Endovascular treatment of idiopathic intracranial hypertension: retrospective analysis of immediate and long-term results in 51 patients.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a disorder of increased intracranial pressure in the absence of any known causative factor. Sinus stenosis is common in these patients. Stenting of stenotic dural sinuses has gained popularity as a treatment option, since these stenoses may contribute to an obstruction of the venous return, and, thereby may contribute to IIH via an increase in venous sinus pressure. We evaluated the safety and efficacy of endovascular treatment in IIH with venous sinus stenosis. METHODS: Fifty-one patients with IIH underwent stenting. Median age was 40 years. Clinical manifestation was headache in 74.5% of the patients and visual obscurations in 78.5%. Papilledema was present in 50/51 patients (98%), and lumbar puncture documented elevated CSF opening pressure in all but one patient (98%). Sinus stenoses were observed in all patients. RESULTS: Endovascular treatment was successfully performed in all patients. There were no major complications encountered (i.e., live threatening or causing a deterioration of a patient's condition equivalent to mRS 3-6). Improvement or resolution of papilledema was observed in 88% of the patients, and 84% reported improvement or resolution of the headache. Follow-up angiographies were performed in 48 patients at a median interval of 49 months and demonstrated in stent-stenosis or a de novo stenosis in 12 patients, eight of them needed re-treatment. CONCLUSION: Venous sinus stenting is a safe and effective alternative to other invasive treatments (e.g., optic nerve sheath fenestration, CSF diversion) in patients with IIH. The majority of patients have a persistent clinical benefit.

Stent Retriever Thrombectomy of Small Caliber Intracranial Vessels Using pREset LITE: Safety and Efficacy.

PURPOSE: Few devices are approved for thrombectomy of distal vessel branches, and clinical experience is limited. Here we report our experience with pREset LITE for thrombectomy of small intracranial vessels. METHODS: From an institutional database we selected consecutive patients treated with pREset LITE for an occlusion of small (≤ 2 mm), intracranial target vessels. Recanalization success was measured by applying the modified Thrombolysis In Cerebral Infarction (mTICI) score. To assess safety, we recorded device-related procedural events and potentially device-related hemorrhages on follow-up imaging. Infarcts in the dependent territory served as a measure for efficacy. RESULTS: Of 536 patients treated between August 2013 and March 2015, 76 met the inclusion criteria. pREset LITE was used in 90 branches with an average diameter of 1.6 mm (1.3-2.0 mm). An mTICI score ≥ 2b was achieved in 70.0 %. Procedural events consisted of 5.6 % significant vasospasm, 2.2 % suspected dissections, 2.2 % downstream emboli, and 1.1 % self-limiting extravasations. On posttreatment imaging 2.2 % parenchymal hemorrhages type I (PHI) and 13.3 % focal subarachnoid hemorrhage (SAH) were potentially device related, but all of these events remained asymptomatic. After successful recanalization, 33.3 % developed no ischemia in the dependent territory while 41.7 % developed a partial infarct, and 25 % developed a complete infarct. Successful recanalization significantly increased the chance to develop no or only partial infarct compared with a complete infarction (p = 0.003, p = 0.013). CONCLUSIONS: Thrombectomy of small vessels with pREset LITE is feasible with good recanalization and reasonable safety margins. Successful recanalization significantly reduces the risk of infarction in the dependent territory. The impact on the overall clinical outcome remains to be determined.

[Mechanical thrombectomy: Acute complications and delayed sequelae]. / Mechanische Thrombektomie : Akutkomplikationen und Spätfolgen.

