✓ The potential role of iron in cerebral vasospasm was examined in the rat femoral artery model by the perivascular application of deferoxamine, a ferric ion chelator and antioxidant. In 25 rats, platelet-rich plasma or fresh autologous whole blood containing deferoxamine at concentrations of 1, 5, 10, or 15 mg/ml was applied to the adventitial surface of the femoral artery in a Silastic cuff to insure chronic exposure to the vessel wall. At 7 days, contralateral femoral arteries exposed to whole blood showed a 70% reduction in luminal cross-sectional area and morphological changes associated with vasospasm. Application of platelet-rich plasma or whole blood containing deferoxamine at 25 mg/ml produced no significant arterial narrowing or structural changes; significant intermediate reductions in arterial narrowing were observed at deferoxamine concentrations of 5 and 10 mg/ml. Presaturation deferoxamine (10 mg/ml) with excess ferric ion prior to application eliminated the protective effect. In addition, deferoxamine chelated the ferric ion released from incubated whole blood in vitro over 7 days in a dose-dependent manner consistent with its protective effect in vivo. Ferric ion may influence the development of chronic arterial narrowing after subarachnoid hemorrhage by a variety of mechanisms.
Tsutomu Harada and Marc R. Mayberg
Report of 35 cases
Marc R. Mayberg and Lindsay Symon
✓ Between March, 1966, and June, 1985, 23 women and 12 men underwent partial or total resection of apical petrous or clivus meningiomas at The National Hospital for Nervous Diseases. Presenting symptoms were typically of long duration (mean 29 months) and consisted primarily of gait disturbance, headache, hearing loss, and facial pain. Cranial nerve deficits, especially affecting the fifth, seventh, and eighth nerves, were observed in nearly every patient. Tumor size, but not location, was generally associated with degree of preoperative disability. Plain skull films were usually unremarkable, but computerized tomography (CT) proved highly accurate in determining tumor location and size. A characteristic pattern of vascular displacement was seen on vertebral angiograms, although blood supply to the tumors was derived primarily from branches of the internal and external carotid arteries.
Subtotal or total resection was undertaken in all cases; nine patients required adjunctive cerebrospinal fluid shunting procedures. Although surgical techniques evolved during the course of the 20-year study, a combined supra- and infratentorial approach proved a relatively safe and effective means of surgical treatment. New or worsened postoperative deficits, especially cranial nerve palsies, and complications in the immediate postoperative period frequently resulted in temporary deterioration of the clinical status during this period; the total operative mortality rate was 9%. Follow-up periods ranged up to 9 years; 70% of patients resumed an independent existence, and none is known to have required subsequent tumor surgery. The size of the lesion was the only significant factor in determining outcome. These data suggest that meningiomas of the clivus and apical petrous bone can be accurately diagnosed by CT and three-vessel angiography, and effectively treated by microsurgical resection.
Marc R. Mayberg and Christian Zimmerman
✓ A 64-year-old man presented with symptoms of obstructive hydrocephalus secondary to a vein of Galen aneurysm associated with a dural arteriovenous malformation and straight sinus thrombosis. The interrelationship of these lesions and their clinical and radiological features are discussed. It is proposed that in this case sinus thrombosis was the primary event in the subsequent development of the other lesions.
Marc R. Mayberg
Marc R. Mayberg, Tomohisa Okada and Don H. Bark
✓ A porcine model was developed to allow quantitative assessment of morphological changes in cerebral arteries after subarachnoid hemorrhage and to determine the significance of structural changes in producing arterial narrowing. Whole blood was selectively applied to the middle cerebral artery (MCA) of seven pigs. After 10 days, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. The MCA's exposed to whole blood for 10 days showed prominent luminal narrowing associated with profound ultrastructural changes affecting all layers of the vessel wall. Morphometric analysis, however, demonstrated that significant reductions in the luminal cross-sectional area (−55.8% ± 12.5%, p < 0.005) and increases in radial wall thickness (75.1% ± 10.5%, p < 0.005) were associated with only minimal increase in the cross-sectional area of the vessel wall (12.5% ± 15%,p < 0.025). By stereological analysis, the volume density of individual components of the arterial wall was unchanged in MCA's exposed to blood. Vessels exposed to blood showed a 44% reduction in smooth-muscle cell immunoreactive actin and increased collagen in the extracellular matrix of the vessel wall. These data suggest that structural changes in cerebral arteries after subarachnoid hemorrhage do not directly contribute to vessel narrowing through increases in wall mass. Nevertheless, such changes may reflect pathological mechanisms which act to augment prolonged vasoconstriction or inhibit the maintenance of normal vascular tone.
