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  • Author or Editor: Marc Mayberg x
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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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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.

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Peter D. le Roux, David W. Newell, Joseph Eskridge, Marc R. Mayberg and H. Richard Winn

✓ The clinical success of angioplasty for symptomatic vasospasm following subarachnoid hemorrhage (SAH) depends on early intervention and can best be achieved after the aneurysm is occluded. However, patients presenting with unsecured ruptured aneurysms and established clinical vasospasm offer a dilemma for the surgeon. The authors describe the cases of five such patients who underwent acute clipping of aneurysms followed by immediate postoperative angioplasty between 1988 and 1992. All were referred at least 5 days after SAH. Severe vasospasm compatible with the clinical presentation was confirmed by angiography. The patients met the department's criteria for angioplasty but, because of unclipped aneurysms, were first taken to the operating room for a craniotomy and aneurysm obliteration. Angiography was repeated immediately after surgery. Arterial narrowing had progressed during surgery in two patients. In all patients, postoperative mechanical dilatation was achieved with the use of a silicone microballoon. Following angioplasty, transcranial Doppler ultrasound flow velocities and single-photon emission computerized tomography evaluation indicated improved cerebral perfusion compared to preoperative determinations. Four patients improved clinically and made a good recovery. In this subgroup of patients presenting with proven symptomatic vasospasm and an unclipped but ruptured aneurysm, urgent surgical obliteration of the aneurysm followed by immediate postoperative angioplasty may be a safe and reasonable means to improve outcome.

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Peter D. Le Roux, J. Paul Elliott, Lois Downey, David W. Newell, M. Sean Grady, Marc R. Mayberg, Joseph M. Eskridge and H. Richard Winn

✓ Several significant diagnostic and therapeutic advances in the management of subarachnoid hemorrhage have emerged during the last 10 years. The present study was undertaken to determine whether these advances have improved overall outcome in patients of low surgical risk and what factors predict outcome. The authors retrospectively reviewed the management of good-grade patients seen at the Harborview Medical Center at the University of Washington, who suffered ruptured anterior circulation aneurysms between 1983 and 1993. The results in this series demonstrate that favorable outcomes occurred in 96.8% of patients designated Hunt and Hess Grade I, 88.3% of those assigned Grade II, and 81.3% of those deemed Grade III after rupture of anterior circulation aneurysms. On the basis of clinical and radiographic factors present at admission, correct prediction can be made about all favorable, but only 17% of unfavorable outcomes. During the decade under investigation, the authors observed a significant (p = 0.002) increase in the number of favorable outcomes: 74.5% of patients treated during the first management period (1983–1987); 87% of patients treated during the second period (1987–1990); and 93.5% of patients treated during the third management period (1990–1993) experienced favorable outcomes. Improvements in critical-care techniques and the management of vasospasm may be associated with the improved outcome observed during this series.

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J. Paul Elliott, David W. Newell, Derek J. Lam, Joseph M. Eskridge, Colleen M. Douville, Peter D. LeRoux, David H. Lewis, Marc R. Mayberg, M. Sean Grady and H. Richard Winn

The authors used daily transcranial Doppler (TCD) evaluation to test the hypothesis that balloon angioplasty is superior to papaverine infusion for the treatment of proximal anterior circulation arterial vasospasm following subarachnoid hemorrhage (SAH). Between 1989 and 1995, 125 vasospastic distal internal carotid artery or proximal middle cerebral artery vessel segments were treated in 52 patients. Blood flow velocities of the involved vessels were assessed using TCD monitoring in relation to the day of treatment with balloon angioplasty or papaverine infusion. Balloon angioplasty and papavarine infusion cohorts were compared based on mean pretreatment velocity and mean posttreatment velocity at 24 and 48 hours using the one-tailed, paired-samples t-test. Balloon angioplasty alone was performed in 101 vessel segments (81%) in 39 patients (75%), whereas papaverine infusion alone was used in 24 vessel segments (19%) in 13 patients (25%). Although repeated treatment following balloon angioplasty was needed in only one vessel segment, repeated treatment following papaverine infusion was required in 10 vessel segments (42%) in six patients because of recurrent vasospasm (p < 0.001). Seven vessel segments (29%) with recurrent spasm following papaverine infusion were treated with balloon angioplasty. Although vessel segments treated with papaverine demonstrated a 20% mean decrease in blood flow velocity (p < 0.009) on posttreatment Day 1, velocities were not significantly lower than pretreatment levels by posttreatment Day 2 (p = 0.133). Balloon angioplasty resulted in a 45% mean decrease in velocity to a normal level following treatment (p < 0.001), which was sustained. The authors conclude that balloon angioplasty is superior to papaverine infusion for the permanent treatment of proximal anterior circulation vasospasm following aneurysmal SAH.

