Low-Profile Intra-Aneurysmal Flow Disruptor WEB 17 versus WEB Predecessor Systems for Treatment of Small Intracranial Aneurysms: Comparative Analysis of Procedural Safety and Feasibility.

BACKGROUND AND PURPOSE: The Woven EndoBridge 17 has recently been introduced to the market for facilitated endovascular treatment of small bifurcation aneurysms (≤7 mm) with low-profile microcatheters. We compared the Woven EndoBridge 17 with its predecessor versions in terms of procedural safety and feasibility. MATERIALS AND METHODS: This was a multicenter review of aneurysms ranging from 3 to 7 mm treated with the Woven EndoBridge between 2011 and 2019. Aneurysm characteristics, procedural parameters, and complications were retrospectively compared between treatment with the Woven EndoBridge 17 and a control group that was treated with its predecessor versions, using inverse probability of treatment weighting. RESULTS: Thirty-eight aneurysms treated with a Woven EndoBridge 17 (mean size, 4.9 ± 1.5 mm) and 70 treated with a predecessor version of the Woven EndoBridge 17 (mean size, 5.6 ± 1.4 mm) were included. The predecessor version of the Woven EndoBridge 17 had a higher failure rate (10.3%) than the Woven EndoBridge 17 (0%, P = .05). Additional stent placement was performed more often with the predecessor version of the Woven EndoBridge 17 (10.0%) than with the Woven EndoBridge 17 (2.6%, adjusted P = .005). The predecessor version of the Woven EndoBridge 17 was associated with a higher thromboembolic event rate (14.3%) than the Woven EndoBridge 17 (5.3%, adjusted P = .002). Neurologic complications (Woven EndoBridge 17: 2.6%; predecessor version of the Woven EndoBridge 17: 2.9%, adjusted P = 1.0) and immediate complete aneurysm occlusion rates (Woven EndoBridge 17: 57.9%; predecessor version of the Woven EndoBridge 17: 54.3%, adjusted P = .21) did not differ significantly between groups. CONCLUSIONS: In the current study, the Woven EndoBridge 17 was associated with a potentially lower thromboembolic event rate than the predecessor version of the Woven EndoBridge 17, without compromising the immediate aneurysm occlusion rate. Long-term clinical and angiographic outcome analysis will be necessary to draw a definite conclusion.

Navigated Transtubular Extraforaminal Decompression of the L5 Nerve Root at the Lumbosacral Junction: Clinical Data, Radiographic Features, and Outcome Analysis.

Purpose. Extraforaminal decompression of the L5 nerve root remains a challenge due to anatomic constraints, severe level-degeneration, and variable anatomy. The purpose of this study is to introduce the use of navigation for transmuscular transtubular decompression at the L5/S1 level and report on radiological features and clinical outcome. Methods. Ten patients who underwent a navigation-assisted extraforaminal decompression of the L5 nerve root were retrospectively analyzed. Results. Six patients had an extraforaminal herniated disc and four had a foraminal stenosis. The distance between the L5 transverse process and the para-articular notch of the sacrum was 12.1 mm in patients with a herniated disc and 8.1 mm in those with a foraminal stenosis. One patient had an early recurrence and another developed dysesthesia that resolved after 3 months. There was a significant improvement from preoperative to postoperative NRS with the results being sustainable at follow-up. ODI was also significantly improved after surgery. According to the Macnab grading scale, excellent or good outcomes were obtained in 8 patients and fair ones in 2. Conclusions. The navigated transmuscular transtubular approach to the lumbosacral junction allows for optimal placement of the retractor and excellent orientation particularly for foraminal stenosis or in cases of complex anatomy.

Spinal cord injury without radiographic abnormality (SCIWORA) in adults: MRI type predicts early neurologic outcome.

