The phase coherence of the neurovascular unit is reduced in Huntington's disease.

Huntington's disease is a neurodegenerative disorder in which neuronal death leads to chorea and cognitive decline. Individuals with ≥40 cytosine-adenine-guanine repeats on the interesting transcript 15 gene develop Huntington's disease due to a mutated huntingtin protein. While the associated structural and molecular changes are well characterized, the alterations in neurovascular function that lead to the symptoms are not yet fully understood. Recently, the neurovascular unit has gained attention as a key player in neurodegenerative diseases. The mutant huntingtin protein is known to be present in the major parts of the neurovascular unit in individuals with Huntington's disease. However, a non-invasive assessment of neurovascular unit function in Huntington's disease has not yet been performed. Here, we investigate neurovascular interactions in presymptomatic (N = 13) and symptomatic (N = 15) Huntington's disease participants compared to healthy controls (N = 36). To assess the dynamics of oxygen transport to the brain, functional near-infrared spectroscopy, ECG and respiration effort were recorded. Simultaneously, neuronal activity was assessed using EEG. The resultant time series were analysed using methods for discerning time-resolved multiscale dynamics, such as wavelet transform power and wavelet phase coherence. Neurovascular phase coherence in the interval around 0.1 Hz is significantly reduced in both Huntington's disease groups. The presymptomatic Huntington's disease group has a lower power of oxygenation oscillations compared to controls. The spatial coherence of the oxygenation oscillations is lower in the symptomatic Huntington's disease group compared to the controls. The EEG phase coherence, especially in the α band, is reduced in both Huntington's disease groups and, to a significantly greater extent, in the symptomatic group. Our results show a reduced efficiency of the neurovascular unit in Huntington's disease both in the presymptomatic and symptomatic stages of the disease. The vasculature is already significantly impaired in the presymptomatic stage of the disease, resulting in reduced cerebral blood flow control. The results indicate vascular remodelling, which is most likely a compensatory mechanism. In contrast, the declines in α and γ coherence indicate a gradual deterioration of neuronal activity. The results raise the question of whether functional changes in the vasculature precede the functional changes in neuronal activity, which requires further investigation. The observation of altered dynamics paves the way for a simple method to monitor the progression of Huntington's disease non-invasively and evaluate the efficacy of treatments.

Subtemporal Approach for the Treatment of Ruptured and Unruptured Distal Basilar Artery Aneurysms: Is There a Contemporary Use?

BACKGROUND AND OBJECTIVES: Distal basilar artery aneurysms (DBAs) are high-risk lesions for which endovascular treatment is preferred because of their deep location, yet indications for open clipping nonetheless remain. The subtemporal approach allows for early proximal control and direct visualization of critical posterior perforating arteries, especially for posterior-projecting aneurysms. Our objective was to describe our clinical experience with the subtemporal approach for clipping DBAs in the evolving endovascular era. METHODS: This was a retrospective, single-institution case series of patients with DBAs treated with microsurgery over a 21-year period (2002-2023). Demographic, clinical, and surgical data were collected for analysis. RESULTS: Twenty-seven patients underwent clipping of 11 ruptured and 16 unruptured DBAs with a subtemporal approach (24 female; mean age 53 years). Ten patients had expanded craniotomies for treatment of additional aneurysms. The aneurysm occlusion rate was 100%. Good neurological outcomes as defined by the modified Rankin Scale score ≤2 and Glasgow Outcome Scale score ≥4 were achieved in 21/27 patients (78%). Two patients died before hospital discharge, one from vasospasm-induced strokes and another from an intraoperative myocardial infarction. CONCLUSION: These results demonstrate that microsurgical clip ligation of DBAs using the subtemporal approach remains a viable option for complex lesions not amenable to endovascular management.

Management of failed flow diversion for intracranial aneurysm beyond the first 6 months of follow-up: an international Delphi consensus.

