Muscarinic cholinergic receptors on the endothelium of human cerebral arteries.

To characterize the muscarinic cholinergic receptors on the endothelium of human cerebral arteries, isometric tension measurement and receptor autoradiographic studies were performed. Acetylcholine (ACh) induced dose-dependent relaxation of human cerebral arteries precontracted by 10(-5) M serotonin, with an EC50 of 1.9 +/- 0.6 X 10(-6) M (n = 7). The relaxation was abolished by 10(-5) M hemoglobin. Autoradiography, using the muscarinic antagonist [3H]propylbenzilycholine mustard, demonstrated the high density of muscarinic cholinergic receptors on the endothelial cells of human cerebral arteries, especially on the luminal surface of the endothelium. These findings suggest that ACh-induced relaxation mediated by muscarinic cholinergic receptors on the endothelium has a physiological function in human cerebral arteries.

The TALON removable head frame system for stereotactic radiosurgery/radiotherapy: measurement of the repositioning accuracy.

PURPOSE: To present the TALON removable head frame system as an immobilization device for single-fraction intensity-modulated stereotactic radiosurgery (IMRS) and fractionated stereotactic intensity-modulated radiotherapy (FS-IMRT); and to evaluate the repositioning accuracy by measurement of anatomic landmark coordinates in repeated computed tomography (CT) examinations. METHODS AND MATERIALS: Nine patients treated by fractionated stereotactic intensity-modulated radiotherapy underwent repeated CTs during their treatment courses. We evaluated anatomic landmark coordinates in a total of 26 repeat CT data sets and respective x, y, and z shifts relative to their positions in the nine treatment-planning reference CTs. An iterative optimization algorithm was employed using a root mean square scoring function to determine the best-fit orientation of subsequent sets of anatomic landmark measurements relative to the original image set. This allowed for the calculation of the x, y, and z components of translation of the target isocenter for each repeat CT. In addition to absolute target isocenter translation, the magnitude (sum vector) of isocenter motion and the patient/target rotation about the three principal axes were calculated. RESULTS: Anatomic landmark analysis over a treatment course of 6 weeks revealed a mean target isocenter translation of 0.95 +/- 0.55, 0.58 +/- 0.46, and 0.51 +/- 0.38 mm in x, y, and z directions, respectively. The mean magnitude of isocenter translation was 1.38 +/- 0.48 mm. The 95% confidence interval ([CI], mean translation plus two standard deviations) for repeated isocenter setup accuracy over the 6-week period was 2.34 mm. Average rotations about the x, y, and z axes were 0.41 +/- 0.36, 0.29 +/- 0.25, and 0.18 +/- 0.15 degrees, respectively. Analysis of the accuracy of the first repeated setup control, representative of single-fraction stereotactic radiosurgery situations, resulted in a mean target isocenter translation in the x, y, and z directions of 0.52 +/- 0.38, 0.56 +/- 0.30, and 0.46 +/- 0.25 mm, respectively. The mean magnitude of isocenter translation was 0.99 +/- 0.28 mm. The 95% confidence interval for these radiosurgery situations was 1.55 mm. Average rotations at first repeated setup control about the x, y, and z axes were 0.24 +/- 0.19, 0.19 +/- 0.17, and 0.19 +/- 0.12 degrees, respectively. CONCLUSION: The TALON relocatable head frame was seen to be well suited for immobilization and repositioning of single-fraction stereotactic radiosurgery treatments. Because of its unique removable design, the system was also seen to provide excellent repeat immobilization and alignment for fractionated stereotactic applications. The exceptional accuracy for the single-fraction stereotactic radiosurgical application of the system was seen to deteriorate only slightly over a 6-week fractionated stereotactic treatment course.

A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage.

