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Eric C. Peterson, Mohamed Samy Elhammady, Stacey Quintero-Wolfe, Timothy G. Murray and Mohammad Ali Aziz-Sultan

Object

Retinoblastoma is the most common ocular neoplasm in children. Left untreated it spreads to the brain via the optic nerve. Traditional therapy is enucleation, and while this procedure is still the most common treatment worldwide, modern eye-preserving therapies can often spare the globe. However, patients with retinoblastoma often present in advanced stages of the disease when these globe-preserving strategies are often insufficient to prevent enucleation. In these challenging cases, direct infusion of chemotherapy into the ophthalmic artery has been attempted to achieve tumor control. The authors' aim in this study was to report on their initial experience with and clinical results for this approach.

Methods

The authors prospectively collected data on all cases of retinoblastoma treated with selective intraophthalmic melphalan at Bascom Palmer Eye Institute. All cases were classified as International Intraocular Retinoblastoma Classification (IIRC) Group D or Reese-Ellsworth Group Vb, had not responded to aggressive multimodal therapy consisting of chemotherapy and focal consolidating laser therapy, and were pending enucleation. Using digital subtraction angiography, a microcatheter was navigated under roadmap guidance into the ophthalmic artery, and melphalan was infused over 40 minutes. Early in the series, patients were treated with 3 or 5 mg of melphalan, but after low response rates occurred all eyes were treated with 7.5 mg of melphalan. All patients were examined with funduscopy while under anesthesia 3 weeks after treatment and every 3 months thereafter. Patients with persistent disease were retreated with repeat infusions of melphalan.

Results

Twenty-six procedures were performed to treat 17 tumors in 15 patients. Successful cannulation of the ophthalmic artery was achieved in all cases. The follow-up ranged from 3 to 12 months, with a mean of 8.6 months. Overall, 76% of the tumors responded to therapy and these cases were spared enucleation. The average number of treatments was 1.5 per tumor. Of the responders, 54% responded to a single dose of melphalan. Treatment with the higher dose of 7.5 mg up front was associated with a lower enucleation rate (0% vs 36%) as compared with the lower starting dose. Delayed vitreous hemorrhage occurred after 4 (15%) of 26 treatments, and these cases were treated with enucleation.

Conclusions

In this challenging group of advanced retinoblastomas refractory to aggressive multimodal therapy, virtually 100% of eyes are generally enucleated. In contrast, the authors' protocol of infusing melphalan directly into the ophthalmic artery led to a dramatic decrease in the enucleation rate to 23.5%. While it is now the treatment of choice for refractory retinoblastoma at their center, its role in less advanced disease remains to be elucidated.

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Mohamed Samy Elhammady, Stacey Quintero Wolfe, Ramsey Ashour, Hamad Farhat, Roham Moftakhar, Baruch B. Lieber and Mohammad Ali Aziz-Sultan

Object

The authors assessed the safety and efficacy of embolization of head, neck, and spinal tumors with Onyx and determined the correlation between tumor embolization and intraoperative blood loss.

Methods

The authors prospectively collected all head, neck, and spinal tumors embolized with Onyx at their institution over a 28-month period. Information on tumor type, location, extent of tumor devascularization, endovascular and surgical complications, and intraoperative estimated blood loss (EBL) was evaluated.

Results

Forty-three patients with various head, neck, and spinal lesions underwent vascular tumor embolization with Onyx. Indications for embolization included uncontrolled tumor bleeding in 8 cases, elective preoperative devascularization in 34, and tumor-induced consumptive thrombocytopenia in 1 case. Embolization was performed via direct tumoral puncture in 14 cases and through the traditional transarterial route in the remaining lesions. Embolization was successful in ending uncontrolled tumor bleeding in all 8 cases and in reversing the consumptive coagulopathy in 1 case. Intraparenchymal penetration of embolic material was possible in all percutaneously embolized tumors and in 4 of the 20 tumors embolized preoperatively via the transarterial route. The mean percentage of devascularization in tumors with intraparenchymal penetration of Onyx was 90.3% compared with 83.7% in tumors without intraparenchymal penetration. The mean EBL with intraparenchymal penetration of Onyx was significantly lower than when there was no intraparenchymal penetration (459 vs 2698 ml; p = 0.0067). There were no neurological complications related to the embolization procedures.

