To prevent further brain tumour growth, malignant tissue should be removed as completely as possible in neurosurgical operations. Therefore, differentiation between tumour and brain tissue as well as detecting functional areas is very important. Hyperspectral imaging (HSI) can be used to get spatial information about brain tissue types and characteristics in a quasi-continuous reflection spectrum. In this paper, workflow and some aspects of an adapted hardware system for intraoperative hyperspectral data acquisition in neurosurgery are discussed. By comparing an intraoperative with a laboratory setup, the influences of the surgical microscope are made visible through the differences in illumination and a pixel- and wavelength-specific signal-to-noise ratio (SNR) calculation. Due to the significant differences in shape and wavelength-dependent intensity of light sources, it can be shown which kind of illumination is most suitable for the setups. Spectra between 550 and 1,000 nm are characterized of at least 40 dB SNR in laboratory and 25 dB in intraoperative setup in an area of the image relevant for evaluation. A first validation of the intraoperative hyperspectral imaging hardware setup shows that all system parts and intraoperatively recorded data can be evaluated. Exemplarily, a classification map was generated that allows visualization of measured properties of raw data. The results reveal that it is possible and beneficial to use HSI for wavelength-related intraoperative data acquisition in neurosurgery. There are still technical facts to optimize for raw data detection prior to adapting image processing algorithms to specify tissue quality and function.:Abstract Introduction Materials and methods (Clinical workflow and setup for hyperspectral imaging process, Characteristics of the lighting, Characteristics of the hyperspectral imaging camera, Spectral data acquisition and raw data pre-processing in neurosurgery, Spectral data evaluation) Results (Spectral characteristics of the lighting, SNR of the HSI camera, Data acquisition and raw data preprocessing during neurosurgical operation, Spectral data evaluation) Discussion Conclusions

The identification of eloquent areas is of utmost importance in the surgery of tumors located near speech-eloquent brain areas, since the classical concept of a constant localization was proven to be untrue and the spatial localization of these areas may show large interindividual differences. Some neurosurgical centers apply intraoperative electrophysiological methods that, however, necessitate the performance of surgery in the awake patient. This might be a severe burden both for the patient and the operating team in a procedure that lasts several hours; in addition, electrical stimulation may generate epileptic seizures. Alternatively, methods of functional brain imaging (e.g., PET, fMRI, MEG) may be applied, which allow individual localization of speech-eloquent areas. Matching of these image data with a conventional 3D-CT or MRI now allows the exact transfer of this information into the surgical field by neuronavigation. Whereas standards concerning electrophysiological stimulation techniques that could prevent a permanent postoperative worsening of language are available, until now it remains unclear whether the resection of regions shown to be active in functional brain imaging will cause a permanent postoperative deficit. / Die Identifikation sprachaktiver Areale ist von höchster Bedeutung bei der Operation von Tumoren in der Nähe des vermuteten Sprachzentrums, da das klassische Konzept einer konstanten Lokalisation des Sprachzentrums sich als unrichtig erwiesen hat und die räumliche Ausdehnung dieser Areale eine hohe interindividuelle Varianz aufweisen kann. Einige neurochirurgische Zentren benutzen deshalb intraoperativ elektrophysiologische Methoden, die jedoch eine Operation am wachen Patienten voraussetzen. Dies kann sowohl für den Patienten als auch das Operations-Team eine schwere Belastung bei diesem mehrstündigen Eingriff darstellen, zusätzlich können epileptische Anfälle durch die elektrische Stimulation generiert werden. Alternativ können Modalitäten des «functional brain imaging» (PET, fMRT, MEG usw.) eingesetzt werden, die die individuelle Lokalisation sprachaktiver Areale gestatten. Die Bildfusion dieser Daten mit einem konventionellen 3D-CT oder MRT erlaubt den exakten Transfer dieser Daten in den OP-Situs mittels Neuronavigation. Während Standards bei elektrophysiologischen Stimulationstechniken existieren, die eine permanente postoperative Verschlechterung der Sprachfunktion weitgehend verhindern, bleibt die Relevanz sprachaktiver Areale bei den neuesten bildgebenden Techniken bezüglich einer Operations-bedingten Verschlechterung der Sprachfunktion bisher noch unklar. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Frameless neuronavigational systems are a recent novelty for a precise approach to intracerebral tumours in open surgery. In this study 66 patients with a variety of intracranial tumours in various locations underwent surgical resection with neuronavigational guidance. Two different neuronavigational systems – the arm- and pointer-based ISG viewing wand and the miroscope-based MKM system – were compared for four different indications. Neuronavigation was used (a) in multiple tumours, e. g. brain metastases, (b) in solitary cortical or subcortical tumours located in eloquent brain areas, e. g. motor cortex or speech region, (c) in deep-situated brain tumours, including brain stem neoplasms, and (d) in infiltratively growing tumours to define the borders of the lesion. Using taped skin markers (MKM system) and a surface-fit algorithm (viewing wand) for registration, an accuracy of 1 to 2 mm deviation was achieved, which was sufficient for removal of all of the intracranial neoplasms investigated. Both systems proved to be safe and useful surgical tools regardless of the patient`s age, positioning of the patient during surgery or the location of the lesion. When these two systems were compared, the viewing wand was found to be preferable for resection of multiple brain tumours located in distant operative sides and solitary tumours in eloquent brain areas; this was because of the wide range of movement of the pointing device and the possibility of 3D reconstruction of the brain surface. As the MKM system provided the option of stereotactical guidance during the operative procedure, it was found to be superior in approaching small and deep-situated lesions. In certain cases brain shifting due to early drainage of the CSF led to minor underestimation of the real depth. For the precise definement of tumour borders of intraparenchymal neoplasms both system were equally suitable. However, intrusion of brain parenchyma into the resection cavity led to minor overestimation of the real tumour size in certain large intraparenchymal tumours. / Rahmenfreie Neuronavigationssysteme stellen eine Neuerung in der offenen operativen Behandlung intrazerebraler Tumoren dar. In dieser Studie wurden 66 Patienten mit verschiedenen intrakraniellen Tumoren in unterschiedlichen Lokalisationen mit Hilfe der Neuronavigation operiert. Hierbei wurden zwei verschiedene Navigationssysteme – ein Arm- und Pointer-basierendes System (ISG Viewing Wand) und ein Mikroskop-basierendes System (MKM) – für vier verschiedene Indikationen miteinander verglichen. Die Neuronavigation wurde verwendet (a) bei multiplen Tumoren, wie z.B. Hirnmetastasen, (b) bei solitären kortikalen oder subkortikalen Prozessen in eloquenten Hirnarealen, wie z.B. Motorkortex oder Sprachregion, (c) bei tiefgelegenen Hirntumoren einschließlich Hirnstammtumoren und (d) bei infiltrativ wachsenden Tumoren zur Bestimmung der Tumorgrenzen. Die Verwendung von Hautklebemarkern (MKM-System) und eines Oberflächen-Anpassungsalgorithmus (Viewing Wand) zur Registrierung war mit einer Genauigkeit von 1 bis 2 mm Abweichung für die operative Entfernung aller intrakraniellen Tumoren ausreichend. Beide Systeme bestätigten sich als sichere und geeignete chirurgische Hilfsmittel unabhängig vom Alter der Patienten, der Lagerung des Patienten unter dem chirurgischen Eingriff und der Lokalisation der Raumforderung. Im Systemvergleich zeigte die Viewing Wand durch einen weiten Bewegungsraum des Pointers und der Möglichkeit einer dreidimensionalen Rekonstruktion der Hirnoberfläche Vorteile in der Entfernung von multiplen, in entfernten Hirnregionen gelegenen Tumoren sowie von solitären Prozessen in eloquenter Lokalisation. Das MKM-System war durch die Bereitstellung einer stereotaktischen Führung während des operativen Eingriffes in der Ansteuerung kleiner tiefgelegener Prozesse zu bevorzugen. Eine frühzeitige Liquordrainage führte zu einem brain shifting mit einer diskreten Unterschätzung der wirklichen Tiefe. Für eine genaue Festlegung der Tumorgrenzen von intraparenchymalen Tumoren waren beide Systeme vergleichbar geeignet. Das Relabieren von Hirngewebe in die Resektionshöhle führte jedoch in einigen Fällen von großen intraparenchymalen Tumoren bei beiden Systemen zu einer geringen Überschätzung der wirklichen Tumorgrenzen. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

[pt] Pacientes com lesões encefálicas adquiridas (LEA) apresentam prejuízos neuropsicológicos e funcionais. O presente estudo teve como objetivo identificar o perfil neuropsicológico destes pacientes atendidos em um serviço de neurocirurgia de um hospital público do Rio de Janeiro, avaliando as evidências de validade clínica da Bateria Breve de Rastreio Cognitivo (BBRC) no comprometimento cognitivo. Método: Participaram do estudo 30 pacientes submetidos a neurocirurgia de crânio e 30 de de coluna atendidos no ambulatório neurocirúrgico. Todos realizaram a BBRC que mostrou que o grupo crânio apresentou um comprometimento do funcionamento cognitivo global (MEEM- 35), memória incidental e imediata e no desenho do relógio. O resultado inicial mostrou prejuízo em alguns domínios das funções executivas, tais como memória operacional, estratégias de memória episódica e planejamento. A pesquisa sugere que a BBRC pode ser utilizada no contexto hospitalar para pacientes com LEA pós cirúrgicos. / [en] Patients with Acquired Brain Injury (ABI) have neuropsychological and functional injuries. The present study aimed to identify the neuropsychological profile of these patients treated at a neurosurgical service of a public hospital in Rio de Janeiro, evaluating the evidence of clinical validity of the Battery Cognitive Screening brief (BCSB) in cognitive injuries. Method: Thirty patients who was submitted to brain s neurosurgery and 30 spinal s neurosurgeries attended at clinic participated in the study. All underwent the BCSB, which showed that the search group had impairment in global cognitive functioning (MMSE-35), memory and in clock drawing test. The initial result showed injuries in the domains of executive functions, such as working memory, episodic memory strategies and planning. Research suggests that BBRC can be used in the hospital setting for post-surgical ABI patients.

