2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BEVEZETÉS A FUNKCIONÁLIS NEUROBIOLÓGIÁBA INTRODUCTION TO FUNCTIONAL NEUROBIOLOGY www.itk.ppke.hu By Imre Kalló Contributed by: Tamás Freund, Zsolt Liposits, Zoltán Nusser, László Acsády, Szabolcs Káli, József Haller, Zsófia Maglóczky, Nórbert Hájos, Emilia Madarász, György Karmos, Miklós Palkovits, Anita Kamondi, Lóránd Erőss, Róbert Gábriel, Zoltán Kisvárdai, Zoltán Vidnyánszky Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu Neurosurgery: Surgical treatment of the diseases of neuronal networks Imre Kalló & Loránd ErőssPázmány Péter Catholic University Faculty of Information Technology I. Neurosurgical techniques II. Application fields of neurosurgery 1. Neurooncology 2. Parkinson’s disease 3. Treatment of epilepsy 4. Treatment of pain slide0003_image003 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu Aims of the neurosurgical treatments Treatmentofpatientssufferingfromneurologicaldiseases,whichcannotbecuredofforsufficientlywellwithconservativeapproaches.Improvinglifequality,preventingdeteriorationofdiseasestate,extendingtheperiodofqualitylife,palliativetreatmentandalleviationofpain. Factors influencing the therapeutic decisions of the neurosurgeon • The preoperative clinical status of the patients • Morphological data obtained with the modern imaging techniques (preoperative, intraoperative) • Data of functional imagingtechniques(preoperative) • Electrophysiologicaldata(preoperative, intraoperative) Specializations in neurosurgery • Neurotraumatology • Pediatric neurosurgery • Vascularneurosurgery • Spinal neurosurgery • Functionalneurosurgery • Neuro-oncology Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu Neurosurgical techniques Minimally invasive surgicaltechniques • From the brain point of view • From the patient’ssomaticpoint of view • Or from the patient’s psycho-somaticpoint of view Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu Neurosurgical techniques Microscope-assisted intracysternal, or gyral microsurgery slide0052_image183 Endoscopic neurosurgery Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu Neurosurgical techniques Lssfront copy Stereotaxicneurosurgery Neuronavigation-and robot-assisted microsurgery Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu Neurosurgical techniques: neuronavigation Neuronavigation1.jpg Neuronavigation2.jpg Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu Neurosurgical techniques: neuronavigation D:\PROJECTS\CNS METASTASIS\NIKA\CT2.tif D:\PROJECTS\CNS METASTASIS\NIKA\ultrasound.tif D:\PROJECTS\CNS METASTASIS\NIKA\navigation roadmap.jpg D:\PROJECTS\CNS METASTASIS\IMAGES\KEP.TIF Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu Image guided neurosurgery slide0077_image235 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu Neurosurgical techniques: gamma ray surgery LGK11 LGK4 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu Gamma knife slide0133_image331 slide0135_image332 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 www.itk.ppke.hu Neurosurgical techniques: linac and cyberknife slide0130_image324 slide0132_image327 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 www.itk.ppke.hu Neurosurgical techniques: radiation surgery slide0135_image336 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 www.itk.ppke.hu Neurosurgical techniques: robot-assisted surgery slide0079_image247 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 www.itk.ppke.hu Neurosurgical techniques: endovascular neurosurgery slide0098_image254 slide0099_image255 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 www.itk.ppke.hu Neurosurgical techniques: preoperative imaging • CT • MR Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 www.itk.ppke.hu Neurosurgical techniques: preoperative imaging slide0103_image257 • MR tractography Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 www.itk.ppke.hu Neurosurgical techniques: intraoperative imaging slide0100_image271 • Focused UH surgery • OpenMRI Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 www.itk.ppke.hu Neurosurgical techniques: intraoperative imaging slide0107_image260 • Functional MR Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 www.itk.ppke.hu Neurosurgical techniques: intraoperative imaging • Functional MR: finger tapping Photo by Lajos Kozák /MRKK Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 www.itk.ppke.hu Application fields: neuro-oncology Complex treatmentof CNS tumors •Diagnostics: Is ittumor? Histology? • Therapy: surgical radiationtherapychemotherapy • Supportive therapy, care • Clinical research Significance •Potentially life-threatening disease •Number of patients with brain tumors ^ •Number of survivingoncological patients ^ Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 www.itk.ppke.hu Application fields: neuro-oncology CNS tumors • 1.5% of all malignant tumors • 2-2.3% of all causes of death • 2.1%of death caused by tumors •Neuroepithelial (intrinsic) tumors(48%) • Extraparenchymal tumors (40-45%) • Metastase(5-10%) Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 www.itk.ppke.hu Neurosurgical techniques: stereotaxia “The tools used by the surgeon must be adapted to the task and where the human brain is concerned they cannot be too refined.” Lars Leksell, M.D., Ph.D., 1907-1986 Ll_arc Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 www.itk.ppke.hu Neurosurgical techniques: stereotaxia Aim: Targeting normal or pathological brain regions byusing their 3D coordinates determined before with precise imaging techniques. Tool: Stereotaxic targetinginstrument Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 www.itk.ppke.hu Leksell stereotaxic instrument Lssfront copy LCFF_14 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 www.itk.ppke.hu Application fields of the stereotaxis Parkinson’s disease and other movement disorders Surgical treatment of epilepsy Surgical treatment of pain Treatment of abscesses, intracerebral haematoms, cysts, tumors Implantation of radioactive izotops (e.g. Yttrium 90) into the tumor Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 www.itk.ppke.hu Application fields: Parkinson’s disease Ablative surgical techniques Stimulation techniques Transplantation techniques Intracerebral navigation with a microelectrode C:\Users\Eross\Pictures\DBS\Amsterdam\PB110608.JPG C:\Users\Eross\Pictures\DBS\Amsterdam\PB110613.JPG Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 www.itk.ppke.hu Intracerebral navigation with a microelectrode ? Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 www.itk.ppke.hu Surgical treatment of epilepsy Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 www.itk.ppke.hu Probability of seizure in diagnosed epilepsy (Brodie, Kwan NEJM 2000) Before the first drug treatment64% Before the second drug treatment32% After thesecond drug treatment 9,6% In case of politherapy3% Surgical treatment of epilepsy Pharmacological treatment Neuromodulation Surgical treatment Aim: Toimprove the psychosocial status of the patient by the abolishment of seizuresor by reducing the number of seizures or by changing the seminology of the seizures. Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 www.itk.ppke.hu Surgical treatment of epilepsy 1 DSCN2375 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 www.itk.ppke.hu Preoperative phase I. • Aim:toset a hypothesis about the source of seizure • Non-invasive phase: • Search for lesion (MRI) • Interictal andictal EEG image • Examining the functional state: building in interictal and ictal SPECT ormaybePET data • Based on the convergence level of the data -lesionectomy -lesionectomy oriented by the epileptogenic zone -epilepsysurgery„sensu stricto„ (usuallyit requires further, invasive phase) Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 www.itk.ppke.hu Preoperative phase II. invasive preoperative examinations • Semi-invasive and invasive (subdural strip or grid, foramen ovale, ormaybeintracerebral electrodes) • Amytal test (dominant hemisphere, speechfunctions, memory) • Decision: surgery? –whatkind of surgery? Surgery plan • Aim: Removal of the primary epileptogenic zone and/orthe areas participating in the early spreading of the seizure, and the secundary „relay stations” e.g.: amygdalo-hippocampal complex withoutthe deficit of eloquent brainregions • Forms: „standard resectio” „tailored surgery” Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 www.itk.ppke.hu Aim of usage of invasive electrodes 3D spatial and temporal mapping of the site of origin and the spreading direction of epileptic seizures. Semi-invasive and invasive electrodes • Sphenoidal electrodes • FO elektrode • Strips, grids • PEG electrodes ?? • Intracerebral (makro-and microelektrodes) • SEEG Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 www.itk.ppke.hu Invasive electrodes: strips, grids 7 6 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 38 www.itk.ppke.hu Preoperative imaging –3D reconstruction Bánhalmi elektródás 3D felülrol aT20003 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 www.itk.ppke.hu Neuronavigation-assisted electrode implantation PICT0212 IMG0060 PICT0204 PICT0207 IMG0062 06a Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 www.itk.ppke.hu Intraoperative electrophysiology • EcOG • SSEP • Electric cortical stimulation: Epileptogenic zone Speechmapping Memory mapping Motor cortex mapping Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 www.itk.ppke.hu The extent of lateral resection in the dominant hemisphere Resection.jpg Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 www.itk.ppke.hu The extent of hippocampal and parahippocampal resection Resection2.jpg Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 43 www.itk.ppke.hu Morell’s subpial transsection in the surgery of eloquent areas 4 5 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 www.itk.ppke.hu Alternative surgical techniques in epilepsy treatment Stimulation of thevagus nerve: in case of high frequency (50Hz) stimulation there is a 50% reduction of CPS in 35% of patients in case of low frequency (1-2Hz) stimulation there is an80% reduction of CPS in10%of patients Stimulation of the right vagus nerve trigger more often bradycardia. Stimulation of the CM nucleus of the thalamus: there is no twofold blind prospective examination, the number of patients participating is low Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 www.itk.ppke.hu Antiepileptic neuromodulatory procedures rTMS Non-invasiv Invasiv Peripheral neuro- stimulation Central neuro- stimulation Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 www.itk.ppke.hu Alternative surgical techniques in epilepsy treatment Stimulation of thecerebellum: bilateral, extratemporal epilepsy, there is a 76% improvement, 27% of patients becomes seizure free, and 44% show reductions in the number of seizures Stimulated region: vermis, interspherial surface Stereotaxicamygdalotomy: not used Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 www.itk.ppke.hu Stimulation of the white matter Vagus Nerve Stimulation (VNS) Frame1 s6 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 www.itk.ppke.hu Cortical stimulation: open/closed loop techniques and local/remote approaches Nagel, Najm 2009 Neuromodulation Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 www.itk.ppke.hu Cortical stimulation trials-fig1[1] >100Hz, closed-loop Direct focus stimulation, preventing the seizure RNS-Neuropace – 45% reduction in the seizures Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 www.itk.ppke.hu Epilepsy surgery –human experimental research Electrode.png Connecting cable Cortical lamination Histology slide Penetration track Electrode shaft Recording site Tip ME1 ME2 Introduction to functional neurobiology: Neurosurgery 2011.10.15. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 51 www.itk.ppke.hu Epilepsy surgery –human experimental research depthandmicro03 electrode1