Cortical Spreading Depolarization in Moyamoya Vasculopathy: A Case Series.

BACKGROUND: Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization. METHODS: In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya. RESULTS: Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation. CONCLUSIONS: The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.

Similarities in the Electrographic Patterns of Delayed Cerebral Infarction and Brain Death After Aneurysmal and Traumatic Subarachnoid Hemorrhage.

While subarachnoid hemorrhage is the second most common hemorrhagic stroke in epidemiologic studies, the recent DISCHARGE-1 trial has shown that in reality, three-quarters of focal brain damage after subarachnoid hemorrhage is ischemic. Two-fifths of these ischemic infarctions occur early and three-fifths are delayed. The vast majority are cortical infarcts whose pathomorphology corresponds to anemic infarcts. Therefore, we propose in this review that subarachnoid hemorrhage as an ischemic-hemorrhagic stroke is rather a third, separate entity in addition to purely ischemic or hemorrhagic strokes. Cumulative focal brain damage, determined by neuroimaging after the first 2 weeks, is the strongest known predictor of patient outcome half a year after the initial hemorrhage. Because of the unique ability to implant neuromonitoring probes at the brain surface before stroke onset and to perform longitudinal MRI scans before and after stroke, delayed cerebral ischemia is currently the stroke variant in humans whose pathophysiological details are by far the best characterized. Optoelectrodes located directly over newly developing delayed infarcts have shown that, as mechanistic correlates of infarct development, spreading depolarizations trigger (1) spreading ischemia, (2) severe hypoxia, (3) persistent activity depression, and (4) transition from clustered spreading depolarizations to a negative ultraslow potential. Furthermore, traumatic brain injury and subarachnoid hemorrhage are the second and third most common etiologies of brain death during continued systemic circulation. Here, we use examples to illustrate that although the pathophysiological cascades associated with brain death are global, they closely resemble the local cascades associated with the development of delayed cerebral infarcts.

Microsurgical Clipping of Unruptured Anterior Circulation Aneurysms-A Global Multicenter Investigation of Perioperative Outcomes.

BACKGROUND AND OBJECTIVES: Microsurgical aneurysm repair by clipping continues to be highly important despite increasing endovascular treatment options, especially because of inferior occlusion rates. This study aimed to present current global microsurgical treatment practices and to identify risk factors for complications and neurological deterioration after clipping of unruptured anterior circulation aneurysms. METHODS: Fifteen centers from 4 continents participated in this retrospective cohort study. Consecutive patients who underwent elective microsurgical clipping of untreated unruptured intracranial aneurysm between January 2016 and December 2020 were included. Posterior circulation aneurysms were excluded. Outcome parameters were postsurgical complications and neurological deterioration (defined as decline on the modified Rankin Scale) at discharge and during follow-up. Multivariate regression analyses were performed adjusting for all described patient characteristics. RESULTS: Among a total of 2192 patients with anterior circulation aneurysm, complete occlusion of the treated aneurysm was achieved in 2089 (95.3%) patients at discharge. The occlusion rate remained stable (94.7%) during follow-up. Regression analysis identified hypertension (P < .02), aneurysm diameter (P < .001), neck diameter (P < .05), calcification (P < .01), and morphology (P = .002) as preexisting risk factors for postsurgical complications and neurological deterioration at discharge. Furthermore, intraoperative aneurysm rupture (odds ratio 2.863 [CI 1.606-5.104]; P < .01) and simultaneous clipping of more than 1 aneurysm (odds ratio 1.738 [CI 1.186-2.545]; P < .01) were shown to be associated with an increased risk of postsurgical complications. Yet, none of the surgical-related parameters had an impact on neurological deterioration. Analyzing volume-outcome relationship revealed comparable complication rates (P = .61) among all 15 participating centers. CONCLUSION: Our international, multicenter analysis presents current microsurgical treatment practices in patients with anterior circulation aneurysms and identifies preexisting and surgery-related risk factors for postoperative complications and neurological deterioration. These findings may assist in decision-making for the optimal therapeutic regimen of unruptured anterior circulation aneurysms.

Template-based target point localization for occlusion of the middle meningeal artery during evacuation of space-occupying chronic subdural hematoma.