No description available.

Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa belonging to the family of primitive neuro-ectodermic tumors (PNET). MB generally occurs in pediatric age, but in 14–30% of cases, it affects the adults, mostly below the age of 40, with an incidence of 0.6 per million per year, representing about 0.4–1% of tumors of the nervous system in adults. Unlike pediatric MB, robust prospective trials are scarce for the post-puberal population, due to the low incidence of MB in adolescent and young adults. Thus, current MB treatments for older patients are largely extrapolated from the pediatric experience, but the transferability and applicability of these paradigms to adults remain an open question. Adult MB is distinct from MB in children from a molecular and clinical perspective. Here, we review the management of adult MB, reporting the recent published literature focusing on the effectiveness of upfront chemotherapy, the development of targeted therapies, and the potential role of a reduced dose of radiotherapy in treating this disease.

Etwa 7000 Menschen erkranken in Deutschland pro Jahr an einem bösartigen Hirntumor. Bei vielen dieser Patienten ist die mikrochirurgische Resektion des pathologischen Gewebes ein wesentlicher Baustein der Therapie. Doch trotz vielfältiger technischer Unterstützungssysteme ist die Hirntumorchirurgie eine der anspruchsvollsten chirurgischen Disziplinen. Dieser Umstand ist u. a. der Tatsache geschuldet, dass entstandene Schäden am Hirngewebe meist irreversibel sind und somit postoperativ zu funktionellen Beeinträchtigungen bei den Patienten führen können. Erschwerend kommt weiterhin hinzu, dass pathologisch verändertes und funktionell intaktes Hirngewebe vor allem bei niedergradigen Gliomen visuell kaum voneinander unterscheidbar sind. Für das postoperative Outcome der Patienten ist sowohl das Ausmaß der Resektion, als auch die Vermeidung von funktionellen Defiziten von essenzieller Bedeutung. Zahlreiche Studien belegen eine deutlich verlängerte Überlebenszeit bei vollständiger Entfernung des Tumorvolumens und gleichzeitiger Vermeidung von durch den Eingriff verursachten neuen funktionellen Defiziten. Primäres Ziel ist daher die möglichst vollständige Entfernung des Tumors bei Erhalt der Hirnfunktion. Zur Unterstützung während dieses Entscheidungsprozesses besteht der Bedarf für vor allem intraoperativ anwendbare Verfahren und Methoden, die mit geringem Aufwand einsetzbar sind und Informationen über Morphologie und/oder Funktion bereitstellen können. Die optische Bildgebung (IOI / Intraoperative Optical Imaging) stellt eine Möglichkeit dar während der Intervention spezifische Hirnfunktionen zu visualisieren. Ursprünglich primär zu Forschungszwecken im Tiermodell eingesetzt, konnte in der Vergangenheit das Potenzial der Methode bei dem Einsatz im klinischen Umfeld gezeigt werden. Ausgehend von diesen Ergebnissen sollten in dieser Arbeit nun zum einen die Methode zur Darstellung der funktionellen Hirnareale weiter optimiert, die Integration in das klinische Umfeld vorangetrieben sowie das Potenzial der Bildgebung in weiteren Anwendungsfeldern evaluiert werden. Zentrale Fragestellungen die untersucht wurden, waren die Evaluation des Nutzens der IOI bei Wachkraniotomien zur Identifikation von Motor- und Spracharealen sowie zum anderen die Optimierung der bisherigen Auswerte- und Visualisierungsmethodik in Hinblick auf eine Maximierung des Informationsgewinns durch die genauere Charakterisierung der hämodynamischen Antwortfunktion. Weiterhin wurde untersucht inwieweit die in klinischer Routine vorhandene Mikroskopkameratechnik zur Anwendung der IOI geeignet ist. Neben diesen Fragestellungen ist auch die Abgrenzung von Tumorgewebe Gegenstand dieser Arbeit. Ausgehend von der Tatsache, dass sich pathologische Veränderungen u. a. auch in einer gestörten neurovaskulären Kopplung manifestieren, wurde untersucht, ob die direkte elektrische Stimulation (DCS) der Hirnoberfläche in Kombination mit der IOI geeignet ist, diese zu testen und somit funktionell intaktes und pathologisch verändertes Gewebe während der Operation zu differenzieren. Die Bewertung der IOI bei Wachoperationen erfolgte an einem Kollektiv aus insgesamt 10 Patienten. Hierbei wurden die mittels IOI aktivierten Areale qualitativ mit den präoperativ aufgezeichneten fMRT-Daten, sowie den intraoperativen Ergebnissen der Sprachtestung durch die direkte elektrische Stimulation verglichen. Zur funktionellen Aktivierung der Sprachareale wurden von den Patienten während der Aufnahmen Objektbenennungsaufgaben durchgeführt. Weiterhin fanden Untersuchungen zum Einsatz der IOI zur Generierung von visuellem Feedback während der Sprachkartierung statt. Zur Beantwortung der Eignung der RGB-Kamera für die IOI, wurden Messungen an insgesamt acht Patienten durchgeführt, bei denen der primär sensorische Kortex durch Stimulation des N. medianus aktiviert wurde. Die Aufnahmen der RGB-Kamera erfolgten hierbei parallel zu dem bisher genutzten Standardsystem, welches