BACKGROUND: Due to the positive evidence for mechanical thrombectomy (mTE), it will be increasingly used in future. Profound knowledge of potential complications, prevention and management of complications is necessary to safely implement mTE into clinical practice. AIM: Description of specific complications of mTE and their clinical relevance, measures for prevention and management. Summary of the current knowledge on long-term side effects of mTE. MATERIAL AND METHODS: Analysis of current trial results and selected case series to address specific topics. Summary of own practical clinical experience. RESULTS: Vascular injury (1-5%) and emboli (5-9%) are the most relevant intraprocedural complications but the clinical outcome is variable. Measures for prevention and management are described in detail. Vasospasms frequently occur (20-26%) but rarely need specific treatment and do not affect the clinical course. In the case of restrictive indications the frequency of symptomatic hemorrhage is similar to that for medicinal treatment (up to 8%). Contrast medium enhancement in the area of the infarction on post-treatment imaging should not be mistaken for hemorrhages. Focal subarachnoid contrast medium enhancement or hemorrhage occurs in up to 24% of cases and is predominantly benign. In follow-up imaging stenoses or occlusions can be detected in 4-10% of the treated vessels, most of which are asymptomatic. They are considered to be caused by microtrauma to the vascular wall. CONCLUSION: Clinically relevant complications of mTE are rare. Preventive measures and effective management of complications may even increase safety. Stenoses occasionally occur as a long-term side effect but are asymptomatic in the majority of cases.

[Not Available]. / IQWiG Arbeitspapier GA15-02: "Stents zur Behandlung intrakranieller Stenosen: VISSIT Studie und Akutbehandlung in Deutschland". Kommentar des Berufsverbandes der Neuroradiologen (BDNR), der Deutschen Gesellschaft für Neuroradiologie (DGNR), der Deutschen Gesellschaft für Neurologie (DGN) und der Deutschen Schlaganfall-Gesellschaft (DSG).

There is an ongoing discussion about reimbursement of stent-angioplasty for the treatment of intracranial stenoses in Germany. The discussion was initiated by the statutory health insurance companies after publication of the SAMMPRIS study results, which were in favor for medical management compared to stent-angioplasty with the Wingspan® stent system. A report (Rapid report N14-01) mainly based on SAMMPRIS was written by the German Institute for Quality and Efficiency in Health Care (IQWiG) and serves as a basis for the decision-making process. This report was previously commented by the medical societies involved. Limitations of the SAMMPRIS trial and vital indications for intracranial stenting were outlined in this comment (acute vessel occlusion, hemodynamic impairment, recurrent symptoms under medical treatment). Currently also emergency stent procedures are a matter of debate. In this context a second IQWiG report was commissioned (GA 15 - 02) addressing the results of the VISSIT trial, the transferability of the results of the first report to emergency treatments and the practice of emergency intracranial stent treatment in Germany. Regarding transferability of results the main conclusion was that there was no evidence that the results of the studies analyzed for the first report (mainly SAMMPRIS) could not be transferred to emergency treatments. From a medical professional and scientific standpoint it is inacceptable to compare outcomes of a secondary prophylactic treatment with emergency procedures. The analysis of emergency treatments in Germany based on retrospective case series with a cumulative number of 31 patients. Since most emergency procedures are performed in a clinical context and are not necessarily subject to scientific evaluation, this does not reflect current practice in Germany. The first part of this statement briefly outlines the design of SAMMPRIS and VISSIT and the interpretation of the trial results from a professional perspective. The current state of discussion regarding reimbursement of intracranial stenting is summarized. The second section contains a detailed comment on the current IQWiG report GA15-02 "Stents for the treatment of intracranial artery stenosis: VISSIT study and acute treatment in Germany".

IQWiG Arbeitspapier GA15-02: "Stents zur Behandlung intrakranieller Stenosen: VISSIT Studie und Akutbehandlung in Deutschland" : Kommentar des Berufsverbandes der Neuroradiologen (BDNR), der Deutschen Gesellschaft für Neuroradiologie (DGNR), der Deutschen Gesellschaft für Neurologie (DGN) und der Deutschen Schlaganfall-Gesellschaft (DSG).

