Global Outcomes for Microsurgical Clipping of Unruptured Intracranial Aneurysms: A Benchmark Analysis of 2245 Cases.

BACKGROUND AND OBJECTIVES: Benchmarks represent the best possible outcome and help to improve outcomes for surgical procedures. However, global thresholds mirroring an optimal and reachable outcome for microsurgical clipping of unruptured intracranial aneurysms (UIA) are not available. This study aimed to define standardized outcome benchmarks in patients who underwent clipping of UIA. METHODS: A total of 2245 microsurgically treated UIA from 15 centers were analyzed. Patients were categorized into low- ("benchmark") and high-risk ("nonbenchmark") patients based on known factors affecting outcome. The benchmark was defined as the 75th percentile of all centers' median scores for a given outcome. Benchmark outcomes included intraoperative (eg, duration of surgery, blood transfusion), postoperative (eg, reoperation, neurological status), and aneurysm-related factors (eg, aneurysm occlusion). Benchmark cutoffs for aneurysms of the anterior communicating/anterior cerebral artery, middle cerebral artery, and posterior communicating artery were determined separately. RESULTS: Of the 2245 cases, 852 (37.9%) patients formed the benchmark cohort. Most operations were performed for middle cerebral artery aneurysms (53.6%), followed by anterior communicating and anterior cerebral artery aneurysms (25.2%). Based on the results of the benchmark cohort, the following benchmark cutoffs were established: favorable neurological outcome (modified Rankin scale ≤2) ≥95.9%, postoperative complication rate ≤20.7%, length of postoperative stay ≤7.7 days, asymptomatic stroke ≤3.6%, surgical site infection ≤2.7%, cerebral vasospasm ≤2.5%, new motor deficit ≤5.9%, aneurysm closure rate ≥97.1%, and at 1-year follow-up: aneurysm closure rate ≥98.0%. At 24 months, benchmark patients had a better score on the modified Rankin scale than nonbenchmark patients. CONCLUSION: This study presents internationally applicable benchmarks for clinically relevant outcomes after microsurgical clipping of UIA. These benchmark cutoffs can serve as reference values for other centers, patient registries, and for comparing the benefit of other interventions or novel surgical techniques.

Microsurgical Clipping of Unruptured Anterior Circulation Aneurysms-A Global Multicenter Investigation of Perioperative Outcomes.

BACKGROUND AND OBJECTIVES: Microsurgical aneurysm repair by clipping continues to be highly important despite increasing endovascular treatment options, especially because of inferior occlusion rates. This study aimed to present current global microsurgical treatment practices and to identify risk factors for complications and neurological deterioration after clipping of unruptured anterior circulation aneurysms. METHODS: Fifteen centers from 4 continents participated in this retrospective cohort study. Consecutive patients who underwent elective microsurgical clipping of untreated unruptured intracranial aneurysm between January 2016 and December 2020 were included. Posterior circulation aneurysms were excluded. Outcome parameters were postsurgical complications and neurological deterioration (defined as decline on the modified Rankin Scale) at discharge and during follow-up. Multivariate regression analyses were performed adjusting for all described patient characteristics. RESULTS: Among a total of 2192 patients with anterior circulation aneurysm, complete occlusion of the treated aneurysm was achieved in 2089 (95.3%) patients at discharge. The occlusion rate remained stable (94.7%) during follow-up. Regression analysis identified hypertension (P < .02), aneurysm diameter (P < .001), neck diameter (P < .05), calcification (P < .01), and morphology (P = .002) as preexisting risk factors for postsurgical complications and neurological deterioration at discharge. Furthermore, intraoperative aneurysm rupture (odds ratio 2.863 [CI 1.606-5.104]; P < .01) and simultaneous clipping of more than 1 aneurysm (odds ratio 1.738 [CI 1.186-2.545]; P < .01) were shown to be associated with an increased risk of postsurgical complications. Yet, none of the surgical-related parameters had an impact on neurological deterioration. Analyzing volume-outcome relationship revealed comparable complication rates (P = .61) among all 15 participating centers. CONCLUSION: Our international, multicenter analysis presents current microsurgical treatment practices in patients with anterior circulation aneurysms and identifies preexisting and surgery-related risk factors for postoperative complications and neurological deterioration. These findings may assist in decision-making for the optimal therapeutic regimen of unruptured anterior circulation aneurysms.