durch Lichtwellenlängenfilterung bei einem isosbestischen Punkt der Hämoglobinabsorption (568 nm) sensitiv für Änderungen des zerebralen Blutvolumens ist. Die aus den einzelnen Farbkanälen berechneten Aktivitätskarten der RGB-Kamera wurden mit der Aktivitätskarte des Standardsystems verglichen, um eine Aussage über die dominierende physiologische Signalkomponente in den einzelnen Farbkanälen zu treffen. Die bisherigen Auswertealgorithmen für die Darstellung funktioneller Areale basieren auf einem Ansatz, welcher die Fouriertransformation nutzt, um die Amplitude der Stimulationsfrequenz in den Bilddaten zu identifizieren. Dieser Ansatz wurde derart optimiert, dass zusätzlich zur Amplitudeninformation nun auch die Phaseninformation des Signals berücksichtigt wird. Somit können die hämodynamischen Vorgänge bei Aktivierung der entsprechenden Hirnareale genauer charakterisiert werden. Diese neue Auswertung und Visualisierung wurde zur Untersuchung der Aufnahmen von insgesamt 22 Patienten genutzt. Hierbei wurden die Aktivierungen nach elektrischer, taktiler und visueller Stimulation sowie die Aktivierung nach Durchführung von Sprachaufgaben bei Wachkraniotomien untersucht. Die Ergebnisse wurden u. a. mittels Phasenwinkelverteilungen in Form von Polarhistogrammen quantifiziert. In Hinblick auf die Differenzierung zwischen Tumor- und Normalgewebe wurden die Änderungen des zerebralen Blutvolumens, nachfolgend auf insgesamt 19 elektrische Stimulationen der Hirnoberfläche bei drei Patienten, mittels IOI beobachtet und die in den aktivierten Arealen gemessenen Reflektanzänderungen anschließend hinsichtlich Amplitude und Dauer quantifiziert. Das Ausmaß der aktivierten Areale wurde dazu mittels Differenzbildberechnung aus der gemittelten Reflektanz der Hirnoberfläche vor Stimulationsbeginn und der Reflektanz direkt nach Stimulationsende bestimmt. Bei dem Einsatz der IOI während Wachoperationen war die Identifizierung von primär motorischen Arealen in guter Übereinstimmung zu den präoperativen fMRT-Daten möglich. Die Auswertung der Daten zur Lokalisierung der Sprachareale ergab, dass bei 5 von 8 Patienten grundsätzlich zwar eine Übereinstimmung zum fMRT sichtbar war, gerade aber in Bezug zu den Ergebnissen der intraoperativen Sprachkartierung mit DCS die Ergebnisse beider Modalitäten (fMRT und IOI) nicht spezifisch genug für eine intraoperative Entscheidungsfindung sind. Die Verwendung einer RGB-Kamera für die Bildgebung ist prinzipiell möglich und kann die Integration der Methode in die operativen Abläufe vereinfachen. Bei allen 8 Patienten ließen sich aus den Daten der Farbkamera Aktivitätskarten berechnen, die eine Abgrenzung des Handareals auf dem primär sensorischen Kortex erlaubten. Bezüglich der Lokalisation der Aktivierung zeigten Blau- als auch Grünkanal die höchste Übereinstimmung mit den Daten des Standardsystems bei 568 nm. Eindeutige Unterschiede in den durch verschiedene Stimulationen ausgelösten hämodynamischen Reaktionen konnten mittels der in dieser Arbeit eingesetzten Phasenauswertung beobachtet werden. Speziell die auf die elektrische Stimulation am N. medianus folgende hämodynamische Antwort grenzt sich bezüglich ihrer temporalen Charakteristik gegenüber den Antworten nach taktiler und visueller Stimulation ab. Während der Stimulationsphasen kam es hierbei zu einer Reduktion des zerebralen Blutvolumens. Sowohl bei der taktilen, als auch bei der visuellen Stimulation zeigte sich eine Zunahme des Blutvolumens während der Stimulation. Die Auswertung der aktiven Sprachproduktion ergab sowohl Areale mit zunehmendem, als auch Areale mit abnehmendem Blutvolumen. Im Rahmen der Untersuchungen zur Gewebeabgrenzung mittels IOI und DCS konnten signifikante Unterschiede zwischen Tumor und morphologisch unverändertem, also mutmaßlich funktionell intaktem Hirngewebe beobachtet werden. Nach der elektrischen Stimulation zeigten sich auf Tumorgewebe in ihrer Amplitude deutlich geminderte optische Änderungen wohingegen auf mutmaßlich funktionell intaktem Hirngewebe eine deutliche hämodynamische Reaktion auf den Stimulus zu beobachten war. Die Ergebnisse verdeutlichen, dass die IOI als universelles Werkzeug bei einer Vielzahl von Anwendungsgebieten in der Neurochirurgie eingesetzt werden kann. Der methodeninhärente Vorteil liegt in der einfachen Anwendbarkeit und unkomplizierten Integration in die operativen Abläufe. Basierend auf den Ergebnissen der Arbeit scheint neben der Identifikation funktioneller Areale vor allem die Kombination von IOI und DCS vielversprechend. Hier kann die IOI zum einen zur Generierung von visuellem Feedback im Rahmen der intraoperativen Sprachkartierung genutzt werden und zum anderen bei Eingriffen unter Vollnarkose zur Gewebedifferenzierung. Die in der Arbeit weiterentwickelte funktionelle Auswertung erlaubt die genauere Charakterisierung der hämodynamischen Antwortfunktion auf verschiedene Stimuli und somit die Nutzung der Methode zum Erlangen vom grundlegendem Wissen über die Funktionsweise von kortikalen Prozessen. / Approximately 