p53 mutations in nonastrocytic human brain tumors.

Genomic DNA from 51 primary human brain tumors was screened for the presence of mutations in the tumor suppressor gene, p53, using the polymerase chain reaction and single strand conformation polymorphism analysis, followed by direct DNA sequencing. Mutations leading to an amino acid change were found in 2 of 17 (12%) oligodendrogliomas and 2 of 19 (11%) medulloblastomas but none of 15 ependymomas. Sites of mutations were in exon 5 (codon 141), exon 6 (codon 193 and 213), and exon 7 (codon 246). In addition, there were silent mutations in exon 6 (codon 213) in one oligodendroglioma and in one ependymoma. This study points to the possible role of the p53 tumor suppressor gene in some central nervous system neoplasms of divergent histogenesis.

Suprasellar neoplasm with a granular cell component.

A classification of granular cell lesions of neuropathologic interest is presented along with an unique case in which a suprasellar neoplasm having light and electron microscopic features of a meningioma contained multifocal nests of granular cells which apparently persisted in this tumor over a period of nearly five years. A spectrum of cell differentiation suggested the development of granular cells from small, electron-dense mesenchymal elements having numerous mitochondria. No evidence for a Schwann cell origin was found. It is proposed that the pituitary-hypothalamic axis, where intracranial granular cell nests and granular cell tumors are most common may also give origin to rare mixed neoplasms with a granular cell component.

Brain tumors: detection of B-cell stimulatory factor-2/interleukin-6 in the absence of oligoclonal bands of immunoglobulins.

24 patients with neoplasia of the central nervous system (CNS-N) were investigated for the presence of B-cell stimulatory factor-2/interleukin-6 (IL-6) in the cerebrospinal fluid (CSF). Whereas IL-6 was detected in 21 (88%) of these CSF samples, only 6% of CSF from non-inflammatory brain diseases and 12% of the samples from multiple sclerosis patients were positive. IL-6 was found in both primary and secondary CNS-N. The presence of IL-6, a cytokine which activates B-lymphocytes to produce high-rate immunoglobulin (Ig) synthesis, is in contrast to the ineffective intrathecal B-cell activation as suggested by the failure to detect oligoclonal bands of Igs in CNS-N.

A legacy of microneurosurgery: memoirs, lessons, and axioms.

This article is written at the request of the editor. It contains my autobiographical sketch, professional memories, lessons, axioms, and reflections on the present problems in neurodiagnosis and neurotherapy. The combination of microsurgical techniques, the bipolar coagulation technique, the concept of arachnoidal exploration, and the concept of segmental and compartmental occurrence of vascular and neoplastic lesions of the central nervous system, with their predilection sites, allowed microneurosurgery to gradually unfold and proceed within the last 30 years as a continuation of conventional neurosurgical principles established by the founder generation. Today, the lesions in each region of the central nervous system can be accessed without using computer-assisted targeting and navigation technology and can be selectively eliminated ("pure lesionectomy") with acceptable outcomes; the mortality and morbidity rates have been reduced remarkably. Further scientific and technological advances will promote the ongoing evolution in neurodiagnosis and neurotherapy. Competitive neurospecialties are welcomed in the interest of patients, medical sciences, and surgical advances. The younger generation of neurosurgeons will have spent more time in laboratory training, deepening their knowledge of neuroanatomy and gaining experience in surgical techniques. The achievements, limits, and problems of neurosurgery in relation to technology, medical and surgical standards, and controversial treatment options have been presented thoroughly in numerous professional publications. However, the relationship of neurosurgery to the evolution of integral neurophysiology and biochemistry has hitherto been inadequately evaluated. The advances in microbiology, anesthesiology, and topographic neurology have been viewed as essential components of neurosurgery's foundations. A critical analysis proves that this is only partially true. The turning point in the development from craniospinal surgery to physiological neurosurgery began with the research of Th. Kocher, V. Horsley, H. Cushing, and W. Dandy concerning the importance of the cerebrospinal fluid system. This was the first step in a trend toward integral neurophysiology, which initiated neurosurgical procedures on a routine basis. The intensive research on the hypothalamus by R.W. Hess and associates led to intensified studies on the autoregulated integral functional units of the central nervous system ("dynamic homeostasis," in the words of W.B. Cannon). This slowly developing but exciting history of neurophysiology requires patient study to seek out solutions for the present difficulties in neurodiagnosis and neurotherapy, which constitute a similar situation to that encountered by the pioneer surgeons at the end of the last century. In pertinent sections, my personal opinions relating to observations and experiences with a large number of operated patients with vascular and neoplastic lesions are presented. The predilection sites of brain tumors in the neopallial and paleopallial (limbic-paralimbic) areas and brainstem, and their expansive but usually not infiltrative growth, are discussed and documented. The current hypothesis of infiltrative growth of gliomas is opposed. The microsurgical technique for the treatment of various types of lesions is summarized. The principal microsurgical instruments and apparatus are presented with some remarks relating to their conception and manufacture.

