Interdisciplinary management of meningioma involving the cavernous sinus

The thesis consists of two parts: an anatomical study of the complex anatomy of the cavernous sinus (CS) and its surrounding structures, and a rerospective clinical study involving 104 patients with CS meningioma who were treated at the University Hospital of Philipps University, Marburg. The aim of the anatomical study was to improve our surgical technique and results through better understanding of the complex anatomical relationships in the CS region. We used 3 skull base approaches commonly used to expose the CS to study this anatomy. Using 5 cadaver heads, each approach was performed 10 times in the same way as live surgery. The extent of exposure and the anatomical landmarks necessary to perform each approach were identified and documented. The second part of this thesis consists of a retrospective study of 104 patients harboring CS meningiomas, who were treated in the departments of Neurosurgery and Radiotherapy of Philipps University, Marburg, between 1997 and 2003. The clinical data, as well as the results and morbidity of treatment were documented analysed. Additionally, post treatment quality of life was assessed using one of the most widely used assessment instruments, which is the Medical Outcome Study Short Form 36 (SF-36). This questionnaire comprises 36 items, which measure patients’ responses in 8 different health domains. There were 80 females and 24 males with an average age of 56 years. The mean follow-up period was 40 months. The most common tumor origin was the medial sphenoid ridge and the petroclival region. Sixty-eight patients in this series underwent at least one surgical resection. Among the patients who were operated upon at our institute, the rate ot total resection was 59.5%.The most common post operative complication was new cranial nerves dysfunction, encountered in 45.9% of our patients but it was permanent in only 13.5% of cases. Seventy-nine patients received SRT either as unique treatment (36 cases) or after subtotal surgical resection (43 cases). The median target volume was 11.8 ml and the mean dose was 55.8 Gy.Apart from temporary local alopecia and local radiodermatitis, symptoms related to acute post-irradiation toxicity were generally uncommon and easily controlled by steroid medication. Late radiation toxicity was also uncommon. Local tumor control was achieved in all but 2 cases, and about 50% of patients showed tumor regression in follow-up according to our definition of tumor shrinkage and enlargement. Two mortalities occurred during the follow-up period: one surgically-treated patient died one year after surgery from an unrelated cause; and the other was treated by a combination of surgery and SRT and died from tumor progress 16 months after treatment. Questionnaires from a total of 96 patients were eligible for analysis. These patients were subdivided into 3 groups according to their treatment protocols. The first group included 22 patients who were surgically treated, the second group included 34 patients who were treated uniquely with fractionated stereotactic radiotherapy (SRT), and the third group included 40 patients who were treated with a combination of microsurgery and SRT. there was no statistically significant difference in all tested domains of post-treatment life quality between the three treatment protocols; however, patients of the second group had the best values in all but one domain. SRT seems to be an efficient and safe initial or adjuvant treatment for meningiomas involving the CS as proved by tumor control rates and long term life quality scores. On the other hand, surgery still plays an important role in the management of these tumors especially in the presence of optic compression, brain stem compression and large tumor volume. In certain cases, both modalities should be combined in order to optimize the management

Charakterisierung molekulargenetischer Prognosefaktoren auf dem kurzen Arm des Chromosoms 1 in humanen Meningeomen.