Sex-dependent characteristics and outcomes after clipping of unruptured intracranial aneurysms: a multicenter propensity score-matched study.

OBJECTIVE: Disparities in the epidemiology and growth rates of aneurysms between the sexes are known. However, little is known about sex-dependent outcomes after microsurgical clipping of unruptured intracranial aneurysms (UIAs). The aim of this study was to examine sex differences in characteristics and outcomes after microsurgical clipping of UIAs and to perform a propensity score-matched analysis using an international multicenter cohort. METHODS: This retrospective cohort study involved the participation of 15 centers spanning four continents. It included adult patients who underwent clipping of UIAs between January 2016 and December 2020. Patients were stratified according to their sex and analyzed for differences in morbidities and aneurysm characteristics. Based on this stratification, female patients were matched to male patients in a 1:1 ratio with a caliper width of 0.1 using propensity score matching. Endpoints included postoperative complications, neurological performance, and aneurysm occlusion at discharge and 24 months after clip placement. RESULTS: A total of 2245 patients with a mean age of 57.3 (range 20-87) years were included. Of these patients, 1675 (74.6%) were female. Female patients were significantly older (mean 57.6 vs 56.4 years, p = 0.03) but had fewer comorbidities. Aneurysms of the internal carotid artery (7.1% vs 4.2%), posterior communicating artery (6.9% vs 1.9%), and ophthalmic artery (6.0% vs 2.8%) were more commonly treated surgically in females, while clipping of aneurysms of the anterior communicating artery was more frequent in males (17.0% vs 25.3%; all p < 0.001). After propensity score matching, female patients were found to have had significantly fewer pulmonary complications (1.4% vs 4.2%, p = 0.01). However, general morbidity (24.5% vs 25.2%, p = 0.72) and mortality (0.5% vs 1.1%, p = 0.34), as well as neurological performance (p = 0.58), were comparable at discharge in both sexes. Lastly, rates of aneurysm occlusion at the time of discharge (95.5% vs 94.9%, p = 0.71) and 24 months after surgery (93.8% vs 96.1%, p = 0.22) did not significantly differ between male and female patients. CONCLUSIONS: Despite overall differences between male and female patients in demographics, comorbidities, and treated aneurysm location, sex did not relevantly affect surgical performance or perioperative complication rates.

Physiological and pathophysiological mechanisms of the molecular and cellular biology of angiogenesis and inflammation in moyamoya angiopathy and related vascular diseases.

Rationale: The etiology and pathophysiological mechanisms of moyamoya angiopathy (MMA) remain largely unknown. MMA is a progressive, occlusive cerebrovascular disorder characterized by recurrent ischemic and hemorrhagic strokes; with compensatory formation of an abnormal network of perforating blood vessels that creates a collateral circulation; and by aberrant angiogenesis at the base of the brain. Imbalance of angiogenic and vasculogenic mechanisms has been proposed as a potential cause of MMA. Moyamoya vessels suggest that aberrant angiogenic, arteriogenic, and vasculogenic processes may be involved in the pathophysiology of MMA. Circulating endothelial progenitor cells have been hypothesized to contribute to vascular remodeling in MMA. MMA is associated with increased expression of angiogenic factors and proinflammatory molecules. Systemic inflammation may be related to MMA pathogenesis. Objective: This literature review describes the molecular mechanisms associated with cerebrovascular dysfunction, aberrant angiogenesis, and inflammation in MMA and related cerebrovascular diseases along with treatment strategies and future research perspectives. Methods and results: References were identified through a systematic computerized search of the medical literature from January 1, 1983, through July 29, 2022, using the PubMed, EMBASE, BIOSIS Previews, CNKI, ISI web of science, and Medline databases and various combinations of the keywords "moyamoya," "angiogenesis," "anastomotic network," "molecular mechanism," "physiology," "pathophysiology," "pathogenesis," "biomarker," "genetics," "signaling pathway," "blood-brain barrier," "endothelial progenitor cells," "endothelial function," "inflammation," "intracranial hemorrhage," and "stroke." Relevant articles and supplemental basic science articles almost exclusively published in English were included. Review of the reference lists of relevant publications for additional sources resulted in 350 publications which met the study inclusion criteria. Detection of growth factors, chemokines, and cytokines in MMA patients suggests the hypothesis of aberrant angiogenesis being involved in MMA pathogenesis. It remains to be ascertained whether these findings are consequences of MMA or are etiological factors of MMA. Conclusions: MMA is a heterogeneous disorder, comprising various genotypes and phenotypes, with a complex pathophysiology. Additional research may advance our understanding of the pathophysiology involved in aberrant angiogenesis, arterial stenosis, and the formation of moyamoya collaterals and anastomotic networks. Future research will benefit from researching molecular pathophysiologic mechanisms and the correlation of clinical and basic research results.

