Strategies, techniques, and approaches for dural arteriovenous malformations of the posterior dural sinuses.
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Cerebral Angiography↗
Biomedical subjects
T M Sundt
Publications and source records attributed to T M Sundt.
Surgery for supratentorial arteriovenous malformations.
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Adolescent↗
Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen.
The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful induction of chimerism and donor-specific transplantation tolerance required pretreatment of recipients with monoclonal antibodies (mAbs) against NK1.1, Thy-1.2, CD4 and CD8, followed by administration of 3 Gy whole body radiation (WBI), 7 Gy thymic irradiation, and infusion of T cell-depleted rat bone marrow cells (BMC). Rat cells appeared among peripheral blood lymphocytes (PBL) of such recipients by 2-3 wk, and rat T cells by 2-5 wk following bone marrow transplantation (BMT). Donor-type rat skin grafts placed 4 mo after BMT were accepted, while simultaneously placed non-donor-type rat skin grafts were promptly rejected. In addition to its clinical potential, the ability to induce donor-specific tolerance across xenogeneic barriers using such a nonlethal preparative regimen provides a valuable model for the study of mechanisms of xenogeneic transplantation tolerance.
Animals↗
The effect of carbon dioxide on the diameter of brain capillaries.
Cerebral capillaries in cats subjected to variations in carbon dioxide tensions were studied using carbon black perfusion fixation. Five animals each were grouped into hypocapnia, normocapnia, and hypercapnia and 500 cortical, 250 white matter and 250 caudate nucleus capillaries per group were analyzed at 400 x magnification. Capillary diameters were found to change significantly in the cortex (6.1-10.0 microns), white matter (6.5-9.6 microns) and caudate nucleus (6.3-8.8 microns) from hypocapnia to hypercapnia, respectively. These findings suggest that capillary vasomotion occurs and that capillaries are not rigid tubes as previously portrayed.
Animals↗
Transplantation in miniature swine: analysis of graft-infiltrating lymphocytes provides evidence for local suppression.
Previous studies from this laboratory have demonstrated that swine tolerant of class I disparate renal allografts show peripheral antidonor cellular reactivity which can be augmented by skin grafting. To assess the possibility of local suppression, cell-mediated lymphocytotoxicity of graft-infiltrating lymphocytes was compared to that of peripheral blood lymphocytes from three tolerant and four acutely rejecting recipients of class I--disparate renal allografts. Mixed lymphocyte cultures using peripheral blood lymphocytes or graft-infiltrating lymphocytes and an equal number of irradiated peripheral blood lymphocyte stimulators were incubated for 6 days and tested in a 6-hr 51Cr release assay. Graft-infiltrating lymphocytes from rejecting animals had potent antidonor cell-mediated lymphocytotoxic activity with or without in vitro stimulation. Anti-third-party reactivity was seen with appropriate stimulation, suggesting heterogeneity of graft-infiltrating lymphocyte cultures. Peripheral blood lymphocytes from rejectors generated donor-specific cell-mediated lymphocytotoxicity. Graft-infiltrating lymphocytes from tolerant animals generated no antidonor cell-mediated lymphocytotoxicity with or without in vitro stimulation, but generated an anti-third-party response. Peripheral blood lymphocytes from tolerant animals displayed both antidonor and anti-third-party reactivity with appropriate in vitro stimulation. These data support the hypothesis that local suppression may contribute significantly to maintenance of tolerance to class I disparate renal allografts in miniature swine.
Animals↗
Prospective study of the effectiveness and durability of carotid endarterectomy.
In a series of 252 consecutive patients who underwent 282 carotid endarterectomies, we conducted clinical and angiographic follow-up for 2 to 6 years (mean, 3.2 years). Digital subtraction angiography (DSA) was done postoperatively in 95% of cases. Clinical follow-up was achieved in 97% of cases, and DSA follow-up was obtained in 66% of cases. The overall group had a 1% operative minor morbidity (three cases of minimal new neurologic deficit), no major morbidity, and a 0.7% mortality (one death from stroke and one from myocardial infarction). Complications correlated well with the patient's preoperative risk category. During follow-up, 10 minor strokes, only 1 of which was attributable to the reconstructed artery, and 10 transient ischemic attacks, 3 of which were presumably related to recurrent stenosis, occurred. Asymptomatic mild to moderate restenosis of the internal carotid or common carotid artery was identified in 10% of follow-up DSAs and severe stenosis or occlusion in 3%. Stenosis in the opposite common carotid or internal carotid artery progressed in 48 cases (26% of follow-up DSAs and ultrasound studies), and 10 of these became symptomatic. An actuarial analysis of patients who had endarterectomy indicated that the cumulative probability of ipsilateral stroke was 1.5% at 1 month and 2% at 5 years. The cumulative probability of ipsilateral stroke, transient ischemic attack, or reversible ischemic neurologic deficit was 4% at 1 month and 8% at 5 years or less than 1% per year after the first month, with censoring at the time of the second surgical procedure.
