Comparison of intraoperative CT- and cone beam CT-based spinal navigation for the treatment of atlantoaxial instability.

BACKGROUND CONTEXT: Due to the complexity of neurovascular structures in the atlantoaxial region, spinal navigation for posterior C1-C2 instrumentation is nowadays a helpful tool to increase accuracy of surgery and safety of patients. Many available intraoperative navigation devices have proven their reliability in this part of the spine. Two main imaging techniques are used: intraoperative CT (iCT) and cone beam computed tomography (CBCT). PURPOSE: Comparison of iCT- and CBCT-based technologies for navigated posterior instrumentation in C1-C2 instability. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 81 consecutive patients from July 2014 to April 2020. OUTCOME MEASURES: Screw accuracy and operating time. METHODS: Patients with C1-C2 instability received posterior instrumentation using C2 pedicle screws, C1 lateral mass or pedicle screws. All screws were inserted using intraoperative imaging either using iCT or CBCT systems and spinal navigation with autoregistration technology. Following navigated screw insertion, a second intraoperative scan was performed to assess the accuracy of screw placement. Accuracy was defined as the percentage of correctly placed screws or with minor cortical breach (<2 mm) as graded by an independent observer compared to misplaced screws. RESULTS: A total of 81 patients with C1-C2 instability were retrospectively analyzed. Of these, 34 patients were operated with the use of iCT and 47 with CBCT. No significant demographic difference was found between groups. In the iCT group, 97.7% of the C1-C2 screws were correctly inserted; 2.3% showed a minor cortical breach (<2 mm); no misplacement (>2 mm). In the CBCT group, 98.9% of screws were correctly inserted; no minor pedicle breach; 1.1% showed misplacement >2 mm. Accuracy of screw placement demonstrated no significant difference between groups. Both technologies allowed sufficient identification of screw misplacement intraoperatively leading to two screw revisions in the iCT and three in the CBCT group. Median time of surgery was significantly shorter using CBCT technology (166.5 minutes [iCT] vs 122 minutes [CBCT]; p<.01). CONCLUSIONS: Spinal navigation using either iCT- or CBCT-based systems with autoregistration allows safe and reliable screw placement and intraoperative assessment of screw positioning. Using the herein presented procedural protocols, CBCT systems allow shorter operating time.

Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism.

The breakdown of the blood-brain barrier (BBB) is a critical event in the development of secondary brain injury after stroke. Among the cellular hallmarks in the acute phase after stroke are a downregulation of tight-junction molecules and the loss of microvascular pericyte coverage and endothelial sealing. Thus, a rapid repair of blood vessel integrity and re-stabilization of the BBB is considered an important strategy to reduce secondary brain damage. However, the mechanisms underlying BBB disruption remain poorly understood. Especially, the role of VEGF in this context remains inconclusive. With the conditional and reversible VEGF expression systems, we studied the time windows of deleterious and beneficial VEGF actions on blood vessel integrity in mice. Using genetic systems for gain of function and loss of function experiments, we activated and inhibited VEGF signaling prior and simultaneously to ischemic stroke onset. In both scenarios, VEGF seems to play a vital role in containing the stroke-induced damage after cerebral ischemia. We report that the transgenic overexpression of VEGF (GOF) prior to the stroke stabilizes the vasculature and prevents blood-brain barrier disruption in young and aged animals after stroke. Whereas inhibition of signals for endogenous VEGF (LOF) prior to stroke results in bigger infarction with massive brain swelling and enhanced BBB permeability, furthermore, activating or blocking VEGF signaling after ischemic stroke onset had comparable effects on BBB repair and cerebral edema. VEGF can function as an anti-permeability factor, and a VEGF-based therapy in the context of stroke prevention and recovery has an enormous potential.

Oblique insertion of a straight cage during single level TLIF procedure proves to be non-inferior in terms of restoring segmental lordosis.