7000 people in Germany are diagnosed with a malignant brain tumor each year. For many of these patients, microsurgical resection of the pathological tissue is an essential component of the therapy. However, despite a variety of technical support systems, brain tumor surgery is one of the most challenging surgical disciplines. This is primary due to the fact, that damage to the brain tissue is usually irreversible, and can therefore lead to postoperative functional impairment. Another complicating factor is that pathologically altered and functionally intact brain tissue are visually almost indistinguishable from each other, especially in low-grade gliomas. For the postoperative outcome of patients, both, the extent of resection, and the avoidance of functional deficits, are of essential importance. Several studies demonstrate a significantly prolonged survival time with complete removal of the tumor volume while simultaneously avoiding new functional deficits caused by the surgery. Therefore, the primary goal is to remove the tumor as completely as possible while preserving brain function. To assist during this decision-making process, there is a need for intraoperative procedures and methods that can be used with minimal effort to provide information about morphology and function of cortical structures. Intraoperative Optical Imaging (IOI) is a technique that allows the visualization of specific brain function during the surgical intervention. Initially used mainly in animal models, developments in the past revealed the potential of IOI in a clinical setting. Based on those results, the scopes of this work are the further development of the method for visualization of functional brain areas, advancements in integration of IOI into surgical environment, and the development of new fields of application in neurosurgical interventions. In detail, this work investigates the use of IOI in awake surgery for identification of motor and speech areas. Another question addressed is the in depth characterization of the hemodynamic response, following functional stimulation. Therefore, new methods for data evaluation and visualization are developed. The integration of IOI into the clinical workflow and routine is essential for a successful application. Here, the potential use of the microscope integrated camera hardware is investigated to answer the question, whether it can be used for imaging. Besides the identification of functional areas, tissue differentiation is of major importance during tumor resection. Therefore, this work evaluates whether direct electrical stimulation (DCS) is suited, to delineate different tissue types (functional intact and tumor tissue), by evaluating the hemodynamic response following to the stimulation, using the IOI technique. This follows the hypothesis, that tumor tissue is in most cases characterized by an impaired neurovascular coupling and therefore by a limited response to electrical stimulation. IOI during awake surgery was evaluated by performing measurements on a total of 10 patients. Localization of IOI activation was compared towards preoperative acquired fMRI data, as well as towards intraoperative DCS language mapping. Object naming tasks were performed by the patients, to activate the corresponding language areas. Additionally, the use of IOI as a feedback tool during DCS mapping was investigated. Here, IOI was used to visualize the spatial extent of each single stimulation. The suitability of microscope integrated RGB camera for IOI was investigated by performing measurements on 8 patients, that underwent surgery near the central region. Activation of hand area on primary sensory cortex was triggered by electrical stimulation of the median nerve while patients were under general anesthesia. Measurements with an RGB camera were performed parallel to the standard research hardware setup, which uses a light wavelength filter (568 nm) that makes the system sensitive to changes in cerebral blood volume. Activity maps, calculated from the data of each RGB camera color channel, were compared, to the activity maps calculated from light wavelength filtered image data. The current algorithms for IOI data evaluation use a Fourier-based approach to localize the activated brain region based on the amplitude of the stimulation frequency component. This approach was refined in this work to incorporate besides the amplitude also the phase of the stimulation frequency component. This allows a more precise characterization of the hemodynamic processes during activation. The refined approach was used to evaluate 22 patient measurements. Datasets from electrical, tactile, visual, and speech activation were investigated. Results were quantitatively assessed using, among other things, the phase angle distribution visualized as polarhistograms. Regarding the differentiation between functional impaired tumor and functional intact non-tumor brain tissue, changes in cerebral blood volume from 19 direct electrical stimulations of three different