Conclusions

Embolization of vascular tumors with Onyx can be performed safely but may not reach optimal effectiveness in reducing intraoperative EBL if the embolic material does not penetrate the tumor vasculature. In the authors' experience, the best method of intraparenchymal penetration is achieved with direct tumor puncture. Transarterial embolization may not result in tumor penetration, particularly when injected from a long distance through small caliber or slow flow vessels.

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Stacey Quintero Wolfe, Nils Mueller-Kronast, Mohammad Ali Aziz-Sultan, Alois Zauner and Sanjiv Bhatia

✓Extracranial carotid artery (CA) aneurysms are rare in the pediatric population and are usually the result of connective tissue disorders, traumatic dissection, or infection. The authors present the case of a large calcified internal carotid artery pseudoaneurysm of obscure origins presenting with embolic stroke in a child. Aneurysm excision and CA reconstruction would have been extremely difficult due to the distal location of the lesion, and CA ligation was contraindicated due to a failed balloon test occlusion. Therefore, after anticoagulation therapy, the patient was treated endovascularly with a covered stent and complete exclusion of the aneurysm from the circulation. The patient recovered all neurological function and has remained in excellent condition. A follow-up angiogram performed at 6 months showed no recurrence or stenosis.

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Brandon G. Gaynor, Mohamed Samy Elhammady, Daniel Jethanamest, Simon I. Angeli and Mohammad A. Aziz-Sultan

Object

The resection of glomus jugulare tumors can be challenging because of their inherent vascularity. Preoperative embolization has been advocated as a means of reducing operative times, blood loss, and surgical complications. However, the incidence of cranial neuropathy associated with the embolization of these tumors has not been established. The authors of this study describe their experience with cranial neuropathy following transarterial embolization of glomus jugulare tumors using ethylene vinyl alcohol (Onyx, eV3 Inc.).

Methods

The authors retrospectively reviewed all cases of glomus jugulare tumors that had been treated with preoperative embolization using Onyx at their institution in the period from 2006 to 2012. Patient demographics, clinical presentation, grade and amount of Onyx used, degree of angiographic devascularization, and procedural complications were recorded.

Results

Over a 6-year period, 11 patients with glomus jugulare tumors underwent preoperative embolization with Onyx. All embolization procedures were completed in one session. The overall mean percent of tumor devascularization was 90.7%. No evidence of nontarget embolization was seen on postembolization angiograms. There were 2 cases (18%) of permanent cranial neuropathy attributed to the embolization procedures (facial nerve paralysis and lower cranial nerve dysfunction).

Conclusions

Embolizing glomus jugulare tumors with Onyx can produce a dramatic reduction in tumor vascularity. However, the intimate anatomical relationship and overlapping blood supply between these tumors and cranial nerves may contribute to a high incidence of cranial neuropathy following Onyx embolization.

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Mohamed Samy Elhammady, Stacey Quintero Wolfe, Hamad Farhat, Roham Moftakhar and Mohammad Ali Aziz-Sultan

Object

The authors conducted a study to determine the safety and efficacy of embolization of carotid-cavernous fistulas (CCFs) with the ethylene vinyl alcohol copolymer, Onyx.

Methods

They prospectively collected data in all patients with CCFs who underwent Onyx-based embolization at their institution over a 3-year period. The type of fistula, route of embolization, viscosity of Onyx, additional use of coils, extent of embolization, procedural complications, and clinical follow-up were recorded.

Results

A total of 12 patients (5 men and 7 women who were age 24–88 years) underwent embolization in which Onyx was used. There were 1 Barrow Type A, 1 Type B, 3 Type C, and 7 Type D fistulas. Embolization was performed via a transvenous route in 8 cases and a transarterial route in 4 cases. Onyx 34 was used in all but 2 cases: a direct Type A fistula embolized with Onyx 500 and an indirect Type C fistula embolized with Onyx 18. Adjuvant embolization with framing coils was performed in 7 cases. All procedures were completed in a single session. Immediate fistula obliteration was achieved in all cases. Clinical resolution of presenting symptoms occurred in 100% of the patients by 2 months. Neurological complications occurred in 3 patients. One patient developed a complete cranial nerve (CN) VII palsy that has not resolved. Two patients developed transient neuropathies—1 a Horner syndrome and partial CN VI palsy, and 1 a complete CN III and partial CN V palsy. Radiographic follow-up (mean 16 months, range 4–35 months) was available in 6 patients with complete resolution of the lesion in all.

