Category: Vascular

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How definitive treatment affects the rupture rate of unruptured cerebral aneurysms: a competing risk survival analysis

J Neurosurg 132:1062–1067, 2020

To investigate the risk of bleeding from unruptured cerebral aneurysms (UCAs), previous studies have used Kaplan-Meier analyses without treating the definitive treatment as a competing risk event, which may underestimate the rupture rate. The authors analyzed the survival of patients with UCAs alongside the occurrence of aneurysm bleeding and its competing risk events.

METHODS A retrospective analysis was conducted on 722 patients diagnosed with UCAs in the period from 2000 to 2009 using an institution’s electronic medical records and telephone interviews. The cumulative incidence of aneurysm rupture was examined, and factors contributing to rupture were assessed using regression analyses.

RESULTS By 2014, 19 patients had experienced aneurysm rupture, with an overall rupture rate of 0.57% per year over 3320.8 person-years. However, cumulative incidence analysis indicated that 1.3% of all patients had a rupture within 2 years after aneurysm identification, and 38.4% of the patients underwent definitive treatment in the same period. Among the patients who experienced rupture, regression analysis revealed that an aneurysm size greater than 5 mm, a location in the anterior or posterior communicating arteries, and an irregular shape contributed to aneurysm rupture, with HRs of 4.4 (95% CI 1.2–15.7), 3.5 (95% CI 1.4–8.7), and 2.1 (95% CI 0.7–6.0), respectively.

CONCLUSIONS Rupture rate analyses using the person-year or standard Kaplan-Meier method are not as informative without consideration of the competing risks. The incidence of aneurysm rupture should be presented clearly with those of competing risks.

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Embolized cerebral arteriovenous malformations: a multivariate analysis of 101 excised specimens

J Neurosurg 132:1140–1146, 2020

Endovascular approaches have evolved from a technique practiced at very few centers to a widely available option in the management of arteriovenous malformations (AVMs) of the central nervous system. Embolization can be employed as definitive therapy or as an adjunct to surgical excision. A wide variety of embolic agents have been successfully developed and used in the clinical setting. In addition to facilitating vascular occlusion, embolic agents induce a number of reactive and destructive changes in vessel walls and the surrounding tissue. However, studies examining the pathological changes induced by different embolic agents and varying times of exposure are scarce. The goal of the present study was to compare embolic agents and time of exposure on the pathology in excised specimens.

METHODS The records of the Department of Pathology at the London Health Sciences Centre were searched for embolized AVMs for the 35-year period 1980–2015. All cases were reevaluated for clinical and technical variables and standardized histopathological findings. Cases were grouped by embolic agent, volume of agent used, and time to excision.

RESULTS A total of 101 specimens were identified. Embolic agents were invariably associated with a range of pathological findings, some of which may affect the integrity of vessel walls or the reestablishment of flow, thrombosis, acute and chronic inflammatory changes, angionecrosis, extravasation, and recanalization. The type of embolic agent did not predict differences in the incidence or severity of histopathological changes. Larger volumes of embolic agent were associated with a greater proportion of vessels containing embolic material. AVMs excised early (< 1 week postembolization) contained more acute vasculitis, while those excised later (≥ 1 week postembolization) were more likely to exhibit recanalization and foreign body giant cell infiltrates.

CONCLUSIONS Embolic agents induce a predictable range and temporal progression of pathological changes in cerebral AVMs. The embolic agents studied are indistinguishable in terms of the range and frequency of pathological reactions induced. Greater volumes of embolic agent are associated with more abundant agent within the lesion, but the proportion of vessels and vascular cross-sectional areas containing agent is small. Several changes are significantly associated with time postembolization. Acute vasculitis is a more common finding in the 1st week, while recanalization and foreign body–type granulomatous inflammation are more common at 1 week and beyond.

 

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Unruptured intracranial aneurysm growth trajectory: occurrence and rate of enlargement in 520 longitudinally followed cases

J Neurosurg 132:1077–1087, 2020

As imaging technology has improved, more unruptured intracranial aneurysms (UIAs) are detected incidentally. However, there is limited information regarding how UIAs change over time to provide stratified, patient-specific UIA follow-up management. The authors sought to enrich understanding of the natural history of UIAs and identify basic UIA growth trajectories, that is, the speed at which various UIAs increase in size.

METHODS From January 2005 to December 2015, 382 patients diagnosed with UIAs (n = 520) were followed up at UCLA Medical Center through serial imaging. UIA characteristics and patient-specific variables were studied to identify risk factors associated with aneurysm growth and create a predicted aneurysm trajectory (PAT) model to differentiate aneurysm growth behavior.