The pathogenesis of cerebral vasospasm occurring after subarachnoid hemorrhage (SAH) is unknown. Several lines of experimentation have suggested a free radical mechanism in the etiology of vasospasm. Iron is an important catalyst in the generation of free radicals and lipid peroxides in response to tissue injury. We hypothesize that the elaboration of iron from the subarachnoid clot might result in enhanced generation of free radicals and lipid peroxidation. If so, then treatment with deferoxamine, an iron-chelating compound, might reduce the formation of free radicals and thereby ameliorate vasospasm. This hypothesis was examined in a rabbit model of experimental cerebral vasospasm. New Zealand White rabbits were divided into the following experimental groups: control (normal) animals (n = 7), control animals treated with deferoxamine (n = 3), animals subjected to SAH and killed on Day 2 (n = 7), animals subjected to SAH on Day 2 and treated with deferoxamine (n = 9), animals subjected to SAH killed on Day 3 (n = 7), and animals subjected to SAH on Day 3 and treated with deferoxamine (n = 7). Deferoxamine treatment (50 mg/kg/8 hours) was begun 16 hours before the induction of SAH and continued until the animals were killed by perfusion fixation. The basilar artery caliber was assessed using morphometric techniques. The diameter of the basilar arteries in the control animals was 0.64 +/- 0.02 mm. Deferoxamine treatment alone did not alter the artery diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydromyelia complicating Apert's syndrome: a case report.

A 7-year-old boy with Apert's syndrome and hydrocephalus presented with scoliosis and lower extremity weakness. Neuroradiological evaluation demonstrated bony abnormalities involving the foramen magnum and a markedly hydromyelic spinal cord. Clinical improvement followed posterior fossa decompression and a myelotomy on the caudal conus medullaris. A possible role of the craniofacial anomaly in the pathogenesis of the hydromyelia is discussed.

The effect of nicardipine on vasospasm in rabbit basilar artery after subarachnoid hemorrhage.

This study was performed to examine the effect of the dihydropyridine calcium antagonist, nicardipine, on vasospasm after experimental subarachnoid hemorrhage (SAH) in the rabbit. The study was carried out in two parts: 1) effect of intravenous nicardipine (n = 45) and 2) effect of intracisternal nicardipine (n = 21). SAH was induced by injecting 5 ml of autologous arterial blood into the cisterna magna. In the intravenous study, there were five groups: 1) SAH without treatment; 2) SAH with vehicle (saline); 3) SAH and intravenous infusion of low-dose nicardipine (0.01 mg/kg/h); 4) SAH and intravenous infusion of high-dose nicardipine (0.15 mg/kg/h); and 5) controls without SAH. The intravenous infusions were started immediately after SAH and continued for 48 hours until death. In the intracisternal study, there were three groups: 1) SAH without treatment; 2) SAH with intracisternal administration of nicardipine (0.37 mg/h); and 3) controls without SAH. Intracisternal infusions were begun 70 hours after SAH and continued for 2 hours until death. After perfusion-fixation, the basilar artery was removed and processed for morphometric analysis. In the intravenous study, vessels from animals subjected to SAH were significantly narrowed when compared with controls, although after high-dose nicardipine vessel caliber was slightly larger than in the other SAH groups. Animals given intracisternal nicardipine showed a nonsignificant reduction of caliber as compared with controls: only 12% decrease in diameter and 22% decrease in luminal area. In the rabbit SAH model, nicardipine had a very modest effect on vasospasm at the doses tested.

An unusual case of the complete Currarino triad: case report, discussion of the literature and the embryogenic implications.

OBJECTIVE AND IMPORTANCE: We present and illustrate an unusual case of the complete familial Currarino triad (an association between a bony sacral defect, a presacral mass, and an anorectal malformation) in which the teratoma arose from the conus medullaris and contained mature neurons, glia, and branching ependymal canals that were in communication with a terminal syrinx. The embryogenic implications are discussed. CLINICAL PRESENTATION: The patient was a term neonate when discovered to have imperforate anus. Further workup revealed lumbosacral dysraphism with a presacral mass, a rectovaginal fistula, and a single pelvic kidney. The family pedigree revealed a familial transmission pattern; the patient had a second cousin with anal atresia and a first cousin with similar sacral anomalies. The motor level was L4 with trace L5, and there was absent sensation in the sacral dermatomes. INTERVENTION: A diverting colostomy was performed on Day 14, and the infant returned at 3 months of age to undergo near-total resection through the previous abdominal approach. Only a subtotal resection was possible because the mass arose from the low-lying conus and was firmly adherent to the sacral nerve roots and iliac vessel. Follow-up magnetic resonance imaging performed 18 months after surgery revealed that the residual tumor had not progressed. CONCLUSION: Complete Currarino triad is rare and is familial in half of the cases. The special features of the tumor in our case were the presence of mature neurons with ependymal canals and its origin from the conus. The possible embryogenesis may provide evidence that the caudal notochord is important for organized secondary neurulation.

