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Purpose: Esthesioneuroblastoma is an uncommon malignancy of the head and neck for which there is no defined treatment protocol. The purpose of this study is to report our experience with the treatment and patterns of failure of this disease.Methods and Materials: From 1994 to 2012, 37 previously unreported patients with esthesioneuroblastoma were evaluated, and 32 eventually treated for cure at 2 academic medical centers. All patients were staged with Kadish criteria. The mean and median follow-ups were 96.1 and 76.5 months respectively (range 6-240 months).Results: The Kadish stage was A in 6 patients, B in 13 patients, and C in 13 patients. Four patients were initially treated with concurrent chemo-radiation therapy. Twenty-eight patients were treated with primary surgery. Two (2) underwent open medial maxillectomy and 26 underwent craniofacial resection (open - 17, endoscopic - 9). Three patients received curative surgical resection only. Seven patients failed either within the cranial axis or distantly, 6 of the 7 are dead of disease, 10-194 months following initial treatment. Six patients had isolated neck recurrences, 4/6 were salvaged with neck dissection and additional chemo-radiation and remain alive 30-194 months following initial treatment. Estimated overall survival rate at 10 years was 78% based on Kadish and T stages.Conclusion: In this retrospective analysis of 32 patients, Kadish stage C and stage T3/T4 tumors were associated with worse outcome. Total radiation dose of 60 Gy, margin status, patient age, were not found to have significant prognostic value. [ABSTRACT FROM AUTHOR]

The article discusses the use of abdominal free fat grafts for the improvement of cosmetic results and prevention of cerebrospinal fluid (CSF) leaks in supratentorial skull base surgery to address the temporal deformity caused by the wasting of the temporalis muscle. The authors found abdominal free fat to be able to provide a source of malleable, autologous material for enhancing cosmesis or supratentorial skull base closures, prevent CSF leaks, and with low incidence of infection.

The pathophysiology of malignant intracranial hypertension is a deleterious cycle of increased intracranial pressure, decreased tissue perfusion, declining intracellular energy production, increasing cellular edema, and subsequent increasing intracranial pressure. The use of decompressive craniectomy as a treatment to interdict this cycle, thereby improving outcome, remains controversial. Decompressive craniectomy offers an effective treatment for intracranial hypertension that is refractory to standard medical treatment. In traumatic brain injury, 2 randomized-controlled trials are underway to compare decompressive craniectomy to maximal medical management. In malignant infarction, recent randomized-controlled trials have demonstrated improved clinical outcomes in patients who underwent a decompressive craniectomy, but information on the optimal time-point remains under investigation. Definitive answers as to who will benefit, when to operate, and how the procedure is best carried out, remain as yet to be determined. [ABSTRACT FROM AUTHOR]

Hematoporphyrin derivative (Hpd) localizes selectively in malignant and rapidly metabolizing tissues and undergoes a cytotoxic reaction when exposed to light of a specific wavelength. Hpd has been studied extensively with regard to the diagnosis and treatment of tumors but not with regard to bactericidal activity. This investigation assessed the effect of light-activated Hpd on various microorganisms, on human polymorphonuclear leukocytes, and on the interactions of polymorphonuclear leukocytes and bacteria. Light-activated Hpd was 99.9% bactericidal against Staphylococcus aureus, Streptococcus faecalis, Bacteroides fragilis, Streptococcus M-G intermedius, Streptococcus mutans, Peptostreptococcus anaerobius, Peptococcus magnus, and Clostridium perfringens, but did not affect Escherichia coli, Pseudomonas aeruginosa, or Candida albicans. Photoactivation of Hpd rendered 98% of polymorphonuclear leukocytes inviable. Combinations of light-activated Hpd and polymorphonuclear leukocytes had a 4-log (99.99%) bactericidal effect on both intra- and extracellular S. aureus. The ability of Hpd to localize in inflammatory tissues may have therapeutic applications in the treatment of abscesses. [ABSTRACT FROM AUTHOR]

This article studies the case of a 72 year old Asian man was transferred to our institution for work-up of hyponatraemia and an intrasellar mass. The patient had been exposed to ill children and reported symptoms of upper respiratory tract infection a week before presentation. Lumbar puncture findings were normal. Computed tomography of the head done at that point showed a 2.1 cm sellar mass with suprasellar extension, elevating the optic chiasm. The neuro-ophthalamic evaluation revealed bitemporal visual field defects with no papilloedema.