RESULTS The PAT model indicated that smoking and hypothyroidism had a large effect on the growth rate of large UIAs (≥ 7 mm), while UIAs < 7 mm were less influenced by smoking and hypothyroidism. Analysis of risk factors related to growth showed that initial size and multiplicity were significant factors related to aneurysm growth and were consistent across different definitions of growth. A 1.09-fold increase in risk of growth was found for every 1-mm increase in initial size (95% CI 1.04–1.15; p = 0.001). Aneurysms in patients with multiple aneurysms were 2.43-fold more likely to grow than those in patients with single aneurysms (95% CI 1.36–4.35; p = 0.003). The growth rate (speed) for large UIAs (≥ 7 mm; 0.085 mm/month) was significantly faster than that for UIAs < 3 mm (0.030 mm/month) and for males than for females (0.089 and 0.045 mm/month, respectively; p = 0.048).

CONCLUSIONS Analyzing longitudinal UIA data as continuous data points can be useful to study the risk of growth and predict the aneurysm growth trajectory. Individual patient characteristics (demographics, behavior, medical history) may have a significant effect on the speed of UIA growth, and predictive models such as PAT may help optimize follow-up frequency for UIA management.

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Association between weekend admissions and mortality after aneurysmal subarachnoid hemorrhage: the “weekend effect” revisited

J Neurosurg 132:1167–1173, 2020

Higher mortality has been reported with weekend or after-hours patient admission across a wide range of surgical and medical specialties, a phenomenon termed the “weekend effect.” The authors evaluated whether weekend admission contributed to death and long-term neurological outcome in patients following aneurysmal subarachnoid hemorrhage.

METHODS A post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) study was conducted. Univariable and stepwise multivariable logistic regression analyses were performed to assess the associations between weekend admission and mortality and long-term neurological outcome.

RESULTS Of 413 subjects included in the CONSCIOUS-1 study, 140 patients had been admitted during the weekend. A significant interaction was identified between weekend admission and neurological grade on presentation, suggesting that the outcomes of patients who had initially presented with a poor grade were disproportionately influenced by the weekend admission. On stepwise multivariable logistic regression in the subgroup of patients who had presented with a poor neurological grade (29 of 100 patients), admission on the weekend was found to be independently associated with death (OR 6.59, 95% CI 1.62–26.88, p = 0.009). Weekend admission was not associated with long-term neurological outcome.

CONCLUSIONS Weekend admission was an independent risk factor for death within 12 weeks following aneurysmal subarachnoid hemorrhage in patients presenting with a poor neurological grade. Further work is required to identify and mitigate any mediating factors.

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A novel proposed grading system for cerebellar arteriovenous malformations

J Neurosurg 132:1105–1115, 2020

The objective of this study was to evaluate the existing Spetzler-Martin (SM), Spetzler-Ponce (SP), and Lawton-Young (LY) grading systems for cerebellar arteriovenous malformations (AVMs) and to propose a new grading system to estimate the risks associated with these lesions.

METHODS Data for patients with cerebellar AVMs treated microsurgically in two tertiary medical centers were retrospectively reviewed. Data from patients at institution 1 were collected from September 1999 to February 2013, and at institution 2 from October 2008 to October 2015. Patient outcomes were classified as favorable (modified Rankin Scale [mRS] score 0–2) or poor (mRS score 3–6) at the time of discharge. Using chi-square and logistic regression analysis, variables associated with poor outcomes were assigned risk points to design the proposed grading system. The proposed system included neurological status prior to treatment (poor, +2 points), emergency surgery (+1 point), age > 60 years (+1 point), and deep venous drainage (deep, +1 point). Risk point totals of 0–1 comprised grade 1, 2–3 grade 2, and 4–5 grade 3.

RESULTS A total of 125 cerebellar AVMs of 1328 brain AVMs were reviewed in 125 patients, 120 of which were treated microsurgically and included in the study. With our proposed grading system, we found poor outcomes differed significantly between each grade (p < 0.001), while with the SM, SP, and LY grading systems they did not (p = 0.22, p = 0.25, and p = 1, respectively). Logistic regression revealed grade 2 had 3.3 times the risk of experiencing a poor outcome (p = 0.008), while grade 3 had 9.9 times the risk (p < 0.001). The proposed grading system demonstrated a superior level of predictive accuracy (area under the receiver operating characteristic curve [AUROC] of 0.72) compared with the SM, SP, and LY grading systems (AUROC of 0.61, 0.57, and 0.51, respectively).

