Advances: H. Duffau: Subpial dissection and subcortical mapping with vasculature and white matter pathways preservation in surgery for brain (low grade) gliomas. - F. Scholtes, G. Brook, D. Martin: Spinal cord injury and its treatment: current management and experimental perspectives. - M. Sindou, M. Messerer, J. Alvernia, G. Saint-Pierre: Percutaneous Biopsy through the Foramen Ovale for Parasellar lesions: Surgical anatomy, Method and Indications. - Technical Standards: C. Raftopoulos, F. Waterkeyn, E. Fomekong, T. Duprez: Percutaneous pedicle screw implantation with robotic intraoperative 2D/3D fluoroscopy for refractory low back pain. I. Zemmoura, S. Velut, P. Francois: The choroidal fissure: anatomy and surgical implications. I. Timofeev, T. Santarius, A.G. Kolias, P.J.A. Hutchinson: Decompressive craniectomy operative technique and perioperative care. - S Fauser, J Zentner: Management of complex cortical dysplasia in epilepsy

"

Detecting residual cognitive function in disorders of consciousness (M. R. COLEMAN, J. D. PICKARD).- Rationale for hypothalamus-deep brain stimulation in food intake disorders and obesity (N. TORRES, S. CHABARDEES, A. L. BENABID).- Gustatory and reward brain circuits in the control of food intake (A. J. OLIVEIRA-MAIA, C. D. ROBERTS, S. A. SIMON, M. A. L. NICOLELIS).- SEEG-guided RF-thermocoagulation of epileptic foci: A therapeutic alternative for drug-resistant non-operable partial epilepsies (M. GUENOT, J. ISNARD, H. CATENOIX, F. MAUGUIERE, M. SINDOU).- Child abuse - some aspects for neurosurgeons (B. MADEA, M. NOEKER, I. FRANKE.- Prophylactic antibiotics and anticonvulsants in neurosurgery (B. RATILAL, C. SAMPAIO).- The dural sheath of the optic nerve: descriptive anatomy and surgical applications (P. FRANCOIS, E. LESCANNE, S. VELUT) -Surgical indications and techniques for failed coiled aneurysms (C. RAFTOPOULOS; with the collaboration of G. VAZ).

The Third Advanced Seminar in Neurosurgical Research was held in the Palazzo Pisani Moretta, Venice, Italy from 30th April to 1st May, 1987 and was devoted to "Neuroendocrinological Aspects of Neurosurgery." The general aim of these advanced seminars is to bring together European Neurosurgeons interested or involved in research work, either clinically, experimentally or both, in a given field in order to achieve in-depth informal discussions not possible in the more conventional large congress. In particular, these advanced seminars seek to provide high level teaching by experienced basic scientists, to provide "state of the art" assessment of the subject and to highlight areas of controversy that may be suitable for future research. A special effort is made to identify younger neurosurgeons through the auspices of the European Directory of Neurosurgical Research, who have a particular interest in the subject under discussion, not all of whom will have immediate access to the most advanced, modern technology. The topic of Neuroendocrinology was chosen because clinically it is an area of controversy that should be amenable to application of new techniques, including molecular biology. There is a tendency on the part of Endocrinologists not to appreciate always that disturbances seen by Neurosurgeons may be different and need special attention. Inevitably there has been a little delay in publication of the manuscripts but these have been updated appropriately.

The 4th Advanced Seminar in Neurosurgical Research was held on May 17th-18th, 1989 in the Abbey of Praglia, a XIIth century Benedictine Monastery, near Padua, Italy, and was devoted to "Neurosurgical Aspects of Epilepsy." The general aim of these Advanced Seminars is to bring together European Neurosurgeons interested or involved in research, either clinically, experimentally or both, in a given field in order to achieve in-depth informal discussions not possible in the more conventional large congress. In particular, these Advanced Seminars seek to provide high level teaching by experienced basic scientists, to provide "state of the art" assessment of the subject and to highlight areas of controversy that might be suitable for future research. A special effort is made to identify younger Neurosurgeons, partly through the auspices of the European Directory of Neurosurgical Research, who have a particular interest in the subject under discussion, not all of whom will have immediate access to the most advanced, modern technology. Surgical treatment of epilepsy is an expanding area of endeavour and an expertise that remains underutilized in many countries. The programme for this Seminar was designed to paint the broad background, moving from basic membrane electrophysiology through to cost benefit analysis and rehabilitation. The perspectives of neu ropathology, neurology, neuroradiology, nuclear medicine, neuropsychology, neurophysiology and the drug in dustry are all included."