There is an ongoing discussion about reimbursement of stent-angioplasty for the treatment of intracranial stenoses in Germany. The discussion was initiated by the statutory health insurance companies after publication of the SAMMPRIS study results, which were in favor for medical management compared to stent-angioplasty with the Wingspan® stent system. A report (Rapid report N14-01) mainly based on SAMMPRIS was written by the German Institute for Quality and Efficiency in Health Care (IQWiG) and serves as a basis for the decision-making process. This report was previously commented by the medical societies involved. Limitations of the SAMMPRIS trial and vital indications for intracranial stenting were outlined in this comment (acute vessel occlusion, hemodynamic impairment, recurrent symptoms under medical treatment).Currently also emergency stent procedures are a matter of debate. In this context a second IQWiG report was commissioned (GA 15 - 02) addressing the results of the VISSIT trial, the transferability of the results of the first report to emergency treatments and the practice of emergency intracranial stent treatment in Germany6. Regarding transferability of results the main conclusion was that there was no evidence that the results of the studies analyzed for the first report (mainly SAMMPRIS) could not be transferred to emergency treatments. From a medical professional and scientific standpoint it is inacceptable to compare outcomes of a secondary prophylactic treatment with emergency procedures. The analysis of emergency treatments in Germany based on retrospective case series with a cumulative number of 31 patients. Since most emergency procedures are performed in a clinical context and are not necessarily subject to scientific evaluation, this does not reflect current practice in Germany.The first part of this statement briefly outlines the design of SAMMPRIS and VISSIT and the interpretation of the trial results from a professional perspective. The current state of discussion regarding reimbursement of intracranial stenting is summarized. The second section contains a detailed comment on the current IQWiG report GA15-02 "Stents for the treatment of intracranial artery stenosis: VISSIT study and acute treatment in Germany".

Initial Experience with p64: A Novel Mechanically Detachable Flow Diverter for the Treatment of Intracranial Saccular Sidewall Aneurysms.

BACKGROUND AND PURPOSE: Flow diverters are important tools for the treatment of intracranial aneurysms. We report a retrospective evaluation of the safety and efficacy of p64, a fully resheathable, detachable flow diverter, in the endovascular treatment of intracranial sidewall aneurysms. MATERIALS AND METHODS: Results of 121 patients with 130 aneurysms (median neck size, 3 mm; median fundus size, 4 mm), treated from April 2012 through October 2014, were analyzed. Aneurysms were unruptured or beyond the acute SAH phase. Thirteen aneurysms were located in the posterior circulation. Twenty-three aneurysms had previous saccular treatment but no previous parent vessel stent placement. In 19 aneurysms, a combination of coiling and flow diversion was performed. RESULTS: Successful p64 deployment was achieved in 127/130 aneurysms. The average number of p64s used was 1.1 per aneurysm. The rates of transient and permanent morbidity and mortality were 5%, 1.7%, and 0.8%, respectively. Three-month DSA follow-up in 123/130 aneurysms showed complete occlusion in 58.5%. Nine-month DSA follow-up in 93/106 (87.7%) eligible aneurysms showed complete occlusion in 79.6%. Late follow-up (median, 496 days) has already been performed in 35 aneurysms, showing complete occlusion in 30 (85.7%). CONCLUSIONS: p64 offers an efficacious treatment option for intracranial sidewall aneurysms with a high aneurysm occlusion and an acceptable complication rate. The possibility of repositioning or removing the device was an advantage. The higher attenuation may lead to fewer devices per case and early aneurysm occlusion. Long-term follow-up data are pending.

Coil occlusion of wide-neck bifurcation aneurysms assisted by a novel intra- to extra-aneurysmatic neck-bridging device (pCONus): initial experience.

BACKGROUND AND PURPOSE: The pCONus is a new stentlike self-expanding nitinol implant with 4 distal petals, which is fully retrievable and electrolytically detachable. The distal end is implanted inside the aneurysm at the neck. The shaft is anchored in the parent vessel. In selected wide-neck bifurcation aneurysms, the pCONus was used to assist coiling. The device was evaluated for its safety and efficacy. MATERIAL AND METHODS: Twenty-eight patients with 28 wide-neck aneurysms (9 recently ruptured) were treated with pCONus-assisted coiling at the discretion of the operator. Other treatment options were considered but were discarded due to anticipated difficulties. Technical issues, immediate posttreatment angiographic findings, clinical outcome, and follow-up imaging were assessed. RESULTS: There were 11 MCA, 7 anterior communicating artery, 1 posterior cerebral artery, 1 A2, and 8 basilar artery aneurysms. Insertion and deployment of the pCONus and subsequent coiling were possible in all cases. There were no clinically evident complications associated with the use of the device. Initial anatomic outcome showed 8 complete occlusions, 9 neck remnants, and 11 incomplete occlusions. Neurologic status remained unchanged at follow-up. Angiographic controls were obtained in 22 patients (mean, 7.5 months). Of these, 13 had complete occlusion, 9 showed improvement, and 7 were unchanged. Four died from SAH sequelae or other diseases, and 2 have not yet undergone follow-up. No intimal hyperplasia was observed. CONCLUSIONS: The pCONus facilitates coil occlusion of unruptured and ruptured wide-neck bifurcation aneurysms. The device can be deployed safely. Coil retention is sufficient to protect the efferent vessels. So far, no intimal hyperplasia in the shaft has been observed.