Actuarial Analysis↗
The novel dihydronaphthyridine Ca2+ channel blocker CI-951 improves CBF, brain pHi, and EEG recovery in focal cerebral ischemia.
The effects of the novel dihydronaphthyridine Ca2+ antagonist CI-951 on focal cerebral ischemia were assessed during MCA occlusion in 30 white New Zealand rabbits under 1.0% halothane anesthesia. In vivo brain pHi and focal CBF were measured with umbelliferone fluorescence. Baseline normocapnic brain pHi and CBF were 7.02 +/- 0.02 and 48.4 +/- 2.9 ml/100 g/min, respectively. In the severe ischemic regions, 15 min postocclusion brain pHi and CBF were 6.62 +/- 0.04 and 14.4 +/- 0.7 ml/100 g/min in controls vs. 6.60 +/- 0.02 and 12.9 +/- 2.3 ml/100 g/min, respectively, in animals destined to receive CI-951. Twenty minutes after MCA occlusion, CI-951 was administered at 0.5 microgram/kg/min and brain pHi and CBF were determined in both regions of severe and moderate ischemia for 4 h postocclusion. Control severe ischemic sites demonstrated no significant improvement in brain pHi and only mild increases in CBF over the next 4 h. CI-951 caused significant improvement in both of these parameters. Postocclusion 4 h brain pHi and CBF measured 6.69 +/- 0.04 and 18.5 +/- 3.2 ml/100 g/min in controls vs. 7.01 +/- 0.04 and 41.7 +/- 5.3 ml/100 g/min, respectively, in CI-951 animals (p less than 0.001). Similar improvements were observed in moderate ischemic sites. In animals that demonstrated postocclusion EEG attenuation, 75% of CI-951 animals had EEG recovery as compared to 18% in controls. CI-951 may be a useful therapeutic agent for focal cerebral ischemia if histological and outcome studies verify these data.
Animals↗
In vivo treatment with antiporcine T cell antibodies.
The effects of in vivo administration of monoclonal antibodies directed against the two major mature T cell subsets of miniature swine have been examined. Antibody 76-2-11, specific for the porcine CD8 cell-surface antigen, caused elimination of CD8+ T cells from the peripheral lymphocyte pool by 4-6 days following a single intravenous infusion. This depletion persisted while excess antibody was detectable in the serum and CD8+ cells returned rapidly to normal levels following the disappearance of serum antibody. In vitro functional assays performed on PBL during the period of depletion showed no effect on proliferative responses but a profound inhibition of ability to generate CTL. In contrast, administration of monoclonal antibody 74-12-4, specific for CD4+ porcine T lymphocytes, caused no consistent change in the level of CD4+ cells in the peripheral lymphocyte pool. By flow microfluorometry, CD4+ peripheral lymphocytes were found to be coated with the antibody, and there also was excess antibody in the serum for at least 4 days in two of the three animals treated. No effects on in vitro proliferative responses or generation of CTL in vitro were observed, even during the period of excess circulating antibody. Treatment with both antibodies was tolerated well by all animals. These findings are similar to those that have been found in clinical studies of monoclonal antibody treatment and suggest that the pig will provide a large animal preclinical model in which the effects of in vivo treatment with monoclonal antibodies on parameters of transplantation immunity can be tested.
Animals↗
Influence of intraoperative antibiotic choice on the incidence of early postcraniotomy seizures.
Because of a suspicion that intraoperative penicillin antibiotics might be causing early postoperative seizures in craniotomy patients, a deliberate effort was initiated in 1987 to avoid these agents in favor of nonpenicillin antibiotics. This permitted a retrospective comparison of the incidence of early postoperative seizures in craniotomy patients who did and who did not receive intraoperative penicillins. Records of patients treated between July 1, 1984, and July 1, 1985, and between July 1, 1987, and July 1, 1988, were reviewed, for a total of 1316 procedures. There were no seizures in the 323 patients who underwent suboccipital craniectomy. However, among the 993 patients receiving supratentorial procedures there were 30 with seizures within the first 6 hours postoperatively, 19 of which were generalized seizures. The incidence of early seizures was 4.7% (20 cases) of the 427 patients given penicillins and only 1.8% (10 cases) of the 566 not given penicillins (p less than 0.01). Since patients undergoing surgery for intractable seizures have a high incidence of early postoperative seizures (11 of 92 in this series, or 12%), creation of a subgroup eliminated these from consideration but did not alter the relationship of penicillins to early seizures (p less than 0.02). The authors conclude that intraoperative (and early postoperative) penicillin antibiotic administration should be avoided, if possible, in patients undergoing craniotomy for supratentorial pathology.
