Alim P. Mitha

Manual aspiration thrombectomy through balloon-tipped guide catheter for rapid clot burden reduction in endovascular therapy for ICA L/T occlusion

IntroductionTimely recanalization during endovascular procedures for acute ischemic stroke can be challenging in cases with large clot burden, such as those encountered in the terminal internal carotid T- or L-type occlusion.MethodsA novel but simple technique to achieve fast reduction in clot burden in stroke patients with occlusion of the internal carotid artery termination is described where manual suction using a 60-ml syringe applied through an 8-F balloon guide catheter positioned in the cervical carotid vasculature with proximal flow arrest allows subsequent revascularization of the residual middle cerebral artery clot.ResultsThe use of manual suction through a balloon-tipped guide catheter in internal carotid artery L- or T-type occlusion is illustrated. This resulted in a significant reduction of the clot burden and facilitated further interventions leading to full recanalization.ConclusionManual suction using a 60-ml syringe through a ballon guide catheter is a useful and feasible technique that facilitates thrombectomy of large burden cerebral clots.

Association of α-Synuclein Immunoreactivity With Inflammatory Activity in Multiple Sclerosis Lesions

Multiple sclerosis (MS) has neurodegenerative features including neuronal and axonal loss and widespread atrophy of the brain and spinal cord. The cause of this neurodegeneration has been largely attributed to inflammation, but other mechanisms, including those associated with classic neurodegenerative diseases such as the &agr;-synucleinopathies, might also be involved in MS pathogenesis. In this study, 96 brain lesions containing varying degrees of inflammatory activity from 12 autopsied MS cases were compared with corresponding regions from 6 neuropathologically normal controls; 2 cerebral biopsy lesions from an MS patient were also studied. We found &agr;-synuclein immunoreactivity in the cytoplasm of cells in MS lesions with inflammatory activity but not in control samples. &agr;-Synuclein-immunoreactive cells were identified in active (15/15 lesions in the brainstem, 9/13 in cerebral hemispheres) and chronic active (14/15 in the brainstem, 12/22 in cerebral hemispheres) lesions but were absent in chronic inactive lesions (0/31); the greater immunoreactivity in brainstem compared with cerebral hemisphere lesions was significant (p < 0.05). Double-immunofluorescence staining revealed localization of &agr;-synuclein immunoreactivity mostly in neurons, microglia/macrophages, and oligodendrocytes, and only rarely in astrocytes. The results suggest that &agr;-synuclein expression regulated by inflammatory signals may contribute to neurodegenerative processes in MS lesions.

Mechanical thrombectomy with the Solitaire stent: is there a learning curve in achieving rapid recanalization times?

Methods In acute ischemic stroke, good outcome following successful recanalization is time dependent. In patients undergoing endovascular therapy at our institution, recanalization times with the Solitaire stent were retrospectively evaluated to assess for the presence of a learning curve in achieving rapid recanalization. Methods We reviewed patients who presented to our stroke center and achieved successful recanalization with the Solitaire stent exclusively. Time intervals were calculated (CT to angiography arrival, angiography arrival to groin puncture, groin puncture to first deployment, and deployment to recanalization) from time stamped images and angiography records. Patients were divided into three sequential groups, with overall CT to recanalization time and subdivided time intervals compared. Results 83 patients were treated with the Solitaire stent from May 2009 to February 2012. Recanalization (Thrombolyis in Cerebral Infarction score 2A) occurred in 75 (90.4%) patients. CT to recanalization demonstrated significant improvement over time, which was greatest between the first 25 and the most recent 25 cases (161–94u2009min; p<0.01). The maximal contribution to this was from improvements in first stent deployment to recanalization time (p=0.001 between the first and third groups), with modest contributions from moving patients from CT to the angiography suite faster (p=0.02 between the first and third groups) and from groin puncture to first stent deployment (p=0.02 between the first and third groups). Conclusions There is a learning curve involved in the efficient use of the Solitaire stent in endovascular acute stroke therapy. Along with improvements in patient transfer to angiography and improved efficiency with intracranial access, mastering this device contributed significantly towards reducing recanalization times.

Rapid delayed growth of ruptured supraclinoid blister aneurysm after successful flow diverting stent treatment

A 62-year-old woman presented with a subarachnoid hemorrhage secondary to a ruptured right supraclinoid internal carotid artery blister aneurysm. She was treated in an emergent fashion with two flow diverting pipeline embolization devices (PED) deployed in a telescoping fashion. CT angiography performed for unrelated reasons at 7u2005months showed successful treatment of the aneurysm without evidence of residual aneurysm. However, a follow-up digital subtraction angiogram performed at 9u2005months showed a large aneurysm in a modified position compared with the original aneurysm. This is the first case of rapid regrowth of a supraclinoid blister aneurysm after successful treatment with a PED, and demonstrates the need for close follow-up for similar aneurysms treated with this novel device.

