.

OBJECTIVE Microsurgical resection of arteriovenous malformations (AVMs) can be aided by staged treatment consisting of stereotactic radiosurgery followed by resection in a delayed fashion. This approach is particularly useful for high Spetzler-Martin (SM) grade lesions because radiosurgery can reduce flow through the AVM, downgrade the SM rating, and induce histopathological changes that additively render the AVM more manageable for resection. The authors present their 28-year experience in managing AVMs with adjunctive radiosurgery followed by resection. METHODS The authors retrospectively reviewed records of patients treated for cerebral AVMs at their institution between January 1990 and August 2019. All patients who underwent stereotactic radiosurgery (with or without embolization), followed by resection, were included in the study. Of 1245 patients, 95 met the eligibility criteria. Univariate and multivariate regression analyses were performed to assess relationships between key variables and clinical outcomes. RESULTS The majority of lesions treated (53.9%) were high grade (SM grade IV-V), 31.5% were intermediate (SM grade III), and 16.6% were low grade (SM grade I-II). Hemorrhage was the initial presenting sign in half of all patients (49.5%). Complete resection was achieved among 84% of patients, whereas 16% had partial resection, the majority of whom received additional radiosurgery. Modified Rankin Scale (mRS) scores of 0-2 were achieved in 79.8% of patients, and 20.2% had poor (mRS scores 3-6) outcomes. Improved (44.8%) or stable (19%) mRS scores were observed among 63.8% of patients, whereas 36.2% had a decline in mRS scores. This includes 22 patients (23.4%) with AVM hemorrhage and 6 deaths (6.7%) outside the perioperative period but prior to AVM obliteration. CONCLUSIONS Stereotactic radiosurgery is a useful adjunct in the presurgical management of cerebral AVMs. Multimodal therapy allowed for high rates of AVM obliteration and acceptable morbidity rates, despite the predominance of high-grade lesions in this series of patients.

BACKGROUND The natural history of unilateral moyamoya disease (MMD) progressing to bilateral MMD remains an enigma in modern vascular neurosurgery. Few, small series with limited follow-up have reported relatively high rates of contralateral stenosis progression. OBJECTIVE To review our large series of unilateral MMD patients and evaluate radiographic and surgical progression rates, and identify any factors associated with progression. METHODS We included all unilateral MMD cases treated from 1991 to 2017 in an observational study. We examined time to contralateral radiographic progression and contralateral progression requiring surgery. Using Cox regression analysis, we evaluated factors potentially associated with contralateral progression. RESULTS There were 217 patients treated for unilateral MMD. About 71% were female, and the average age at first surgery was 33.8 yr. Average follow-up was 5.8 yr (range 1-22 yr). A total of 18 patients (8.3%) developed contralateral progression. And 8 of these (3.7%) developed progression requiring bypass surgery. Baseline stenosis and hyperlipidemia (HLD) were significantly associated with radiographic progression (hazard ratio [HR] = 9.7, P = .006; HR = 4.0, P = .024). Baseline stenosis was associated with surgical progression (HR = 44.2, P = .002). Results were similar when controlling for possible confounders using multivariate regression. CONCLUSION Previous series showed relatively high rates of progression in unilateral MMD (15%-30%), but these studies were small and long-term follow-up was rarely available. Our large series indicates that the rate of progression is lower than previously reported but still warrants yearly noninvasive screening. These data may provide indirect support for statin therapy in MMD.