patients were recorded and evaluated with IOI. The extent of the activated regions as well as the amplitude and duration of reflectance / hemodynamic changes were quantized. Therefore, a difference imaging technique was implemented. During awake surgery, the identification of primary motor areas with IOI was possible in good agreement with preoperatively acquired fMRI data. The evaluation of speech activation revealed that, although in 5 out of 8 cases a partial agreement between IOI and fMRI was visible, the results of both modalities (IOI as well as fMRI) are too unspecific to be useful for surgical decision-making. Here, DCS will remain the method of choice. The use of an RGB camera for IOI is generally possible and allows an easy integration of the method into the surgical workflow. Evaluation of data from all 8 patients, showed that color camera data is suitable to calculate activity maps that allow the identification of the median nerve area on primary sensory cortex. Regarding the localization of activation, activity maps calculated from green and blue channel data showed the highest agreements towards the CBV maps acquired at 568 nm. Using the refined evaluation protocol that considers the phase information of the optical signal, significant differences were found in the hemodynamic responses following the different stimulation types. Especially the evaluation of the hemodynamic response after electrical median nerve stimulation revealed distinct characteristics. Here, a decrease in CBV during stimulation trials was visible, whereas the hemodynamic responses after tactile as well as visual stimulation were characterized by an increase of CBV during stimulation trials. The evaluation of speech activations, revealed locally adjacent areas with CBV increase as well as with CBV decrease. Evaluation of optical changes of the brain surface after DCS revealed significant differences, dependent of the underlying type of tissue. The stimulation of functional impaired tumor tissue triggered a hemodynamic response that was, compared towards the stimulation of presumably functional intact cortical tissue, reduced in amplitude as well as in its spatial extent. The results of this work illustrate the potential of IOI in a wide variety of applications during neurosurgical intervention. The inherent advantage of the method is its ease in use and the easy integration into clinical workflow and environment. Based on the results of this work, the combination of IOI and DCS seems, besides the identification of functional areas, especially promising. IOI can be used here to either generate visual feedback for DCS during speech mapping in awake surgery, or it can be used to differentiate between tissue types by assessment of neurovascular coupling, even under general anesthesia of the patients. The algorithms for functional data evaluation developed in this work, allow a more precise characterization of the hemodynamic response. Therefore, IOI enables the user to gain fundamental knowledge about cortical hemodynamics and processes. Future work should address each of these presented use cases to address the open questions arising from this initial work on the extended fields of application for IOI.

Die Arbeit behandelt die Ergebnisse von Experimenten über die Wirkung des Dipeptides Carnosin (β Alanyl L Histidin) und der Aminosäuren L Histidin und β-Alanin auf Kulturen der humanen Zellreihen U87, T98G und LN405, welche von Zellen des malignen Hirntumors Glioblastoma multiforme abgeleitet sind. Die Vitalität der Zellen nach Inkubation mit Carnosin oder L Histidin wurde anhand der Adenosintriphosphatproduktion und der Dehydrohenaseaktivität für Inkubationszeiträume von 24, 48 und 72 Stunden bestimmt. Dabei zeigte sich eine signifikant niedrigere Vitalität der mit Carnosin oder L Histidin inkubierten Zellen gegenüber der unbehandelten Kontrolle. Dieser Effekt war bei L Histidin stärker ausgeprägt. Bei Messungen der Lakatdehydrogenaseaktivität im Medium der Zellen, welche als Indikator für Zellnekrosen diente, zeigten nur die mit L Histidin inkubierte Zellen Zeichen von Nekrose. Die gleichen Messungen wurden auch an humanen embryonalen Nierenzellen durchgeführt (HEK 293), wobei sich ein ähnliches Ergebnis feststellen ließ. In den drei Zellreihen wurde zudem mittels qRT-PCR die mRNA-Expression für die beiden Enzyme Carnosinase 1 und Carnosinase 2 bestimmt, welche L Histidin von Carnosin abspalten. Im Vergleich mit Proben aus normalem Hirngewebe war die Expression beider Enzyme in den Glioblastomzellen deutlich geringer, wenngleich nachweisbar. Nachdem vorhergehende Studien [8] einen Anstieg der Expression von mRNA der Pyruvatdehydrogenasekinase 4 (PDK4) in mit Carnosin inkubierten Glioblastomzellen gezeigt hatten, wurde dieser Effekt hier auch mittels qRT-PCR in mit L Histidin inkubierten Zellen nachgewiesen. Eine Wirkung von Carnosin oder L Histidin auf ein Reportergen des PDK4-Promoters wurde ebenfalls untersucht, wobei sich kein signifikanter Effekt nachweisen ließ.

