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.

Volumetric accuracy of different imaging modalities in acute intracerebral hemorrhage.

BACKGROUND: Follow-up imaging in intracerebral hemorrhage is not standardized and radiologists rely on different imaging modalities to determine hematoma growth. This study assesses the volumetric accuracy of different imaging modalities (MRI, CT angiography, postcontrast CT) to measure hematoma size. METHODS: 28 patients with acute spontaneous intracerebral hemorrhage referred to a tertiary stroke center were retrospectively included between 2018 and 2019. Inclusion criteria were (1) spontaneous intracerebral hemorrhage (supra- or infratentorial), (2) noncontrast CT imaging performed on admission, (3) follow-up imaging (CT angiography, postcontrast CT, MRI), and (4) absence of hematoma expansion confirmed by a third cranial image within 6 days. Two independent raters manually measured hematoma volume by drawing a region of interest on axial slices of admission noncontrast CT scans as well as on follow-up imaging (CT angiography, postcontrast CT, MRI) using a semi-automated segmentation tool (Visage image viewer; version 7.1.10). Results were compared using Bland-Altman plots. RESULTS: Mean admission hematoma volume was 18.79 ± 19.86 cc. All interrater and intrarater intraclass correlation coefficients were excellent (1; IQR 0.98-1.00). In comparison to hematoma volume on admission noncontrast CT volumetric measurements were most accurate in patients who received postcontrast CT (bias of - 2.47%, SD 4.67: n = 10), while CT angiography often underestimated hemorrhage volumes (bias of 31.91%, SD 45.54; n = 20). In MRI sequences intracerebral hemorrhage volumes were overestimated in T2* (bias of - 64.37%, SD 21.65; n = 10). FLAIR (bias of 6.05%, SD 35.45; n = 13) and DWI (bias of-14.6%, SD 31.93; n = 12) over- and underestimated hemorrhagic volumes. CONCLUSIONS: Volumetric measurements were most accurate in postcontrast CT while CT angiography and MRI sequences often substantially over- or underestimated hemorrhage volumes.

Spinal alignment shift between supine and prone CT imaging occurs frequently and regardless of the anatomic region, risk factors, or pathology.

Computer-assisted spine surgery based on preoperative CT imaging may be hampered by sagittal alignment shifts due to an intraoperative switch from supine to prone. In the present study, we systematically analyzed the occurrence and pattern of sagittal spinal alignment shift between corresponding preoperative (supine) and intraoperative (prone) CT imaging in patients that underwent navigated posterior instrumentation between 2014 and 2017. Sagittal alignment across the levels of instrumentation was determined according to the C2 fracture gap (C2-F) and C2 translation (C2-T) in odontoid type 2 fractures, next to the modified Cobb angle (CA), plumbline (PL), and translation (T) in subaxial pathologies. One-hundred and twenty-one patients (C1/C2: n = 17; C3-S1: n = 104) with degenerative (39/121; 32%), oncologic (35/121; 29%), traumatic (34/121; 28%), or infectious (13/121; 11%) pathologies were identified. In the subaxial spine, significant shift occurred in 104/104 (100%) cases (CA: *p = .044; T: *p = .021) compared to only 10/17 (59%) cases that exhibited shift at the C1/C2 level (C2-F: **p = .002; C2-T: *p < .016). The degree of shift was not affected by the anatomic region or pathology but significantly greater in cases with an instrumentation length > 5 segments ("∆PL > 5 segments": 4.5 ± 1.8 mm; "∆PL ≤ 5 segments": 2 ± 0.6 mm; *p = .013) or in revision surgery with pre-existing instrumentation ("∆PL presence": 5 ± 2.6 mm; "∆PL absence": 2.4 ± 0.7 mm; **p = .007). Interestingly, typical morphological instability risk factors did not influence the degree of shift. In conclusion, intraoperative spinal alignment shift due to a change in patient position should be considered as a cause for inaccuracy during computer-assisted spine surgery and when correcting spinal alignment according to parameters that were planned in other patient positions.

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.

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.