OBJECTIVE: Endovascular middle meningeal artery (MMA) occlusion may help reduce the risk of recurrence after burr hole evacuation of chronic subdural hematoma (cSDH) but carries an additional periprocedural risk and remains hampered by logistical and financial requirements. In this study, the authors aimed to describe a simple and fast technique for preoperative MMA localization to permit burr hole cSDH evacuation and MMA occlusion through the same burr hole. METHODS: The authors performed a preclinical anatomical and prospective clinical study, followed by a retrospective feasibility analysis. An anatomical cadaver study with 33 adult human skulls (66 hemispheres) was used to localize a suitable frontal target point above the pterion, where the MMA can be accessed via burr hole trephination. Based on anatomical landmark measurements, the authors designed a template for projected localization of this target point onto the skin. Next, the validity of the template was tested using image guidance in 10 consecutive patients undergoing elective pterional craniotomy, and the feasibility of the target point localization for cSDH accessibility was determined based on hematoma localization in 237 patients who were treated for a space-occupying cSDH in the authors' department between 2014 and 2018. RESULTS: In the anatomical study, the mean perpendicular distance from the zygomatic process to the target point in the frontoparietal bone was 4.1 cm (95% CI 4-4.2 cm). The mean length along the upper margin of the zygomatic process from the middle of the external auditory canal to the point of the perpendicular distance was 2.3 cm (95% CI 2.2-2.4 cm). The template designed according to these measurements yielded high agreement between the template-based target point and the proximal MMA groove inside the frontoparietal bone (right 90.9%; left 93.6%). In the clinical validation, we noted a mean distance of 4 mm (95% CI 2.1-5.9 mm) from the template-based target point to the actual MMA localization. The feasibility analysis yielded that 95% of all cSDHs in this cohort would have been accessible by the new frontal burr hole localization. CONCLUSIONS: A template-based target point approach for MMA localization may serve as a simple, fast, reliable, and cost-effective technique for surgical evacuation of space-occupying cSDHs with MMA obliteration through the same burr hole in a single setting.

Global Outcomes for Microsurgical Clipping of Unruptured Intracranial Aneurysms: A Benchmark Analysis of 2245 Cases.

BACKGROUND AND OBJECTIVES: Benchmarks represent the best possible outcome and help to improve outcomes for surgical procedures. However, global thresholds mirroring an optimal and reachable outcome for microsurgical clipping of unruptured intracranial aneurysms (UIA) are not available. This study aimed to define standardized outcome benchmarks in patients who underwent clipping of UIA. METHODS: A total of 2245 microsurgically treated UIA from 15 centers were analyzed. Patients were categorized into low- ("benchmark") and high-risk ("nonbenchmark") patients based on known factors affecting outcome. The benchmark was defined as the 75th percentile of all centers' median scores for a given outcome. Benchmark outcomes included intraoperative (eg, duration of surgery, blood transfusion), postoperative (eg, reoperation, neurological status), and aneurysm-related factors (eg, aneurysm occlusion). Benchmark cutoffs for aneurysms of the anterior communicating/anterior cerebral artery, middle cerebral artery, and posterior communicating artery were determined separately. RESULTS: Of the 2245 cases, 852 (37.9%) patients formed the benchmark cohort. Most operations were performed for middle cerebral artery aneurysms (53.6%), followed by anterior communicating and anterior cerebral artery aneurysms (25.2%). Based on the results of the benchmark cohort, the following benchmark cutoffs were established: favorable neurological outcome (modified Rankin scale ≤2) ≥95.9%, postoperative complication rate ≤20.7%, length of postoperative stay ≤7.7 days, asymptomatic stroke ≤3.6%, surgical site infection ≤2.7%, cerebral vasospasm ≤2.5%, new motor deficit ≤5.9%, aneurysm closure rate ≥97.1%, and at 1-year follow-up: aneurysm closure rate ≥98.0%. At 24 months, benchmark patients had a better score on the modified Rankin scale than nonbenchmark patients. CONCLUSION: This study presents internationally applicable benchmarks for clinically relevant outcomes after microsurgical clipping of UIA. These benchmark cutoffs can serve as reference values for other centers, patient registries, and for comparing the benefit of other interventions or novel surgical techniques.

A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Post-hemorrhagic vasospasm with neurological deterioration is a major concern in this context. NicaPlant®, a modified release formulation of the calcium channel blocker nicardipine, has shown vasodilator efficacy preclinically and a similar formulation known as NPRI has shown anti-vasospasm activity in aSAH patients under compassionate use. Research question: The study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH. Material and methods: In this multicenter, controlled, randomized, dose escalation trial we assessed the safety and tolerability of NicaPlant®. aSAH patients treated by clipping were randomized to receive up to 13 NicaPlant® implants, similarly to the dose of NPRIs previous used, or standard of care treatment. Results: Ten patients across four dose groups were treated with NicaPlant® (3-13 implants) while four patients received standard of care. 45 non-serious and 13 serious adverse events were reported, 4 non-serious adverse events and 5 serious adverse events assessed a probable or possible causal relationship to the investigational medical product. Across the NicaPlant® groups there was 1 case of moderate vasospasm, while in the standard of care group there were 2 cases of severe vasospasm. Discussion and conclusion: The placement of NicaPlant® during clip ligation of a ruptured cerebral aneurysm raised no safety concern. The dose of 10 NicaPlant® implants was selected for further clinical studies.