Introdução: Radiocirurgia estereotática (RCE) e radioterapia estereotática fracionada (RCEF) são inovações modernas de procedimentos radioterápicos, de alta precisão que modelam o feixe de radiação para coincidir com o contorno da lesão, por meio de um sistema de imobilização exata do paciente ao aparelho, com definição do alvo através da fusão de imagens de RM, TC, Angiografia e PET/CT; em que pelas coordenadas de referência estereotática, determina-se que a dose de radiação de alta energia prescrita pelo médico seja depositada somente no volume-alvo, com preservação dos tecidos sadios, órgãos ou estruturas localizadas em suas adjacências. Meningeomas do seio cavernoso (MSCs) representam um problema especial porque podem evoluir comprimindo ou infiltrando estruturas neurovasculares presentes no seio cavernoso. Há evidências de que a RCE e a RCEF proporcionam controle satisfatório do crescimento dos meningeomas do seio cavernoso (MSCs) com efeitos adversos reduzidos. Objetivo: Avaliar resultados da avaliação clínica e da neuroimagem de doentes sintomáticos com MSCs tratados com RCEF ou RCE exclusivamente ou de modo adjuvante à neurocirurgia. Casuística e métodos: Estudo tipo coorte e retrospectivo sobre a avaliação de 89 doentes com MSC sintomático tratados com RCE (36%) ou RCEF (64%) entre janeiro de 1994 e março de 2009 e acompanhados até o final de 2012. Haviam sido submetidos à ressecação neurocirúrgica parcial (Simpson IV) ou à biopsia (Simpson V) previamente à radioterapia 29,2% dos doentes. A dose média de RCE foi de 14Gy, e a dose total de RCEF variou entre 50,4 e 54Gy, sendo fracionada em 1,8-2Gy/dose/dia. Resultados: O período de acompanhamento variou entre 36 e 180 meses (mediana de 73 meses). A percentagem de melhora dos sintomas neuroclínicos individuais e de melhora clínica e radiológica (p > 0,05) apresentou valores semelhantes nos doentes tratados com RCE ou RCEF, sendo respectivamente de 41,6% e 48,3%. Em 37% dos doentes, houve manutenção de, pelo menos, uma queixa neurológica apresentada antes do tratamento e, em 43,8%, a imagem do MSC manteve-se inalterada. O período livre de progressão do MSC em 5, 10 e 15 anos foi de 98,8%, 92,3% e 92,3%, respectivamente. Houve progressão da doença em quatro doentes (4,5%). A melhora dos sintomas neurológicos em doentes submetidos previamente à neurocirurgia ocorreu de maneira mais lenta em relação aos não operados, em razão de manipulação de nervos cranianos. Alguns sintomas pós-operatórios, como a ptose palpebral unilateral, persistiram permanentemente. Nenhuma complicação grave foi observada. Sete doentes apresentaram neuropatia óptica transitória durante 3 meses que melhorou com o uso de corticoides, dois neuropatia trigeminal que melhorou com uso de esteroides e um doente apresentou obstrução total da artéria carótida interna sem repercussão neurológica. Letargia e cefaléia foram os sintomas temporários imediatos mais frequentes. Conclusões: A RCEF e a RCE são métodos seguros e eficazes para tratar doentes com MSC sintomático. Proporcionam melhora ou estabilização da sintomatologia na maioria dos casos, e estabilização ou regressão do tumor demonstrado pela neuroimagem em mais de 90% deles. Ocorreu recuperação dos sintomas neurológicos preexistentes mais rapidamente em doentes não submetidos previamente à neurocirurgia. Houve recorrência do tumor em 4,5% dos doentes. Em até 15 anos de acompanhamento, não se evidenciou indução tumoral com o tratamento / Introduction: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRS) are modern innovations in radiotherapy procedures, precision shaping the radiation beam to match the contour of the lesion, through a system of accurate patient immobilization to the device, defining target through the fusion of MRI, CT, angiography and PET / CT, which is determined by reference to stereotactic coordinates. The radiation dose of high energy prescribed by the doctor to be delivery only in the target interest, with preservation of healthy tissues, organs or structures located in their vicinity. Cavernous sinus meningiomas (CSMs) pose a special problem because they can evolve compressing or infiltrating the neurovascular structures present of the cavernous sinus. There are evidences that SRS and FRS are efficient in the treatment of CSMs. Objectives: The evaluation of the long-term clinical results and neuroimaging findings in patients with symptomatic CSM treated with FSRT or SRS as single therapy or after a previous neurosurgical treatment. Patients and methods: Retrospective cohort study involving 89 patients with symptomatic CSMs treated with SRS (36%) or FSRS (64%) from January 1994 to March 2009, and followed until the end of 2012. Previous neurosurgical partial resection (Simpson IV) or biopsies (Simpson V) had been performed in 29.2% of the patients. The median dose of SRS was 14Gy and the total dose of FSRT ranged from 50.4 to 54Gy, fractionated in 1.8 to 2Gy/dose/day. Results: The follow-up period ranged from 36 to 180 months (median= 73months). There was improvement in the individual symptoms and in the clinical and radiological findings regardless the radiotherapeutic method in 41.6% and 48.3% of the patients treated with SRS or FSRT, respectively (p > 0,05). In 37% of the patients, at least one neurological complaint present before the treatment did not change and