Management of hangman's fractures using anchored anterior cervical cages.

Background: Hangman's fractures comprise approximately 20% of C2 fractures and often require surgery to correct significant angulation and/or subluxation. Recently, anchored anterior cervical cages (ACCs) have been used to fuse C2-3 as they reduce the risks of soft-tissue dissection, bone drilling, operative time, and postoperative dysphagia. Methods: This single-center and retrospective study (2012-2019) included 12 patients (3 type I, 6 type II, and 3 type IIa fractures) undergoing C2-3 ACCs (zero profile, half plate, full plate). Preoperative and postoperative radiographic and clinical data were analyzed. Results: The 12 patients demonstrated the following findings: a mean operative time of 106 ± 21 min, blood loss averaging 67 ± 58 mL, and mean length of stay of 9.8 ± 7.7 days (6.4 ± 5.5 days in intensive care). The mean differences in preoperative versus postoperative radiographs showed an increase in disc angle (9.0° ± 9.4° vs. 14.0° ± 7.2°), reduction of subluxation (18.5% ± 13.6% vs. 2.6% ± 6.2%), and maintenance of C2-7 lordosis (14.3° ± 9.5° vs. 14.4° ± 9.5°). All patients demonstrated fusion on dynamic films obtained >6 months postoperatively. In addition, only one patient had Grade 0 subsidence, three had transient postoperative dysphagia, whereas none had either intraoperative complications or 90-day readmissions. Conclusion: ACCs proved to be a viable alternative to traditional anterior cervical discectomy/fusion to treat 12 patients with C2-3 hangman's fractures in this preliminary study.

Occipital Artery to Middle Cerebral Artery Direct Bypass: A Salvage Revascularization Technique for Ischemic Moyamoya Disease.

OBJECTIVE: The main treatment for moyamoya disease (MMD) is revascularization surgery. Most bypasses use the superficial temporal artery (STA) as the donor vessel. However, even if the STA-middle cerebral artery (MCA) bypass is functioning, the affected hemisphere can continue to be symptomatically malperfused. We sought to assess the efficacy of salvage direct revascularization surgery using the occipital artery (OA) as a donor vessel in patients with ischemic MMD who experience continued cerebral malperfusion despite previous successful STA-MCA bypass. METHODS: We retrospectively analyzed the cerebrovascular databases of 2 surgeons and described patients in whom the OA was used as the donor vessel for direct revascularization. RESULTS: Seven patients were included (5 women). Previous STA-MCA bypasses were direct (n = 2), indirect (n = 3), or combined/multiple (n = 2). The mean (SD) interval between STA-MCA and OA-MCA procedures was 29.2 (13.1) months. Despite an intact STA-MCA bypass in all 7 cases, all 7 patients had recurrent symptoms and demonstrated residual impaired cerebral perfusion. All 7 patients underwent successful OA-MCA direct revascularization. Follow-up perfusion imaging was obtained for 6 of 7 patients. All 6 of these patients demonstrated improved cerebral blood flow to the revascularized hemispheres. All 7 patients demonstrated clinical improvement. CONCLUSIONS: Patients with ischemic MMD who have continued symptoms and cerebral malperfusion despite previous successful STA-MCA bypass present a challenging clinical scenario. Our series highlights the potential utility of the OA-MCA direct bypass as a salvage therapy for these patients.

Genetic and Proteomic Contributions to the Pathophysiology of Moyamoya Angiopathy and Related Vascular Diseases.

