Camillo Sherif

Ruptured carotid artery aneurysms of the ophthalmic (C6) segment: clinical and angiographic long-term follow-up of a multidisciplinary management strategy

Background: The management of ruptured C6 aneurysms remains controversial. Detailed long-term outcome data are still lacking. Thus the present study provided a detailed long term follow-up for a multidisciplinary approach combining microsurgical clipping, endovascular embolisation and parent artery occlusion with/without bypass protection. Methods: In our single centre analysis of 64 consecutive patients, indications for microsurgery were: superior aneurysm projection, giant/large or wide necked aneurysms and aneurysms at branching sites. Indications for embolisation were: narrow necks, neck calcification, close aneurysm relation to the clinoid process or adhesion to the distal dural ring, and aneurysm location in the concavity of the carotid siphon curve. Results: 23 patients (35.9%) underwent microsurgery, 38 patients (59.4%) embolisation and three patients (4.7%) parent artery occlusion under bypass protection. Retreatment was required in 20.9% (surgery 8.7%, endovascular 31.6%). Procedure related transient complications occurred in 10.9% (surgery 13.0%, endovascular 10.5%). Procedure related permanent morbidities occurred in 6.3% (surgery 8.7%, endovascular 5.3%), including visual deficits in 4.7% (surgery 4.4%, endovascular 5.3%). One endovascular patient died. Angiographic follow-up (29.2 (SD 31.9) months) revealed total aneurysm occlusion in 94.4% of the surgical and 82.9% of the endovascular patients. Clinical follow-up (58.7 (SD 47.6) months) showed 73.4% of the population reaching Glasgow Outcome Scale 4–5, these data being equivalent to the International Subarachnoid Aneurysm Trial (ISAT) outcomes. Conclusions: Based on favourable neuroradiological and ophthalmological outcomes, microsurgery is recommended for superiorly projecting aneurysms, especially aneurysms involving the ophthalmic artery, and for giant/large or wide necked aneurysms. Based on stable aneurysm occlusion and excellent clinical outcomes, embolisation can be recommended for inferiorly/medially projecting small, narrow necked aneurysms.

Angioarchitectural heterogeneity in human glioblastoma multiforme: A fractal-based histopathological assessment

There is currently no standard technique to objectively quantify the microvascularization of brain tumors. Fractal analysis has been proposed as a useful descriptor of tumor microvascularity. Standardization of the fractal analysis methodology could offer a new tool for this type of characterization. In this study, we applied fractal analysis to the characterization of the different angioarchitectures found in specimens of glioblastoma multiforme (GBM), the most common and most malignant type of human brain tumor. A retrospective series of 114 primary GBM specimens was carried out. To quantify neoplastic microvascularity, the level of two-dimensional geometrical complexity of the microvascular patterns was assessed using the box-counting algorithm, which estimates the microvascular fractal dimension (mvFD). mvFD makes information on the non-Euclidean space filled by vessels embedded in the tumor microenvironment available because it depends on vessel number, shape, magnitude and distribution pattern. A mean mvFD value of 1.44 ± 0.17 (range: 1.06-1.87) was found. The coefficient of variation was 44%. The high geometric variability, found objectively, in these samples reflects the angioarchitectural heterogeneity underlying GBM. The present study shows that angioarchitectural subtypes can be identified by mvFD, making this parameter a potential tool for quantifying different neoplastic microvascular patterns.

