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…