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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.

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Feres Chaddad-Neto, Marcos Devanir Silva da Costa, Baran Bozkurt, Hugo Leonardo Doria-Netto, Daniel de Araujo Paz, Ricardo da Silva Centeno, Andrew W. Grande, Sergio Cavalheiro, Kaan Yağmurlu, Robert F. Spetzler, and Mark C. Preul

OBJECTIVE

The authors report a novel surgical route from a superior anatomical aspect—the contralateral anterior interhemispheric-transcallosal-transrostral approach—to a lesion located in the subcallosal region. The neurosurgical approach to the subcallosal region is challenging due to its deep location and close relationship with important vascular structures. Anterior and inferior routes to the subcallosal region have been described but risk damaging the branches of the anterior cerebral artery.

METHODS

Three formalin-fixed and silicone-injected adult cadaveric heads were studied to demonstrate the relationships between the transventricular surgical approach and the subcallosal region. The surgical, clinical, and radiological history of a 39-year-old man with a subcallosal cavernous malformation was retrospectively used to document the neurological examination and radiographic parameters of such a case.

RESULTS

The contralateral anterior interhemispheric-transcallosal-transrostral approach provides access to the subcallosal area that also includes the inferior portion of the pericallosal cistern, lamina terminalis cistern, the paraterminal and paraolfactory gyri, and the anterior surface of the optic chiasm. The approach avoids the neurocritical perforating branches of the anterior communicating artery.

CONCLUSIONS

The contralateral anterior interhemispheric-transcallosal-transrostral approach may be an alternative route to subcallosal area lesions, with less risk to the branches of the anterior cerebral artery, particularly the anterior communicating artery perforators.

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Eberval Gadelha Figueiredo, Manoel J. Teixeira, Robert F. Spetzler, and Mark C. Preul

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Daniel D. Cavalcanti, Mark C. Preul, M. Yashar S. Kalani, and Robert F. Spetzler

OBJECT

The aim of this study was to enhance the planning and use of microsurgical resection techniques for intrinsic brainstem lesions by better defining anatomical safe entry zones.

METHODS

Five cadaveric heads were dissected using 10 surgical approaches per head. Stepwise dissections focused on the actual areas of brainstem surface that were exposed through each approach and an analysis of the structures found, as well as which safe entry zones were accessible via each of the 10 surgical windows.

RESULTS

Thirteen safe entry zones have been reported and validated for approaching lesions in the brainstem, including the anterior mesencephalic zone, lateral mesencephalic sulcus, intercollicular region, peritrigeminal zone, supratrigeminal zone, lateral pontine zone, supracollicularzone, infracollicularzone, median sulcus of the fourth ventricle, anterolateral and posterior median sulci of the medulla, olivary zone, and lateral medullary zone. A discussion of the approaches, anatomy, and limitations of these entry zones is included.

CONCLUSIONS

A detailed understanding of the anatomy, area of exposure, and safe entry zones for each major approach allows for improved surgical planning and dissemination of the techniques required to successfully resect intrinsic brainstem lesions.

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Richard Leblanc and Mark C. Preul

William Howard Feindel (1918–2014) was one of the world's most distinguished neurosurgeons and a brilliant neuroscientist. As the Montreal Neurological Institute's third director, having succeeded Theodore Rasmussen and Wilder Penfield, he proved to be a visionary medical and scientific administrator. His keen interests in epilepsy and brain imaging were enhanced by a passion for medical history. Students and young people invariably gravitated to Dr. Feindel; he was a kind, patient, thoughtful, intelligent, and caring mentor who was never too busy for them. A pioneer in his own right, Dr. Feindel linked our modern neurosurgical world with the legacy of the first generations of important neurosurgeons and neuroscientists.

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Celeste R. Brennecka, Mark C. Preul, Timothy A. Becker, and Brent L. Vernon

Object

Over the past 20 years, endovascular embolization has become the preferred method of treating cerebral aneurysms. While there are many embolic devices on the market, none is ideal. In this study the authors investigated the use of a liquid-to-solid gelling polymer system—that is, poly(propylene glycol) diacrylate and pentaerythritol tetrakis (3-mercaptopropionate) (PPODA-QT)—to embolize in vivo aneurysms over a 6-month period.