Direct puncture of the carotid artery as a bailout vascular access technique for mechanical thrombectomy in acute ischemic stroke-the revival of an old technique in a modern setting.

PURPOSE: To describe our single-center experience of mechanical thrombectomy (MTE) via a direct carotid puncture (DCP) with regard to indication, time metrics, procedural details, as well as safety and efficacy aspects. METHODS: DCP thrombectomy cases performed at our center were retrospectively identified from a prospectively maintained institutional MTE database. Various patient (age, sex, stroke cause, comorbidities), clinical (NIHSS, mRS), imaging (occlusion site, ASPECT score), procedural (indication for DCP, time from DCP to reperfusion, materials used, technical nuances), and outcome data (NIHSS, mRS) were tabulated. RESULTS: Among 715 anterior circulation MTEs, 12 DCP-MTEs were identified and analyzed. Nine were left-sided M1 occlusions, one right-sided M1 occlusion, and two right-sided M2 occlusions. DCP was successfully carried out in 91.7%; TICI 2b/3-recanalization was achieved in 83.3% via direct lesional aspiration and/or stent-retrieval techniques. Median time from DCP to reperfusion was 23 min. Indications included futile transfemoral catheterization attempts of the cervical target vessels as well as iliac occlusive disease. Neck hematoma occurred in 2 patients, none of which required further therapy. CONCLUSION: MTE via DCP in these highly selected patients was reasonably safe, fast, and efficient. It thus represents a valuable technical extension of MTE, especially in patients with difficult access.

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

Deep brain stimulation induced normalization of the human functional connectome in Parkinson's disease.

Neuroimaging has seen a paradigm shift away from a formal description of local activity patterns towards studying distributed brain networks. The recently defined framework of the 'human connectome' enables global analysis of parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distributed brain networks in the human brain. We acquired resting-state functional MRI in 20 patients with Parkinson's disease with subthalamic DBS switched on and off. An age-matched control cohort of 15 subjects was acquired from an open data repository. DBS lead placement in the subthalamic nucleus was localized using a state-of-the art pipeline that involved brain shift correction, multispectral image registration and use of a precise subcortical atlas. Based on a realistic 3D model of the electrode and surrounding anatomy, the amount of local impact of DBS was estimated using a finite element method approach. On a global level, average connectivity increases and decreases throughout the brain were estimated by contrasting on and off DBS scans on a voxel-wise graph comprising eight thousand nodes. Local impact of DBS on the motor subthalamic nucleus explained half the variance in global connectivity increases within the motor network (R = 0.711, P < 0.001). Moreover, local impact of DBS on the motor subthalamic nucleus could explain the degree to how much voxel-wise average brain connectivity normalized towards healthy controls (R = 0.713, P < 0.001). Finally, a network-based statistics analysis revealed that DBS attenuated specific couplings known to be pathological in Parkinson's disease. Namely, coupling between motor thalamus and motor cortex was increased while striatal coupling with cerebellum, external pallidum and subthalamic nucleus was decreased by DBS. Our results show that resting state functional MRI may be acquired in DBS on and off conditions on clinical MRI hardware and that data are useful to gain additional insight into how DBS modulates the functional connectome of the human brain. We demonstrate that effective DBS increases overall connectivity in the motor network, normalizes the network profile towards healthy controls and specifically strengthens thalamo-cortical connectivity while reducing striatal control over basal ganglia and cerebellar structures.

Evaluation of diagnostic accuracy of intracranial aneurysm detection using medical-grade versus commercial consumer-grade displays and different image reconstructions against the background of process optimization for telemedicine.

