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Robert T. Wicks, Xiaochun Zhao, Douglas A. Hardesty, Brandon D. Liebelt and Peter Nakaji

Ethmoidal dural arteriovenous fistulas (DAVFs) have a near-universal association with cortical venous drainage and a malignant clinical course. Endovascular treatment options are often limited due to the high frequency of ophthalmic artery ethmoidal supply. A 64-year-old gentleman presented with syncope and was found to have a right ethmoidal DAVF. Rather than the traditional bicoronal craniotomy, an endoscope-assisted mini-pterional approach for clip ligation is demonstrated. The mini-pterional craniotomy allows a minimally invasive approach to ethmoidal DAVF via a lateral trajectory. The endoscope can help achieve full visualization in the narrow corridor.

The video can be found here: https://youtu.be/ZroXp-T35DI.

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Robert F. Spetzler, Felipe C. Albuquerque, Joseph M. Zabramski and Peter Nakaji

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Robert F. Spetzler, Cameron G. McDougall, Joseph M. Zabramski, Felipe C. Albuquerque, Nancy K. Hills, Peter Nakaji, John P. Karis and Robert C. Wallace

OBJECTIVE

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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Robert Lynagh, Mark Ishak, Joseph Georges, Danielle Lopez, Hany Osman, Michael Kakareka, Brandon Boyer, H. Warren Goldman, Jennifer Eschbacher, Mark C. Preul, Peter Nakaji, Alan Turtz, Steven Yocom and Denah Appelt

OBJECTIVE

Accurate histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining suspicious tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in some cases. Failure to obtain diagnostic tissue can delay initiation of treatment and may result in further invasive procedures for patients. In this study, the authors sought to determine if the coupling of in vivo optical imaging with an STB system is an effective method for identification of diagnostic tissue at the time of biopsy.

METHODS

A minimally invasive fiber optic imaging system was developed by coupling a 0.65-mm-diameter coherent fiber optic fluorescence microendoscope to an STB system. Human U251 glioma cells were transduced for stable expression of blue fluorescent protein (BFP) to produce U251-BFP cells that were utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by fluorescein sodium (FNa) was quantified with fluorescence microscopy. In vivo, transgenic athymic rats implanted with U251-BFP cells (n = 4) were utilized for experiments. Five weeks postimplantation, the rats received 5–10 mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65-mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest ipsilateral and contralateral to tumor implantation were obtained and quantified.

RESULTS

Live-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2 = 0.91, p < 0.001). Normalized to background, in vivo FNa-mediated fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (301.7 ± 34.18 relative fluorescence units, p < 0.001). Fluorescence intensity measured from the tumor margin was not significantly greater than that from normal brain (p = 0.89). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor.

CONCLUSIONS

The authors found that in vivo fluorescence imaging with an STB needle containing a submillimeter-diameter fiber optic fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. These results were confirmed in vivo with positive control cells and by post hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies.

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David G. Brachman, Emad Youssef, Christopher J. Dardis, Nader Sanai, Joseph M. Zabramski, Kris A. Smith, Andrew S. Little, Andrew G. Shetter, Theresa Thomas, Heyoung L. McBride, Stephen Sorensen, Robert F. Spetzler and Peter Nakaji

OBJECTIVE

Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas.

METHODS

Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression.

RESULTS

Nineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9–92.0 cm3). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically.

CONCLUSIONS

R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

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Seungwon Yoon, Michael A. Mooney, Michael A. Bohl, John P. Sheehy, Peter Nakaji, Andrew S. Little and Michael T. Lawton

OBJECTIVE

With drastic changes to the health insurance market, patient cost sharing has significantly increased in recent years. However, the patient financial burden, or out-of-pocket (OOP) costs, for surgical procedures is poorly understood. The goal of this study was to analyze patient OOP spending in cranial neurosurgery and identify drivers of OOP spending growth.

METHODS

For 6569 consecutive patients who underwent cranial neurosurgery from 2013 to 2016 at the authors’ institution, the authors created univariate and multivariate mixed-effects models to investigate the effect of patient demographic and clinical factors on patient OOP spending. The authors examined OOP payments stratified into 10 subsets of case categories and created a generalized linear model to study the growth of OOP spending over time.

RESULTS

In the multivariate model, case categories (craniotomy for pain, tumor, and vascular lesions), commercial insurance, and out-of-network plans were significant predictors of higher OOP payments for patients (all p < 0.05). Patient spending varied substantially across procedure types, with patients undergoing craniotomy for pain ($1151 ± $209) having the highest mean OOP payments. On average, commercially insured patients spent nearly twice as much in OOP payments as the overall population. From 2013 to 2016, the mean patient OOP spending increased 17%, from $598 to $698 per patient encounter. Commercially insured patients experienced more significant growth in OOP spending, with a cumulative rate of growth of 42% ($991 in 2013 to $1403 in 2016).

