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M. Sean Grady

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Raphael Guzman and M. Sean Grady

✓ A case of cerebellar hemangioblastoma with a coexistent arterial aneurysm on the feeding artery of the tumor is reported. The patient presented with an acute onset of headache, loss of consciousness, and left-sided hemiparesis due to a posterior fossa hemorrhage found adjacent to a hemangioblastoma. Four-vessel angiography revealed an aneurysm on the anterior inferior cerebellar artery (AICA), which was the main feeding vessel of the hemangioblastoma. Successful total excision of the hemangioblastoma and clipping of the AICA aneurysm achieved in a one-stage operation was demonstrated on postoperative angiography.

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James M. Schuster and M. Sean Grady

Metastatic spinal tumors are an increasingly common and difficult problem encountered by neurosurgeons and orthopedic surgeons. To improve therapies and increase life expectancy for patients with tumors such as those of the breast and prostate, a global, systematic approach is required to maximize the preservation of neurological function, maintenance of spinal stability, and relief of pain, all with the ultimate goal of improved functional capacity and quality of life (QOL). Although radiotherapy and surgery are still the primary therapeutic options, several new adjuvant therapies initially implemented to control pain more effectively have also been shown to reduce overall skeleton-related complications (pathological fractures and hypercalcemia) and may ultimately improve and extend QOL. This more global approach to spinal metastases also includes optimizing each patient's overall medical condition and potential for healing (that is, nutrition), as well as avoiding potential complications associated with metastatic disease (such as deep vein thrombosis), including excessive blood loss in the case of renal metastasis. A thorough knowledge and understanding of these therapeutic adjuvants is required to optimize care and to respond to our increasingly medically knowledgable patient population whose access to prevalent medical information has been increased because of the internet.

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M. Sean Grady, Robert F. Bedford and T. S. Park

✓ Air embolism is a potential hazard during craniotomy whenever intracranial venous pressure is subatmospheric. In order to better understand both the risk of air embolism and its treatment in neurosurgical patients, the authors have investigated the relationship of superior sagittal sinus pressure (SSP) to head position in 15 children and examined the effects of both jugular venous compression and positive end-expiratory airway pressure (PEEP) on SSP. Progressive head elevation significantly decreased mean SSP and, in five patients, SSP was less than 0 mm Hg at 90° torso elevation. A PEEP of 10 cm H2O was ineffective in significantly increasing SSP at any degree of head elevation, whereas bilateral internal jugular compression always caused a significant increase in SSP. The authors conclude that children are at risk for venous air embolism when undergoing suboccipital craniectomy in the sitting position because intracranial venous pressure is often subatmospheric when the head is elevated. Furthermore, maintaining PEEP does not appear to be a reliable treatment for increasing SSP, whereas bilateral internal jugular compression is effective.

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Mark G. Burnett, Sherman C. Stein and M. Sean Grady

Object. The goal of this study was to create a searchable database of research manuscripts authored by members of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS) to describe the nature and character of the research currently being undertaken by neurosurgeons.

Methods. Manuscripts published by all physician members listed in the 2001 AANS/CNS Membership Directory (6921 physicians) were gathered into a database through individual literature searches of the author name for the calendar year 2001. Duplicate publications were purged and the database was reviewed for accuracy. An internal verification of the database revealed a 4% underreporting rate. Statistics from the database were compiled and displayed with information about AANS/CNS members and their clinical activities.

The AANS/CNS members published a total of 2748 research the manuscripts in 479 different journals during 2001. Thirty-eight percent of the manuscripts (1042 of 2748) were authored by US members and 62% (1706 of 2748) by non-US members. The focus of the majority of manuscripts included the areas of brain tumor (26%; 707 of 2748), vascular disease (20%; 558 of 2748), spine (10%; 282 of 2748), and trauma (8%; 233 of 2748). Sixty-nine percent of manuscripts (1897 of 2748) were retrospective and technical clinical studies, and of these 39% (744 of 1897) were case reports. Laboratory investigations made up 15% (414 of 2748) of all manuscripts, whereas prospective randomized clinical trials represented 1% (34 of 2748).

Conclusions. The majority of AANS/CNS member manuscripts are authored by non—US members despite their small AANS/CNS representation. Most research is clinical, based on retrospective data, and includes a large number of case reports. A disparity exists between what neurosurgeons do clinically and both the quantity and subject of their research.

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Richard H. Schmidt and M. Sean Grady

✓ Disturbances in memory, concentration, and problem solving are common after even mild to moderate traumatic brain injury. Because these functions are mediated in part by forebrain cholinergic and catecholaminergic innervation, in this study the authors sought to determine if experimental concussive injury produces detectable morphological damage to these systems.

Fluid-percussion head injury, sufficient to cause a 13- to 14-minute loss of righting reflex, was produced in rats that had been anesthetized with halothane. Injury was delivered either at midline or 2 mm off midline and compared with appropriate sham-injured controls. After 11 to 15 days, the rat brains were stained in serial sections for choline acetyltransferase, tyrosine hydroxylase, dopamine β-hydroxylase, acetylcholinesterase, and nicotinamide adenine dinucleotide phosphate diaphorase. Cell counts were determined for the entire population of ventrobasal forebrain cholinergic cells. Midline injury produced a bilateral loss of cholinergic neurons averaging 36% in area Ch1 (medial septal nucleus), 45% in Ch2 (nucleus of the diagonal band of Broca), and 41% in Ch4 (nucleus basalis of Meynart), (p ≤ 0.05). Lateralized injury resulted in cholinergic neuron loss of similar magnitude ipsilaterally (p ≤ 0.05), but a smaller contralateral loss of between 11% and 28%. No loss of neurons was detected in the pontomesencephalic cholinergic groups Ch5 and Ch6. There was no visible effect of head injury on forebrain dopamine or noradrenergic innervation.

A significant and apparently selective loss of ventrobasal forebrain cholinergic neurons following brief concussive injury in rats is demonstrated in this study. This type of injury is known to produce significant disturbance in cognitive tasks linked to neocortical and hippocampal cholinergic function. It remains to be determined how this neuron loss occurs, whether it can be prevented with neuroprotective agents, how it affects innervation in target tissues, and whether it occurs in human victims of traumatic brain injury.

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M. Sean Grady, John A. Jane and Oswald Steward

✓ Behavioral recovery following brain injury in humans is well recognized; however, the anatomical basis for such recovery has not been demonstrated. Two cases are presented that show reorganization of synaptic connections (plasticity) in the dentate gyrus of human brain following uncal herniation. The neurohistological appearance of these cases is very similar to a well-described animal model of anatomical, physiological, and behavioral recovery following experimental surgical injury.

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Michael F. Stiefel and M. Sean Grady

The DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumor to alkylating agents. METHODS: We analyzed the MGMT promoter in tumor DNA by a methylation-specific polymerase-chain-reaction assay. The gliomas were obtained from patients who had been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU). The molecular data were correlated with the clinical outcome. RESULTS: The MGMT promoter was methylated in gliomas from 19 of 47 patients (40 percent). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status. CONCLUSIONS: Methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents.

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H. Grady Rylander III, Jim L. Story and H. Lyndon Taylor

✓ Chronic measurements of epidural pressure made with an induction-powered oscillator transducer revealed several problems with the current design of the device. All transducers failed over a period of months due to the diffusion of extracellular fluid through epoxy seals, which resulted in corrosion of the electrical components. Significant fibrosis occurred around the circumference of the burr hole, which reduced the sensitivity of the transducers. Design modifications are suggested to circumvent these problems.