Search

Objective/Background A small number of complex intracranial aneurysms are not amenable to direct clipping strategies or endovascular treatment. In these patients, parent artery sacrifice and bypass revascularization for aneurysm occlusion is an option. There are 3 strategies for parent artery sacrifice: trapping, complete occlusion of the inflow, and outflow segment; proximal occlusion of the inflow vessel; and distal occlusion of the outflow vessel(s). This study aimed to compare these techniques with regard to aneurysm occlusion rates. Methods We reviewed our database for cerebral revascularization before parent artery sacrifice to treat cerebral aneurysms. We assessed aneurysm occlusion rates 3 and 12 months after surgery, outcome, and postoperative aneurysm rupture. Results In total, 121 patients underwent parent artery sacrifice for complex aneurysms; 30% of the parent arteries were trapped, 58% proximally, and 12% distally occluded. Postoperative digital subtraction angiography revealed an aneurysm occlusion rate of 100% after trapping. Proximal occlusion led to early complete aneurysm occlusion in 71% of the cases, 21% occluded during follow-up. The complete occlusion rate was 96%, distal occlusion had an early aneurysm occlusion rate of 40%, 40% occluded during follow-up. Complete aneurysm occlusion rate was only 80%. All 3 techniques resulted in a volume reduction of more than 60% without a significant difference between the groups. The annual aneurysm rupture rate after distal parent artery sacrifice was 15%; there was no rupture after trapping or proximal parent artery sacrifice. Conclusions Trapping and proximal parent artery sacrifice seem to be superior to distal parent artery sacrifice regarding occlusion and rupture rates.

BACKGROUND: Extracranial-to-intracranial bypass surgery is a well-established technique that has been practiced for over 50 years. Since then, numerous technical variants have developed nationally and internationally. OBJECTIVE: Based on a survey, to collect information on cerebrovascular bypass surgeons and their background, surgical volume, and technical steps of extracranial-to-intracranial bypasses with focus on superficial temporal artery to middle cerebral artery (STA-MCA) bypass. METHODS: An electronic survey was distributed among bypass neurosurgeons. Responses were analyzed for national-international variations of STA-MCA bypass surgery techniques. The survey focused on the technical aspects of the surgery itself rather than patient selection or perioperative management. RESULTS: Survey responses were collected from 51 neurosurgeons performing cerebrovascular bypass, from 11 different countries across North America, Europe, and Asia. The largest age block was early-to mid-career (66.7% aged 36-50 years). Most participating surgeons (80.40%) performed less than 20 bypasses annually, whereas a select few surgeons (3) performed more than 50 annually. The most common bypass was STA-M4MCA bypass with a linear incision (34%) over the parietal branch (44%) and choosing an MCA recipient based on diameter (61.2%). The interrupted anastomosis technique was most common (74%). CONCLUSIONS: The results of this electronic survey will help to identify common patterns in STA-MCA bypass surgery and will serve as a guide to other neurosurgeons to modify and improve their technique. Cerebrovascular bypass is still widely practiced, including by young neurosurgeons, who are actively learning from established masters who share their experience.

Physiological effects of spreading depolarizations (SD) are only well studied in the first hours after experimental stroke. In patients with malignant hemispheric stroke (MHS), monitoring of SDs is restricted to the postoperative ICU stay, typically day 2-7 post-ictus. Therefore, we investigated the role of physiological variables (temperature, intracranial pressure, mean arterial pressure and cerebral perfusion pressure) in relationship to SD during the late phase after MHS in humans. Additionally, an experimental stroke model was used to investigate hemodynamic consequences of SD during this time window. In 60 patients with MHS, the occurrence of 1692 SDs was preceded by a decrease in mean arterial pressure (−1.04 mmHg; p = .02) and cerebral perfusion pressure (−1.04 mmHg; p = .03). Twenty-four hours after middle cerebral artery occlusion in 50 C57Bl6/J mice, hypothermia led to prolonged SD-induced hyperperfusion (+2.8 min; p