CONCLUSIONS

Even after controlling for inflation, case-mix differences, and partial fiscal periods, OOP spending for cranial neurosurgery patients significantly increased from 2013 to 2016. The mean OOP spending for commercially insured neurosurgical patients exceeded $1400 in 2016, with an average annual growth rate of 13%. As patient cost sharing in health insurance plans becomes more prevalent, patients and providers must consider the potential financial burden for patients receiving specialized neurosurgical care.

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Evgenii Belykh, Kaan Yağmurlu, Ting Lei, Sam Safavi-Abbasi, Mark E. Oppenlander, Nikolay L. Martirosyan, Vadim A. Byvaltsev, Robert F. Spetzler, Peter Nakaji and Mark C. Preul

OBJECTIVE

The best approach to deep-seated lateral and third ventricle lesions is a function of lesion characteristics, location, and relationship to the ventricles. The authors sought to examine and compare angles of attack and surgical freedom of anterior ipsilateral and contralateral interhemispheric transcallosal approaches to the frontal horn of the lateral ventricle using human cadaveric head dissections. Illustrative clinical experiences with a contralateral interhemispheric transcallosal approach and an anterior interhemispheric transcallosal transchoroidal approach are also related.

METHODS

Five formalin-fixed human cadaveric heads (10 sides) were examined microsurgically. CT and MRI scans obtained before dissection were uploaded and fused into the navigation system. The authors performed contralateral and ipsilateral transcallosal approaches to the lateral ventricle. Using the navigation system, they measured areas of exposure, surgical freedom, angles of attack, and angle of view to the surgical surface. Two clinical cases are described.

RESULTS

The exposed areas of the ipsilateral (mean [± SD] 313.8 ± 85.0 mm2) and contralateral (344 ± 87.73 mm2) interhemispheric approaches were not significantly different (p = 0.12). Surgical freedom and vertical angles of attack were significantly larger for the contralateral approach to the most midsuperior reachable point (p = 0.02 and p = 0.01, respectively) and to the posterosuperior (p = 0.02 and p = 0.04) and central (p = 0.04 and p = 0.02) regions of the lateral wall of the lateral ventricle. Surgical freedom and vertical angles of attack to central and anterior points on the floor of the lateral ventricle did not differ significantly with approach. The angle to the surface of the caudate head region was less steep for the contralateral (135.6° ± 15.6°) than for the ipsilateral (152.0° ± 13.6°) approach (p = 0.02).

CONCLUSIONS

The anterior contralateral interhemispheric transcallosal approach provided a more expansive exposure to the lower two-thirds of the lateral ventricle and striothalamocapsular region. In normal-sized ventricles, the foramen of Monro and the choroidal fissure were better visualized through the lateral ventricle ipsilateral to the craniotomy than through the contralateral approach.

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Michael A. Mooney, Elias D. Simon, Scott Brigeman, Peter Nakaji, Joseph M. Zabramski, Michael T. Lawton and Robert F. Spetzler

OBJECTIVE

A direct comparison of endovascular versus microsurgical treatment of ruptured middle cerebral artery (MCA) aneurysms in randomized trials is lacking. As endovascular treatment strategies continue to evolve, the number of reports of endovascular treatment of these lesions is increasing. Herein, the authors report a detailed post hoc analysis of ruptured MCA aneurysms treated by microsurgical clipping from the Barrow Ruptured Aneurysm Trial (BRAT).

METHODS

The cases of patients enrolled in the BRAT who underwent microsurgical clipping for a ruptured MCA aneurysm were reviewed. Characteristics of patients and their clinical outcomes and long-term angiographic results were analyzed.

RESULTS

Fifty patients underwent microsurgical clipping of a ruptured MCA aneurysm in the BRAT, including 21 who crossed over from the endovascular treatment arm. Four patients with nonsaccular (e.g., dissecting, fusiform, or blister) aneurysms were excluded, leaving 46 patients for analysis. Most (n = 32; 70%) patients presented with a Hunt and Hess grade II or III subarachnoid hemorrhage, with a high prevalence of intraparenchymal blood (n = 23; 50%), intraventricular blood (n = 21; 46%), or both. At the last follow-up (up to 6 years after treatment), clinical outcomes were good (modified Rankin Scale score 0–2) in 70% (n = 19) of 27 Hunt and Hess grades I–III patients and in 36% (n = 4) of 11 Hunt and Hess grade IV or V patients. There were no instances of rebleeding after the surgical clipping of aneurysms in this series at the time of last clinical follow-up.