CONCLUSIONS The authors propose a novel grading system for cerebellar AVMs based on emergency surgery, venous drainage, preoperative neurological status, and age that provides a superior prognostication power than the formerly proposed SM, SP, and LY grading systems. This grading system is clinically predictive of patient outcomes and can be used to better guide vascular neurosurgeons in clinical decision-making.

 

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Comprehensive analysis of perforator territory infarction on postoperative diffusion-weighted imaging in patients with surgically treated unruptured intracranial saccular aneurysms

J Neurosurg 132:1088–1095, 2020

Perforator territory infarction (PTI) is still a major problem needing to be solved to achieve good outcomes in aneurysm surgery. However, details and risk factors of PTI diagnosed on postoperative MRI remain unknown. The authors aimed to investigate the details of PTI on postoperative diffusion-weighted imaging (DWI) in patients with surgically treated unruptured intracranial saccular aneurysms (UISAs).

METHODS The data of 848 patients with 1047 UISAs were retrospectively evaluated. PTI was diagnosed on DWI, which was performed the day after aneurysm surgery. Clinical and radiological characteristics were compared between UISAs with and without PTI. Poor outcome was defined as an increase in 1 or more modified Rankin Scale scores at 12 months after aneurysm surgery.

RESULTS Postoperative DWI was performed in all cases, and it revealed PTI in 56 UISA cases (5.3%). Forty-three PTIs occurred without direct injury and occlusion of perforators (43 of 56, 77%). Poor outcome was more frequently observed in the PTI group (17 of 56, 30%) than the non-PTI group (57 of 1047, 5.4%) (p < 0.0001). Thalamotuberal arteries (p < 0.01), lateral striate arteries (p < 0.01), Heubner’s artery (p < 0.01), anterior median commissural artery (p < 0.05), terminal internal carotid artery perforators (p < 0 0.01), and basilar artery perforator (p < 0 0.01) infarctions were related to poor outcome by adjusted residual analysis. On multivariate analysis, statin use (OR 10, 95% CI, 3.3–31; p < 0.0001), specific aneurysm locations (posterior communicating artery [OR 4.1, 95% CI 2.1–8.1; p < 0.0001] and basilar artery [OR 3.1, 95% CI 1.1–8.9; p = 0.031]), larger aneurysm size (OR 1.1, 95% CI 1.1–1.2; p = 0.043), and permanent decrease of motor evoked potential (OR 38, 95% CI 3.1–468; p = 0.0045) were related to PTI.

CONCLUSIONS Despite efforts to avoid PTI, it occurred even without direct injury, occlusion of perforators, or evoked potential abnormality. Therefore, surgical treatment of UISAs, especially with the aforementioned risk factors of PTI, should be more carefully considered. The evaluation of PTI in the territory of the above-mentioned perforators could be useful in helping predict the clinical course in patients after aneurysm surgery.

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Embolization of the middle meningeal artery in patients with chronic subdural hematoma—a systematic review and meta-analysis

Acta Neurochirurgica (2020) 162:777–784

Chronic subdural hematoma (CSDH) remains a neurosurgical condition with high recurrence rate after surgical treatment. The primary pathological mechanism is considered to be repeated microbleedings from fragile neo-vessels within the outer hematoma membrane. The neo-vessels are supplied from peripheral branches of the middle meningeal artery, and embolization of MMA (eMMA) has been performed to prevent re-bleeding episodes and thereby CSDH recurrence.

Objective To evaluate the published evidence for the effect of eMMA in patients with recurrent CSDH. Secondarily, to investigate the effect of eMMA as an alternative to surgery for primary treatment of CSDH. Method A systematic review of the literature on eMMA in patients with recurrent CSDH was conducted. PubMed, Embase, and Cochrane databases were reviewed using the search terms: Embolization, Medial Meningeal Artery, Chronic Subdural Haematoma, and Recurrence. Furthermore, the following mesh terms were used: Chronic Subdural Haematoma AND embolization AND medial meningeal artery AND recurrence. Eighteen papers were found and included. No papers were excluded. The number of patients with primary CSDH and the number of patients with recurrent CSDH treated with eMMA were listed. Furthermore, the number of recurrences in both categories was registered.

Results Eighteen papers with a total of 191 included patients diagnosed with CSDH treated with eMMA for primary and recurrent CSDH were identified. Recurrence rate for patients treated with eMMA for recurrent CSDH was found to be 2.4%, 95%CI (0.5%; 11.0%), whereas the recurrence rate for patients treated with eMMAfor primary CSDH was 4.1%, 95%CI (1.4%; 11.4%).