Contract negotiation is a reality in the career of any neurosurgeon. However, little formal training exists for physicians - including neurosurgeons - on potential techniques and strategies for conducting meaningful contract negotiation. Increasing numbers of neurosurgeons seek hospital employment for which an employment contract will be provided. During contract negotiation, it is likely that a young neurosurgeon will be in discussion with an experienced negotiator acting on behalf of a hospital, practice, or department. Understanding and adapting to this imbalance in experience and using basic negotiating techniques as a means of approaching and resolving key contract issues is critical for the neurosurgeon to maximize his or her value in the course of contract negotiation. Even without formal training in negotiation in residency, negotiation skills can be taught, practiced, and improved. In affiliation with the Medical Director's Ad-Hoc Representational Section of Council of State Neurosurgical Societies (CSNS) this article is intended to serve as a practical guide for contract negotiation. Contract basics, negotiation terms, strategies, unique neurosurgical issues, and value creation are explored., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: Accurate placement of ventricular catheters decreases the incidence of proximal catheter failure. The use of a frameless, interactive neuronavigational system can optimize catheter placement., Methods: Thirty-four ventricular catheters were placed using a Medtronic electromagnetic frameless neuronavigational system (Medtronic Navigation, Inc., Louisville, CO) during a 12-month period. The patients ranged in age from 11 months to 79 years; the mean age was 40.8 years. Nineteen male and 12 female patients participated in the study. The indications for ventricular catheter placement included obstructive hydrocephalus, normal pressure hydrocephalus, pseudotumor cerebri, intrathecal therapy, and tumor cyst aspiration., Results: No proximal failures have been reported to date. One infection necessitated shunt removal. Three postoperative deaths occurred because of non-catheter-related events., Conclusion: Frameless neuronavigation in the placement of ventricular catheters assures accurate catheter placement, thereby decreasing the incidence of proximal catheter failure. The absence of rigid head fixation allows additional cohorts to benefit from the apparatus. The use of the electromagnetic system provides a safe, simple, and easy adjunct to optimal catheter placement.

We conducted a retrospective study of 51 cases of spontaneous transtemporal cerebrospinal fluid (CSF) leakage in 48 adults who had presented to our tertiary care academic referral center between July 1, 1988, and June 30, 2002. All patients had undergone high-resolution temporal bone computed tomography, and 26 patients had undergone magnetic resonance imaging. All patients were treated with a middle fossa craniotomy to repair the CSF fistulae. During a mean follow-up of 4.9 years, 46 of the 48 patients (95.8%) had experienced a complete cessation of CSF leakage (49 of 51 cases [96.1%]). The 2 patients whose leakage recurred were successfully managed with a subtotal petrosectomy with occlusion of the eustachian tube and obliteration of the middle ear and mastoid. No patient developed meningitis.

Background: Intracranial dural arteriovenous fistulas account for 10 to 15% of all intracranial arteriovenous malformations. Tentorial dural arteriovenous fistulas with spinal medullary venous drainage causing spinal cord myelopathy are very rare, but have been previously described. We describe a case using a cranio-orbito zygomatic approach with intraoperative angiography for the surgical treatment of a tentorial artery dural arteriovenous fistula causing spinal cord myelopathy., Case Presentation: A 42-year-old male presented complaining of a 1-year history of incoordination and dizziness and a 2-month history of progressive myelopathy with bowel and bladder incontinence. The patient had magnetic resonance imaging (MRI) performed along with cerebral and spinal angiography that revealed a right tentorial artery dural arteriovenous fistula with spinal medullary venous involvement down to T11. Angiographic embolization was attempted, but selective catheterization was unsuccessful. The patient underwent a cranio-orbito zygomatic approach with obliteration of the dural arteriovenous fistula. An intraoperative angiogram confirmed complete obliteration of the dural arteriovenous fistula., Conclusion: Intracranial dural arteriovenous fistulas are a rare cause of spinal cord myelopathy. When a patient presents with suspicion of spinal dural fistula and negative spinal angiography, an intracranial origin should be suspected and a cerebral angiogram performed. Skull base approaches along with intraoperative angiography provide an alternative modality for obliteration of the dural arteriovenous fistula nidus, thereby eliminating the venous congestion and hence the spinal cord ischemia.

The etiology, classification, clinical presentation, complications, and intravascular routes to image and treat carotid-cavernous fistulas percutaneously are described. Endoarterial and transvenous approaches (through the jugular, inferior petrosal, or cavernous veins) are discussed in relation to the etiology, size, and characteristics of the fistulas, as well as in relation to the planned therapeutic approach and its possible complications. Possible outcomes, with particular attention to the internal carotid circulation, side effects, and complications also are discussed in relation to etiology and type of fistula. Four exemplary cases are presented.

Transverse-sigmoid sinus dural arteriovenous malformations (DAVM) are uncommon vascular lesions for which complete cure may be difficult to obtain. A wide variety of treatments for these lesions include observation, arterial compression, surgical resection, and endovascular embolization. We propose that transverse-sigmoid sinus DAVM can be completely cured by occluding the ipsilateral dural sinus with detachable balloon and Guglielmi detachable coils (GDC) coils before arterial feeder embolization with histoacryl. Three patients who presented with pulsatile tinnitus and normal magnetic resonance imaging (MRI) studies underwent angiography, which demonstrated transverse-sigmoid sinus DAVM. All three patients wer treated with retrograde transvenous sinus embolization with complete occlusion of the transverse-sigmoid sinus with detachable balloons and GDC coils with preservation of the vein of Labbé. Subsequently, the various feeders from the external carotid artery were embolized. The tentorial arteries arising from the ipsilateral internal carotid arteries were not embolized in any of the cases, which were still contributing to the DAVM. Complete cure with thrombosis of the tentorial branch of the internal carotid artery (ICA) was seen on follow-up angiogram 1 day after embolization in one patient and on 4-week and 6-week follow-up angiograms in the other two patients. Complete occlusion of the transverse sinus proximal to the vein of Labbé, in spite of incomplete arterial feeder embolization, can result in complete cure of the transversesinus dural AVF if adequate time is given for the remaining feeders to occlude, once the fistula is obliterated.