COMPUTER-ASSISTED QUANTIFICATION OF OCCLUSION AND COIL DENSITIES ON ANGIOGRAPHIC AND HISTOLOGICAL IMAGES OF EXPERIMENTAL ANEURYSMS

OBJECTIVE: Occlusion rates (OR) and coil densities were quantified by computer-assisted morphometry on angiograms and histological ground sections of coil-embolized experimental aneurysms. The aims of this study were 1) to develop computer-assisted evaluations of angiographic OR and histometrical OR, 2) to compare these results to subjectively estimated angiographic OR from clinical practice, and 3) to test the correlation between histometrical data of coil density and occlusion. METHODS: Eight rabbit carotid-bifurcation aneurysms had been followed by digital subtraction angiography (DSA) before and after Guglielmi detachable coil embolization and at sacrifice (1 h to 24 wk postembolization). Angiographic OR was subjectively estimated, then determined by computer-assisted density-gradient distinction on digitized DSAs. Histometrically, maximum length, neck width, total area, recanalized area, and coil-occupied area were measured on digitized and calibrated color micrographs from surface-stained histological ground sections of the aneurysms. Histometrical OR and coil density were calculated as indirect parameters. RESULTS: Subjective versus computer-assisted angiographic OR yielded for one aneurysm, 100% versus 100%, and for three aneurysms less than 90% versus 65 to 60% occlusion. For four aneurysms, OR was estimated greater than 90%, whereas computer-assisted OR ranged between 45 to 80%, the latter being more precise because of better definition of the aneurysms total area on digitized DSA. Histometrical OR ranged between 32.8 and 87.6%, but did not correlate significantly with computer-assisted angiographic OR (r = 0.467, P > 0.1) because of differences in two aneurysms. Coil densities between 5.5 and 22.1% were slightly lower than reported in literature but significantly correlated to histometrical OR (r = 0.646, P < 0.05). CONCLUSION: Computer-assisted DSA evaluation, delivering more precise values than subjectively estimated occlusion, may be a useful tool for follow-up studies. Comparing computer-assisted angiographic with histometrical occlusion demonstrates limits of DSA in displaying the real morphology of coil-embolized aneurysms. The clinically postulated correlation of OR and coil densities was statistically corroborated.

Computerized assessment of angiographic occlusion rate and coil density in embolized human cerebral aneurysms.

BACKGROUND AND PURPOSE: Computerized methods have been introduced for more objective quantification of angiographic occlusion rate and coil density as parameters of successful embolization. This study aimed 1) to evaluate this new computerized method for angiographic occlusion rating and coil density calculations by comparison with corresponding histometric parameters from retrieved human aneurysms, and 2) to compare the new computerized method with the present standard of subjective angiographic occlusion rating. MATERIALS AND METHODS: From 14 postmortem-retrieved human aneurysms, angiographic occlusion rate was determined by contrast medium attenuation-gradient distinction on digital subtraction angiographs after Guglielmi detachable coil (GDC) embolization. Angiographic coil density was calculated, approximating aneurysms as ellipsoid and coils as cylindric volumes. On surface-stained histologic ground sections of the respective aneurysms, the occluded aneurysm area and coil area were measured. Then, we calculated and compared the histometric occlusion rates and coil densities with the corresponding angiographic parameters by using the Wilcoxon paired signed-rank test and the Spearman rank correlation. RESULTS: Computerized angiographic occlusion rates (75%–100%) showed good correlation (r = 0.799; P < .01) with histometric occlusion-rates (61%–100%), resulting in no statistically significant differences (P = .2163). With 5.1% (±3.8), the mean difference between computerized angiographic occlusion rates and histometry was substantially lower compared with 10.7% (±8.7) mean difference between subjective angiographic estimations and histometry. Calculated angiographic coil density (13%–32%) significantly differed from histometric coil density (8%–35%; P < .05). CONCLUSIONS: For recanalized aneurysms, computerized angiographic occlusion rating showed better correspondence with histometry compared with subjective angiographic occlusion rating. Clinical application of this new tool may lead to more objective cutoff values for re-embolization indications. The value of coil density calculations seems limited by the approximation of the aneurysms as ellipsoid volumes.

