Preferential labeling of glial and meningial brain tumors with [2-(14)C]acetate.

UNLABELLED: Acetate is preferentially transported into and metabolized by astrocytes, rather than synaptosomes or neurons, and labeled acetate is used as a glial reporter molecule to assess glial metabolism and glial-neuronal interactions. Because monocarboxylic acid transporter specificity might confer a phenotype to help localize, detect, and characterize brain tumors of glial origin, use of [2-(14)C]acetate and [(14)C]deoxyglucose (a glucose analog metabolized by all brain cells) was compared in rat and human brain tumors. METHODS: Cultured C6 glioma or U-373 glioblastoma/astrocytoma tumor cells were injected into the caudate nucleus of anesthetized CDF Fisher rats; 2--3 wk later, an intravenous pulse of [2-(14)C]acetate or [(14)C]deoxyglucose was given, and timed blood samples were drawn during the 5- or 45-min experiment, respectively. Local (14)C levels in the brain were assayed by quantitative autoradiography, and acetate uptake or glucose use was calculated. Uptake and metabolism of the [(14)C]acetate was also assayed in C6 glioma and human surgical tumor samples in vitro. RESULTS: [(14)C]Acetate uptake into rat brain C6 tumors was 9.9 +/- 2.1 mL/100 g/min, compared with 3.9 +/- 1.0 mL/100 g/min in contralateral tissue (n = 6; P < 0.001), and was much higher than that into other brain structures (e.g., 5:1 for white matter and 2:1 for cortical gray matter). Glucose use in C6 tumors was 111 +/- 34 micromol/100 g/min, versus 81 +/- 5 micromol/100 g/min in contralateral tissue (n = 6; P = 0.08); no left-right differences in glucose use or acetate uptake were seen in other brain structures. The tumor-to-contralateral-tissue ratio for acetate (2.3 +/- 0.3) exceeded that for deoxyglucose (1.4 +/- 0.5) (P < 0.05), indicating that acetate is a sensitive C6 glioma marker. [(14)C]Acetate uptake also demarcated a few 3-wk-old C6 tumors that had unlabeled necrotic cores. U-373 tumors were smaller than C6 tumors in rat brain and were detected equally well with [(14)C]acetate and [(14)C]deoxyglucose. In vitro uptake of [(14)C]acetate into human glioblastoma or meningioma tumors was higher than uptake into pituitary adenoma. Rat C6 and human tumors with high uptake metabolized acetate to acidic compounds and amino acids. CONCLUSION: Tumor imaging with radiolabeled acetate can help to localize and classify brain tumors. Transporter and metabolic substrate specificity are traits that can be exploited further for in vivo imaging of brain glial tumors.

Histologic effects of collagen-filled interlocking detachable coils in the ablation of experimental aneurysms in swine.

PURPOSE: To assess the histologic changes produced by platinum microcoils with an inner core of cross-linked bovine collagen in experimentally induced aneurysms in swine, and to assess the feasibility of the system for the delivery of the collagen. METHODS: Bilateral pouch aneurysms were created in the side wall of the common carotid artery in seven barnyard pigs. Eight aneurysms were treated with coils designed with an interlocking detachment mechanism: in four of these, the coils had an inner core of collagen; in the other four, the platinum microcoils had a similar design but without the collagen mandrel. The packing density of the coils within the aneurysm was approximately the same for both types of coils. The other six aneurysms were left untreated and served as controls. Angiograms were obtained at the time of treatment (2 weeks after the aneurysms were created) and at 1, 4, and 8 weeks after treatment. All animals were killed 8 weeks after the treatment (10 weeks after the aneurysms were created). Arteries and aneurysms were resected en bloc and fixed for histopathologic study. RESULTS: The interlocking detachment mechanism worked well. Little difference was noted between the two types of coils in their ability to effect complete aneurysmal thrombosis (three of four aneurysms treated with collagen-core coils and two of four aneurysms treated with conventional coils). The collagen-core coils stimulated new collagen formation in areas proximal to the coils, and more fibroblasts were noted near the collagen-core coils than near the conventional coils. CONCLUSION: Local fibroblast proliferation and collagen production were stimulated by heterologous cross-linked collagen embedded in micro-coils in this experimental model. Such biologic stimulation holds promise for improving the endovascular cure rate of aneurysms in humans.

Combined pretemporal and endovascular approach to the cavernous sinus for the treatment of carotid-cavernous dural fistulae: technical case report.