Mastery of the three-dimensional anatomic relationships of the cranial base/paranasal sinuses is required to reduce the incidence of iatrogenic surgical complications, facilitate complete tumor extirpation, and enhance functional outcomes. Real-time intraoperative localization technology is one method available to assist the cranial base surgeon. We report our institutional experience with the StealthStationtrade mark treatment guidance platform. Eighty-eight consecutive patients with pathology of the cranial base/paranasal sinuses were operated on with the aid of real-time frameless stereotactic localization. Preoperative image data sets were acquired with either CT or MRI scans. Patient demographics, accuracy of the data sets, surgical approaches, pathology, complications, and further applications of this technology are presented. Procedures were performed on 47 women and 41 men ranging in age from 6 to 85 years. In these 88 procedures, 44 MRI and 44 CT scans with a mean accuracy of 1.57 and 1.23 mm, respectively, were used. Approaches to the cranial base included midface degloving (25), endoscopic (23), craniofacial (13), maxillectomy (12), rhinotomy without maxillectomy (5), transoral (5), pterional (2), transcondylar (1), and transcervical (2). Indications for surgery included severe inflammatory disease of the paranasal sinuses with epidural or subdoral abscess, or both (7), cerebrospinal fluid fistula or encephalocele, or both (11), and 40 benign and 30 malignant tumors. Complications occurred in 10 of 88 patients (11%). Real-time intraoperative localization can be applied to cranial base surgery in a variety of scenarios. The instantaneous transfer of imaging data to the surgical field is useful in localizing pathology, enhancing operative safety, and reducing morbidity, thereby improving outcomes. This technology will certainly play an integral role in minimizing complications and improving surgical outcomes as cranial base surgery moves into the next millennium.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer occurring in less than 10% of patients with thyroid cancer. Brain metastasis from MTC is exceedingly rare. Only six cases of brain metastasis from MTC have been reported in the literature and none had MTC as a part of multiple endocrine neoplasia (MEN) syndrome. We report a 42-year-old Caucasian male with MEN 2A who presented with neurological symptoms 25 years after total thyroidectomy with lymphadenectomy for MTC metastatic to local lymph nodes. A brain magnetic resonance imaging (MRI) showed a 4-cm cystic mass and a 1-cm nodule in the left frontal-parietal lobe in addition to a 0.8-cm cystic mass in the left frontal lobe and multiple tiny cerebellar metastatic lesions. Partial resection of the cerebral metastasis followed by whole brain radiotherapy resulted in resolution of the neurological symptoms. However, the patient had multiple systemic metastasis from the MTC and he died of systemic complications due to metastatic MTC. To our knowledge this is the first report of brain metastases from MTC in a patient with MEN 2A.

Background: The actual incidence of residual aneurysm after clipping is unknown. The natural history of residual aneurysm can be regrowth and hemorrhage. Intraoperative angiography offers a cost-effective, safe interdiction to the problem of residual aneurysm and parent vessel stenosis., Methods/results: Forty consecutive patients harboring 54 aneurysms underwent 42 operative procedures to clip 52 aneurysms, during which 220 intraoperative angiographic runs were performed. Ninety-three percent of the procedures were performed on patients with acute subarachnoid hemorrhage. There were 4 giant (>2.5 cm, 4/52 = 8%, all anterior circulation), 21 large (1.0-2.5 cm, 21/52 = 40%, 16/ 21 = 76% anterior circulation, 6/21 = 28% posterior circulation), and 27 small (<1.0 cm, 27/52-52%, 22/27 = 81% anterior circulation, 5/27 = 18% posterior circulation) aneurysms. Intraoperative angiography led to clip adjustment in 18/52 = 34% of aneurysms (4/18 = 22% for parent artery stenosis, 8/18 = 44% for residual aneurysm and 6/18 = 33% for both). Of the 18 adjustments made, 16 = 88% were made on giant or large aneurysms and two were small (one was a complex anterior communicating and one was a vertebral junction aneurysm). Follow-up angiography was performed on 26/42 = 62% of operative cases. Postoperative angiography confirmed intraoperative angiography in all cases. Two complications occurred during 220 angiographic runs: one embolic stroke and one incident of equipment failure., Conclusion: A grading scale was applied to test the relationship between anatomical site and size as they relate to the necessity for clip adjustment for complete aneurysm obliteration and/or parent artery compromise. Significance was related to site (basilar bifurcation, anterior communicating, middle cerebral bifurcation, and ophthalmic) and size (>1.0 cm), both as independent and codependent variables. An analysis of the cost-effectiveness of intraoperative angiography was demonstrated.