BACKGROUND: Process optimization in computed tomography (CT) and telemedicine. PURPOSE: To compare image quality and objective diagnostic accuracy of medical-grade and consumer-grade digital displays/computer terminals for detection of intracranial aneurysms. MATERIAL AND METHODS: Four radiologists with different levels of experience retrospectively read a total of 60 patients including 30 cases of proven therapy-naïve intracranial aneurysm detectable on a medical-grade grayscale calibrated display. They had 5 min per case reading the first 20 datasets using only axial slices, the next 20 patients using axial slices and multiplanar reconstructions (MPRs), and the last 20 patients using axial slices, MPRs, and maximum intensity projections (MIPs). Three months after the first reading session on a medical-grade display, they read all datasets again under the same standardized conditions but on a consumer-grade display. Diagnostic performance, subjective diagnostic confidence, and reading speed were analyzed and compared. Readers rated image quality on a five-point Likert scale. RESULTS: Diagnostic accuracy did not differ significantly with areas under the curve of 0.717-0.809 for all readers on both display devices. Sensitivity and specificity did not increase significantly when adding MPRs and/or MIPs. Reading speed was similar with both devices. There were no significant differences in subjective image quality scores, and overall inter-reader variability of all subjective parameters correlated positively between the two devices (P <0.001-0.011). CONCLUSION: Diagnostic accuracy and readers' diagnostic confidence in detecting and ruling out intracranial aneurysm were similar on commercial-grade and medical-grade displays. Additional reconstructions did not increase sensitivity/specificity or reduce the time needed for diagnosis.

Navigated percutaneous versus open pedicle screw implantation using intraoperative CT and robotic cone-beam CT imaging.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.0001), regional placement accuracy in the lumbar (PPSI 97.8%; Open 91.5%; p < 0.001), and lumbar-sacral spine (PPSI 100%; Open 81.2%; p < 0.05), next to the duration of surgery and length of hospitalization. CONCLUSIONS: PPSI with iCT- and CBCT-based spinal navigation improves the accuracy, safety, and workflow of navigated spinal instrumentation. Next, a cost-effectiveness and outcome analysis should determine whether iCT and CBCT imaging are truly economically justified. These slides can be retrieved under Electronic Supplementary Material.

Intraoperative CT and cone-beam CT imaging for minimally invasive evacuation of spontaneous intracerebral hemorrhage.

BACKGROUND: Minimally invasive surgery (MIS) for evacuation of spontaneous intracerebral hemorrhage (ICH) has shown promise but there remains a need for intraoperative performance assessment considering the wide range of evacuation effectiveness. In this feasibility study, we analyzed the benefit of intraoperative 3-dimensional imaging during navigated endoscopy-assisted ICH evacuation by mechanical clot fragmentation and aspiration. METHODS: 18 patients with superficial or deep supratentorial ICH underwent MIS for clot evacuation followed by intraoperative computerized tomography (iCT) or cone-beam CT (CBCT) imaging. Eligibility for MIS required (a) availability of intraoperative iCT or CBCT, (b) spontaneous lobar or deep ICH without vascular pathology, (c) a stable ICH volume (20-90 ml), (d) a reduced level of consciousness (GCS 5-14), and (e) a premorbid mRS ≤ 1. Demographic, clinical, and radiographic patient data were analyzed by two independent observers. RESULTS: Nine female and 9 male patients with a median age of 76 years (42-85) presented with an ICH score of 3 (1-4), GCS of 10 (5-14) and ICH volume of 54 ± 26 ml. Clot fragmentation and aspiration was feasible in all cases and intraoperative imaging determined an overall evacuation rate of 80 ± 19% (residual hematoma volume: 13 ± 17 ml; p < 0.0001 vs. Pre-OP). Based on the intraoperative imaging results, 1/3rd of all patients underwent an immediate re-aspiration attempt. No patient experienced hemorrhagic complications or required conversion to open craniotomy. However, routine postoperative CT imaging revealed early hematoma re-expansion with an adjusted evacuation rate of 59 ± 30% (residual hematoma volume: 26 ± 37 ml; p < 0.001 vs. Pre-OP). CONCLUSIONS: Routine utilization of iCT or CBCT imaging in MIS for ICH permits direct surgical performance assessment and the chance for immediate re-aspiration, which may optimize targeting of an ideal residual hematoma volume and reduce secondary revision rates.

Functional Outcome Following Stroke Thrombectomy in Clinical Practice.