Conclusion eMMA is a minimally invasive procedure for treatment of CSDH. Although this study is limited by publication bias, it seems that this procedure may reduce recurrence rates compared with burr hole craniostomy for both primary and recurrent hematomas. A controlled study is warranted.

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Ten-year analysis of saccular aneurysms in the Barrow Ruptured Aneurysm Trial

J Neurosurg 132:771–776, 2020

The authors present the 10-year results of the Barrow Ruptured Aneurysm Trial (BRAT) for saccular aneurysms. The 1-, 3-, and 6-year results of the trial have been previously reported, as have the 6-year results with respect to saccular aneurysms. This final report comparing the safety and efficacy of clipping versus coiling is limited to an analysis of those patients presenting with subarachnoid hemorrhage (SAH) from a ruptured saccular aneurysm.

METHODS In the study, 362 patients had saccular aneurysms and were randomized equally to the clipping and the coiling cohorts (181 each). The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. The extent of aneurysm obliteration was adjudicated by a nontreating neuroradiologist.

RESULTS There was no statistically significant difference in poor outcome (mRS score > 2) or deaths between these 2 treatment arms during the 10 years of follow-up. Of 178 clip-assigned patients with saccular aneurysms, 1 (< 1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. After the initial hospitalization, 2 of 241 (0.8%) clipped saccular aneurysms and 23 of 115 (20%) coiled saccular aneurysms required retreatment (p < 0.001). At the 10-year follow-up, 93% (50/54) of the clipped aneurysms were completely obliterated, compared with only 22% (5/23) of the coiled aneurysms (p < 0.001). Two patients had documented rebleeding, both died, and both were in the assigned and treated coiled cohort (2/83); no patient in the clipped cohort (0/175) died (p = 0.04). In 1 of these 2 patients, the hemorrhage was not from the target aneurysm but from an incidental basilar artery aneurysm, which was coiled at the same time.

CONCLUSIONS There was no significant difference in clinical outcomes between the 2 assigned treatment groups as measured by mRS outcomes or deaths. Clinical outcomes in the patients with posterior circulation aneurysms were better in the coiling group at 1 year, but after 1 year this difference was no longer statistically significant. Rates of complete aneurysm obliteration and rates of retreatment favored patients who actually underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov)

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Outcomes after coverage of lenticulostriate vessels by flow diverters: a multicenter experience

J Neurosurg 132:473–480, 2020

With the increasing use of flow diversion as treatment for intracranial aneurysms, there is a concomitant increased vigilance in monitoring complications. The low porosity of flow diverters is concerning when the origins of vessels are covered, whether large circle of Willis branches or critical perforators. In this study, the authors report their experience with flow diverter coverage of the lenticulostriate vessels and evaluate their safety and outcomes.

METHODS The authors retrospectively reviewed 5 institutional databases of all flow diversion cases from August 2012 to June 2018. Information regarding patient presentation, aneurysm location, treatment, and outcomes were recorded. Patients who were treated with flow diverters placed in the proximal middle cerebral artery (MCA), proximal anterior cerebral artery, or distal internal carotid artery leading to coverage of the medial and lateral lenticulostriate vessels were included. Clinical outcomes according to the modified Rankin Scale were reviewed. Univariate and multivariate analyses were performed to establish risk factors for lenticulostriate infarct.

RESULTS Fifty-two patients were included in the analysis. Postprocedure cross-sectional images were available in 30 patients. Two patients experienced transient occlusion of the MCA during the procedure; one was asymptomatic, and the other had a clinical and radiographic ipsilateral internal capsule stroke. Five patients had transient symptoms without radiographic infarct in the lenticulostriate territory. Two patients experienced in-stent thrombosis, leading to clinical MCA infarcts (one in the ipsilateral caudate) after discontinuing antiplatelet therapy. Discontinuation of dual antiplatelet therapy prior to 6 months was the only variable that was significantly correlated with stroke outcome (p < 0.01, OR 0.3, 95% CI 0–0.43), and this significance persisted when controlled for other risk factors, including age, smoking status, and aneurysm location.

CONCLUSIONS The use and versatility of flow diversion is increasing, and safety data are continuing to accumulate. Here, the authors provide early data on the safety of covering lenticulostriate vessels with flow diverters. The authors concluded that the coverage of these perforators does not routinely lead to clinically significant ischemia when dual antiplatelet therapy is continued for 6 months. Further evaluation is needed in larger cohorts and with imaging follow-up as experience develops in using these devices in more distal circulation.

