Aneurysm healing following treatment with biodegradable embolization materials: assessment in a rat sidewall aneurysm model.

BACKGROUND: Biodegradable materials that dissolve after aneurysm healing are promising techniques in the field of neurointerventional surgery. We investigated the effects of various bioabsorable materials in combination with degradable magnesium alloy stents and evaluated aneurysm healing in a rat aneurysm model. METHODS: Saccular aneurysms were created by end-to-side anastomosis in the abdominal aorta of Wistar rats. Untreated arterial grafts were immediately transplanted (vital aneurysms) whereas aneurysms with loss of mural cells were chemically decellularized before implantation. All aneurysms were treated with biodegradable magnesium stents. The animals were assigned to vital aneurysms treated with stent alone or decellularized aneurysms treated with stent alone, detachable coil, or long-term or short-term biodegradable thread. Aneurysm healing, rated microscopically and macroscopically at follow-up days 7 and 21, was defined by both neointima formation and absence of aneurysm volume increase over time. RESULTS: Of 56 animals included, significant increases in aneurysm volume 7 days after surgery were observed in aneurysms with vital and decellularized walls treated with a stent only (P=0.043 each group). Twenty-one days after surgery an increase in aneurysm volume was observed in decellularized aneurysms treated with long- and short-term biodegradable threads (P=0.027 and P=0.028, respectively). Histological changes associated with an increase in aneurysm volume were seen for aneurysm wall inflammation, periadventitial fibrosis, and luminal thrombus. CONCLUSIONS: An increase in aneurysm volume was associated with an absence of intrasaccular embolization material (early phase) and the breakdown of intrasaccular biodegradable material over time (late phase). Thrombus remnant and aneurysm wall inflammation promote aneurysm volume increase.

The modified occipital condyle screw: A quantitative anatomic study investigating the feasibility of a novel instrumented fixation technique for craniocervical fusion.

Study Design: Prospective human anatomical study. Objective: Occipitocervical fusion with occipital plate or condyle screws has shown higher failure rates in those with skeletal dysplasia. The modified occipital condyle screw connects the occipital condyle to the pars basilaris of the occipital bone that may achieve fortified bony purchase and serve as a more rigid fixation point. We evaluate anatomical feasibility of a novel cranial fixation technique designed to decrease risk of pseudarthrosis. Materials and Methods: Occipital condyles were analyzed morphologically using multiplanar three-dimensional reconstructed, ultra-thin section computed tomography. The following parameters were obtained: occipital condyle length, maximal cross section, location of hypoglossal canal, axial and sagittal orientation of the long axis, occipital condyle pedicle (OCP) diameter, maximal length of OCP screw, and entry point. Results: Forty patients with total of 80 occipital condyles were analyzed and the following measurements were obtained: occipital condyle length 24.1 mm (20.5-27.7, standard deviation [SD]: 2.2); condyle maximum axial cross-section 12.6 mm (9-15.8, SD: 1.9); length of OCP screw 38.9 mm (29.3-44, SD: 5.7); diameter of OCP 3.4 mm (3.2-3.6, SD: 0.2); clearance below hypoglossal canal 4.5 mm (3.4-7, SD: 1.1); and distance of screw entry point from condylar foramen 2 mm (range 0-4, SD 1.6). Conclusion: The modified occipital condyle screw connects the condyle with the clivus through the pars basilaris and represents a safe and technically feasible approach to achieve craniocervical fusion in skeletally mature individuals. This cephalad anchor point serves as an alternate fixation point of the occipitocervical junction with increased strength of construct and decreased risk of hardware failure or pseudarthrosis given cortical bone purchase and longer screw instrumentation.

Growing Fat Tissue After Grafting for Dural Sealing.

We report on a young patient with a growing retroauricular benign fat tissue tumor after juvenile fat grafting for dural sealing of a placed ventriculoperitoneal shunt. The clinical images indicate fat tissue rather than a cerebrospinal fluid leak due to potential shunt malfunction suspected on plain radiography. Human adipose tissue is a source of stem cells that can replicate rather than undergoing necrosis, in particular when transplanted during development.