Results of microsurgical extra-intracranial arterial bypass in the treatment of cerebral ischemia.

The authors report the operative and follow-up results (3 months to 9 years) of 86 consecutive extra-intracranial bypass operations on 84 patients with cerebral ischemia, emphasizing both the prophylactic role of the operation in preventing further catastrophic cerebral ischemia, and the low morbidity and mortality of the operation.

Brain vascularization by transplanted omentum: a possible treatment of cerebral ischemia.

The authors report their experience with experimental brain vascularization with the use of transplanted omentum majus. The possibility of treating cerebral ischemia with this method is discussed.

Is there a superior occipitofrontal fasciculus? A microsurgical anatomic study.

OBJECTIVE: Using a fiber-dissection technique, our aim was to expose and study the myelinated fiber bundles of the brain to achieve a clearer conception of their configurations and locations. During the course of our study, the superior occipitofrontal fasciculus became the focus of our interest. Many publications have defined this as a bundle of association fibers, located between the corpus callosum and the caudate nucleus, that connects the frontal and occipital lobes. By examining this area using fiber dissection, we realized that the descriptions of the anatomy are inadequate; thus, we focused on the elucidation of the anatomic structures of this region and, in particular, that known as the superior occipitofrontal fasciculus. METHODS: Twenty previously frozen, formalin-fixed human brains were dissected under the operating microscope using the fiber-dissection technique. RESULTS: On coronal sections of the brain, a structure on the superolateral aspect of the caudate nucleus usually has been identified as the superior occipitofrontal fasciculus. However, our fiber dissections revealed that this structure is the superior thalamic peduncle, that it is composed of projection fibers rather than association fibers, and that it does not interconnect the occipital and frontal lobes. CONCLUSION: The structures of the brain are better understood when the fiber-dissection technique is used to explore their configurations and locations. The resulting information is especially beneficial for planning strategies and tactics of neurosurgical procedures.

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.

Microneurosurgical treatment of intracranial dermoid and epidermoid tumors.

Forty-three patients with intracranial, intradural dermoid (8) and epidermoid (35) tumors underwent radical surgical resection utilizing strict microneurosurgical technique. The average age was 37.3 years for the patients with epidermoid tumors and 36.2 years for the patients with dermoid tumors. The male to female ratio was 3:2 for the epidermoid group and 3:1 for the dermoid group. Common clinical presentations included cerebellar dysfunction, cranial nerve impairment, and seizures. Typically, computed tomography scans revealed the epidermoid tumors (30 cases studied) as nonhomogeneous hypodense lesions with irregular borders and without contrast enhancement. The dermoid tumors (7 cases studied) had a similar appearance, but with a wider range of attenuation values. Magnetic resonance imaging findings for the epidermoid tumors (6 cases studied) consisted of increased T1 and increased T2 relaxation times. Supratentorial tumors were excised by the pterional (frontosphenotemporal) approach, mesencephalic tumors by either a supratentorial posterior interhemispheric transtentorial approach or an infratentorial/supracerebellar method, and posterior fossa tumors by either a medially or laterally positioned suboccipital osteoplastic craniotomy. One epidermoid tumor and one dermoid tumor were considered to be subtotally resected because of dense adherences left attached to vital structures; the remaining 41 tumors were completely excised. The most frequent complications were aseptic/chemical meningitis and transient cranial nerve palsies. There were no perioperative deaths. Mean follow-up was 5.2 years. Eighty-six percent of patients reported good to excellent results. No patient had experienced symptomatic or radiographic evidence of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Fiber dissection technique: lateral aspect of the brain.