OBJECTIVE: The placement of flow-diverting devices has become a common method of treating unruptured intracranial aneurysms of the internal carotid artery. The progressive improvement of aneurysm occlusion after treatment-with low complication and rupture rates-has led to a dilemma regarding the management of aneurysms in which occlusion has not occurred within 6-24 months. The authors aimed to identify clinical consensus regarding management of intracranial aneurysms displaying persistent filling 6-24 months after flow diversion and to ascertain questions that may drive future investigation. METHODS: An international panel of 67 experts was invited to participate in a multistep Delphi consensus process on the treatment of intracranial aneurysms after failed flow diversion. RESULTS: Of the 67 experts invited, 23 (34%) participated. Qualitative analysis of an initial survey with open-ended questions resulted in 51 statements regarding management of aneurysms showing persistent filling after flow diversion. The statements were grouped into 8 categories, and in the second round, respondents rated the degree of their agreement with each statement on a 5-point Likert scale. Flow diverters with surface modifiers did not influence administration of dual-antiplatelet therapy according to 83%. Consensus was also reached regarding the definition of treatment failure at specific time points, including at 6 months if there is aneurysm growth or persistent rapid flow through the entirety of the aneurysm (96%), at 12 months if there is aneurysm growth or symptom onset (78%), and at 24 months if there is persistent filling regardless of size and filling characteristics (74%). Although experts agreed that the degree of intimal hyperplasia or in-device stenosis could not be ascertained by noninvasive imaging alone (83%), only 65% chose digital subtraction angiography as the preferred modality. At 6 and 12 months, retreatment is preferred if there is persistent filling with aneurysm growth (96%, 96%), device malposition (48%, 87%), or a history of subarachnoid hemorrhage (65%, 70%), respectively, and at 24 months if there is persistent filling without reduction in aneurysm size (74%). Experts favored treatment with an additional flow diverter (87%) over aneurysm clipping, applying the same principles for follow-up (83%) and treatment failure (91%) as for the first flow diverter. CONCLUSIONS: The authors present the consensus practices of experts in the management of intracranial aneurysms without occlusion 6-24 months after treatment with a flow-diverting device.

Preservation of cranial nerve function in large and giant trigeminal schwannoma resection: a case series.

BACKGROUND: Trigeminal schwannomas (TSs) are intracranial tumors that can cause significant brainstem compression. TS resection can be challenging because of the risk of new neurologic and cranial nerve deficits, especially with large (≥ 3 cm) or giant (≥ 4 cm) TSs. As prior surgical series include TSs of all sizes, we herein present our clinical experience treating large and giant TSs via microsurgical resection. METHODS: This was a retrospective, single-surgeon case series of adult patients with large or giant TSs treated with microsurgery in 2012-2023. RESULTS: Seven patients underwent microsurgical resection for TSs (1 large, 6 giant; 4 males; mean age 39 ± 14 years). Tumors were classified as type M (middle fossa in the interdural space; 1 case, 14%), type ME (middle fossa with extracranial extension; 3 cases, 43%), type MP (middle and posterior fossae; 2 cases, 29%), or type MPE (middle/posterior fossae and extracranial space; 1 case, 14%). Six patients were treated with a frontotemporal approach (combined with transmastoid craniotomy in the same sitting in one patient and a delayed transmaxillary approach in another), and one patient was treated using an orbitofrontotemporal approach. Gross total resection was achieved in 5 cases (2 near-total resections). Five patients had preoperative facial numbness, and 6 had immediate postoperative facial numbness, including two with worsened or new symptoms. Two patients (28%) demonstrated new non-trigeminal cranial nerve deficits over mean follow-up of 22 months. Overall, 80% of patients with preoperative facial numbness and 83% with facial numbness at any point experienced improvement or resolution during their postoperative course. All patients with preoperative or new postoperative non-trigeminal tumor-related cranial nerve deficits (4/4) experienced improvement or resolution on follow-up. One patient experienced tumor recurrence that has been managed conservatively. CONCLUSIONS: Microsurgical resection of large or giant TSs can be performed with low morbidity and excellent long-term cranial nerve function.

The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report.

OBJECTIVE: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. METHODS: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. CONCLUSION: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

Half-and-Half Approach for Multiple Aneurysms at the Superior Cerebellar and Middle Cerebral Arteries.

Aneurysms at the superior cerebellar artery (SCA) are commonly treated endovascularly because of their location around the basilar artery,1,2 but they are not intimately related with thalamoperforators. Therefore in younger patients, those with wide-necked aneurysms, or those with multiple ipsilateral aneurysms, surgery remains a treatment option.3 We present a 52-year-old woman with dizziness in whom multiple, unruptured intracranial aneurysms were identified. Imaging demonstrated a 9-mm right-sided SCA aneurysm and 5-mm right and mirror 3-mm left M1 segment middle cerebral artery aneurysms. The patient gave consent to undergo surgery after counseling regarding her treatment options. A pterional and temporal craniotomy was performed to allow for half-and-half subtemporal and transsylvian approaches (Video 1). Here, we discuss the nuances of the approach related to the anatomy of SCA aneurysms. The challenges of the surgery can be mediated with techniques including division of the tentorium for enhanced exposure and early proximal control with temporary clinping or the use of adenosine (cardiac arrest). Our patient remained neurologically stable postoperatively and in 1-year follow-up. SCA aneurysms are easily visualized by the subtemporal and transsylvian approaches; they are frequently located adjacent to the posterior cerebral artery above and the SCA below. A modified transcavernous approach using the orbitozygomatic craniotomy has been described for access to basilar tip aneurysms.4 While comparable, this case demonstrates the efficient workflow to clip multiple aneurysms using a single, combined approach. In patients with multiple aneurysms presenting ipsilaterally or with comorbid conditions that complicate endovascular embolization, surgery should be considered as a definitive and safe treatment strategy. The patient consented to publication.