Abnormalities of the clivus/skull base occur most commonly as a result of disease spread from adjacent structures, but can also occur from primary involvement of the clivus. Traditionally, definitive diagnosis was made by CT guided biopsy or craniotomy. However, lesions can occur in this area that are not amenable to CT guided biopsy or craniotomy. Endoscopic transsphenoidal surgery can provide a safe method for obtaining a clival biopsy, debulking of tumor tissue, or definitive treatment without the morbidity and mortality of a craniotomy. This study was designed to describe our experience with the endoscopic approach to the skull base and clivus via the sphenoid sinus. A series of seven patients underwent endoscopic transsphenoidal biopsy of a sphenoid clival lesion. All patients avoided anticipated craniotomy, and definitive pathology was obtained in five of six patients. In two cases, excisional biopsy proved to be therapeutic. There were no deaths, and major complications included one CSF leak and one intraoperative hemorrhage, both of which were controlled immediately. The experience gained with these patients demonstrates the feasibility and safety of this new application of endoscopic sinus surgery for the diagnosis and possible treatment of lesions of the sphenoid and clivus.

The objective of this study is to determine the role of arachidonic acid (AA) in cell proliferation by inhibiting AA synthetic enzyme phospholipase A2 (PLA2) and to determine its involvement in the role of the second messenger intracellular calcium (Ca2+). Methods used to determine the effects on proliferation of cell cultures of primary meningioma and astrocytoma U373-MG included treatment with micromolar concentrations of PLA2 inhibitors 4-bromophenacylbromide and quinacrine. Effects of these drugs on proliferation were further investigated by the application of concentrations that inhibit growth by 50% while antagonizing these agents with AA replacement. Free cytosolic Ca2+ was measured with the use of fluorescent dye Fura-2 during PLA2 agonist/antagonist studies. These Ca2+ measurements were performed in the absence of extracellular Ca2+ to identify the contribution of intracellular Ca2+ sources. PLA2 inhibition resulted in decreased growth of cultured astrocytoma and meningioma cells in a dose-dependent manner in the micromolar range. This inhibitory effect was antagonized by the addition of AA. PLA2 inhibition caused an elevation of basal-cytosolic-free [Ca2+] while depleting internal Ca2+ stores. These Ca2+ changes were also antagonized by the addition of AA. In conclusion, these results demonstrate that AA, a PLA2 enzyme product, is involved in regulating the growth rate of these cell types. The PLA2 pathway also regulates the maintenance of the internal Ca2+ stores. Ca2+ is known to be a growth-related intracellular second messenger. These results suggest that the growth regulatory functions of AA are mediated by Ca2+-dependent mechanisms., (Copyright 1998 Academic Press.)

Cervical spondylosis is a disease that is often attributed to aging and considered the result of degenerative changes in the spine. The idea that there is a genetic predisposition to develop diseases of the skeletal elements of the spine has been discussed previously, but has never been proven conclusively. The authors report three cases of severe cervical spondylosis in patients who are first-degree relatives: a mother and her two sons. All three individuals had cervical disc herniations and stenosis at C3-4, C4-5, C5-6, and C6-7, and all three required decompressive procedures. The location and degree of cervical spondylosis were as similar among these three patients as they have been in identical twins reported in other studies. Such familial inheritance of cervical spondylosis has been reported only once. The existence of familial cervical spondylosis is not an unrealistic proposal because other studies have shown that genetics determines the shape of one's spine and that similar spines tend to degenerate in similar ways. Therefore, genetic counseling for a family such as the one reported here may prove to be of great benefit to warn siblings that they are at high risk for cervical spine injury. However rare it might be, familial cervical spondylosis may be a phenomenon that any spine surgeon should suspect in a family with cervical spine abnormalities found in several members.

Objective: Intimate to the application of lateral transtemporal approaches to the cranial base are the identification, manipulation, and/or the sacrifice of the venous anatomy of the inferolateral temporal lobe and the superior petrosal sinus and the transection of the tentorium. This study demonstrates the relationship and variability of the venous drainage of the lateral and inferior surfaces of the temporal lobe., Methods: Twenty-one specially prepared, injected cadaver specimens yielded 40 temporal lobes for examination. The venous systems in these specimens were traced from their origins on the temporal lobe (venous drainage complexes) to the transverse/petrosal sinuses, and the geometry of these venous complexes (venous configuration) was noted. The measurements of each complex's entry to the sinuses were noted., Results: Four distinct venous drainage complexes were identified: 1) the lateral complex, 2) the anteroinferior complex, 3) the medial-inferior complex, and 4) the posteroinferior complex. Three basic venous configurations were found: 1) the candelabra of veins uniting to form one large draining vein, 2) multiple independent draining veins, and 3) venous lakes running in the tentorium before entering the sinuses. The lateral complex, incorporating the classic "vein of Labbé," was present in 100% of the specimens. However, in the majority of cases, it did not represent the dominant venous drainage of the lateral and inferior surfaces of the temporal lobe., Conclusion: An understanding of the complexity and diversity of the venous drainage complexes and their configurations is necessary to avoid venous complications during lateral cranial base surgery.