Outcome and management of decompressive hemicraniectomy in malignant hemispheric stroke following cardiothoracic surgery.

Management of malignant hemispheric stroke (MHS) after cardiothoracic surgery (CTS) remains difficult as decision-making needs to consider severe cardiovascular comorbidities and complex coagulation management. The results of previous randomized controlled trials on decompressive surgery for MHS cannot be generally translated to this patient population and the expected outcome might be substantially worse. Here, we analyzed mortality and functional outcome in patients undergoing decompressive hemicraniectomy (DC) for MHS following CTS and assessed the impact of perioperative coagulation management on postoperative hemorrhagic and cardiovascular complications. All patients that underwent DC for MHS resulting as a complication of CTS between June 2012 and November 2021 were included in this observational cohort study. Outcome was determined according to the modified Rankin Scale (mRS) score at 1 and 3-6 months. Clinical and demographic data, anticoagulation management and postoperative hemorrhagic and thromboembolic complications were assessed. In order to evaluate a predictive association between clinical and radiological parameters and the outcome, we used a multivariate logistic regression analysis. Twenty-nine patients undergoing DC for MHS after CTS with a female-to-male ratio of 1:1.9 and a median age of 60 (IQR 49-64) years were identified out of 123 patients undergoing DC for MHS. Twenty-four patients (83%) received pre- or intraoperative substitution. At 30 days, the in-hospital mortality rate and neurological outcome corresponded to 31% and a median mRS of 5 (5-6), which remained stable at 3-6 months [Mortality: 42%, median mRS: 5 (4-6)]. Postoperatively, 15/29 patients (52%) experienced new hemorrhagic lesions and Bayesian logistic regression predicting mortality (mRS = 6) after imputing missing data demonstrated a significantly increased risk for mortality with longer aPPT (OR = 13.94, p = .038) and new or progressive hemorrhagic lesions after DC (OR = 3.03, p = .19). Notably, all but one hemorrhagic lesion occurred before discontinued anticoagulation and/or platelet inhibition was re-initiated. Despite perioperative discontinuation of anticoagulation and/or platelet inhibition, no coagulation-associated cardiovascular complications were noted. In conclusion, Cardiothoracic surgery patients suffering MHS will likely experience severe neurological disability after DC, which should remain a central aspect during counselling and decision-making. The complex coagulation situation after CTS, however, should not per se rule out the option of performing life-saving surgical decompression.

Comparison of intraoperative CT- and cone beam CT-based spinal navigation for the treatment of atlantoaxial instability.

BACKGROUND CONTEXT: Due to the complexity of neurovascular structures in the atlantoaxial region, spinal navigation for posterior C1-C2 instrumentation is nowadays a helpful tool to increase accuracy of surgery and safety of patients. Many available intraoperative navigation devices have proven their reliability in this part of the spine. Two main imaging techniques are used: intraoperative CT (iCT) and cone beam computed tomography (CBCT). PURPOSE: Comparison of iCT- and CBCT-based technologies for navigated posterior instrumentation in C1-C2 instability. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 81 consecutive patients from July 2014 to April 2020. OUTCOME MEASURES: Screw accuracy and operating time. METHODS: Patients with C1-C2 instability received posterior instrumentation using C2 pedicle screws, C1 lateral mass or pedicle screws. All screws were inserted using intraoperative imaging either using iCT or CBCT systems and spinal navigation with autoregistration technology. Following navigated screw insertion, a second intraoperative scan was performed to assess the accuracy of screw placement. Accuracy was defined as the percentage of correctly placed screws or with minor cortical breach (<2 mm) as graded by an independent observer compared to misplaced screws. RESULTS: A total of 81 patients with C1-C2 instability were retrospectively analyzed. Of these, 34 patients were operated with the use of iCT and 47 with CBCT. No significant demographic difference was found between groups. In the iCT group, 97.7% of the C1-C2 screws were correctly inserted; 2.3% showed a minor cortical breach (<2 mm); no misplacement (>2 mm). In the CBCT group, 98.9% of screws were correctly inserted; no minor pedicle breach; 1.1% showed misplacement >2 mm. Accuracy of screw placement demonstrated no significant difference between groups. Both technologies allowed sufficient identification of screw misplacement intraoperatively leading to two screw revisions in the iCT and three in the CBCT group. Median time of surgery was significantly shorter using CBCT technology (166.5 minutes [iCT] vs 122 minutes [CBCT]; p<.01). CONCLUSIONS: Spinal navigation using either iCT- or CBCT-based systems with autoregistration allows safe and reliable screw placement and intraoperative assessment of screw positioning. Using the herein presented procedural protocols, CBCT systems allow shorter operating time.