CONCLUSIONS

Microsurgical clipping of ruptured MCA aneurysms has several advantages over endovascular treatment, including durability over time. The authors report detailed outcome data of patients with ruptured MCA aneurysms who underwent microsurgical clipping as part of a prospective, randomized trial. These results should be used for comparison with future endovascular and surgical series to ensure that the best results are being achieved for patients with ruptured MCA aneurysms.

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Michael A. Mooney, Elias D. Simon, Scott Brigeman, Peter Nakaji, Joseph M. Zabramski, Michael T. Lawton and Robert F. Spetzler

OBJECTIVE

A direct comparison of endovascular versus microsurgical treatment of ruptured middle cerebral artery (MCA) aneurysms in randomized trials is lacking. As endovascular treatment strategies continue to evolve, the number of reports of endovascular treatment of these lesions is increasing. Herein, the authors report a detailed post hoc analysis of ruptured MCA aneurysms treated by microsurgical clipping from the Barrow Ruptured Aneurysm Trial (BRAT).

METHODS

The cases of patients enrolled in the BRAT who underwent microsurgical clipping for a ruptured MCA aneurysm were reviewed. Characteristics of patients and their clinical outcomes and long-term angiographic results were analyzed.

RESULTS

Fifty patients underwent microsurgical clipping of a ruptured MCA aneurysm in the BRAT, including 21 who crossed over from the endovascular treatment arm. Four patients with nonsaccular (e.g., dissecting, fusiform, or blister) aneurysms were excluded, leaving 46 patients for analysis. Most (n = 32; 70%) patients presented with a Hunt and Hess grade II or III subarachnoid hemorrhage, with a high prevalence of intraparenchymal blood (n = 23; 50%), intraventricular blood (n = 21; 46%), or both. At the last follow-up (up to 6 years after treatment), clinical outcomes were good (modified Rankin Scale score 0–2) in 70% (n = 19) of 27 Hunt and Hess grades I–III patients and in 36% (n = 4) of 11 Hunt and Hess grade IV or V patients. There were no instances of rebleeding after the surgical clipping of aneurysms in this series at the time of last clinical follow-up.

CONCLUSIONS

Microsurgical clipping of ruptured MCA aneurysms has several advantages over endovascular treatment, including durability over time. The authors report detailed outcome data of patients with ruptured MCA aneurysms who underwent microsurgical clipping as part of a prospective, randomized trial. These results should be used for comparison with future endovascular and surgical series to ensure that the best results are being achieved for patients with ruptured MCA aneurysms.

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Michael A. Mooney, Joseph Georges, Mohammedhassan Izady Yazdanabadi, Katherine Y. Goehring, William L. White, Andrew S. Little, Mark C. Preul, Stephen W. Coons, Peter Nakaji and Jennifer M. Eschbacher

OBJECTIVE

The objective of this study was to evaluate the feasibility of using confocal reflectance microscopy (CRM) ex vivo to differentiate adenoma from normal pituitary gland in surgical biopsy specimens. CRM allows for rapid, label-free evaluation of biopsy specimens with cellular resolution while avoiding some limitations of frozen section analysis.

METHODS

Biopsy specimens from 11 patients with suspected pituitary adenomas were transported directly to the pathology department. Samples were immediately positioned and visualized with CRM using a confocal microscope located in the same area of the pathology department where frozen sections are prepared. An H & E–stained slide was subsequently prepared from imaged tissue. A neuropathologist compared the histopathological characteristics of the H & E–stained slide and the matched CRM images. A second neuropathologist reviewed images in a blinded fashion and assigned diagnoses of adenoma or normal gland.

RESULTS

For all specimens, CRM contrasted cellularity, tissue architecture, nuclear pleomorphism, vascularity, and stroma. Pituitary adenomas demonstrated sheets and large lobules of cells, similar to the matched H & E–stained slides. CRM images of normal tissue showed scattered small lobules of pituitary epithelial cells, consistent with matched H & E–stained images of normal gland. Blinded review by a neuropathologist confirmed the diagnosis in 15 (94%) of 16 images of adenoma versus normal gland.

CONCLUSIONS

CRM is a simple, reliable approach for rapidly evaluating pituitary adenoma specimens ex vivo. This technique can be used to accurately differentiate between pituitary adenoma and normal gland while preserving biopsy tissue for future permanent analysis, immunohistochemical studies, and molecular studies.