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Nardin Samuel and Ivan Radovanovic

OBJECTIVE

Despite the prevalence and impact of intracranial aneurysms (IAs), the molecular basis of their pathogenesis remains largely unknown. Moreover, there is a dearth of clinically validated biomarkers to efficiently screen patients with IAs and prognosticate risk for rupture. The aim of this study was to survey the literature to systematically identify the spectrum of genetic aberrations that have been identified in IA formation and risk of rupture.

METHODS

A literature search was performed using the Medical Subject Headings (MeSH) system of databases including PubMed, EMBASE, and Google Scholar. Relevant studies that reported on genetic analyses of IAs, rupture risk, and long-term outcomes were included in the qualitative analysis.

RESULTS

A total of 114 studies were reviewed and 65 were included in the qualitative synthesis. There are several well-established mendelian syndromes that confer risk to IAs, with variable frequency. Linkage analyses, genome-wide association studies, candidate gene studies, and exome sequencing identify several recurrent polymorphic variants at candidate loci, and genes associated with the risk of aneurysm formation and rupture, including ANRIL (CDKN2B-AS1, 9p21), ARGHEF17 (11q13), ELN (7q11), SERPINA3 (14q32), and SOX17 (8q11). In addition, polymorphisms in eNOS/NOS3 (7q36) may serve as predictive markers for outcomes following intracranial aneurysm rupture. Genetic aberrations identified to date converge on posited molecular mechanisms involved in vascular remodeling, with strong implications for an associated immune-mediated inflammatory response.

CONCLUSIONS

Comprehensive studies of IA formation and rupture have identified candidate risk variants and loci; however, further genome-wide analyses are needed to identify high-confidence genetic aberrations. The literature supports a role for several risk loci in aneurysm formation and rupture with putative candidate genes. A thorough understanding of the genetic basis governing risk of IA development and the resultant aneurysmal subarachnoid hemorrhage may aid in screening, clinical management, and risk stratification of these patients, and it may also enable identification of putative mechanisms for future drug development.

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Eveline M. Gutzwiller, Ivan Cabrilo, Ivan Radovanovic, Karl Schaller, and Colette Boëx

OBJECTIVE

The goal of this study was to determine the performance of intraoperative visual evoked potentials (VEPs) in detecting visual field changes.

METHODS

Assessments of VEPs were performed with simultaneous retinal responses by using white light-emitting diodes protected from scialytic microscope lights. The alarm criterion was a reproducible decrease in amplitude of the VEP P100 wave of 20% or more. Visual fields were assessed preoperatively and 1 month postsurgery (Goldmann perimetry).

RESULTS

The VEPs were analyzed for 29 patients undergoing resection of a brain lesion. In 89.7% of patients, steady VEP and retinal responses were obtained for monitoring. The absence of alarm was associated in 94.4% of cases with the absence of postoperative visual changes (specificity). The alarms correctly identified 66.7% of cases with any postoperative changes and 100% of cases with changes more severe than just a discrete quadrantanopia or deterioration of an existing quadrantanopia (sensitivity, new diffuse deterioration < 2 dB). In 11.5% of patients, a transitory VEP decrease with subsequent recovery was observed without postoperative defects.

CONCLUSIONS

Intraoperative VEPs were performed with simultaneous recording of electroretinograms, with protection from lights of the operating room and with white light-emitting diodes. Intraoperative VEPs were shown to be reliable in predicting postoperative visual field changes. In this series of intraaxial brain procedures, reliable intraoperative VEP monitoring was achieved, allowing at minimum the detection of new quadrantanopia. The standardization of this technique appears to be a valuable effort in regard to the functional risks of homonymous hemianopia.

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Eveline M. Gutzwiller, Ivan Cabrilo, Ivan Radovanovic, Karl Schaller, and Colette Boëx

OBJECTIVE

The goal of this study was to determine the performance of intraoperative visual evoked potentials (VEPs) in detecting visual field changes.

METHODS

Assessments of VEPs were performed with simultaneous retinal responses by using white light-emitting diodes protected from scialytic microscope lights. The alarm criterion was a reproducible decrease in amplitude of the VEP P100 wave of 20% or more. Visual fields were assessed preoperatively and 1 month postsurgery (Goldmann perimetry).

RESULTS

The VEPs were analyzed for 29 patients undergoing resection of a brain lesion. In 89.7% of patients, steady VEP and retinal responses were obtained for monitoring. The absence of alarm was associated in 94.4% of cases with the absence of postoperative visual changes (specificity). The alarms correctly identified 66.7% of cases with any postoperative changes and 100% of cases with changes more severe than just a discrete quadrantanopia or deterioration of an existing quadrantanopia (sensitivity, new diffuse deterioration < 2 dB). In 11.5% of patients, a transitory VEP decrease with subsequent recovery was observed without postoperative defects.