Background and Purpose- Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of endovascular treatment reperfusion rates and functional outcome on a countrywide scale. Methods- Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0-2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders. Results- Median age was 75 years (interquartile range, 64-82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10-19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio [OR], 1.06; 95% CI, 1.05-1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03-1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08-1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15-1.39), alteplase use (OR, 1.49; 95% CI, 1.08-2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45-1.96). Conclusions- High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Mechanical recanalization in basilar artery occlusion: the ENDOSTROKE study.

OBJECTIVE: A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion. METHODS: ENDOSTROKE is an investigator-initiated multicenter registry for patients undergoing EVT. This analysis includes 148 consecutive patients with BA occlusion, with 59% having received intravenous thrombolysis prior to EVT. Recanalization (defined as Thrombolysis in Cerebral Infarction [TICI] score 2b-3) and collateral status (using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system) were assessed by a blinded core laboratory. Good (moderate) outcome was defined as a modified Rankin Scale score of 0 to 2 (0-3) assessed after at least 3 months (median time to follow-up = 120 days). RESULTS: Thirty-four percent had good and 42% had moderate clinical outcome; mortality was 35%. TICI 2b-3 recanalization was achieved by 79%. Age, hypertension, National Institutes of Health Stroke Scale scores, collateral status, and the use of magnetic resonance imaging prior to EVT predicted clinical outcome, the latter 3 remaining independent predictors in multivariate analysis. Independent predictors of recanalization were better collateral status and the use of a stent retriever. However, recanalization did not significantly predict clinical outcome. INTERPRETATION: Beside initial stroke severity, the collateral status predicts clinical outcome and recanalization in BA occlusion. Our data suggest that the use of a stent retriever is associated with high recanalization rates, but recanalization on its own does not predict outcome. The role of other modifiable factors, including the choice of pretreatment imaging modality and time issues, warrants further investigation.

Collateral vessels in proximal middle cerebral artery occlusion: the ENDOSTROKE study.

PURPOSE: To determine the impact of collateral vessel status on clinical and imaging outcomes in patients undergoing endovascular therapy (EVT) for proximal middle cerebral artery (MCA) occlusion. MATERIALS AND METHODS: There were 160 patients with proximal MCA occlusion at six centers in this institutional review board-approved multicenter EVT registry. Angiograms were analyzed at a blinded core laboratory, and collateral vessel status was assessed by using the American Society of Interventional and Therapeutic Neuroradiology (ASITN)/Society of Interventional Radiology (SIR) collateral vessel grading system, while reperfusion was assessed by using the Thrombolysis in Cerebral Infarction (TICI) scale. Good outcome was defined as a modified Rankin Scale score of 0-2 at follow-up. Binary logistic regression analysis was performed by using parameters with P < .2 in univariate analysis. RESULTS: Good clinical outcome was attained in 62 (39%) of the 160 patients, and TICI 2b-3 reperfusion was achieved in 94 (59%) patients. Nineteen patients had ASITN/SIR collateral vessel grades of 0 or 1, 63 patients had a grade of 2, and 78 patients had grades of 3 or 4. Better collateral vessels were associated with higher reperfusion rates (21%, 48%, and 77% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), a higher proportion of infarcts smaller than one-third of the MCA territory (32%, 48%, and 69% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P < .001), and a higher proportion of good clinical outcome (11%, 35%, and 49% for ASITN/SIR grades of 0 or 1, 2, and 3 or 4, respectively; P = .007). At multivariable analysis, collateral vessel status independently predicted reperfusion, final infarct size, and clinical outcome. Within an onset-to-treatment time (OTT) of 0-3 hours, collateral vessel status predicted final infarct size and reperfusion. Within an OTT of 3-6 hours, it additionally predicted clinical outcome, with 53% of patients with ASITN/SIR grades of 3 or 4 having a good outcome, as compared with 0% of patients with grades of 0 or 1 and 27% of patients with a grade of 2 (P = .008). CONCLUSION: In this patient population, collateral vessel status independently predicted the pivotal outcome parameters of reperfusion, infarct size, and clinical outcome. These data underscore the utility of patient selection for EVT on the basis of collateral vessel status.

Endovascular procedures versus intravenous thrombolysis in stroke with tandem occlusion of the anterior circulation.