Conclusions

Onyx is a liquid embolic agent that is effective in the treatment of CCFs but not without hazards. Postembolization cavernous sinus thrombosis and swelling may result in transient compressive cranial neuropathies. The inherent gradual polymerization properties of Onyx allow for casting of the cavernous sinus but may potentially result in deep penetration within arterial collaterals that can cause CN ischemia/infarction. Although not proven, the angiotoxic effects of dimethyl sulfoxide may also play a role in postembolization CN deficits.

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Mohamed Samy Elhammady, Hamad Farhat, Mohammad Ali Aziz-Sultan and Jacques J. Morcos

Juxtafacet cysts of the atlantooccipital joint that present with isolated hypoglossal nerve palsy are rare and may mimic more common pathological entities. The authors report on the third such case in the literature and discuss the differential diagnosis, imaging hallmarks, preoperative recognition, and surgical management of this lesion, and provide a review of the literature.

The authors discuss their experience with the treatment of a 67-year-old woman who presented with an isolated hypoglossal nerve palsy caused by a nonenhancing cystic septated lesion abutting the lateral medulla just medial to the left hypoglossal canal. The lesion was presumed to be a necrotic hypoglossal schwannoma or epidermoid tumor. Intradural surgical exploration failed to demonstrate an intradural lesion, but confirmed the presence of an extradural mass caudal to the hypoglossal nerve. Extradural exploration revealed a synovial cyst of the atlantooccipital joint, which was then resected. Postoperatively, the patient developed worsening dysphagia and hoarseness. Failure to recognize this rare entity preoperatively resulted in unnecessary intradural exploration and cranial nerve morbidity. In retrospect, the preoperative diagnosis of this lesion was suggested by lack of central enhancement, absence of dumbbell formation and the presence of erosive synovial changes. Regardless, the extreme rarity of this lesion at this location will always make its recognition challenging.

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Hormuzdiyar H. Dasenbrock, Robert F. Rudy, Pui Man Rosalind Lai, Timothy R. Smith, Kai U. Frerichs, William B. Gormley, M. Ali Aziz-Sultan and Rose Du

OBJECTIVE

Although cigarette smoking is one of the strongest risk factors for cerebral aneurysm development and rupture, there are limited data evaluating the impact of smoking on outcomes after aneurysmal subarachnoid hemorrhage (SAH). Additionally, two recent studies suggested that nicotine replacement therapy was associated with improved neurological outcomes among smokers who had sustained an SAH compared with smokers who did not receive nicotine.

METHODS

Patients who underwent endovascular or microsurgical repair of a ruptured cerebral aneurysm were extracted from the Nationwide Inpatient Sample (NIS, 2009–2011) and stratified by cigarette smoking. Multivariable logistic regression analyzed in-hospital mortality, complications, tracheostomy or gastrostomy placement, and discharge to institutional care (a nursing or an extended care facility). Additionally, the composite NIS-SAH outcome measure (based on mortality, tracheostomy or gastrostomy, and discharge disposition) was evaluated, which has been shown to have excellent agreement with a modified Rankin Scale score greater than 3. Covariates included in regression constructs were patient age, sex, race/ethnicity, insurance status, socioeconomic status, comorbidities (including hypertension, drug and alcohol abuse), the NIS-SAH severity scale (previously validated against the Hunt and Hess grade), treatment modality used for aneurysm repair, and hospital characteristics. A sensitivity analysis was performed matching smokers to nonsmokers on age, sex, number of comorbidities, and NIS-SAH severity scale score.

RESULTS

Among the 5784 admissions evaluated, 37.1% (n = 2148) had a diagnosis of tobacco use, of which 31.1% (n = 1800) were current and 6.0% (n = 348) prior tobacco users. Smokers were significantly younger (mean age 51.4 vs 56.2 years) and had more comorbidities compared with nonsmokers (p < 0.001). There were no significant differences in mortality, total complications, or neurological complications by smoking status. However, compared with nonsmokers, smokers had significantly decreased adjusted odds of tracheostomy or gastrostomy placement (11.9% vs 22.7%, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51–0.78, p < 0.001), discharge to institutional care (OR 0.71, 95% CI 0.57–0.89, p = 0.002), and a poor outcome (OR 0.65, 95% CI 0.55–0.77, p < 0.001). Similar statistical associations were noted in the matched-pairs sensitivity analysis and in a subgroup of poor-grade patients (the upper quartile of the NIS-SAH severity scale).

