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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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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.

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Ali M. Elhadi, Samuel Kalb, Luis Perez-Orribo, Andrew S. Little, Robert F. Spetzler and Mark C. Preul

The field of anatomy, one of the most ancient sciences, first evolved in Egypt. From the Early Dynastic Period (3100 bc) until the time of Galen at the end of the 2nd century ad, Egypt was the center of anatomical knowledge, including neuroanatomy. Knowledge of neuroanatomy first became important so that sacred rituals could be performed by ancient Egyptian embalmers during mummification procedures. Later, neuroanatomy became a science to be studied by wise men at the ancient temple of Memphis. As religious conflicts developed, the study of the human body became restricted. Myths started to replace scientific research, squelching further exploration of the human body until Alexander the Great founded the city of Alexandria. This period witnessed a revolution in the study of anatomy and functional anatomy. Herophilus of Chalcedon, Erasistratus of Chios, Rufus of Ephesus, and Galen of Pergamon were prominent physicians who studied at the medical school of Alexandria and contributed greatly to knowledge about the anatomy of the skull base. After the Royal Library of Alexandria was burned and laws were passed prohibiting human dissections based on religious and cultural factors, knowledge of human skull base anatomy plateaued for almost 1500 years. In this article the authors consider the beginning of this journey, from the earliest descriptions of skull base anatomy to the establishment of basic skull base anatomy in ancient Egypt.

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Wolfgang K. Pfisterer, Ronald A. Nieman, Adrienne C. Scheck, Stephen W. Coons, Robert F. Spetzler and Mark C. Preul

Object

The goal in this study was to determine if proton (1H) MR spectroscopy can differentiate meningioma grade and is associated with interpretations of biological behavior; the study was performed using ex vivo high-resolution spectra indicating metabolic characteristics.

Methods

Sixty-eight resected tissue samples of meningiomas were examined using ex vivo 1H MR spectroscopy. Of these meningiomas, 46 were WHO Grade I, 14 were WHO Grade II, and 8 were WHO Grade III. Fifty-nine were primary meningiomas and 9 were recurrences. Invasion of adjacent tissue (dura mater, bone, venous sinus, brain) was found in 32 cases. Thirty-nine meningiomas did not rapidly recur (as defined by expansion on MR imaging within a 5-year follow-up period), whereas rapid recurrence was confirmed in 24 meningiomas, and follow-up status was unknown in 5 cases.

Results

The absolute concentrations of total alanine and creatine were decreased in high-grade compared with low-grade meningiomas, as was the ratio of glycine to alanine (all p < 0.05). Additionally, alanine and the glycine/alanine ratio distinguished between primary and recurrent meningiomas (all p < 0.05). Finally, the absolute concentrations of alanine and creatine, and the glycine/alanine and choline/glutamate ratios were associated with rapid recurrence (p < 0.05).

Conclusions

. These data indicate that meningioma tissue can be characterized by metabolic parameters that are not typically identified by histopathological analysis alone. Creatine, glycine, and alanine may be used as markers of meningioma grade, recurrence, and the likelihood of rapid recurrence. These data validate a previous study of a separate group of Grade I meningiomas.

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Ulises García-González, Daniel D. Cavalcanti, Abhishek Agrawal, L. Fernando Gonzalez, Robert C. Wallace, Robert F. Spetzler and Mark C. Preul

Object

There are few systematic investigations of the dissected surgical anatomy of the diploic venous system (DVS) in the neuroanatomical literature. The authors describe the DVS relative to different common neurosurgical approaches. Knowledge of this system can help avoid potential sources of unacceptable bleeding and may impact healing of the cranium.

Methods

Using a high-speed drill with a 2-mm bit, the authors removed the outer layer of the compact bone in the skull to expose the DVS in 12 formalin-fixed cadaver heads. Pterional, supraorbital, and modified orbitozygomatic craniotomies were performed to delineate the relationship of the DVS.

Results

The draining point of the frontal diploic vein (FDV) was located near the supraorbital notch. The draining point of the anterior temporal diploic vein (ATDV) was located in all pterional areas; the draining point of the posterior temporal diploic vein (PTDV) was located in all asterional areas. The PTDV was the dominant diploic vessel in all sides. The FDV and ATDV could be damaged during supraorbital, modified orbitozygomatic, and pterional craniotomies. The anterior DVS connected with the sphenoparietal and superior sagittal sinus (SSS). The posterior DVS connected with the transverse and sigmoid sinuses and was the dominant diploic vessel in all 24 sides. Of all the major diploic vessels, the location and pattern of distribution of the FDV were the most constant. The parietal bone contained the most diploic vessels. No diploic veins were found in the area delimited by the temporal squama.

