Is Histologic Thrombus Composition in Acute Stroke Linked to Stroke Etiology or to Interventional Parameters?

BACKGROUND AND PURPOSE: Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results. MATERIALS AND METHODS: Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate. RESULTS: Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis (P = .021 and .003) or the embolic stroke of undetermined source (P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval (P = .021) and were associated with an increased number of retrieving maneuvers (P = .001), longer procedural times (P = .001), and a higher lymphocyte content (P = .035). CONCLUSIONS: We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi.

The Dural AV-Fistula (DAVF), the Most Frequent Acquired Vascular Malformation of the Central Nervous System (CNS).

Acquired arteriovenous malformations, such as is the case with dural arteriovenous fistulae (DAVF), are the consequence of a pathological new arterial ingrowth into venous spaces that reaches directly the venous lumen, without interposition of a capillary network, thereby creating an AV-shunt.The following concise text will provide elements in regards to diagnosis, indication for treatment discussion and choice of endovascular treatment (EVT) method.

Benefit of second catheter angiography in patients with nontraumatic subarachnoidal hemorrhage.

PURPOSE: This study aimed to determine the yield of repetitive catheter angiography (digital subtraction angiography (DSA)) for the detection of causative vascular lesions in patients with nontraumatic subarachnoidal hemorrhage (SAH) and negative initial DSA. We hypothesize that a second DSA might be helpful to detect an initially occult bleeding source. METHODS: We retrospectively evaluated 649 patients with acute SAH and invasive catheter angiographies between 2004 and 2012. In 90 SAH patients initial imaging was negative concerning a causative bleeding source. A total of 113 repetitive DSA were performed. Two neuroradiologists reanalyzed the initial imaging and the result of the reangiography independently. RESULTS: In 4/90 patients (4.5 %) bleeding source was first detected in the second or third DSA. In all other patients, no causative vascular lesion was found. Reasons for the initially false negative diagnostics were one dissecting aneurysm and thrombosis of three aneurysms within the acute phase of SAH. CONCLUSIONS: Repetitive DSA revealed the cause of SAH in 4.5 % of the cases. These findings have a therapeutic and prognostic impact. We think that at least a second DSA should be part of diagnostic work-up in patients with SAH and missing bleeding source, even considering the risk of an additional invasive angiography itself.

Association of aneurysms and variation of the A1 segment.

BACKGROUND AND PURPOSE: Previous studies have described a correlation between variants of the circle of Willis and pathological findings, such as cerebrovascular diseases. Moreover, anatomic variations of the anterior cerebral artery (ACA) seem to correspond to the prevalence of aneurysms in the anterior communicating artery (ACoA). The aim of this study was to assess the prevalence of aneurysms in patients with anatomical/morphological variations of the circle of Willis. METHODS: We retrospectively analyzed 223 patients who underwent cerebral angiography between January 2002 and December 2010 for aneurysm of the ACoA. Diagnostic imaging was reviewed and statistically evaluated to detect circle of Willis anomalies, aneurysm size, and rupture. 204 patients with an unrelated diagnosis served as the control group. RESULTS: Variations of the A1 segment occurred significantly more frequently in the aneurysm group than in the control group. Mean aneurysm size in patients with grades I and III hypoplasia or aplasia was 6.58 mm whereas in patients with grade II hypoplasia it was 7.76 mm. CONCLUSIONS: We found that variations in the A1 segment of the ACAs are correlated with a higher prevalence of ACoA aneurysms compared with patients with a symmetric circle of Willis.

Silent embolism after stent-assisted coiling of cerebral aneurysms: diffusion-weighted MRI study of 75 cases.