Risk of intracranial aneurysm recurrence after microsurgical clipping based on 3D digital subtraction angiography.

OBJECTIVE: Current knowledge of recurrence rates after intracranial aneurysm (IA) surgery relies on 2D digital subtraction angiography (DSA), which fails to detect more than 75% of small aneurysm remnants. Accordingly, the discrimination between recurrence and growth of a remnant remains challenging, and actual assessment of recurrence risk of clipped IAs could be inaccurate. The authors report, for the first time, 3D-DSA-based long-term durability and risk factor data of IA recurrence and remnant growth after microsurgical clipping. METHODS: Prospectively collected data for 305 patients, with a total of 329 clipped IAs that underwent baseline 3D-DSA, were evaluated. The incidence of recurrent IA was described by Kaplan-Meier curves. Risk factors for IA recurrence were analyzed by multivariable Cox proportional hazards and logistic regression models. RESULTS: The overall observed proportion of IA recurrence after clipping was 2.7% (9 of 329 IAs) at a mean follow-up of 46 months (0.7% per year). While completely obliterated IAs did not recur during follow-up, incompletely clipped aneurysms (76 of 329) demonstrated remnant growth in 11.8% (3.4% per year). Young age and large initial IA size significantly increased the risk of IA recurrence. CONCLUSIONS: The findings support those in previous studies that hypothesized that completely clipped IAs have an extremely low risk of recurrence. Conversely, the results highlight the significant risk posed by incompletely clipped IAs. Young patients with initial large IAs and incomplete obliteration have an especially high risk for IA recurrence and therefore should be monitored more closely.

Parent artery-initiated and stent-mediated neointima formation in a rat saccular side wall model.

BACKGROUND: Unlike clipping that forms an immediate barrier of blood flow into intracranial aneurysms, endovascular treatments rely on thrombus organization and neointima formation. Therefore, a continuous endothelial cell layer is crucial to prevent blood flow in the former aneurysm. This study investigates the origin of endothelial cells in the neointima of endovascular treated aneurysms, specifically whether cells from the parent artery play a role in neointima formation. METHODS: In male rats, decellularized and vital side wall aneurysms were treated by coil (n=16) or stent embolization (n=15). The cell tracer CM-Dil dye was injected into the clamped aorta before aneurysm suture to mark initial endothelial cells in the parent artery and enable tracking of their proliferation during follow-up. Aneurysms were analyzed for growth, thrombus formation, and recurrence. Histological evaluation followed with cell counts for specific regions-of-interest. RESULTS: During follow-up, none of the 31 aneurysms ruptured. Macroscopic residual perfusion was observed in 12/16 rats after coiling and in 1/15 after stenting. Amounts of CM-Dil +cells in coiled versus stented decellularized aneurysms significantly decreased in the thrombus on day 7 (p=0.01) and neointima on day 21 (p=0.04). For vital aneurysms, the number of CM-Dil +cells in the neointima on day 21 showed no significant difference. CONCLUSIONS: Healing patterns were worse in coil-treated than stent-treated aneurysms. Cell migration forming a neointima seemed mainly dependent on the adjacent vessel in decellularized aneurysms, but appeared buoyed by recruitment from aneurysm wall cells in vital aneurysms. Therefore, a cell-rich parent artery might be crucial.

Aspirin treatment prevents inflammation in experimental bifurcation aneurysms in New Zealand White rabbits.