CONCLUSIONS

Intraoperative VEPs were performed with simultaneous recording of electroretinograms, with protection from lights of the operating room and with white light-emitting diodes. Intraoperative VEPs were shown to be reliable in predicting postoperative visual field changes. In this series of intraaxial brain procedures, reliable intraoperative VEP monitoring was achieved, allowing at minimum the detection of new quadrantanopia. The standardization of this technique appears to be a valuable effort in regard to the functional risks of homonymous hemianopia.

Open access

Armaan K. Malhotra, Jerry C. Ku, Vitor M. Pereira, and Ivan Radovanovic

BACKGROUND

Angiogram-negative nontraumatic subarachnoid hemorrhage (SAH) can be diagnostically challenging, and a broad differential diagnosis must be considered. Particular attention to initial radiographic hemorrhage distribution is essential to guide adjunctive investigations. Posterior spinal artery aneurysms are rare clinical entities with few reported cases in the literature. An understanding of isolated spinal artery aneurysm natural history, diagnosis, and management is evolving as more cases are identified.

OBSERVATIONS

Isolated thoracic posterior spinal artery aneurysm can be the culprit lesion in perimesencephalic distribution SAH. Embolization resulted in complete aneurysm occlusion and did not result in periprocedural morbidity. At the 1-year follow-up, the patient was neurologically intact with no recurrence on magnetic resonance angiography.

LESSONS

This case report highlighted the presentation, diagnostic workup, clinical decision-making, and endovascular intervention for a woman who presented with SAH secondary to posterior spinal artery aneurysm. After initially negative results on vascular imaging, dedicated spinal vascular imaging revealed the location of the aneurysm. Multiple treatment modalities exist for isolated spinal artery aneurysms and must be selected on the basis of patient- and lesion-specific characteristics.

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Ann Mansur, Alex Kostynskyy, Timo Krings, Ronit Agid, Ivan Radovanovic, and Vitor Mendes Pereira

OBJECTIVE

The aim of this study was to 1) compare the safety and efficacy of acute targeted embolization of angiographic weak points in ruptured brain arteriovenous malformations (bAVMs) versus delayed treatment, and 2) explore the angioarchitectural changes that follow this intervention.

METHODS

The authors conducted a retrospective analysis of a prospectively acquired database of ruptured bAVMs. Three hundred sixteen patients with ruptured bAVMs who presented to the hospital within 48 hours of ictus were included in the analysis. The first analysis compared clinical and functional outcomes of acutely embolized patients to those with delayed management paradigms. The second analysis compared these outcomes of patients with acute embolization to those with angiographic targets who did not undergo acute embolization. Finally, a subset of 20 patients with immediate postembolization angiograms and follow-up angiograms within 6 weeks of treatment were studied to determine the angioarchitectural changes after acute targeted embolization. Kaplan-Meier curves for survival between the groups were devised. Multivariate logistical regression analysis was conducted.

RESULTS

There were three deaths (0.9%) and an overall rerupture rate of 4.8% per year. There was no statistical difference in demographic variables, mortality, and rerupture rate between patients with acute embolization and those with delayed management. Patients with acute embolization were more likely to present functionally worse (46.9% vs 69.8%, modified Rankin Scale score 0–2, p = 0.018) and to require an adjuvant therapy (71.9% vs 26.4%, p < 0.001). When comparing acutely embolized patients to those nonacutely embolized angiographic targets, there was a significant protective effect of acute targeted therapy on rerupture rate (annual risk 1.2% vs 4.3%, p = 0.025) and no difference in treatment complications. Differences in the survival curves for rerupture were statistically significant. Multivariate analyses significantly predicted lower rerupture in acute targeted treatment and higher rerupture in those with associated aneurysms, deep venous anatomy, and higher Spetzler-Martin grade. All patients with acute embolization experienced complete obliteration of the angiographic weak point with various degrees of resolution of the nidus; however, some had spontaneous recurrence of their bAVM, while others had spontaneous resolution over time. No patients developed new angiographic weak points.

CONCLUSIONS

This study demonstrates that acute targeted embolization of angiographic weak points, particularly aneurysms, is technically safe and protective in the early phase of recovery from ruptured bAVMs. Serial follow-up imaging is necessary to monitor the evolution of the nidus after targeted and definitive treatments. Larger prospective studies are needed to validate these findings.