Background: Common carotid artery occlusion (CCA-occlusion) is a rare condition where standard revascularization is not feasible. Here, we analyzed our experience with surgical revascularization of CCA-occlusion to develop an algorithm for selection of the most suitable bypass strategy according to the Riles classification. Methods: During a 10-year period, 16 out of 288 patients with cerebrovascular disease and compromised hemodynamic reserve underwent revascularization for unilateral CCA-occlusion. The utilized bypass strategies included (1) a saphenous vein graft from the subclavian artery (SA) to the internal carotid artery (ICA), (2) a radial artery graft from the V3 segment of the vertebral artery (VA) to a superficial branch of the middle cerebral artery (MCA), or (3) a saphenous vein graft from the SA to a deep branch of the MCA. Results: In CCA-occlusion with maintained external carotid artery (ECA)/ICA patency (Riles type 1A), an SA-ICA bypass was performed (25%). In cases without ECA/ICA patency (Riles type 1B or 2) but suitable VA, a VA-MCA bypass was grafted (31%). In cases with unsuitable VA, a long SA-MCA interposition bypass was performed (38%). Transient postoperative neurological deficits occurred in 5 patients (31%) with 1 patient (6%) suffering permanent neurological worsening and 1 mortality (6%). Overall, no difference was found between the median preoperative mRS (2; range, 1–4) and the mRS at the time point of the last follow-up (2; range, 1–6; p = 0.75). The long-term graft patency was 94%. Conclusions: Although surgical revascularization for CCA-occlusion is feasible, it is associated with a higher risk than standard bypass grafting. Considering the poor natural history of CCA-occlusion, however, this risk may be justified in carefully selected patients.

Objective: Loss of cerebral autoregulation (CA) plays a key role in secondary neurologic injury. However, the regional distribution of CA impairment after acute cerebral injury remains unclear because, in clinical practice, CA is only assessed within a limited compartment. Here, we performed large-scale regional mapping of cortical perfusion and CA in patients undergoing decompressive surgery for malignant hemispheric stroke. Methods: In 24 patients, autoregulation over the affected hemisphere was calculated based on direct, 15 to 20-minute cortical perfusion measurement with intraoperative laser speckle imaging and mean arterial blood pressure (MAP) recording. Cortical perfusion was normalized against noninfarcted tissue and 6 perfusion categories from 0% to >100% were defined. The interaction between cortical perfusion and MAP was estimated using a linear random slope model and Pearson correlation. Results: Cortical perfusion and CA impairment were heterogeneously distributed across the entire hemisphere. The degree of CA impairment was significantly greater in areas with critical hypoperfusion (40-60%: 0.42% per mmHg and 60-80%: 0.46% per mmHg) than in noninfarcted (> 100%: 0.22% per mmHg) or infarcted (0-20%: 0.29% per mmHg) areas (*p < 0.001). Pearson correlation confirmed greater CA impairment at critically reduced perfusion (20-40%: r = 0.67; 40-60%: r = 0.68; and 60-80%: r = 0.68) compared to perfusion > 100% (r = 0.36; *p < 0.05). Tissue integrity had no impact on the degree of CA impairment. Interpretation: In hemispheric stroke, CA is impaired across the entire hemisphere to a variable extent. Autoregulation impairment was greatest in hypoperfused and potentially viable tissue, suggesting that precise localization of such regions is essential for effective tailoring of perfusion pressure-based treatment strategies. ANN NEUROL 2020

Background To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. Methods In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. Results During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. Conclusions Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.

A prospective case-series study and a retrospective analysis of historical patients for comparison of data.To compare accuracy and limitations of intraoperative computed tomography (iCT)- versus 3D C-arm-based spinal navigation for posterior pedicle screw implantation.Despite the higher accuracy of navigated compared to non-navigated pedicle screw implantation, it remains a matter of debate whether the use of iCT imaging may further benefit navigated spinal instrumentation compared to more commonly used isocentric 3D C-arm imaging.Between 2013 and 2016, 1527 pedicle screws were implanted in 260 patients with iCT (1219 screws) or 3D C-arm (308 screws)-based spinal navigation. Screw positioning was intraoperatively assessed by a second iCT or 3D C-arm (intraoperative accuracy). If necessary, immediate intraoperative screw revision was performed. Thereafter, a third iCT or 3D C-arm scan was performed to confirm repositioning (final accuracy). Clinical and patient data, intraoperative screw assessability, and accuracy rates were retrospectively reviewed and analyzed by an independent observer.Intraoperative CT permitted immediate intraoperative assessment of each implanted screw. In contrast, 39 of the screws visualized with 3D C-arm imaging were intraoperatively not clearly assessable. Regarding the overall precision, iCT and 3D C-arm navigation yielded a comparable intraoperative accuracy (iCT 94.7% vs 3D C-arm 89.4%) and immediate correction of misplaced screws was feasible with both modalities (final accuracy: iCT 95.4% vs 3D C-arm 91.6%). Regarding the region specific performance, however, iCT-based navigation yielded significantly higher final accuracy rates in the cervical (iCT 99.5% vs 3D C-arm 88.9%, P 0.01) and thoracic (iCT 97.7% vs 3D C-arm 88.8%, P 0.001) regions.Both iCT and 3D C-arm-based spinal navigation provides high pedicle screw accuracy rates. Immediate screw assessability and placement accuracy in the cervical-thoracic spine, however, appear to be limited with intraoperative 3D C-arm imaging alone.3.