BACKGROUND: Aneurysm wall degeneration is linked to growth and rupture. To address the effect of aspirin (ASA) on aneurysm formation under various wall conditions, this issue was analyzed in a novel rabbit bifurcation model. METHODS: Bifurcation aneurysms created in 45 New Zealand White rabbits were randomized to vital (n=15), decellularized (n=13), or elastase-degraded (n=17) wall groups; each group was assigned to a study arm with or without ASA. At follow-up 28 days later, aneurysms were evaluated for patency, growth, and wall inflammation at macroscopic and histological levels. RESULTS: 36 rabbits survived to follow-up at the end of the trial. None of the aneurysms had ruptured. Patency was visualized in all aneurysms by intraoperative fluorescence angiography and confirmed in 33 (92%) of 36 aneurysms by MRI/MRA. Aneurysm size was significantly increased in the vital (without ASA) and elastase-degraded (with and without ASA) groups. Aneurysm thrombosis was considered complete in three (50%) of six decellularized aneurysms without ASA by MRI/MRA. Locoregional inflammation of the aneurysm complex was significantly reduced in histological analysis among all groups treated with ASA. CONCLUSION: ASA intake prevented inflammation of both the periadventitial tissue and aneurysm wall, irrespective of initial wall condition. Although ASA prevented significant growth in aneurysms with vital walls, this preventive effect did not have an important role in elastase-degraded pouches. In possible translation to the clinical situation, ASA might exert a potential preventive effect during early phases of aneurysm formation in patients with healthy vessels but not in those with highly degenerative aneurysm walls.

Compensatory mechanisms in adult degenerative thoracolumbar spinal deformity - Radiographic patterns, their reversibility after corrective surgery, and the influence of pelvic morphology.

Objective: Loss of lumbar lordosis (LL) in degenerative deformity activates spinal compensatory mechanisms to maintain neutral C7 sagittal vertical axis (C7SVA), such as an increase in pelvic tilt (PT) and decreased thoracic kyphosis (TK). We study the extent to which PT increase and TK reduction contribute to the compensation of pelvic incidence (PI)-LL mismatch. Methods: A cohort of 43 adult patients with adult degenerative thoracolumbar deformity were included in this retrospective study. Radiographic spinopelvic measurements were obtained before and after corrective surgery. Pearson correlations were calculated. Results: Preoperative PI-LL mismatch significantly correlated with an increase in PT and a decrease in TK in the whole cohort r = +0.66 (95% confidence interval [CI] 0.44-0.8) and r = -0.67 (95% CI - 0.81--0.47), respectively, at a relative rate of 0.37 (standard deviation [SD]: 0.07) and - 0.57 (SD: 0.09), respectively. In patients with low PI, only TK showed a significant correlation with PI-LL mismatch, r = -0.56 (95% CI - 0.8 to - 0.16), at a rate of - 0.57 (SD: 0.19). The high PI subgroup showed a significant correlation with PT, TK, and C7SVA, r = 0.62 (95% CI 0.26-0.82), r = -0.8 (95% CI - 0.9--0.58), and r = 0.71 (95% CI 0.41-0.87) at rates of 0.48 (SD: 0.11), -0.72 (SD: 0.12), and 0.62 (SD: 1.27). Conclusions: Decreased TK represented a more consistent compensatory mechanism in patients with high and low PI when compared to an increase in PT. PI-LL mismatch induced more pronounced changes in TK than did PT in both subgroups. Patients with high PI relied more on increases in PT and a relative decrease in TK to compensate for PI-LL mismatch than patients with low PI.

An unexpected intracerebral lesion - case report of a superinfected aspergillosis mimicking a brain metastasis.

BACKGROUND: Invasive aspergillosis of the central nervous system is a rare but increasingly prevalent disease. We present the unusual case of an immunosuppressed patient suffering from unexpected superinfected invasive aspergillosis with cerebral, pulmonal, and adrenal manifestations, mimicking a metastasized bronchial carcinoma. This report reveals the importance of including aspergillosis in the differential diagnosis of a cerebral mass lesion in the light of unspecific clinical findings. CASE PRESENTATION: A 58-year-old immunocompromised female presented to our emergency department with a single tonic-clonic seizure. Imaging showed a ring enhancing cerebral mass with perifocal edema and evidence of two smaller additional hemorrhagic cerebral lesions. In the setting of a mass lesion in the lung, and additional nodular lesions in the left adrenal gland the diagnosis of a metastasized bronchus carcinoma was suspected and the cerebral mass resected. However, histology did not reveal any evidence for a neoplastic lesion but septate hyphae consistent with aspergillus instead and microbiological cultures confirmed concomitant staphylococcal infection. CONCLUSIONS: A high index of suspicion for aspergillus infection should be maintained in the setting of immunosuppression. Clinical and radiological findings are often unspecific and even misleading. Definite confirmation usually relies on tissue diagnosis with histochemical stains. Surgical resection is crucial for establishing the diagnosis and guiding therapy with targeted antifungal medications.