CONCLUSIONS

In this nationwide study, smokers experienced SAH at a younger age and had a greater number of comorbidities compared with nonsmokers, highlighting the negative ramifications of cigarette smoking among patients with cerebral aneurysms. However, smoking was also associated with paradoxical superior outcomes on some measures, and future research to confirm and further understand the basis of this relationship is needed.

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Hormuzdiyar H. Dasenbrock, Timothy R. Smith, Robert F. Rudy, William B. Gormley, M. Ali Aziz-Sultan and Rose Du

OBJECTIVE

Although reoperation and readmission have been used as quality metrics, there are limited data evaluating the rate of, reasons for, and predictors of reoperation and readmission after microsurgical clipping of unruptured aneurysms.

METHODS

Adult patients who underwent craniotomy for clipping of an unruptured aneurysm electively were extracted from the prospective National Surgical Quality Improvement Program registry (2011–2014). Multivariable logistic regression and recursive partitioning analysis evaluated the independent predictors of nonroutine hospital discharge, unplanned 30-day reoperation, and readmission. Predictors screened included patient age, sex, comorbidities, American Society of Anesthesiologists (ASA) classification, functional status, aneurysm location, preoperative laboratory values, operative time, and postoperative complications.

RESULTS

Among the 460 patients evaluated, 4.2% underwent any reoperation at a median of 7 days (interquartile range [IQR] 2–17 days) postoperatively, and 1.1% required a cranial reoperation. The most common reoperation was ventricular shunt placement (23.5%); other reoperations were tracheostomy, craniotomy for hematoma evacuation, and decompressive hemicraniectomy. Independent predictors of any unplanned reoperation were age greater than 51 years and longer operative time (p ≤ 0.04). Readmission occurred in 6.3% of patients at a median of 6 days (IQR 5–13 days) after discharge from the surgical hospitalization; 59.1% of patients were readmitted within 1 week and 86.4% within 2 weeks of discharge. The most common reason for readmission was seizure (26.7%); other causes of readmission included hydrocephalus, cerebrovascular accidents, and headache. Unplanned readmission was independently associated with age greater than 65 years, Class II or III obesity (body mass index > 35 kg/m2), preoperative hyponatremia, and preoperative anemia (p ≤ 0.04). Readmission was not associated with operative time, complications during the surgical hospitalization, length of stay, or discharge disposition. Recursive partitioning analysis identified the same 4 variables, as well as ASA classification, as associated with unplanned readmission. The most potent predictors of nonroutine hospital discharge (16.7%) were postoperative neurological and cardiopulmonary complications; other predictors were age greater than 51 years, preoperative hyponatremia, African American and Asian race, and a complex vertebrobasilar circulation aneurysm.

CONCLUSIONS

In this national analysis, patient age greater than 65 years, Class II or III obesity, preoperative hyponatremia, and anemia were associated with adverse events, highlighting patients who may be at risk for complications after clipping of unruptured cerebral aneurysms. The preponderance of early readmissions highlights the importance of early surveillance and follow-up after discharge; the frequency of readmission for seizure emphasizes the need for additional data evaluating the utility and duration of postcraniotomy seizure prophylaxis. Moreover, readmission was primarily associated with preoperative characteristics rather than metrics of perioperative care, suggesting that readmission may be a suboptimal indicator of the quality of care received during the surgical hospitalization in this patient population.

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Hormuzdiyar H. Dasenbrock, Robert F. Rudy, Timothy R. Smith, William B. Gormley, Nirav J. Patel, Kai U. Frerichs, M. Ali Aziz-Sultan and Rose Du

OBJECTIVE

The complex decision analysis of unruptured intracranial aneurysms entails weighing the benefits of aneurysm repair against operative risk. The goal of the present analysis was to build and validate a predictive scale that identifies patients with the greatest odds of a postsurgical adverse event.

METHODS

Data on patients who underwent surgical clipping of an unruptured aneurysm were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP; 2007–2014); NSQIP does not systematically collect data on patients undergoing intracranial endovascular intervention. Multivariable logistic regression evaluated predictors of any 30-day adverse event; variables screened included patient demographics, comorbidities, functional status, preoperative laboratory values, aneurysm location/complexity, and operative time. A predictive scale was constructed based on statistically significant independent predictors, which was validated using both NSQIP (2015–2016) and the Nationwide Inpatient Sample (NIS; 2002–2011).