Frequency and relevance of anterior cerebral artery embolism caused by mechanical thrombectomy of middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Spread of thrombus material in previously unaffected vessels is a potential hazard of mechanical thrombectomy, but it has not yet been investigated in detail, to our knowledge. Our purpose was to evaluate the frequency and relevance of these events in mTE of M1 occlusions. MATERIALS AND METHODS: We retrospectively reviewed all patients treated for isolated M1 occlusion between January 2008 and July 2012. Angiographic images were analyzed to assess emboli in anterior cerebral artery branches induced by mTE and associated devices. Recanalization attempts in the ACA were reported as well as technical success and adverse events of rescue therapies. ACA infarcts on follow-up imaging served as a surrogate for clinical relevance. ACA infarcts were quantified volumetrically and assessed visually for involvement of motor or supplementary motor areas. RESULTS: New ACA emboli occurred in 12 of 105 (11.4%) M1 recanalization procedures and were caused by a stent-retriever in 11 intances. Attempts to recanalize the ACA were made in 6 patients and were deemed technically successful in 5 with no adverse events. We detected 6 (5.7%) new infarcts on follow-up imaging with an average volume of 26.9 cm(3). Involvement of motor or supplementary motor areas was seen in 4 (3.8%) cases. Three patients developed ACA infarcts despite successful endovascular ACA recanalization. CONCLUSIONS: The frequency of ACA emboli in mTE of M1 occlusions is relevant, causing ACA infarcts in 5.7% of patients; 3.8% of emboli were likely to hamper motor-function recovery. Endovascular recanalization of major ACA branches reduced the incidence of infarcts with no adverse events.

[New options in the therapeutic management of acute ischaemic stroke. Good results with combined i. v. and i. a. lysis and mechanical thrombectomy]. / Neue Wege bei der Akuttherapie des ischämischen Schlaganfalls. Behandlungserfolge mit kombinierter i. v. und i. a. Lyse sowie mechanischer Thrombektomie.

BACKGROUND: Standard therapy for acute ischaemic stroke is the intravenous thrombolysis with rtPA. A combined therapy with intravenous bridging and consecutive intraarterial thrombolysis and mechanical thrombectomy is a relatively new option in patients with proximal vessel occlusion. PATIENTS AND METHODS: 10 Patients with a CTA proven proximal vessel occlusion in the anterior circulation (ACI, carotis bifurcation, MCA) in CTA were treated with a combined therapy with i. v. and i. a. thrombolysis and thrombectomy with a Solitaire FR stent device. RESULTS: All Patients were recanalized, the NIHSS changed from 15.6 to 3.3. 8 out of 10 patients had nearly no symptoms when dismissed. There were no direct therapeutic complications. CONCLUSION: Combined therapy with i. v. and i. a. thrombolysis and thombectomy with the Solitaire FR stent device is a promising option in patients with acute proximal vessel occlusion in the anterior circulation.

Materials and techniques for coiling of cerebral aneurysms: how much scientific evidence do we have?