Over the last years, intraoperative use of fluorescein is gaining ground in the field of neurosurgery, due to development of a microscope-integrated YELLOW 560 module, with reported experiences in brain malignancies, aneurysms, and arteriovenous malformation surgery. The aim of this study is to determine the feasibility and value of fluorescein videoangiography during bypass procedures. The authors enrolled 11 patients who underwent extracranial-to-intracranial bypass for moyamoya disease, atherosclerotic steno-occlusive cerebrovascular disease, and flow replacement during a giant middle cerebral artery (MCA) aneurysm treatment. Patients underwent fluorescein videoangiography using microscope-integrated fluorescence module. In all 11 cases, good bypass patency was intraoperatively demonstrated through fluorescein videoangiography and confirmed by post-operative digital subtraction angiography or computed tomographic angiography. The technique seems to be less sensible than standard indocyanine green videoangiography in terms of flow velocity assessment during first pass and does not benefit from a dedicated software to perform hemodynamic parameter analysis (i.e., FLOW 800). Fluorescein videoangiography was able to show a higher number of vessels than indocyanine green videoangiography, providing an extremely well-defined view of cortical vascular network, also in deeper cortical areas. In case of deep-seated anastomosis, it allowed real-time manipulation of neurovascular structures, making it possible a safe analysis of vessels in deep surgical field during videoangiography observation. Fluorescein videoangiography is a cost-effective, easy-to-use, fast and safe intraoperative tool and is useful to assess graft patency and extent of cortical vascular network also in deeper cortical areas. In case of deep-seated anastomosis, it provides the great advantage of performing real-time manipulation of neurovascular structures during videoangiography observation. It could represent a valuable complementary or alternative technique to assess intraoperative bypass function.

Percutaneous paraspinal pedicle screw implantation (PPSI) reduces soft tissue trauma, blood loss, and postoperative pain but remains technically challenging and associated with radiation exposure and implant-related artefacts. Here, we determined the feasibility, screw accessibility, and the accuracy of navigated PPSI in the thoraco-lumbar sacral spine using intraoperative computed tomography (iCT) and robotic cone-beam CT (CBCT) imaging. Between 2015 and 2018, 465 percutaneous paraspinal pedicle screws were implanted in 75 patients using iCT- or CBCT-based spinal navigation with 230 screws connected to rod reducers during screw assessment imaging (iCT 198; CBCT 32). Clinical and demographic data, intraoperative screw accessibility, and screw accuracy were analyzed and compared to a case-matched cohort of 75 patients undergoing navigated implantation of 481 pedicle screws through an open midline approach. Both iCT and CBCT permitted reliable assessment of each implanted screw, regardless of artifacts caused by rod reducers. Although overall accuracy for correct placement was comparable between PPSI and open surgery (PPSI 96.6%; Open 94.2%), PPSI compared favorably to open surgery regarding complete placement within the pedicle (PPSI 90.1%; Open 75.1%; p