The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats

After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of CD68(+) cells with concomitant reduction of oxidative stress as reflected by lower expression of inducible nitric oxide synthase. Notably, MNC-secretome showed angiogenic properties ex vivo in aortic rings and spinal cord tissue, and experiments showed that the angiogenic potential of MNC-secretome may be regulated by CXCL-1 upregulation in vivo. Moreover, systemic application of MNC-secretome activated the ERK1/2 pathway in the spinal cord. Taken together, these results indicate that factors in MNC-secretome can mitigate the pathophysiological processes of secondary damage after SCI and improve functional outcomes in rats.

The subdiaphragmatic cistern: historic and radioanatomic findings

BackgroundIn the past, sporadic demonstrations of the existence of a subarachnoid subdiaphragmatic cistern have been published. The aim of this study was to evaluate the anatomical characteristics of the subdiaphragmatic cistern of the pituitary gland.MethodsAfter a complete review of the literature published on the topic, we report anatomical observations of the subdiaphragmatic cistern and its relationship to the pituitary gland and to the chiasmatic cistern. Ten cadaveric heads were studied using different techniques and surgical methods (plastination, plastic casts of the subarachnoid spaces, microscopic and transsphenoidal endoscopic approaches). Moreover, 3-T magnetic resonance images of ten healthy volunteers were analyzed to investigate the presence and anatomical variability of the subdiaphragmatic cistern.ResultsBy means of our qualitative radioanatomic study, we found that the roof of the subdiaphragmatic cistern is formed by the diaphragma sellae, the floor by the superior face of the pituitary gland, the lateral walls by the arachnoidea extending laterally through the medial walls of the cavernous sinus, and the medial walls by the infundibular stem. The subdiaphragmatic cistern communicates by means of the ostium of the diaphragm with the chiasmatic cistern.ConclusionWe confirmed the existence of the subdiaphragmatic cistern. The overused term “suprasellar cistern” refers more to a complex of cisterns, formed by the subdiaphragmatic cistern, below the diaphragma sella, and by the chiasmatic cistern, above it, in direct communication with the lamina terminalis and carotid cisterns.

Deep brain pulse-generator and lead-extensions: subjective sensations related to measured parameters.

This study analyzed subjective sensations caused by DBS pulse‐generator and lead‐extensions in relation with objectively measured parameters. In 50 patients implant‐related sensations were evaluated. The pulse‐generator mobility was video‐analyzed. Insufficient lead‐extension/pulse‐generator tolerability (72%/84%) was documented. Furthermore, 54% of the patients described movement impairments and 48% cosmetic deformity. High body mass index (BMI) was associated with low lead‐extension related pain (P < 0.001). High generator mobility resulted in high lead‐extension related pain (P < 0.001). Compared with lead‐extension type 7482, type 7495 showed less lead‐extension related pain (P = 0.0138), we suppose secondary to surgical tunneling instruments with a larger tip diameter. The lead‐extension path with one tissue tunnel for both lead‐extensions had 36% lead‐extension related pain versus 11% for the path with one single tunnel for each lead‐extension. Smaller pulse‐generators for better cosmetic results, surgical procedures using larger tunneling instruments and one single tunnel for each lead‐extension would provide better results forpatients with BMI <30.

Very large and giant microsurgical bifurcation aneurysms in rabbits: Proof of feasibility and comparability using computational fluid dynamics and biomechanical testing