Analysis of treatment cost differences in patients undergoing femoral versus radial access in outpatient diagnostic cerebral arteriograms.

BACKGROUND: Outpatient diagnostic cerebral arteriograms are the most common procedure in neuroendovascular surgery, and the use of transradial access for these studies is growing. Although transradial access has been associated with lower hospital costs for elective diagnostic and interventional neuroendovascular procedures, no study has compared transfemoral access and transradial access costs for a homogenous population of patients undergoing outpatient diagnostic cerebral arteriogram. METHODS: In this single-center retrospective study, the Value Driven Outcomes database was used to evaluate treatment costs for patients who underwent outpatient diagnostic cerebral arteriogram from January 2019 to December 2022. Propensity-score matching was performed to reduce confounders. Costs from each encounter were subcategorized into imaging, supplies, pharmacy, procedures, labs, and facility costs. RESULTS: After matching, 337 patients each for transradial access and transfemoral access were available for analysis. A total of 118,992 cost data points were associated with all encounters. Overall, per-visit costs were 15.2% cheaper for patients who underwent transradial access versus transfemoral access (p < 0.001). Most of the cost difference was due to supplies (35.2% cost difference, p < 0.001) and procedure costs (9.3% cost difference, p < 0.001). No statistical differences were observed between the two approaches in imaging, pharmacy, labs, and facility costs (all p > 0.05). CONCLUSIONS: Costs for outpatient diagnostic cerebral arteriogram were lower in patients who underwent transradial access versus transfemoral access because of supply and procedure costs. Understanding reasons for cost differences in common procedures is important for creating strategies to reduce overall healthcare costs. Additionally, addressing the cost differences of newer techniques may increase the likelihood that they are more readily implemented by hospitals and providers.

Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis.

IMPORTANCE: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

Results of Surgical Treatment of Aneurysmal Subarachnoid Hemorrhage in a Single Institution Over 12 Years.

OBJECTIVE: For patients with aneurysmal subarachnoid hemorrhage (aSAH) in whom endovascular treatment is not the optimal treatment strategy, microsurgical clipping remains a viable option. We examined changes in morbidity and outcome over time in patients treated surgically and in relation to surgeon volume and experience. METHODS: All patients who underwent microsurgery for aSAH from 2007 to 2019 at our institution were included. We compared technical complication rates and surgical outcomes between experienced (≥50 independent cases) and inexperienced (<50 independent cases) surgeons and between high-volume (≥20 cases/year) and low-volume (<20 cases/year) surgeons. RESULTS: Most of the 1,003 aneurysms (970 patients, median age 56 years) were in the middle cerebral (41.4%), anterior communicating (27.6%), and posterior communicating (17.5%) arteries; 46.5% were <7 mm. The technical complication rate was 7%, resulting in postoperative infarct in 4.9% of patients. Nineteen patients (2%) died within 30 days of admission. There were no significant changes in rates of technical complication, postoperative infarct, or mortality over the study period. There were no differences in postoperative infarction and technical complication rates between experienced and inexperienced surgeons (P = 0.28 and P = 0.05, respectively), but there were differences when comparing high-volume and low-volume surgeons (P = 0.03 and P < 0.001, respectively). The independent predictors of postoperative infarctions were aneurysm size (P = 0.001), intraoperative large-vessel injury (P < 0.001), and low surgeon volume (P = 0.03). CONCLUSIONS: We present real-world data on surgical morbidity and outcomes after aSAH. We demonstrated a relationship between surgeon volume and outcome for surgical treatment of aSAH, which supports the benefit of subspecialization in cerebrovascular surgery.

Multiple approaches to a spheno-orbital and deep face meningioma: how I do it.

BACKGROUND: The integration of multiple approaches is sometimes needed for the safe resection of complex multicompartment skull base tumors. METHOD: We present the case of a spheno-orbital and deep face meningioma that required a staged resection strategy using transnasal, transoral, transfacial, and transcranial approaches for airway protection and maximal safe tumor removal. CONCLUSION: Limitations in individual skull base approaches for complex tumors can be anticipated and overcome by combining approaches.