PURPOSE: New ischemic brain lesions are common findings after cerebral diagnostic angiography and endovascular therapy. Diffusion-weighted MRI (DWI) can be used for detection of these lesions. The aim of the present study was to investigate the incidence of DWI lesions after stent-assisted coiling and the evaluation of possible risk factors. METHODS: The study included a total of 75 consecutive patients treated with stent-assisted coiling. Post-procedural DWI of the brain was performed to detect ischemic lesions. Demographic data, aneurysm characteristics and angiographic parameters were correlated with properties of DWI lesions. RESULTS: In post-procedural DWI, 48 of the 75 patients (64%) had 163 DWI lesions in a pattern consistent with embolic events. The number of patients with DWI lesions was significantly increased in older patients (≥55 years) and longer intervention times (≥120 min). The ischemic brain volume was significantly increased in older patients (≥55 years) as well as in patients who were implanted with a shorter stent (<20 mm). CONCLUSIONS: Thromboembolic events are common after stent-assisted coiling with an incidence comparable to DWI studies after coiling alone. Despite several devices and low operator experience, stent-assisted coiling for intracranial aneurysms has a very low risk of permanent neurologic disability. Further studies are necessary to improve the safety of stent-assisted coiling for patients in conditions with increased risk potential (age, procedure time, stent length).

Glucose regulates secretion of exogenously expressed insulin from HepG2 cells in vitro and in a mouse model of diabetes mellitus in vivo.

Glucose-controlled insulin secretion is a key component of its regulation. Here, we examined whether liver cell secretion of insulin derived from an engineered construct can be regulated by glucose. Adenovirus constructs were designed to express proinsulin or mature insulin containing the conditional binding domain (CBD). This motif binds GRP78 (HSPA5), an endoplasmic reticulum (ER) protein that enables the chimeric hormone to enter into and stay within the ER until glucose regulates its release from the organelle. Infected HepG2 cells expressed proinsulin mRNA and the protein containing the CBD. Immunocytochemistry studies suggested that GRP78 and proinsulin appeared together in the ER of the cell. The amount of hormone released from infected cells varied directly with the ambient concentration of glucose in the media. Glucose-regulated release of the hormone from infected cells was rapid and sustained. Removal of glucose from the cells decreased release of the hormone. In streptozotocin-induced diabetic mice, when infected with adenovirus expressing mature insulin, glucose levels declined. Our data show that glucose regulates release of exogenously expressed insulin from the ER of liver cells. This approach may be useful in devising new ways to treat diabetes mellitus.

[3-year follow-up after endovascular aneurysm treatment with Silk® flow diverter]. / 3-Jahres-Follow nach Aneurysmabehandlung mit dem Silk® Flow Diverter.

PURPOSE: Flow diverters may occlude aneurysms by endoluminal reconstruction of the parent artery and by reducing the blood flow into the aneurysm. The purpose of this study was to assess the rate of intervention-associated complications and a 3-year-follow-up. MATERIALS AND METHODS: We retrospectively analyzed 18 patients treated with Silk® FD. Only patients with unruptured aneurysms were included. Treatment indications were fusiform, giant or recurrent aneurysms. We considered all aneurysms to have a high likelihood of failure and/or recurrence when treated with conventional endovascular techniques. RESULTS: Silk FD could directly be placed in a proper position across the whole length of the aneurysm in 16/18 patients. In one case an additional PTA was necessary. In another case the first FD could not be properly deployed. 17 of 18 aneurysms (95 %) were occluded immediately, in the mid-term follow-up after 6 months or 3 years after treatment. The overall complication rate including technical (11.1 %), acute or delayed thromboembolic complication without (11.1 %) or with (16.6 %) severe complications was documented. CONCLUSION: FD treatment is effective with a high occlusion rate of aneurysms also in long-term follow-up. In these complex aneurysms the complication rate is higher than in conventional stent-assisted coiling.

The management of arteriovenous malformations.

Arteriovenous malformations (AVM) can occur in the entire central nervous system with a predilection of the supratentorial intracranial compartment. Intracerebral hemorrhage is the most common clinical presentation of AVM and associated with a high morbidity and mortality rate. Correct management of these lesions is therefore of utmost importance. In this review, the authors present actual diagnostic and interdisciplinary treatment modalities based on their experience in a major neurovascular center and taking into consideration actual literature data. Different treatment strategies are discussed.

