MEDICAL LITERATURE has been deluged during the past few years with books and papers on penicillin; but a book which has been produced under the general editorship of Sir Alexander Fleming himself represents a complete and authoritative summary of penicillin therapy as it stands today.' The book contains a series of independent contributions by \"experienced and eminent men who have worked with penicillin in Great Britain\". Their opinions and practical methods differ slightly, and there is some overlapping; but these are not disadvantageous, comparison and contrast lending interest to the reading. In the first or general section of the book Fleming contributes two chapters, one on the history and development of penicillin, introducing some interesting sidelights in the romance of discovery, the other on the bacteriological control of penicillin therapy. In both chapters the information is set out in meticulous detail and with a clarity and simplicity which can be enjoyed by all readers. Fleming also gives the right perspective to the place of penicillin amongst the antibiotics and lays down the principles of treatment. Both chapters are well illustrated and are the most outstanding in the book. Included in this first section also are chapters on the chemistry and manufacture of penicillin and its pharmacy, pharmacology and methods of administration. The second section of the book is entirely clinical, giving each author's view on the use of penicillin therapy in a disease or an infection of some particular region of the body. The entire range of peniCillin-sensitive conditions is considered in twenty authoritative and clearly written chapters; these contain many references and illustrations. Dental and veterinary diseases are also given fairly full consideration. The final section is a condensed resume of much of the preceding chapters and is written for. the general practttioner. This chapter is superttuous: it does not contain enough detall to be of much practical value. The book as a Whole, however, will undoubtedly be considered a classical contribution to medical literature and is strongly recommended, not only because of the general interest of its topic, but as a reference book on penicillin therapy of hitherto unequalled excellence. The typography, although conforming to war economy standards, is clear and the paper is good. There is an excellent list of references and the index is satisfactory.

Gray's Anatomy

Object The middle third of the clivus and the region around the petrous internal carotid artery (ICA) is a difficult area of the skull base in terms of access. This is a deep area rich with critical neurovascular structures, which is often host to typical skull base diseases. Expanded endoscopic endonasal approaches offer a potential option for accessing this difficult region. The objective of this paper was to establish the clinical feasibility of gaining access to the paraclival space in the region of the middle third of the clivus, to provide a practical modular and clinically applicable classification, and to describe the relevant critical surgical anatomy for each module. Methods The anatomical organization of the region around the petrous ICA, cavernous sinus, and middle clivus is presented, with approaches divided into zones. In an accompanying paper in this issue by Cavallo, et al., the anatomy of the pterygopalatine fossa is presented; this was observed through cadaveric dissection for which an e...

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Expanded endonasal approach: fully endoscopic, completely transnasal approach to the middle third of the clivus, petrous bone, middle cranial fossa, and infratemporal fossa.

OBJECT An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade. METHODS The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas. RESULTS The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas. CONCLUSIONS The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previously found using the microscopic technique. In cases in which the intracavernous internal carotid artery was encased (Grade 4), all the adenomas were invasive and the GTR/ER rate was 0%/0%. The authors suggest the addition of Grades 3A and 3B to distinguish the strikingly different outcomes of adenomas invading the superior CS compartments and those invading the inferior CS compartments.

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Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification.

OBJECTIVE: We sought to investigate the three-dimensional structure of the white matter of the brain by means of the fiber-dissection technique and diffusion-tensor magnetic resonance imaging to assess the usefulness of the combination of both techniques, compare their results, and review the potential functional role of fiber tracts. METHODS: Fifteen formalin-fixed human hemispheres were dissected according to Klingler’s fiber-dissection technique with the aid of 6 to 40 magnification. Threedimensional anatomic images were created with the use of specific software. Two hundred patients with neurological symptoms and five healthy volunteers were studied with diffusion-tensor magnetic resonance imaging (3 T) and tractographic reconstruction. RESULTS: The most important association, projection, and commissural fasciculi were identified anatomically and radiologically. Analysis of their localization, configuration, and trajectory was enhanced by the combination of both techniques. Threedimensional anatomic reconstructions provided a better perception of the spatial relationships among the white matter tracts. Tractographic reconstructions allowed for inspection of the relationships between the tracts as well as between the tracts and the intracerebral lesions. The combination of topographical anatomic studies of human fiber tracts and neuroanatomic research in experimental animals, with data from the clinicoradiological analysis of human white matter lesions and intraoperative subcortical stimulation, aided in establishing the potential functional role of the tracts. CONCLUSION: The fiber-dissection and diffusion-tensor magnetic resonance imaging techniques are reciprocally enriched not only in their application to the study of the complex intrinsic architecture of the brain, but also in their practical use for diagnosis and surgical planning.

Three-dimensional microsurgical and tractographic anatomy of the white matter of the human brain.

