By John D. Pickard, Nejat Akalan, Concezio Di Rocco, Vinko V. Dolenc, J. Lobo Antunes, J.J.A. Mooij, Johannes Schramm, Marc Sindou

Advances and Technical criteria in Neurosurgery was once conceived in 1972byitsfoundingfathersJeanBrihaye, BernardPertuiset, FritzLoew andHugoKrayenbuuhlatacombinedmeetingoftheItalianandGerman NeurosurgicalSocietiesinTaormina. Itwasdesignedtocomplementthe Europeanpost-graduatetrainingsystemforyoungneurosurgeonsandwas ?rst released in 1974 in the beginning via sponsorship through the eu AssociationofNeurosurgicalSocieties. Allcontributionshavebeenp- lishedinEnglishtofacilitateinternationalunderstanding. Theambitionofallsuccessiveeditorialboardshasbeentoprovidean opportunityformaturescholarshipandre?ection, notconstrainedbyar- ?ciallimitsonspace. Theseriesprovidesaremarkableaccountofprogress overthepast35years, bothwithregardtoadvances, detaileddescriptions of normal operative strategies and in- intensity studies of demonstrated wisdom. Thepresentvolumeisnoexceptionandshouldappealtoboth experiencedneurosurgeonsandyoungneurosurgeonsintrainingalike. TheEditors Contents Listofcontributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XIII Advances current and strength destiny adjuvant matters in high-grade astrocytic glioma 1,2 1 1 2 1 remedy. F. LEFRANC, M. RYNKOWSKI, O. DEWITTE, andR. KISS, division ofNeurosurgery, ErasmeUniversityHospital, FreeUniversityofBrussels(U. L. B. ), 2 Brussels, Belgium, LaboratoryofToxicology, InstituteofPharmacy, FreeUniversity ofBrussels(U. L. B. ), Brussels, Belgium summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . four advent. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . five Naturalresistanceofmigratingmalignantgliomacellstoapoptosis (radiotherapyandchemotherapy). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Patternsofcelldeath. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eight Autophagy: apotentialTrojanhorseformalignantgliomas. . . . . . . . . . . . . . . . eleven Therapeuticbene?tsoftemozolomide. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . thirteen Localtherapiesforglioblastomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Ongoingclinicaltrialsforglioblastomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . sixteen 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 Deepbrainstimulationforpsychiatricdisorders stateoftheart. T. E. SCHLA APFER and B. H. BEWERNICK, mind Stimulation staff, division of Psychiatry and Psychotherapy, UniversityHospitalBonn, GermanyandDepartmentsofPsychiatry andMentalHealth, TheJohnsHopkinsUniversity, MD, united states summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 advent. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Historyofdeepbrainstimulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 PrinciplesofDBS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty NeurobiologyofdepressionandOCD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty-one Neurobiologyofdepression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty-one NeurobiologyofOCD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty two StudiesofDBSandpsychiatricdisorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . forty three Problemsintargetselection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty three Targetsindepression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty three TargetsinOCD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty six SafetyandadvantagesofDBS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . forty seven EthicalaspectsandstandardsinDBS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . fifty one Ethicalconsiderations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . fifty one ThepathtowardsmandatorystandardsforDBSinpsychiatricdisorders. . . . . . . . fifty two Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . fifty three ThefutureofDBS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . fifty four References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . fifty four criteria High?owextracranialtointracranialvascularbypassprocedureforgiantan- rysms: symptoms, surgicaltechnique, complicationsandoutcome. H. C. PATEL and P. J. KIRKPATRICK, division of educational Neurosurgery, Addenbrooke s health facility, UniversityofCambridge, Cambridge, united kingdom summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . sixty one creation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . sixty two Surgicaltechnique. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . sixty seven Cranialexposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . sixty nine Cervicalexposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Saphenousveinexposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy one Preauriculartunnel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy two Contents IX Anastamoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy three Distalanastamosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy three Externalcarotidanastamosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy four Closureandpostoperativecare. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy seven dialogue. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy seven Comparisonofoutcomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy seven Choosingthetypeofgraft. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy eight Longtermpatencyofgrafts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy nine Ischaemiccomplications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . seventy nine Anticoagulationrelatedmorbidity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eighty one end. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Advances and Technical Standards in Neurosurgery: Volume 34

Advances and Technical criteria in Neurosurgery was once conceived in 1972byitsfoundingfathersJeanBrihaye, BernardPertuiset, FritzLoew andHugoKrayenbuuhlatacombinedmeetingoftheItalianandGerman NeurosurgicalSocietiesinTaormina. Itwasdesignedtocomplementthe Europeanpost-graduatetrainingsystemforyoungneurosurgeonsandwas ?

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2008) Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 22(5): e8 17. Crighton D, Wilkinson S, O’Prey J, et al. (2006) DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 126: 121–34 18. Dean M, Fojo T, Bates S (2005) Tumor stem cells and drug resistance. Nat Rev Cancer 5: 275–84 19. Denker SP, Barber DL (2002) Ion transport proteins anchor and regulate the cytoskeleton. Curr Opin Cell Biol 14: 214–20 20.

Lefranc F, Kiss R (2006) Autophagy, the Trojan horse to combat glioblastomas. Neurosurg Focus 20: E7 65. Lefranc F, Kiss R (2008) The Sodium Pump 1 Subunit as a Potential Target to Combat Apoptosis-Resistant Glioblastomas. Neoplasia 10: 198–206 32 F. LEFRANC et al. 66. Lefranc F, Mijatovic T, Kondo Y, et al. (2008) Targeting the 1 subunit of the sodium pump (the Na+=K+-ATPase) to combat glioblastoma cells. Neurosurgery 62: 211–21 67. Lefranc F, Sadeghi N, Camby I, et al. (2006) Present and potential future issues in glioblastoma treatment.

Control of glioblastomas by topical therapy applied to the resection cavity during surgery may reduce the rate of local failure and increase the time for local tumor progression. New local agents including targeted pro-autophagic therapies as well as advances in delivery systems including CED are likely to play a role in the future trial for migrating glioma cells. Until recently, the new treatments for malignant gliomas have focused largely on the intrinsic properties of glioma cells with the targeted therapy.

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