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George A. C. Mendes, Curtis A. Dickman, Nestor G. Rodriguez-Martinez, Samuel Kalb, Neil R. Crawford, Volker K. H. Sonntag, Mark C. Preul and Andrew S. Little

OBJECT

The primary disadvantage of the posterior cervical approach for atlantoaxial stabilization after odontoidectomy is that it is conducted as a second-stage procedure. The goal of the current study is to assess the surgical feasibility and biomechanical performance of an endoscopic endonasal surgical technique for C1–2 fixation that may eliminate the need for posterior fixation after odontoidectomy.

METHODS

The first step of the study was to perform endoscopic endonasal anatomical dissections of the craniovertebral junction in 10 silicone-injected fixed cadaveric heads to identify relevant anatomical landmarks. The second step was to perform a quantitative analysis using customized software in 10 reconstructed adult cervical spine CT scans to identify the optimal screw entry point and trajectory. The third step was biomechanical flexibility testing of the construct and comparison with the posterior C1–2 transarticular fixation in 14 human cadaveric specimens.

RESULTS

Adequate surgical exposure and identification of the key anatomical landmarks, such as C1–2 lateral masses, the C-1 anterior arch, and the odontoid process, were provided by the endonasal endoscopic approach in all specimens. Radiological analysis of anatomical detail suggested that the optimal screw entry point was on the anterior aspect of the C-1 lateral mass near the midpoint, and the screw trajectory was inferiorly and slightly laterally directed. The custommade angled instrumentation was crucial for screw placement. Biomechanical analysis suggested that anterior C1–2 fixation compared favorably to posterior fixation by limiting flexion-extension, axial rotation, and lateral bending (p > 0.3).

CONCLUSIONS

This is the first study that demonstrates the feasibility of an endoscopic endonasal technique for C1–2 fusion. This novel technique may have clinical utility by eliminating the need for a second-stage posterior fixation operation in certain patients undergoing odontoidectomy.

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Ali M. Elhadi, Joseph M. Zabramski, Kaith K. Almefty, George A. C. Mendes, Peter Nakaji, Cameron G. McDougall, Felipe C. Albuquerque, Mark C. Preul and Robert F. Spetzler

OBJECT

Hemorrhagic origin is unidentifiable in 10%–20% of patients presenting with spontaneous subarachnoid hemorrhage (SAH). While the patients in such cases do well clinically, there is a lack of long-term angiographic followup. The authors of the present study evaluated the long-term clinical and angiographic follow-up of a patient cohort with SAH of unknown origin that had been enrolled in the Barrow Ruptured Aneurysm Trial (BRAT).

METHODS

The BRAT database was searched for patients with SAH of unknown origin despite having undergone two or more angiographic studies as well as MRI of the brain and cervical spine. Follow-up was available at 6 months and 1 and 3 years after treatment. Analysis included demographic details, clinical outcome (Glasgow Outcome Scale, modified Rankin Scale [mRS]), and repeat vascular imaging.

RESULTS

Subarachnoid hemorrhage of unknown etiology was identified in 57 (11.9%) of the 472 patients enrolled in the BRAT study between March 2003 and January 2007. The mean age for this group was 51 years, and 40 members (70%) of the group were female. Sixteen of 56 patients (28.6%) required placement of an external ventricular drain for hydrocephalus, and 4 of these subsequently required a ventriculoperitoneal shunt. Delayed cerebral ischemia occurred in 4 patients (7%), leading to stroke in one of them. There were no rebleeding events. Eleven patients were lost to followup, and one patient died of unrelated causes. At the 3-year follow-up, 4 (9.1%) of 44 patients had a poor outcome (mRS > 2), and neurovascular imaging, which was available in 33 patients, was negative.

CONCLUSIONS

Hydrocephalus and delayed cerebral ischemia, while infrequent, do occur in SAH of unknown origin. Long-term neurological outcomes are generally good. A thorough evaluation to rule out an etiology of hemorrhage is necessary; however, imaging beyond 6 weeks from ictus has little utility, and rebleeding is unexpected.

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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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Sam Safavi-Abbasi, Adrian J. Maurer, Jacob B. Archer, Ricardo A. Hanel, Michael E. Sughrue, Nicholas Theodore and Mark C. Preul

During his lifetime and a career spanning 42 years, James Watson Kernohan made numerous contributions to neuropathology, neurology, and neurosurgery. One of these, the phenomenon of ipsilateral, false localizing signs caused by compression of the contralateral cerebral peduncle against the tentorial edge, has widely become known as “Kernohan's notch” and continues to bear his name. The other is a grading system for gliomas from a neurosurgical viewpoint that continues to be relevant for grading of glial tumors 60 years after its introduction. In this paper, the authors analyze these two major contributions in detail within the context of Kernohan's career and explore how they contributed to the development of neurosurgical procedures.