Marc R. Mayberg, Tomohisa Okada and Don H. Bark
✓ A porcine model for subarachnoid hemorrhage has been developed to allow the selective application of blood and its components to cerebral arteries. Whole blood was centrifuged to produce two fractions consisting of washed erythrocytes (red blood cells, RBC's) and white blood cells (WBC) plus platelet-rich plasma (PRP); the RBC fraction was subsequently separated into hemoglobin (Hb)-containing cytosol and erythrocyte membranes. Each fraction was selectively applied to the middle cerebral artery (MCA) of pigs for 10 days; after which, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemical studies. By morphometric analysis, a marked reduction in the MCA lumen cross-sectional area was observed after selective application of RBC's or Hb/cytosol but not of WBC/PRP or erythrocyte membranes. In both RBC- and Hb/cytosol-treated vessels, luminal narrowing was associated with a differential increase in vessel wall thickness of the ventral (subarachnoid) compared to the dorsal (brain) aspect of the artery, but no significant change in cross-sectional area of the vessel wall. After 10 days of exposure to RBC's or Hb/cytosol, there was a spectrum of ultrastructural changes in the vessel wall comparable to those seen after periadventitial application of whole blood. Selective application of commercially available Hb to MCA produced similar structural and morphometric changes. The degree of luminal narrowing after exposure to whole blood or RBC's was proportional to the volume of the erythrocyte mass adjacent to the vessel at sacrifice. These data suggest that arterial narrowing after SAH is mediated by mechanisms related to prolonged exposure of the vessel wall to hemoglobin or its catabolites from lysing subarachnoid erythrocytes.
Narendra Nathoo, Marc R. Mayberg and Gene H. Barnett
✓ W. James Gardner, a skillful neurosurgeon and inventor, is best remembered for his cervical tongs and hydrodynamic theory of syringomyelia.
A pioneer of modern neurosurgery, Gardner trained under Charles Frazier in Philadelphia, and in 1929 he moved to Ohio where he became chief of neurosurgery at the Cleveland Clinic, a position he was to hold for the next 33 years. A large surgical practice made it imperative for Gardner to develop surgical methods that were quick, effective, and advantageous for patient and surgeon. He was an early proponent of the sitting position for patients undergoing cranial surgery, which led to the development of a neurosurgical chair with a head fixation device. To reduce the risks of hypotension and air embolism when the patient is in the sitting position, Gardner invented the clinical G suit. He was the first to advocate and use induced arterial hypotension for intracranial surgery and the first neurosurgeon in the US to publish his experiences performing lumbar discography. He converted an operating table so that he could induce hypothermia during aneurysm surgery and then applied pneumatic cuffs to occlude the major arterial supply to the brain. His pioneering work has been documented in many other areas such as hemifacial spasm and trigeminal neuralgia, for which he performed the first vascular decompression, in cervical sympathectomy for treatment of various ailments, and in the use of intrathecally delivered steroid drugs for sciatica. During his career, he authored 256 publications and one book on the dysraphic states. Many of his contributions to the discipline of neurosurgery are now taken for granted.
Marc R. Mayberg
Marc R. Mayberg, Eric LaPresto and Edwin J. Cunningham
Neuroendoscopic approaches to lesions of the central nervous system and spine are limited by the loss of stereoscopic vision and high-fidelity image quality inherent in the operating microscope. Image-guided endoscopy (IGE) and image-guided surgery (IGS) have the potential to overcome these limitations. The goal of this study was to evaluate IGE for its potential applications in neurosurgery.
To determine the feasibility of IGE, a rigid endoscope was tracked using an IGS system that provided navigational data for the endoscope tip and trajectory as well as a computer-generated, three-dimensional, virtual representation of the image provided by the endoscope.
The IGE procedure was successfully completed in 14 patients (nine with pituitary adenomas, one with a temporal cavernous malformation, and four with unruptured aneurysms). No complications could be attributed to the procedure. Compared with direct microscopy performed using anatomical landmarks, registration of the endoscope, and virtual image were highly accurate.
This procedure offers many potential advantages for central nervous system and spinal endoscopy. Advances in IGE may enable its application to regions outside the central nervous system as well.
Marc R. Mayberg, O. Wayne Houser and Thoralf M. Sundt Jr.
✓ Scanning electron microscopy of feline basilar arterial endothelium 4 hours and 1, 3, 5, and 7 days after subarachnoid hemorrhage (SAH) showed longitudinal furrows that correlated with angiographically demonstrated vasospasm. These ridges persisted after fixation at physiological pressure, and probably reflected medial contraction with undulation of the underlying elastic lamina. No change in endothelial cell morphology or thrombogenesis was observed as long as 7 days after SAH. There is no evidence from this study to suggest that ischemia from vasospasm is a product of thromboembolism from damaged endothelial surfaces.