An endovascular assisted, nonocclusive cerebral bypass: a technical feasibility study in a rabbit model.

OBJECTIVE: Temporary parent vessel occlusion performed to establish a high-flow interpositional bypass carries the risk of infarcts. The authors investigated the feasibility of a novel technique to establish a high-flow bypass without temporary parent vessel occlusion in order to lower the risk of ischemic complications. METHODS: In 10 New Zealand white rabbits, a carotid artery side-to-end anastomosis was performed under parent artery patency with a novel endovascular balloon device. Intraoperative angiography, postoperative neurological assessments, and postoperative MRI/MRA were performed to evaluate the feasibility and safety of the novel technique. RESULTS: A patent anastomosis was established in 10 of 10 animals; 3 procedure-related complications occurred. No postoperative focal neurological deficits were observed. The MRI/MRA findings include no infarcts and bypass patency in 50% of the animals. CONCLUSIONS: The authors demonstrated the feasibility of an endovascular assisted, nonocclusive high-flow bypass. Future refinement of the device and technique in an animal model is necessary to lower the complication rate and increase patency rates.

Comparison of Aneurysm Patency and Mural Inflammation in an Arterial Rabbit Sidewall and Bifurcation Aneurysm Model under Consideration of Different Wall Conditions.

Background: Biological processes that lead to aneurysm formation, growth and rupture are insufficiently understood. Vessel wall inflammation and degeneration are suggested to be the driving factors. In this study, we aimed to investigate the natural course of vital (non-decellularized) and decellularized aneurysms in a rabbit sidewall and bifurcation model. Methods: Arterial pouches were sutured end-to-side on the carotid artery of New Zealand White rabbits (vital [n = 6] or decellularized [n = 6]), and into an end-to-side common carotid artery bifurcation (vital [n = 6] and decellularized [n = 6]). Patency was confirmed by fluorescence angiography. After 28 days, all animals underwent magnetic resonance and fluorescence angiography followed by aneurysm harvesting for macroscopic and histological evaluation. Results: None of the aneurysms ruptured during follow-up. All sidewall aneurysms thrombosed with histological inferior thrombus organization observed in decellularized compared to vital aneurysms. In the bifurcation model, half of all decellularized aneurysms thrombosed whereas the non-decellularized aneurysms remained patent with relevant increase in size compared to baseline. Conclusions: Poor thrombus organization in decellularized sidewall aneurysms confirmed the important role of mural cells in aneurysm healing after thrombus formation. Several factors such as restriction by neck tissue, small dimensions and hemodynamics may have prevented aneurysm growth despite pronounced inflammation in decellularized aneurysms. In the bifurcation model, rarefication of mural cells did not increase the risk of aneurysm growth but tendency to spontaneous thrombosis.

Junctional kyphosis and junctional failure after multi-segmental posterior cervicothoracic fusion - A retrospective analysis of 64 patients.