OBJECTIVE: The fiber dissection technique involves peeling away the white matter tracts of the brain to display its three-dimensional anatomic organization. Early anatomists demonstrated many tracts and fasciculi of the brain using this technique. The complexities of the preparation of the brain and the execution of fiber dissection have led to the neglect of this method, particularly since the development of the microtome and histological techniques. Nevertheless, the fiber dissection technique is a very relevant and reliable method for neurosurgeons to study the details of brain anatomic features. METHODS: Twenty previously frozen, formalin-fixed human brains were dissected from the lateral surface to the medial surface, using the operating microscope. Each stage of the process is described. The primary dissection tools were handmade, thin, wooden spatulas with tips of various sizes. RESULTS: We exposed and studied the myelinated fiber bundles of the brain and acquired a comprehensive understanding of their configurations and locations. CONCLUSION: The complex structures of the brain can be more clearly defined and understood when the fiber dissection technique is used. This knowledge can be incorporated into the preoperative planning process and applied to surgical strategies. Fiber dissection is time-consuming and complex, but it greatly adds to our knowledge of brain anatomic features and thus helps improve the quality of microneurosurgery. Because other anatomic techniques fail to provide a true understanding of the complex internal structures of the brain, the reestablishment of fiber dissection of white matter as a standard study method is recommended.

Conservative treatment of patients with acoustic tumors.

Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 +/- 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 +/- 0.4 mm the 1st year, and 1.9 +/- 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 +/- 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate determined during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 +/- 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 +/- 3.4 mm vs. 21.3 +/- 0.9 mm, P less than 0.05), and a faster 1-year growth rate (7.9 +/- 2.3 mm/y vs. 1.3 +/- 0.3 mm/y, P less than 0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracranial venous hypertension and the effects of venous outflow obstruction in a rat model of arteriovenous fistula.

A model of rat arteriovenous fistula (AVF) was created using a proximal common carotid artery to distal external jugular vein anastomosis. Anatomical dissections revealed that the external jugular vein is the primary vessel draining intracranial venous blood. Physiological measurements were made with the AVF open and closed, and during venous outflow occlusion of the contralateral external jugular vein. Opening the AVF increased torcular pressure from 6.5 +/- 0.6 to 13.5 +/- 1.1 mm Hg and decreased mean arterial pressure from 82.7 +/- 1.8 to 62.8 +/- 1.8 mm Hg (both P less than .05), decreasing cerebral perfusion pressure from 76.2 +/- 1.7 to 49.3 +/- 2.2 mm Hg (P less than .05). Middle cerebral artery blood flow velocity (MCA BFV) decreased from 6.8 +/- 1.1 to 4.2 +/- 0.7 cm/s (P less than 0.05). In rats with an AVF, occlusion of venous outflow increased torcular pressure to 34.8 +/- 3.1 mm Hg (P less than 0.05), MCA BFV decreased to 1.8 +/- 0.5 cm/s (P less than 0.05), and severe ischemic changes were seen on the electroencephalogram. Under this condition, torcular pressure and systemic arterial pressure had a positive linear relationship (P less than 0.05), whereas in control rats torcular pressure and arterial pressure had no relationship. Restoration of cerebral perfusion pressure by release of venous outflow occlusion and AVF closure transiently increased MCA BFV to 69% above baseline (P less than 0.05). Histological examination 1 week after permanent venous outflow occlusion revealed venous infarction, subarachnoid hemorrhage, and severe brain edema in rats with an AVF but not in control rats without an AVF. This model of cerebrovascular steal with venous hypertension reproduces both hemodynamic and hemorrhagic complications of human AVF and emphasizes the importance of venous outflow obstruction and venous hypertension in the pathophysiology of these lesions.

The transcallosal-transforaminal approach to the third ventricle with regard to the venous variations in this region.