OBJECTIVES: The present study aimed to analyse the clinical and neuroimaging features of a consecutive series of adult patients with spinal cord injury without radiographic abnormality (SCIWORA) receiving early magnetic resonance imaging (MRI), and to apply the recently proposed MRI classification system. METHODS: Grade of neurologic impairment at admission and discharge was reported according to the American Spinal Injury Association Impairment Scale (AIS). A detailed analysis and categorisation of the extra- and intramedullary MRI findings was performed, and the relationship between imaging type and neurological outcome was described. RESULTS: Twenty-six adult patients (17 male and 9 female) with SCIWORA were identified (mean age of 52 years). The distribution of the initial AIS grade was 8% A (n=2), 19% B (n=5), 31% C (n=8) and 42% D (n=11) at admission and 15% (n=4) C, 58% (n=15) D and 27% (n=7) E at discharge, respectively. Type I SCIWORA was found in 23% (n=6) and type II in 77% (n=20) (IIa: 0%, IIb: 25%, IIc: 75%). The mean improvement of AIS grade in patients with type I lesions was 1.5 (median 1, range 1-3) and 0.9 (median 1, range 0-3) in type II. CONCLUSION: The findings underline the prognostic role of early MRI for adult patients with SCIWORA and support the use of the recently introduced MRI classification system. LEVEL OF EVIDENCE: Prognostic study, level III.

Inheritance of moyamoya disease in a Caucasian family.

BACKGROUND AND PURPOSE: Moyamoya disease is a very rare occlusive cerebrovascular disorder characterized by progressive stenosis or occlusion of the intracranial portion of the internal carotid artery and proximal cerebral arteries with an extensive network of fine collaterals. The aetiology and genetic susceptibility of moyamoya disease, especially in Caucasians, still remains unclear. METHODS AND RESULTS: We describe the cases of affected German father, daughter and son with juvenile stroke because of idiopathic moyamoya disease. The rare existing literature is reviewed and discussed. CONCLUSIONS: This is the first report on a father-to-child inheritance pattern in Caucasian patients with idiopathic Moyamoya disease (MMD). Our cases indicate possible genetic risk factors for the genesis of Caucasian Moyamoya disease.

Meta-analysis of microarray gene expression studies on intracranial aneurysms.

The rupture of intracranial aneurysms (IAs) is one of the most devastating neurological conditions known to date. Although treatment has changed dramatically throughout the last decades, the outcome of patients still has a poor prognosis. Besides environmental factors, genomics seem to be a very important factor in the genesis of this disease. Different approaches to decrypt genomic causes were pursued throughout the last years. Microarray gene expression studies comparing aneurysmal and healthy tissue seem to be one of the most promising approaches. However, large amounts of data created with each study, make a comparison or interpretation of results difficult. We analyzed microarray gene expression studies on IAs (vs. control tissue) and compared lists of genes with altered expression provided by the authors. Additionally functional pathway analysis was performed. We identified five microarray gene expression studies analyzing a total of 60 samples of IA tissue (30 ruptured IA, 30 unruptured IA). A total of 507 genes with altered expression were listed, of which 57 showed differences in more than two studies and seven in more than three studies (BCL2, COL1A2, COL3A1, COL5A2, CXCL12, TIMP4, TNC). The meta-analysis of five microarray gene expression studies on IAs revealed seven genes that are very likely to be involved in the genesis of IAs. Further analysis of these genes might provide valuable information on mechanisms causing this disease.

Association of the Jun dimerization protein 2 gene with intracranial aneurysms in Japanese and Korean cohorts as compared to a Dutch cohort.

In a previous study a linkage region for association to IA patients was found on chromosome 14q22. In this study, we report the findings of a positional candidate gene, Jun dimerization Protein 2 (JDP2), and single nucleotide polymorphisms (SNP) of that gene that are associated with intracranial aneurysms in different ethnic populations. We screened the linkage region around chromosome 14q22 and narrowed it down to JDP2. We then genotyped case and control groups of three different ethnic populations: 403 Japanese intracranial aneurysm (IA) cases and 412 controls, 181 Korean IA cases and 181 controls, 379 Dutch cases and 642 Dutch controls. Genotyping was performed using polymerase chain reaction and direct sequencing technology. The allele distribution of three SNPs (two intronic: rs741846; P=0.0041 and rs175646; P=0.0014, and one in the untranslated region: rs8215; P=0.019) and their genotype distribution showed significant association in the Japanese IA patients. The allelic and genotypic frequency of one intronic SNP (rs175646; P=0.0135 and P=0.0137, respectively) and the genotypic frequency for the SNP in the UTR region (rs8215; P=0.049) was also significantly different between cases and controls of the Korean cohort. There was no difference in allelic or genotypic frequencies in the Dutch population. These SNPs in JDP2 are associated with intracranial aneurysms, suggesting that variation in or near JDP2 play a role in susceptibility to IAs in East Asian populations.