RESULTS

The NSQIP unruptured aneurysm scale was proposed: 1 point was assigned for a bleeding disorder; 2 points for age 51–60 years, cardiac disease, diabetes mellitus, morbid obesity, anemia (hematocrit < 36%), operative time 240–330 minutes; 3 points for leukocytosis (white blood cell count > 12,000/μL) and operative time > 330 minutes; and 4 points for age > 60 years. An increased score was predictive of postoperative stroke or coma (NSQIP: p = 0.002, C-statistic = 0.70; NIS: p < 0.001, C-statistic = 0.61), a medical complication (NSQIP: p = 0.01, C-statistic = 0.71; NIS: p < 0.001, C-statistic = 0.64), and a nonroutine discharge (NSQIP: p < 0.001, C-statistic = 0.75; NIS: p < 0.001, C-statistic = 0.66) in both validation populations. Greater score was also predictive of increased odds of any adverse event, a major complication, and an extended hospitalization in both validation populations (p ≤ 0.03).

CONCLUSIONS

The NSQIP unruptured aneurysm scale may augment the risk stratification of patients undergoing microsurgical clipping of unruptured cerebral aneurysms.

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Hormuzdiyar H. Dasenbrock, Michael O. Nguyen, Kai U. Frerichs, Donovan Guttieres, William B. Gormley, M. Ali Aziz-Sultan and Rose Du

OBJECTIVE

Although the prevalence of obesity is increasing rapidly both nationally and internationally, few studies have analyzed outcomes among obese patients undergoing cranial neurosurgery. The goal of this study, which used a nationwide data set, was to evaluate the association of both obesity and morbid obesity with treatment outcomes among patients with aneurysmal subarachnoid hemorrhage (SAH); in addition, the authors sought to analyze how postoperative complications for obese patients with SAH differ by the treatment modality used for aneurysm repair.

METHODS

Clinical data for adult patients with SAH who underwent microsurgical or endovascular aneurysm repair were extracted from the Nationwide Inpatient Sample (NIS). The body habitus of patients was classified as nonobese (body mass index [BMI] < 30 kg/m2), obese (BMI ≥ 30 kg/m2 and ≤ 40 kg/m2), or morbidly obese (BMI > 40 kg/m2). Multivariable logistic regression analyzed the association of body habitus with in-hospital mortality rate, complications, discharge disposition, and poor outcome as defined by the composite NIS-SAH outcome measure. Covariates included patient demographics, comorbidities (including hypertension and diabetes), health insurance status, the NIS-SAH severity scale, treatment modality used for aneurysm repair, and hospital characteristics.

RESULTS

In total, data from 18,281 patients were included in this study; the prevalence of morbid obesity increased from 0.8% in 2002 to 3.5% in 2011. Obese and morbidly obese patients were significantly younger and had a greater number of comorbidities than nonobese patients (p < 0.001). Mortality rates for obese (11.5%) and morbidly obese patients (10.5%) did not significantly differ from those for nonobese patients (13.5%); likewise, no differences in neurological complications or poor outcome were observed among these 3 groups. Morbid obesity was associated with significantly increased odds of several medical complications, including venous thromboembolic (OR 1.52, 95% CI 1.01–2.30, p = 0.046) and renal (OR 1.64, 95% CI: 1.11–2.43, p = 0.01) complications and infections (OR 1.34, 95% CI 1.08–1.67, p = 0.009, attributable to greater odds of urinary tract and surgical site infections). Moreover, morbidly obese patients had higher odds of a nonroutine hospital discharge (OR 1.33, 95% CI 1.03–1.71, p = 0.03). Patients with milder obesity had decreased odds of some medical complications, including cardiac, pulmonary, and infectious complications, primarily among patients who had undergone coil embolization.

CONCLUSIONS

In this study involving a nationwide administrative database, milder obesity was not significantly associated with increased mortality rates, neurological complications, or poor outcomes after SAH. Morbid obesity, however, was associated with increased odds of venous thromboembolic, renal, and infectious complications, as well as of a nonroutine hospital discharge. Notably, milder obesity was associated with decreased odds of some medical complications, primarily in patients treated with coiling.