Venous thromboembolism and intracranial hemorrhage in patients undergoing glioblastoma surgery.

In the perioperative management of patients with glioblastoma (GBM), physicians face the question of whether and when to administer prophylactic or therapeutic anticoagulation (AC). In this study, we investigate the effects of the timing of postoperative heparinization on thromboembolic events (TE) and postoperative hemorrhage (bleeding, PH) as well as the interactions between the two in the context of an underlying intracerebral malignancy. For this retrospective data analysis, 222 patients who underwent surgery for grade IV glioblastoma, IDH-wildtype (2016 CNS WHO) between 01/01/2014 and 31/12/2019 were included. We followed up for 12 months. We assessed various biographical and clinical data for risk factors and focused on the connection between timepoint of AC and adverse events. Subgroup analyses were performed for pulmonary artery embolism (PE), deep vein thrombosis, and postoperative intracranial hemorrhage (PH) that either required surgical intervention or was controlled radiologically only. Statistical analysis was performed using Mann-Whitney U-Test, Chi-square test, Fisher's exact test and univariate binomial logistic regression. p values below 0.05 were considered statistically significant. There was no significant association between prophylactic AC within 24 h and more frequent major bleeding (p = 0.350). AC in patients who developed major bleeding was regularly postponed by the physician/surgeon upon detection of the re-bleeding; therefore, patients with PH were anticoagulated significantly later (p = 0.034). The timing of anticoagulant administration did not differ significantly between patients who experienced a thromboembolic event and those who did not (p = 0.634). There was considerable overlap between the groups. Three of the six patients (50%) with PE had to be lysed or therapeutically anticoagulated and thereafter developed major bleeding (p < 0.001). Patients who experienced TE were more likely to die during hospitalization than those with major bleeding (p = 0.022 vs. p = 1.00). Prophylactic AC within 24 h after surgery does not result in more frequent bleeding. Our data suggests that postoperative intracranial hemorrhage is not caused by prophylactic AC but rather is a surgical complication or the result of antithrombotic therapy. However, thromboembolic events worsen patient outcomes far more than postoperative bleeding. The fact that bleeding may occur as a complication of life-saving lysis therapy in the setting of a thromboembolic event should be included in this cost-benefit consideration.

Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm.

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment.

Flow diversion beyond the circle of Willis: endovascular aneurysm treatment in peripheral cerebral arteries employing a novel low-profile flow diverting stent.

BACKGROUND: Flow diversion (FD) has emerged as superior minimally invasive therapy for cerebral aneurysms. However, aneurysms of small peripheral vessel segments have not yet been adequately treatable. More specifically, currently established devices necessitate large microcatheters which impede atraumatic maneuvering. The Silk Vista Baby (SVB), a novel flow diverter, offers the as yet unique feature of deliverability via a 0.017 inch microcatheter. This study reports our first experience with the SVB in challenging intracranial vessels employing a vessel-specific tailored microcatheter strategy. MATERIALS AND METHODS: 25 patients (27 aneurysms) were prospectively included. A total of 30 SVBs were employed, predominantly targeting demanding aneurysms of the anterior communicating artery complex. The efficacy of the FD was assessed using two-dimensional vector-based perfusion and conventional digital subtraction angiography (DSA) after implantation and at the first follow-up at 3 months. The first follow-up was available in 22 patients. RESULTS: All devices were implanted without technical or clinical complications. Eleven treatments were performed using the recommended Headway 17. In 14 interventions the even more maneuverable Excelsior SL10 was used, which was previously tried and tested for safety 'in vitro' as an alternative delivery system. Aneurysmal influx was strongly reduced after implantation. All parent vessels remained patent. 17/27 aneurysms were completely occluded at first follow-up (∼2.7 months), 6/27 aneurysms showed decreased influx or delayed washout and one remained unchanged. In three cases follow-up DSAs are remaining. CONCLUSIONS: SVB provides enhanced controllability in vulnerable segments beyond the circle of Willis. Smaller variants (2.25 mm and 2.75 mm) can safely be implanted via the superiorly navigable Excelsior SL10. Hence, the SVB represents the next evolutionary step in minimally invasive treatment of cerebral aneurysms.