Large diameter hemicraniectomy does not improve long-term outcome in malignant infarction.

INTRODUCTION: In malignant cerebral infarction decompressive hemicraniectomy has demonstrated beneficial effects, but the optimum size of hemicraniectomy is still a matter of debate. Some surgeons prefer a large-sized hemicraniectomy with a diameter of more than 14 cm (HC > 14). We investigated whether this approach is associated with reduced mortality and an improved long-term functional outcome compared to a standard hemicraniectomy with a diameter of less than 14 cm (HC ≤ 14). METHODS: Patients from the DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY) registry who received hemicraniectomy were dichotomized according to the hemicraniectomy diameter (HC ≤ 14 cm vs. HC > 14 cm). The primary outcome was modified Rankin scale (mRS) score ≤ 4 after 12 months. Secondary outcomes were in-hospital mortality, mRS ≤ 3 and mortality after 12 months, and the rate of hemicraniectomy-related complications. The diameter of the hemicraniectomy was examined as an independent predictor of functional outcome in multivariable analyses. RESULTS: Among 130 patients (32.3% female, mean (SD) age 55 (11) years), the mean hemicraniectomy diameter was 13.6 cm. 42 patients (32.3%) had HC > 14. There were no significant differences in the primary outcome and mortality by size of hemicraniectomy. Rate of complications did not differ (HC ≤ 14 27.6% vs. HC > 14 36.6%, p = 0.302). Age and infarct volume but not hemicraniectomy diameter were associated with outcome in multivariable analyses. CONCLUSION: In this post-hoc analysis, large hemicraniectomy was not associated with an improved outcome or lower mortality in unselected patients with malignant middle cerebral artery infarction. Randomized trials should further examine whether individual patients could benefit from a large-sized hemicraniectomy. CLINICAL TRIAL REGISTRATION INFORMATION: German Clinical Trials Register (URL: https://www.drks.de ; Unique Identifier: DRKS00000624).

Spreading depolarization and angiographic spasm are separate mediators of delayed infarcts.

In DISCHARGE-1, a recent Phase III diagnostic trial in aneurysmal subarachnoid haemorrhage patients, spreading depolarization variables were found to be an independent real-time biomarker of delayed cerebral ischaemia. We here investigated based on prospectively collected data from DISCHARGE-1 whether delayed infarcts in the anterior, middle, or posterior cerebral artery territories correlate with (i) extravascular blood volumes; (ii) predefined spreading depolarization variables, or proximal vasospasm assessed by either (iii) digital subtraction angiography or (iv) transcranial Doppler-sonography; and whether spreading depolarizations and/or vasospasm are mediators between extravascular blood and delayed infarcts. Relationships between variable groups were analysed using Spearman correlations in 136 patients. Thereafter, principal component analyses were performed for each variable group. Obtained components were included in path models with a priori defined structure. In the first path model, we only included spreading depolarization variables, as our primary interest was to investigate spreading depolarizations. Standardised path coefficients were 0.22 for the path from extravascular bloodcomponent to depolarizationcomponent (P = 0.010); and 0.44 for the path from depolarizationcomponent to the first principal component of delayed infarct volume (P < 0.001); but only 0.07 for the direct path from bloodcomponent to delayed infarctcomponent (P = 0.36). Thus, the role of spreading depolarizations as a mediator between blood and delayed infarcts was confirmed. In the principal component analysis of extravascular blood volume, intraventricular haemorrhage was not represented in the first component. Therefore, based on the correlation analyses, we also constructed another path model with bloodcomponent without intraventricular haemorrhage as first and intraventricular haemorrhage as second extrinsic variable. We found two paths, one from (subarachnoid) bloodcomponent to delayed infarctcomponent with depolarizationcomponent as mediator (path coefficients from bloodcomponent to depolarizationcomponent = 0.23, P = 0.03; path coefficients from depolarizationcomponent to delayed infarctcomponent = 0.29, P = 0.002), and one from intraventricular haemorrhage to delayed infarctcomponent with angiographic vasospasmcomponent as mediator variable (path coefficients from intraventricular haemorrhage to vasospasmcomponent = 0.24, P = 0.03; path coefficients from vasospasmcomponent to delayed infarctcomponent = 0.35, P < 0.001). Human autopsy studies shaped the hypothesis that blood clots on the cortex surface suffice to cause delayed infarcts beneath the clots. Experimentally, clot-released factors induce cortical spreading depolarizations that trigger (i) neuronal cytotoxic oedema and (ii) spreading ischaemia. The statistical mediator role of spreading depolarization variables between subarachnoid blood volume and delayed infarct volume supports this pathogenetic concept. We did not find that angiographic vasospasm triggers spreading depolarizations, but angiographic vasospasm contributed to delayed infarct volume. This could possibly result from enhancement of spreading depolarization-induced spreading ischaemia by reduced upstream blood supply.