The myoblast-mediated delivery of angiogenic genes represents a cell-based approach for targeted induction of therapeutic collateralization. Here, we tested the superiority of myoblast-mediated co-delivery of vascular endothelial growth factor-A (VEGF) together with platelet-derived growth factor-BB (PDGF-BB) on transpial collateralization of an indirect encephalomyosynangiosis (EMS) in a model of chronic cerebral ischemia. Mouse myoblasts expressing a reporter gene alone (empty vector), VEGF, PDGF-BB or VEGF and PDGF-BB through a single bi-cistronic vector (VIP) were implanted into the temporalis muscle of an EMS following permanent ipsilateral internal carotid artery occlusion in adult, male C57BL/6N mice. Over 84 days, myoblast engraftment and gene product expression, hemodynamic impairment, transpial collateralization, angiogenesis, pericyte recruitment and post-ischemic neuroprotection were assessed. By day 42, animals that received PDGF-BB in combination with VEGF (VIP) showed superior hemodynamic recovery, EMS collateralization and ischemic protection with improved pericyte recruitment around the parenchymal vessels and EMS collaterals. Also, supplementation of PDGF-BB resulted in a striking astrocytic activation with intrinsic VEGF mobilization in the cortex below the EMS. Our findings suggest that EMS surgery together with myoblast-mediated co-delivery of VEGF/PDGF-BB may have the potential to serve as a novel treatment strategy for augmentation of collateral flow in the chronically hypoperfused brain.

Multimodal neuromonitoring in neurocritical care increasingly includes electrocorticography to measure epileptic events and spreading depolarizations. Spreading depolarization causes spreading depression of activity (=isoelectricity) in electrically active tissue. If the depression is long-lasting, further spreading depolarizations occur in still isoelectric tissue where no activity can be suppressed. Such spreading depolarizations are termed isoelectric and are assumed to indicate energy compromise. However, experimental and clinical recordings suggest that long-lasting spreading depolarization-induced depression and isoelectric spreading depolarizations are often recorded outside of the actual ischemic zones, allowing the remote diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Here, we analyzed simultaneous electrocorticography and tissue partial pressure of oxygen recording in 33 aneurysmal subarachnoid hemorrhage patients. Multiple regression showed that both peak total depression duration per recording day and mean baseline tissue partial pressure of oxygen were independent predictors of outcome. Moreover, tissue partial pressure of oxygen preceding spreading depolarization was similar and differences in tissue partial pressure of oxygen responses to spreading depolarization were only subtle between isoelectric spreading depolarizations and spreading depressions. This further supports that, similar to clustering of spreading depolarizations, long spreading depolarization-induced periods of isoelectricity are useful to detect energy compromise remotely, which is valuable because the exact location of future developing pathology is unknown at the time when the neurosurgeon implants recording devices.

Background: Decompressive hemicraniectomy (DHC) reduces mortality and improves outcome after malignant middle cerebral artery infarction (MMI) but early in-hospital mortality remains high between 22 and 33%. Possibly, this circumstance is driven by cerebral herniation due to space-occupying brain swelling despite decompressive surgery. As the size of the removed bone flap may vary considerably between surgeons, a size too small could foster herniation. Here, we investigated the effect of the additional volume created by an extended DHC (eDHC) on early in-hospital mortality in patients suffering from MMI. Methods: We performed a retrospective single-center cohort study of 97 patients with MMI that were treated either with eDHC (n = 40) or standard DHC (sDHC; n = 57) between January 2006 and June 2012. The primary study end point was defined as in-hospital mortality due to transtentorial herniation. Results: In-hospital mortality due to transtentorial herniation was significantly lower after eDHC (0 vs. 11%; p = 0.04), which was paralleled by a significantly larger volume of the craniectomy (p < 0.001) and less cerebral swelling (eDHC 21% vs. sDHC 25%; p = 0.03). No statistically significant differences were found in surgical or non-surgical complications and postoperative intensive care treatment. Conclusion: Despite a more aggressive surgical approach, eDHC may reduce early in-hospital mortality and limit transtentorial herniation. Prospective studies are warranted to confirm our results and assess general safety of eDHC. �� In Copyright http://rightsstatements.org/vocab/InC/1.0/, publishedVersion