Cervical vagus nerve morphometry and vascularity in the context of nerve stimulation - A cadaveric study.

Vagus nerve stimulation (VNS) has become a well-established therapy for epilepsy and depression, and is emerging to treat inflammatory disease, with the cervical vagus nerve (CVN) as major stimulation site. CVN morphometries are missing for VNS, considering its variability. Morphometric data were obtained from CVNs in 27 cadavers, including branching patterns and histology. Cross-sectional area, greater and lesser diameters averaged 7.2 ± 3.1 mm2, 5.1 ± 1.5 and 4.1 ± 1.3 mm, and were ≤11.0 mm2, ≤7.0 and ≤5.8 mm in 90% of the specimens, respectively. Midline distance (position lateral to the laryngeal eminence) and skin distance (anterior-posterior from skin) averaged 34.5 ± 6.2 and 36.2 ± 9.4 mm, ≤49.0 and ≤41.0 mm in 90%, respectively. Nerve dimensions and surface topography correlated closely, but without gender-, side- or branching-dependent differences. The nerve fascicle number averaged 5.2 ± 3.5. Vagal arteries were observed in 49% of the cases. Negative correlations were found for age and cross-sectional area, as well as subperineural vessel count. Detailed anatomical data on the CVN and its vascularity are given, forming the morphometric basis for VNS refinement, filling an evident gap in light of the CVN being a structure with variable positions and branching. A 35 × 35-mm rule may apply for the CVN position, irrespective of branching or positional variation.

Positional Relations of the Cervical Vagus Nerve Revisited.

OBJECTIVES: The cervical part of the vagus nerve (CVN) has become an important target for stimulation therapy to treat epilepsy and psychiatric conditions. For this purpose, the CVN is visualized in the carotid sheath, assuming it to be localized dorsomedially between the carotid artery (CA) and the internal jugular vein (JV). The aim of our morphological study was therefore to revisit the CVN relationships to the CA and JV, hypothesizing it to have common variations to this classical textbook anatomy. MATERIALS AND METHODS: Positional relations of the CVN, CA and JV were investigated in the carotid sheath of 35 cadavers at the C3 to C6 level. Positional relations of the CVN, CA and JV were documented on the basis of a 3 × 3 chart. RESULTS: Eighteen different arrangements of the CVN, CA and JV were observed. The typical topographic relationship of the CVN dorsomedially between the CA and JV was only found in 42% of all cases. The CVN was located dorsally or (dorso-)laterally to the CA in 80% and dorsally or (dorso-)medially of the JV in 96% of all cases. CONCLUSIONS: Classical textbook anatomy of the CVN is only present in a minority of cases. Positional variations in contrast to textbook anatomy are considerably more frequent than previously described, which might be a hypothetical morphological explanation for the lack of efficacy or side effects of CVN stimulation. Furthermore, the position of the CVN relative to the internal jugular vein is more consistent than to the CA.

Subthalamic nucleus volumes are highly consistent but decrease age-dependently-a combined magnetic resonance imaging and stereology approach in humans.