Objective: To present four cases of life-threatening intracranial complications associated with temporal bone osteoradionecrosis., Study Design: This study was a retrospective case review of four patients combined with a literature review., Setting: All patients were treated at Loyola University Medical Center, which is a tertiary care facility., Patients: The four patients were retrospectively reviewed without demographic constraints., Interventions: All patients underwent preoperative radiographic assessment (magnetic resonance imaging/computed tomography scan), and three of the four patients underwent surgery., Main Outcome Measure: The role of surgical intervention in the management of advanced temporal bone osteoradionecrosis., Results: Three patients underwent mastoid surgery after medical treatment of intracranial complications associated with temporal bone osteoradionecrosis. All three patients had dry, epithelialized mastoid cavities. One patient died as a result of meningitis., Conclusions: Mastoid surgery should be used in the overall management of patients with advanced temporal bone osteoradionecrosis to prevent secondary intracranial complications.

Background: The development of frameless stereotaxis allows for repetitive intraoperative localization with millimeter accuracy. High-resolution computed tomographic (CT) angiography provides multiplanar, three-dimensional imaging of cerebral vascular lesions. The image data set generated during CT angiography can be used for localization in frameless stereotaxis when performed with appropriate fiducials in place., Methods: The feasibility of melding these two technologies was tested on a patient with a small (5 mm), distal ruptured posterior inferior cerebellar artery aneurysm, which was visualized by CT angiography and localized by frameless stereotaxis., Results: Visualization by CT angiography and intraoperative localization by frameless stereotaxis were successful., Conclusions: The practical application of this technology meld is demonstrated in this sample case. Applications to distal anterior cerebral artery aneurysms, abnormal flow-related aneurysms associated with arteriovenous malformations, and mycotic aneurysms are discussed.

Objective: The primary objective of this study is to present an alternative technique to closure of anterior cranial fossa cerebrospinal fluid (CSF) leaks. This study also serves to review our experience with our technique and presents some technical "tricks" we have learned through experience., Methods: The design of this study is a clinical chart review. The setting is an academic medical center., Results: Eight patients were referred for closure of postsurgical CSF leaks. Seven of eight patients underwent closure with one attempt and closure was achieved after a second attempt in one patient. Follow-up ranged from 1.5 to 4.0 years. There were no complications. No patient developed an acute or delayed episode of meningitis., Conclusion: The technique of endoscopic closure of a CSF leak is a safe and effective means for closure of a postsurgical anterior cranial fossa CSF fistula when performed by an experienced operator.

Lazaroids (or 21-aminosteroids) are potent lipid peroxidation inhibitors and are more potent antioxidants than steroids which have been shown to suppress tumor proliferation. The effects of two lazaroid compounds (U-75389G and U-83836E) were tested on the proliferation of a human brain astrocytoma cell line U-373MG. Both lazaroids had dose-dependent growth-inhibitory effects on the proliferation of U-373MG. For purposes of comparison, two steroids (methylprednisolone and dexamethasone) and a highly potent antioxidant (alpha-tocopherol) were tested under similar experimental conditions and were found to have antiproliferative effects as well, although at higher dose ranges. As cell growth-inhibitors, lazaroids are more effective than alpha-tocopherol while they are advantageous over glucocorticoids for their actions are devoid of the usual glucocorticoid side-effects.

The Decade of the Brain has brought recognition of the contributions neurological surgery has made to modern medicine, and neurological surgery training programs are a cornerstone of these achievements. While neurosurgeons are celebrating their achievements, however, a number of social, political, and administrative issues threaten to undermine the future of these programs. We discuss the ramifications of departmental status to the future of neurological surgery. These include the implications for operative experience-for example, carotid endarterectomy, spine instrumentation, acoustic tumors-the economic impact of a department versus a division, the ability to direct research, administrative input at the institutional level, and self-determination. We discuss the requirements for programmatic change and recommendations for national support.

We have previously reported that calcium channel antagonists can block both the growth of meningiomas in culture and the potent growth stimulation of meningioma cells by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). This study further defines the nature of this growth inhibition. Primary meningioma cultures were established, and cells were characterized. Fibroblast growth factor or insulin-like growth factor-I growth stimulation in the presence of calcium channel antagonists was examined. In addition, the effects of ethylene glycol-bis-(aminoethylether) N,N,N',N"-tetraacetic acid and Bay K 8644, a calcium channel agonist, on the growth factors were analyzed. Growth factor receptor immunohistochemistry was performed on the original tumors and the in vitro meningioma cells. Twelve of 17 (71%) meningiomas in this study were positive for the EGF receptor, and 14 of 17 (82%) were positive for the PDGF receptor. Five of six (83%) of the culture cells were positive for the EGF receptor, and four of five (80%) were positive for the PDGF receptor. Intracellular calcium changes were quantified using the intracellular calcium-chelating, fluorescent dye, Fura-2. The growth stimulation of fibroblast growth factor and insulin-like growth factor-I on meningioma cells in culture was decreased in a dose-dependent manner by calcium channel antagonists. The growth stimulation of fibroblast growth factor and insulin-like growth factor-I was not affected by a reduction of extracellular calcium, whereas the growth stimulation of EGF and PDGF was. Interestingly, intracellular calcium was not increased after exposure to growth factors but was increased after serum stimulation. This increase could be blocked by preincubation with verapamil. Calcium channel antagonists can inhibit proliferation of meningioma cells in culture after stimulation with a number of growth factors. These drugs might disrupt intracellular calcium homeostasis or interfere with key elements of the growth factor signal transduction pathways. These mechanisms as well as the potential clinical relevance of these findings are discussed.