Introduction: With increasing relevance of the postoperative spinopelvic alignment, achieving optimal restoration of segmental lordosis (SL) during transforaminal lumbar interbody fusion (TLIF) has become increasingly important. However, despite the easier insertion of the straight cage, its potential to restore SL is still considered inferior to the preferred insert-and-rotate technique with a banana-shaped cage. Research question: To determine, if simple oblique insertion of a straight cage allows for an equally effective restoration of SL, but reduces risk for intraoperative cage subsidence requiring revision surgery. Material and methods: The authors retrospectively identified 81 patients who underwent single-level TLIF between 11/2017-03/2020. 40 patients were included in the straight cage group, 41 patients in the banana cage group. The authors determined pre- and postoperative SL from plain lateral radiographs. Bone density was analyzed on computed tomographs using Hounsfield unit (HU) values. Results: Both cage types were equally effective in restoring SL. However, 7.3% in the banana cage group, but none in the straight cage group, had to undergo revision surgery due to intraoperative cage subsidence. This was related to reduced bone density with lower HU values. Discussion: With an extended dorsal release, the straight cage may be equally effective in restoring SL. Since no repositioning is needed after oblique insertion, the straight cage might cause less intraoperative endplate violation. Conclusion: Provided an adequate surgical technique, both cage types might be equally effective in restoring SL after one-level TLIF surgery. However, the straight cage might represent the safer alternative in patients with reduced bone quality.

In vitro and in vivo testing of a novel local nicardipine delivery system to the brain: a preclinical study.

OBJECTIVE: The management of patients with aneurysmal subarachnoid hemorrhage (aSAH) remains a highly demanding challenge in critical care medicine. Despite all efforts, the calcium channel antagonist nimodipine remains the only drug approved for improving outcomes after aSAH. However, in its current form of application, it provides less than optimal efficacy and causes dose-limiting hypotension in a substantial number of patients. Here, the authors tested in vitro the release dynamics of a novel formulation of the calcium channel blocker nicardipine and in vivo local tolerance and tissue reaction using a chronic cranial window model in mice. METHODS: To characterize the release kinetics in vitro, dissolution experiments were performed using artificial cerebrospinal fluid over a time period of 21 days. The excipients used in this formulation (NicaPlant) for sustained nicardipine release are a mixture of two completely degradable polymers. A chronic cranial window in C57BL/6 mice was prepared, and NicaPlant slices were placed in proximity to the exposed cerebral vasculature. Epifluorescence video microscopy was performed right after implantation and on days 3 and 7 after surgery. Vessel diameter of the arteries and veins, vessel permeability, vessel configuration, and leukocyte-endothelial cell interaction were quantified by computer-assisted analysis. Immunofluorescence staining was performed to analyze inflammatory reactions and neuronal alterations. RESULTS: In vitro the nicardipine release profile showed an almost linear curve with about 80% release at day 15 and full release at day 21. In vivo epifluorescence video microscopy showed a significantly higher arterial vessel diameter in the NicaPlant group due to vessel dilatation (21.6 ± 2.6 µm vs 17.8 ± 1.5 µm in controls, p < 0.01) confirming vasoactivity of the implant, whereas the venous diameter was not affected. Vessel dilatation did not have any influence on the vessel permeability measured by contrast extravasation of the fluorescent dye in epifluorescence microscopy. Further, an increased leukocyte-endothelial cell interaction due to the implant could not be detected. Histological analysis did not show any microglial activation or accumulation. No structural neuronal changes were observed. CONCLUSIONS: NicaPlant provides continuous in vitro release of nicardipine over a 3-week observation period. In vivo testing confirmed vasoactivity and lack of toxicity. The local application of this novel nicardipine delivery system to the subarachnoid space is a promising tool to improve patient outcomes while avoiding systemic side effects.

Lateral Chronic Cranial Window Preparation Enables In Vivo Observation Following Distal Middle Cerebral Artery Occlusion in Mice.

Focal cerebral ischemia (i.e., ischemic stroke) may cause major brain injury, leading to a severe loss of neuronal function and consequently to a host of motor and cognitive disabilities. Its high prevalence poses a serious health burden, as stroke is among the principal causes of long-term disability and death worldwide1. Recovery of neuronal function is, in most cases, only partial. So far, treatment options are very limited, in particular due to the narrow time window for thrombolysis2,3. Determining methods to accelerate recovery from stroke remains a prime medical goal; however, this has been hampered by insufficient mechanistic insights into the recovery process. Experimental stroke researchers frequently employ rodent models of focal cerebral ischemia. Beyond the acute phase, stroke research is increasingly focused on the sub-acute and chronic phase following cerebral ischemia. Most stroke researchers apply permanent or transient occlusion of the MCA in mice or rats. In patients, occlusions of the MCA are among the most frequent causes of ischemic stroke4. Besides proximal occlusion of the MCA using the filament model, surgical occlusion of the distal MCA is probably the most frequently used model in experimental stroke research5. Occlusion of a distal (to the branching of the lenticulo-striate arteries) MCA branch typically spares the striatum and primarily affects the neocortex. Vessel occlusion can be permanent or transient. High reproducibility of lesion volume and very low mortality rates with respect to the long-term outcome are the main advantages of this model. Here, we demonstrate how to perform a chronic cranial window (CW) preparation lateral to the sagittal sinus, and afterwards how to surgically induce a distal stroke underneath the window using a craniotomy approach. This approach can be applied for sequential imaging of acute and chronic changes following ischemia via epi-illuminating, confocal laser scanning, and two-photon intravital microscopy.