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Angiographically occult intracranial aneurysms found during microsurgical aneurysm clipping of known aneurysms

J Neurosurg 132:434–441, 2020

During the microsurgical clipping of known aneurysms, angiographically occult (AO) aneurysms are sometimes found and treated simultaneously to prevent their growth and protect the patient from future rupture or reoperation. The authors analyzed the incidence, treatment, and outcomes associated with AO aneurysms to determine whether limited surgical exploration around the known aneurysm was safe and justified given the known limitations of diagnostic angiography.

METHODS An AO aneurysm was defined as a saccular aneurysm detected using the operative microscope during dissection of a known aneurysm, and not detected on preoperative catheter angiography. A prospective database was retrospectively reviewed to identify patients with AO aneurysms treated microsurgically over a 20-year period.

RESULTS One hundred fifteen AO aneurysms (4.0%) were identified during 2867 distinct craniotomies for aneurysm clipping. The most common locations for AO aneurysms were the middle cerebral artery (60 aneurysms, 54.1%) and the anterior cerebral artery (20 aneurysms, 18.0%). Fifty-six AO aneurysms (50.5%) were located on the same artery as the known saccular aneurysm. Most AO aneurysms (95.5%) were clipped and there was no attributed morbidity. The most common causes of failed angiographic detection were superimposition of a large aneurysm (type 1, 30.6%), a small aneurysm (type 2, 18.9%), or an adjacent normal artery (type 3, 36.9%). Multivariate analysis identified multiple known aneurysms (odds ratio [OR] 3.45, 95% confidence interval [CI] 2.16–5.49, p < 0.0001) and young age (OR 0.981, 95% CI 0.965–0.997, p = 0.0226) as independent predictors of AO aneurysms.

CONCLUSIONS Meticulous inspection of common aneurysm sites within the surgical field will identify AO aneurysms during microsurgical dissection of another known aneurysm. Simultaneous identification and treatment of these additional undiagnosed aneurysms can spare patients later rupture or reoperation, particularly in those with multiple known aneurysms and a history of subarachnoid hemorrhage. Limited microsurgical exploration around a known aneurysm can be performed safely without additional morbidity.

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Embolization of brain arteriovenous malformations with intent to cure: a systematic review

J Neurosurg 132:388–399, 2020

Endovascular embolization has been established as an adjuvant treatment strategy for brain arteriovenous malformations (AVMs). A growing body of literature has discussed curative embolization for select lesions. The transition of endovascular embolization from an adjunctive to a definitive treatment modality remains controversial. Here, the authors reviewed the literature to assess the lesional characteristics, technical factors, and angiographic and clinical outcomes of endovascular embolization of AVMs with intent to cure.

METHODS Electronic databases—Ovid MEDLINE, Ovid Embase, and PubMed—were searched for studies in which there was evidence of AVMs treated using endovascular embolization with intent to cure. The primary outcomes of interest were angiographic obliteration immediately postembolization and at follow-up. The secondary outcomes of interest were complication rates. Descriptive statistics were used to calculate rates and means.

RESULTS Fifteen studies with 597 patients and 598 AVMs treated with intent-to-cure embolization were included in this analysis. Thirty-four percent of AVMs were Spetzler-Martin grade III. Complete obliteration immediately postembolization was reported in 58.3% of AVMs that had complete treatment and in 45.8% of AVMs in the entire patient cohort. The overall clinical complication rate was 24.1%. The most common complication was hemorrhage, occurring in 9.7% of patients. Procedure-related mortality was 1.5%.

CONCLUSIONS While endovascular embolization with intent to cure can be an option for select AVMs, the reported complication rates appear to be increased compared with those in studies in which adjunctive embolization was the goal. Given the high complication rate related to a primary embolization approach, the risks and benefits of such a treatment strategy should be discussed among a multidisciplinary team. Curative embolization of AVMs should be considered an unanticipated benefit of such therapy rather than a goal.

 

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Intraoperative facial motor evoked potential monitoring for pontine cavernous malformation resection

J Neurosurg 132:265–271, 2020

The aim of this study was to predict postoperative facial nerve function during pontine cavernous malformation surgery by monitoring facial motor evoked potentials (FMEPs).