Network-based gene expression analysis of intracranial aneurysm tissue reveals role of antigen presenting cells.

Little is known about the pathology and pathogenesis of the rupture of intracranial aneurysms. For a better understanding of the molecular processes involved in intracranial aneurysm (IA) formation we performed a gene expression analysis comparing ruptured and unruptured aneurysm tissue to a control artery. Tissue samples of six ruptured and four unruptured aneurysms, and four cerebral arteries serving as controls, were profiled using oligonucleotide microarrays. Gene ontology classification of the differentially expressed genes was analyzed and regulatory functional networks and canonical pathways were identified with a network-based computational pathway analysis tool. Real time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were performed as confirmation. Analysis of aneurysmal and control tissue revealed 521 differentially expressed genes. The most significantly associated gene ontology term was antigen processing (P=1.64E-16). Further network-based analysis showed the top scoring regulatory functional network to be built around overexpressed major histocompatibility class (MHC) I and II complex related genes and confirmed the canonical pathway "Antigen Presentation" to have the highest upregulation in IA tissue (P=7.3E-10). Real time RT-PCR showed significant overexpression of MHC class II genes. Immunohistochemical staining showed strong positivity for MHC II molecule specific antibody (HLA II), for CD68 (macrophages, monocytes), for CD45RO (T-cells) and HLA I antibody. Our results offer strong evidence for MHC class II gene overexpression in human IA tissue and that antigen presenting cells (macrophages, monocytes) play a key role in IA formation.

The influence of genetics on intracranial aneurysm formation and rupture: current knowledge and its possible impact on future treatment.

The etiology of intracranial aneurysm formation and rupture remains mostly unknown, but lately several studies have increasingly supported the role of genetic factors. In reports so far, genome-wide linkage studies suggest several susceptibility loci that may contain one or more predisposing genes. Depending on the examined ethnic population, several different non-matching chromosomal regions have been found. Studies of several candidate genes report association with intracranial aneurysms. To date, no single gene has been identified as responsible for intracranial aneurysm formation or rupture. In addition to the well-published environmental factors, such as alcohol intake, hypertension and smoking, only the recent progress in molecular genetics enables us to investigate the possible genetic determinants of this disease. Although a familial predisposition is the strongest risk factor for the development of intracranial aneurysms, the mode of Mendelian inheritance is uncertain in most families. Therefore, multiple genetic susceptibilities in conjunction with the environmental factors are considered to act together in the disease's etiology. Accordingly, researchers performed linkage studies and case-control association studies for the genetic analysis and have identified several genes to be susceptible to intracranial aneurysms. The identification of susceptible genes may lead to the understanding of the mechanism of formation and rupture and possibly lead to the development of a pharmacological therapy. Furthermore, should it be possible to identify a genetic marker associated with an increased risk of formation and rupture of an intracranial aneurysm, the necessity for screening and urgency of treatment could be determined more easily. In this review we summarize the current knowledge of intracranial aneurysm genetics and also discuss the method to detect the causalities. In view of the recent advances made in this field, we also give an outlook on possible future genetically engineered therapies, whose development are well underway.

The use of high-frequency electromagnetics in brain tumour surgery.