The subthalamic nucleus (STN) is a main target structure of deep brain stimulation (DBS) in idiopathic Parkinson's disease. Nevertheless, there is an ongoing discussion regarding human STN volumes and neuron count, which could potentially have an impact on STN-DBS. Moreover, a suspected functional subdivision forms the basis of the tripartite hypothesis, which has not yet been morphologically substantiated. In this study, it was aimed to investigate the human STN by means of combined magnetic resonance imaging (MRI) and stereology. STN volumes were obtained from 14 individuals (ranging from 65 to 96 years, 25 hemispheres) in 3 T MRI and in luxol-stained histology slices. Neuron number and cell densities were investigated stereologically over the entire STN and in pre-defined subregions in anti-human neuronal protein HuC/D-stained slices. STN volumes measured with MRI were smaller than in stereology but appeared to be highly consistent, measuring on average 99 ± 6 mm3 (MRI) and 132 ± 20 mm3 (stereology). The neuron count was 431,088 ± 72,172. Both STN volumes and cell count decreased age-dependently. Neuron density was different for the dorsal, medial and ventral subregion with significantly higher values ventrally than dorsally. Small variations in STN volumes in both MRI and stereology contradict previous findings of large variations in STN size. Age-dependent decreases in STN volumes and neuron numbers might influence the efficacy of STN-DBS in a geriatric population. Though the study is limited in sample size, site-dependent differences for the STN subregions form a morphological basis for the tripartite theory. Hum Brain Mapp 38:909-922, 2017. © 2016 Wiley Periodicals, Inc.

Human vagus nerve branching in the cervical region.

BACKGROUND: Vagus nerve stimulation is increasingly applied to treat epilepsy, psychiatric conditions and potentially chronic heart failure. After implanting vagus nerve electrodes to the cervical vagus nerve, side effects such as voice alterations and dyspnea or missing therapeutic effects are observed at different frequencies. Cervical vagus nerve branching might partly be responsible for these effects. However, vagus nerve branching has not yet been described in the context of vagus nerve stimulation. MATERIALS AND METHODS: Branching of the cervical vagus nerve was investigated macroscopically in 35 body donors (66 cervical sides) in the carotid sheath. After X-ray imaging for determining the vertebral levels of cervical vagus nerve branching, samples were removed to confirm histologically the nerve and to calculate cervical vagus nerve diameters and cross-sections. RESULTS: Cervical vagus nerve branching was observed in 29% of all cases (26% unilaterally, 3% bilaterally) and proven histologically in all cases. Right-sided branching (22%) was more common than left-sided branching (12%) and occurred on the level of the fourth and fifth vertebra on the left and on the level of the second to fifth vertebra on the right side. Vagus nerves without branching were significantly larger than vagus nerves with branches, concerning their diameters (4.79 mm vs. 3.78 mm) and cross-sections (7.24 mm2 vs. 5.28 mm2). DISCUSSION: Cervical vagus nerve branching is considerably more frequent than described previously. The side-dependent differences of vagus nerve branching may be linked to the asymmetric effects of the vagus nerve. Cervical vagus nerve branching should be taken into account when identifying main trunk of the vagus nerve for implanting electrodes to minimize potential side effects or lacking therapeutic benefits of vagus nerve stimulation.

Median nerve fascicular anatomy as a basis for distal neural prostheses.

INTRODUCTION: Functional electrical stimulation (FES) serves as a possible therapy to restore missing motor functions of peripheral nerves by means of cuff electrodes. FES is established for improving lower limb function. Transferring this method to the upper extremity is complex, due to a lack of anatomical data on the physiological configuration of nerve fascicles. Our study's aim was to provide an anatomical basis for FES of the median nerve in the distal forearm and hand. METHODS: We investigated 21 distal median nerves from 12 body donors. The peripheral fascicles were traced back by removing the external and interfascicular epineurium and then assigned to 4 quadrants. RESULTS: A distinct motor and sensory distribution was observed. The fascicles innervating the thenar eminence and the first lumbrical muscle originated from the nerves' radial parts in 82%. The fascicle supplying the second lumbrical muscle originated from the ulnar side in 78%. No macroscopically visible plexus formation was observed for the distal median nerve in the forearm. CONCLUSIONS: The findings on the distribution of the motor branches of the median nerve and the missing plexus formation may likely serve as an anatomical basis for FES of the distal forearm. However, due to the considerable variability of the motor branches, cuff electrodes will need to be adapted individually in FES. Taking into account the sensory distribution of the median nerve, FES may also possibly be applied in the treatment of regional pain syndromes.