OBJECTIVE AND IMPORTANCE: The endovascular treatment of carotid-cavernous dural fistulae is becoming the prominent treatment modality for these lesions. The intractability of these lesions and their tendency to recur, especially after previous endovascular treatment sessions, exhausts the available routes and tends to present a difficulty in accessing the cavernous sinus. To avoid the risks associated with a direct surgical approach, an alternative, less invasive route to the cavernous sinus using a pretemporal extradural approach is combined with a direct endovascular approach. CLINICAL PRESENTATION: A 38-year-old woman presented with a history of right visual and ocular symptoms related to a Type D cavernous carotid dural fistula, which was fed by internal carotid and external carotid branches. The fistula was initially treated with embolization of the external carotid arterial supply. After a transient improvement, the patient's visual acuity worsened. A follow-up angiogram showed the major supply from the intracavernous internal carotid branches and draining through the inferior ophthalmic vein. The transvenous route was not accessible. An attempt to cannulate the intracavernous branches was not successful. The combined pretemporal and endovascular approach was then used. INTERVENTION: The pretemporal extradural region of the superior orbital fissure was exposed. Using microsurgical techniques and Doppler flow guidance, the anterior cavernous sinus was cannulated through the orbital venous drainage channels. Using intraoperative angiography, thrombogenic coils were deployed at the level of the fistula. Intraoperative angiography confirmed complete obliteration of the fistula. CONCLUSION: The combined pretemporal (extradural) and endovascular approach to the cavernous sinus is a less invasive alternative for the treatment of intractable carotid-cavernous dural fistulae.

The arteries of the corpus callosum: a microsurgical anatomic study.

OBJECTIVE: The corpus callosum is the major commissural pathway connecting the hemispheres of the human brain. It is particularly important, because various tumors and vascular lesions can be located in and around the corpus callosum, and it is a route through which pass several surgical approaches. Performing accurate surgery in this region and avoiding damage to normal structures require that the neurosurgeon have adequate knowledge of the anatomy of the intricate blood supply to this area. METHODS: In 20 cadaver brains, the arteries of the corpus callosum were examined under the operating microscope, with particular attention to the origin, course, anastomoses, number, and caliber of the arteries. RESULTS: In all specimens, the pericallosal and posterior pericallosal arteries were found to be the main sources of blood supply to the corpus callosum. In 80% of the specimens, the anterior communicating artery gave rise to either a subcallosal artery or a median callosal artery, each of which made a substantial contribution to the blood supply of the corpus callosum. A detailed examination of the anatomic features of all the main arteries of supply revealed anastomoses within the callosal sulcus that formed the pericallosal pial plexus. This network supplied the corpus callosum, the radiation of the corpus callosum, and the cingulate gyrus. CONCLUSION: Familiarity with the details of the vascularity of the corpus callosum is crucial when performing surgery in this region. The additional, significant data described expands the knowledge of this anatomy, which can enhance the surgeon's ability to accomplish a more accurate and successful exploration.

Acquired mirror-image cerebellopontine angle arachnoid cysts: case report.

Arachnoid cysts are neurosurgical entities that have long been considered to be congenital in origin. Many examples in the literature suggest that there is a subgroup of arachnoid cysts that are required. The authors present the clinical history of a 17-month-old girl who developed two cerebellopontine angle arachnoid cysts after posterior fossa surgery for a brain tumor. After surgical excision of the tumor the child developed a left cerebellopontine angle cyst. This was treated through a suboccipital craniectomy by evacuating the cyst and excising the cyst wall. Two months later the child developed a second right-sided cerebellopontine angle cyst. It was treated by inserting a cystoperitoneal shunt. This article presents the case with radiological evidence of the acquired nature of the cysts. It also includes a brief review of the clinical presentation, pathogenesis, radiological evaluation, and surgical treatment of arachnoid cysts with emphasis on those occurring in the posterior fossa.

The blood supply of the intracavernous cranial nerves: an anatomic study.

