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Sergiy V. Kushchayev, Morgan B. Giers, Doris Hom Eng, Nikolay L. Martirosyan, Jennifer M. Eschbacher, Martin M. Mortazavi, Nicholas Theodore, Alyssa Panitch and Mark C. Preul

OBJECTIVE

Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue.

METHODS

A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells).

RESULTS

The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed.

CONCLUSIONS

The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

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Evgenii Belykh, Kashif Malik, Isabelle Simoneau, Kaan Yagmurlu, Ting Lei, Daniel D. Cavalcanti, Vadim A. Byvaltsev, Nicholas Theodore and Mark C. Preul

André Feil (1884–1955) was a French physician best recognized for his description, coauthored with Maurice Klippel, of patients with congenital fusion of cervical vertebrae, a condition currently known as Klippel-Feil syndrome. However, little is known about his background aside from the fact that he was a student of Klippel and a physician who took a keen interest in describing congenital anomalies. Despite the relative lack of information on Feil, his contributions to the fields of spinal disease and teratology extended far beyond science to play an integral role in changing the misguided perception shrouding patients with disfigurements, defects, deformities, and so-called monstrous births. In particular, Feil's 1919 medical school thesis on cervical abnormalities was a critical publication in defying long-held theory and opinion that human “monstrosities,” anomalies, developmental abnormalities, and altered congenital physicality were a consequence of sinful behavior or a reversion to a primitive state. Indeed, his thesis on a spinal deformity centering on his patient, L. Joseph, was at the vanguard for a new view of a patient as nothing less than fully human, no matter his or her physicality or appearance.

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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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Nikolay L. Martirosyan, Jennifer M. Eschbacher, M. Yashar S. Kalani, Jay D. Turner, Evgenii Belykh, Robert F. Spetzler, Peter Nakaji and Mark C. Preul

OBJECTIVE

This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors.

METHODS

CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging–matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard.

RESULTS

CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3–73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas.

CONCLUSIONS

CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.

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Paul A. Gardner, Juan C. Fernandez-Miranda, Carl H. Snyderman and Eric W. Wang

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Sergiy V. Kushchayev, Evgenii Belykh, Yakiv Fishchenko, Aliaksei Salei, Oleg M. Teytelboym, Leonid Shabaturov, Mark Cruse and Mark C. Preul

General Mikhail Kutuzov (circa 1745–1813) brilliantly repelled Napoleon’s invasion of Russia. Honored as a national hero and a savior of Russia, Kutuzov has a unique medical story. He was shot in the head twice while fighting the Turks (1774 and 1788) and survived the serious injuries seemingly against all odds. The first bullet “ran through the head from one temple to the other behind both eyes.” The second bullet entered the cheek, destroyed upper teeth, traveled through the head, and exited the occiput. Massot, a French surgeon with the Russian army, wrote after treating Kutuzov’s seemingly two mortal wounds: “It must be believed that fate appoints Kutuzov to something great, because he was still alive after two injuries, a death sentence by all the rules of medical science.” Aided by Massot’s expert surgical technique, Kutuzov lived to become intimately engaged in events that altered world history. His health did, however, suffer significant effects due to the bullet wounds. In 1812, as Napoleon’s Grande Armée approached, Kutuzov realized he could not confront Napoleon and he strategically retreated from Moscow, submitting the French to the harsh winter and Russian cavalry. Napoleon’s devastated army retreated to Paris, and Kutuzov became the personification of Russian spirit and character. Kutuzov’s survival of two nearly mortal head wounds created the legends, additional mystery, and drama surrounding him, not the least astonishing of which was the skilled neurosurgical care that probably saved his life.