Studies have shown that a majority of meningiomas contain receptors for platelet-derived growth factor and epidermal growth factor and that these growth factors promote the proliferation of meningioma cells in culture. Although the mechanism of action has not been elucidated, intracellular calcium appears to be part of the signal transduction mechanism. Because alterations in intracellular calcium could interrupt this pathway and decrease cellular proliferation, we investigated the effects of calcium channel-blocking agents on the growth of meningioma cells in vitro. Primary meningioma cell cultures were established, and the cells were characterized by light and electron microscopy and by immunohistochemical studies. Then, the cultures were given growth factors and/or various calcium channel antagonists, and growth rates were measured. A dose-response decrease in cell growth was seen when verapamil, nifedipine, or diltiazem (voltage-dependent calcium channel-blocking agents) was added to serum-containing media. Also, these drugs blocked the growth stimulation of epidermal growth factor and platelet-derived growth factor in a similar fashion. Dantrolene, which inhibits the release of sequestered intracellular calcium, was also an effective blocker of the mitogenic stimulation of these growth factors.

Large cranial defects (70 cm(2) or more) of complex geometric shapes (bifrontal or involving supraorbital ridges) that are associated with significant cutaneous contracture or soft tissue loss are challenging to reconstruct. We have treated 10 patients with complex cranial defects through a staged approach. Reconstructing the defect involved several steps. Before each surgery, we constructed a craniofacial prosthesis from polymethyl methacrylate to fit the patient's individual defect. When indicated, adjacent skin was expanded with a subcutaneous tissue expander. Finally, we carried out a cranioplasty and placed the prosthesis. Operative closure of the defect was facilitated by microplate and screw fixation with minimal prothesis contouring. Secure, vital, nontension skin closure was performed with the delayed, expanded local flap. Exposure to free polymer and exothermic reaction was avoided. Cosmetic results in these patients with high-volume, geometrically complex defects were excellent. No complications occurred, and the overall operative time was shortened.

The technical evolution of cranial base surgery has resulted in approaches that allow more radical surgical extirpation of complex cranial base lesions. Our service has extensively applied these cranial base approaches for lesions of the cranial base. A subgroup of 100 patients who had cranial base tumors involving potential manipulation or sacrifice of carotid arteries underwent 20-minute balloon test occlusions coordinated with vascular assessments consisting of a combination of the following: 1) four-vessel cerebral angiogram with compression studies; 2) occlusion transcranial Doppler ultrasonography; 3) occlusion single-photon emission computed tomography perfusion studies; and 4) xenon-133 cerebral blood flow studies. Transient neurological deficits associated with balloon test occlusion occurred in 7 of 100 patients (7%). Subsequently, 18 patients underwent permanent carotid occlusion by endovascular detachable balloons. Delayed ischemic complications (> 72 h) occurred in 4 of 18 (22%) patients. Additionally, a number of vascular complications not predicted by the balloon occlusion tests and vascular assessments were experienced. Repeat vascular assessments defined the causes and guided treatment of ischemic patients. Ischemic complications were caused by hemodynamic insufficiency, embolization, vasospasm, radiation vasculopathy, and venous anomaly. Our experience leads us to believe that no vascular assessment exists today that can predict the occurrence of vascular complications accurately. The current enthusiasm for cranial base surgery must be tempered with the sober reality that management of cerebrovascular anatomy and physiology remain significant limitations. Consideration of potential cerebrovascular complications is paramount to successful outcome and implementation of cranial base surgery.

The authors used skull base approaches to improve the surgical treatment of cerebral aneurysms. These approaches facilitate aneurysm surgery by allowing early proximal and distal vascular control, shortening and widening of the operative field, increasing the range of the surgeon's operative view and motion, and alleviating brain retraction. Twenty-two patients with ruptured giant or complex aneurysms were operated upon acutely using skull base approaches appropriate for their location: (1) the orbitocranial approach for anterior circulation, ophthalmic artery, and intracavernous lesions (n = 10); (2) the orbitozygomatic approach for aneurysms of the upper third of the basilar artery (n = 6); (3) the petrosal approach for aneurysms of the middle third of the basilar artery (n = 2); and (4) the far lateral-transcondylar approach for vertebrobasilar aneurysms (n = 4). Clipping and dissection of the aneurysms was facilitated by the skull base approaches. No surgical mortality occurred in this series of patients; transient cranial nerve paresis was the only morbidity related to the approaches. We compare the three-dimensional spatial geometry of skull base and conventional approaches, and discuss the advantages and nuances of skull base approaches.