MR imaging of carotid webs

PurposeWe propose a magnetic resonance (MR) imaging protocol for the characterization of carotid web morphology, composition, and vessel wall dynamics. The purpose of this case series was to determine the feasibility of imaging carotid webs with MR imaging.MethodsFive patients diagnosed with carotid web on CT angiography were recruited to undergo a 30-min MR imaging session. MR angiography (MRA) images of the carotid artery bifurcation were acquired. Multi-contrast fast spin echo (FSE) images were acquired axially about the level of the carotid web. Two types of cardiac phase resolved sequences (cineFSE and cine phase contrast) were acquired to visualize the elasticity of the vessel wall affected by the web.ResultsCarotid webs were identified on MRA in 5/5 (100%) patients. Multi-contrast FSE revealed vessel wall thickening and cineFSE demonstrated regional changes in distensibility surrounding the webs in these patients.ConclusionOur MR imaging protocol enables an in-depth evaluation of patients with carotid webs: morphology (by MRA), composition (by multi-contrast FSE), and wall dynamics (by cineFSE).

Hemodynamic alterations measured with phase-contrast MRI in a giant cerebral aneurysm treated with a flow-diverting stent

Many risk factors have been proposed in the development of the cerebral aneurysms. Hemodynamics including blood velocity, volume flow rate (VFR), and intravascular pressure are thought to be prognostic indicators of aneurysm development. We hypothesize that treatment of cerebral aneurysm using a flow-diverting stent will bring these hemodynamic parameters closer to those observed on the contralateral side. In the current study, a patient with a giant cerebral aneurysm was studied pre- and postoperatively using phase contrast MRI (PC-MRI) to measure the hemodynamic changes resulting from the deployment of a flow-diverting stent. PC-MRI was used to calculate intravascular pressure, which was compared to more invasive endovascular catheter-derived measurements. After stent placement, the measured VFRs in vessels of the treated hemisphere approached those measured on the contralateral side, and flow symmetry changed from a laterality index of -0.153 to 0.116 in the middle cerebral artery. Pressure estimates derived from the PC-MRI velocity data had an average difference of 6.1% as compared to invasive catheter transducer measurements. PC-MRI can measure the hemodynamic parameters with the same accuracy as invasive methods pre- and postoperatively.

Accuracy and precision of venous pressure measurements of endovascular microcatheters in the setting of dural venous sinus stenosis

Introduction Dural venous sinus stenosis (DVSS) may lead to increased intracranial pressure, sometimes requiring a stent if a high pressure gradient exists. Many neuroendovascular physicians use microcatheters to measure gradients, yet there are no studies comparing the accuracies and precisions of modern day microcatheters. We examined pressure recordings from five commonly used microcatheters in an experimental DVSS model. Methods Using a programmable pump, dynamic flow was established in a closed circuit mimicking the venous sinus waveform. Microcatheters with 150 cm effective lengths were connected proximally to pressure transducers. Mean recording pressures were compared with a high fidelity microcatheter (HFM) in several configurations including no stenosis, proximal to a focal stenosis, and distal to a focal stenosis in opposing orientations. Results All microcatheters recorded lower pressures than the HFM. Three of the five microcatheters successfully met intracranial pressure monitoring device standards in all conditions, while one did not meet standards in any configuration. The performance of the final microcatheter was variable, with inaccuracies occurring in unrestricted flow. All microcatheters demonstrated relatively high precision, but with variable accuracies. The larger diameter microcatheters displayed the least damping and therefore the greatest accuracies. Of the three smaller microcatheters, dimensions did not predict performance, suggesting that microcatheter construction may also play a role in pressure accuracy. Conclusion The use of microcatheters to record dural venous sinus pressures must be done with an understanding of the inherent limitations and inaccuracies, especially if clinical decisions are made from the results.

Verapamil eluting stents as a possible treatment for vasospasm after subarachnoid hemorrhage

Objective The only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm. Methods Nitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning. Morphology of the coatings were studied with scanning electron microscopy. 12 verapamil eluting stents were then prepared using different verapamil concentrations and coatings with different numbers of layers. Drug release behaviors were studied using UV spectroscopy for 21u2005days. Results Electrospinning at 20% w/v resulted in a smooth uniform coating without significant surface irregularities, and may be the most effective technique to coat stents. Stents with a single layer of PLGA/verapamil coating showed a two phase release profile (initial burst release followed by a slow rate of release) whereas stents with a bilayer coating showed a lower level of initial release followed by a slower sustained release phase. Conclusions Development of verapamil eluting stents that elute drug over the time course typical of cerebral vasospasm, and for either immediate or prophylactic treatment, is technically feasible. Further in vitro and in vivo studies are required to determine whether this can improve the outcome of patients after subarachnoid hemorrhage.