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Kathryn E. Fenton, Nikolay L. Martirosyan, Mohammed G. Abdelwahab, Stephen W. Coons, Mark C. Preul and Adrienne C. Scheck

Object

For patients with glioblastoma multiforme, median survival time is approximately 14 months. Longer progression-free and overall survival times correlate with gross-total resection of tumor. The ability to identify tumor cells intraoperatively could result in an increased percentage of tumor resected and thus increased patient survival times. Available labeling methods rely on metabolic activity of tumor cells; thus, they are more robust in high-grade tumors, and their utility in low-grade tumors and metastatic tumors is not clear. The authors demonstrate intraoperative identification of tumor cells by using labeled tumor-specific antibodies.

Methods

GL261 mouse glioma cells exhibit high expression of a membrane-bound protein called second tyrosinase-related protein (TRP-2). The authors used these cells to establish an intracranial, immunocompetent model of malignant glioma. Antibodies to TRP-2 were labeled by using Alexa Fluor 488 fluorescent dye and injected into the tail vein of albino C57BL/6 mice. After 24 hours, a craniotomy was performed and the tissue was examined in vivo by using an Optiscan 5.1 handheld portable confocal fiber-optic microscope. Tissue was examined ex vivo by using a Pascal 5 scanning confocal microscope.

Results

Labeled tumor cells were visible in vivo and ex vivo under the respective microscopes.

Conclusions

Fluorescently labeled tumor-specific antibodies are capable of binding and identifying tumor cells in vivo, accurately and specifically. The development of labeled markers for the identification of brain tumors will facilitate the use of intraoperative fluorescence microscopy as a tool for increasing the extent of resection of a broad variety of intracranial tumors.

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Joseph Georges, Aqib Zehri, Elizabeth Carlson, Joshua Nichols, Michael A. Mooney, Nikolay L. Martirosyan, Layla Ghaffari, M. Yashar S. Kalani, Jennifer Eschbacher, Burt Feuerstein, Trent Anderson, Mark C. Preul, Kendall Van Keuren-Jensen and Peter Nakaji

Glioblastoma is the most common primary brain tumor with a median 12- to 15-month patient survival. Improving patient survival involves better understanding the biological mechanisms of glioblastoma tumorigenesis and seeking targeted molecular therapies. Central to furthering these advances is the collection and storage of surgical biopsies (biobanking) for research. This paper addresses an imaging modality, confocal reflectance microscopy (CRM), for safely screening glioblastoma biopsy samples prior to biobanking to increase the quality of tissue provided for research and clinical trials. These data indicate that CRM can immediately identify cellularity of tissue biopsies from animal models of glioblastoma. When screening fresh human biopsy samples, CRM can differentiate a cellular glioblastoma biopsy from a necrotic biopsy without altering DNA, RNA, or protein expression of sampled tissue. These data illustrate CRM's potential for rapidly and safely screening clinical biopsy samples prior to biobanking, which demonstrates its potential as an effective screening technique that can improve the quality of tissue biobanked for patients with glioblastoma.

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Nikolay L. Martirosyan, Joseph Georges, Jennifer M. Eschbacher, Daniel D. Cavalcanti, Ali M. Elhadi, Mohammed G. Abdelwahab, Adrienne C. Scheck, Peter Nakaji, Robert F. Spetzler and Mark C. Preul

Object

The authors sought to assess the feasibility of a handheld visible-wavelength confocal endomicroscope imaging system (Optiscan 5.1, Optiscan Pty., Ltd.) using a variety of rapid-acting fluorophores to provide histological information on gliomas, tumor margins, and normal brain in animal models.

Methods

Mice (n = 25) implanted with GL261 cells were used to image fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA), acridine orange (AO), acriflavine (AF), and cresyl violet (CV). A U251 glioma xenograft model in rats (n = 5) was used to image sulforhodamine 101 (SR101). A swine (n = 3) model with AO was used to identify confocal features of normal brain. Images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope. Histological samples were acquired through biopsies from matched imaging areas. Samples were visualized with a benchtop confocal microscope. Histopathological features in corresponding confocal images and photomicrographs of H & E–stained tissues were reviewed.

Results

Fluorescence induced by FNa, 5-ALA, AO, AF, CV, and SR101 and detected with the confocal endomicroscope allowed interpretation of histological features. Confocal endomicroscopy revealed satellite tumor cells within peritumoral tissue, a definitive tumor border, and striking fluorescent cellular and subcellular structures. Fluorescence in various tumor regions correlated with standard histology and known tissue architecture. Characteristic features of different areas of normal brain were identified as well.

Conclusions

Confocal endomicroscopy provided rapid histological information precisely related to the site of microscopic imaging with imaging characteristics of cells related to the unique labeling features of the fluorophores. Although experimental with further clinical trial validation required, these data suggest that intraoperative confocal imaging can help to distinguish normal brain from tumor and tumor margin and may have application in improving intraoperative decisions during resection of brain tumors.