Combined retrosigmoid and middle fossa approach for a small, superiorly located petroclival meningioma: how I do it.

BACKGROUND: Petroclival meningiomas pose significant surgical challenges because of their deep location and complex surrounding neurovasculature. The use of multiple surgical approaches can optimize safe tumor removal from multiple anatomic compartments. METHOD: We describe a patient with a growing superior petroclival meningioma centered at the posterior clinoid with extension into Meckel's cave that was successfully removed with a combined retrosigmoid and subtemporal middle fossa approach. This strategy avoided the need for anterior petrous bone drilling and tentorial splitting. CONCLUSION: A combined retrosigmoid and subtemporal middle fossa approach can provide safe access to tumors spanning the supra- and infratentorial compartments.

Combined and staged retrosigmoid, extended middle fossa, and endoscopic transnasal approach to a petroclival chondrosarcoma: how I do it.

BACKGROUND: Tumors of the petroclival region with multicompartment extension can be difficult to address with a single surgical approach. METHOD: We present the case of a patient with a large chondrosarcoma centered at the right petroclival fissure with extension into the cavernous sinus, the region beneath the cavernous sinus, cerebellopontine angle with deformation of the pons, and prevertebral space. A staged complete resection was performed using a stage 1 single-incision combined right retrosigmoid craniotomy and extended middle fossa craniotomy, followed by a stage 2 endoscopic transnasal approach. CONCLUSION: A combined approach to selected petroclival tumors can maximize safe resection.

Safety and efficacy of the Pipeline Flex embolization device with Shield Technology for the acute treatment of ruptured internal carotid artery pseudoaneurysms: a multi-institution case series.

OBJECTIVE: Ruptured blister, dissecting, and iatrogenic pseudoaneurysms are rare pathologies that pose significant challenges from a treatment standpoint. Endovascular treatment via flow diversion represents an increasingly popular option; however, drawbacks include the requirement for dual antiplatelet therapy and the potential for thromboembolic complications, particularly acute complications in the ruptured setting. The Pipeline Flex embolization device with Shield Technology (PED-Shield) offers reduced material thrombogenicity, which may aid in the treatment of ruptured internal carotid artery pseudoaneurysms. METHODS: The authors conducted a multi-institution, retrospective case series to determine the safety and efficacy of PED-Shield for the treatment of ruptured blister, dissecting, and iatrogenic pseudoaneurysms of the internal carotid artery. Clinical, radiographic, treatment, and outcomes data were collected. RESULTS: Thirty-three patients were included in the final analysis. Seventeen underwent placement of a single device, and 16 underwent placement of two devices. No thromboembolic complications occurred. Four patients were maintained on aspirin alone, and all others were treated with long-term dual antiplatelet therapy. Among patients with 3-month follow-up, 93.8% had a modified Rankin Scale score of 0-2. Complete occlusion at follow-up was observed in 82.6% of patients. CONCLUSIONS: PED-Shield represents a new option for the treatment of ruptured blister, dissecting, and iatrogenic pseudoaneurysms of the internal carotid artery. The reduced material thrombogenicity appeared to improve the safety of the PED-Shield device, as this series demonstrated no thromboembolic complications even among patients treated with only single antiplatelet therapy. The efficacy of PED-Shield reported in this series, particularly with placement of two devices, demonstrates its potential as a first-line treatment option for these pathologies.

Occipital artery-to-PICA bypass: how I do it.

BACKGROUND: Posterior inferior cerebellar artery (PICA) aneurysms are uncommon, and their management is challenging because of the complex angioarchitecture of the PICA and the frequently nonsaccular aneurysm presentation. Endovascular therapy may not be feasible. METHODS: We describe our technique of clip trapping with occipital artery (OA)-to-PICA bypass to treat a PICA aneurysm. Because the aneurysm affected the ipsilateral, dominant PICA, an OA-PICA bypass was chosen to ensure adequate flow and reduce risk to the contralateral PICA supply. CONCLUSION: The OA-PICA anastomosis is a safe and effective method to successfully achieve flow preservation with bypass reconstruction and aneurysm trapping.

Spheno-Orbital Meningiomas.

Meningiomas are the most common intracranial brain tumor. Spheno-orbital meningiomas are a rare subtype that originate at the sphenoid wing and characteristically extend to the orbit and surrounding neurovascular structures via bony hyperostosis and soft tissue invasion. This review summarizes early characterizations of spheno-orbital meningiomas, presently understood tumor characteristics, and current management strategies.

A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

BACKGROUND AND OBJECTIVES: There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery. METHODS: To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed. RESULTS: Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (ß = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach. CONCLUSION: Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices.