Fluorescein sodium-guided surgery of a brain abscess – A Case Report

Background: Up to now, the feasibility and benefit of using fluorescein sodium under a dedicated surgical microscope filter (YE560, YELLOW 560 nm filter, Carl Zeiss Meditec, Germany) has never been clinically evaluated in infectious disorders of the brain. Case Description: Here, we report the case of a male patient with a brain abscess in the right parietal lobe that was removed under fluorescence-guidance (intravenous administration of fluorescein sodium 10%, 5 mg/kg bodyweight). The abscess capsule showed intensive yellow fluorescent staining, while − under white light − the cortex appeared normal. Conclusion: This technique may improve the identification and surgical removal of brain abscesses

Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications.

Given the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery

Endoscopic Assistance in the Deep and Narrow Spaces of the Brain—Microscopic Tumor Surgery Supported by the New Micro-Inspection Tool QEVO® (Technical Note)

Introduction: To evaluate the feasibility and efficacy of the innovative micro-inspection tool QEVO® (Carl Zeiss Meditec, Oberkochen, Germany) as an endoscopic adjunct to microscopes for better visualization of the surgical field in complex deep-seated intracranial tumors in infants and adults. Materials and Methods: We retrospectively assessed the surgical videos of 25 consecutive patients with 26 complex intracranial lesions (time frame 2018–2020). Lesions were classified according to their anatomical area: 1 = sellar region (n = 6), 2 = intra-ventricular (except IV.ventricle, n = 9), 3 = IV.ventricle and rhomboid fossa (n = 4), and 4 = cerebellopontine angle (CPA) and foramen magnum (n = 7). Indications to use the QEVO® tool were divided into five “QEVO® categories”: A = target localization, B = tailoring of the approach, C = looking beyond the lesion, D = resection control, and E = inspection of remote areas. Results: Overall, the most frequent indications for using the QEVO® tool were categories D (n = 19), C (n = 17), and E (n = 16). QEVO® categories B (n = 8) and A (n = 5) were mainly applied to intra-ventricular procedures (anatomical area 2). Discussion: The new micro-inspection tool QEVO® is a powerful endoscopic device to support the comprehensive visualization of complex intracranial lesions and thus instantly increases intraoperative morphological understanding. However, its use is restricted to the specific properties of the respective anatomical area

German Cranial Reconstruction Registry (GCRR): protocol for a prospective, multicentre, open registry

Introduction: Owing to increasing numbers of decompressive craniectomies in patients with malignant middle cerebral artery infarction, cranioplastic surgery becomes more relevant. However, the current literature mainly consists of retrospective single-centre (evidence class III) studies. This leads to a wide variability of technical approaches and clinical outcomes. To improve our knowledge about the key elements of cranioplasty, which may help optimising clinical treatment and long-term outcome, a prospective multicentre registry across Germany, Austria and Switzerland will be established. Methods: All patients undergoing cranioplastic surgery in participating centres will be invited to join the registry. Technical methods, materials, medical history, adverse events and clinical outcome measures, including modified Rankin scale and EQ-5D, will be assessed at several time points. Patients will be accessible to inclusion either at initial decompressive surgery or when cranioplasty is planned. Scheduled monitoring will be carried out at time of inclusion and subsequently at time of discharge, if any readmission is necessary, and at follow-up presentation. Cosmetic results and patient satisfaction will also be assessed. Collected data will be managed and statistically analysed by an independent biometric institute. The primary endpoint will be mortality, need for operative revision and neurological status at 3 months following cranioplasty. Ethics and dissemination: Ethics approval was obtained at all participating centres. The registry will provide reliable prospective evidence on surgical techniques, used materials, adverse events and functional outcome, to optimise patient treatment. We expect this study to give new insights in the treatment of skull defects and to provide a basis for future evidence-based therapy regarding cranioplastic surgery. Trial registration number: This trial is indexed in the German Clinical Trials Register (DRKS-ID: DRKS00007931). The Universal Trial Number (UTN) is U1111-1168-7425

Clinical Benefits of Combining Different Visualization Modalities in Neurosurgery