An in vitro comparative study of conducting vessels and penetrating arterioles after experimental subarachnoid hemorrhage in the rabbit.

The reactivity of rabbit basilar artery and penetrating arteriolar microvessels was studied in vitro using an isometric-tension measurement technique and an isolated perfused arteriole preparation, respectively. Comparisons were made between reactivities of normal vessels and those obtained from animals subjected to experimental subarachnoid hemorrhage (SAH) 3 days prior to examination. Subarachnoid hemorrhage produced significant increases in basilar artery contraction in response to increasing concentrations of serotonin (5-hydroxytryptamine) (10(-9) to 10(-5) M) and prostaglandin F2 alpha (10(-9) to 10(-5) M) when compared to normal arteries. In addition, SAH attenuated the relaxing effect of acetylcholine following serotonin-induced contraction and of adenosine triphosphate after KCl-induced basilar artery contractions. In contrast to the changes observed in large arteries, cerebral microvessels did not demonstrate significant differences in spontaneous tone or in reactivity to a number of vasoactive stimuli including application of calcium, serotonin, and acetylcholine. On the other hand, small but significant changes in arteriolar responsiveness to changes in extraluminal pH and to application of KCl were noted. Findings from this study suggest that intracerebral resistance vessels of the cerebral microcirculation are not greatly affected by the presence of subarachnoid clot, in contrast to the large arteries in the basal subarachnoid space. The small changes that do occur are qualitatively different from those observed for large arteries. These findings are consistent with the observation of significant therapeutic benefit with the use of calcium channel blockers without changes in angiographically visible vasospasm in large vessels. It is likely, therefore, that calcium antagonists may act to decrease total cerebrovascular resistance at the level of the relatively unaffected microcirculation after SAH without changing large vessel diameter.

Whipple's disease presenting with isolated neurological symptoms. Case report.

Whipple's disease is infrequently considered in the differential diagnosis of patients presenting with progressive neurological deterioration. This is in part a result of the relative rarity of this entity and in part due to the more frequent initial presentation of the disease with gastrointestinal, musculoskeletal, or cardiovascular symptoms. A case is described in which the neurological symptoms of progressive dementia and weakness were seen in the relative absence of non-neurological symptomatology. The diagnosis of Whipple's disease was made from a brain biopsy. The neuropathology of Whipple's disease of the central nervous system is described and the importance of considering it as a treatable entity in the differential diagnosis of progressive neurological deterioration, despite the absence of systemic symptomatology, is stressed.

Effect of intracisternal antithrombin III on subarachnoid hemorrhage-induced arterial narrowing.

The ability of antithrombin III, an endogenous plasma glycoprotein, to reverse the arterial narrowing in a rabbit model of cerebral vasospasm was evaluated. The vasodilator activity of antithrombin III on rabbit arteries was first assessed in vitro using a myograph-arterial ring preparation. Antithrombin III (10 IU/ml) induced a 55.4% +/- 2.66% (mean +/- standard error of the mean) relaxation in basilar artery precontracted with serotonin (5-HT) in five specimens as compared with a 9.8% +/- 1.6% relaxation of common carotid artery in six specimens. For in vivo analysis, 21 New Zealand White male rabbits were separated into three groups: Group 1 served as normal controls; Group 2 received a subarachnoid blood injection (SAH) and were sacrificed on Day 3 thereafter; and Group 3 animals were subjected to SAH, then received a 2-hour intracisternal infusion of antithrombin III (100 IU) in saline prior to sacrifice on Day 3. Basilar artery caliber was determined using a morphometric method to analyze perfusion-fixed arterial segments. Control basilar artery diameter in Group 1 was 0.64 +/- 0.02 mm. In Group 2 a 27% reduction in arterial caliber to 0.47 +/- 0.03 mm was observed by Day 3 post SAH (p less than 0.0001). Group 3 animals had a mean basilar artery diameter of 0.68 +/- 0.02 mm. This was significantly larger than the untreated SAH rabbits in Group 2 (p less than 0.0001), but not different from control artery diameters in Group 1. The findings demonstrate that antithrombin III in saline has a significant ability to reverse delayed narrowing of the rabbit basilar artery after SAH.