INTRODUCTION: Since coils were approved for aneurysm treatment, materials and techniques developed rapidly. It still remains an open question whether one material or method is superior. This article reviews the literature on various coil types and treatment approaches assessing the scientific evidence of its use. MATERIALS AND METHODS: Studies on aneurysm treatment with Guglielmi detachable platinum coils, bioactive coils, hydrogel coated coils, and complex designs as well as balloon- and stent-assisted techniques were retrieved by a PubMed database search from 1990 until May 2008. Data were analyzed in terms of aneurysm occlusion, permanent morbidity and mortality, recanalization, and retreatment. We also assessed the level of evidence of the published studies. RESULTS: Only the International Subarachnoid Aneurysm Trial provides level I evidence proving the superiority of endovascular over surgical therapy in ruptured aneurysms. Randomized trials comparing bioactive or hydrogel coated devices with bare coils are ongoing. Other studies were based on registries or case series mainly conducted without control groups. Morbidity, mortality, and initial occlusion rates appear similar for all devices. No clear evidence exists for the superiority of bioactive- or hydrocoils regarding long-term stability. It remains ambiguous whether morbidity and mortality rises with the use of balloons and stents. There is no evidence that routine use of balloons improves treatment durability. Mid-term results of stent-assisted coiling of complex aneurysms appear favorable. CONCLUSION: There is a lack of studies with a high level of evidence comparing different coiling materials and techniques. Case series and registries were not able to prove the superiority of any device or method.

Treatment of symptomatic high-grade intracranial stenoses with the balloon-expandable Pharos stent: initial experience.

INTRODUCTION: We report our first clinical experience with a CE-marked flexible monorail balloon-expandable stent for treatment of high-grade intracranial stenoses. METHODS: Between April 2006 and November 2007 21 patients with symptomatic intracranial stenoses (>70%) were treated with the PHAROS stent. In seven patients, the procedure was performed during acute stroke intervention. Procedural success, clinical complication rates and mid-term follow-up data were prospectively recorded. RESULTS: During a median follow-up period of 7.3 months one additional patient died of an unknown cause 3 months after the intervention. A patient with a significant residual stenosis presented with a new stroke after further progression of the residual stenosis. None of the successfully treated patients experienced ipsilateral stroke. CONCLUSION: Recanalization of intracranial stenoses with the balloon-expandable Pharos stent is technically feasible. The periprocedural complication rate and mid-term follow-up results were in the range of previously reported case series. This pilot study was limited by the small sample size and severe morbidity of the included patients. Final evaluation of the efficacy of Pharos stent treatment demands further investigation.

[Endovascular treatment for intracranial stenoses. A common statement by neurologists and neuroradiologists]. / Endovaskuläre Behandlung intrakranieller Stenosen. Eine gemeinsame Stellungnahme von Neurologen und Neuroradiologen.

Intracranial stenoses cause 5-10% of all strokes and are increasingly detected by means of modern imaging methods. The stroke danger of high-grade symptomatic stenoses is relatively high, with an annual risk of approximately 10% under medical treatment. Coumadin increases the risk of hemorrhage, and after risk/benefit considerations, antiplatelets should be preferred for antithrombotic therapy. Despite optimized medical treatment, a small group of patients with recurrent symptoms or symptomatic stenoses without adequate collateral supply probably carry higher spontaneous stroke risk and may be considered for intracranial stenting, which itself is associated with procedural risks of up to 10%. Currently published case series show relatively high complication rates as a major drawback of endovascular treatment, mainly strokes after occlusion of perforating branches extending from the stenotic vessel segment or hemorrhagic complications. According to data from smaller feasibility studies, stroke rates in follow-up after successful stenting seem to be low. The average rate of high-grade restenosis with possible indication for reintervention is 10%. Improvements in endovascular treatment aim at reducing vessel wall trauma during balloon angioplasty by underdilatation or the use of self-expanding stents. Until complication rates are dependably reduced to values of 5-6%, indication for endovascular treatment should be restricted to patients without therapeutic alternatives. According to limited data with large variation between different studies, a prospective multicentric registry is proposed for systematic evaluation and further development of the method.

Development of the osteoblast phenotype in primary human osteoblasts in culture: comparison with rat calvarial cells in osteoblast differentiation.