The prevailing philosophy in oncologic neurosurgery, has shifted from maximally invasive resection to the preservation of neurologic function. The foundation of safe surgery is the multifaceted visualization of the target region and the surrounding eloquent tissue. Recent advancements in pre-operative and intraoperative visualization modalities have changed the face of modern neurosurgery. Metabolic and functional data can be integrated into intraoperative guidance software, and fluorescent dyes under dedicated filters can potentially visualize patterns of blood flow and better define tumor borders or isolated tumor foci. High definition endoscopes enable the depiction of tiny vessels and tumor extension to the ventricles or skull base. Fluorescein sodium-based confocal endomicroscopy, which is under scientific evaluation, may further enhance the neurosurgical armamentarium. We aim to present our institutional workup of combining different neuroimaging modalities for surgical neuro-oncological procedures. This institutional algorithm (IA) was the basis of the recent publication by Haj et al. describing outcome and survival data of consecutive patients with high grade glioma (HGG) before and after the introduction of our Neuro-Oncology Center

Local Application of BMP-2 Specific Plasmids in Fibrin Glue does not Promote Implant Fixation

<p>Abstract</p> <p>Background</p> <p>BMP-2 is known to accelerate fracture healing and might also enhance osseointegration and implant fixation. Application of recombinant BMP-2 has a time-limited effect. Therefore, a gene transfer approach with a steady production of BMP-2 appears to be attractive. The aim of this study was to examine the effect of locally applied BMP-2 plasmids on the bone-implant integration in a non-weight bearing rabbit tibia model using a comparatively new non-viral copolymer-protected gene vector (COPROG).</p> <p>Methods</p> <p>Sixty rabbits were divided into 4 groups. All of them received nailing of both tibiae. The verum group had the nails inserted with the COPROG vector and BMP-2 plasmids using fibrin glue as a carrier. Controls were a group with fibrin glue only and a blank group. After 28 and 56 days, these three groups were sacrificed and one tibia was randomly chosen for biomechanical testing, while the other tibia underwent histomorphometrical examination. In a fourth group, a reporter-gene was incorporated in the fibrin glue instead of the BMP-2 formula to prove that transfection was successful.</p> <p>Results</p> <p>Implant fixation strength was significantly lower after 28 and 56 days in the verum group. Histomorphometry supported the findings after 28 days, showing less bone-implant contact.</p> <p>In the fourth group, successful transfection could be confirmed by detection of the reporter-gene in 20 of 22 tibiae. But, also systemic reporter-gene expression was found in heterotopic locations, showing an undesired spreading of the locally applied gene formula.</p> <p>Conclusion</p> <p>Our results underline the transfecting capability of this vector and support the idea that BMP-2 might diminish osseointegration. Further studies are necessary to specify the exact mechanisms and the systemic effects.</p

The effect of locally applied BMP-2 specific plasmid on implant fixation- biomechanical testing

Weltweit werden jedes Jahr über 2 Mio. Gelenke durch eine Total- oder Hemiendoprothese ersetzt. Nach Implantation einer Hüftendoprothese kommt es in den ersten drei Monaten zum Knochenverlust von bis zu 14%. In der Folge treten bei vielen Patienten Prothesenlockerungen oder Infektionen auf, die einen erneuten Eingriff unabwendbar machen. Wechseloperationen sind mit größerem Blutverlust, längerer Eingriffsdauer und einer Zunahme von Komplikationen verbunden, die auch die Mortalität erhöhen. Die demographischen Daten sprechen weltweit für eine Zunahme der Indikationen für Gelenkersatz. Schätzungen zufolge wird die Zahl der häufig benötigten Prothesenoperationen in Deutschland jährlich um 3-5% ansteigen. Ein volkswirtschaftlicher Kostenanstieg und die psychologische Belastung für die Patienten sind mögliche Folgen. Schlecht einheilende Prothesen, periprothetische Frakturen und Implantatlockerung mit anschließender Revision machen eine Optimierung der Implantateinheilung notwendig. Osteoinduktive Zytokine sind seit Urist‘ Entdeckung der BMPs erforscht worden. BMP-2 und BMP-7 sind klinisch zugelassen und werden als rekombinant hergestellte Proteine verabreicht. Ein anderer Ansatz in der Applikation ist die Gentherapie. Dazu wird das für den Wachstumsfaktor kodierende Gen in das Zielgewebe eingeschleust. Die Zellen exprimieren das therapeutische Protein unmittelbar im Zielgewebe und somit örtlich und zeitlich limitiert. Für die klinische Anwendung bei der unzementierten Endoprothetik wäre diese Form des Gentransfers optimal, da hauptsächlich der Peri-Implantatknochen als Zielgewebe betroffen ist und die unerwünschten Nebenwirkungen reduziert werden könnten. In der Gentherapie werden die nicht-viralen Vektoren kontinuierlich verbessert. Eine Neuentwicklung sind sogenannte COPROGs. Dabei wird die DNA, kodierend für den Wachstumsfaktor BMP-2, mit dem häufig verwendeten PEI (Polyethylenimin) komplexiert und von einem Schutzpolymer umhüllt. In einer tierexperimentellen Studie wurden 64 Kaninchen (New Zealand White Rabbit) in 4 Gruppen aufgeteilt und beidseitig an der Tibia mit Implantation eines Titannagels operiert. Gruppe I galt als Kontrollgruppe mit einfacher Implantation des Titannagels. Gruppe II war die erste Versuchsgruppe mit zusätzlicher Fibrinkleberapplikation. Gruppe III stellte die zweite Versuchsgruppe dar mit Implantatimplantation und kombinierter Fibrinkleber- BMP-2-Plasmid Applikation. Für die Sicherheitsuntersuchung, d.h. insbesondere zum Ausschluss einer systemischen Transfektion, diente die Gruppe IV. Einziger Unterscheid zur Gruppe III war, dass das Plasmid für ein Reportergen anstelle von BMP-2 kodiert. Untersucht wurden in den Gruppen I-III zwei Behandlungszeiträume, 28 oder 56 Tage. In der Gruppe IV gab es vier Untersuchungszeitpunkte, 3,7,28 oder 56 Tage. In der vorliegenden Arbeit werden die Ergebnisse der biomechanischen Untersuchungen der Tiere aus den Gruppen I-III vorgestellt. Dazu wurde der push-out Test verwendet. Es erfolgte eine zusätzliche Bestimmung der Blut- und Serumparameter bei allen Tieren und eine radiographische Analyse der postoperativ und post mortem erstellten Röntgenbilder. Die statistisch ausgewerteten Daten zeigten eine signifikante Zunahme der Implantateinheilung in der Kontrollgruppe von Tag 28 zu Tag 56. Dies war auch bei der BMP-Plasmid Gruppe zu erkennen, jedoch war wie bei der Fibringruppe der Unterscheid von Tag 28 zu Tag 56 nicht signifikant. Der Vergleich der Gruppen untereinander zeigte keinen signifikanten Einheilungsunterschied zwischen der Kontroll- und der Fibringruppe an beiden Untersuchungszeiträumen. Die BMP-2-Applikation resultierte in einer verminderten biomechanischen Festigkeit des Implantats im Knochen beim push- out Test. Die Auswertung der Röntgenbilder zeigte eine generelle Zunahme der Knochendicke, die jedoch nicht mit der biomechanischen Festigkeit korrelierten Die bestimmten Blut- und Serumparameter blieben gruppenübergreifend im Verlauf unauffällig. Bedeutsam war die durch den Nachweis des Reportergens in verschiedenen Organen gewonnene Erkenntnis, dass eine systemische Transfektion stattgefunden hatte. Dieser Aspekt muss Gegenstand weiterer Forschung sein. Möglicherweise wurde der Fibrinkleber inklusive BMP-2 Genvektor durch den intramedullären Druck bei der Applikation des Implantats in den Markraum aus diesem herausgepresst und konnte sich über die Blutbahn systemisch verteilen. Die prinzipielle Anwendbarkeit von Fibrinkleber wurde gezeigt, da kein retardierender Effekt auf die Einheilungsdauer und keine verminderte Festigkeit festgestellt wurde. In diesem Versuch war der Gentransfer des BMP-2 Plasmids im neu entwickelten nicht-viralen Vektor mit Fibrinkleber als Trägermaterial zwar erfolgreich, brachte jedoch keine biomechanischen Vorteile. Im Gegenteil zeigten die biomechanischen Resultate, dass das Implantat in der BMP-2-Versuchsgruppe verglichen mit der Fibrin Versuchsgruppe und der Kontrollgruppe deutlich schlechter inkorporiert wurde. Diese Erkenntnis kontrastiert das bisherige Verständnis der biologischen Wirkung von BMP-2, einem Protein mit stark osteoinduktivem Potential. In der Frakturheilung zeigen BMPs eine deutliche Stimulation der Heilungsprozesse. Eine mögliche Erklärung für den negativen Effekt von BMP-2 bei der Implantateinheilung könnte eine unterschiedliche Knochenbildung sein. Im vorliegenden Im vorliegenden Versuch geschah das Knochenwachstum direkt um das Implantat, anders als im Frakturmodell, wo Knochenbildung über die Zwischenstufe der Knorpelbildung geschieht. Die Ergebnisse der noch nicht abgeschlossenen histologischen Untersuchung werden weitere Erkenntnisse bringen und das Bild vervollständigen. Um die komplexe biologische Wirkung von BMP-2 auf die Knochenheilung und die ihr zugrunde liegenden Mechanismen aufzuschlüsseln, bedarf es weiterer Forschung mit dem Ziel, neue und sichere Behandlungsstrategien für die klinische Anwendung zu entwickeln.More than 2 million joint are replaced each year by use of a total- or hemi endoprosthesis. Up to 14% of bone substance is lost after implantation. Consecutive periprosthetic fractures, infections or implant loosening is a possible consequence. Revision of the prosthesis implies a greater surgical risk with possible blood loss and higher mortality. Demographic data shows an increased need for operations involving the replacement of joints. Recombinant growth factors are frequently used in research and clinical application or regeneration of tissues and cells. Since the genetic code of most growth factors is known, genetic manipulation of cells in order to express a certain growth factor, is an attractive alternative tot he application of recombinant growth factors. Not only for economic reasons but also to maintain a constant level of an effective dosis of the protein over a longer time period by only one application. The effect of locally applied plasmids encoding for Bone Morphogenetic Protein-2 (BMP-2) on implant ingrowth was studied. A non-viral vector and fibrin glue as carrier was used in a non weight bearing model. 48 animals were divided in 2 groups with postoperative time periods of 28 (A) and 56 days (B). Each group consisted of 3 subgroups (SG 1-3 A/B, 8 animals each), each receiving a different application. In anaethsia both tibiae of the animals were reamed in anterograde direction. The reamed tibiae were not filled in the first subgroup(SG 1), filled with fibrin glue (SG 2) or filled with fibrin glue plus a copolymer protected gene vector (COPROG) carrying the BMP-2 encoding plasmid (SG 3). After filling the tibia a titanium nail diameter was inserted in anterograde direction. The the position was then controlled radiographically. A further 12 rabbits received fibrin glue carrying COPROG combined in this case with the Luciferase marker-gene, as part of a safety study. They also were divided in subgroups. After 28 and 56 days (4, 7 and 28 days in the marker-gene group respectively) animals were sacrificed. Both tibiae were explanted, one for histological analysis (not part of this dissertation), the other one for biomechanical testing. For biomechanical testing we used an approved push out device4 to measure the peak force needed to loosen the nail from the bone. The peak force was set in ratio to the largest possible area of the bone-implant interface. In the marker gene groups (not part of this dissertation) the bone was opened and the endosteum removed for testing using an ELISA assay. Additional Specimens were taken from brain, lung, liver, testicles and muscle tissue. Statistical tests were conducted using the Mann-Whitney-U-Test. The results of the biomechanical testing showed significantly lower shear strength in subgroup 3 at both timepoints. The difference between group 1and 2 was not significant in either of the timepoints. In the histological analysis the fibrin/BMP-2-plasmid group showed less bone-implant contact than both other groups and thus support the results of the biomechanical testing. In the additional safety study traces of the Luciferase marker gene were found in 22/24 tibiae at all timepoints. 15/72 specimens of ectopic organs were also positive. A preference could be found for lung and testicles. Muscle tissue was affected least. In this investigation it could be proven that a gene transfer using the non-viral gene vector COPROG and fibrin glue as a carrier works. Anyway the biomechanical and histological results showed signifigantly less implant incorporation when a BMP-2 plasmid was used compared to the two control groups and one fibrin group. These findings are in contrast to the presently preexisting notion that BMP-2 has a strong osteogenic potential. In the literature hardly any clinical experience exists for BMP-2 to support implant incorporation. The inhibitory effect might be model-related but could as well indicatecurrently unknown effects of BMP-2. One explanation might be, that these effects could be based upon the different mechanisms of bony implant incorporation where bone is formed directly without formation of cartilage and fracture healing where bone develops secondary from cartilage tissue. Which is supported by data showing greater expression of BMP-2 in a cartilage than a bone environment. The positive testing for Luciferase in organs outside the local application demand further investigation. It can be hypothesized that fibrin glue carrying the vector entered the blood vessels due to the increased intramedullary pressure during application of the nail. To further elucidate the mechanisms underlying the promotion of bone formation more research is needed. The molecular characterization of the BMP-2 signal transduction cascade could yield more knowledge about how to safely and effectively use therapeutic gene therapy in impleant growth

Retrosigmoid Craniotomy for Cerebellopontine Epidermoid Cyst

Epidermoid cysts are benign lesions. The goal of this surgery is complete removal while preserving cranial nerves. Here, we illustrate the case of a 31-year-old male who presented with persistent headache following a short period of impaired consciousness. Imaging revealed a mass at the cerebellopontine angle (CPA) which at surgery proved to be an epidermoid cyst. In this video, we present the key steps of surgery. The postoperative course was uneventful and the patient was symptom-free at the 3 months of follow-up. The link to the video can be found at: https://youtu.be/0xwpkKwQoLI

Fluorescence-guided surgery of brain abscesses

Objectives: Fluorescein Sodium (FL) enhances areas in the brain with a disrupted blood brain barrier (BBB). Solitary brain abscesses (BA) are characterized by the pathognomonic finding of BBB disruption. Consequently, FL may have the potential to improve the intra-operative visualization of BA. Here, we report a series of patients with BA that where treated surgically after application of FL in combination with a dedicated light filter integrated in the surgical microscope. Methods: 7 patients (4 female, 3 male; mean age 53.8 years) with BA were included, all of them gave written informed consent. 5 mg/kg bodyweight of FL was administered via the central venous line at induction of anesthesia, approximately 30-45 min prior to surgery. We screened the surgical reports for any statement concerning the intensity of fluorescent staining. Results: Fluorescent staining was bright in all patients. Surgical removal of all parts of the BA, aspiration of pus and dissection of the capsule, were performed in the fluorescence-mode under the filtered light. We encountered no adverse events. Conclusion: The accumulation of FL resulted in brilliant visualization of the infected area under the YELLOW 560 nm filter. This small clinical study adds to the rapidly emerging clinical experiences of the use of fluorescein in neurosurgery, even for non-neoplastic lesions. However, prospective and randomized clinical trials are still necessary to establish the beneficial use of FL. (C) 2017 Elsevier B.V. All rights reserved

Feasibility of the custom-made titanium cranioplasty CRANIOTOP(®)

BACKGROUND: With decompressive craniectomy for ischemic stroke, traumatic brain injury, and skull-infiltrating tumors, the need for cranioplasty has increased. Different materials for custom-made cranioplasties have been evaluated, but a gold standard could not yet be established. We report our experience with the new custom-made titanium CRANIOTOP(®)cranioplasty (CL Instruments, Germany). METHODS: A total of 50 consecutive patients received a CRANIOTOP cranioplasty within a 2 year interval. We reviewed the charts for time between initial surgery and cranioplasty, indication, complications, operative time, and cosmetic outcome. Postoperative imaging (computed tomography [CT] scan n = 48, magnetic resonance imaging (MRI) n = 5) was screened for fitting accuracy and for hemorrhages. RESULTS: The most common indication for craniectomy were diffuse edema due to traumatic brain injury (n = 17, 34%) and ischemic stroke (n = 12, 24%). All patients were satisfied with the cosmetic result. In the postoperative CT scan accurate fitting was confirmed in all patients, the postoperative MRI was free of artifacts. Surgical revision was necessary in five patients because of empyema (n = 2), wound exposure (n = 2), and one cerebrospinal fluid fistula. Thus, the surgical morbidity was 10%. CONCLUSION: With due consideration of the limitations of this retrospective study, we feel the present data allow concluding that the custom-made titanium cranioplasty CRANIOTOP(®)is safe and feasible