OBJECTIVE: The first commercially available high-frequency electromagnetic field (EMF) system promises additional functionality for neurosurgical procedures. In a prospective study, we evaluated the optimal use as well as the limitations of this system designed for vaporizing tissue and for coagulation in brain tumour surgery. METHODS: For the microsurgical treatment of 63 consecutive patients with various intracranial tumours, the EMF system was used in addition to the standard neurosurgical instrumentarium. The system was assessed with respect to its compatibility with the operating room environment. Furthermore, attention was given to the particular techniques required to use the system most effectively. The efficiency of the investigated tool was monitored throughout the study. RESULTS: The EMF system functioned properly in all procedures and did not cause any complications. Specific handling techniques and electrode tip configurations could be defined for optimal use of high-frequency electromagnetics for vaporization and coagulation in different intraoperative settings. Thereby, the efficiency of the device could be increased throughout the study while ineffective use decreased from 7 to 2 cases. Although this tool is designed ergonomically and offers high tactile control, it cannot be used submerged in cerebrospinal fluid or under continuous irrigation, which makes it necessary to use it in tandem with suction devices to obtain a clear view on the surgical field. CONCLUSION: Maneuvering with the EMF system was substantially different to both monopolar and bipolar systems, clearly necessitating a learning curve for the surgeon. This device was found to be a valuable complementary tool to standard electrosurgical instruments when applied effectively and with elaborated techniques.

Image-guided craniotomy for frontal sinus preservation during meningioma surgery.

OBJECTIVE: Preservation of the frontal sinus (FS) during the frontolateral approach to the skull base reduces morbidity, enhances patient comfort, and speeds up the surgical procedure. Due to its irregular outline, mental reconstruction of the borders of FS from two-dimensional images is challenging during surgery. This study was designed to evaluate the impact of neuronavigation on identification and preservation of the FS during frontolateral craniotomies. METHODS: Forty-five patients with pathologies located in the anterior skull base and in the parasellar region were included. A standard computed tomography (CT) sequence was obtained from each patient and uploaded onto an image-guidance system for volumetric rendering of 3D images. The outline of the FS was visualized and the distance between its lateral border and the mid-pupillary line (MPL) was measured. The results were used for navigated craniotomies and compared to the intra-operative findings. RESULTS: The FS was located medial, on and lateral to the MPL in 32, 4 and 9 cases, respectively. The individual outline of the FS could be identified with a mean target registration error of 1.4mm (+/-0.7 mm). The craniotomy could be custom-tailored for each patient according to the individualized landmarks while visualizing the lesion and the surgical landmarks simultaneously. Unintended opening of the frontal sinus or orbit did not occur in any of these cases. CONCLUSION: Image-guided craniotomies based on 3D volumetric image rendering allow for fast and reliable demarcation of complex anatomical structures hidden from direct view in frontolateral approaches. The outline of the frontal sinus and the orbit can be appraised at a glance providing additional safety and precision during craniotomy.

The Doppler-guided transfalcine venous approach in selected cases of vein of Galen malformations.

OBJECTIVE: This investigation was performed to evaluate the specific procedural issues and indications of a surgically assisted Doppler-guided endovascular transfalcine venous approach for the treatment of vein of Galen aneurysmal malformations (VGAM) in critically ill neonates. PATIENTS AND METHODS: Two neonates out of a clinical series of 15 children (8 males and 7 females) with vein of Galen malformations were treated by our neurovascular team, using a combined surgically assisted endovascular transfalcine approach. In the biplanar angiography room a radiographically guided craniotomy (1.5 cm) was placed over the cranial projection of the falciforme sinus. After craniotomy the orthograd flow of the falciforme sinus was identified by Doppler ultrasonography. The sinus was punctured by an i. v. cannula with injection port and was sutured to the skin. A microcatheter was maneuvered over a guide into the malformation under fluoroscopic control. For embolization Guglielmi electrolytically detachable platinum coils were placed into the malformation as an embolic agent. Neurological examination records, available MR images, computed tomographic scans, pre- and postembolization angiograms and follow-up data were analyzed. RESULTS: In both individuals the malformation was classified as VGAM. The follow-up was 6 and 7 months, respectively. No technique associated morbidity or mortality occurred in the present series. At discharge both selected neonates were in stable condition and the flow in the VGAMs could be significantly reduced by a combination of approaches including the venous transfalcine approach. Meanwhile, 6 months after birth one neonate died due to a deterioration of the pulmonary hypertension. CONCLUSIONS: Endovascular treatment is presently the most efficient strategy to allow neonates and infants survive the early manifestation of vein of Galen malformations and probably render a normal neurological development. Consequently, a combination of approaches in selected cases including the Doppler guided venous transfalcine route should be regarded as a preferential treatment modality, especially in patients with arterial vasospasms and venous stenosis.