Recovery of ophthalmoplegia after endovascular treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: Recovery of aneurysm induced CNP after endosaccular coiling has been reported in the literature. The aim of this study was to assess in detail the parameters that affect the outcome after endovascular treatment of ophthalmoplegic aneurysms due CNP. MATERIALS AND METHODS: Between November 1999 and March 2008, 30 consecutive patients (8 men, 22 women; mean age, 54.9 years) presenting with CNP underwent endosaccular coiling with or without additional use of stents in the parent artery. Subarachnoid hemorrhage was present in 10 patients, whereas 20 patients had unruptured aneurysms. The mean size of the aneurysms was 10 mm. Initial CNP was complete in 11 patients and partial in 19. Mean follow-up after coiling was 19 months. RESULTS: The mean interval between the onset of CNP and aneurysm embolization was 48 days. Fifteen patients (50%) had complete recovery of oculomotor function, 12 had incomplete recovery (40%), and 3 (10%) remained unchanged after treatment. In 4 aneurysms (13.3%), 1 additional embolization was performed, whereas in 4 other aneurysms, 2 additional embolization procedures were necessary. Procedure-related permanent morbidity occurred in 2 patients (6.6%). CONCLUSIONS: Endosaccular coiling is an effective and safe method for the treatment of ophthalmoplegic aneurysms. Age, neck size, and time of treatment do not seem to constitute prognostic factors with respect to CNP recovery, though patients with small aneurysms, unruptured status, and/or location in the posterior circulation showed a tendency for better outcome. The degree of initial CNP was the only statistically significant prognostic factor concerning the final outcome, resulting in better recovery, in case of incomplete initial CNP.

Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment.

BACKGROUND AND PURPOSE: FD technology enables reconstructive repair of otherwise difficult-to-treat intracranial aneurysms. These stentlike devices may induce progressive aneurysm thrombosis without additional implants and may initiate complete reverse vessel remodeling. The associated vascular biologic processes are as yet only partially understood. MATERIALS AND METHODS: From 12 different centers, 13 cases of delayed postprocedural aneurysm rupture were recorded and analyzed. Symptom, aneurysm location and morphology, and the time elapsed from treatment until rupture were analyzed. RESULTS: There were 10 internal carotid and 3 basilar artery aneurysms. Mean aneurysm diameter was 22 ± 6 mm. Eleven patients were symptomatic before treatment. A single FD was used for all saccular aneurysms, while fusiform lesions were treated by using multiple devices. A supplementary loose coiling of the aneurysm was performed in 1 patient only. Ten patients developed early aneurysm rupture after FD treatment (mean, 16 days; range, 2-48 days); in 3 patients, rupture occurred 3-5 months after treatment. In all cases, most of the aneurysm cavity was thrombosed before rupture. The biologic mechanisms predisposing to rupture under these conditions are reviewed and discussed CONCLUSIONS: FDs alone may modify hemodynamics in ways that induce extensive aneurysm thrombosis. Under specific conditions, however, instead of reverse remodeling and cicatrization, aggressive thrombus-associated autolysis of the aneurysm wall may result in delayed rupture.

The pipeline embolization device for the intracranial treatment of aneurysms trial.

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow diverting devices represents a novel constructive technique for the treatment of cerebral aneurysms. We present the results of the first prospective multicenter trial of a flow-diverting construct for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with unruptured aneurysms that were wide-necked (> 4 mm), had unfavorable dome/neck ratios (<1.5), or had failed previous therapy were enrolled in the PITA trial between January and May 2007 at 4 (3 European and 1 South American) centers. Aneurysms were treated with the PED with or without adjunctive coil embolization. All patients underwent clinical evaluation at 30 and 180 days and conventional angiography 180 days after treatment. Angiographic results were adjudicated by an experienced neuroradiologist at a nonparticipating site. RESULTS: Thirty-one patients with 31 intracranial aneurysms (6 men; 42-76 years of age; average age, 54.6 years) were treated during the study period. Twenty-eight aneurysms arose from the ICA (5 cavernous, 15 parophthalmic, 4 superior hypophyseal, and 4 posterior communicating segments), 1 from the MCA, 1 from the vertebral artery, and 1 from the vertebrobasilar junction. Mean aneurysm size was 11.5 mm, and mean neck size was 5.8 mm. Twelve (38.7%) aneurysms had failed (or recurred after) a previous endovascular treatment. PED placement was technically successful in 30 of 31 patients (96.8%). Most aneurysms were treated with either 1 (n = 18) or 2 (n = 11) PEDs. Fifteen aneurysms (48.4%) were treated with a PED alone, while 16 were treated with both PED and embolization coils. Two patients experienced major periprocedural stroke. Follow-up angiography demonstrated complete aneurysm occlusion in 28 (93.3%) of the 30 patients who underwent angiographic follow-up. No significant in-construct stenosis (≥ 50%) was identified at follow-up angiography. CONCLUSIONS: Intracranial aneurysm treatment with the PED is technically feasible and can be achieved with a safety profile analogous to that reported for stent-supported coil embolization. PED treatment elicited a very high rate (93%) of complete angiographic occlusion at 6 months in a population of the most challenging anatomic subtypes of cerebral aneurysms.

[Comparison of superselective intraarterial fibrinolysis with conservative therapy. Use in patients with acute non-arteritic central retinal artery occlusion]. / Vergleich der superselektiven intraarteriellen Fibrinolyse mit konservativer Therapie. Einsatz bei Patienten mit akutem nichtarteriitischem Zentralarterienverschluss.

The results of conservative treatment for central retinal artery occlusion (CRAO) vary considerably and although local intraarterial fibrinolysis (LIF) is a promising treatment, outcomes have not been compared in randomized trials. The prospective randomized multicenter study by the European Assessment Group for Lysis in the Eye (EAGLE) is the first clinical trial to compare treatment outcomes of conservative standard treatment (CST) and LIF for acute non-arteritic CRAO. Patients (age 18-75 years) with CRAO present for less than 20 h and best-corrected visual acuity (BCVA) <0.5 logMAR were randomized to either CST or LIF group. Primary endpoint was BCVA after 1 month and secondary endpoint was safety. Mean BCVA (logMAR) improved significantly in both groups and did not differ between the groups. Because of similar efficacy and the higher rate of adverse events in the LIF group the study was halted after the first interim analysis. Due to the similar outcomes of the two therapies and the higher rate of adverse reactions associated with LIF superselective lysis cannot be recommended for the management of acute CRAO.

Imaging of brain metastases of bronchial carcinomas with 7 T MRI - initial results.

PURPOSE: To compare the depiction of brain metastases of bronchial carcinomas on susceptibility-weighted and contrast-enhanced images with 7 T and at 1.5 T MRI. MATERIALS AND METHODS: Twelve patients with brain metastases of bronchial carcinomas underwent 7 T and 1.5 T MRI. Minimum intensity projections (MinIP) of a 1.5 T SWI sequence (voxel size = 0.9 x 0.9 x 2.0 mm(3)) were compared to 7 T SWI MinIPs (voxel size = 0.4 x 0.4 x 1.5 mm(3)). A T 1-w 3D MPRAGE at 1.5 T (voxel size = 1 x 1 x 1 mm(3) after double-dose (DD) gadoterate meglumine, Gd-DOTA) was compared to a 7 T MPRAGE sequence (voxel size = 0.7 x 0.7 x x 0.7 mm(3), single dose (SD) Gd-DOTA) in all patients, and to DD Gd-DOTA in 6 patients after a 10 minute delay. The number of intracranial microhemorrhages in SWI MinIPs and the number of contrast-enhancing metastases in MPRAGE images were compared in each patient grouped into three size ranges (< or = 2 mm, > 2 mm and < 6 mm, > or = 6 mm) by two radiologists in consensus. RESULTS: In all 12 patients the 7 T SWI with spatially higher resolution allowed the identification of 87 versus 67 cerebral microhemorrhages at 1.5 T. 7 T T 1-w images after SD Gd-DOTA depicted 198 brain metastases versus 238 at 1.5 T after DD Gd-DOTA. After doubling the contrast dose in six patients, 4 additional brain metastases were identified at 7 T. CONCLUSION: Our preliminary results indicate that despite the higher spatial resolution the detection of brain metastases on 7 T MPRAGE images is almost equal to 1.5 T MPRAGE images. The 7 T SWI sequence with spatially higher resolution allowed the detection of 20 % more microhemorrhages in brain metastases compared to the 1.5 T SWI sequence.