Conclusions

The pterional, orbitozygomatic, and supraorbital approaches place the FDV and ATDV at risk. The major anterior diploic system connects the SSS with the sphenoparietal sinus. The posterior diploic system connects the SSS with the transverse and sigmoid sinuses.

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Robert W. Ryan, Robert F. Spetzler and Mark C. Preul

In this historical review the authors examine the important developments that have led to the availability of laser energy to neurosurgeons as a unique and sometimes invaluable tool. They review the physical science behind the function of lasers, as well as how and when various lasers based on different lasing mediums were discovered. They also follow the close association between advances in laser technology and their application in biomedicine, from early laboratory experiments to the first clinical experiences. Because opinions on the appropriate role of lasers in neurosurgery vary widely, the historical basis for some of these views is explored. Initial enthusiasm for a technology that appears to have innate advantages for safe resections has often given way to the strict limitations and demands of the neurosurgical operating theater. However, numerous creative solutions to improve laser delivery, power, safety, and ergonomics demonstrate the important role that technological advances in related scientific fields continue to offer neurosurgery. Benefiting from the most recent developments in materials science, current CO2 laser delivery systems provide a useful addition to the neurosurgical armamentarium when applied in the correct circumstances and reflect the important historical advances that come about from the interplay between neurosurgery and technology.

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Eric M. Horn, Nicholas Theodore, Rachid Assina, Robert F. Spetzler, Volker K. H. Sonntag and Mark C. Preul

Object

Venous stasis and intrathecal hypertension are believed to play a significant role in the hypoperfusion present in the spinal cord following injury. Lowering the intrathecal pressure via cerebrospinal fluid (CSF) drainage has been effective in treating spinal cord ischemia during aorta surgery. The purpose of the present study was to determine whether CSF drainage increases spinal cord perfusion and improves outcome after spinal injury in an animal model.

Methods

Anesthetized adult rabbits were subjected to a severe contusion spinal cord injury (SCI). Cerebrospinal fluid was then drained via a catheter to lower the intrathecal pressure by 10 mm Hg. Tissue perfusion was assessed at the site of injury, and values obtained before and after CSF drainage were compared. Two other cohorts of animals were subjected to SCI: 1 group subsequently underwent CSF drainage and the other did not. Results of histological analysis, motor evoked potential and motor function testing were compared between the 2 cohorts at 4 weeks postinjury.

Results

Cerebrospinal fluid drainage led to no significant improvement in spinal cord tissue perfusion. Four weeks after injury, the animals that underwent CSF drainage demonstrated significantly smaller areas of tissue damage at the injury site. There were no differences in motor evoked potentials or motor score outcomes at 4 weeks postinjury.

Conclusions

Cerebrospinal fluid drainage effectively lowers intrathecal pressure and decreases the amount of tissue damage in an animal model of spinal cord injury. Further studies are needed to determine whether different draining regimens can improve motor or electrophysiological outcomes.

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Nicholas C. Bambakidis, John Butler, Eric M. Horn, Xukui Wang, Mark C. Preul, Nicholas Theodore, Robert F. Spetzler and Volker K. H. Sonntag

✓ The development of an acute traumatic spinal cord injury (SCI) inevitably leads to a complex cascade of ischemia and inflammation that results in significant scar tissue formation. The development of such scar tissue provides a severe impediment to neural regeneration and healing with restoration of function. A multimodal approach to treatment is required because SCIs occur with differing levels of severity and over different lengths of time. To achieve significant breakthroughs in outcomes, such approaches must combine both neuroprotective and neuroregenerative treatments. Novel techniques modulating endogenous stem cells demonstrate great promise in promoting neuroregeneration and restoring function.

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Sam Safavi-Abbasi, Leonardo B. C. Brasiliense, Ryan K. Workman, Melanie C. Talley, Iman Feiz-Erfan, Nicholas Theodore, Robert F. Spetzler and Mark C. Preul

✓In 25 years, the Mongolian army of Genghis Khan conquered more of the known world than the Roman Empire accomplished in 400 years of conquest. The recent revised view is that Genghis Khan and his descendants brought about “pax Mongolica” by securing trade routes across Eurasia. After the initial shock of destruction by an unknown barbaric tribe, almost every country conquered by the Mongols was transformed by a rise in cultural communication, expanded trade, and advances in civilization. Medicine, including techniques related to surgery and neurological surgery, became one of the many areas of life and culture that the Mongolian Empire influenced.