Resection of skull base tumors may sometimes result in massive extirpation defects that are not amenable to local tissue closure. Closure of large basicranial defects can be performed with either a myocutaneous, a deepithelialized myocutaneous, or a simple muscle free flap designed from the ample rectus abdominis vascular territory. This free-tissue donor site has abundant and reliable well-vascularized tissue that can easily be customized to seal these tenuous areas. The rectus abdominis muscle and its vascularized territory were used in 18 of 19 consecutive patients at our center to close basicranial ablation defects. Of these, 6 were rectus abdominis muscle flaps, 5 were myocutaneous rectus abdominis flaps, and 7 were deepithelialized rectus abdominis muscle flaps. All free flaps survived. The intracranial space was sealed successfully in all but one patient. This patient underwent reconstruction with a muscle free flap and had a postoperative cerebrospinal fluid leak. This complication could have been avoided by using a deepithelialized myocutaneous flap to obliterate the central dead space with the vascularized subcutaneous fat. Two patients experienced minor wound infections, and one had a subdural abscess that was fully contained by a free flap placed over the duraplasty. One patient had a donor-site hernia. There was no incidence of meningitis. Knowledge of the anatomy of the vascular territory of the deep inferior epigastric vessels can be used judiciously to secure three-dimensional reconstruction of the skull base. The donor site supplies ample tissue for reconstruction and allows individual tailoring for obliteration of geometrically complex extirpation defects in and around the cranial base without the need to reposition the patient.

Photodynamic therapy is being studied as an adjuvant therapy for malignant gliomas. Therapeutic efficacy is based on photosensitizer uptake kinetics and the ability to deliver adequate light doses to an appropriate treatment volume at the optimal time. Our laboratory has developed an image-based, computer-assisted treatment-planning protocol to study the treatment variables leading to optimizing photodynamic therapy for intracranial neoplasms. Fifteen patients with recurrent malignant glial tumors underwent 16 treatments in the developmental phase of the project in which light treatment volume was progressively expanded. Group I (n = 4) received postresection intracavitary photoillumination only, Group II (n = 3) received limited interstitial/intracavitary photoillumination, and Group III (n = 9) received multiple interstitial/intracavitary photoillumination. Between 3 and 18 interstitial fiber probes were placed through optically lucent tumor access catheters. Computed three-dimensional image-based treatment planning provided reproducible data-based tumor volumes, treatment volumes, and stereotactic accuracy for tumor volume resection and interstitial light fiber insertion. Initial observations include: 1) treatment failures occur outside of the effective light treatment volumes; 2) effective light volumes can be expanded safely with multiple stereotactically implanted interstitial light fibers; and 3) optimal treatment involves individualized tailoring of light dose volume and geometry. This protocol allows standardized scientific study of the variables affecting the application of photodynamic therapy for intracranial neoplasms.

Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms. The efficacy of this therapy is based on the uptake of photosensitizer by neoplastic tissue, its clearance from surrounding brain tissue, and the timing and placement of photoactivating sources. Photofrin-II is the photosensitizer most actively being investigated. We labeled Photofrin-II with Indium-111 and studied the uptake and distribution of this agent in 20 patients with intracranial neoplasms, using single photon emission computed tomography (SPECT) with volume rendering in three dimensions. Of these patients, 16 had malignant glial tumors, 2 had metastatic deposits, 1 had a chordoma, and 1 had a meningioma. Anatomical-spatial data correlated well between the SPECT images and contrast-enhanced computed tomography or magnetic resonance images. Regions of focal uptake on SPECT images correlated with the surgical histopathological findings of the neoplasm. The kinetics of photosensitizer uptake varied according to the tumor's histological findings, the patient's use of steroids, and among patients with similar types of tumor histology. Peak ratios of target-to-nontarget tissue varied from 24 to 72 hours after injection. The study data show that, to be most effective, photodynamic therapy may need to be tailored for each patient by correlating SPECT images with anatomical data produced by computed tomography or magnetic resonance images. Photoactivating sources then can be placed, using computer-assisted stereotactics, to activate a prescribed volume of photosensitized tumor at the optimal time for treatment.

Resection of large skull base tumors may sometimes result in extirpation defects that are not amenable to local tissue closure. Patients with these tumors require free tissue transfer for closure of the intracranial space after basicranial tumor extirpation. The deep inferior epigastric artery supplies the rectus abdominis muscle and the skin and subcutaneous tissue of the lower abdomen. The closure of massive, central defects can be performed with a free flap designed from the ample rectus abdominis vascular territory. This free tissue donor site has abundant and reliable well-vascularized skin and subcutaneous tissue that can be customized to seal these tenuous areas and provide three-dimensional reconstruction. We have modified the rectus abdominis myocutaneous free flap in seven patients for reconstruction of the skull base. The subcutaneous fat was sculptured to form a soft, vascularized "cork" and was used for obliteration of the irregular deep portions of defects at the midcranial base against the repaired or unrepaired dura. All patients who had the vascularized fat used to obliterate the deep space had successful closure of the defect without cerebral spinal fluid leak. There were two wound infections and one donor-site hernia in this group. The judicious use of the vascular territory of the deep inferior epigastric vessels can accomplish secure three-dimensional reconstruction of the skull base. The flap can be reliably transferred, and the vascularized subcutaneous fat can be used to sequester and seal the dura repair.(ABSTRACT TRUNCATED AT 250 WORDS)