Oscillation analysis as a supporting element toward safe and reliable lumbar catheter intracranial pressure monitoring.

OBJECTIVE: Lumbar drainage of cerebrospinal fluid for treatment of refractory increased intracranial pressure (ICP) is associated with the risk of infratentorial herniation, but real-time biomarkers for signaling herniation at bedside are lacking. Here, the authors tested whether an alteration of pulsatile waveform conduction across the level of the foramen magnum could serve as an indicator of insufficient hydrostatic communication and impending herniation. METHODS: This prospective observational cohort study included patients with severe acute brain injury who underwent continuous external ventricular drain monitoring of ICP and lumbar drain pressure monitoring. Continuous recordings of ICP, lumbar pressure (LP), and arterial blood pressure (ABP) were screened throughout a recording period of 4-10 days. Pressure differences between ICP and LP > 5 mm Hg for 5 minutes were defined as a Δ-event, implicating nonsufficient hydrostatic communication. During this period, oscillation analysis of the ICP, LP, and ABP waveforms was performed by determining the eigenfrequencies (EFs) and their amplitudes (AEF) via Fourier transformation scripted in Python. RESULTS: Of 142 patients, 14 exhibited a Δ-event, with a median (range) ICP of 12.2 (10.7-18.8) mm Hg and LP of 5.6 (3.3-9.8) mm Hg during 2993 hours of recording time. The AEF ratio between ICP and LP (p < 0.01) and between ABP and LP (p = 0.032) increased significantly during Δ-events compared with the baseline values determined 3 hours prior to the event. The ratio between ICP and ABP remained unaffected. CONCLUSIONS: Oscillation behavior analysis of LP and ABP waveforms during controlled lumbar drainage may serve as a personalized, simple, and effective biomarker to signal impending infratentorial herniation in real time without the need for simultaneous ICP monitoring.

A minimally invasive tubular retractor-assisted retropleural approach for thoracic disc herniations - case series and technical note.

PURPOSE: Thoracic disc herniations are uncommon and carry a high risk for neurological deterioration. Traditional surgical approaches include thoracotomy, costotransversectomy or posterior approaches with considerable morbidity. In this technical note with case series, we describe a minimally invasive tubular retractor-assisted retropleural approach for simple and less invasive microsurgical exploration of thoracic disc herniations from a lateral angle. METHODS: Surgical technique consisted of partial rib resection and retropleural dissection followed by the placement of a tubular retractor (METRx Tubes, Medtronic) for an anterior-lateral exposure of the disc and neuroforamen. Epidemiological, clinical and surgical patient data were acquired. RESULTS: Between 2017 and 2020, six patients were surgically treated using the minimally invasive tubular retractor-assisted retropleural approach. Microsurgical exposure of the disc and neural structures was achieved from a lateral direction without requiring thoracotomy or lung deflation. Control imaging confirmed resection in all cases without relevant residuum. As postoperative complications, one dural injury and one postoperative pneumothorax occured. No neurologic deterioration or recurrence occurred during a median follow-up of 3 months. CONCLUSION: The described tubular retractor-assisted retropleural exposure serves as a feasible minimally invasive microsurgical approach to the anterior-lateral thoracic spine.