Variants of sagittal synostosis: strategies for surgical correction.

Sagittal synostosis is discussed with respect to the variations seen with the deformity. The morphological spectrum ranging from marked frontal bossing to prominent occipital bulging is described. Surgical techniques have been specifically designed for these variants. These techniques provide an immediate correction of scaphocephaly, and achieve a reduction of the specific deformity with morbidity comparable to that associated with conventional operations. The lack of large areas of craniectomy and the avoidance of synthetic materials are cited as additional advantages of these techniques. The importance of altering the surgical approach to the specific clinical problem is underscored. Two illustrative cases of sagittal synostosis variants are described, and recent experience with the modified operative techniques in treating these and similar cases is discussed.

Subarachnoid hemorrhage inhibition of endothelium-derived relaxing factor in rabbit basilar artery.

Vascular contractions in response to KCl and serotonin (5-hydroxytryptamine, 5-HT) in rabbit basilar artery were studied in vitro using an isometric tension-measurement technique. Hemoglobin (10(-5)M) markedly augmented contractions induced by 5-HT (10(-9) to 10(-6)M) and slightly augmented those induced by KCl (20 to 80 mM) in arteries with intact endothelium. On the other hand, the augmentation induced by hemoglobin was almost abolished in arteries that were chemically denuded of endothelial cells by pretreatment with saponin. Since hemoglobin is known to be a selective inhibitor of endothelium-derived relaxing factor (EDRF), it is possible that the augmentation of contraction by hemoglobin in endothelium-intact arteries was mediated via an inhibition of spontaneously released EDRF. The effect of subarachnoid hemorrhage (SAH) on spontaneously released EDRF was investigated by injecting 5 ml of blood into the cisterna magna and sacrificing the rabbits 2 days later. Arteries after SAH showed a significant reduction in hemoglobin-induced augmentation compared to that seen in control arteries with intact endothelium. This result suggests that spontaneously released EDRF is significantly reduced after SAH. It is concluded that EDRF is released spontaneously in the rabbit basilar artery and that inhibition of its release might be involved in pathogenesis of cerebral vasospasm.

Pharmacological comparison of endothelium-dependent relaxation in isolated cerebral and extracerebral arteries.

Endothelium-dependent relaxation was induced by acetylcholine (ACh), adenosine triphosphate (ATP), and thrombin in isolated cerebral and extracerebral arteries obtained from rabbits and dogs. Using an isometric tension-recording method, the authors then examined the difference in the extent of relaxation between the cerebral and extracerebral arteries. In rabbits, the dose-response curve of the basilar artery for ACh was significantly different (p less than 0.05) from curves of the femoral and common carotid arteries. The IC50 value (the concentration inducing a one-half inhibition of the initial contractile tone) for the basilar artery in ACh-induced relaxation was significantly higher (p less than 0.05) than for the common carotid artery, although the mean maximum relaxation of the basilar artery to ACh was not significantly different from that seen in extracerebral arteries. The relaxing effect of ACh in dogs was much less in the middle cerebral and basilar arteries than in the common carotid, vertebral, and femoral arteries. On the other hand, both ATP (in rabbits and dogs) and thrombin (in dogs) induced significantly more (p less than 0.05) relaxation in the cerebral arteries than in the extracerebral arteries. Endothelium-dependent relaxation induced by ACh or ATP has been demonstrated in a wide range of arteries from a variety of animals. The present results suggest that ATP has a more important role than ACh in the regulation of the vascular tone of the major cerebral arteries in these two species.

Fulminant radiation-induced necrosis after stereotactic radiation therapy to the posterior fossa. Case report and review of the literature.