A High CSF Signal on FLAIR: It Is Not Always Blood.

We describe a patient with progressive neurologic deficit due to middle cerebral branch occlusion. Temporary partial balloon occlusion of the abdominal aorta led to an increased signal in the subarachnoid space on fluid-attenuated inversion recovery images with no evidence of subarachnoid hemorrhage. After spontaneous recanalization, the increased signal of the subarachnoid space returned to normal. We assume that signal changes in the subarachnoid space were due to a temporary increase in blood volume in the superficial brain vessels.

[Embolization of life-threatening intercostal hemorrhaging in a severely injured patient: a rarity in trauma care]. / Embolisation einer lebensbedrohlichen Interkostalblutung bei einem Schwerstverletzten : Eine Rarität in der Traumaversorgung.

Transarterial embolization of ruptured intercostal arteries due to massive bleeding represents an infrequent indication in severely injured patients. The current literature shows isolated case descriptions but no clinical trials exist. In the case depicted here embolization is represented as a form of therapy after haemorrhagic shock caused by a ruptured intercostal artery. The embolization carried out led to an immediate cessation of bleeding. The vital signs returned to normal immediately after the procedure and surgical intervention could be avoided. The course of the disease represented in the following shows the effectiveness of this type of treatment not only for bleeding due to pelvic fractures and abdominal injuries, but also for isolated arterial bleeding in other body regions.

Percutaneous embolization of carotid paragangliomas using solely Onyx.

BACKGROUND AND PURPOSE: Paragangliomas are highly vascularized usually benign neoplasms arising from nerve tissue. Endovascular preoperative embolization is used to facilitate surgery but is often not complete, due to tiny feeding arteries not feasible for selective catheterization. Our purpose was to evaluate angiographic and clinical outcome using Onyx for percutaneous glomus tumor embolization. MATERIALS AND METHODS: A consecutive series of 4 patients with 6 paragangliomas located at the bifurcation of the common carotid artery were treated with percutaneous embolization using Onyx as the sole embolic material. RESULTS: Complete devascularization of the 6 paragangliomas was achieved using a percutaneous embolization technique with Onyx as a sole agent, combined with an endovascular microballoon that offered protection of the internal carotid artery. CONCLUSIONS: Further documentation is necessary to prove the higher grade of devascularization of paragangliomas with Onyx compared with other embolic material and the associated potential to facilitate surgery. Nevertheless, Onyx seems to be safe when used percutaneously due to its lavalike pattern flow and its controllable properties, allowing slow tumor bed penetration.

First clinical study on ultra-high-field MR imaging in patients with multiple sclerosis: comparison of 1.5T and 7T.