INTRODUCTION: Junctional kyphosis (JK) and junctional failure (JF) are known complications after thoracolumbar spinal deformity surgery. This study aims to define the incidence and possible risk factors for JK/JF following multi-segmental cervicothoracic fusion. METHODS: This is a retrospective analysis of 64 consecutive patients undergoing cervicothoracic fusion surgery, including at least five segments. Clinical and radiographic outcome measures were analyzed. A univariate analysis was performed to determine the effect of the level of upper instrumented vertebra (UIV) and lower instrumented vertebra (LIV), fusion status, C2 sagittal vertical axis (SVA), C2-C7 lordotic angle and T1 slope angle on the occurrence of JK/JF. RESULTS: A total of 46 patients were followed up for a median of 1.1 years (range 0.3-4) with a median age of 65.5 years (range 42.2-84.5). Indication for surgery was spinal stenosis in 87%, trauma in 7%, and tumor in 6% of cases. The median number of levels fused was 7; the most frequent UIV was C2, and the most frequent LIV was T2. Solid fusion was achieved in 78% at the last follow-up. Postoperatively, the median C2 SVA was 32 mm (range - 7-75), median T1 slope angle was 33° (range 2°-57°), C2-C7 sagittal cobb angle was 4° (-29°-12°). JK developed in 4% of cases, no case of JF was observed. No statistically significant impact of bone density, level of UIV, level of LIV or postoperative sagittal parameters on the occurrence of JK/JF was observed, even though fusion status and pathologic T1 slope angle showed a trend toward significance. CONCLUSION: In this cohort of patients with mildly pathologic sagittal balance, JK was a rare event after multi-segmental fusion, observed in only 4% of cases. Neither level of UIV nor LIV had an influence on its occurrence; however, nonunion and pathologic sagittal alignment showed a nonsignificant trend.

Aneurysm wall cellularity affects healing after coil embolization: assessment in a rat saccular aneurysm model.

BACKGROUND AND PURPOSE: Despite significant technical advances, recanalization rates after endovascular therapy of ruptured intracranial aneurysms (IAs) remain a clinical challenge. A histopathological hallmark of ruptured human IA walls is mural cell loss. Mural smooth muscle cells (SMCs) are known to promote intraluminal healing in thrombosed experimental aneurysms. In this rat model we assess the natural history and healing process after coil embolization in SMC-rich and decellularized aneurysms. METHODS: Saccular aneurysms were created by end-to-side anastomosis of an arterial graft from the descending thoracic aorta of a syngeneic donor rat to the infrarenal abdominal aorta of recipient male Wistar rats. Untreated arterial grafts were immediately transplanted, whereas aneurysms with loss of mural cells were chemically decellularized before implantation. Aneurysms underwent coil implantation during aneurysm anastomosis. Animals were randomly assigned either to the non-decellularized or decellularized group and underwent macroscopic and histological analyses on days 3, 7, 21, or 90 post-coil implantation. RESULTS: A total of 55 rats underwent macroscopic and histologic analysis. After coil embolization, aneurysms with SMC-rich walls showed a linear course of thrombosis and neointima formation whereas decellularized aneurysms showed marked inflammatory wall degeneration with increased recanalization rates 21 days (p=0.002) and 90 days (p=0.037) later. The SMCs showed the ability to actively migrate into the intra-aneurysmal thrombus and participate in thrombus organization. CONCLUSIONS: Coil embolization of aneurysms with highly degenerated walls is prone to further wall degeneration, increased inflammation, and recanalization compared with aneurysms with vital SMC-rich walls.

Fluorescence Video Angiography for Evaluation of Dynamic Perfusion Status in an Aneurysm Preclinical Experimental Setting.

BACKGROUND: Experimental studies to assess aneurysm occlusion or perfusion typically rely on macroscopic examination or histological analysis but cannot assess dynamic perfusion. OBJECTIVE: To describe an easy-to-implement and inexpensive fluorescence angiographic technique for the in vivo assessment and imaging of the dynamic perfusion status of aneurysms and their underlying blood vessels in a rat model. METHODS: In a rat sidewall aneurysm model, the angiographic setup included 2 bandpass filters, a video camera, and a bicycle spotlight. After 48 rats underwent fluorescein angiography, dissections were performed to confirm the perfusion status by macroscopic and histologic examination of the aneurysm. RESULTS: Direct injection of 0.2 mL fluorescein 10% Faure achieved strong, clear visibility in all 48 aneurysms. Macro-/microscopic examination identified residual perfusion in 25 and complete healing in 23 aneurysms. Fluorescein imaging identified 21 of these 25 aneurysms (84%) with residual perfusion and 22 of 23 aneurysms (96%) with no residual perfusion. CONCLUSION: Our fluorescein imaging technique proved efficient for the evaluation of aneurysm patency and parent artery integrity in this experimental setting. Fluorescein is nontoxic, can be re-administered if needed, and, in this technique, can expand the armamentarium for the preclinical evaluation of dynamic perfusion status.

