Epilepsy surgery is defined as any neurosurgical intervention whose pri- mary objective is to relieve medically intractable epilepsy (European Fed- eration of Neurological Societies Task Force 2000). The aim of epilepsy surgery is to reduce the number and intensity of seizures, minimise neuro- logical morbidity and antiepileptic drug (AED) toxicity, and improve quality of life. By definition, epilepsy surgery does not include normal surgical treatment of intracranial lesions where the primary goal is to di- agnose and possibly remove the pathological target, often an advancing tumour. In these patients, epileptic seizures are only one symptom of the lesion and will be treated concomitantly as part of the procedure. Temporal lobe epilepsy (TLE) is recognised as the most common type of refractory, focal epilepsy. In one third of all cases the neuronal systems responsible for the seizures that characterise this form of epilepsy fail to respond to currently available AEDs (Andermann F 2002). New imaging methods, especially magnetic resonance imaging (MRI), identify localising abnormalities in an increasing proportion of patients with intractable focal epilepsy. Consequently, the accuracy of the preoperative diagnostic pro- cedures has been significantly improved during the last decade; and suit- able candidates for surgery can be selected more reliably. Currently the main resources in most epilepsy surgery centres have been used to evaluate candidates for TLE surgery.

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbiihl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this series. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publi cation of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.

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.

As an addition to the European postgraduate training system for young neurosurgeons, we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbuhl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have been associated throughout with this senes. The fact that the English language is now the international medium for communication at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contri butions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publication of any volume for scrutiny and suggestions for revision. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.

The latest in this already classic series presents recent progress and detailed descriptions of standard procedures, to assist young neurosurgeons in their post-graduate training. With contributions from experienced European and American clinicians.

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

"

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo KrayenbtihI. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this series. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publi cation of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.

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).

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.

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.

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbiihl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this serIes. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publication of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by spe cialists in the given fields and constitute the first part of each volume.

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

"

Epilepsy surgery is defined as any neurosurgical intervention whose pri- mary objective is to relieve medically intractable epilepsy (European Fed- eration of Neurological Societies Task Force 2000). The aim of epilepsy surgery is to reduce the number and intensity of seizures, minimise neuro- logical morbidity and antiepileptic drug (AED) toxicity, and improve quality of life. By definition, epilepsy surgery does not include normal surgical treatment of intracranial lesions where the primary goal is to di- agnose and possibly remove the pathological target, often an advancing tumour. In these patients, epileptic seizures are only one symptom of the lesion and will be treated concomitantly as part of the procedure. Temporal lobe epilepsy (TLE) is recognised as the most common type of refractory, focal epilepsy. In one third of all cases the neuronal systems responsible for the seizures that characterise this form of epilepsy fail to respond to currently available AEDs (Andermann F 2002). New imaging methods, especially magnetic resonance imaging (MRI), identify localising abnormalities in an increasing proportion of patients with intractable focal epilepsy. Consequently, the accuracy of the preoperative diagnostic pro- cedures has been significantly improved during the last decade; and suit- able candidates for surgery can be selected more reliably. Currently the main resources in most epilepsy surgery centres have been used to evaluate candidates for TLE surgery.

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).

As an addition to the European postgraduate training system for young neurosurgeons, we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbuhl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have been associated throughout with this senes. The fact that the English language is now the international medium for communication at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contri butions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publication of any volume for scrutiny and suggestions for revision. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbiihl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this series. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publi cation of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbiihl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this series. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publication of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by spe cialists in the given fields and constitute the first part of each volume."

The latest in this already classic series presents recent progress and detailed descriptions of standard procedures, to assist young neurosurgeons in their post-graduate training. With contributions from experienced European and American clinicians.

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.

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo KrayenbtihI. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this series. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publi cation of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.