Cranial nerve deficits are the most common complications of cavernous sinus surgery. Often the deficit occurs despite anatomic preservation of the nerve, and ischemic injury is thought to be the cause. A better understanding of the blood supply of these nerves may help to prevent such complications. The authors performed a cadaveric microsurgical study of the intracavernous cranial nerves and their blood supply in 20 cavernous sinuses. The oculomotor nerve received branches from the inferolateral trunk or its equivalent in all specimens (100%). The proximal trochlear nerve received branches from the inferolateral trunk in 80% of the specimens and from the tentorial artery of the meningohypophyseal trunk in 20%. The distal half was supplied by the branches from the inferolateral trunk only. In the region of Dorello's canal, the proximal third of the abducens nerve received branches from the dorsal clival artery of the meningohypophyseal trunk. The middle and distal thirds received branches from the inferolateral trunk. The ophthalmic and proximal maxillary segments of the trigeminal nerve received branches from the inferolateral trunk. The distal maxillary segment was supplied by the artery of the foramen rotundum. In the majority of cases, the medial third of the Gasserian ganglion received branches from both the inferolateral trunk and the tentorial artery. The middle third of the ganglion received branches from either the inferolateral trunk or the middle meningeal artery. Our findings indicate the important role the intracavernous branches of the internal carotid artery play in the blood supply of the intracavernous cranial nerves, and stress the need to preserve these branches to prevent or minimize postoperative deficits.

The microsurgical anatomy of the superior hypophyseal artery.

Interest in the anatomy of the proximal segment of the intracranial internal carotid artery has been kindled by the recognition that there are multiple potential sites of aneurysm formation in this region. These various aneurysm locations have characteristic hemodynamic and clinical features as well as surgical considerations. Recently recognized as a distinct clinical and anatomical entity are aneurysms that are hemodynamically related to the superior hypophyseal artery. Although aneurysms arising in proximity to the superior hypophyseal artery are not rare, the anatomy of this vessel arising from the medial or posteromedial aspect of the proximal internal carotid artery is poorly understood. We performed a cadaveric microsurgical anatomical study of 20 internal carotid arteries between the ophthalmic and posterior communicating arteries to develop a better understanding of the anatomical relationships of the superior hypophyseal artery. There were an average of 1.8 superior hypophyseal arteries arising from each carotid artery with an average diameter of 0.22 mm. The origin of the superior hypophyseal arteries was within 5 mm of the ophthalmic artery origin in 85% of the specimens. There were two distinct patterns of superior hypophyseal artery anatomy. In 42%, a large, dominant superior hypophyseal artery branched like a candelabra with smaller branches to the pituitary stalk, optic nerve, and chiasm. The average diameter of the larger branches was 0.3 mm. In the absence of a large dominant branch, two or three medial vessels were found. In one specimen, an incidental aneurysm was discovered at the origin of the superior hypophyseal artery on the medial aspect of the internal carotid artery at the origin of a large candelabra-like branch.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of epidermal growth factor receptor gene amplification and alteration in stereotactic biopsies of brain tumors.

In recent years, results from molecular-based investigations of central nervous system neoplasms have indicated that the occurrence of specific genetic alterations correlates with tumor malignancy and clinical behavior. One such example is epidermal growth factor receptor gene amplification and alteration in association with tumors histologically classified as glioblastoma multiforme. As our understanding of the implications of these changes develops, detection of epidermal growth factor receptor alteration and amplification may have diagnostic, prognostic, and ultimately, therapeutic value. The goal of this communication is to demonstrate the usefulness of stereotactic specimens for molecular genetic analysis, in this case, the analysis of the epidermal growth factor receptor gene for amplification and alterations. The techniques used here will maximize the number of cases from which useful information can be obtained. Properly adapted, the value of these techniques for expanding our understanding of these lesions is enormous.

Treatment of experimental aneurysms using collagen-coated microcoils.

Endovascular treatment of certain surgically difficult aneurysms is currently performed using fibered microcoils or electrolytically detachable microcoils to obliterate these lesions by forming an intra-aneurysmal thrombus. Unfortunately, this treatment option results in a significant incidence of incomplete obliteration of treated aneurysms. A thrombus can recanalize, resulting in further aneurysm growth and subsequent rupture. Nineteen aneurysms were surgically created in 10 pigs using jugular venous pouches. The aneurysms were allowed to mature for periods of 7 days to as long as 11 weeks prior to embolization. Fourteen remained patent for embolization. The aneurysms were then embolized (9 with collagen-coated microcoils, 5 with dacron-fibered platinum microcoils). Follow-up angiograms were obtained prior to sacrifice at 1, 3, 6, 9, and 12 weeks postembolization, and the embolized aneurysms and parent vessels were harvested for histopathological studies. The current study was designed to evaluate the potential efficacy of collagen-coated microcoils in providing an enduring therapy for aneurysms by comparing this new embolic device with the standard dacron-fibered platinum microcoils in a swine common carotid artery side wall aneurysm model. The aneurysms treated with collagen microcoils were completely obliterated with a collagen-rich fibrous scar with no histological evidence of residual thrombus or recanalization. Additionally, after treatment of experimental aneurysms with collagen microcoils, re-endothelialization across the former aneurysm neck was seen. In contrast, aneurysms embolized with dacron-fibered microcoils contained persistent thrombus surrounded by a relatively immature scar with residual aneurysmal lumen and lack of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

The suboccipital cavernous sinus.