PURPOSE: Stroke with tandem occlusion within the anterior circulation presents a lower probability of recanalization and good clinical outcome after intravenous (IV) thrombolysis than stroke with single occlusion. The present study describes the impact of endovascular procedures (EPs) compared with IV thrombolysis alone on recanalization and clinical outcome. MATERIALS AND METHODS: Thirty patients with symptom onset less than 4.5 hours and tandem occlusion within the anterior circulation were analyzed retrospectively. Recanalization was assessed per Thrombolysis In Cerebral Infarction (TICI) classification on computed tomography, magnetic resonance imaging, or digital subtraction angiography within 24 hours. Infarct size was detected on follow-up imaging as a dichotomized variable, ie, more than one third of the territory of the middle cerebral artery. Clinical outcomes were major neurologic improvement, independent outcome (90-d modified Rankin Scale [mRS] score), symptomatic intracerebral hemorrhage (sICH; per European Cooperative Acute Stroke Study criteria), and death within 7 days. RESULTS: Patients treated with EPs (n = 14) were significantly younger and had a history of arterial hypertension more frequently than patients treated with IV thrombolysis alone (n = 16). Recanalization (ie, TICI score 2b/3; EP, 64%; IV, 19%; P = .01), major neurologic improvement (EP, 64%; IV, 19%; P = .01), and independent outcome (mRS score ≤ 2; EP, 54% IV, 13%; P = .02) occurred more often in the EP group, whereas infarct sizes greater than one third of the MCA territory (EP, 43%; IV, 81%; P = .03) were observed less often. Rates of sICH (P = .12) and death within 7 days (P = .74) did not differ significantly. CONCLUSIONS: Higher recanalization rate, smaller infarct volume, and better clinical outcome in the EP group should encourage researchers to include this subgroup of patients in prospective randomized trials comparing IV thrombolysis versus EP in stroke.

MRI study: objective olfactory function and CNS pathologies in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease characterized by CNS lesions causing physical and cognitive impairment. Using psychophysical testing, an olfactory disorder is diagnosed in 15-38.5% of patients with MS. Olfactometry permits objective testing of the sensory nerve function. METHODS: The study looked at 20 patients with MS. Clinical, olfactory (chemosensory evoked potentials), and MRI data (volume of the bulbus olfactorius (BO), olfactory brain (OB), lesions in the CNS) were analyzed. RESULTS: 25 percent of patients were hyposmic, exhibiting higher OB lesion volumes and smaller bulb volumes. H2S and CO2 latencies and the BO volume (inversely) correlated with the volume and number of MS lesions of the olfactory brain in all patients. Patients with a smaller olfactory bulb volume exhibited longer H2S latencies (p = 0.025). CONCLUSION: A relationship between olfactory bulb volume, olfactory brain lesion load, and objective olfactory function testing in MS patients was investigated in all patients. Our data shows that brain damage characteristic of MS, including reduced bulb volume, causes an increase in chemosensory potential latencies and an olfactory function deficit.

Reevaluating the relevance of 18F-FDG PET findings for diagnosis of neurosarcoidosis: a case series.

OBJECTIVE: The diagnosis of neurosarcoidosis (NS) remains challenging due to the difficulty to obtain central nervous system (CNS) biopsies. Various diagnostic parameters are considered for the definition of possible, probable and definite NS. Magnetic resonance imaging (MRI) is the imaging gold standard and considered in diagnostic criteria. Fluorodeoxyglucose positron emission (18F-FDG PET) is sometimes performed additionally to identify possible systemic biopsy targets. However, at present, its findings are not incorporated into the diagnostic criteria for neurosarcoidosis (NS). METHODS: We conducted a single center retrospective search for the period 2020-2022, for patients with neurological symptoms in a diagnostic context of suspected NS who underwent MRI and additional 18F-FDG PET scans to identify potential hypermetabolism in the CNS and biopsy targets. RESULTS: We identified three cases of NS, where Gadolinium-enhanced MRI scans did not show abnormalities while 18F-FDG PET revealed hypermetabolic lesions in areas of the CNS. Additional MRI scans were still inconclusive for structural changes. We diagnosed a "probable" NS in all cases with histopathological confirmation of systemic sarcoidosis which led to an intensified therapy regime. DISCUSSION: 18F-FDG PET is an early indicator for metabolic changes. It appears to be a useful add-on to improve accuracy of diagnostic criteria in suspected NS without MRI findings.