Purpose: Current solutions for navigated spine surgery remain hampered by restrictions in surgical workflow as well as a limited versatility and applicability. Against this background, we report the first experience of navigated spinal instrumentation with the mobile AIRO® intraoperative computed tomography (iCT) scanner. Methods: AIRO® iCT was used for navigated posterior spinal instrumentation of 170 screws in 23 consecutive patients operated on in our Department between the first use of the system in May 2014 and August 2014. The indications for AIRO® were based on the surgical region, anatomical complexity and the need for >3 segment instrumentation. Following navigated screw insertion, screw positions were confirmed intraoperatively by a second iCT scan. CT data on screw placement accuracy were retrospectively reviewed and analyzed by an independent observer. Results: AIRO®-based spinal navigation was easy to implement and successfully accomplished in all patients, adding around 18–34 min to the net surgery time. A systematic description of the authors’ approach, setup in the OR and workflow integration of the AIRO® is presented. Analysis of screw placement accuracy revealed 9 (5.3 %) screws with minor pedicle breaches (2 mm, resulting in an accuracy rate of 95.9 %. Conclusions: The AIRO® system is an easy-to-use and versatile iCT for navigated spinal instrumentation and provides high pedicle screw accuracy rates. Although the authors’ experience suggests that the learning curve associated with AIRO®-based spinal navigation is steep, a systematic user-based approach to the technology is required.

The decision to perform decompressive hemicraniectomy (DHC) by default in malignant hemispheric stroke (MHS) remains controversial. Even under ideal conditions, DHC usually results in moderate to severe disability. The present study for the first time uses neuroimaging to identify independent outcome predictors in a prospective cohort of 96 MHS patients undergoing DHC. The primary outcome was functional status according to the modified Rankin Scale (mRS) at 12 months and categorized as favorable (mRS 0–3) or unfavorable (mRS 4–6). At 12 months, 19 patients (20%) reached favorable and 77 patients (80%) unfavorable outcome. The overall mean infarct volume was 328 ± 114 ml. Multivariable logistic regression identified age per year (OR 1.14, 95% CI 1.04–1.24; p = 0.005), infarct volume per cm3 (OR 1.012, 95% CI 1.003–1.022; p = 0.013), thalamic involvement (OR 8.65, 95% CI 1.04–72.15; p = 0.046) and postoperative pneumonia (OR 5.52, 95% CI 1.03–29.57; p = 0.046) as independent outcome predictors, which was confirmed by multivariable ordinal regression for age ( p = 0.004) and infarct volume ( p = 0.015). The infarct volume threshold for reasonable prediction of unfavorable outcome in our patients was 270 cm3, which in the future may help prognostication and development of clinical trials on DHC and outcome in MHS.

OBJECTIVESpinal navigation techniques for surgical fixation of unstable C1–2 pathologies are challenged by complex osseous and neurovascular anatomy, instability of the pathology, and unreliable preoperative registration techniques. An intraoperative CT scanner with autoregistration of C-1 and C-2 promises sufficient accuracy of spinal navigation without the need for further registration procedures. The aim of this study was to analyze the accuracy and reliability of posterior C1–2 fixation using intraoperative mobile CT scanner–guided navigation.METHODSIn the period from July 2014 to February 2016, 10 consecutive patients with instability of C1–2 underwent posterior fixation using C-2 pedicle screws and C-1 lateral mass screws, and 2 patients underwent posterior fixation from C-1 to C-3. Spinal navigation was performed using intraoperative mobile CT. Following navigated screw insertion in C-1 and C-2, intraoperative CT was repeated to check for the accuracy of screw placement. In this study, the accuracy of screw positioning was retrospectively analyzed and graded by an independent observer.RESULTSThe authors retrospectively analyzed the records of 10 females and 2 males, with a mean age of 80.7 ± 4.95 years (range 42–90 years). Unstable pathologies, which were verified by fracture dislocation or by flexion/extension radiographs, included 8 Anderson Type II fractures, 1 unstable Anderson Type III fracture, 1 hangman fracture Levine Effendi Ia, 1 complex hangman-Anderson Type III fracture, and 1 destructive rheumatoid arthritis of C1–2. In 4 patients, critical anatomy was observed: high-riding vertebral artery (3 patients) and arthritis-induced partial osseous destruction of the C-1 lateral mass (1 patient). A total of 48 navigated screws were placed. Correct screw positioning was observed in 47 screws (97.9%). Minor pedicle breach was observed in 1 screw (2.1%). No screw displacement occurred (accuracy rate 97.9%).CONCLUSIONSpinal navigation using intraoperative mobile CT scanning was reliable and safe for posterior fixation in unstable C1–2 pathologies with high accuracy in this patient series.