The medical community has not yet identified cerebrovascular pathophysiological factors that distinguish patients at high risk for stroke or aid in selecting patients for microvascular cerebral bypass. In this study, we describe the courses of 13 patients, all of whom suffered recurrent episodes of transient cerebral ischemia after previous cerebral infarction. These patients underwent regional cerebral blood flow studies using xenon inhalation with a CO2 challenge before and at various times after extracerebral-to-intracerebral microvascular anastomosis. Collateral circulation was assessed in all patients before surgery using four-vessel cerebral angiography. Patients were followed for a mean of 30 months (range, 1-7 yr) after the anastomosis. Measurements of mean cortical cerebral blood flow, as measured using the initial Slope Index, and CO2 cerebrovascular reactivity of these 13 patients were compared with those in a group of 20 patients designed as controls. Hemispheric cortical blood flow was significantly depressed in these patients before surgery compared with those in the control group (P less than 0.05). After the bypass, the mean resting Initial Slope Index in these patients increased 14% (P = 0.0005). Cerebral blood flow both before and after CO2 inhalation improved significantly in these patients after surgery (P = 0.001). Detectors bordering computed tomographic or magnetic resonance image documented infarctions, identified as peri-infarct regions, and demonstrated significant mean increases in both cerebral blood flow (38.8-43.2 ml/min/100 g, P = 0.05) and CO2 cerebrovascular reactivity in these patients after bypass (1.71 + 1.91% to 4.00 + 2.38% change Initial Slope Index/mm Hg CO2, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The complexity of missile injuries to the cervical spine has increased as the technology that causes these injuries has become more sophisticated. Management requires adaptation of conventional neurosurgical approaches to the cervical spine in an effort to limit neurological deficit and establish stability. We report an unusual case of a 19-year-old man who suffered transoral penetration of the cervical spine by an arrow released by a crossbow at close range.

Delayed cerebral ischemia is the major cause of death and disability in patients who initially survive an aneurysmal subarachnoid hemorrhage (SAH). In the present study, a protocol for prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) was utilized in the treatment of SAH, and the response of cerebral blood flow (CBF) was evaluated. Serial CBF measurements, f1 and CBF15, were performed using the xenon-133 inhalation technique to maximize therapy. Surgery within 24 hours of subarachnoid hemorrhage was preferred. In 43 patients with SAH, mean hemoglobin and hematocrit were lowered 3.0 +/- 0.3 g/dL and 8.9 +/- 0.5%, respectively, over the first 24 hours. Mean f1 and mean CBF15 over the same period increased 34.2 +/- 5.8% and 21.2 +/- 3.6%, respectively. The maximum mean increase in CBF was 47.2 +/- 4.7% for f1 and 30.1 +/- 3.2% for CBF15. Cerebral blood flow remained elevated during the 21 days after SAH, irrespective of neurological grade on admission, age, sex, or angiographic arterial narrowing. This is the first report of a consistent method for establishing sustained improvement in CBF after SAH. All patients managed in total compliance with the protocol remained neurologically stable or improved. Two patients developed delayed ischemia and infarction because of the inability to sustain protocol requirements. Thirty-six of the 43 patients (84%) were discharged capable of an independent lifestyle. Triple-H therapy is a safe and effective modality for elevating and sustaining CBF after SAH. In combination with early aneurysm surgery, it can minimize delayed cerebral ischemia and lead to an improved overall outcome.

The metabolism of 6,7-dihydroxy (catecholic)-1,2,3,4-tetrahydroisoquinolines (TIQs) is of interest because the heterocyclic substances may form in mammals normally or during certain disease via condensations of catecholamines (CAs) with aldehydes or alpha-keto acids. With a specific capillary gas chromatography procedure and confirmatory liquid chromatographic assays, we have determined the structural isomers and relative amounts of mono-O-methylated (phenolic) TIQ metabolites in several rat brain regions 40 min following the acute intracerebroventricular injection of four structurally related catecholic TIQs. In sharp contrast with the established selective m-O-methylation of dopamine (DA) by catechol-O-methyltransferase in brain, the two simple TIQs derived from DA produced predominantly or even exclusively the metabolic isomer arising from methylation of the original p-hydroxyl group (7-O-methylation). In three catecholaminergic brain regions examined, the 7-O-methyl isomer was the only detectable phenolic metabolite of (+/-) salsolinol-1-carboxylic acid (a condensation product of DA and pyruvic acid) and, as first noted by Bail et al. (1980), constituted 95% of the two possible isomeric mono-O-methyl metabolites of (+/-) salsolinol (TIQ derivative of DA and acetaldehyde). Though less, the 7-O-methyl isomers still were a significant proportion (40-55%) of the two mono-O-methylated metabolites of (+/-) 4-hydroxy-desmethylsalsolinol (a TIQ derived from norepinephrine and formaldehyde), or of the DOPA/acetaldehyde-derived TIQ, (cis) salsolinol-3-carboxylic acid. In the time frame of the study, all four administered TIQs showed higher levels in hypothalamus than in striatum or hippocampus, with the two carboxylated alkaloids displaying the greatest differences.(ABSTRACT TRUNCATED AT 250 WORDS)