A refined experimental model of fusiform aneurysms in a rabbit carotid artery

OBJECTIVEReliable animal models are an important aspect of translational research, especially for relatively uncommon clinical entities such as fusiform aneurysms. While several animal models exist, very few are tailored to cerebral fusiform aneurysms, which have unique attributes compared to abdominal fusiform aneurysms. The authors aimed to build from previous models to create a cerebral fusiform aneurysm model that is simple to use and reliable.METHODSTwelve female New Zealand White rabbits were assigned to 3 groups: group E, elastase only; group C, CaCl2 only; group EC, elastase + CaCl2. All rabbits underwent surgical exposure of the right common carotid artery (CCA) and 20 minutes of peri-carotid incubation with their respective chemicals. Angiography was performed 6 weeks later for arterial dilation measurements, with 50% increase in diameter being defined as fusiform aneurysm formation. The arterial segments, along with the contralateral CCAs, were harvested and assessed histologically for wall component measurements and elastin semiquantification. A separate rabbit underwent aneurysm creation per the group EC protocol and was treated with an endovascular flow-diversion device.RESULTSAll of the group EC rabbits developed fusiform aneurysms (mean dilation of 88%), while none of the group E or group C rabbits developed aneurysms (p = 0.001). Histological analysis revealed increased internal elastic lamina fragmentation in the group EC aneurysms, which also had less tunica intima hyperplasia. All aneurysms exhibited thinning of the tunica media and reduction in elastin content. The use of an endovascular flow-diverting stent was successful, with complete parent vessel remodeling, as expected, 4 weeks after deployment.CONCLUSIONSThe peri-arterial application of combined elastase and CaCl2 to the CCA appears sufficient to reliably produce fusiform aneurysms after 6 weeks. Exposure to elastase or CaCl2 individually appears insufficient, despite the observed histological changes to the arterial wall. The proposed fusiform aneurysm model is able to accommodate endovascular devices, simulating the tortuous pathway experienced in using such devices in human cerebral aneurysms and thus is a satisfactory model to use in translational research.

P-029 Mesenchymal stem cells inhibit saccular aneurysm pathogenesis in a rabbit model

Introduction Intracranial aneurysms are relatively common entities, with rupture being a largely unpredictable event associated with significant morbidity and mortality. While current treatment modalities are effective at addressing mature aneurysms, disrupting aneurysm formation would potentially avoid the need for more invasive treatments. To inhibit saccular aneurysm pathogenesis would likely require blunting of the complex inflammatory cascade in the arterial wall. Mesenchymal stem cells (MSCs) are readily available cells found in adult tissues, such as bone marrow and adipose tissue, that have immunomodulatory properties and are immune evasive.1 They have been studied as potential treatments for many diseases associated with inflammation and have shown promise for clinical translation.2 While some studies have investigated MSCs as a treatment adjunct for aneurysms, none have examined their potential role in inhibiting aneurysm pathogenesis. We hypothesize that injecting MSCs IV will minimize the radiographic formation of aneurysms in a rabbit elastase-induced saccular aneurysm model by blunting the inflammatory process. Materials and methods Thirteen New Zealand White Rabbits were randomly assigned to either control (n=5) or intervention (n=8) groups. All rabbits underwent right common carotid artery saccular aneurysm creation using approximately 35 units of elastase as previously described in this accepted and effective model.(3) At both the time of surgery and 14 days post-operatively, intervention group rabbits received an IV injection of 5 × 106 MSCs in 2u2009mL saline, while control group rabbits received 2u2009mL of vehicle. On day 28, the right femoral artery was cannulated in all rabbits and digital subtraction angiography performed. Aneurysm volume was calculated and compared between groups. Results All rabbits tolerated the surgical procedures well with no peri-operative complications, and every procedure resulted in aneurysm formation. Mean volume of right common carotid saccular aneurysms in the control and intervention groups were 36.9 mm3 and 15.4 mm3, respectively. A Mann-Whitney U test was performed due to the heterogeneity of variances and found that the intervention group aneurysms were significantly smaller than control aneurysms (p=0.030). Conclusion This is the first study investigating the ability of MSCs to inhibit the formation of saccular aneurysms. We postulate that the observed effects are secondary to MSC-induced inhibition of the initial inflammatory cascade of aneurysm pathogenesis. MSCs are known to have immunomodulatory effects in many other scenarios, either by migrating to a site of inflammation or by releasing factors from afar.4 It is unclear by which mechanism the observed effect is occurring, but these findings suggest that MSCs may perhaps be utilized for inhibiting aneurysm formation. References . Kean TH, Lin P, Caplan AI, Dennis JE. MSCs: Delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int. 2013. 2013: Article ID732742. . Kim N, Cho SG. Clinical applications of mesenchymal stem cells. Korean J Intern Med2013;28:387–402. . Hoh BL, Rabinov JD, Pryor JC, Ogilvy CS. A modified technique for using elastase to create saccular aneurysms in animals that histologically and hemodynamically resemble aneurysms in human. Acta Neurochir2004;146:705–711. . English K. Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol2013;91:19–26. Disclosures M. Avery: None. A. Sen: None. A. Mitha: None.