Anti-Bacterial Agents↗
Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients.
The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified.
Animals↗
A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat.
A model of a carotid-jugular fistula in the rat was created such that the arterial feeding vessel is derived from the intracranial arterial circulation and the venous drainage communicates with a major intracranial venous drainage system. This fistula was created in 28 rats on the right side with an additional 11 rats designed as controls with a right carotid ligation and 6 rats without previous surgery. After 12 weeks convalescence, 6 rats with a carotid-jugular fistula and 6 rats without previous surgery underwent cerebral angiography. All fistulae were patent and the model was verified. All of the 33 remaining rats underwent regional cerebral blood flow (rCBF) determination by [14C]iodoantipyrine autoradiography under barbiturate anesthesia. Of the rats with the fistula, 11 had this fistula obliterated 5 min prior to rCBF determination ('closed' group) while 11 had rCBFs determined with the fistula ('open' group). The rCBF was measured from each hemisphere from 7 anatomical regions. The rCBF in the control animals ranged from a median of 82 to 112 ml/100 g/min, in the 'open fistula' group 46 to 68 ml/100 g/min, and in the 'closed' group 118 to 187 ml/100 g/min. This experimental model stimulates the pathophysiologic perturbations in the parenchyma induced by cerebral arteriovenous malformations. It supports the findings that non-infarctional hypoperfusion can result from arteriovenous malformations and that following extirpation of arteriovenous malformations hyperemia may ensue.
Animals↗
Blue nevus and nevus of Ota associated with dural melanoma.
A 41-year-old woman with a complex congenital nevus that possessed features of both a blue nevus and a nevus of Ota is described. She was found to have melanotic hyperpigmentation of the underlying subcutaneous tissue and dura mater. Two separate melanomas developed in the tissues underlying her nevus (one in the subcutaneous tissue and another intracranially, arising from the dura).
Adult↗
The case against staged operative resection of cerebral arteriovenous malformations.
Three cases of large cerebral arteriovenous fistulae are presented in which surgical ablation was complicated by brain swelling from hyperperfusion breakthrough believed to be caused by acute intraoperative hypoperfusion superimposed on chronic preoperative hypoperfusion. On the basis of these cases, experimental data, and theoretical considerations, we seriously question the wisdom of using staged surgical resection of cerebral arteriovenous malformation to prevent complications related to alterations in cerebral hemodynamics. The reasons for this concern are: the repeated occurrence of acute-on-chronic hypoperfusion during staged resection; a lack of understanding of the time course for the correction of a disordered autoregulation; risk of hemorrhage between the initial and final resection; difficulty in assessing and substantiating flow reduction after subtotal resection; the rapidity of collateralization; the divergence of flow from large, readily accessible feeding arteries to deep penetrating vessels; and attenuation of the wall thickness in collateral vessels as a consequence of increased flow.
Adult↗
The effects of hyperventilation on cerebral blood flow in the rat with an open and closed carotid-jugular fistula.
Perturbations in cerebral hemodynamics at the time of ablation of an arteriovenous shunt have been regarded as important in the pathogenesis of swelling and hemorrhage complicating resection of arteriovenous malformations (AVMs). A carotid-jugular fistula model in the rat had previously been investigated and found to simulate in part the nonhemorrhagic pathophysiology of a large cerebral arteriovenous fistula. Utilizing this model and measuring cerebral blood flow in 14 regions with a [14C]iodoantipyrine autoradiographic technique, the effects of hypocapnea on the cerebral circulation in opened and closed fistulas were investigated. Regional cerebral blood flow (rCBF) in control animals ranged from a median of 53 to 64 ml/100 g/min at a partial arterial carbon dioxide pressure (PaCO2) of 28 +/- 2 mm Hg and 85 to 112 ml/100 g/min at a PaCO2 of 40 +/- 5 mm Hg. In animals with an open carotid-jugular fistula created 12 weeks before the study, these median rCBF values at comparable PaCO2 levels ranged, respectively, from 15 to 39 ml/100 g/min and 50 to 68 ml/100 g/min (the 25th percentile for the open fistula in the hypocapneic group was 15 ml/100 g/min in 5 of the 14 regions studied). In contrast, median rCBF in the closed fistula group ranged from 73 to 100 ml/100 g/min in hypocapneic animals and from 118 to 187 ml/100 g/min in normocapneic animals. These results demonstrate the preservation of CO2 reactivity; hypoperfusion in the presence of a carotid-jugular fistula, hyperemia on fistula occlusion, and the potential to induce cerebral ischemia with hyperventilation in this model of a cerebral arteriovenous fistula.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Arterio-inferior sagittal sinus fistulae: case report.