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.

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...

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.

AsanadditiontotheEuropeanpostgraduatetrainingsystemforyoung neurosurgeons, we began to publish in 1974 this series of Advancesand Technical Standards in Neurosurgery which was later sponsored by the EuropeanAssociationofNeurosurgicalSocieties. This series was ?rst discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathersoftheseriesbeingJeanBrihaye,BernardPertuiset,FritzLoewand HugoKrayenbuhl. ThuswereestablishedtheprinciplesofEuropean- operationwhich havebeenbornfromthe Europeanspirit,?ourishedin theEuropeanAssociation,andhavebeenassociatedthroughoutwiththis series. ThefactthattheEnglishlanguageisnowtheinternationalmediumfor communicationatEuropeanscienti?cconferencesisagreatassetinterms ofmutualunderstanding. Thereforewehavedecidedtopublishallcont- butionsinEnglish,regardlessofthenativelanguageoftheauthors. All contributions are submitted to the entire editorial board before publicationofanyvolumeforscrutinyandsuggestionsforrevision. Ourseriesisnotintendedtocompetewiththepublicationsoforiginal scienti?cpapersinotherneurosurgicaljournals. Ourintentionis,rather,to present?eldsofneurosurgeryandrelatedareasinwhichimportantrecent advanceshavebeenmade. Thecontributionsarewrittenbyspecialistsin thegiven?eldsandconstitutethe?rstpartofeachvolume. Inthesecondpartofeachvolume,wepublishdetaileddescriptionsof standardoperativeproceduresandindepthreviewsofestablishedkno- edge in all aspects of neurosurgery, furnished by experienced clinicians. This part is intended primarily to assist young neurosurgeons in their postgraduatetraining. However,weareconvincedthatitwillalsobeu- fultoexperienced,fullytrainedneurosurgeons. We hope therefore that surgeons not only in Europe, but also throughouttheworld,willpro?tbythisseriesofAdvancesandTechnical StandardsinNeurosurgery. TheEditors Contents ListofContributors...XIII Advances .. Gene Technology Based Therapies in the Brain. T. Wirth1,4 and S. Yla- Herttuala1,2,3, 1A. I. Virtanen Institute,University of Kuopio, Kuopio,F- land, 2DepartmentofMedicine,UniversityofKuopioandGeneTherapyUnit, Kuopio, Finland, 3Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland,4ArkTherapeuticsOy,Kuopio,Finland Abstract...3 IntroductiontoGeneTherapy:ThePast,PresentandFuture...4 PotentialAreasforGeneTherapyintheBrain...6 GeneTherapyforParkinson'sDisease...7 GeneTherapyforAlzheimer'sDisease...8 GeneTherapyforVascularBrainDiseases...9 GeneTherapyforBrainTumours...11 ChallengesofGeneTherapyintheBrain...12 GeneTransferVectors...15 ViralGeneTransferVectors...17 Retroviruses...17 HerpesSimplexVirus-1(HSV-1)...17 Adenoviruses...18 Adeno-AssociatedVirus(AAV's)...18 Non-ViralVectors...19 Ethics...20 ConcludingRemarks...21 Acknowledgement...21 References...21 VIII Contents TechnicalStandards AnatomyoftheOrbitanditsSurgicalApproach. G. Hayek,Ph. Mercier,and H. D. Fournier, Laboratory of Anatomy, Faculty of Medicine, University of Angers,Angers,France Abstract...35 Introduction...36 AnatomyoftheOrbit...36 TheOrbitalCavity...36 TheOrbitalFasciaorPeriorbita...38 OrbitalContents...39 OrbitalMuscles...40 TheArteriesoftheOrbit...42 VeinsoftheOrbit...47 NervesoftheOrbit...48 LacrymalGland...55 ApproachRoutestotheOrbit...56 Incision...56 TheLateralApproachRoute...57 OsteoplasticTechniques...58 Non-OsteoplasticTechniques...58 TheSuperiorApproachRoute...60 TheHybridLateral/SuperiorRoute...63 Discussion...