BACKGROUND Giant aneurysms are challenging lesions with unacceptable high rates of aneurysm recanalization and rerupture following embolization. Reliable in vivo models are urgently needed to test the performance of new more efficient endovascular devices. MATERIALS AND METHODS Aneurysms were created in 11 New Zealand white rabbits (4.5-5.5kg): A long venous pouch (length 25-30mm) mimicking the aneurysm sac was derived from the external jugular vein and sutured into a microsurgically created bifurcation between both common carotid arteries. After 4 weeks the rabbits underwent 3T Magnetic resonance angiography (3T-MRA). Exemplary computational fluid dynamics (CFD) simulations were performed to compare the flow conditions of giant rabbit and human aneurysms. We used species-related boundary conditions, in particular, we measured blood viscosity values. Biaxial mechanical tests were performed for the mechanical characterization and comparison. COMPARISON WITH EXISITING METHOD(S) None. RESULTS No peri- or postoperative mortality was observed. 3T-MRA showed aneurysm patency in 10 out of 11 aneurysms (90.9%). Aneurysm lengths ranged from 21.5-25.6mm and aneurysm necks from 7.3-9.8mm. CFD showed complex flow profiles with multiple vortices in both, rabbit and human aneurysms. Lower blood viscosity values of the rabbit (3.92mPas vs. human 5.34mPas) resulted in considerable lower wall shear stress rates (rabbit 0.38Pa vs. human 1.66Pa). Mechanical tests showed lower stiffness of rabbit aneurysms compared to unruptured human aneurysms. CONCLUSIONS The proposed model showed favorable aneurysm patency rates, low morbidity and good hemodynamic comparability with complex flow patterns. Biomechanical testing suggests that experimental aneurysms might be even more fragile compared to human aneurysms.

Long-term patency of complex bilobular, bisaccular, and broad-neck aneurysms in the rabbit microsurgical venous pouch bifurcation model.

Abstract Objectives: In experimental aneurysm models, long-term patency without spontaneous thrombosis is the most important precondition for analyses of embolization devices. We recently reported the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, low mortality, and high short-term aneurysm patency. In order to further evaluate our model, we examined the long-term patency rate. Methods: Various sizes of complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both common carotid arteries in 17 rabbits. Early aggressive anticoagulation was continued for 1 month. The rabbits were followed up using contrast-enhanced three-dimensional 1·5-T magnetic resonance angiography (CE-3D-MRA) at 1 month and up to 1 year after creation of the bifurcation. Results: At 1-month follow-up, all but one of the created aneurysms and all parent vessels proved to be patent. Three animals (18%) were lost during follow-up for reasons unrelated to aneurysm surgery. At 1-year follow-up, one animal showed partial and one complete spontaneous aneurysm thrombosis (aneurysm patency rate: 86%). Six out of 42 parent vessels were occluded at that time (vessel patency rate: 86%). Conclusions: Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model demonstrates a high long-term patency rate but is complicated by high rates of unrelated procedural mortality and morbidity. There is no need for prolonged (>4 weeks) anticoagulation to achieve good long-term patency in complex venous pouch bifurcation aneurysms.

New mechanical thrombectomy model in the rabbit: A feasibility study.

BACKGROUND AND PURPOSE Thrombolytic therapy represented the gold standard for the treatment of ischemic stroke. Its drawbacks include increased bleeding risk and low recanalization rates. Mechanical thrombectomy is a new promising therapy option. Devices used for this procedure were substantially improved during recent years. New devices require extensive preclinical invivo testing. We therefore sought to translate the commonly used pig model to a simplified and cheaper rabbit model. MATERIALS AND METHODS We performed thromboembolisation in eight intubated and sedated adult female New Zealand white rabbits. The thrombus was created by careful rotation of autologous blood in a silicone tube and addition of barium sulfate for radiopacity. We injected the artificial thrombus via a catheter through the cannulated femoral artery. After thromboembolisation, 2D-DSA was performed to evaluate location and thrombus dimensions. COMPARISON WITH EXISITING METHOD(S) None. RESULTS No complications or mortality were observed in our series. In seven cases (87.5%) the location of the thromboembolism was the maxillary artery and in one case (12.5%) the thrombus reached the occipital artery. The radiopaque thrombus had a length of 7.0±4.55mm invivo. Vessel diameters in angiographic evaluation were 2.44±0.21mm for the common carotid artery and 2.1±0.16mm for the maxillary artery. CONCLUSIONS The novel small animal model for mechanical thrombectomy in rabbit is technically feasible and cheap. It offers comparable vessel diameters to cranial arteries and closely mimics human coagulation system.