METHODS From 2008 to 2017, 10 patients with pontine cavernous malformations underwent total resection via the trans–fourth ventricle floor approach with FMEP monitoring. House-Brackmann grades and Karnofsky Performance Scale (KPS) scores were obtained pre- and postoperatively. The surgeries were performed using one of 2 safe entry zones into the brainstem: the suprafacial triangle and infrafacial triangle approaches. Six patients underwent the suprafacial triangle approach, and 4 patients underwent the infrafacial triangle approach. A cranial peg screw electrode was used to deliver electrical stimulation for FMEP by a train of 4 or 5 pulse anodal constant current stimulation. FMEP was recorded from needle electrodes on the ipsilateral facial muscles and monitored throughout surgery by using a threshold- level stimulation method.

RESULTS FMEPs were recorded and analyzed in 8 patients; they were not recorded in 2 patients who had severe preoperative facial palsy and underwent an infrafacial triangle approach. Warning signs appeared in all patients who underwent the suprafacial triangle approach. However, after temporarily stopping the procedures, FMEP findings during surgery showed recovery of the thresholds. FMEPs in patients who underwent the infrafacial triangle approach were stable during the surgery. House-Brackmann grades were unchanged postoperatively in all patients. Postoperative KPS scores improved in 3 patients, decreased in 1, and remained the same in 6 patients.

CONCLUSIONS FMEPs can be used to monitor facial nerve function during surgery for pontine cavernous malformations, especially when the suprafacial triangle approach is performed.

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Overview of Different Flow Diverters and Flow Dynamics

Neurosurgery 86:S21–S34, 2020

Over the past decade, flow diverter technology for endocranial aneurysms has seen rapid evolution, with the development of new devices quickly outpacing the clinical evidence base. However, flow diversion has not yet been directly compared to surgical aneurysm clipping or other endovascular procedures. The oldest and most well-studied device is the Pipeline Embolization Device (PED; Medtronic), recently transitioned to the Pipeline Flex (Medtronic), which still has sparse data regarding outcomes.

To date, other flow diverting devices have not been shown to outperform the PED, although information comes primarily from retrospective studies with short follow-up, which are not always comparable.

Because of this lack of high-quality outcome data, no reliable recommendations can be made for choosing among flow diversion devices yet. Moreover, the decision to proceed with flow diversion should be individualized to each patient.

In this work, we wish to provide a comprehensive overview of the technical specifications of all flow diverter devices currently available, accompanied by a succinct description of the evidence base surrounding each device.

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Stereotactic radiosurgery for arteriovenous malformations of the basal ganglia and thalamus: an international multicenter study

J Neurosurg 132:122–131, 2020

Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects.

METHODS The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation- induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome.

RESULTS The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044).

CONCLUSIONS SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

 

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Incidence of Spontaneous Obliteration in Untreated Brain Arteriovenous Malformations

Neurosurgery 86:139–149, 2020

Spontaneous obliteration (SpO) of untreated arteriovenous malformations (AVMs) is rare with fewer than 100 cases reported. The incidence and predisposing factors of SpO remain unclear, impeding our understanding of lesion progression in untreated patients.

OBJECTIVE: To determine the incidence rate and predisposing factors of SpO in a North American cohort.

METHODS: AVMswere retrospectively evaluated at our institution for over 25 yr.Untreated AVMs were divided into 2 groups: SpO-AVMs and non-SpO-AVMs. All statistical results were based on univariate analyses. Incidence was generated from counts of SpO over the untreated interval in patient years frombirth until obliteration, treatment, or last follow-up.

RESULTS: One hundred fifty-four patients had untreated AVMs; SpO was observed in 4. Average ages were 49.0 ± 23.6 and 48.7 ± 20.4 yr in the SpO-AVM and non-SpO-AVM group, respectively (P=.98). Average AVMsizeswere 2.0±1.8 cm(SpO-AVMs) and 3.7±2.6 cm (non-SpO-AVMs, P= .25). All SpO-AVMs and 40 (27.0%) non-SpO-AVMs had a ruptured presentation (P=.006). A single draining veinwas observed in all SpO-AVMs and 39 (32.8%) non-SpO-AVMs (P=.01). Deep venous drainage was not observed in any SpO-AVMs, but in 81 (57.9%) non-SpO-AVMs (P = .04). Mean follow-up time was 37.0 ± 42.6 and 75.6 ± 161.7 mo in SpO-AVMand non-SpO-AVMs patients, respectively. Of the 2 SpO-AVMpatientswith postobliteration follow-up, 1 experienced recanalization. From a 672-patient cohort, the incidence of SpO over 28 961 patient years was 0.014%.

CONCLUSION: SpO-AVMs have an annual incidence rate of approximately 0.014% and tend to present with rupture, a single draining vein, and superficial venous drainage. Expectation of SpO for untreated AVMs is not justified, and patients should anticipate life-long hemorrhagic risk for untreated AVMs.