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J. Paul Elliott, David W. Newell, Derek J. Lam, Joseph M. Eskridge, Colleen M. Douville, Peter D. Le Roux, David H. Lewis, Marc R. Mayberg, M. Sean Grady and H. Richard Winn

Object. The purpose of this study was to test the hypothesis that balloon angioplasty is superior to papaverine infusion for the treatment of proximal anterior circulation arterial vasospasm following subarachnoid hemorrhage (SAH). Between 1989 and 1995, 125 vasospastic distal internal carotid artery or proximal middle cerebral artery vessel segments were treated in 52 patients.

Methods. Blood flow velocities of the involved vessels were assessed by using transcranial Doppler (TCD) monitoring in relation to the day of treatment with balloon angioplasty or papaverine infusion. Balloon angioplasty and papaverine infusion cohorts were compared based on mean pre- and posttreatment velocity at 24 and 48 hours using the one-tailed, paired-samples t-test. Balloon angioplasty alone was performed in 101 vessel segments (81%) in 39 patients (75%), whereas papaverine infusion alone was used in 24 vessel segments (19%) in 13 patients (25%). Although repeated treatment after balloon angioplasty was needed in only one vessel segment, repeated treatment following papaverine infusion was required in 10 vessel segments (42%) in six patients because of recurrent vasospasm (p < 0.001). Seven vessel segments (29%) with recurrent spasm following papaverine infusion were treated with balloon angioplasty. Although vessel segments treated with papaverine demonstrated a 20% mean decrease in blood flow velocity (p < 0.009) on posttreatment Day 1, velocities were not significantly lower than pretreatment levels by posttreatment Day 2 (p = 0.133). Balloon angioplasty resulted in a 45% mean decrease in velocity to a normal level following treatment (p < 0.001), a decrease that was sustained.

Conclusions. Balloon angioplasty is superior to papaverine infusion for the permanent treatment of proximal anterior circulation vasospasm following aneurysmal SAH.

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Gerald A. Grant, Robert R. Rostomily, D. Kyle Kim, Marc R. Mayberg, Donald Farrell, Anthony Avellino, Larry G. Duckert, George A. Gates and H. Richard Winn

Object. In this study the authors investigate delayed facial palsy (DFP), which is an underreported phenomenon after surgery for vestibular schwannoma (VS). The authors identified 15 (4.8%) patients from a consecutive series of 314 who underwent surgery for VS between 1988 and 2000, and in whom DFP developed. Delayed facial palsy was defined as a deterioration of facial nerve function from House—Brackmann Grades 1 or 2 more than 3 days postoperatively.

Methods. All patients underwent intraoperative neurophysiological monitoring of facial nerve function. The average latency of DFP was 10.9 days (range 4–30 days). In six patients (40%) minor deterioration (≤ two House—Brackmann grades) had occurred at a mean of 10.2 days postsurgery, whereas in nine patients (60%) moderate deterioration (≥ three House—Brackmann grades) had occurred at a mean of 11.8 days postoperatively. Five (33%) of 15 patients recovered to Grade 1 of 2 function within 6 weeks of DFP onset. Of the 15 patients with DFP, 14 had completed 1 year of follow up at the time of this study. Twelve (80%) of these 15 patients recovered to Grade 1 or 2 function within 3 months, and 13 (93%) of 14 patients recovered within 1 year. In all cases, stimulation of the seventh cranial nerve on completion of tumor resection revealed the nerve to be intact, both anatomically and functionally, to proximal and distal stimulation at 0.1 mA. A smaller tumor diameter correlated with greater recovery of facial nerve function. There was no correlation between the latency or severity of or recovery from DFP, and the patient's age or sex, the surgical approach, frequency of neurotonic seventh nerve discharges, anatomical relationship of the facial nerve to the tumor, patient's history of tobacco use, or cardiovascular disease.

Conclusions. It appears that DFP is an uncommon consequence of surgery for VS. Although excellent recovery of facial nerve function to its original postoperative status nearly always occurs after DFP, the magnitude and time course of the disorder were not predictors for subsequent recovery of facial nerve function.