Methods

Experimental aneurysms were created in the carotid arteries of 9 canines. Aneurysms were embolized with the polymer only (PPODA-QT, 3 dogs), filled with PPODA-QT after placement of a “framing” platinum coil (coil + PPODA-QT, 3 dogs), or packed with platinum coils (coils only, 3 dogs). Aneurysm occlusion was angiographically monitored immediately and 6 months after embolization. After 6 months, the ostial regions of explanted aneurysms were assessed macroscopically and histologically.

Results

All aneurysms showed 100% angiographic occlusion at 6 months, but turbulent blood flow was observed in 1 coils-only sample. Ostial regions of explanted coils-only aneurysms showed neointimal tissue surrounding individual coils but no continuous tissue layer over the aneurysm neck. All PPODA-QT aneurysms displayed smooth ostial surfaces, but 2 of 3 coil + PPODA-QT aneurysms showed polymer (unassociated with the coil) protruding into the vessel lumen, contributing to rough ostial surfaces. Neointimal tissue was present in PPODA-QT and coil + PPODA-QT aneurysms and covered smooth ostial surfaces more completely than in coils-only aneurysms.

Conclusions

This study compared neointimal tissue overgrowth in the ostium of experimental aneurysms embolized with PPODA-QT, PPODA-QT plus a framing coil, or coils alone. The coils-only and coil + PPODA-QT groups showed rough and discontinuous ostial surfaces, which hindered neointimal tissue coverage. The PPODA-QT aneurysms consistently produced smooth ostial surfaces that facilitated more complete neointimal tissue coverage over aneurysm necks.

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Jennifer Eschbacher, Nikolay L. Martirosyan, Peter Nakaji, Nader Sanai, Mark C. Preul, Kris A. Smith, Stephen W. Coons, and Robert F. Spetzler

Object

Frozen-section analysis is the current standard for the intraoperative diagnosis of brain tumors. Intraoperative confocal microscopy is an emerging technology with the potential to visualize tumor histopathological features and cell morphology in real time. The authors report their findings using this new intraoperative technology in vivo with sodium fluorescein contrast during the course of 50 microsurgical tumor resections.

Methods

Eighty-eight regions were visualized with confocal microscopy, and corresponding biopsy samples were examined with routine neuropathological analysis. The tumors studied included meningiomas, schwannomas, gliomas of various grades, and a hemangioblastoma. The confocal microscopic features of each tumor and of various artifacts inherent to the technology were documented. A pathologist working in a blinded fashion reviewed a subset of the images in a further evaluation of the usefulness of the device as a diagnostic tool.

Results

Overall, intraoperative confocal imaging correlated surprisingly well with corresponding traditional histological findings, including the identification of many pathognomonic cytoarchitectural features of various brain tumors. In the blinded study, 26 (92.9%) of 28 lesions were diagnosed correctly.

Conclusions

Further study will be necessary for better definition of the role of intraoperative confocal microscopy as a routine adjunct for intraoperative brain tumor diagnosis.

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Daniel D. Cavalcanti, M. Yashar S. Kalani, Nikolay L. Martirosyan, Justin Eales, Robert F. Spetzler, and Mark C. Preul

Over the past half century molecular biology has led to great advances in our understanding of angio- and vasculogenesis and in the treatment of malformations resulting from these processes gone awry. Given their sporadic and familial distribution, their developmental and pathological link to capillary telangiectasias, and their observed chromosomal abnormalities, cerebral cavernous malformations (CCMs) are regarded as akin to cancerous growths. Although the exact pathological mechanisms involved in the formation of CCMs are still not well understood, the identification of 3 genetic loci has begun to shed light on key developmental pathways involved in CCM pathogenesis. Cavernous malformations can occur sporadically or in an autosomal dominant fashion. Familial forms of CCMs have been attributed to mutations at 3 different loci implicated in regulating important processes such as proliferation and differentiation of angiogenic precursors and members of the apoptotic machinery. These processes are important for the generation, maintenance, and pruning of every vessel in the body. In this review the authors highlight the latest discoveries pertaining to the molecular genetics of CCMs, highlighting potential new therapeutic targets for the treatment of these lesions.

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Editorial

Cavernous malformations

Issam A. Awad