The authors studied the microsurgical anatomy of the suboccipital region, concentrating on the third segment (V3) of the vertebral artery (VA), which extends from the transverse foramen of the axis to the dural penetration of the VA, paying particular attention to its loops, branches, supporting fibrous rings, adjacent nerves, and surrounding venous structures. Ten cadaver heads (20 sides) were fixed in formalin, their blood vessels were perfused with colored silicone rubber, and they were dissected under magnification. The authors subdivided the V3 into two parts, the horizontal (V3h) and the vertical (V3v), and studied the anatomical structures topographically, from the superficial to the deep tissues. In two additional specimens, serial histological sections were acquired through the V3 and its encircling elements to elucidate their cross-sectional anatomy. Measurements of surgically and clinically important features were obtained with the aid of an operating microscope. This study reveals an astonishing anatomical resemblance between the suboccipital complex and the cavernous sinus, as follows: venous cushioning; anatomical properties of the V3 and those of the petrous-cavernous internal carotid artery (ICA), namely their loops, branches, supporting fibrous rings, and periarterial autonomic neural plexus; adjacent nerves; and skull base locations. Likewise, a review of the literature showed a related embryological development and functional and pathological features, as well as similar transitional patterns in the arterial walls of the V3 and the petrous-cavernous ICA. Hence, due to its similarity to the cavernous sinus, this suboccipital complex is here named the "suboccipital cavernous sinus." Its role in physiological and pathological conditions as they pertain to various clinical and surgical implications is also discussed.

A role for telomeric and centromeric instability in the progression of chromosome aberrations in meningioma patients.

BACKGROUND: The primary chromosome aberration in meningiomas is monosomy or deletion of chromosome 22. Common secondary aberrations include losses or deletions of chromosomes 1p, 14q, and 10q and unstable chromosome aberrations including rings, dicentrics, and telomeric associations. Despite the analysis of several hundred tumors by cytogenetic and molecular techniques, the mechanisms involved in the progression of chromosome aberrations in meningioma remain poorly understood. METHODS: Sixty-seven meningiomas were cultured successfully using a short term in situ technique and harvested incorporating a high resolution G-banding technique with ethidium bromide. RESULTS: Twenty-six tumors (39%) showed normal karyotypes, whereas 41 tumors (61%) showed clonal chromosome aberrations. The most frequently observed aberration was the loss of chromosome 22 or structural aberrations involving 22q12, which occurred in 30 tumors (45%). The second most common aberrations were whole arm translocations involving the centromeric breakpoint at 1q10, resulting in the loss of the entire 1p chromosome in 12 tumors (18%). Two tumors showed a new, recurring, unbalanced, whole arm translocation der(1;2)(q10;q10). A third aberration, telomeric associations, were observed in 16 tumors (24%), occurring transiently in 11 tumors and recurring clonally in 5 tumors. Dicentric chromosome 22 was found in 7 tumors (10%), with the progressive loss of chromosome 22q material being found in 2 tumors. CONCLUSIONS: The chromosome instability demonstrated in the current series of tumors suggests that the progression of chromosome aberrations in meningioma is mediated in some respects by both telomeric and centromeric instability. These two types of instability may be early events in the progression of chromosome aberrations in meningioma and each can account for at least some of the loss of heterozygosity of chromosomes 22q and 1p detected by molecular analysis.

Bilateral persistent trigeminal arteries associated with cerebral aneurysms and aortic arch vessel anomaly.

We present the case of a patient with headache who, on computed tomography, was found to have subarachnoid hemorrhage. Angiography revealed bilateral persistent trigeminal arteries, anterior communicating artery and left pericallosal artery aneurysms, and an absent left vertebral artery. An anomalous right subclavian artery, originating at a common trunk with the left subclavian artery, was also present. To our knowledge, this is the fifth case of bilateral persistent trigeminal arteries and the sixth case of bilateral persistent carotid-basilar anastomosis of any type reported in the literature. A mechanism for the pathogenesis of multiple cerebrovascular anomalies is briefly discussed.