Meningeome, zumeist benigne Neoplasien des ZNS, stellen bis heute in manchen Fällen eine diagnostische und therapeutische Herausforderung dar: Zum einen ist für die kleine Gruppe der atypischen und anaplastischen Tumoren das Grading aufgrund histopathologischer Marker trotz revidierter WHO-Klassifikation schwierig. Zum anderen ist die Rezidivhäufigkeit auch benigner Tumorvarianten ein Problem. Sichere klinische und histopathologische Diagnosekriterien von prädiktivem Wert für Rezidivhäufigkeit und maligne Transformation sind bisher nicht bekannt. Deshalb haben Prognosefaktoren auf molekularer Ebene in letzter Zeit zunehmend an Bedeutung gewonnen. Als häufigste chromosomale Veränderung bei Meningeomen wurde die Monosomie 22 oder Teildeletion eines Chromosoms 22 entdeckt. Dabei scheint es sich um den primären Schritt zur Tumorentstehung zu handeln. Der zusätzliche Verlust genomischer Sequenzen auf 1p (LOH) scheint sich signifikant häufiger in atypischen und anaplastischen Meningeomen zu finden und wird deshalb als Prognosefaktor für malignes Wachstumsverhalten diskutiert. Ziel der vorliegenden Studie war die Expressionsanalyse 1p-spezifischer Transkripte, um funktionelle Konsequenzen von 1p-Deletionen in der Tumorprogression zu untersuchen und daraus diagnostische Marker zur besseren prognostischen Einschätzung zu gewinnen. Zur Validierung der m-RNA-Expression ergänzten eine Analyse der genomischen Ebene mit ausgewählten Mikrosatelliten-Markern und eine Proteinexpressionsanalyse die Untersuchung. Eine zusätzliche immunhistochemische Untersuchung der ALPL-Aktivität diente dazu, die molekulargenetischen Ergebnisse mit Hilfe einer leicht zugänglichen praktisch-diagnostischen Methode zu überprüfen. Die Ergebnisse der Transkriptionsanalyse zeigten Expressionsdefizite als Hinweis auf genomische Veränderungen gehäuft im Bereich der Gene ALPL, RAB3B und GADD45. Es konnten Zielbereiche der Deletion, aber kein einzelnes Zielgen definiert werden. Die deutliche Konzentration der Transkriptionsdefizite in den WHO II- und III-Tumoren bestätigte die von anderen Autoren beschriebene Progressionsassoziation der 1p-Alterationen in Meningeomen. Die Mikrosatellitenanalyse mit 1p-spezifischen Markern unterstützte den Verlust genomischer Sequenzen in diesem Bereich mit zunehmendem Malignitätsgrad. Die gute Korrelation der ALPL-Expression mit der Transkriptionsanalyse bestärkte die Hypothese genomischer Veränderungen des für ALPL kodierenden Gens im Rahmen der Tumorprogression. Die immunhistochemische Bestätigung eines progressionsassoziierten ALPL-Verlustes unterstützt die Erfassung eines molekulargenetischen Prognosefaktors mit Hilfe einer der Routinediagnostik leicht zugänglichen Methode. Dagegen ergaben sich für RAB3B divergente Ergebnisse, die auf komplexe Regulationsmechanismen hinweisen könnten. Die in der Studie nachgewiesenen 1p-spezifischen Transkriptionsdefizite werfen bei Annahme eines intakten Allels die Frage auf, welche molekularen Mechanismen zur vollständigen funktionellen Inaktivierung des Gens führen könnten. Eine mögliche Erklärung liefert Knudson’s „two-hit“-Modell, die jedoch in Meningeomen bisher nicht bewiesen werden konnte. Wahrscheinlicher ist ein komplexer Prozess, der morphologische, funktionelle und regulatorische Alterationen auf mehreren Ebenen beinhaltet. Die prädiktive Bedeutung von 1p-Deletionen bei Meningeomen konnte in dieser Studie bestätigt werden. Wenn es gelänge, diese Erkenntnis im klinischen Alltag nutzbar zu machen, könnten insbesondere rezidivgefährdete Meningeompatienten davon profitieren

Motor-evoked potentials (MEP) during brainstem surgery to preserve corticospinal function

Background: Brainstem surgery bears a risk of damage to the corticospinal tract (CST). Motor-evoked potentials (MEPs) are used intraoperatively to monitor CST function in order to detect CST damage at a reversible stage and thus impede permanent neurological deficits. While the method of MEP is generally accepted, warning criteria in the context of brainstem surgery still have to be agreed on. Method: We analyzed 104 consecutive patients who underwent microsurgical resection of lesions affecting the brainstem. Motor grade was documented prior to surgery, early postoperatively and at discharge. A baseline MEP stimulation intensity threshold was defined and intraoperative testing aimed to keep MEP response amplitude constant. MEPs were considered deteriorated and the surgical team was notified whenever the threshold was elevated by ≥20mA or MEP response fell under 50%. Findings: On the first postoperative day, 18 patients experienced new paresis that resolved by discharge in 11. MEPs deteriorated in 39 patients, and 16 of these showed new postoperative paresis, indicating a 41% risk of new paresis. In the remaining 2/18 patients, intraoperative MEPs were stable, although new paresis appeared postoperatively. In one of these patients, intraoperative hemorrhage caused postoperative swelling, and the new motor deficit persisted until discharge. Of all 104 patients, 7 deteriorated in motor grade at discharge, 92 remained unchanged, and 5 patients have improved. Conclusions: Adjustment of surgical strategy contributed to good motor outcome in 33/39 patients. MEP monitoring may help significantly to prevent motor deficits during demanding neurosurgical procedures on the brainste