The problem of radiation-induced necrosis of normal brain surrounding the target area has been a major catalyst for the development of stereotactically focused radiation therapy. According to current opinion, the effects of stereotactic irradiation are confined to the region targeted. The authors present a case in which the administration of a conventional dose of stereotactically focused irradiation for treatment of a pilocytic astrocytoma produced fulminant necrosis that necessitated a combination of intensive surgical and medical management, after which the patient improved over the course of 1 year. Concomitant with his improvement, the initially remarkable findings on magnetic resonance imaging gradually resolved. In this presentation the authors emphasize the need to evaluate alternatives carefully before a decision is made to administer therapeutic irradiation. Furthermore, they explore the roles that target, host, and dosage factors play in hypersensitivity to radiation injury, the detection of these factors before treatment, and the administration of radioprotective agents. With the growing use of stereotactically focused irradiation as a primary treatment modality for a variety of neurosurgical conditions, it is important to be cognizant of its uncommon but potentially lethal side effects. A cooperative multicenter database in which the outcomes and morbidity following stereotactic irradiation are recorded is essential to the detection of relatively uncommon but severe complications such as those observed in this case.

Multiple-revolution spiral osteotomy for cranial reconstruction. Technical note.

Various combinations of cranial remodeling techniques are used in an attempt to provide optimal cosmetic results and to reduce possible sequelae associated with craniosynostosis. One element of deformity that is difficult to correct directly is an overly flattened area such as that found in the parietal area in sagittal synostosis, unilaterally in lambdoid synostosis, or even in severe positional molding. The authors present a novel application for recontouring cranial bone, namely the multiple-revolution spiral osteotomy. The advantages of this technique include the avoidance of large areas of craniectomy and immediate correction of the cranial deformity. The surgical procedure, illustrative cases, early results, and apparent benefits of this technique are discussed.

Intraoperative transligamentous ultrasound in the evaluation of thoracic intraspinal disease. Technique.

STUDY DESIGN: Intraoperative transligamentous ultrasonography was used in a variety of different thoracic surgical procedures for spinal cord compression secondary to neoplastic disease. OBJECTIVES: The utility and practicality of intraoperative transligamentous ultrasonography for thoracic intraspinal disease was evaluated. SUMMARY OF BACKGROUND DATA: Because intraoperative localization and evaluation of targeted levels in the thoracic spine using radiographs is often difficult or imprecise, alternative or complementary techniques may be helpful. Intraoperative transligamentous ultrasound, performed before laminectomy, via an interlaminar window, has not been widely used for thoracic intraspinal pathology. METHODS: A standard 7.5-MHz hand-held probe, used in conjunction with a Codman OR 330 ultrasound machine, was used to evaluate the practicality of intraoperative transligamentous ultrasound in the thoracic spine. RESULTS: A clear sonographic window, permitting visualization of the spine and the intraspinal contents, can frequently be found. However, densely calcified ligamentum flavum or overlapping laminas do not allow effective insonation. Four illustrative cases are presented. CONCLUSIONS: Transligamentous ultrasound before laminectomy can be used for localization and evaluation of intraspinal disease in many patients. Overlapping laminas or calcified ligamentum flavum can impede adequate sonographic visualization, but in these cases adequate intraoperative transligamentous ultrasound evaluation is usually possible through a small laminotomy. Evaluation of intraspinal lesions and localization of the correct surgical level is facilitated by dynamic real time sonographic imaging.

Biomechanical analysis of thoracolumbar interbody constructs. How important is the endplate?

STUDY DESIGN: A biomechanical study of human cadaveric thoracic vertebral bodies was conducted using several anterior fusion options subjected to axial loads. This study emphasized the contribution of the endplate to resistance of graft subsidence. OBJECTIVES: To determine the importance of the vertebral endplate in resisting subsidence of various constructs into the vertebral body; the relative efficacy of potential alternative graft constructs such as iliac crest, ribs, humerus, and titanium mesh cage; and the importance of bone mineral content, vertebral level, and cross-sectional graft area on construct subsidence. SUMMARY OF BACKGROUND DATA: As the fixation length of anterior and posterior spinal constructs is reduced, load sharing of the anterior column has become more important to reduce failure of the shorter devices. Several alternative graft constructs and surgical techniques have been used for reconstruction of the anterior column. There exist little comparative data as to whether any of these constructs are superior and whether the vertebral endplate contributes significantly to the integrity of the construct. METHODS: Sixty-three isolated human cadaveric vertebral bodies from T3 to T12 were used to test seven different constructs in direct axial load onto prepared endplates with an electrohydraulic testing device. These constructs were: 1) titanium mesh cage (17 x 22 mm) on intact endplate, 2) C-shaped humerus on intact endplate, 3) tricorticated iliac graft in "tee configuration" on intact endplate, 4) tricorticated iliac graft in cancellous trough, 5) triple rib strut graft, 6) single rib on endplate, and 7) single rib on cancellous body. Dual X-ray absorptiometry assessment of bone mineral content was performed. A uniaxial load was applied with force and displacement data collected to determine maximal load to "failure" of the vertebral body. RESULTS: Preservation of vertebral endplate did not significantly increase the resistance to graft subsidence. The titanium cage construct provided the greatest resistance to axial load. CONCLUSIONS: Preservation of the vertebral endplate may not offer a significant biomechanical advantage in reconstructing the anterior column. Several alternative constructs are mechanically equivalent.