Advances: H. Duffau: Subpial dissection and subcortical mapping with vasculature and white matter pathways preservation in surgery for brain (low grade) gliomas. - F. Scholtes, G. Brook, D. Martin: Spinal cord injury and its treatment: current management and experimental perspectives. - M. Sindou, M. Messerer, J. Alvernia, G. Saint-Pierre: Percutaneous Biopsy through the Foramen Ovale for Parasellar lesions: Surgical anatomy, Method and Indications. - Technical Standards: C. Raftopoulos, F. Waterkeyn, E. Fomekong, T. Duprez: Percutaneous pedicle screw implantation with robotic intraoperative 2D/3D fluoroscopy for refractory low back pain. I. Zemmoura, S. Velut, P. Francois: The choroidal fissure: anatomy and surgical implications. I. Timofeev, T. Santarius, A.G. Kolias, P.J.A. Hutchinson: Decompressive craniectomy operative technique and perioperative care. - S Fauser, J Zentner: Management of complex cortical dysplasia in epilepsy

"

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.

S. Price: Advances in imaging low-grade gliomas - M. J. Riemenschneider, G. Riefenberger: Molecular neuropathology of low-grade gliomas and its clinical impact - I . R. Whittle: What is the place of conservative management for adult supratentorial low-grade glioma - D. Kurzwelly, U. Herrlinger, M. Simon: Seizures in patients with low-grade gliomas -- incidence, pathogenesis, surgical management, and pharmacotherapy - L. Bello et al: Present day's standards in microsurgery of low-grade gliomas - B. Baumert and R. Stupp: Is there a place for radiotherapy in low-grade gliomas? - F. W. Kreth et al: The place of interstitial brachytherapy and radiosurgery for low-grade gliomas - M. Klein: Health- related quality of life aspects in patients with low-grade glioma.

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...

Advances J. Maarrawi, P. Mertens, R. Peyron, L. Garcia-Larrea, M. Sindou: Functional exploration for neuropathic pain. - Z. H. Rappaport: The neuroscientific foundations of free will. - A. Hejcl, P. Jendelova, E. Sykova: Experimental reconstruction of the injured spinal cord. - M. Visocchi: Advances in video-assisted anterior surgical approach to the craniovertebral junction. Technical Standards N. Akalan: Myelomeningocele (Open spina bifida): Surgical management. - M. Stoffel, C. Stuer, F. Ringel, B. Meyer: Treatment of infections of the spine. - I. Massimi, F. Novegno, C. di Rocco: Chiari Type 1 malformation in children.

Advances
J. Maarrawi, P. Mertens, R. Peyron, L. Garcia-Larrea, M. Sindou: Functional exploration for neuropathic pain. - Z. H. Rappaport: The neuroscientific foundations of free will. - A. Hejcl, P. Jendelova, E. Sykova: Experimental reconstruction of the injured spinal cord. - M. Visocchi: Advances in video-assisted anterior surgical approach to the craniovertebral junction.
Technical Standards
N. Akalan: Myelomeningocele (Open spina bifida): Surgical management. - M. Stoffel, C. St er, F. Ringel, B. Meyer: Treatment of infections of the spine. - I. Massimi, F. Novegno, C. di Rocco: Chiari Type 1 malformation in children.

Detecting residual cognitive function in disorders of consciousness (M. R. COLEMAN, J. D. PICKARD).- Rationale for hypothalamus-deep brain stimulation in food intake disorders and obesity (N. TORRES, S. CHABARDEES, A. L. BENABID).- Gustatory and reward brain circuits in the control of food intake (A. J. OLIVEIRA-MAIA, C. D. ROBERTS, S. A. SIMON, M. A. L. NICOLELIS).- SEEG-guided RF-thermocoagulation of epileptic foci: A therapeutic alternative for drug-resistant non-operable partial epilepsies (M. GU NOT, J. ISNARD, H. CATENOIX, F. MAUGUIERE, M. SINDOU).- Child abuse some aspects for neurosurgeons (B. MADEA, M. NOEKER, I. FRANKE.- Prophylactic antibiotics and anticonvulsants in neurosurgery (B. RATILAL, C. SAMPAIO).- The dural sheath of the optic nerve: descriptive anatomy and surgical applications (P. FRANCOIS, E. LESCANNE, S. VELUT) -Surgical indications and techniques for failed coiled aneurysms (C. RAFTOPOULOS; with the collaboration of G. VAZ).

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.