RATIONALE: This literature review describes the pathophysiological mechanisms of the current classes of proteins, cells, genes, and signaling pathways relevant to moyamoya angiopathy (MA), along with future research directions and implementation of current knowledge in clinical practice. OBJECTIVE: This article is intended for physicians diagnosing, treating, and researching MA. METHODS AND RESULTS: References were identified using a PubMed/Medline systematic computerized search of the medical literature from January 1, 1957, through August 4, 2020, conducted by the authors, using the key words and various combinations of the key words "moyamoya disease," "moyamoya syndrome," "biomarker," "proteome," "genetics," "stroke," "angiogenesis," "cerebral arteriopathy," "pathophysiology," and "etiology." Relevant articles and supplemental basic science articles published in English were included. Intimal hyperplasia, medial thinning, irregular elastic lamina, and creation of moyamoya vessels are the end pathologies of many distinct molecular and genetic processes. Currently, 8 primary classes of proteins are implicated in the pathophysiology of MA: gene-mutation products, enzymes, growth factors, transcription factors, adhesion molecules, inflammatory/coagulation peptides, immune-related factors, and novel biomarker candidate proteins. We anticipate that this article will need to be updated in 5 years. CONCLUSION: It is increasingly apparent that MA encompasses a variety of distinct pathophysiologic conditions. Continued research into biomarkers, genetics, and signaling pathways associated with MA will improve and refine our understanding of moyamoya's complex pathophysiology. Future efforts will benefit from multicenter studies, family-based analyses, comparative trials, and close collaboration between the clinical setting and laboratory research.

Pathophysiology of Vascular Stenosis and Remodeling in Moyamoya Disease.

Moyamoya disease (MMD) and moyamoya syndrome (MMS) are progressive vascular pathologies unique to the cerebrovasculature that are important causes of stroke in both children and adults. The natural history of MMD is characterized by primary progressive stenosis of the supraclinoid internal carotid artery, followed by the formation of fragile collateral vascular networks. In MMS, stenosis and collateralization occur in patients with an associated disease or condition. The pathological features of the stenosis associated with MMD include neointimal hyperplasia, disruption of the internal elastic lamina, and medial attenuation, which ultimately lead to progressive decreases in both luminal and external arterial diameter. Several molecular pathways have been implicated in the pathophysiology of stenosis in MMD with functions in cellular proliferation and migration, extracellular matrix remodeling, apoptosis, and vascular inflammation. Importantly, several of these molecular pathways overlap with those known to contribute to diseases of systemic arterial stenosis, such as atherosclerosis and fibromuscular dysplasia (FMD). Despite these possible shared mechanisms of stenosis, the contrast of MMD with other stenotic pathologies highlights the central questions underlying its pathogenesis. These questions include why the stenosis that is associated with MMD occurs in such a specific and limited anatomic location and what process initiates this stenosis. Further investigation of these questions is critical to developing an understanding of MMD that may lead to disease-modifying medical therapies. This review may be of interest to scientists, neurosurgeons, and neurologists involved in both moyamoya research and treatment and provides a review of pathophysiologic processes relevant to diseases of arterial stenosis on a broader scale.

Corrigendum: Pathophysiology of Vascular Stenosis and Remodeling in Moyamoya Disease.

[This corrects the article DOI: 10.3389/fneur.2021.661578.].

The evolution of the treatment of traumatic cerebrovascular injury during wartime.

The approach to traumatic craniocervical vascular injury has evolved significantly in recent years. Conflicts prior to Operations Iraqi and Enduring Freedom were characterized by minimal intervention in the setting of severe penetrating head injury, in large part due to limited far-forward resource availability. Consequently, sequelae of penetrating head injury like traumatic aneurysm formation remained poorly characterized with a paucity of pathophysiological descriptions. The current conflicts have seen dramatic improvements with respect to the management of severe penetrating and closed head injuries. As a result of the rapid field resuscitation and early cranial decompression, patients are surviving longer, which has led to diagnosis and treatment of entities that had previously gone undiagnosed. Therefore, in this paper the authors' purpose is to review their experience with severe traumatic brain injury complicated by injury to the craniocervical vasculature. Historical approaches will be reviewed, and the importance of modern endovascular techniques will be emphasized.

Superficial Femoral Artery Interposition Graft for Repair of a Ruptured Mycotic Common Carotid Artery Pseudoaneurysm: Case Report and Review of the Literature.

