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 via the ecu AssociationofNeurosurgicalSocieties. Allcontributionshavebeenp- lishedinEnglishtofacilitateinternationalunderstanding. Theambitionofallsuccessiveeditorialboardshasbeentoprovidean opportunityformaturescholarshipandre?ection, notconstrainedbyar- ?ciallimitsonspace. Theseriesprovidesaremarkableaccountofprogress overthepast35years, bothwithregardtoadvances, detaileddescriptions of normal operative methods and in- intensity studies of confirmed wisdom. Thepresentvolumeisnoexceptionandshouldappealtoboth experiencedneurosurgeonsandyoungneurosurgeonsintrainingalike. TheEditors Contents Listofcontributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XIII Advances current and power destiny adjuvant concerns in high-grade astrocytic glioma 1,2 1 1 2 1 therapy. 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 creation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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 workforce, 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 clinic, 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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Nature 428: 267–69 75. Megalizzi V, Mathieu V, Mijatovic T, et al. (2007) 4-IBP, a sigma1 receptor agonist, decreases the migration of human cancer cells, including glioblastoma cells, in vitro and sensitizes them in vitro and in vivo to cytotoxic insults of proapoptotic and proautophagic drugs. Neoplasia 9: 358–69 76. Mellinghoff IK, Wang MY, Vivanco I, et al. (2005) Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. ) 77. Mijatovic T, Op De Beeck A, Van Quaquebeke E, et al.

Targets in depression . . . . . . . . . . . . . . . . . . . Targets in OCD . . . . . . . . . . . . . . . . . . . . . Safety and advantages of DBS . . . . . . . . . . . . . . . . Ethical aspects and standards in DBS . . . . . . . . . . . . . . Ethical considerations . . . . . . . . . . . . . . . . . . . The path towards mandatory standards for DBS in psychiatric disorders .

In turn, tumor vasculature and other glioma cells secrete factors that maintain aberrant cancer stem cell self-renewal. Recent results show for the first time that brain tumor stem cells are susceptible to adenovirus-mediated cell death via autophagy in vitro and in vivo [45]. Because adenoviral proteins can completely overcome the molecular machinery of the infected cell, the authors hypothesized that Delta-24-RGD, an oncolytic adenovirus with enhanced tropism to glioma cells and selective replication in cancers cells with an abnormal Rb pathway [25], may act as a potent therapeutic agent to target brain tumor stem cells and prevent them from developing resistance to standard adjuvant therapy.

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