BACKGROUND Patients with moyamoya disease who develop incidental cerebral microhemorrhages (CMHs) on magnetic resonance imaging (MRI) have higher risk of developing subsequent symptomatic repeat macro hemorrhages. OBJECTIVE To evaluate the effect of surgical revascularization on development of de novo CMHs and assess its correlation with repeat hemorrhage rates and functional outcome in hemorrhagic onset moyamoya disease (HOMMD). METHODS We retrospectively reviewed a prospectively managed departmental database of all patients presenting with HOMMD treated between 1987 and 2019. The search yielded 121 patients with adequate MRI follow-up for inclusion into the study. RESULTS In total, 42 preoperative CMHs were identified in 18 patients (15%). Patients presenting with preoperative CMH were more likely to develop de novo CMH after surgical revascularization. 7 de novo CHMs were identified in 6 patients (5%) on routine postoperative MRI at distinct locations from previous sites of hemorrhage or CMH. Symptomatic repeat macro hemorrhage was confirmed radiographically in 15 patients (12%). A total 5 (83%) of 6 patients with de novo CMHs later suffered symptomatic repeat macro hemorrhage with 4 of 5 (80%) hemorrhages occurring at sites of previous CMH. On univariate and multivariate analysis, de novo CMHs was the only significant variable predictive for developing repeat symptomatic hemorrhage. Development of delayed repeat symptomatic hemorrhage was prognostic for higher modified Rankin Score and therefore poorer functional status, whereas preoperative functional status was predictive of final outcome. CONCLUSION De novo CMHs after surgical revascularization might serve as a radiographic biomarker for refractory disease and suggest patients are at risk for future symptomatic macro hemorrhage.

Background: Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive occlusion of the internal carotid arteries leading to ischemic and hemorrhagic events. The underlying pathogenesis of MMD remains unclear. In this study we investigated key secreted molecules in the cerebrospinal fluid (CSF) of MMD patients including relation to the extent of neovascularization and eventual functional outcomes. Methods: This study included intraoperative CSF collected from 32 controls (Chiari malformation and cranial nerve hyperactive syndromes) and 73 MMD patients (ischemic: 39; hemorrhagic: 34) that underwent combined direct and indirect superficial temporal artery-middle cerebral artery revascularization procedure. 62 factors were analyzed using multiplex luminex assay, including angiogenic growth factors, cytokines, and chemokines. Cellular retinoic acid binding protein (CRBP1) was also measured using ELISA. Functional outcome was assessed using the modified Rankin scale score (mRS). Matsushima criteria was used for grading the neovascularization. Results: Forty molecules were significantly elevated in both MMD subtypes in comparison with controls. The common top highly secreted CSF proteins included platelet-derived growth factor bb, chemokine ligand 5 and plasminogen activator inhibitor 1 (p<0.001). CRBP1 and other growth factors such as brain-derived nerve growth factor and basic fibroblast growth factor were also elevated in both MMD subtypes (p<0.01). Our results also revealed a number of proteins not previously reported in MMD. Ingenuity pathway analysis indicated that the ischemic and hemorrhagic MMD subtypes exhibited similar cellular/molecular functions and pathways including cellular activation, migration and inflammatory response. Interestingly, while neuro-inflammation and dendritic cell pathways were activated in MMD patients, lipid signaling pathways involving nuclear receptors PPAR and LXR/RXR signaling were inhibited. Conclusions: CSF analysis revealed that a number of cytokines, chemokines and growth factors are elevated in both MMD subtypes. These molecules potentially contribute to the pathogenesis of MMD and could be potential future therapeutic targets.

Introduction: Surgical treatment of arteriovenous malformations (AVMs), particularly higher grade lesions, can be aided by staged treatment consisting of stereotactic radiosurgery (SRS) followed by surgical resection in a delayed fashion. This strategy can be used to downgrade the AVM S-M grade, reduce blood flow through the AVM and often results in histopathological changes making AVMs more amenable to microsurgical resection. We present our 28-year clinical experience in managing AVMs with pre-operative SRS as a surgical adjunct. Methods: We retrospectively reviewed and analyzed records of all patients treated for cerebral AVMs between February 1991 and July 2019 at our institution. All patients that underwent SRS, with and without embolization, followed by microsurgery were included in the study. Of the 1245 cerebral AVM patients treated at our institution, 62 patients met eligibility criteria. Univariate and multivariate regression analysis was performed where appropriate to examine relationships between key variables and outcomes. Results: The majority of lesions (50%) were high grade (SM 4-5), 28.6% were intermediate (SM 3), while 21.4% were low grade (SM 1-2). Hemorrhage was the presenting sign among 22.6% of patients. Complete resection was achieved among 64.5%, 79% and 82% of patients after first, second and third surgical stages respectively; 16.1% of patients had partial resection requiring further treatment. Radiographic cure was achieved among 53 patients (85.5%), while 8 (12.9%) patients had residual AVM at last follow up. Six of 8 patients without radiographic cure received post-operative SRS. Thirty-seven patients (63.8%) had improved (26, 44.8%) or stable mRS scores (11, 19%), while 21 (36.2%) had a decline in mRS at final follow up compared to mRS at presentation; this includes 4 (6.9%) deaths due to hemorrhage, outside of the perioperative period, but occurring during follow up prior to AVM obliteration. Conclusion: SRS is a useful adjunct in the surgical management of cerebral AVMs. Multimodal therapy allowed for high obliteration rates with acceptable morbidity in this series of patients with predominantly high grade AVMs.