The management of mild and moderate head injuries.

The majority of patients seeking medical care after head trauma have sustained injuries of mild or moderate severity, i.e., GCS scores of 13 to 15 or 9 to 12, respectively. Mortality rates under these circumstances are generally low; however, serious complications must be detected and treated early. The initial evaluation involves determination of level of consciousness and examination for the presence of focal neurologic deficits. Skull radiography has a limited role in the management of mild and moderate head injuries, but consideration must be given to local factors such as the availability of cranial CT. CT scanning is a safe, noninvasive, and generally cost-effective means of assessing patients at risk for developing intracranial complications. The role of MR imaging in evaluating minor head injuries is not yet established. Patients with an altered level of consciousness require hospitalization in essentially all cases. Selected patients with a GCS score of 15 also benefit from overnight hospitalization and observation. After mild and moderate head injury, significant neuropsychologic deficits are frequent, but are generally finite in their duration. Postconcussive symptoms are also generally self-limited. Although objective evidence suggests that structural brain damage results from mild injuries, the relationship between postconcussional symptoms and structural damage is unclear. Persistent postconcussional symptomatology probably arises from a combination of physiogenic and psychogenic causes. It is possible that early patient education and reassurance will reduce the incidence of prolonged postconcussional symptomatology.

Thoracolumbar spinal anatomy.

Management of disorders affecting the thoracolumbar spine is predicated on a thorough study of normal anatomy combined with a complete understanding of the ways in which forces act on these anatomic structures (i.e., spinal biomechanics). In this article, the authors review the anatomy of the thoracolumbar spine relevant to the management of disorders affecting the region. This discussion of anatomy is not intended to be exhaustive or definitive but rather to serve as an introductory discussion to consideration of surgical approaches and issues of patient management.

Classification and acute management of thoracolumbar fractures.

Successful management of traumatic injuries of the thoracolumbar spine requires understanding of the concepts of spinal stability and instability. There are numerous classifications of injury patterns based on fracture type and the probable forces involved. This article focuses on Denis's three-column theory of spinal stability and its utility in categorizing five injury patterns and the forces involved: specifically, wedge compression fractures, burst fractures, flexion distraction injuries, fracture dislocations, and miscellaneous injuries. The authors also highlight the acute management and evaluation of patients suspected to have these types of injuries.

Hearing improvement after conservative approach for large posterior fossa meningioma.

Hearing preservation during the posterior fossa surgery depends on many factors, including tumor size and site of origin. In many cases, regardless of the presumed tumor origin, the severity of the pure-tone loss or decline in speech discrimination on preoperative testing prompts the surgeon to choose a surgical approach (translabyrinthine or transcochlear) that negates the chance for postoperative functional hearing in the involved ear. We describe a 41-year-old woman with unilateral severe sensorineural hearing loss who experienced a remarkable recovery of hearing after combined retrolabyrinthine and retrosigmoid removal of a 4 cm petrous ridge meningioma using intraoperative cochlear monitoring. Despite the tumor size, early intraoperative loss of wave I and proximity of the tumor to the porus, complete tumor removal was accomplished with preservation of the cochleovestibular bundle. Three weeks postoperatively, the patient noted marked subjective improvement and speech audiometry demonstrated an improvement in word recognition, from 0% to 86%. This improvement has remained 1 year postoperatively, with no evidence of persistent tumor on repeat MRI scan. The case report illustrates the possibility of not just hearing preservation but improvement after removal of even large posterior fossa meningiomas that do not directly invade the cochlear nerve itself.