Surgical approaches to lesions located in the anterior and middle portions of the third ventricle are challenging, even for experienced neurosurgeons. Various exposures involving the foramen of Monro, the choroidal fissure, the fornices, and the lamina terminalis have been advocated in numerous publications. The authors conducted a microsurgical anatomical study in 20 cadaveric brain specimens (40 hemispheres) to identify an exposure of the third ventricle that would avoid compromising vital structures. An investigation of the variations in the subependymal veins of the lateral ventricle in the region of the foramen of Monro was performed, as these structures are intimately associated with the surgical exposure of the third ventricle. In 16 (80%) of the brain specimens studied, 19 (47.5%) of the hemispheres displayed a posterior location of the anterior septal vein-internal cerebral vein (ASV-ICV) junction, 3 to 13 mm (average 6 mm) beyond the foramen of Monro within the velum interpositum, not adjacent to the posterior margin of the foramen of Monro (the classic description). Based on this finding, the authors advocate opening the choroidal fissure as far as the ASV-ICV junction to enlarge the foramen of Monro posteriorly. This technique achieves adequate access to the anterior and middle portions of the third ventricle without causing injury to vital neural or vascular structures. The high incidence of posteriorly located ASV-ICV junctions is a significant factor influencing the successful course of surgery. Precise planning of the surgical approach is possible, because the location of the junction is revealed on preoperative neuroradiological studies, in particular on magnetic resonance venography. It can therefore be determined in advance which foramen of Monro qualifies for posterior enlargement to gain the widest possible access to the third ventricle. This technique was applied in three patients with a third ventricular tumor, and knowledge of the venous variations in this region was an important resource in guiding the operative exposure.

Preservation of the frontotemporal branch of the facial nerve using the interfascial temporalis flap for pterional craniotomy. Technical article.

The pterional craniotomy as described previously by the first author requires creation of a special flap over the temporalis muscle for increased visibility. Topographical variations of the course taken by the frontal branches of the facial nerve were studied and are described in this report.

Arteries of the insula.

OBJECT: The insula is located at the base of the sylvian fissure and is a potential site for pathological processes such as tumors and vascular malformations. Knowledge of insular anatomy and vascularization is essential to perform accurate microsurgical procedures in this region. METHODS: Arterial vascularization of the insula was studied in 20 human cadaver brains (40 hemispheres). The cerebral arteries were perfused with red latex to enhance their visibility, and they were dissected with the aid of an operating microscope. Arteries supplying the insula numbered an average of 96 (range 77-112). Their mean diameter measured 0.23 mm (range 0.1-0.8 mm), and the origin of each artery could be traced to the middle cerebral artery (MCA), predominantly the M2 segment. In 22 hemispheres (55%), one to six insular arteries arose from the M1 segment of the MCA and supplied the region of the limen insulae. In an additional 10 hemispheres (25%), one or two insular arteries arose from the M3 segment of the MCA and supplied the region of either the superior or inferior periinsular sulcus. The insular arteries primarily supply the insular cortex, extreme capsule, and, occasionally, the claustrum and external capsule, but not the putamen, globus pallidus, or internal capsule, which are vascularized by the lateral lenticulostriate arteries (LLAs). However, an average of 9.9 (range four-14) insular arteries in each hemisphere, mostly in the posterior insular region, were similar to perforating arteries and some of these supplied the corona radiata. Larger, more prominent insular arteries (insuloopercular arteries) were also observed (an average of 3.5 per hemisphere, range one-seven). These coursed across the surface of the insula and then looped laterally, extending branches to the medial surfaces of the opercula. CONCLUSIONS: Complete comprehension of the intricate vascularization patterns associated with the insula, as well as proficiency in insular anatomy, are prerequisites to accomplishing appropriate surgical planning and, ultimately, to completing successful exploration and removal of pathological lesions in this region.

The terminal vascular bed in the superficial cortex of the rat. An SEM study of corrosion casts.

The capillaries in the vascular bed of the rat brain have been investigated by means of scanning electron microscopy of corrosion casts. A technique is described that allowed the finer ramifications to be observed. A series of representative sites from the arteriovenous terminal pathway are described in detail. Contrary to previous reports, the dichotomic pattern of vessel distribution is shown to prevail over the network pattern. Arteriovenous shunts of discrete size were not seen. "Thoroughfare channels" could be recognized. The findings are considered in light of current physiological knowledge, and their significance for microcerebrovascular flow is indicated.