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Kathleen Joy Khu, Francesco Doglietto, Ivan Radovanovic, Faisal Taleb, Daniel Mendelsohn, Gelareh Zadeh, and Mark Bernstein

Object

Routine and nonselective use of awake and outpatient craniotomy for supratentorial tumors has been shown to be safe and effective from a medical standpoint. In this study the authors aim was to explore patients' perceptions about awake and outpatient craniotomy.

Methods

Qualitative research methodology was used. Two semistructured, open-ended interviews were conducted with 27 participants, who were ambulatory adult patients who underwent craniotomy for brain tumor excision between October 2008 and April 2009. The participants were each assigned to one of the following categories: 1) awake outpatient; 2) awake inpatient; 3) outpatient under general anesthesia; and 4) inpatient under general anesthesia. Interviews were audiotaped and transcribed, and the data were subjected to thematic analysis.

Results

The following 6 overarching themes emerged from the data: 1) patients had a positive experience with awake craniotomy; 2) patient satisfaction with outpatient surgery was high; 3) patients understood the rationale behind awake surgery; 4) patients were surprised that brain surgery can be done on an outpatient basis; 5) trust in one's surgeon was important; and 6) patients were more concerned about the disease than the procedure.

Conclusions

The results reflected positively on the patients' awake and outpatient surgery experience, but there were some areas that require improvement, specifically perioperative pain control and postoperative care. These insights on patients' perspectives can lead to better delivery of care, and ultimately, improved health outcomes.

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Hengwei Jin, Stephanie Lenck, Timo Krings, Ronit Agid, Yibin Fang, Youxiang Li, Alex Kostynskyy, Michael Tymianski, Vitor Mendes Pereira, and Ivan Radovanovic

OBJECTIVE

The goal of this study was to describe changes in the angioarchitecture of brain arteriovenous malformations (bAVMs) between acute and delayed cerebral digital subtraction angiography (DSA) obtained after hemorrhage, and to examine bAVM characteristics predicting change.

METHODS

This is a retrospective study of a prospective institutional bAVM database. The authors included all patients with ruptured bAVMs who had DSA in both acute and delayed phases, with no interval treatment of their bAVM, between January 2000 and April 2017. The authors evaluated the existence or absence of angioarchitectural changes. Demographic data, radiological characteristics of hemorrhages, and angioarchitectural features of the bAVMs of the two patients’ groups were analyzed. Univariate and multivariate logistic analyses were performed to identify predictors of angioarchitectural change.

RESULTS

A total of 42 patients were included in the series. Seventeen (40.5%) patients had angioarchitectural changes including bAVM only visible on the delayed DSA study (n = 8), spontaneous thrombosis of the AVM (n = 3), or alteration of the size or the opacification of the nidus (n = 6). The factors associated with angioarchitectural changes were a small nidus (3.8 ± 7.9 ml vs 6.1 ± 9.5 ml, p = 0.046), a superficial location (94.1% vs 5.9%, p = 0.016), and a single superficial draining vein (58.8% vs 24.0%, p = 0.029).

CONCLUSIONS

Angioarchitectural changes can be seen in 40% of ruptured bAVMs between the acute- and delayed-phase DSA. A small nidus, a superficial location, and a single superficial draining vein were statistically associated with the occurrence of angioarchitectural changes. These changes included either enlargement or spontaneous occlusion of the bAVM, as well as subsequent diagnosis of a bAVM following an initial negative DSA study.

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Hugo Andrade-Barazarte, Krunal Patel, Mazda K. Turel, Francesco Doglietto, Anne Agur, Fred Gentili, Rachel Tymianski, Vitor Mendes Pereira, Michael Tymianski, and Ivan Radovanovic

OBJECTIVE

The evolution of microsurgical and endoscopic techniques has allowed the development of less invasive transcranial approaches. The authors describe a purely endoscopic transpterional port craniotomy to access lesions involving the cavernous sinus and the anterolateral skull base.

METHODS

Through single- or dual-port incisions and with direct endoscopic visualization, the authors performed an endoscopic transpterional port approach (ETPA) using a 4-mm straight endoscope in 8 sides of 4 formalin-fixed cadaveric heads injected with colored latex. A main working port incision is made just below the superior temporal line and behind the hairline. An optional 0.5- to 1-cm second skin port incision is made on the lateral supraorbital region, allowing multiangle endoscopic visualization and maneuverability. A 1.5- to 2-cm craniotomy centered over the pterion is done through the main port, which allows an extradural exposure of the cavernous sinus region and extra/intradural exposure of the frontal and temporal cranial fossae. The authors present a pilot surgical series of 17 ETPA procedures and analyze the surgical indications and clinical outcomes retrospectively.