BACKGROUND: Indications for reconstruction of the common carotid artery (CCA) include trauma, iatrogenic injury, neoplastic growth (such as invasive neck carcinomas), postoperative infection, and cervical carotid aneurysm. Although various techniques and conduits have been described, the clinical scenario may preclude the use of the most commonly used grafts. We describe a case using a superficial femoral artery (SFA) interposition graft to repair the CCA and review the available literature, highlighting the feasibility of this technique for carotid artery reconstruction. CASE DESCRIPTION: A patient aged 51 years presented with a ruptured mycotic CCA pseudoaneurysm that developed in the setting of a pharyngeal-carotid fistula. Because of the presence of a pharyngeal-carotid fistula and active infection within the vessel wall, endovascular treatment of the pseudoaneurysm was not feasible, and open surgical correction was required to repair the fistulous connection. Furthermore, owing to the extensive soft tissue infection, the use of a synthetic or venous autograft conduit for repair of the artery was contraindicated. Therefore, we harvested a segment of the SFA and used it as an interposition graft to reconstruct the diseased CCA, achieving an excellent anatomic and clinical result. CONCLUSIONS: This case highlights the feasibility of using an SFA interposition graft for short-segment CCA reconstruction, which can provide significant utility in the setting of a hostile operative field due to prior infection or radiation.

Revascularization of Moyamoya Angiopathy in Older Adults.

BACKGROUND: Moyamoya angiopathy most often manifests in patients in the second and third decades of life. Although uncommon, it can also manifest later in life. We present our results in patients >50 years old with moyamoya angiopathy who were treated with surgical revascularization via either direct bypass or indirect bypass (encephaloduroarteriosynangiosis). METHODS: A retrospective review was conducted to identify patients with moyamoya disease who were treated with surgical revascularization at our institution between 2002 and 2015. Outcomes and complications were analyzed. RESULTS: We identified 33 patients with moyamoya angiopathy >50 years old (mean age 59.0 years ± 7.6) who were treated with surgical revascularization of 45 affected hemispheres. Of the affected hemispheres, 27 (60%) were treated with indirect bypasses and 18 (40%) were treated with direct bypasses. Neurologic complications occurred in 4 (12%) patients. The mean length of follow-up was 18.7 months ± 18.6; 4 patients were lost to follow-up. At last follow-up, 11 of 18 (61%) direct bypasses were patent. Treatment failed in 5 of 45 (11%) treated hemispheres (stroke in 2 and persistent transient ischemic attacks in 3). In terms of functional outcome at last follow-up, 16 of 29 (55%) patients were the same as before surgery, 10 (35%) were better, and 3 (10%) were worse (including 1 death). CONCLUSIONS: Although uncommon, moyamoya angiopathy can manifest in older adults. Surgical revascularization is a reasonable treatment option with good functional outcomes and an acceptable complication rate.

Keyhole Supraorbital Craniotomy for Aneurysm Clipping in the Setting of Bypass for Moyamoya Disease.

BACKGROUND: In 3%-15% of patients with moyamoya disease, aneurysms occur throughout the circle of Willis. In moyamoya patients treated with a superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass, treatment of a new or an enlarging aneurysm can be complicated by the presence of the bypass and by limitations on the use of standard frontotemporal craniotomies to gain access to the aneurysm. Furthermore, endovascular access can be limited by the presence of fragile moyamoya vessels and precluded by atresia of large vessels. CASE DESCRIPTION: A 45-year-old female patient with a history of moyamoya disease and previous left STA-MCA bypass presented with an enlarging left superior cerebellar artery aneurysm. We used a keyhole supraorbital craniotomy as a minimally invasive route to treat this aneurysm of the circle of Willis, with minimal interruption to the existing bypass or collateral circulation. CONCLUSIONS: In patients with moyamoya disease who have existing STA-MCA bypass and de novo or expanding aneurysms, treatment is fraught with challenges. We advocate the use of a minimally invasive keyhole supraorbital craniotomy with an eyebrow incision for aneurysms associated with moyamoya disease occurring on the proximal anterior cerebral and middle cerebral arteries, the anterior communicating artery, the basilar apex, the posterior communicating artery, the proximal superior cerebellar artery, and the posterior cerebral artery.