Surgical treatment of tentorial dural arteriovenous fistulae located around the tentorial incisura

Tentorial dural arteriovenous fistulae (DAVF) are relatively uncommon and are the most dangerous type of DAVF. Because of a high incidence of hemorrhage and subsequent neurological deficits, treatment is mandatory. A consecutive series of nine surgically treated patients with symptomatic tentorial DAVF were analyzed in this study. All lesions were located around the tentorial incisura and were treated microsurgically using a subtemporal approach in eight cases and a supracerebellar approach in one case. The dural bases of the lesions were located adjacent to the tentorial edge in six patients and the tentorial apex in three patients. Complete obliteration was achieved in all treated tentorial DAVF. In one patient, the torcular fistula remained untreated without cortical venous reflux. Postoperative asymptomatic temporal lobe hemorrhage was diagnosed in one patient with a tentorial apex DAVF; however, no new neurological symptoms were present after surgical treatment. The subtemporal approach for unilateral tentorial DAVF is a favorable and direct approach for the highly skilled surgeon. Perimesencephalic venous dilatation or varix is an important finding on MRI to help localize tentorial DAVF in the tentorial edge or ape

Neurosurgical education in Europe and the United States of America

Training in neurological surgery is one of the most competitive and demanding specializations in medicine. It therefore demands careful planning in both the scientific and clinical neurosurgery arena to finally turn out physicians that can be clinically sound and scientifically competitive. National and international training and career options are pointed out, based on the available relevant literature, with the objective of comparing the neurosurgical training in Europe and the USA. Despite clear European Association of Neurosurgical Societies guidelines, every country in Europe maintains its own board requirements, which is reflected in an institutional curriculum that is specific to the professional society of that particular country. In contrast, the residency program in the USA is required to comply with the Accreditation Council for Graduate Medical Education guidelines. Rather similar guidelines exist for the education of neurosurgical residents in the USA and Europe; their translation into the practical hospital setting and the resulting clinical lifestyle of a resident diverges enormously. Since neurosurgical education remains heterogeneous worldwide, we argue that a more standardized curriculum across different nations would greatly facilitate the interaction of different centers, allow a direct comparison of available services, and support the exchange of vital information for quality control and future improvements. Furthermore, the exchange of residents between different training centers may improve education by increasing their knowledge base, both technically as well as intellectuall

Intra-operative high frequency ultrasound improves surgery of intramedullary cavernous malformations

Intra-operative ultrasound (ioUS) is a very useful tool in surgery of spinal lesions. Here we focus on modern ioUS to analyze its use for localisation, visualisation and resection control in intramedullary cavernous malformations (IMCM). A series of 35 consecutive intradural lesions were operated in our hospital in a time period of 24months using modern ioUS with a high frequency 7-15MHz transducer and a true real time 3D transducer (both Phillips iU 22 ultrasound system). Six of those cases were treated with the admitting diagnosis of a deep IMCM (two cervical, four thoracic lesions). IoUS images were performed before and after the IMCM resection. Pre-operative and early postoperative MRI images were performed in all patients. In all six IMCM cases a complete removal of the lesion was achieved microsurgically resulting in an improved neurological status of all patients. High frequency ioUS emerged to be a very useful tool during surgery for localization and visualization. Excellent resection control by ultrasound was possible in three cases. Minor resolution of true real time 3D ioUS decreases the actual advantage of simultaneous reconstruction in two planes. High frequency ioUS is the best choice for intra-operative imaging in deep IMCM to localize and to visualize the lesion and to plan the perfect surgical approach. Additionally, high frequency ioUS is suitable for intra-operative resection control of the lesion in selected IMCM case