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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.

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Nicholas T. Zervas, Theodore M. Liszczak, Marc R. Mayberg and Peter McL. Black

✓ Cerebral blood vessels are devoid of vasa vasorum. Therefore, the authors have studied the microarchitecture of the adventitia of large feline cerebral vessels and systemic vessels of the same size, in an effort to determine how the vessels are nourished. The cerebral vessels contain a rete vasorum in the adventitia that is permeable to large proteins and is in continuity with the subarachnoid space. This substructure may be analogous to the systemic vasa vasorum and may contribute to the nutrition of the cerebral arteries.

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Brian D. Beyerl, Robert G. Ojemann, Kenneth R. Davis, E. Tessa Hedley-Whyte and Marc R. Mayberg

✓ A case of cervical diastematomyelia in an adult is reported. The patient first noted sensory and motor symptoms at 34 years of age after two episodes of cervical trauma. Metrizamide computerized tomography myelography of the cervical spine and cord showed the region of diastematomyelia and revealed a spur containing both bone and fat tissue projecting into the spinal canal and cord. The spur arose from the laminae and spinous processes of C-2 and C-3, and was successfully excised. Postoperatively, the patient's deficits gradually improved. The literature concerning adult cervical diastematomyelia is reviewed.

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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.

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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.

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Matthew A. Howard III, Alan Gross, M. Sean Grady, Robert S. Langer, Edith Mathiowitz, H. Richard Winn and Marc R. Mayberg

✓ Pharmacological treatments directed at increasing cortical acetylcholine activity in patients with Alzheimer's disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to adequate amounts of drug. A new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using a polymeric drug delivery system. Microspheres of a polyanhydride sebacic acid copolymer were impregnated with bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run an eight-arm radial maze, after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 days. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similarly, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however, displayed significant improvement within 10 days after implantation; this improvement persisted for the duration of the experiment (p < 0.05, Student's t-test). Histological analysis of regional acetylcholinesterase staining showed widespread loss of activity throughout the hippocampus bilaterally in all animals. The microsphere implants were visible within the hippocampus, with minimal reactive changes in surrounding brain. It is concluded that intracerebral polymeric drug delivery successfully reversed lesion-induced memory deficits, and has potential as a neurosurgical treatment method for Alzheimer's disease and other neurodegenerative disorders.

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David W. Newell, Joseph M. Eskridge, Marc R. Mayberg, M. Sean Grady and H. Richard Winn

✓ Angioplasty of narrowed cerebral arteries was performed in 10 patients who became symptomatic from vasospasm following subarachnoid hemorrhage. This procedure was accomplished with a microballoon catheter via percutaneous transfemoral insertion. Patients were selected for treatment if they had delayed neurological deficits due to vasospasm which were not responsive to hypervolemic hypertensive therapy. Eight patients (80%) showed sustained improvement in neurological function following the procedure. In two patients transcranial Doppler ultrasound recordings were obtained which revealed decreased mean blood flow velocities following angioplasty. Two patients died, one from an aneurysmal rebleed, and one secondary to diffuse vasospasm. There was one case of delayed stroke 6 weeks following the procedure. The overall results of this series indicate that in selected cases percutaneous balloon angioplasty can offer marked improvement to patients with ischemic deficits due to vasospasm following subarachnoid hemorrhage.

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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.

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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.

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Robert C. Rostomily, Marc R. Mayberg, Joseph M. Eskridge, Robert Goodkin and H. Richard Winn

✓ Percutaneous transluminal angioplasty is commonly used for treatment of peripheral vascular disease, but only recently has it been applied to craniocervical lesions. The successful use of percutaneous transluminal angioplasty for treatment of an isolated high-grade stenosis of the petrous internal carotid artery is described in a patient with progressive ischemic symptoms despite maximum medical management. At his 2-year follow-up examination, the patient remained asymptomatic with angiographic evidence of progressive resolution of the stenotic lesion and indirect evidence of improved hemispheric blood flow ipsilateral to the lesion. Percutaneous transluminal angioplasty may provide an effective means of treatment for selective intracranial atherosclerotic stenosis.