Pathways traversed by peripherally administered protein tracers for entry to the mammalian brain were investigated by light and electron microscopy. Native horseradish peroxidase (HRP) and wheat germ agglutinin (WGA) conjugated to peroxidase were administered intranasally, intravenously, or intraventricularly to mice; native HRP was delivered intranasally or intravenously to rats and squirrel monkeys. Unlike WGA-HRP, native HRP administered intranasally passed freely through intercellular junctions of the olfactory epithelia to reach the olfactory bulbs of the CNS extracellularly within 45-90 minutes in all species. The olfactory epithelium labeled with intravenously delivered HRP, which readily escaped vasculature supplying this epithelium. Blood-borne peroxidase also exited fenestrated vessels of the dura mater and circumventricular organs. This HRP in the mouse, but not in the other species, passed from the dura mater through patent intercellular junctions within the arachnoid mater; in time, peroxidase reaction product in the mouse brain was associated with the pial surface, the Virchow-Robin spaces of vessels penetrating the pial surface, perivascular clefts, and with phagocytic pericytes located on the abluminal surface of superficial and deep cerebral microvasculature. Blood-borne HRP was endocytosed avidly at the luminal face of the cerebral endothelium in all species. WGA-HRP and native HRP delivered intraventricularly to the mouse were not endocytosed appreciably at the abluminal surface of the endothelium; hence, the endocytosis of protein and internalization of cell surface membrane within the cerebral endothelium are vectorial. The low to non-existent endocytic activity and internalization of membrane from the abluminal endothelial surface suggests that vesicular transport through the cerebral endothelium from blood to brain and from brain to blood does not occur. The extracellular pathways through which probe molecules enter the mammalian brain offer potential routes of passage for blood-borne and air-borne toxic, carcinogenic, infectious, and neurotoxic agents and addictive drugs, and for the delivery of chemotherapeutic agents to combat CNS infections and deficiency states. Methodological considerations are discussed for the interpretation of data derived from application of peroxidase to study the blood-brain barrier.

Trigeminal neurinomas have traditionally been excised through conventional approaches. Because symptomatic tumor recurrence exceeds 50% after conventional procedures, the authors evaluated the use of skull base approaches to achieve complete resection and a lower rate of symptomatic recurrence. Comparisons of skull base with conventional approaches to trigeminal neurinomas have been limited to small series with short-term follow-up periods. The authors reviewed their experiences with conventional (frontotemporal transsylvian, subtemporal-intradural, subtemporal-transtentorial, and suboccipital) and skull base (frontotemporal extradural-intradural, frontoorbitozygomatic, subtemporal anterior petrosal, and presigmoid posterior petrosal) surgical approaches for the excision of trigeminal neurinomas. In this paper they report the results of 15 patients with trigeminal neurinoma who underwent 27 surgical procedures between 1980 and 1990. Seventeen of the procedures used conventional and 10 used skull base approaches. All patients had tumors arising from Meckel's cave and the porus trigeminus either initially or on recurrence. Tumors located in the cavernous sinus recurred most frequently (83%); other tumors that recurred frequently were those located in Meckel's cave and the porus trigeminus (67%), and the posterior fossa (17%). The tumor extended into the anterolateral wall of the cavernous sinus in 38% of patients with cavernous sinus involvement. Tumor exposure and ease of dissection were superior with skull base approaches. Residual or recurrent tumors were found in 65% of patients following conventional approaches compared with 10% of patients following skull base approaches. Using skull base approaches, the surgeon was more accurate (90%) in estimating tumor excision than when using conventional approaches (43%). Perioperative complications were similar with both. The authors discuss the indications, advantages, and limitations of each approach. Based on anatomical considerations, they propose a strategy to best resect these tumors.

The lateral dural wall of the cavernous sinus is composed of two layers, the outer dural layer (dura propria) and the inner membranous layer. Tumors arising from the contents of the lateral dural wall are located between these two layers and are classified as interdural. They are in essence extradural/extracavernous. The inner membranous layer separates these tumors from the venous channels of the cavernous sinus. Preoperative recognition of tumors in this location is critical for selecting an appropriate microsurgical approach. Characteristics displayed by magnetic resonance imaging show an oval-shaped, smooth-bordered mass with medial displacement but not encasement of the cavernous internal carotid artery. Tumors in this location can be resected safely without entering the cavernous sinus proper by using techniques that permit reflection of the dura propria of the lateral wall (methods of Hakuba or Dolenc). During the last 5 years, the authors have identified and treated five patients with interdural cavernous sinus tumors, which included two trigeminal neurinomas arising from the first division of the fifth cranial nerve, two epidermoid tumors, and one malignant melanoma presumed to be primary. The pathoanatomical features that make this group of tumors unique are discussed, as well as the clinical and radiological findings, and selection of the microsurgical approach. A more favorable prognosis for tumor resection and cranial nerve preservation is predicted for interdural tumors when compared with other cavernous sinus tumors.

This report describes a surgical approach to the cavernous sinus. Based on the work of Parkinson, Dolenc, and other pioneering investigators, a comprehensive surgical approach for the treatment of lesions of the cavernous sinus is distilled and presented in 12 simple steps. The approach to surgical exploration of this region is divided into an extradural and intradural phase, each with six steps. The bony, neural, and/or vascular structures of each step are discussed. These steps may be used in their entirety for total exploration of the cavernous sinus, but also in part for lesions that involve only limited regions of the cavernous sinus. Either by design or circumstance, every intracranial neurosurgeon will eventually be led to the cavernous sinus region, and a clear understanding of cavernous sinus anatomy should be part of their armamentarium.