BACKGROUND AND PURPOSE: Higher magnetic field strengths and continuous improvement of high-resolution imaging in multiple sclerosis (MS) are expected to provide unique in-vivo and non-invasive insights in pathogenesis and clinical monitoring. The purpose of this study was to investigate the potential of high-resolution imaging of MS lesions in vivo comparing 7T with conventional 1.5T. MATERIALS AND METHODS: Twelve consecutive patients with clinically definite MS were scanned on a 7T whole-body scanner and on a 1.5T Avanto. The 1.5T and 7T imaging protocol consisted of high-resolution axial proton density (PD) + T2-weighted turbo spin-echo and T2*-weighted gradient-echo (GRE), and sagittal T1-weighted 3D magnetization-prepared rapid acquisition of gradient echo. RESULTS: The sequence parameters at 7T had to be modified because of specific absorption rate (SAR) restrictions while keeping contrast parameters equivalent to 1.5T. White matter lesions were better detected and delineated from adjacent structures at 7T compared with 1.5T. There were 42% of the patients who showed additional lesions at 7T: there were 97 white matter lesions detected on 1.5T versus 126 lesions at 7T, an increase of 23%. The perivascular migration of MS lesions was well visualized on T2*-weighted GRE sequences. In larger lesions (10 mm), a multilayer structure was revealed on T2*-weighted GRE not seen at 1.5T. Because of the higher resolution, it was possible to differentiate between juxtacortical white matter lesions and cortical lesions. There were 44% of the subcortical lesions depicted at 7T that showed cortical involvement. CONCLUSIONS: Ultra-high-field imaging of patients with MS at 7T was well tolerated and provided better visualization of MS lesions in the gray matter and demonstrated structural abnormalities within the MS lesions themselves more effectively.

Evaluation of intracranial aneurysms with 7 T versus 1.5 T time-of-flight MR angiography - initial experience.

PURPOSE: The purpose of this study was to compare the depiction of intracranial aneurysms by 3D time-of-flight (TOF) magnetic resonance angiography (MRA) at 7 Tesla (T) with the clinical standard TOF MRA at 1.5 T and with digital subtraction angiography (DSA). MATERIALS AND METHODS: 7 T and 1.5 T TOF MRA images optimized for both field strengths were compared in ten patients with an unruptured intracranial aneurysm. Two blinded neuroradiologists independently rated the image quality of the dome, the neck, and the vessel of origin of all aneurysms in MRA source and maximum intensity projection (MIP) images. DSA was obtained in all subjects and served as reference standard. The mean values of image quality were compared by Wilcoxon signed rank test. In all patients the number and location of the aneurysms was confirmed by DSA. RESULTS: Both readers identified twelve aneurysms in ten patients in 7 T, 1.5 T TOF MRA and DSA. The image quality of the aneurysm dome was rated higher in 8 of 12 aneurysms and the image quality of the aneurysm neck was superior in 9 of 12 aneurysms at 7 T TOF MRA compared to 1.5 T TOF MRA. The depiction of the parent vessel was graded almost equally by both readers. CONCLUSION: Our initial results indicate that image quality of intracranial aneurysms may benefit from the increased spatial resolution of 7 T TOF MRA compared with 1.5 T TOF MRA. Tailored scan protocols and optimized radiofrequency head coils are needed to further improve the image quality of 7 T TOF MRA.

Endovascular treatment resolves non-hemorrhagic brainstem dysfunction due to tentorial dural AV fistula.

Tentorial dural arteriovenous fistulas (tDAVF) clinically present usually with subarachnoid and/or intraparenchymal hemorrhage. Reported rates range from 58% to 92% and neurological deficits occur in 79% to 92% of patients. This is due to venous congestion resulting from retrograde leptomeningeal venous drainage, which rarely, can be clinically silent. A 69-year-old woman presented with vertigo, double vision and gait instability. Cerebral digital subtraction angiography revealed a tDAVF with retrograde cerebellar venous drainage directed through the vein of Galen into the straight sinus. MRI showed extensive cerebellar edema due to venous congestion. Clinical manifestations of cerebellar and brainstem dysfunction resolved completely after transarterial embolization with N-butylcyanoacrylate.