Cerebrovascular Pressure Reactivity According to Long-Pressure Reactivity Index During Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Spreading depolarization (SD) has been linked to the impairment of neurovascular coupling. However, the association between SD occurrence and cerebrovascular pressure reactivity as a surrogate of cerebral autoregulation (CA) remains unclear. Therefore, we analyzed CA using the long-pressure reactivity index (L-PRx) during SDs in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A retrospective study of patients with aSAH who were recruited at two centers, Heidelberg (HD) and Berlin (BE), was performed. Continuous monitoring of mean arterial pressure (MAP) and intracranial pressure (ICP) was recorded. ICP was measured using an intraparenchymal probe in HD patients and was measure in BE patients through external ventricular drainage. Electrocorticographic (ECoG) activity was continuously recorded between 3 and 13 days after hemorrhage. Autoregulation according to L-PRx was calculated as a moving linear Pearson's correlation of 20-min averages of MAP and ICP. For every identified SD, 60-min intervals of L-PRx were averaged, plotted, and analyzed depending on SD occurrence. Random L-PRx recording periods without SDs served as the control. RESULTS: A total of 19 patients (HD n = 14, BE n = 5, mean age 50.4 years, 9 female patients) were monitored for a mean duration of 230.4 h (range 96-360, STD ± 69.6 h), during which ECoG recordings revealed a total number of 277 SDs. Of these, 184 represented a single SD, and 93 SDs presented in clusters. In HD patients, mean L-PRx values were 0.12 (95% confidence interval [CI] 0.11-0.13) during SDs and 0.07 (95% CI 0.06-0.08) during control periods (p < 0.001). Similarly, in BE patients, a higher L-PRx value of 0.11 (95% CI 0.11-0.12) was detected during SDs than that during control periods (0.08, 95% CI 0.07-0.09; p < 0.001). In a more detailed analysis, CA changes registered through an intraparenchymal probe (HD patients) revealed that clustered SD periods were characterized by signs of more severely impaired CA (L-PRx during SD in clusters: 0.23 [95% CI 0.20-0.25]; single SD: 0.09 [95% CI 0.08-0.10]; control periods: 0.07 [95% CI 0.06-0.08]; p < 0.001). This group also showed significant increases in ICP during SDs in clusters compared with single SD and control periods. CONCLUSIONS: Neuromonitoring for simultaneous assessment of cerebrovascular pressure reactivity using 20-min averages of MAP and ICP measured by L-PRx during SD events is feasible. SD occurrence was associated with significant increases in L-PRx values indicative of CA disturbances. An impaired CA was found during SD in clusters when using an intraparenchymal probe. This preliminary study validates the use of cerebrovascular reactivity indices to evaluate CA disturbances during SDs. Our results warrant further investigation in larger prospective patient cohorts.

The Use of Intraoperative CT Hounsfield Unit Values for the Assessment of Bone Quality in Patients Undergoing Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: To evaluate the accuracy of intraoperatively measured computed tomography (CT) Hounsfield unit (HU) values by comparison with preoperative CT HU values and to compare the radiation exposure between preoperative and intraoperative CT scans. METHODS: HU values of lumbar vertebrae were measured and compared between preoperative and intraoperative CT scans in patients undergoing lumbar interbody fusion. In patient group one, Canon CT scanners were used preoperatively and the AIRO CT scanner was used intraoperatively. In patient group two, Canon CT scanners were used preoperatively and the O-arm Cone Beam CT (CBCT) scanner was used intraoperatively. In a subgroup analysis of patient group one, radiation by means of CT Dose Index (CTDI) was compared between Canon and AIRO CT scanners. RESULTS: In the first patient group, a total of 250 vertebrae were analysed in 74 patients showing a strong Pearson correlation of >.94 between pre- and intraoperative HU values. Bland-Altman analysis indicated consistency and equivalence with a bias of 3.9 and 95% limits of agreement from -27.17 to 34.97 when comparing all pre- and intraoperative HU values of L1-5. In the second patient group, a total of 27 vertebrae were analysed in 10 patients showing weak Pearson correlation and Bland-Altman analysis indicated no equivalence. CTDI did not differ between Canon and AIRO CT scanners. CONCLUSION: Correct and reliable CT HU measurement as mandatory key factor for the intraoperative assessment of bone quality and robotic-assisted surgery is feasible with intraoperative AIRO CT imaging without increase of radiation exposure.

Navigation accuracy and assessability of carbon fiber-reinforced PEEK instrumentation with multimodal intraoperative imaging in spinal oncology.

Radiolucent carbon-fiber reinforced PEEK (CFRP) implants have helped improve oncological follow-up and radiation therapy. Here, we investigated the performance of 3D intraoperative imaging and navigation systems for instrumentation and precision assessment of CFRP pedicle screws across the thoraco-lumbar spine. Thirty-three patients with spinal tumors underwent navigated CFRP instrumentation with intraoperative CT (iCT), robotic cone-beam CT (rCBCT) or cone-beam CT (CBCT) imaging. Two different navigation systems were used for iCT-/rCBCT- and CBCT-based navigation. Demographic, clinical and outcome data was assessed. Four blinded observers rated image quality, assessability and accuracy of CFRP pedicle screws. Inter-observer reliability was determined with Fleiss` Kappa analysis. Between 2018 and 2021, 243 CFRP screws were implanted (iCT:93, rCBCT: 99, CBCT: 51), of which 13 were non-assessable (iCT: 1, rCBCT: 9, CBCT: 3; *p = 0.0475; iCT vs. rCBCT). Navigation accuracy was highest using iCT (74%), followed by rCBCT (69%) and CBCT (49%) (*p = 0.0064; iCT vs. CBCT and rCBCT vs. CBCT). All observers rated iCT image quality higher than rCBCT/CBCT image quality (*p < 0.01) but relevant pedicle breaches were reliably identified with substantial agreement between all observers regardless of the imaging modality. Navigation accuracy for CFRP pedicle screws was considerably lower than expected from reports on titanium implants and CT may be best for reliable assessment of CFRP materials.