The WHO categorizes pituitary tumours as typical adenomas, atypical adenomas and pituitary carcinomas, with typical adenomas constituting the major class. However, the WHO classification does not provide an accurate correlation between histopathological findings and clinical behaviour. Tumours lacking typical histological features are classified as atypical, but not all are clinically atypical or exhibit aggressive behaviour. Pituitary carcinomas, by definition, have craniospinal or systemic metastases, although not all display classical cytological features of malignancy. Aggressive pituitary adenomas, defined from a clinical perspective, have earlier and more frequent recurrences and can be resistant to conventional treatments. Specific biomarkers have not yet been identified that can distinguish between clinically aggressive and nonaggressive pituitary adenomas, although the antigen Ki-67 proliferation index might be of value. This Review highlights the need to develop new biomarkers to facilitate the early detection of clinically aggressive pituitary adenomas and discusses emerging markers that hold promise for their identification. Defining aggressiveness is of crucial importance for improving the management of patients by enhancing prognostic predictions and effectiveness of treatment. New drugs, such as temozolomide, have potential use in the management of these patients; anti-VEGF therapy, mTOR and tyrosine kinase inhibitors are also potentially useful in managing selected patients.

Aggressive pituitary adenomas—diagnosis and emerging treatments

Objective The aim of this article is to describe the anatomy of the cavernous sinus and to provide a guide for use when performing surgery in this complex area. Clinical cases are used to illustrate routes to the cavernous sinus and its contents and to demonstrate how the cavernous sinus can be used as a pathway for exposure of deeper structures. Methods Thirty cadaveric cavernous sinuses were examined using x3 to x40 magnification after the arteries and veins were injected with colored silicone. Distances between the entrance of the oculomotor and trochlear nerves and the posterior clinoid process were recorded. Stepwise dissections of the cavernous sinuses, performed to demonstrate the intradural and extradural routes, are accompanied by intraoperative photographs of those approaches. Results The anatomy of the cavernous sinus is complex because of the high density of critically important neural and vascular structures. Selective cases demonstrate how a detailed knowledge of cavernous sinus anatomy can provide for safer surgery with low morbidity. Conclusion A precise understanding of the bony relationships and neurovascular contents of the cavernous sinus, together with the use of cranial base and microsurgical techniques, has allowed neurosurgeons to approach the cavernous sinus with reduced morbidity and mortality, changing the natural history of selected lesions in this region. Complete resection of cavernous sinus meningiomas has proven to be difficult and, in many cases, impossible without causing significant morbidity. However, surgical reduction of such lesions enhances the chances for success of subsequent therapy.

Microsurgical anatomy and approaches to the cavernous sinus.

Objective The objective was to examine the microsurgical anatomy basic to the microsurgical and endovascular management of lesions involving the dural arteries. Methods Adult cadaveric heads and skulls were examined using the magnification provided by the surgical microscope to define the origin, course, and distribution of the individual dural arteries. Results The pattern of arterial supply of the dura covering the cranial base is more complex than over the cerebral convexity. The internal carotid system supplies the midline dura of the anterior and middle fossae and the anterior limit of the posterior fossa; the external carotid system supplies the lateral segment of the three cranial fossae; and the vertebrobasilar system supplies the midline structures of the posterior fossa and the area of the foramen magnum. Dural territories often have overlapping supply from several sources. Areas supplied from several overlapping sources are the parasellar dura, tentorium, and falx. The tentorium and falx also receive a contribution from the cerebral arteries, making these structures an anastomotic pathway between the dural and parenchymal arteries. A reciprocal relationship, in which the territories of one artery expand if the adjacent arteries are small, is common. Conclusion The carotid and vertebrobasilar arterial systems give rise to multiple branches that supply the dura in a complex and overlapping pattern. A knowledge of the microsurgical anatomy of these dural arteries and their assessment on pretreatment evaluations plays a major role in safe and accurate treatment of multiple lesions.

Microsurgical anatomy of the dural arteries.

Objective This study was conducted to clarify the boundaries, relationships, and components of the medial wall of the cavernous sinus (CS). Methods Forty CSs, examined under x3 to x40 magnification, were dissected from lateral to medial in a stepwise fashion to expose the medial wall. Four CSs were dissected starting from the midline to lateral. Results The medial wall of the CS has two parts: sellar and sphenoidal. The sellar part is a thin sheet that separates the pituitary fossa from the venous spaces in the CS. This part, although thin, provided a barrier without perforations or defects in all cadaveric specimens studied. The sphenoidal part is formed by the dura lining the carotid sulcus on the body of the sphenoid bone. In all of the cadaveric specimens, the medial wall seemed to be formed by a single layer of dura that could not be separated easily into two layers as could the lateral wall. The intracavernous carotid was determined to be in direct contact with the pituitary gland, being separated from it by only the thin sellar part of the medial wall in 52.5% of cases. In 39 of 40 CSs, the venous plexus and spaces in the CS extended into the narrow space between the intracavernous carotid and the dura lining the carotid sulcus, which forms the sphenoidal part of the medial wall. The lateral surface of the pituitary gland was divided axially into superior, middle and inferior thirds. The intracavernous carotid coursed lateral to some part of all the superior, middle, and inferior thirds in 27.5% of the CSs, along the inferior and middle thirds in 32.5%, along only the inferior third in 35%, and below the level of the gland and sellar floor in 5%. In 18 of the 40 CSs, the pituitary gland displaced the sellar part of the medial wall laterally and rested against the intracavernous carotid, and in 6 there was a tongue-like lateral protrusion of the gland that extended around a portion of the wall of the intracavernous carotid. No defects were observed in the sellar part of the medial wall, even in the presence of these protrusions. Conclusion The CS has an identifiable medial wall that separates the CS from the sella and capsule of the pituitary gland. The medial wall has two segments, sellar and sphenoidal, and is formed by just one layer of dura that cannot be separated into two layers as can the lateral wall of the CS. In this study, the relationships between the medial wall and adjacent structures demonstrated a marked variability.