OBJECTIVE:Perforator arteries, the absence of an aneurysm discrete neck, and the often-extensive nature of posterior circulation fusiform aneurysms present treatment challenges. There have been advances in microsurgical and endovascular approaches, including flow diversion, and the authors sought to review these treatments in a long-term series at their neurovascular referral center. METHODS:The authors performed a retrospective chart review from 1990 to 2018. Primary outcomes were modified Rankin Scale (mRS) scores and Glasgow Outcome Scale (GOS) scores at follow-up. The authors also examined neurological complication rates. Using regression techniques, they reviewed independent and dependent variables, including presenting features, aneurysm location and size, surgical approach, and pretreatment and posttreatment thrombosis. RESULTS:Eighty-four patients met the inclusion criteria. Their mean age was 53 years, and 49 (58%) were female. Forty-one (49%) patients presented with subarachnoid hemorrhage. Aneurysms were located on the vertebral artery (VA) or posterior inferior cerebellar artery (PICA) in 50 (60%) patients, basilar artery (BA) or vertebrobasilar junction (VBJ) in 22 (26%), and posterior cerebral artery (PCA) in 12 (14%). Thirty-one (37%) patients were treated with microsurgical and 53 (63%) with endovascular approaches. Six aneurysms were treated with endovascular flow diversion. The authors found moderate disability or better (mRS score ≤ 3) in 85% of the patients at a mean 14-month follow-up. The GOS score was ≥ 4 in 82% of the patients. The overall neurological complication rate was 12%. In the regression analysis, patients with VA or PICA aneurysms had better functional outcomes than the other groups (p < 0.001). Endovascular strategies were associated with better outcomes for BA-VBJ aneurysms (p < 0.01), but microsurgery was associated with better outcomes for VA-PICA and PCA aneurysms (p < 0.05). There were no other significant associations between patient, aneurysm characteristics, or treatment features and neurological complications (p > 0.05). Patients treated with flow diversion had more complications than those who underwent other endovascular and microsurgical strategies, but the difference was not significant in regression models. CONCLUSIONS:Posterior circulation fusiform aneurysms remain a challenging aneurysm subtype, but an interdisciplinary treatment approach can result in good outcomes. While flow diversion is a useful addition to the armamentarium, traditional endovascular and microsurgical techniques continue to offer effective options.

BACKGROUND:Cerebral vasospasm following clipping of an unruptured aneurysm is a rare phenomenon. When it does occur, cerebral vasospasm usually occurs on the side ipsilateral to the surgical intervention.CASE DESCRIPTION:A 68-year-old man underwent right-sided pterional craniotomy for clipping of an unruptured anterior communicating artery aneurysm and experienced contralateral vasospasm 5 days later.CONCLUSIONS:We further discuss the pathophysiology underlying vasospasm after uncomplicated craniotomy and nonhemorrhagic aneurysm clipping.

Cavernous malformations of the midbrain require careful consideration of the risks and benefits of intervention as well as the optimal surgical approach for these challenging lesions. Excellent results can be achieved with careful surgical planning and technique. We demonstrate a contralateral left pterional craniotomy for a translamina terminalis approach to carbon dioxide lasereassisted microsurgical resection of a thalamomesencephalic cavernoma in a 59-year-old woman with progressive debilitating diplopia secondary to partial third nerve palsy (Video 1). We performed a contralateral left modified pterional craniotomy in which we limited dissection of the temporalis muscle to approximately one third rather than extending the muscle split down to the zygoma. The cavernous malformation was resected with no complications, and the patient was discharged from the hospital on postoperative day 3. She noted immediate improvement and nearly complete resolution of symptoms over ensuing weeks. This approach offers a direct route to the lesion with minimal brain transgression, while avoiding the critical structures within the interpeduncular cistern, including the basilar artery and thalamomesencephalic perforating arteries, as well as bordering neural structures, including cerebral peduncles, oculomotor nerves, and mamillary bodies. Use of the carbon dioxide laser with its 0.55-mm tip offers a low surgical profile and allows for precise cutting, thus minimizing thermal damage to surrounding tissues. The translamina terminalis approach through a pterional craniotomy offers a safe and potentially less morbid alternative to select thalamomesencephalic lesions compared with exposure through the mesencephalic surface, which in our experience often necessitates an orbitozygomatic craniotomy.