Perioperative Complications and Long-Term Outcomes After Bypasses in Adults with Moyamoya Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgical revascularization for adults with moyamoya disease (MD) includes direct, indirect, or combination bypasses. It is unclear which provides the best outcomes. We sought to determine the best surgical management for adults with MD by comparing perioperative complications and long-term outcomes among 3 bypass types. METHODS: Literature databases were searched for articles reporting revascularization bypass outcomes for adults with MD. A pooled analysis of all qualified studies and meta-analysis using only studies reporting direct comparisons of 2 bypass types were performed. Overall odds ratios (ORs) comparing 2 bypass types were computed and publication bias was assessed. Rates of perioperative and long-term hemorrhage and ischemia and favorable outcomes were compared. RESULTS: Forty-seven studies were analyzed; 8 had level 1 or 2 evidence. Pooled analyses showed that perioperative hemorrhage rates were significantly (P = 0.02) lower with indirect compared with direct (OR, 0.03; 95% confidence interval [CI], 0.002-0.55) or combined (OR, 0.03; 95% CI, 0.002-0.53) bypasses. Meta-analysis showed that direct bypass was better at preventing long-term hemorrhage than was indirect bypass (OR, 0.26; 95% CI, 0.09-0.79; P = 0.02). Pooled analyses showed that direct is significantly better (P < 0.01) than indirect (OR, 0.51; 95% CI, 0.33-0.77) and combined (OR, 0.47; 95% CI, 0.31-0.72) bypasses in preventing long-term ischemia. Meta-analysis showed that direct was better than indirect bypass in producing long-term favorable outcomes (OR, 2.62; 95% CI, 1.19-5.79; P = 0.02), and the pooled analysis showed that combined bypass was better than indirect bypass in producing long-term favorable outcomes (OR, 1.26; 95% CI, 1.03-1.54; P = 0.02). CONCLUSIONS: Overall, our analyses suggest that direct bypass with or without indirect augmentation provides the best outcomes for adults with MD.

Use of a side branch in a saphenous vein interposition graft for high-flow extracranial-intracranial bypass procedures. Technical note.

Saphenous vein (SV) interposition grafts are often used for high-flow extracranial-intracranial bypass procedures. During these procedures, it is essential to remove air and debris from the graft and to evaluate blood flow through the graft after it has been anastomosed to other cortical vessels. In this paper, the authors describe the preservation of a large side branch on the proximal end of the SV. This side branch can be used to flush out air and debris from the graft and to evaluate blood flow during revascularization.

Assessing success after cerebral revascularization for ischemia.

Cerebral revascularization continues to evolve as an option in the setting of ischemia. The potential to favorably influence stroke risk and the natural history of cerebrovascular occlusive disease is being evaluated by the ongoing Carotid Occlusion Surgery Study and the Japanese Extracranial-Intracranial Bypass Trial. For those patients who undergo bypass in the setting of ischemia, four key areas of follow-up include functional neurological status, neurocognitive status, bypass patency, and status of cerebral blood flow and perfusion. Several stroke scales that can be used to assess functional status include the National Institutes of Health Stroke Scale, Bathel Index, Modified Rankin Scale, and Stroke Specific Quality of Life. Neurocognition can be checked using the Repeatable Battery for the Assessment of Neuropsychological Status, among other tests. Bypass patency is checked intraoperatively using various flow probes and postoperatively using magnetic resonance angiography (MRA) or computed tomographic angiography (CTA). Cerebral blood flow and perfusion can be assessed using a host of modalities that include positron emission tomography (PET), xenon CT, single photon emission computed tomography (SPECT), transcranial Doppler (TCD), CT, and MR. Paired blood flow studies after a cerebral vasodilatory stimulus using one of these modalities can determine the state of autoregulatory vasodilation (Stage 1 hemodynamic compromise). However, only PET with oxygen extraction fraction measurements can reliably assess for Stage 2 compromise (misery perfusion). This article discusses the various clinical, neuropsychological, and radiographic techniques available to assess a patient's clinical state and cerebral blood flow before and after cerebral revascularization.

Graft harvesting for revascularization in the head and neck.

The techniques for revascularization in the neurocranium, skull base, and neck continue to evolve at an exciting pace. In this body of literature, however, techniques for harvesting radial artery and saphenous vein grafts are mainly reported using traditional open techniques. Minimally invasive procedures are fast becoming an alternative to open techniques in many fields and have the potential to become the standard of care. The cardiovascular literature is replete with reports of endoscopically harvested vascular grafts. This article reviews both methods, since the current state of the art involves knowledge of open and endoscopic harvesting techniques.