Spreading depolarizations (SD) occur in high frequency in patients with malignant hemispheric stroke (MHS). Experimentally, SDs cause marked increases in glutamate and lactate, whereas glucose decreases. Here, we studied extracellular brain glutamate, glucose, lactate, pyruvate and the lactate/pyruvate ratio in relationship to SDs after MHS. We inserted two microdialysis probes in peri-infarct tissue at 5 and 15 mm to the infarct in close proximity to a subdural electrode strip. During 2356.6 monitoring hours, electrocorticography (ECoG) revealed 697 SDs in 16 of 18 patients. Ninety-nine SDs in electrically active tissue (spreading depressions, SDd) were single (SDds) and 485 clustered (SDdc), whereas 10 SDs with at least one electrode in electrically inactive tissue (isoelectric SDs, SDi) were single (SDis) and 103 clustered (SDic). More SDs and a significant number of clustered SDs occurred during the first 36 h post-surgery when glutamate was significantly elevated (> 100 µM). In a grouped analysis, we observed minor glutamate elevations with more than two SDs per hour. Glucose slightly decreased during SDic at 5 mm from the infarct. Directions of SD-related metabolic changes correspond to the experimental setting but the long sampling time of standard microdialysis precludes a more adequate account of the dynamics revealed by ECoG.

Background FLOW 800 delivers a color-coded map for snapshot visualization of the temporal distribution dynamics after indocyanine green angiography with post hoc calculation of FLOW 800-specific hemodynamic parameters. However, the value of these parameters regarding quantitative flow assessment remains unclear. Objective To determine the value of FLOW 800-specific hemodynamic parameters in neurosurgical patients that permit assessment of hemodynamic changes within the microcirculation and macrocirculation. Methods FLOW 800 was performed in 25 patients undergoing superficial temporal artery to middle cerebral artery bypass grafting and in 5 patients undergoing high- or intermediate-flow bypass grafting. The time to half-maximum fluorescence (t1/2max) and the cerebral blood flow index were calculated in the recipient vessel (macrocirculation) and the cortical territory (microcirculation) surrounding the anastomosis. For further evaluation, FLOW 800-specific hemodynamic parameters were compared with cortical laser speckle imaging and quantitative Doppler flow within the graft. Results FLOW 800 provided color-coded information on the temporospatial distribution dynamics of the dye with excellent assessment of bypass patency. In the recipient vessel and in the cortical territory surrounding the anastomosis, FLOW 800 detected hemodynamic changes after superficial temporal artery to middle cerebral artery bypass grafting in terms of a significant decrease in t1/2max and increase in cerebral blood flow index. Interestingly, comparison of t1/2max with semiquantitative laser speckle imaging-specific cortical perfusion within the microcirculation demonstrated poor agreement, and neither t1/2max nor the cerebral blood flow index within the graft correlated with quantitative graft flow assessed by Doppler. Conclusion FLOW 800 may detect procedure-related hemodynamic changes within the microcirculation and macrocirculation but should not be used as a stand-alone tool for quantitative flow assessment.

Currently, there is no adequate technique for intraoperative monitoring of cerebral blood flow (CBF). To evaluate laser speckle imaging (LSI) for assessment of relative CBF, LSI was performed in 30 patients who underwent direct surgical revascularization for treatment of arteriosclerotic cerebrovascular disease (ACVD), Moyamoya disease (MMD), or giant aneurysms, and in 8 control patients who underwent intracranial surgery for reasons other than hemodynamic compromise. The applicability and sensitivity of LSI was investigated through baseline perfusion and CO2 reactivity testing. The dynamics of LSI were assessed during bypass test occlusion and flow initiation procedures. Laser speckle imaging permitted robust (pseudo-) quantitative assessment of relative microcirculatory flow and standard bypass grafting resulted in significantly higher postoperative baseline perfusion values in ACVD and MMD. The applicability and sensitivity of LSI was shown by a significantly reduced CO2 reactivity in ACVD (9.6 ± 9%) and MMD (8.5 ± 8%) compared with control (31.2 ± 5%; P < 0.0001). In high- and intermediate-flow bypass patients, LSI was characterized by a dynamic real-time response to acute perfusion changes and ultimately confirmed a sufficient flow substitution through the bypass graft. Thus, LSI can be used for sensitive and continuous, non-invasive real-time visualization and measurement of relative cortical CBF in excellent spatial-temporal resolution.