Correlation of clinical and pathological features in surgically treated craniopharyngiomas.

Surgical specimens of 104 craniopharyngiomas from 93 patients were reviewed and characterized histopathologically. They were found to have either a classic adamantinous or a squamous papillary structure. The clinical features of each group were then assessed. The frequently solid (50%), always uncalcified squamous papillary tumor type was found in one-third of the adult patients (greater than or equal to 20 years) but did not occur in children. It was associated with a good functional postoperative outcome (84.6%). There have been no cases of tumor recurrence in the squamous papillary group. However, in the group with the adamantinous type of craniopharyngioma, the recurrence rate was 13% in adult patients and 9% in children. When compared to the adult adamantinous cases, the incidence of visual deficits was lower in the squamous papillary group (75% vs. 84%) but the incidence of endocrine abnormalities was higher (75% vs. 52%). Thus, the preoperative, operative, and postoperative features of the two types of craniopharyngioma were found to be distinctly different in adults and children.

Topographic anatomy of the insular region.

OBJECT: The insula is one of the paralimbic structures and constitutes the invaginated portion of the cerebral cortex, forming the base of the sylvian fissure. The authors provide a detailed anatomical study of the insular region to assist in the process of conceptualizing a reliable surgical approach to allow for a successful course of surgery. METHODS: The topographic anatomy of the insular region was studied in 25 formalin-fixed brain specimens (50 hemispheres). The periinsular sulci (anterior, superior, and inferior) define the limits of the frontoorbital, frontoparietal, and temporal opercula, respectively. The opercula cover and enclose the insula. The limen insula is located in the depths of the sylvian fissure and constitutes the anterobasal portion of the insula. A central insular sulcus divides the insula into two portions, the anterior insula (larger) and the posterior insula (smaller). The anterior insula is composed of three principal short insular gyri (anterior, middle, and posterior) as well as the accessory and transverse insular gyri. All five gyri converge at the insular apex, which represents the most superficial aspect of the insula. The posterior insula is composed of the anterior and posterior long insular gyri and the postcentral insular sulcus, which separates them. The anterior insula was found to be connected exclusively to the frontal lobe, whereas the posterior insula was connected to both the parietal and temporal lobes. Opercular gyri and sulci were observed to interdigitate within the opercula and to interdigitate the gyri and sulci of the insula. Using the fiber dissection technique, various unique anatomical features and relationships of the insula were determined. CONCLUSIONS: The topographic anatomy of the insular region is described in this article, and a practical terminology for gyral and sulcal patterns of surgical significance is presented. This study clarifies and supplements the information presently available to help develop a more coherent surgical concept.

Anatomical observations of the subarachnoid cisterns of the brain during surgery.

Subarachnoid cisterns and their contents are described briefly in the light of observations made during microsurgical explorations. The concept of intracranial surgery in terms of moving from one cistern to another is presented here with particular emphasis on the cisterns in surgical approaches to intracranial vessels and nerves for the treatment of aneurysms, arteriovenous malformations, and for surgery of basal tumors.

Total removal of craniopharyngiomas. Approaches and long-term results in 144 patients.

The clinical features, perioperative course, and postoperative outcomes of 144 patients who underwent microsurgical resection of craniopharyngioma were reviewed. Overall, 90% of the tumors were completely resected and 7% recurred. Evaluation of those patients who underwent primary resection revealed much better results. The operative techniques and approaches are reviewed in detail. The results of this series suggest that primary total removal of craniopharyngiomas yields the best long-term outcome for the patient. Experience has shown that the larger the tumor the greater will be the damage, both preoperatively and intraoperatively, to vital intracranial structures. Consequently, early diagnosis, at a stage when the tumor is still small, improves the chances of accomplishing complete removal and of achieving good operative results. The early diagnosis of craniopharyngioma, before it can produce devastating neurological defects, continues to be the principal goal of our medical and pediatric colleagues.