In rat osteoblast-like cells, a time-dependent sequence of growth and differentiation-dependent genes has been identified and a model of osteoblast differentiation in culture suggested. We investigated the expression of the bone matrix-associated proteins osteonectin and procollagen I and of the bone cell phenotype-related proteins alkaline phosphatase and osteocalcin during cell culture in primary human osteoblast like cells. Primary human explant cultures from nine young healthy donors were established under highly standardized conditions. Cells in the second passage were analyzed on different days from day 1 to 32, comparing cells growing under the influence of ascorbate with controls. Gene expression was determined by Northern blot analysis or polymerase chain reaction. Osteocalcin expression was also investigated after 1,25-(OH)(2)D(3) stimulation. On the protein level, newly synthesized collagen I, alkaline phosphatase activity, and secretion of osteocalcin were analyzed at all time points. On comparing our findings to the pattern of gene expression suggested for the rat calvarial osteoblast system, we found a similar developmental sequence for the so-called "proliferation" as well as a similar, but lengthened, sequence for the "matrix maturation stage." During "matrix maturation," we found an ongoing proliferation despite increased alkaline phosphatase and decreased procollagen I gene expression. Our study, therefore, shows that in pHOB the gene expression profile proceeded to the "matrix maturation stage," as defined by Owen and colleagues, independent of ongoing proliferation. We were unable to observe the mineralization period as demonstrated by the missing increase of osteocalcin expression and lack of nodule formation in our human osteoblast model. In contrast to the rat system, we found a proliferation stimulating influence of ascorbate, suggesting species-specific differences in response to differentiation factors. From these data, we conclude that general considerations on physiology and pathophysiology of bone cell differentiation have to be confirmed in the human osteoblastic cell system.

In vitro differentiation potential of a new human osteosarcoma cell line (HOS 58).

Cultured rodent osteoblastic cells reiterate the phenotypic maturation of osteoblasts seen in vivo. Under appropriate culture conditions this maturation is a stepwise sequence of phenotypic changes culminating in the production of a mineralised matrix. Although individual components of the osteoblast phenotype are apparent in transformed osteosarcoma cell lines, the co-ordination of the maturation sequence appears to be compromised. Because to date no comparable human cell differentiation system has been developed we investigated the recently introduced HOS 58 osteosarcoma cell line up to 3 months in culture. Proliferation, the secretion of osteoblast specific proteins, gene expression and mineralisation were analysed at different time points. Low-density HOS 58 cultures exhibit rapid proliferation and high levels of c-myc, collagen type I and osteopontin mRNAs. This phenotypic stage was maximum between the 4th and 5th days of culture. As cell density increased expression of these genes declined and by day 14 the predominant mRNAs was alkaline phosphatase. Osteocalcin secretion was detected after confluence at an increasing level. In the presence of ascorbate and beta-glycerophosphate the production of alkaline phosphatase and collagen type I increased coincident with the elaboration of a Von Kossa staining matrix. Nevertheless no proper mineralisation of the collagenous matrix was detectable by electron microscopy. Hence, the human osteosarcoma cell line HOS 58 expressed a rather differentiated phenotype with further maturation during a culture period of 21 days. We conclude that the developmental sequence exhibited by the HOS 58 human osteosarcoma cell line is comparable to that described for primary rat osteoblasts. However, in detailed analysis considerable differences to other species are evident. Further evaluation of the HOS 58 system and comparison to other human osteoblast cell lines will be necessary to establish the most appropriate differentiation model for human bone cell cultures.

Analysis of human primary bone cells by fluorescence activated cell scanning: methodological problems and preliminary results.

We describe the development of flowcytometrical methods to analyse human primary osteoblast-like cultures obtained from trabecular bone explants in comparison to the human osteosarcoma cell line HOS 58. Two antigens typical of osteoblasts were studied: bone alkaline phosphatase and collagen/procollagen I; the non-specific attachment protein fibronectin served as control. The morphology of all different antigens is shown by immunocytochemistry before flowcytometrical analysis. The establishment of flowcytometry is described in detail. While all antigens tested were nearly 100% positive in the HOS 58 cells in immunocytochemistry and flowcytometry, in primary osteoblast-like cells results varied widely between both methods. Cell permeabilisation before flowcytometry improved the homogeneity of results, probably by increasing the accessibility of the specific antibody to intracellular compartments. Though up to 80% of cells were lost during preparation the ratio of positive versus negative cells in specific experiment was not dependent on the cell recovery. Therefore, the cells finally analysed seemed to be representative of the total population.