The medial wall of the cavernous sinus: microsurgical anatomy.

Objective To describe the exposure obtained through six approaches to the perimesencephalic cisterns with an emphasis on exposure of the posterior cerebral artery and its branches. Methods Dissections in 12 hemispheres exposed the crural, ambient, and quadrigeminal cisterns and related segments of the posterior cerebral artery. A Stealth Image Guidance workstation (Medtronic Surgical Navigation Technologies, Louisville, CO) was used to compare the approaches. Results The transsylvian approach exposed the interpeduncular and crural cisterns. The subtemporal approach exposed the interpeduncular and crural cisterns as well as the lower half of the ambient cistern. Temporal lobe retraction and the position of the vein of Labbe limited exposure of the quadrigeminal cistern. Occipital transtentorial and infratentorial supracerebellar approaches exposed the quadrigeminal and lower two-thirds of the ambient cistern. Transchoroidal approaches exposed the posterior third of the crural cistern, the upper two-thirds of the ambient cistern, and the proximal quadrigeminal cistern. Transchoroidal approaches exposed the posterior portion of the P2 segment (P2p) in 9 of 10 hemispheres and were the only approaches that exposed the lateral posterior choroidal arteries and the plexal segment of the anterior choroidal artery. Occipital transtentorial and infratentorial supracerebellar approaches provided access to the P3 segment in all cases and exposed the P2p segment in 4 of 10 hemispheres. The subtemporal approach provided access to the cisternal and crural segments of the anterior choroidal and medial posterior choroidal arteries and exposed the P2p segment in 3 of 10 hemispheres. Conclusion Surgical approaches to lesions of the perimesencephalic cisterns must be tailored to the site of the pathological findings. The most challenging area to expose is the upper half of the ambient cistern, particularly the P2p segment of the posterior cerebral artery.

Microsurgical approaches to the perimesencephalic cisterns and related segments of the posterior cerebral artery: comparison using a novel application of image guidance.

Objective To describe the surgical anatomy of the anterior, middle, and posterior portions of the medial temporal region and to present an anatomic-based classification of the approaches to this area. Methods Twenty formalin-fixed, adult cadaveric specimens were studied. Ten brains provided measurements to compare different surgical strategies. Approaches were demonstrated using 10 silicon-injected cadaveric heads. Surgical cases were used to illustrate the results by the different approaches. Transverse lines at the level of the inferior choroidal point and quadrigeminal plate were used to divide the medial temporal region into anterior, middle, and posterior portions. Surgical approaches to the medial temporal region were classified into four groups: superior, lateral, basal, and medial, based on the surface of the lobe through which the approach was directed. The approaches through the medial group were subdivided further into an anterior approach, the transsylvian transcisternal approach, and two posterior approaches, the occipital interhemispheric and supracerebellar transtentorial approaches. Results The anterior portion of the medial temporal region can be reached through the superior, lateral, and basal surfaces of the lobe and the anterior variant of the approach through the medial surface. The posterior group of approaches directed through the medial surface are useful for lesions located in the posterior portion. The middle part of the medial temporal region is the most challenging area to expose, where the approach must be tailored according to the nature of the lesion and its extension to other medial temporal areas. Conclusion Each approach to medial temporal lesions has technical or functional drawbacks that should be considered when selecting a surgical treatment for a given patient. Dividing the medial temporal region into smaller areas allows for a more precise analysis, not only of the expected anatomic relationships, but also of the possible choices for the safe resection of the lesion. The systematization used here also provides the basis for selection of a combination of approaches.

Alvaro Campero

Papers

Microsurgical anatomy and approaches to the cavernous sinus.

Microsurgical anatomy of the dural arteries.

The medial wall of the cavernous sinus: microsurgical anatomy.

Microsurgical approaches to the perimesencephalic cisterns and related segments of the posterior cerebral artery: comparison using a novel application of image guidance.

Microsurgical approaches to the medial temporal region: an anatomical study.