in 43.8% patients, the image of the tumor remained stable. The progression-free survival in 5, 10 and 15 years was 98.8%, 92.3% and 92.3%, respectively. The improvement of neurological symptoms in patients previously treated with neurosurgery was slower or did not occur as in nonpreviously operated patients. Lethargy and headache were the most frequent transient immediate post-radiotherapy symptoms. Seven patients presented transient optic neuropathy during 3 months and improved with corticosteroids, 2 presented trigeminal neuropathy that remitted rapidly with steroids, and one, had total occlusion of the internal carotid artery without neurological consequences. Conclusions: Both FSRT and SRS were equally safe and effective in the management of symptomatic CSMs. There was improvement or stabilization of the neurological symptoms in the majority ofthe patients and stabilization or regression of the neuroimaging of the lesion in more them 90% of them. The recovery of preexisting cranial neuropathies occurred faster and was more frequent in patients not previously treated with surgical procedure. There was recurrence in 4.5% of the patients. No radiation-induced tumor was observed term during the longest 15 years follow-up

INTRODUÇÃO: A craniotomia pterional é, frequentemente, utilizada para clipagem de aneurismas cerebrais e ressecção de tumores de base de crânio. O traumatismo cirúrgico ao músculo temporal pode levar à cefaléia pós-craniotomia e disfunção mandibular (DTM). Por outro lado, as doenças bucais como cárie dentária, periodontite e câncer bucal são um problema de saúde pública e podem confundir o diagnóstico diferencial das dores orofaciais. O objetivo deste estudo foi avaliar quantitativamente a sensibilidade trigeminal, a condição de saúde oral, a função mastigatória e a qualidade de vida de doentes submetidos à craniotomia pterional para tratamento de aneurisma. MÉTODOS: doentes adultos de ambos os sexos com aneurismas cerebrais, internados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram avaliados nos momentos pré e pós-operatório de 30 dias. RESULTADOS: 39 doentes examinados, dos quais 15 foram incluídos na pesquisa. A idade média foi de 47,7 anos e 73,3% eram mulheres; o valor médio de dor foi 3,7; a abertura bucal média foi 49,5 mm, no momento pré-operatório, e 29,9 mm, no pósoperatório; 86,7% tiveram DTM moderada a grave após a cirurgia; as áreas anatômicas próximas ao traumatismo cirúrgico (no lado operado) apresentaram hipoestesia na maioria dos doentes; a sensibilidade trigeminal foi afetada e a dor esteve presente em todos os pacientes; os doentes apresentavam, em média, 17,3 dentes cariados, extraídos ou restaurados, 42,9% apresentavam periodontite e 42,9% gengivite. Não houve alteração significativa na qualidade de vida no momento pós-operatório de 30 dias, comparado ao pré-operatório. CONCLUSÕES: Todos os indivíduos dentados apresentaram algum grau de doença periodontal e a cárie dentária ocorreu na maioria. A craniotomia pterional afetou o aparelho mastigatório, causando disfunção clínica grave da mandíbula na maioria dos doentes. As sensibilidades álgica (cutânea e nas mucosas orais), térmica e tátil trigeminais foram afetadas, apenas, no lado ipsilateral à cirurgia e, preponderantemente, em regiões anatômicas próximas à área de incisão e diérese / INTRODUCTION: Pterional craniotomy is frequently used for clipping of cerebral aneurisms and resection of cranial base tumors. The surgical trauma to the temporal muscle may cause post-craniotomy headache and temporomandibular dysfunction (TMD). Conversely, oral diseases as dental caries, periodontitis and oral cancer are a public health problem and may confound the differential diagnosis of orofacial pains. This study quantitatively evaluated the trigeminal sensitivity, oral health status, masticatory function and quality of life of patients submitted to pterional craniotomy for treatment of aneurism. METHODS: adult patients of both genders with cerebral aneurysms were evaluated at Clinics Hospital of the University of São Paulo Medical School, preoperatively and at 30 days postoperatively. RESULTS: 39 patients were evaluated, among which 15 were included in the study. The mean age was 47.7 years and 73.3% were females; the mean pain value was 3.7; the mean mouth opening was 49.5 mm (preoperatively) and 29.9 mm (postoperatively); 86.7% had moderate to severe TMD after surgery; the anatomical areas close to the surgical trauma (on the operated side) presented hypoesthesia in most patients; trigeminal sensitivity was affected and pain was present in all patients; in the average, the patients presented 17.3 decayed, missing or filled teeth, 42.9% exhibited periodontitis and 42.9% gingivitis. There was no significant alteration in the quality of life at 30 days postoperatively compared to the preoperative period. CONCLUSIONS: all dentate individuals presented some degree of periodontal disease and dental caries affected most patients. Pterional craniotomy affected the masticatory system, causing severe clinical dysfunction in the mandible in most patients. The trigeminal painful sensitivity (cutaneous and oral mucosa) was affected, as well as the thermal and tactile sensitivities, only on the same side of surgery, and especially in anatomical regions close to the areas of incision and dissection