FRED X flow diverter for the treatment of intracranial aneurysms: Two-center experience and mini-review of the literature.

OBJECTIVE: The flow re-direction endoluminal device (FRED) is a safe and effective treatment option for intracranial aneurysms. The novel FRED X features an antithrombotic surface coating ("X Technology") on an otherwise unmodified stent design. This two-center study evaluates the clinical safety and efficacy of FRED X and compares it to the literature. METHODS: Consecutive patients treated between 2020 and 2023 were retrospectively reviewed for aneurysm characteristics, procedural details and complications, and angiographic outcomes. A mini-review of the literature for FRED X clinical trials was performed and results were pooled using a random effects model. RESULTS: Thirty-four patients (mean age 56 years) were treated for 34 aneurysms. The mean aneurysm size was 7.7 ± 5.0 mm, 7 (21%) were ruptured, 6 (18%) were recurrent after previous treatment, 11 (32.3%) were located in the posterior circulation, and 4 (12.5%) had non-saccular morphology. All procedures were technically successful and no balloon angioplasty was required. There was 1 (2.9%) symptomatic complication (a transient ischemic attack) and no procedural morbidity or mortality. Technical asymptomatic events included 1 procedural stent occlusion that was reopened with thrombectomy and 3 cases of vasospasm. Complete and adequate occlusion rates were 68% (19/28) and 89% (25/28) at a mean follow-up time of 6 months, respectively. The results of this study are comparable to previous FRED X studies. CONCLUSIONS: The results demonstrate a high feasibility and procedural safety of the FRED X with adequate mid-term occlusion rates. Long-term and comparative studies are needed to evaluate the full potential of the FRED X.

Safety and efficacy of coated flow diverters in the treatment of ruptured intracranial aneurysms: a retrospective multicenter study.

BACKGROUND: This multicenter study evaluated the safety and efficacy of coated flow diverters (cFDs) for the treatment of ruptured intracranial aneurysms. METHODS: Consecutive patients treated with different cFDs for ruptured aneurysms under tirofiban at eight neurovascular centers between 2016 and 2023 were retrospectively analyzed. The majority of patients were loaded with dual antiplatelet therapy after the treatment. Aneurysm occlusion was determined using the O'Kelly-Marotta (OKM) grading scale. Primary outcome measures were major procedural complications and aneurysmal rebleeding during hospitalization. RESULTS: The study included 60 aneurysms (posterior circulation: 28 (47%)) with a mean size of 5.8±4.7 mm. Aneurysm morphology was saccular in 28 (47%), blister-like in 12 (20%), dissecting in 13 (22%), and fusiform in 7 (12%). Technical success was 100% with a mean of 1.1 cFDs implanted per aneurysm. Adjunctive coiling was performed in 11 (18%) aneurysms. Immediate contrast retention was observed in 45 (75%) aneurysms. There was 1 (2%) major procedural complication (a major stroke, eventually leading to death) and no aneurysmal rebleeding. A good outcome (modified Rankin Scale 0-2) was achieved in 40 (67%) patients. At a mean follow-up of 6 months, 27/34 (79%) aneurysms were completely occluded (OKM D), 3/34 (9%) had an entry remnant (OKM C), and 4/34 (12%) had residual filling (OKM A or B). There was 1 (3%) severe in-stent stenosis during follow-up that was treated with balloon angioplasty. CONCLUSIONS: Treatment of ruptured aneurysms with cFDs was reasonably safe and efficient and thus represents a valid treatment option, especially for complex cases.

Age dependency of successful recanalization in anterior circulation stroke: the ENDOSTROKE study.

BACKGROUND: Clinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion. METHODS: ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later. RESULTS: The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization ('futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with 'futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile). CONCLUSIONS: This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).