"Letter to the Editor. Microsurgical rhizotomy as treatment for trigeminal neuralgia in patients with multiple sclerosis: turnpike or dirt road?" published on 05 Oct 2018 by American Association of Neurological Surgeons.

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.

OBJECTIVEMoyamoya disease (MMD) disproportionately affects young to middle-aged women. The main treatment for this challenging disease is cerebral bypass surgery. Vascular neurosurgeons often need to counsel women regarding pregnancy following bypass for MMD, but there is a paucity of data. The authors set out to examine neurological and obstetric outcomes in an extensive cohort of MMD patients who had pregnancies following cerebral revascularization at the Stanford Medical Center.METHODSThe authors identified all patients at their institution who underwent cerebral bypass for MMD from 1990 through 2018 and who later became pregnant. Some of these patients also had pregnancies prior to undergoing bypass surgery, and the authors examined these pregnancies as well. They performed a chart review and brief telephone survey to identify obstetric complications, transient ischemic attacks (TIAs), and strokes. Neurological and obstetric outcomes were compared to published rates. They also compared pre- and post-bypass pregnancy complication rates using logistic regression techniques.RESULTSThere were 71 pregnancies among 56 women whose mean age was 30.5 years. Among 59 post-bypass pregnancies, there were 5 (8%) perinatal TIAs. There were no MRI-confirmed strokes or strokes with residual deficits. Among 12 pre-bypass pregnancies, there were 3 (25%) TIAs and 2 (17%) MRI-confirmed strokes. There were no hemorrhagic complications in either group. In the generalized estimating equations analysis, performing cerebral revascularization prior to pregnancy versus after pregnancy was associated with lower odds of perinatal stroke or TIA (OR 0.15, p = 0.0061). Nine pregnancies (13%) were complicated by preeclampsia, and there was one (1%) instance of eclampsia. The overall rate of cesarean delivery was 39%. There were 2 miscarriages, both occurring in the first trimester. There were no maternal deaths.CONCLUSIONSThe authors present neurological and obstetric outcomes data in a large cohort of MMD patients. These data indicate that post-bypass pregnancy is accompanied by low complication rates. There were no ischemic or hemorrhagic strokes among post-bypass pregnant MMD patients. The rate of obstetric complications was low overall. The authors recommend close collaboration between the vascular neurosurgeon and the obstetrician regarding medical management, including blood pressure goals and continuation of low-dose aspirin.

Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure performed in patients with life-threatening conditions, but can be associated with complications. The objectives of this study are to evaluate data on national practice patterns and complications rates in order to optimize clinical care Methods: The Canadian Neurosurgery Research Collaborative conducted a prospective multi-centre registry of patients undergoing EVD insertions at Canadian residency programs Results: In this interim analysis, 4 sites had recruited 46 patients (mean age: 53.9 years, male:female 2:1). Most EVD insertions occurred outside of the operating theatre, using free-hand technique, and performed by junior neurosurgery residents (R1-R3). The catheter tip was in the ipsilateral frontal horn or body of the lateral ventricle in 76% of cases. Suboptimally placed catheters did not have higher rates of short-term occlusion. EVD-related hemorrhage occurred in 6.5% (3/45) with only 1 symptomatic patient. EVD-related infection occurred in 13% (6/46) at a mean of 6 days and was associated with longer duration of CSF drainage (P=0.039; OR: 1.13) Conclusions: Interim results indicate rates of EVD-related complications may be higher than previously thought. This study will continue to recruit patients to confirm these findings and determine specific risk factors associated with them

An abstract is not available for this content so a preview has been provided. As you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