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Cavernous sinus aneurysms: risk of growth over time and risk factors

J Neurosurg 132:22–26, 2020

Cavernous internal carotid artery (ICA) aneurysms are frequently diagnosed incidentally and the benign natural history of these lesions is well known, but there is limited information assessing the risk of growth in untreated patients. The authors sought to assess and analyze risk factors in patients with cavernous ICA aneurysms and compare them to those of patients with intracranial berry aneurysms in other locations.

METHODS Data from consecutive patients who were diagnosed with a cavernous ICA aneurysm were retrospectively reviewed. The authors evaluated patients for the incidence of cavernous ICA aneurysm growth and rupture. In addition, the authors analyzed risk factors for cavernous ICA aneurysm growth and compared them to risk factors in a population of patients diagnosed with intracranial berry aneurysms in locations other than the cavernous ICA during the same period.

RESULTS In 194 patients with 208 cavernous ICA aneurysms, the authors found a high risk of aneurysm growth (19.2% per patient-year) in patients with large/giant aneurysms. Size was significantly associated with higher risk of growth. Compared to patients with intracranial berry aneurysms in other locations, patients with cavernous ICA aneurysms were significantly more likely to be female and have a lower incidence of hypertension.

CONCLUSIONS Aneurysms of the cavernous ICA are benign lesions with a negligible risk of rupture but a definite risk of growth. Aneurysm size was found to be associated with aneurysm growth, which can be associated with new onset of symptoms. Serial follow-up imaging of a cavernous ICA aneurysm might be indicated to monitor for asymptomatic growth, especially in patients with larger lesions.

 

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Stroke Thrombectomies Using ADAPT With Increasing Aspiration Catheter Size

Neurosurgery 86:61–70, 2020

Endovascular thrombectomy is currently the standard of care for acute ischemic stroke (AIS). Although earlier trials on endovascular thrombectomy were performed using stent retrievers, recently completed the contact aspiration vs stent retriever for successful revascularization (ASTER) and a comparison of direct aspiration versus stent retriever as a first approach (COMPASS) trials have shown the noninferiority of direct aspiration.

OBJECTIVE: To report the largest experience withADAPT thrombectomy and compare the impact of advancement in reperfusion catheter technologies on outcomes.

METHODS:We reviewed a retrospective database of AIS patients who underwent ADAPT thrombectomy between January 2013 and November 2017 at the Medical University of South Carolina. Demographics and baseline characteristics, technical variables, and radiological and clinical outcomes were reviewed.

RESULTS: Among 510 patients (mean age: 67.7, 50.6% females), successful recanalization at first pass was achieved in 61.8%, and with aspiration only in 77.5%.Mean procedure time was 27.4 min, and the rate of good outcomes (mRS 0-2) at 90 d was 42.9%. The rate of recanalization with aspiration only was significantly higher, and procedure timewas significantly lower in patients treated with larger catheters (ACE 064 and ACE 068) compared to smaller catheters (5MAX and ACE, P<.05). Therewere no differences in complication rates or postoperative parenchymal hemorrhage across groups (P > .05); however, use of ACE 068 was an independent predictor of good outcomes at 90 d on multivariate regression analysis (odds ratio = 1.6, P< .05).

CONCLUSION: Refinement of ADAPT thrombectomy by incorporating reperfusion catheters with higher inner diameters and thus higher aspiration forces is associated with better outcomes, shorter procedure times, and lower likelihood of using additional devices without impacting complication rates.

 

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Rupture risk of small unruptured cerebral aneurysms

J Neurosurg 132:69–78, 2020

OBJECTIVE
The annual rupture rate of small (3–4 mm) unruptured cerebral aneurysms (UCAs) is 0.36% per year, however, the proportion of small ruptured aneurysms < 5 mm is 35%. This discrepancy is explained by the hypothesis that most acute subarachnoid hemorrhage (SAH) is from recently formed, unscreened aneurysms, but this hypothesis is without definitive proof. The authors aimed to clarify the actual number of screened, ruptured small aneurysms and risk factors for rupture.

METHODS
The Unruptured Cerebral Aneurysm Study Japan, a project of the Japan Neurosurgical Society, was designed to clarify the natural course of UCAs. From January 2001 through March 2004, 6697 UCAs among 5720 patients were prospectively registered. At registration, 2839 patients (49.6%) had 3132 (46.8%) small UCAs of 3–4 mm. The registered, treated, and rupture numbers of these small aneurysms and the annual rupture rate were investigated. The rate was assessed per aneurysm. The characteristics of patients and aneurysms were compared to those of larger unruptured aneurysms (≥ 5 mm). Cumulative rates of SAH were estimated per aneurysm. Risk factors underwent univariate and multivariate analysis.

