A distinction between primary and secondary brain damage of vari ous origin, particularly in acute lesions, such as head injury and ische mia is not entirely new. The concept is of practical significance, be cause it is the foremost intention of all clinical efforts to prevent, or at least attenuate the development of secondary sequelae. Primary dam age to nervous elements usually cannot be influenced by treatment. Its prevention is the objective of prophylactic measures. The current volume gathered prominent scientists and clinicians from various fields to pro vide a competent introduction and survey of the various aspects involved in secondary brain damage. It was attempted to provide criteria for the distinction between the primary and secondary phenomena on a morpho logical and functional level, on the basis of the kinetics involved and, most importantly, regarding the different specific manifestations, such as disturbances of microcirculation, aspects of the blood-brain barrier, and of cellular structure and function at a molecular level. Although it was not expected that a grand unifying hypothesis will be reached recon cilable with the many, occasionally opposing views on such a complex subject, nevertheless, the present volume attains an appropriate result. It can best be described as a mosaic of many different pieces which only as an ensemble reflect the current state of the art."

Brain edema is a simple phenomenon - an abnormal increase of brain tissue volume by the increase of brain tissue water content. However the etiology is not simple and relating to a wide variety of neurological disorders including ischemia, trauma, tumor, hemorrhage and hydrocephalus. It is still a major cause of death in the neurological/neurosurgical ward. This volume is an up-to-date report on progress in brain edema research, diagnosis and treatment, including papers presented at the 12th International Symposium on Brain Edema and Brain Tissue Injury in 2002. Major topics include molecular biology and blood-brain barrier disorders, ischemic and traumatic brain edema, imaging and diagnosis of brain edema, treatment and radiation effect. Various papers in the rapidly growing fields of neuroimaging and molecular medicine are also included.

The international interdisciplinary gathering of top of secondary brain damage in brain trauma, as ac- level clinical and laboratory scientists in Mauls, Italy knowledged from the beginning of these workshops in has developed from its beginning in 1984into a fruitful Mauls, the significance of inflammation is all but clear. tradition where worldwide experts active and knowl- Although inflammatory phenomena are seen in trauma edgeable in cerebral ischemia and trauma convene for and ischemia ofthe brain, as activation ofwhite blood update and exchanges of their most recent clinical and cells with emigration into the tissue presumably en- experimental findings and concepts. These meetings hancing damage, inflammatory cells may have benefi- have, of course, experienced shifts in emphasis from cial properties as well. Thechapter on the Janus-faceof the past until now, corresponding to the most actual inflammation isanalyzing this ambiguity. developments, which were fascinating clinicians and The exploration of novel cell-biological mechanisms laboratory scientists alike. The current Supplement of on a molecular or more systemic basis causing apop- Acta Neurochirurgica is an example in case. Its virtue totic cell death, inflammation, or regeneration, provide as before is that authors contribute articles in a review- useful objectives for therapeutical interventions ex- like manner on their own field of research, according pected to be more specific than the present treatment to the platform presentations at the meeting as indis- modalities.

Contrary to the neurological manifestations of arterial cerebral blood flow disturbances, respective conditions resulting fram obstruction of the cerebro-venous system are far less well understood. Hence, cerebral sinus vein thrombosis (CSVT) ranks prominently among the group of neglected diseases of the brain. This might be attributable (a) to the diagnostic difficulties of the disorder and (b) to the fact that CSVT is associated with a host of heterogeneous neurological symptoms which often are not specific for the underlying venous flow disorder. Another complicating aspect is that CSVT is a consequence of other diseases as disparate as focal infection, trauma, neoplasia, or a thrombosis disposition caused by oral contraceptive use. Although progress has been made in establishing the correct diagnosis of the syndrome, many problems remain as the discussions contained within this volume vividly demonstrate. The same is true for the present understanding of the pathophysiological basis of the disease, eg, concerning the cerebro-venous circulation, the hemodynamic and neuropathological consequences in particular. Part of these deficits may be attributed to a scarcity of solid experimental data due to the limited availability of animal models. However, relevant experimental models are required for an in-depth analysis of the pathophysiological mechanisms, eg, causing brain tissue damage in relationship with the topographical distribution of the venous flow obstruction and, most importantly, for the testing of specific methods of treatment.

Information is provided from the basic and clinical sciences on the mechanisms damaging the brain from trauma or ischemia. New aspects involve the endoplasmic reticulum, mitochondrial failure, pathobiology of axonal injury, molecular signals activating glial elements, or the emerging therapeutical role of neurotrophins. Experimental issues involve a better analysis of the ischemic penumbra, the salvagable tissue. Therapeutic contributions reach from the environmental influence to gene expression, including neuroprotection, such as hibernation - mother nature's experiment - or hypothermia which is reported to induce cell swelling. Treatment issues deal also with thrombolysis and combination therapies, or with the clearance of adverse blood components - LDL/fibrinogen - by a novel procedure using heparin. Other highlights are discussing the specificities of pediatric vs. adult brain trauma, or the evolving role of the Apolipoprotein-E e4 gene in severe head injury. An update is also provided on an online assessment of the patient management during the pre- and early hospital phase in Southern Bavaria. The empirical observation of neuroworsening is analyzed in further details, whether this is a specificity autonomously driving the posttraumatic course. Finally, the unsolved question why drug trials in severe head injury have failed so far in view of the promising evidence from the laboratory is subjected to an expert analysis.

This volume is a compilation of papers presented at the Tenth International Symposium on Brain Edema held on October 20-23, 1996, in San Diego, California. This follows the sequence of meetings that was initiated 31 years ago in the First International Symposium held in Vienna. Subsequent symposiums were held in Mainz, Montreal, Berlin, Groningen, Tokyo, Baltimore, Bern, and Tokyo CY okohama). A considerable number of papers was chosen from over 100 papers that were received. The organizers wish to thank the Advisory Committee for the excellent work done in selection of the papers. We also wish to thank all the persons who contributed to the success of the Tenth International Symposium, especially the staff who worked behind the scenes. These papers were reviewed, edited, approved or disapproved by the Editorial Board. Those manuscripts that were felt not pertinent to this publication were not accepted by the Editorial Board. Therefore, the excellent quality of those that are in the book are a reflection of the authors' dedication and work and that of those of the Editorial Board in their review process. For the reader's convenience, the papers are structured according to the various disease processes which are associated with the primary topic: hypertension, hydrocephalus, infection, ischemia, tumor, etc. We do hope that the reader will enjoy the articles and that they will provide an impetus and insight for future work.