Biodegradable implants in neurosurgery.

BACKGROUND: Biodegradable materials have been used for osteosynthesis by orthopedic surgeons and craniomaxillofacial surgeons for many years. However, such materials are not yet widely used by neurosurgeons despite potential applications. This prospective study was undertaken to evaluate potential applications of biodegradable materials in neurosurgical interventions. METHODS: A total of 104 4-hole plates and 228 screws consisting of copolymer of poly-70 L/30 D,L-lactide were inserted for fixation of bone flaps in 8 patients and for reinsertion of laminoplasties at 28 levels in 16. The craniotomies were performed for removal of a brain tumour in 4 cases, for surgical management of an aneurysm or cerebral AVM in 2, and for treatment of craniocerebral trauma in another 2. Laminoplasties were performed at 25 levels for intraspinal hemangioblastomas in 15 patients. One patient with an ependymoma underwent 3-level laminoplasty. FINDINGS: One patient with severe head injury in whom the bone flap was re-implanted several months following the craniectomy, developed an aseptic necrosis of the bone flap, which had to be removed. Implant rejection was not observed. One patient suffered from mild local pain in the area of a biodegradeable screw in the frontal region following removal of a sphenoid wing meningeoma. None of the patients with laminoplasty showed signs of functional instability or spinal cord compression. Implant rejection was not observed. No delayed healing or infection occurred. Healing was not delayed and no infections occurred. INTERPRETATION: The results encourage further use of biodegradable materials for the described applications. Additional studies will be performed to investigate the usefulness of biodegradable devices in neurosurgery and to obtain long-term results.

Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in intensive care treated with R-hirudin.

Patients in intensive care may be at high risk of in vivo platelet activation because comorbid conditions, such as infections, septicemia, shock, disseminated intravascular coagulation, and cancer represent procoagulant states. Hyperreactivity of platelets with or without a decline of cell count may result in thromboembolic complications potentially associated with the phenomenon of heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly suspected of having heparin-induced thrombocytopenia during their intensive care treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia coincided with thromboembolic complications. Six patients had additionally undergone fibrinolytic therapy before starting activated partial thromboplastin time-adapted alternative anticoagulation with r-hirudin. In three patients, the platelet count decreased without a clinical manifestation, of heparin-induced thrombocytopenia. R-Hirudin treatment monitored by activated partial thromboplastin time and prothrombin time (PT) was effective and safe. The target value for activated partial thromboplastin time was a twofold prolongation. In four of five patients with deep venous thrombosis, a partial recanalization of the lower extremity could be achieved. Three patients with pulmonary embolism associated with deep venous thrombosis in two cases and in one additional case with an acute myocardial infarction did clinically profit from fibrinolysis with recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two lethal events probably caused by the underlying multimorbidity could not be prevented. No recurrence of thrombosis occurred, and there were no severe bleeding complications attributed to r-hirudin treatment. Platelet counts were significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in all cases (>50% decrease related to the initial values) from 224,000 plus or minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10 cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result in four of eight analyzed cases. In four cases, the assays were concordantly positive. The PF4 enzyme-linked immunosorbent assay was not performed in two cases.

Improved therapeutic safety of oral anticoagulant therapy in Germany: the Saarland model.

In contrast to other European countries, in Germany more than 90% of oral anticoagulated patients are controlled by general practitioners. The International Normalized Ratio (INR) system in laboratory control is not in widespread use, often leading to misinterpretations of prothrombin time (PT) measurements. To improve the management of anticoagulated patients, a model was developed, consisting of different questionnaires and on the base of the INR system. Since 1993, 60 patients in our Department's outpatient anticoagulant clinic and since 1996 16 patients in the office of a general practitioner were followed for 146.32 patient years. There were no thromboembolic events and no major bleedings during follow-up. A total of 126 minor bleedings occurred in 30 patients. There were no significant differences in INR values and stable phases between the two centers; however, significantly shorter stable phases in patients with bleeding episodes were noted. Thus, this model seems to be useful also in general practitioners' hands.