Safety and Efficacy of Surgical Resection of Unruptured Low-grade Arteriovenous Malformations From the Modern Decade.

BACKGROUND: Recent studies have questioned the utility of surgical resection of unruptured brain arteriovenous malformations (bAVMs). OBJECTIVE: We performed an assessment of outcomes and complications of surgical resection of low-grade bAVMs (Spetzler-Martin grade I or II) at a single high-volume neurosurgical center. METHODS: We reviewed all unruptured low-grade bAVMs treated with surgery (with or without preoperative embolization) between January 2004 and January 2014. Stroke rate, mortality, and clinical and radiographic outcomes were examined. RESULTS: Of 95 patients treated surgically, 85 (25 grade I, 60 grade II) met inclusion criteria, and all achieved radiographic cure postoperatively. Ten patients (11.8%) were lost to follow-up; the mean follow-up of the remaining 85 was 3.3 years. Three patients (3.5%) with grade II bAVMs experienced a stroke; no patients died. Although 20 patients (23.5%) had temporary postoperative neurological deficit, only 3 (3.5%) had new clinical impairment (modified Rankin Scale score ≥2) at last follow-up. Eight of the 13 patients (61.5%) with preexisting clinical impairment had improved modified Rankin Scale scores of 0 or 1; and 17 of 30 patients (56.7%) with preoperative seizures were seizure-free without antiepileptic medication postoperatively. No significant differences existed in stroke rate or clinical outcome between grades I and II patients at follow-up (Fisher exact test, P = .55 and P > .99, respectively). CONCLUSION: Surgical resection of low-grade unruptured bAVMs is safe, with a high rate of improvement in functional status and seizure reduction. Although transient postoperative neurological deficit was observed in some patients, permanent treatment-related neurological morbidity was rare. ABBREVIATIONS: ARUBA, A Randomized Trial of Unruptured Brain Arteriovenous MalformationsbAVM, brain arteriovenous malformationmRS, modified Rankin Scale.

The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease.

OBJECT: The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel-Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment. METHODS: The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia. The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts. CONCLUSION: In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect-producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment.

Surgical management of brainstem hemangioblastomas in patients with von Hippel-Lindau disease.

OBJECT: Hemangioblastomas of the brainstem constitute 5 to 10% of central nervous system (CNS) tumors in patients with von Hippel-Lindau (VHL) disease. At present, optimal management of brainstem hemangioblastomas associated with VHL disease is incompletely defined. In an attempt to clarify some of the uncertainty about the operative treatment of these lesions and its outcome, the authors reviewed all cases of VHL disease in which resection of brainstem hemangioblastomas was performed at the National Institutes of Health during a 10-year period. METHODS: Twelve consecutive patients with VHL disease (six male and six female patients [mean age 31.7 +/- 9 years; range 15-46 years]) who underwent 13 operations to remove 17 brainstem hemangioblastomas were included in this study (mean follow-up period, 88.4 +/- 37.4 months; range 37-144 months). Serial examinations, hospital charts, magnetic resonance images, and operative records were reviewed. To evaluate clinical course, clinical grades were assigned to each patient before and after surgery. Preoperative neurological function was the best predictor of long-term outcome. In addition, patients who underwent CNS surgeries for hemangioblastomas were more likely to improve or to remain neurologically stable. Tumor or cyst size, the presence of a cyst, or the location of the tumor (intramedullary, extramedullary, or mixed; posterior medullary, obex, or lateral) did not affect outcome. No patient was neurologically worse after brainstem surgery. At long-term follow-up review (mean 88.4 months), only one patient had declined neurologically and this was due to the cumulative neurological effects caused by eight additional hemangioblastomas of the spinal cord and their surgical treatment. CONCLUSIONS: Brainstem hemangioblastomas in patients with VHL disease can be removed safely; they generally should be resected when they become symptomatic or when the tumor has reached a size such that further growth will increase the risks associated with surgery, or in the presence of an enlarging cyst. Magnetic resonance imaging is usually sufficient for preoperative evaluation and presurgical embolization is unnecessary. The goal of surgery is complete resection of the lesion before the patient experiences a disabling neurological deficit.