Targeted at clinicians and residents, this series has already become a classic, with one volume published each year. The Advances section presents fields of neurosurgery and related areas in which important recent progress has been made. The Technical Standards section features detailed descriptions of standard procedures to assist young neurosurgeons in their post-graduate training. The contributions have been written by experienced clinicians and are reviewed by all members of the editorial board.

Advances and Technical Standards in Neurosurgery was conceived in 1972byitsfoundingfathersJeanBrihaye,BernardPertuiset,FritzLoew andHugoKrayenbuuhlatacombinedmeetingoftheItalianandGerman NeurosurgicalSocietiesinTaormina. Itwasdesignedtocomplementthe Europeanpost-graduatetrainingsystemforyoungneurosurgeonsandwas ?rst published in 1974 initially through sponsorship by the European AssociationofNeurosurgicalSocieties. Allcontributionshavebeenp- lishedinEnglishtofacilitateinternationalunderstanding. Theambitionofallsuccessiveeditorialboardshasbeentoprovidean opportunityformaturescholarshipandre?ection,notconstrainedbyar- ?ciallimitsonspace. Theseriesprovidesaremarkableaccountofprogress overthepast35years,bothwithregardtoadvances,detaileddescriptions of standard operative procedures and in- depth reviews of established knowledge. Thepresentvolumeisnoexceptionandshouldappealtoboth experiencedneurosurgeonsandyoungneurosurgeonsintrainingalike. TheEditors Contents Listofcontributors...XIII Advances Present and potential future adjuvant issues in high-grade astrocytic glioma 1,2 1 1 2 1 treatment. F. LEFRANC ,M. RYNKOWSKI,O. DEWITTE,andR. KISS, Department ofNeurosurgery,ErasmeUniversityHospital,FreeUniversityofBrussels(U. L. B. ), 2 Brussels,Belgium, LaboratoryofToxicology,InstituteofPharmacy,FreeUniversity ofBrussels(U. L. B. ),Brussels,Belgium Abstract...4 Introduction...5 Naturalresistanceofmigratingmalignantgliomacellstoapoptosis (radiotherapyandchemotherapy)...6 Patternsofcelldeath...8 Autophagy:apotentialTrojanhorseformalignantgliomas...11 Therapeuticbene?tsoftemozolomide...13 Localtherapiesforglioblastomas...15 Ongoingclinicaltrialsforglioblastomas...16 Growthfactorreceptorinhibitors ...17 PI3K=Akt,mTORandNF- Binhibitors...17 Matrixmetalloproteinase(MMP)inhibitors(MMPI)...18 Angiogenesistargeting ...19 Cellularandvaccinationtherapies...20 Genetherapy...20 Reducingmalignantgliomacellmotilityinordertorestore pro-apoptoticdrugsensitivity...20 Thesodiumpumpconstitutesapotentialtargettocombat malignantgliomas...21 Thesodiumpump...22 Cardiotonicsteroids:ligandsofthesodiumpump...24 VIII Contents Thesodiumpumpisinvolvedincancercellproliferation, migrationanddeath...24 Braintumorstemcellsapotentialtargettocombatmalignantgliomas...26 Conclusions...27 References...2 8 Deepbrainstimulationforpsychiatricdisorders-stateoftheart. T. E. SCHLA APFER and B. H. BEWERNICK, Brain Stimulation Group, Department of Psychiatry and Psychotherapy,UniversityHospitalBonn,GermanyandDepartmentsofPsychiatry andMentalHealth,TheJohnsHopkinsUniversity,MD,USA Abstract...37 Introduction...38 Historyofdeepbrainstimulation...39 PrinciplesofDBS...40 NeurobiologyofdepressionandOCD...41 Neurobiologyofdepression...41 NeurobiologyofOCD...42 StudiesofDBSandpsychiatricdisorders...43 Problemsintargetselection...43 Targetsindepression...43 TargetsinOCD ...46 SafetyandadvantagesofDBS...47 EthicalaspectsandstandardsinDBS...51 Ethicalconsiderations...51 ThepathtowardsmandatorystandardsforDBSinpsychiatricdisorders...52 Conclusions...53 ThefutureofDBS...54 References...54 Standards High?owextracranialtointracranialvascularbypassprocedureforgiantan- rysms:indications,surgicaltechnique,complicationsandoutcome. H. C. PATEL and P. J. KIRKPATRICK, Department of Academic Neurosurgery, Addenbrooke's Hospital,UniversityofCambridge,Cambridge,UK Abstract...61 Introduction...62 Surgicaltechnique...67 Cranialexposure...69 Cervicalexposure...70 Saphenousveinexposure...71 Preauriculartunnel...7 2 Contents IX Anastamoses...73 Distalanastamosis...73 Externalcarotidanastamosis...74 Closureandpostoperativecare...77 Discussion...77 Comparisonofoutcomes...77 Choosingthetypeofgraft...78 Longtermpatencyofgrafts...79 Ischaemiccomplications...79 Anticoagulationrelatedmorbidity...81 Conclusion...