Rotatory subluxation: experience from the Hospital for Sick Children.

OBJECT: Diagnosis and management of atlantoaxial rotatory subluxation (AARS) is challenging because of its variability in clinical presentation. Although several treatment modalities have been employed, there remains no consensus on the most appropriate therapy. The authors explore this issue in their 9-year series on AARS. METHODS: Records of patients diagnosed radiologically and clinically with AARS between May 2001 and March 2010 were retrospectively reviewed. Of 40 patients identified, 24 were male and were on average 8.5 years of age (range 15 months-16 years). Causes of AARS included trauma, congenital abnormalities, juvenile rheumatoid arthritis, infection, postsurgical event, and cryptogenic disease. Four patients had dual etiologies. Symptom duration varied: 29 patients had symptoms for less than 4 weeks, 5 patients had symptoms between 1 and 3 months, and 6 patients had symptoms for 3 months or more. RESULTS: Treatment with a cervical collar was sufficient in 21 patients. In 1 patient collar management failed and halter traction was used to reduce the subluxation. Seven patients underwent initial halter traction, but in 4 the subluxation progressed and the patients required halo traction. A halo vest was placed in 2 patients on presentation because the rotatory subluxation was severe; both patients required subsequent operative fusion. One patient required decompression and fusion due to severe canal compromise and myelopathy. All patients requiring fusion presented with subacute symptoms. CONCLUSIONS: Management of AARS varies due to the spectrum of clinical presentations. Patients presenting acutely without neurological deficits can likely undergo collar therapy; those in whom the subluxation cannot be reduced or who present with a neurological deficit may require traction and/or surgical fixation. Patients presenting subacutely may be more prone to requiring operative intervention.

Microvascular biodistribution of L19-SIP in angiogenesis targeting strategies.

INTRODUCTION: Various strategies using L19-mediated fibronectin targeting have become useful clinical tools in anti-tumour therapy and diagnostics. The aim of our study was to characterise the microvascular biodistribution and binding process during tumour angiogenesis and after anti-angiogenic therapy. MATERIALS AND METHODS: SF126 glioma and F9 teratocarcinoma cells were implanted into dorsal skin fold chambers (SF126: n = 4; F9: n = 6). Using fluorescence and confocal intravital microscopy the biodistribution process was assessed at t = 0 h, t = 4 h and t = 24 h after intravenous application of Cy3-L19-SIP. Sunitinib treatment was applied for six days and microscopy was performed 2 and 6 days after treatment initiation. Analysed parameters included: vascular and interstitial binding, preferential binding sites of L19-SIP, microvascular blood flow rate, microvascular permeability. Histological analysis included CD31 and DAPI. RESULTS: L19-SIP showed a specific and time-dependent neovascular binding with a secondary extravasation process reaching optimal vascular/interstitial binding ratio 4 hours after iv administration (F9: L19-SIP: vascular binding: 74.6 ± 14.5; interstitial binding: 46.8 ± 12.1; control vascular: 22,2 ± 16.6). Angiogenic sprouts were preferred binding sites (F9: L19-SIP: 188 ± 15.5; RTV: 90.6 ± 13.5). Anti-angiogenic therapy increased microvascular hemodynamics (SF126: Su: 106.6 ± 13.3 µl/sec; Untreated: 19.7 ± 9.1 µl/sec) and induced increased L19-SIP accumulation (SF 126: t24; Su: 92.6 ± 2.7; Untreated: 71.9 ± 5.9) in therapy resistant tumour vessels. CONCLUSION: L19-SIP shows a time and blood-flow dependent microvascular biodistribution process with angiogenic sprouts as preferential binding sites followed by secondary extravasation of the antibody. Microvascular biodistribution is enhanced in anti-angiogenic-therapy resistant tumour vessels.