The management of the case of a 9-year-old boy with progressive cognitive impairment due to arteriovenous fistulae at the apex of the inferior sagittal sinus is reported. This represents a unique location for an extraparenchymal deep central arteriovenous malformation. The patient underwent staged ablation of the lesion by surgery. The postoperative course was complicated by expansion of an aneurysmal vein of Galen undergoing thrombosis and hyperperfusion syndrome, but the patient ultimately made a satisfactory recovery.
Arteriovenous Fistula↗
Improvement of cortical perfusion, intracellular pH, and electrocorticography by nimodipine during transient focal cerebral ischemia.
The alterations in metabolism and cerebral blood flow that occur following transient focal ischemia were studied in rabbits anesthetized with halothane and subjected to transient occlusion of an M2 segment of the middle cerebral artery (MCA). The parameters measured included intracellular brain pH and focal cortical blood flow (fCBF)--assessed by the umbelliferone technique--electrocorticograms, and cortical microcirculatory changes. A gradient of ischemia developed in the cortex between the patent and occluded vessels. Cortical sites with moderate and severely diminished flow were examined as a function of time before and after occlusion. Mean preocclusion fCBF was 50.8 +/- 2.1 ml/100 g/min, and brain pH was 6.99 +/- 0.04. Following occlusion, fCBF fell to 14.6 +/- 2.3 ml/100 g/min, with an intracellular pH of 6.53 +/- 0.03 in sites of severe ischemia in the territory of the occluded vessel. Sites between the patent and occluded branches revealed moderate changes in fCBF and intracellular pH of 26.7 +/- 3.6 ml/100 g/min and 6.74 +/- 0.03 ml/100 g/min, respectively. Sites adjacent to the patent M2 branch remained similar to baseline. Pretreatment intravenously with nimodipine, a dihydropyridine class of Ca2+ channel antagonist, improved flow in the territory of the occluded segment of the middle cerebral artery to 30.6 +/- 2.2 ml/100 g/min, while maintaining the brain pH at 6.83 +/- 0.03. Similarly, at sites intermediate between the patent and occluded M2 segments of the MCA, cortical blood flow remained at 53.5 +/- 4.0 ml/100 g/min, and the pH at 6.95 +/- 0.04, in 10 animals pretreated with nimodopine.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Radiation-associated atheromatous disease of the cervical carotid artery: report of seven cases and review of the literature.
The natural history of postirradiation extracranial cerebrovascular disease is uncertain. Previous reported cases spanning 20 years of carotid surgery are difficult to evaluate, because patients may sometimes have unspecified symptoms, physical examinations, postoperative results, and follow-up. Also, the evolution of carotid surgery over the past two decades makes it impossible to compare earlier operative technique with the state-of-the-art technique of today. Our series of 7 patients underwent 9 carotid endarterectomies with an average follow-up period of 46 months. The number of patients is small, and although technically this is a more difficult operation, we feel the results are favorable and may be comparable with endarteerctomy procedures in nonirradiated patients. These patients should be approached as if radiation changes are not a major factor when they are considered for reconstructive arterial surgery.
Aged↗
Normal perfusion pressure breakthrough complicating surgery for the vein of Galen malformation: report of three cases.
Three cases are described of infants who developed malignant brain swelling (and in one case hemorrhage) after surgery for vein of Galen malformations. The cause for the brain swelling was felt to be due to hyperperfusion, or the "normal perfusion pressure breakthrough" syndrome. Although well-described for cerebral parenchymal arteriovenous malformations, cases of this complication occurring in vein of Galen malformations have not previously been reported. It is concluded from these cases that infants with large arteriovenous shunts, as attested by cardiac failure and cerebral atrophy, have an increased risk of developing this complication.
Brain Edema↗