OBJECTIVEPatients with multiple sclerosis (MS)-associated trigeminal neuralgia (TN) have higher recurrence and retreatment rates than non-MS patients. The optimal management strategy and role for microsurgical rhizotomy (MSR) for MS-TN remains to be determined. The aim of this study was to report time to treatment failure (TTF) and pain scores following MSR compared to percutaneous and Gamma Knife procedures.METHODSTime to treatment failure was analyzed after MSR (n = 14) versus prior procedures (n = 53) among MS-TN patients. Kaplan-Meier curves and log-rank test were utilized to compare TTF after MSR versus prior procedures using the same cohort of patients as their own control group. Subsequent analysis compared TTF after MSR to TTF after 93 other procedures among a second cohort of 18 MS-TN patients not undergoing MSR. BNI pain scores were compared between MSR and other procedures among the MS-TN cohort using a chi-square test.RESULTSTTF was significantly longer after MSR than after other procedures in the MSR cohort (median TTF 79 vs 10 months, respectively, p < 0.0001). Similarly, TTF was longer after MSR than after prior procedures in the non-MSR cohort (median TTF 79 vs 13 months, respectively, p < 0.001). MSR resulted in a higher proportion of excellent pain scores when compared to other procedures in the non-MSR cohort (77% vs 29%, p < 0.001). Probability of treatment survival was higher after MSR than after other procedures at all time points (3, 6, 12, 24, 36, and 48 months). There were no deaths or major complications after MSR.CONCLUSIONSTTF was significantly longer following MSR compared to prior procedures in MS-TN patients. Additionally, a higher proportion of patients achieved excellent BNI pain scores after MSR.

Background: MS related trigeminal neuralgia (MS-TN) is associated with high recurrence and retreatment rates. Optimal treatment and role for partial sensory rhizotomy (PSR) for MS-TN remains to be determined. Methods: We analyzed time to treatment failure (TTF) after PSR (n=14) versus other prior procedures (n=53) among 12 consecutively treated MS-TN patients. Kaplan-Meier curves and Log-Rank tests were utilized to compare BNI pain scores and TTF after PSR vs prior procedures using the same patient cohort as their own control group. Subsequent analysis compared TTF after PSR to other procedures (n=93) among a second cohort of 18 MS-TN patients not undergoing PSR. Results: TTF was significantly longer after PSR compared to prior procedures among the PSR cohort (p<0.0001) with median TTF of 79 vs 10 months respectively. Similarly, there was a longer TTF after PSR compared to prior procedures among the MS-TN cohort with median TTF 79 vs 16 months respectively (p<0.001). PSR resulted in a higher proportion of excellent pain scores when compared to prior procedures in the MS-TN cohort (77% vs 29%, p<0.001). Conclusions: TTF was significantly longer following partial sensory rhizotomy compared to other prior procedures in MS-TN patients. A higher proportion of patients achieved excellent BNI pain scores after PSR.

BACKGROUND:Smartphones and their apps are used ubiquitously in medical practice. However, in some cases their use can be at odds with current patient data safety regulations such as Canada's Personal Health Information Protection Act of 2004. To assess current practices and inform mobile application development, we sought to better understand mobile device usage patterns among Canadian neurosurgery residents.METHODS:Through the Canadian Neurosurgery Research Collaborative, an online survey characterizing smartphone ownership and usage patterns was developed and sent to all Canadian neurosurgery resident in April of 2016. Questionnaires were collected and completed surveys analyzed.RESULTS:Of 146 eligible residents, 76 returned completed surveys (52% response rate). Of these 99% of respondents owned a smartphone, with 79% running on Apple's iOS. Four general mobile uses were identified: 1) communication between members of the medical team, 2) decision support, 3) medical reference, and 4) documentation through medical photography. Communication and photography were areas where the most obvious breaches in the Canadian Personal Health Information Protection Act were noted, with 89% of respondents taking pictures of patients' radiologic studies and 75% exchanging them with Short Message System. Hospital policies had no impact on user behaviors.CONCLUSIONS:Smartphones are used daily by most neurosurgery residents. Identified usage patterns are associated with perceived gains in efficacy and challenges in privacy and data reliability. We believe creating and improving workflows that address these usage patterns has a greater potential to improve privacy than changing policies and enforcing regulations.