RESULTS
Treatment and rupture numbers of small UCAs were 1132 (37.1% of all treated aneurysms) and 23 (20.7% of all ruptured aneurysms), respectively. The registered, treated, rupture number, and annual rupture rates were 1658 (24.8%), 495 (16.2%), 11 (9.9%), and 0.30%, respectively, among 3-mm aneurysms, and 1474 (22.0%), 637 (20.9%), 12 (10.8%), and 0.45%, respectively, among 4-mm aneurysms. Multivariate risk-factor analysis revealed that a screening brain checkup (hazard ratio [HR] 4.1, 95% confidence interval [CI] 1.2–14.4), history of SAH (HR 10.8, 95% CI 2.3–51.1), uncontrolled hypertension (HR 5.2, 95% CI 1.8–15.3), and location on the anterior communicating artery (ACoA; HR 5.0, 95% CI 1.6–15.5) were independent predictors of rupture.

CONCLUSIONS
Although the annual rupture rate of small aneurysms was low, the actual number of ruptures was not low. Small aneurysms that ruptured during follow-up could be detected, screened, and managed based on each risk factor. Possible selection criteria for treating small UCAs include a history of SAH, uncontrolled hypertension, location on the ACoA, and young patients. Further large prospective and longitudinal trials are needed.

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Outcomes of Retreatment for Intracranial Aneurysms—A Meta-Analysis

Neurosurgery. 2019 Dec 1;85(6):750-761

Long-term results from the International Subarachnoid Hemorrhage Trial (ISAT) and Barrow Ruptured Aneurysm Trial (BRAT) indicate considerably higher retreatment rates for aneurysms treated with coiling compared to clipping, but do not report the outcome of retreatment.

OBJECTIVE: To evaluate retreatment related outcomes.

METHODS: A meta-analysis in accordance with PRISMA guidelines was conducted using Medline search engines PubMed and EMBASE to identify articles describing outcomes after retreatment for intracranial aneurysms. Pooled prevalence rates for complete occlusion rate and mortality were calculated. Outcomes of different treatment and retreatment combinations were not compared because of indication bias.

RESULTS: Twenty-five articles that met the inclusion criteria were included in the metaanalysis. Surgery after coiling had a pooled complete occlusion rate of 91.2% (95% confidence interval [CI]: 87.0-94.1) and a pooled mortality rate of 5.6% (95% CI: 3.7-8.3). Coiling after coiling had a pooled complete occlusion rate of 51.3% (95% CI: 22.1-78.0) and a pooled mortality rate of 0.8% (95% CI: 0.15-3.7). Surgery after surgery did not provide a pooled estimate for complete occlusion as only one study was identified but had a pooled mortality rate of 5.9% (95% CI: 3.1-11.2). Coiling after surgery had a pooled complete occlusion rate of 56.1% (95% CI: 11.4-92.7) and a pooled mortality rate of 9.3% (95% CI: 4.1- 19.9). All pooled incidence rates were produced using random-effect models.

CONCLUSION: Surgical retreatment was associated with a high complete occlusion rate but considerable mortality. Conversely, endovascular retreatment was associated with low mortality but also a low complete occlusion rate.

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Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial

Neurosurgery 2019 Dec 1;85(6):843-853

More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit.

OBJECTIVE: To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year. Secondary aims shall assess effects on vascular permeability, ROCKactivity in peripheral leukocytes, signal effects on clinical outcomes, adverse events, and prespecified subgroups.

METHODS: The phase I/IIa placebo-controlled, double-blinded, single-site clinical trial aims to enroll 80 subjects randomized 1-1 to atorvastatin (starting dose 80 mg PO daily) or placebo. Dosing shall continue for 24-mo or until reaching a safety endpoint.

EXPECTED OUTCOMES: The trial is powered to detect an absolute difference of 20% in the mean percent change in lesional QSM per year (2-tailed, power 0.9, alpha 0.05). A decrease in QSM change would be a signal of potential benefit, and an increase would signal a safety concern with the drug.

DISCUSSION: With firm mechanistic rationale, rigorous preclinical discoveries, and biomarker validations, the trial shall explore a proof of concept effect of a widely used repurposed drug in stabilizing CAs after a symptomatic hemorrhage. This will be the first clinical trial of a drug aimed at altering rebleeding in CA.

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