Background and Purpose— Age is the most important risk factor for ischemic stroke. Recent experiments evidenced an age-associated rarefaction of the native collateral vasculature. The purpose of this study was to assess in what way age and arteriogenesis influence cortical perfusion and recovery of hemodynamic impairment in aged and young C57/BL6 mice. Methods— After model establishment of chronic cerebral hypoperfusion in the C57/BL6 strain, sustained hemodynamic impairment was induced by permanent unilateral internal carotid artery occlusion in animals aged 4 to 6 weeks, 12 weeks, and 18 months. Functional and morphological outcome was assessed by laser speckle imaging before and during acetazolamide challenge on Days 0, 3, 7, and 14 and latex/carbon black angiography and immunohistochemistry on Day 21. Results— Although internal carotid artery occlusion did not result in a reduction of baseline perfusion, it led to significant hemodynamic impairment in all age groups. Furthermore, baseline perfusion in sham and cerebrovascular reactivity after internal carotid artery occlusion were significantly lower in animals aged 18 months (468±57 Flux; 20.8%±17%) compared with mice aged 4 to 6 weeks (568±120 Flux; 30.3%±17%) and 12 weeks (591±72 Flux; 34.2%±12%) from the beginning until Day 7 of the monitoring period. Functional outcome was in line with a 27% reduction of native leptomeningeal anastomoses in aged mice and only limited collateral outgrowth compared with young animals. Strikingly, all age groups reached spontaneous functional compensation by Day 14. Conclusions— Next to limited collateral remodeling, our results suggest that a hampered cerebrovascular response with age could intensify the risk for hemodynamic stroke in the elderly.

An encephalomyosynangiosis (EMS) is a temporal muscle graft that is placed onto the surface of the brain to serve as a source for collateral vessel growth for brain revascularization in patients with Moyamoya Disease (MMD). To facilitate an EMS in patients with occlusive cerebrovascular diseases other than MMD, the transfer of pro-angiogenic genes via transplantation of retrovirally transduced myoblasts into the temporal muscle may represent an innovative approach to augment collateralization. Thus, we tested whether retrovirally transfected myoblasts can spontaneously fuse with the non-ischemic and uninjured muscle tissue and if a reporter gene can be stably expressed within the temporal muscle of the EMS. Primary mouse myoblasts expressing a reporter gene were implanted into the temporal muscle prior to an EMS being performed on C57/BL6 mice. Three different implantation modalities were evaluated: (a) intramuscular injection, (b) application of a cell pellet and (c) a combination of both techniques. Myoblast implantation resulted in spontaneous fusion with the host muscle fibers and stable reporter gene expression at both the muscle/brain interface and within the non-ischemic and uninjured temporal muscle in all animals. The mean number of fused hybrid myofibers was 59 ± 28 after injection, 37 ± 30 after pellet application and 60 ± 23 after a combination of both techniques. Regardless of the implantation modality, an abundant extracellular expression of the reporter gene was evident at the muscle/brain interface; in the case of myoblast delivery by injection, expression was also observed around the needle tract marking the implantation site. This method could be used in the future to deliver angiogenic growth factors to the muscle/brain interface in order to improve revascularization after an EMS.

Background and Purpose— We investigated to what extent excitotoxicity and metabolic changes in the peri-infarct region of patients with malignant hemispheric stroke are associated with delayed infarct progression. Methods— In 18 patients with malignant hemispheric stroke, 2 microdialysis probes were implanted within the peri-infarct tissue at a distance of 5 and 15 mm to the infarct. Precise probe placement was achieved by intraoperative laser speckle imaging. Glutamate, glucose, pyruvate, and lactate levels were monitored for 5 days after surgery. Delayed infarct progression was determined from serial MRI on the day after surgery and after the monitoring period. Results— Initial stroke volume ranged from 122 to 479 cm 3 with a median of 295 cm 3 . Nine of 18 patients (50%) had delayed infarct progression (median, 44 cm 3 ; range, 19–93 cm 3 ). In these patients, glucose and individual pyruvate levels were significantly lower when compared with patients without infarct progression, whereas glutamate and the lactate–pyruvate ratio were significantly elevated in patients with infarct progression early after surgery (12–36 hours) at the 15-mm microdialysis probe location. Lactate was elevated but without difference between groups. Conclusions— Excitotoxic or metabolic impairment was associated with delayed infarct progression and could serve as a treatment target.