Testing bioresorbable stent feasibility in a rat aneurysm model.

BACKGROUND: Advances in stent-assisted coiling have incrementally expanded endovascular treatment options for complex cerebral aneurysms. After successful coil consolidation and aneurysm occlusion, endovascular scaffolds are no longer needed. Thus, bioresorbable stents that disappear after aneurysm healing could avoid future risks of in-stent thrombosis and the need for lifelong antiplatelet therapy. OBJECTIVE: To assess the applicability and compatibility of a bioresorbable magnesium- alloy stent (brMAS) for assisted coiling. METHODS: Saccular sidewall aneurysms were created in 84 male Wistar rats and treated with brMAS alone, brMAS + aspirin, or brMAS + coils + aspirin. Control groups included no treatment (natural course), solely aspirin treatment, or conventional cobalt-chromium stent + coils + aspirin treatment. After 1 and 4 weeks, aneurysm specimens were harvested and macroscopically, histologically, and molecularly examined for healing, parent artery perfusion status, and inflammatory reactions. Stent degradation was monitored for up to 6 months with micro-computed and optical coherence tomography. RESULTS: Aneurysms treated with brMAS showed advanced healing, neointima formation, and subsequent stent degradation. Additional administration of aspirin sustained aneurysm healing while reducing stent-induced intraluminal and periadventitial inflammatory responses. No negative interaction was detected between platinum coils and brMAS. Progressive brMAS degradation was confirmed. CONCLUSIONS: brMAS induced appropriate healing in this sidewall aneurysm model. The concept of using bioresorbable materials to promote complete aneurysm healing and subsequent stent degradation seems promising. These results should encourage further device refinements and clinical evaluation of this treatment strategy for cerebrovascular aneurysms.

Comparison of 3D intraoperative digital subtraction angiography and intraoperative indocyanine green video angiography during intracranial aneurysm surgery.

OBJECTIVE: During the last decade, improvements in real-time, high-resolution imaging of surgically exposed cerebral vasculature have been realized with the successful introduction of intraoperative indocyanine green video angiography (ICGVA) and technical advances in intraoperative digital subtraction angiography (DSA). With the availability of 3D intraoperative DSA (3D-iDSA) in hybrid operating rooms, the present study offers a contemporary comparison for rates of accuracy and discordance. METHODS: In this retrospective study of prospectively collected data, 140 consecutive patients underwent microsurgical treatment of intracranial aneurysms (IAs) in a hybrid operating room. Variables analyzed included patient demographics, aneurysm-specific characteristics, intraoperative ICGVA and 3D-iDSA findings, and the need for intraoperative clip readjustment. The authors defined the discordance rate of the two modalities as a false-negative finding that necessitated clip repositioning after 3D-iDSA. RESULTS: In 120 patients, ICGVA and 3D-iDSA were used to evaluate 134 IA obliterations. Of 215 clips used, 29 (14%) were repositioned intraoperatively, improving the surgical result in all 29 patients (24%). Repositioning was prompted by visual inspection and microvascular Doppler ultrasonography in 8 (28%), ICGVA in 13 (45%), and 3D-iDSA in 7 (24%) patients. Clip repositioning was needed in 7 patients (6%) based on 3D-iDSA, yielding an ICGVA accuracy rate of 94%. Five (71%) of the ICGVA-3D-iDSA discordances that prompted clip repositioning occurred at the anterior communicating artery complex. CONCLUSIONS: A combination of vascular monitoring techniques most often achieved correct intraoperative interpretation of complete IA occlusion and parent artery integrity. Compared with 3D-iDSA imaging, ICGVA demonstrated high accuracy. Despite the relatively low discordance rate, iDSA was confirmed to be the gold standard. Improved imaging quality, including 3D-iDSA, supports its routine use in IA surgery, obviating the need for postoperative DSA.