Phenprocoumon from a neurosurgical perspective.

A 9-year series of 45 intracranial and spinal hematomas in patients under oral anticoagulant treatment with phenprocoumon was analyzed and compared to data from the literature. In 42% of the patients, International Normalized Ratio (INR) values >4.5 were found on admission, 36% were older than 70 years and most patients (38%) were under long-term treatment after cardiac valve replacement. Patients who recovered did not report to have given informed consent at the start of anticoagulant therapy. Because an average of five serious hemorrhages are reported/year from German neurosurgical departments, it can be estimated that about 650 intracerebral or intraspinal hematomas, including about 250 fatalities/year occur in Germany under oral anticoagulant treatment. These complications reach the same incidence than spontaneous hematomas either from aneurysms or angiomas. Standards for indications, clinical control, quality INR testing and INR targets not exceeding 4.0, and collecting more data on incidences and causative factors of complications may be an important contribution to reduce these fatalities.

The overdosed patient and bleedings with oral anticoagulation.

Overdose or bleeding with oral anticoagulation requires gradual antagonization of the drugs. Minor bleedings are most commonly managed by temporarily discontinuing treatment and by giving vitamin K to antagonize the coumarin derivative effects. Major bleedings, in contrast, especially intracranial hemorrhages, require immediate antagonization of anticoagulation. This is also necessary in required major surgery of anticoagulated patients. Instant normalization of hemostasis in such cases is achieved by the administration of clotting factors, in particular prothrombin complex concentrates. The use of fresh frozen plasma, instead, is less useful. The treatment with prothrombin complex concentrates requires a strict risk-benefit estimation and laboratory monitoring is recommended to optimize dosage adjustment. A 2-year follow-up of 45 out-patients receiving phenprocoumon at our center revealed a total of 11 bleeding complications (11.6/100 treatment-years, 10 minor and 1 major bleeding). Discontinuing or reducing oral anticoagulation together with vitamin K were the methods most frequently used to efficiently manage hemorrhages, whereas prothrombin complex concentrates were only used in one case with major bleeding. Oral anticoagulation appeared to be an enhancing factor for an otherwise existing bleeding diathesis rather than a genuine cause for hemorrhages.

Training of patients for self-management of oral anticoagulant therapy: standards, patient suitability, and clinical aspects.

Self-control and self-management of oral anticoagulant therapy have become more and more attractive for patients undergoing long-term treatment. In our training center, we examined 50 patients who took part in a standardized training course for self-management. Patients (36 men, 14 women) were preselected according to the guidelines of the German Association for Self-management of Oral Anticoagulation (ASA e.V.) and were all trained by the same physician. The complete course took an average of eight sessions. Patients older than 59 years needed significantly more training time in theoretical advising than younger patients; they did not need more training time in practical matters. The values between International Normalized Ratio (INR) measured in venous blood samples and by self-assessment were comparable for both groups. There was a good overall correlation between self-controlled INRs and laboratory assays, however, the self-assayed INRs were significantly lower than those from the venous blood samples.

Dimensions of quality of life and self-monitoring therapy with oral anticoagulants--still research or everyday practice?

In correlation with increased life expectancy of patients, quality of life (QOL) has become a factor of increasing interest by the patient himself and also of importance in health-care planning and recruitment of financial resources. In this context, self-monitoring of long-term anticoagulant treatment might be a strategy that could mean a step forward in health-related as well as general life satisfaction for patients participating in self-monitoring programs. Also, the new strategy of increased home-control of anticoagulant treatment illustrates the complexity of multiple factors that can lead to changes in the subjective feeling and objective aspects of QOL. Our intention in a pilot study was to probe the feasibility of QOL research and relevant factors of influence by retrospectively evaluating data from two groups of outpatients seen in a large treatment center. The high frequency (n = 8 in sample 2) of disturbed sleep as a simple screening indicator stresses the probable importance of undetected depression, which might require treatment and could confound research as to QOL. Instruments to measure QOL in oral anticoagulation self-monitoring should therefore be adapted to the heterogeneous structure of factors in the target population, and include psychological parameters, especially in regard to health-related locus of control and mood.