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia. Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[ 14 C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections. Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20–40 ml 100 g − 1 min − 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm 3 (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct. Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.

Currently, a reliable method for real-time prediction of ischemia in the human brain is not available. Here, we took a first step towards validating non-invasive intraoperative laser speckle imaging (iLSI) for prediction of infarction in 22 patients undergoing decompressive surgery for treatment of malignant hemispheric stroke. During surgery, cortical perfusion was visualized and recorded in real-time with iLSI. The true morphological infarct extension within the iLSI imaging field was superimposed onto the iLSI blood flow maps according to a postoperative MRI (16 h [95% CI: 13, 19] after surgery) with three-dimensional magnetization-prepared rapid gradient-echo and diffusion-weighted imaging reconstruction. Based on the frequency distribution of iLSI perfusion values within the infarcted and non-infarcted territories, probability curves and perfusion thresholds of normalized cerebral blood flow predictive of eventual infarction or non-infarction were calculated. Intraoperative LSI predicted and excluded cortical ischemia with 95% probability at normalized perfusion levels below 40% and above 110%, respectively, which represented 73% of the entire cortical surface area. Together, our results suggest that iLSI is valid for (pseudo-) quantitative assessment of blood flow in the human brain and may be used to identify tissue at risk for infarction at a given time-point in the course of ischemic stroke.

Recently, cerebral blood flow changes were re-discussed to contribute to tissue protection after preconditioning. In the present study, we demonstrate increased vessel diameters of the leptomeningeal anastomoses after hypoxic preconditioning by visualization of the brain angioarchitecture using the latex perfusion technique. This finding may display the anatomical correlate to previously described perfusion changes after preconditioning.

Surgical flow augmentation for treatment of cerebral hemodynamic impairment remains controversial. Here, we investigated the benefit of endothelial progenitor cell (EPC) treatment in a rat model of chronic cerebral hypoperfusion. At repeated time points after 3-vessel occlusion (3-VO), animals were treated with 1 × 10 6 Dil-labeled (a) ex vivo-expanded embryonic-EPC (e-EPC), (b) cyclic AMP-differentiated embryonic-endothelial progenitor-derived cells (e-EPDC as biologic control) or, (c) saline. The cerebrovascular reserve capacity (CVRC) was assessed immediately before and on days 7 and 21 after 3-VO. Structural effects were assessed by latex perfusion, immunohistochemistry, and intravital fluorescence video microscopy on day 21. Three-vessel occlusion resulted in a significant impairment of the CVRC with better functional recovery after treatment with e-EPC (16.4 ± 8%) compared with e-EPDC (3.7 ± 8%) or saline (6.4 ± 9%) by day 21 ( P

Object Currently, reliable low-cost and noninvasive techniques to assess cerebral perfusion in the operating room are not available. The authors report on their first clinical experience with laser speckle contrast analysis (LASCA) as a complementary imaging tool for the noninvasive and dynamic assessment of cerebral blood flow (CBF) during neurovascular surgery. The purpose of this preliminary study was to address the general feasibility of LASCA in terms of handling and image quality and to provide an example of its clinical implications. Methods Laser speckle contrast analysis was performed in patients undergoing cerebral revascularization procedures for the treatment of hemodynamic compromise and complex aneurysms. The portable LASCA device was centered over the surgical field, and continuous 5-minute recordings of relative CBF were obtained. In the case of flow augmentation for hemodynamic compromise, CBF monitoring was performed before and after completion of the anastomosis. In the case of flow replacement for parent artery sacrifice, CBF monitoring was performed during consecutive 30-second test occlusions of the radial artery graft after proximal internal carotid artery sacrifice and the subsequent initiation of blood flow through the bypass. Results In all cases, the authors achieved good visualization of relative CBF in addition to flow imaging in both the bypass graft and the cortical vasculature. During a sudden CBF decrease after test occlusion of the radial artery graft and subsequent flow initiation through the bypass, LASCA allowed immediate visualization and measurement of relative CBF in excellent spatiotemporal resolution. Conclusions In this study LASCA offered noninvasive and rapid intraoperative assessment of relative CBF, which can be used for optimizing neurovascular procedures.