RESULTS

The initial stage of this work on cadavers provided familiarity with the technique, standardized its steps, and showed its anatomical limits. The clinical ETPA was applied to gain access into the cavernous sinus, as well as for aneurysm clipping and meningioma resection. Overall, perioperative complications occurred in 1 patient (6%), there was no mortality, and at last follow-up all patients had a modified Rankin Scale score of 0 or 1.

CONCLUSIONS

The ETPA provides a less invasive, focused, and direct route to the cavernous sinus, and to the frontal and temporal cranial fossae, and it is feasible in clinical practice for selected indications with good results.

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Benoit Jenny, Ivan Radovanovic, Charles-Antoine Haenggeli, Jacqueline Delavelle, Daniel Rüfenacht, André Kaelin, Jean-Louis Blouin, Armand Bottani, and Bénédict Rilliet

✓The PTEN hamartoma tumor syndrome, manifestations of which include Cowden disease and Bannayan-Riley-Ruvalcaba syndrome, is caused by various mutations of the PTEN gene located at 10q23. Its major criteria are macrocephaly and a propensity to develop breast and thyroid cancers as well as endometrial carcinoma. Minor diagnostic criteria include hamartomatous intestinal polyps, lipomas, fibrocystic disease of the breasts, and fibromas. Mutations of PTEN can also be found in patients with Lhermitte–Duclos disease (dysplastic gangliocytoma of the cerebellum). The authors report the case of a 17-year-old girl who had a severe cyanotic cardiac malformation for which surgery was not advised and a heterozygous missense mutation (c.406T>C) in exon 5 of PTEN resulting in the substitution of cysteine for arginine (p.Cys136Arg) in the protein, which was also found in her mother and sister. The patient presented in the pediatric emergency department with severe spastic paraparesis. A magnetic resonance imaging study of the spine showed vertebral hemangiomas at multiple levels, but stenosis and compression were maximal at level T5–6. An emergency T5–6 laminectomy was performed. The decompression was extremely hemorrhagic because the rapid onset of paraparesis necessitated prompt treatment, and there was no time to perform preoperative embolization. The patient's postoperative course was uneventful with gradual recovery.

This represents the first report of an association of a PTEN mutation and multiple vertebral angiomas. The authors did not treat the remaining angiomas because surgical treatment was contraindicated without previous embolization, which in itself would present considerable risk in this patient with congenital cyanotic heart disease.

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Adam A. Dmytriw, Anish Kapadia, Alejandro Enriquez-Marulanda, Carmen Parra-Fariñas, Anna Luisa Kühn, Patrick J. Nicholson, Muhammad Waqas, Leonardo Renieri, Caterina Michelozzi, Paul M. Foreman, Kevin Phan, I-Hsiao Yang, Vincent M. Tutino, Christopher S. Ogilvy, Ivan Radovanovic, Mark R. Harrigan, Adnan H. Siddiqui, Elad I. Levy, Nicola Limbucci, Christophe Cognard, Timo Krings, Vitor Mendes Pereira, Ajith J. Thomas, Thomas R. Marotta, and Christoph J. Griessenauer

OBJECTIVE

Coverage of the anterior spinal artery (ASA) ostia is a source of considerable consternation regarding flow diversion (FD) in vertebral artery (VA) aneurysms due to cord supply. The authors sought to assess the association between coverage of the ASA, posterior spinal artery (PSA), or lateral spinal artery (LSA) ostia when placing flow diverters in distal VAs and clinical outcomes, with emphasis on cord infarction.

METHODS

A multicenter retrospective study of 7 institutions in which VA aneurysms were treated with FD between 2011 and 2019 was performed. The authors evaluated the risk of ASA and PSA/LSA occlusion, associated thromboembolic complication, complications overall, aneurysm occlusion status, and functional outcome.

RESULTS

Sixty patients with 63 VA and posterior inferior cerebellar artery aneurysms treated with FD were identified. The median aneurysm diameter was 7 mm and fusiform type was the commonest morphology (42.9%). During a procedure, 1 (61.7%) or 2 (33.3%) flow diverters were placed. Complete occlusion was achieved in 71.9%. Symptomatic thromboembolic complications occurred in 7.4% of cases and intracranial hemorrhage in 10.0% of cases. The ASA and PSA/LSA were identified in 51 (80.9%) and 35 (55.6%) complications and covered by the flow diverter in 29 (56.9%) and 13 (37.1%) of the procedures, respectively. Patency after flow diverter coverage on last follow-up was 89.2% for ASA and 100% for PSA/LSA, not significantly different between covered and noncovered groups (p = 0.5 and p > 0.99, respectively). No complications arose from coverage.

CONCLUSIONS

FD aneurysm treatment in the posterior circulation with coverage of ASA or PSA/LSA was not associated with higher rates of occlusion of these branches or any instances of cord infarction.