Intraoperative imaging and navigated spinopelvic instrumentation: S2-alar-iliac screws combined with tricortical S1 pedicle screw fixation.

PURPOSE: The present study aimed to assess the feasibility, safety and accuracy of navigated spinopelvic fixation with focus on S2-alar-iliac screws (S2AIS) and tricortical S1 pedicle screw implantation with the use of high-resolution three-dimensional intraoperative imaging and real-time spinal navigation. METHODS: Patients undergoing navigated intraoperative CT-based spinopelvic stabilization between January 2016 and September 2019 were included. Pelvic fixation was achieved by implantation of S2AIS or iliac screws (IS). S1 screws were implanted with the goal of achieving tricortical purchase. In all cases, instrumentation was performed with real-time spinal navigation and intraoperative screw positioning was assessed using intraoperative computed tomography (iCT), cone-beam CT (CBCT) and robotic cone-beam CT (rCBCT). Screw accuracy was evaluated based on radiographic criteria. To identify predictors of complications, univariate analysis was performed. RESULTS: Overall, 52 patients (85%) received S2AIS and nine patients (15%) received IS instrumentation. Intraoperative imaging and spinal navigation were performed with iCT in 34 patients, CBCT in 21 patients and rCBCT in six patients. A total number of 10/128 (7.8%) iliac screws underwent successful intraoperative correction due to misalignment. Tricortical purchase was successfully accomplished in 58/110 (53%) of the S1 screws with a clear learning curve in the course of time. S2AIS implantation was associated with significantly fewer surgical side infection-associated surgeries. CONCLUSIONS: Real-time navigation facilitated spinopelvic instrumentation with increasing accuracy of S2AIS and tricortical S1 screws. Intraoperative imaging by iCT, CBCT or rCBCT permitted screw assessment with the chance of direct navigated revision of misplaced iliac screws to avoid secondary screw revision surgery.

Spreading depolarizations in ischaemia after subarachnoid haemorrhage, a diagnostic phase III study.

Focal brain damage after aneurysmal subarachnoid haemorrhage predominantly results from intracerebral haemorrhage, and early and delayed cerebral ischaemia. The prospective, observational, multicentre, cohort, diagnostic phase III trial, DISCHARGE-1, primarily investigated whether the peak total spreading depolarization-induced depression duration of a recording day during delayed neuromonitoring (delayed depression duration) indicates delayed ipsilateral infarction. Consecutive patients (n = 205) who required neurosurgery were enrolled in six university hospitals from September 2009 to April 2018. Subdural electrodes for electrocorticography were implanted. Participants were excluded on the basis of exclusion criteria, technical problems in data quality, missing neuroimages or patient withdrawal (n = 25). Evaluators were blinded to other measures. Longitudinal MRI, and CT studies if clinically indicated, revealed that 162/180 patients developed focal brain damage during the first 2 weeks. During 4.5 years of cumulative recording, 6777 spreading depolarizations occurred in 161/180 patients and 238 electrographic seizures in 14/180. Ten patients died early; 90/170 developed delayed infarction ipsilateral to the electrodes. Primary objective was to investigate whether a 60-min delayed depression duration cut-off in a 24-h window predicts delayed infarction with >0.60 sensitivity and >0.80 specificity, and to estimate a new cut-off. The 60-min cut-off was too short. Sensitivity was sufficient [= 0.76 (95% confidence interval: 0.65-0.84), P = 0.0014] but specificity was 0.59 (0.47-0.70), i.e. <0.80 (P < 0.0001). Nevertheless, the area under the receiver operating characteristic (AUROC) curve of delayed depression duration was 0.76 (0.69-0.83, P < 0.0001) for delayed infarction and 0.88 (0.81-0.94, P < 0.0001) for delayed ischaemia (reversible delayed neurological deficit or infarction). In secondary analysis, a new 180-min cut-off indicated delayed infarction with a targeted 0.62 sensitivity and 0.83 specificity. In awake patients, the AUROC curve of delayed depression duration was 0.84 (0.70-0.97, P = 0.001) and the prespecified 60-min cut-off showed 0.71 sensitivity and 0.82 specificity for reversible neurological deficits. In multivariate analysis, delayed depression duration (ß = 0.474, P < 0.001), delayed median Glasgow Coma Score (ß = -0.201, P = 0.005) and peak transcranial Doppler (ß = 0.169, P = 0.016) explained 35% of variance in delayed infarction. Another key finding was that spreading depolarization-variables were included in every multiple regression model of early, delayed and total brain damage, patient outcome and death, strongly suggesting that they are an independent biomarker of progressive brain injury. While the 60-min cut-off of cumulative depression in a 24-h window indicated reversible delayed neurological deficit, only a 180-min cut-off indicated new infarction with >0.60 sensitivity and >0.80 specificity. Although spontaneous resolution of the neurological deficit is still possible, we recommend initiating rescue treatment at the 60-min rather than the 180-min cut-off if progression of injury to infarction is to be prevented.