This series has already become a classic. In general, one volume is published per year. The advances section presents fields of neurosurgery and related areas in which important recent progress has been made. The technical standards section features detailed descriptions of standard procedures to assist young neurosurgeons in their post-graduate training. The contributions are written by experienced clinicians and are reviewed by all members of the editorial board.

Metaphor lies at the heart of the contemporary debate in aesthetics, semantics and the philosophy of science. It is generally recognised now that metaphor is not an obfuscation of the truth (as so many philosophers since Plato have argued); on the contrary, it is essential that we consider metaphor if we strive for an optimal understanding of how truth is gained both in science and in our everyday dealings with reality. Hence, metaphor is not of interest only for the literary theorists, but for all those who wish to understand science and how to grasp the structure of our social world. This volume presents eleven essays on the role of metaphor in philosophy, poetry, semiotics, art, literary criticism, economics, medical science and in political theory. Through the use of metaphor, the contributors provide a unique and exciting picture of these disciplines.

Advances and Technical Standards in Neurosurgery was conceived in 1972byitsfoundingfathersJeanBrihaye,BernardPertuiset,FritzLoew andHugoKrayenbuuhlatacombinedmeetingoftheItalianandGerman NeurosurgicalSocietiesinTaormina. Itwasdesignedtocomplementthe Europeanpost-graduatetrainingsystemforyoungneurosurgeonsandwas ?rst published in 1974 initially through sponsorship by the European AssociationofNeurosurgicalSocieties. Allcontributionshavebeenp- lishedinEnglishtofacilitateinternationalunderstanding. Theambitionofallsuccessiveeditorialboardshasbeentoprovidean opportunityformaturescholarshipandre?ection,notconstrainedbyar- ?ciallimitsonspace. Theseriesprovidesaremarkableaccountofprogress overthepast35years,bothwithregardtoadvances,detaileddescriptions of standard operative procedures and in- depth reviews of established knowledge. Thepresentvolumeisnoexceptionandshouldappealtoboth experiencedneurosurgeonsandyoungneurosurgeonsintrainingalike. TheEditors Contents Listofcontributors...XIII Advances Present and potential future adjuvant issues in high-grade astrocytic glioma 1,2 1 1 2 1 treatment. F. LEFRANC ,M. RYNKOWSKI,O. DEWITTE,andR. KISS, Department ofNeurosurgery,ErasmeUniversityHospital,FreeUniversityofBrussels(U. L. B. ), 2 Brussels,Belgium, LaboratoryofToxicology,InstituteofPharmacy,FreeUniversity ofBrussels(U. L. B. ),Brussels,Belgium Abstract...4 Introduction...5 Naturalresistanceofmigratingmalignantgliomacellstoapoptosis (radiotherapyandchemotherapy)...6 Patternsofcelldeath...8 Autophagy:apotentialTrojanhorseformalignantgliomas...11 Therapeuticbene?tsoftemozolomide...13 Localtherapiesforglioblastomas...15 Ongoingclinicaltrialsforglioblastomas...16 Growthfactorreceptorinhibitors ...17 PI3K=Akt,mTORandNF- Binhibitors...17 Matrixmetalloproteinase(MMP)inhibitors(MMPI)...18 Angiogenesistargeting ...19 Cellularandvaccinationtherapies...20 Genetherapy...20 