Migraine Aura, Transient Ischemic Attacks, Stroke, and Dying of the Brain Share the Same Key Pathophysiological Process in Neurons Driven by Gibbs-Donnan Forces, Namely Spreading Depolarization.

Neuronal cytotoxic edema is the morphological correlate of the near-complete neuronal battery breakdown called spreading depolarization, or conversely, spreading depolarization is the electrophysiological correlate of the initial, still reversible phase of neuronal cytotoxic edema. Cytotoxic edema and spreading depolarization are thus different modalities of the same process, which represents a metastable universal reference state in the gray matter of the brain close to Gibbs-Donnan equilibrium. Different but merging sections of the spreading-depolarization continuum from short duration waves to intermediate duration waves to terminal waves occur in a plethora of clinical conditions, including migraine aura, ischemic stroke, traumatic brain injury, aneurysmal subarachnoid hemorrhage (aSAH) and delayed cerebral ischemia (DCI), spontaneous intracerebral hemorrhage, subdural hematoma, development of brain death, and the dying process during cardio circulatory arrest. Thus, spreading depolarization represents a prime and simultaneously the most neglected pathophysiological process in acute neurology. Aristides Leão postulated as early as the 1940s that the pathophysiological process in neurons underlying migraine aura is of the same nature as the pathophysiological process in neurons that occurs in response to cerebral circulatory arrest, because he assumed that spreading depolarization occurs in both conditions. With this in mind, it is not surprising that patients with migraine with aura have about a twofold increased risk of stroke, as some spreading depolarizations leading to the patient percept of migraine aura could be caused by cerebral ischemia. However, it is in the nature of spreading depolarization that it can have different etiologies and not all spreading depolarizations arise because of ischemia. Spreading depolarization is observed as a negative direct current (DC) shift and associated with different changes in spontaneous brain activity in the alternating current (AC) band of the electrocorticogram. These are non-spreading depression and spreading activity depression and epileptiform activity. The same spreading depolarization wave may be associated with different activity changes in adjacent brain regions. Here, we review the basal mechanism underlying spreading depolarization and the associated activity changes. Using original recordings in animals and patients, we illustrate that the associated changes in spontaneous activity are by no means trivial, but pose unsolved mechanistic puzzles and require proper scientific analysis.

Workflow and performance of intraoperative CT, cone-beam CT, and robotic cone-beam CT for spinal navigation in 503 consecutive patients.

OBJECTIVE: A direct comparison of intraoperative CT (iCT), cone-beam CT (CBCT), and robotic cone-beam CT (rCBCT) has been necessary to identify the ideal imaging solution for each individual user's need. Herein, the authors sought to analyze workflow, handling, and performance of iCT, CBCT, and rCBCT imaging for navigated pedicle screw instrumentation across the entire spine performed within the same surgical environment by the same group of surgeons. METHODS: Between 2014 and 2018, 503 consecutive patients received 2673 navigated pedicle screws using iCT (n = 1219), CBCT (n = 646), or rCBCT (n = 808) imaging during the first 24 months after the acquisition of each modality. Clinical and demographic data, workflow, handling, and screw assessment and accuracy were analyzed. RESULTS: Intraoperative CT showed image quality and workflow advantages for cervicothoracic cases, obese patients, and long-segment instrumentation, whereas CBCT and rCBCT offered independent handling, around-the-clock availability, and the option of performing 2D fluoroscopy. All modalities permitted reliable intraoperative screw assessment. Navigated screw revision was possible with each modality and yielded final accuracy rates > 92% in all groups (iCT 96.2% vs CBCT 92.3%, p < 0.001) without a difference in the accuracy of cervical pedicle screw placement or the rate of secondary screw revision surgeries. CONCLUSIONS: Continuous training and an individual setup of iCT, CBCT, and rCBCT has been shown to permit safe and precise navigated posterior instrumentation across the entire spine with reliable screw assessment and the option of immediate revision. The perceived higher image quality and larger scan area of iCT should be weighed against the around-the-clock availability of CBCT and rCBCT technology with the option of single-handed robotic image acquisition.