Reducingmalignantgliomacellmotilityinordertorestore pro-apoptoticdrugsensitivity...20 Thesodiumpumpconstitutesapotentialtargettocombat malignantgliomas...21 Thesodiumpump...22 Cardiotonicsteroids:ligandsofthesodiumpump...24 VIII Contents Thesodiumpumpisinvolvedincancercellproliferation, migrationanddeath...24 Braintumorstemcellsapotentialtargettocombatmalignantgliomas...26 Conclusions...27 References...2 8 Deepbrainstimulationforpsychiatricdisorders-stateoftheart. T. E. SCHLA APFER and B. H. BEWERNICK, Brain Stimulation Group, Department of Psychiatry and Psychotherapy,UniversityHospitalBonn,GermanyandDepartmentsofPsychiatry andMentalHealth,TheJohnsHopkinsUniversity,MD,USA Abstract...37 Introduction...38 Historyofdeepbrainstimulation...39 PrinciplesofDBS...40 NeurobiologyofdepressionandOCD...41 Neurobiologyofdepression...41 NeurobiologyofOCD...42 StudiesofDBSandpsychiatricdisorders...43 Problemsintargetselection...43 Targetsindepression...43 TargetsinOCD ...46 SafetyandadvantagesofDBS...47 EthicalaspectsandstandardsinDBS...51 Ethicalconsiderations...51 ThepathtowardsmandatorystandardsforDBSinpsychiatricdisorders...52 Conclusions...53 ThefutureofDBS...54 References...54 Standards High?owextracranialtointracranialvascularbypassprocedureforgiantan- rysms:indications,surgicaltechnique,complicationsandoutcome. H. C. PATEL and P. J. KIRKPATRICK, Department of Academic Neurosurgery, Addenbrooke' andHugoKrayenbuuhlatacombinedmeetingoftheItalianandGerman NeurosurgicalSocietiesinTaormina. Itwasdesignedtocomplementthe Europeanpost-graduatetrainingsystemforyoungneurosurgeonsandwas ?rst published in 1974 initially through sponsorship by the European AssociationofNeurosurgicalSocieties. Allcontributionshavebeenp- lishedinEnglishtofacilitateinternationalunderstanding. Theambitionofallsuccessiveeditorialboardshasbeentoprovidean opportunityformaturescholarshipandre?ection,notconstrainedbyar- ?ciallimitsonspace. Theseriesprovidesaremarkableaccountofprogress overthepast35years,bothwithregardtoadvances,detaileddescriptions of standard operative procedures and in- depth reviews of established knowledge. Thepresentvolumeisnoexceptionandshouldappealtoboth experiencedneurosurgeonsandyoungneurosurgeonsintrainingalike. TheEditors Contents Listofcontributors...XIII Advances Present and potential future adjuvant issues in high-grade astrocytic glioma 1,2 1 1 2 1 treatment. F. LEFRANC ,M. RYNKOWSKI,O. DEWITTE,andR. KISS, Department ofNeurosurgery,ErasmeUniversityHospital,FreeUniversityofBrussels(U. L. B. ), 2 Brussels,Belgium, LaboratoryofToxicology,InstituteofPharmacy,FreeUniversity ofBrussels(U. L. B. ),Brussels,Belgium Abstract...4 Introduction...5 Naturalresistanceofmigratingmalignantgliomacellstoapoptosis (radiotherapyandchemotherapy)...6 Patternsofcelldeath...8 Autophagy:apotentialTrojanhorseformalignantgliomas...11 Therapeuticbene?tsoftemozolomide...1 3 Localtherapiesforglioblastomas...15 Ongoingclinicaltrialsforglioblastomas...16 Growthfactorreceptorinhibitors ...17 PI3K=Akt,mTORandNF- Binhibitors...17 Matrixmetalloproteinase(MMP)inhibitors(MMPI)...18 Angiogenesistargeting ...19 Cellularandvaccinationtherapies...20 Genetherapy...20 Reducingmalignantgliomacellmotilityinordertorestore pro-apoptoticdrugsensitivity...20 Thesodiumpumpconstitutesapotentialtargettocombat malignantgliomas...21 Thesodiumpump...22 Cardiotonicsteroids:ligandsofthesodiumpump...24 VIII Contents Thesodiumpumpisinvolvedincancercellproliferation, migrationanddeath...24 Braintumorstemcellsapotentialtargettocombatmalignantgliomas...26 Conclusions...27 References...28 EURO Deepbrainstimulationforpsychiatricdisorders-stateoftheart. T. E. SCHLA APFER and B. H. BEWERNICK, Brain Stimulation Group, Department of Psychiatry and Psychotherapy,UniversityHospitalBonn,GermanyandDepartmentsofPsychiatry andMentalHealth,TheJohnsHopkinsUniversity,MD,USA Abstract...37 Introduction...38 Historyofdeepbrainstimulation...39 PrinciplesofDBS...40 NeurobiologyofdepressionandOCD...41 Neurobiologyofdepression...41 NeurobiologyofOCD...42 StudiesofDBSandpsychiatricdisorders...4 3 Problemsintargetselection...43 Targetsindepression...43 TargetsinOCD ...46 SafetyandadvantagesofDBS...47 EthicalaspectsandstandardsinDBS...51 Ethicalconsiderations...51 ThepathtowardsmandatorystandardsforDBSinpsychiatricdisorders...52 Conclusions...53 ThefutureofDBS...54 References...54 Standards High?owextracranialtointracranialvascularbypassprocedureforgiantan- rysms:indications,surgicaltechnique,complicationsandoutcome. H. C. PATEL and P. J. KIRKPATRICK, Department of Academic Neurosurgery, Addenbrooke' andHugoKrayenbuuhlatacombinedmeetingoftheItalianandGerman NeurosurgicalSocietiesinTaormina. Itwasdesignedtocomplementthe Europeanpost-graduatetrainingsystemforyoungneurosurgeonsandwas ?rst published in 1974 initially through sponsorship by the European AssociationofNeurosurgicalSocieties. Allcontributionshavebeenp- lishedinEnglishtofacilitateinternationalunderstanding. Theambitionofallsuccessiveeditorialboardshasbeentoprovidean opportunityformaturescholarshipandre?ection,notconstrainedbyar- ?ciallimitsonspace. Theseriesprovidesaremarkableaccountofprogress overthepast35years,bothwithregardtoadvances,detaileddescriptions of standard operative procedures and in- depth reviews of established knowledge. Thepresentvolumeisnoexceptionandshouldappealtoboth experiencedneurosurgeonsandyoungneurosurgeonsintrainingalike. TheEditors Contents Listofcontributors...XIII Advances Present and potential future adjuvant issues in high-grade astrocytic glioma 1,2 1 1 2 1 treatment. F. LEFRANC ,M. RYNKOWSKI,O. DEWITTE,andR. KISS, Department ofNeurosurgery,ErasmeUniversityHospital,FreeUniversityofBrussels(U. L. B. ), 2 Brussels,Belgium, LaboratoryofToxicology,InstituteofPharmacy,FreeUniversity ofBrussels(U. L. B. ),Brussels,Belgium Abstract...4 Introduction...5 Naturalresistanceofmigratingmalignantgliomacellstoapoptosis (radiotherapyandchemotherapy)...6 Patternsofcelldeath...8 Autophagy:apotentialTrojanhorseformalignantgliomas...11 Therapeuticbene?tsoftemozolomide...13 Localtherapiesforglioblastomas...15 Ongoingclinicaltrialsforglioblastomas...16 Growthfactorreceptorinhibitors ...17 PI3K=Akt,mTORandNF- Binhibitors...17 Matrixmetalloproteinase(MMP)inhibitors(MMPI)...18 Angiogenesistargeting ...1 9 Cellularandvaccinationtherapies...20 Genetherapy...20 Reducingmalignantgliomacellmotilityinordertorestore pro-apoptoticdrugsensitivity...20 Thesodiumpumpconstitutesapotentialtargettocombat malignantgliomas...21 Thesodiumpump...22 Cardiotonicsteroids:ligandsofthesodiumpump...24 VIII Contents Thesodiumpumpisinvolvedincancercellproliferation, migrationanddeath...24 Braintumorstemcellsapotentialtargettocombatmalignantgliomas...26 Conclusions...27 References...28 EURO Deepbrainstimulationforpsychiatricdisorders-stateoftheart. T. E. SCHLA APFER and B. H. BEWERNICK, Brain Stimulation Group, Department of Psychiatry and Psychotherapy,UniversityHospitalBonn,GermanyandDepartmentsofPsychiatry andMentalHealth,TheJohnsHopkinsUniversity,MD,USA Abstract...37 Introduction...38 Historyofdeepbrainstimulation...39 PrinciplesofDBS...40 NeurobiologyofdepressionandOCD...41 Neurobiologyofdepression...41 NeurobiologyofOCD...42 StudiesofDBSandpsychiatricdisorders...43 Problemsintargetselection...43 Targetsindepression...43 TargetsinOCD ...46 SafetyandadvantagesofDBS...47 EthicalaspectsandstandardsinDBS...51 Ethicalconsiderations...51 ThepathtowardsmandatorystandardsforDBSinpsychiatricdisorders...5 2 Conclusions...53 ThefutureofDBS...54 References...54 Standards High?owextracranialtointracranialvascularbypassprocedureforgiantan- rysms:indications,surgicaltechnique,complicationsandoutcome. H. C. PATEL and P. J. KIRKPATRICK, Department of Academic Neurosurgery, Addenbrooke's Hospital,UniversityofCambridge,Cambridge,UK Abstract...61 Introduction...62 Surgicaltechnique...67 Cranialexposure...69 Cervicalexposure...70 Saphenousveinexposure...71 Preauriculartunnel...72 Contents IX Anastamoses...73 Distalanastamosis...73 Externalcarotidanastamosis...74 Closureandpostoperativecare...77 Discussion...77 Comparisonofoutcomes...77 Choosingthetypeofgraft...78 Longtermpatencyofgrafts...79 Ischaemiccomplications...79 Anticoagulationrelatedmorbidity...81 Conclusion...

This series has already become a classic. In general, one volume is published per year. The advances section presents fields of neurosurgery and related areas in which important recent progress has been made. The technical standards section features detailed descriptions of standard procedures to assist young neurosurgeons in their post-graduate training. The contributions are written by experienced clinicians and are reviewed by all members of the editorial board.

Targeted at clinicians and residents, this series has already become a classic, with one volume published each year. The Advances section presents fields of neurosurgery and related areas in which important recent progress has been made. The Technical Standards section features detailed descriptions of standard procedures to assist young neurosurgeons in their post-graduate training. The contributions have been written by experienced clinicians and are reviewed by all members of the editorial board.

This series has already become a classic. In general, one volume is published per year. The advances section presents fields of neurosurgery and related areas in which important recent progress has been made. The technical standards section features detailed descriptions of standard procedures to assist young neurosurgeons in their post-graduate training. The contributions are written by experienced clinicians and are reviewed by all members of the editorial board.