Differences in Olivo-Cerebellar Circuit and Cerebellar Network Connectivity in Essential Tremor: a Resting State fMRI Study.

The olivo-cerebellar circuit is thought to play a crucial role in the pathophysiology of essential tremor (ET). Whether olivo-cerebellar circuit dysfunction is also present at rest, in the absence of clinical tremor and linked voluntary movement, remains unclear. Assessing this network in detail with fMRI is challenging, considering the brainstem is close to major arteries and pulsatile cerebrospinal fluid-filled spaces obscuring signals of interest. Here, we used methods tailored to the analysis of infratentorial structures. We hypothesize that the olivo-cerebellar circuit shows altered intra-network connectivity at rest and decreased functional coupling with other parts of the motor network in ET. In 17 ET patients and 19 healthy controls, we investigated using resting state fMRI intracerebellar functional and effective connectivity on a dedicated cerebellar atlas. With independent component analysis, we investigated data-driven cerebellar motor network activations during rest. Finally, whole-brain connectivity of cerebellar motor structures was investigated using identified components. In ET, olivo-cerebellar pathways show decreased functional connectivity compared with healthy controls. Effective connectivity analysis showed an increased inhibitory influence of the dentate nucleus towards the inferior olive. Cerebellar independent component analyses showed motor resting state networks are less strongly connected to the cerebral cortex compared to controls. Our results indicate the olivo-cerebellar circuit to be affected at rest. Also, the cerebellum is "disconnected" from the rest of the motor network. Aberrant activity, generated within the olivo-cerebellar circuit could, during action, spread towards other parts of the motor circuit and potentially underlie the characteristic tremor of this patient group.

Detection of Large Vessel Occlusion Stroke in the Prehospital Setting: Electroencephalography as a Potential Triage Instrument.

A reliable and fast instrument for prehospital detection of large vessel occlusion (LVO) stroke would be a game-changer in stroke care, because it would enable direct transportation of LVO stroke patients to the nearest comprehensive stroke center for endovascular treatment. This strategy would substantially improve treatment times and thus clinical outcomes of patients. Here, we outline our view on the requirements of an effective prehospital LVO detection method, namely: high diagnostic accuracy; fast application and interpretation; user-friendliness; compactness; and low costs. We argue that existing methods for prehospital LVO detection, including clinical scales, mobile stroke units and transcranial Doppler, do not fulfill all criteria, hindering broad implementation of these methods. Instead, electroencephalography may be suitable for prehospital LVO detection since in-hospital studies have shown that quantification of hypoxia-induced changes in the electroencephalography signal have good diagnostic accuracy for LVO stroke. Although performing electroencephalography measurements in the prehospital setting comes with challenges, solutions for fast and simple application of this method are available. Currently, the feasibility and diagnostic accuracy of electroencephalography in the prehospital setting are being investigated in clinical trials.

Defining the Dorsal STN Border Using 7.0-T MRI: A Comparison to Microelectrode Recordings and Lower Field Strength MRI.

BACKGROUND: 7.0-T T2-weighted MRI offers excellent visibility of the subthalamic nucleus (STN), which is used as a target for deep brain stimulation (DBS) in Parkinson's disease (PD). A comparison of 7.0-T MRI to microelectrode recordings (MER) for STN border identification has not been performed. OBJECTIVE: To compare representation of STN borders on 7.0-T T2 MRI with the borders identified during MER in patients undergoing DBS for PD and to evaluate whether STN identification on 7.0-T T2 MRI leads to alterations in stereotactic target planning. DESIGN/METHODS: STN border identification was done using volumetric 7.0-T T2 MRI acquisitions. This was compared to the STN borders identified by MER. STN target planning was independently performed by 3 DBS surgeons on T2 imaging using 1.5-, 3.0-, and 7.0-T MRI. RESULTS: A total of 102 microelectrode tracks were evaluated in 19 patients. Identification of the dorsal STN border was well feasible on 7-T T2, whereas the ventral STN was un-distinguishable from the substantia nigra. The dorsal STN border on MRI was located more dorsal than MER in 73% of trajectories. The average distance from MRI to MER border was 0.9 mm (range -4.4 to +3.5 mm). STN target planning showed high correspondence between the 3 field strengths. CONCLUSION: 7.0-T T2 MRI offers the possibility of easy identification of the dorsal border of the STN. However, higher field strength MRI does not change the planning of the target. Compared to MER, the dorsal border on MRI was located more dorsal in the majority of cases, situating MER activity within STN representation.

Regional assessment of carotid artery pulse wave velocity using compressed sensing accelerated high temporal resolution 2D CINE phase contrast cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) allows for non-invasive assessment of arterial stiffness by means of measuring pulse wave velocity (PWV). PWV can be calculated from the time shift between two time-resolved flow curves acquired at two locations within an arterial segment. These flow curves can be derived from two-dimensional CINE phase contrast CMR (2D CINE PC CMR). While CMR-derived PWV measurements have proven to be accurate for the aorta, this is more challenging for smaller arteries such as the carotids due to the need for both high spatial and temporal resolution. In this work, we present a novel method that combines retrospectively gated 2D CINE PC CMR, high temporal binning of data and compressed sensing (CS) reconstruction to accomplish a temporal resolution of 4 ms. This enables accurate flow measurements and assessment of PWV in regional carotid artery segments. METHODS: Retrospectively gated 2D CINE PC CMR data acquired in the carotid artery was binned into cardiac frames of 4 ms length, resulting in an incoherently undersampled ky-t-space with a mean undersampling factor of 5. The images were reconstructed by a non-linear CS reconstruction using total variation over time as a sparsifying transform. PWV values were calculated from flow curves by using foot-to-foot and cross-correlation methods. Our method was validated against ultrasound measurements in a flow phantom setup representing the carotid artery. Additionally, PWV values of two groups of 23 young (30 ± 3 years, 12 [52%] women) and 10 elderly (62 ± 10 years, 5 [50%] women) healthy subjects were compared using the Wilcoxon rank-sum test. RESULTS: Our proposed method produced very similar flow curves as those measured using ultrasound at 1 ms temporal resolution. Reliable PWV estimation proved possible for transit times down to 7.5 ms. Furthermore, significant differences in PWV values between healthy young and elderly subjects were found (4.7 ± 1.0 m/s and 7.9 ± 2.4 m/s, respectively; p < 0.001) in accordance with literature. CONCLUSIONS: Retrospectively gated 2D CINE PC CMR with CS allows for high spatiotemporal resolution flow measurements and accurate regional carotid artery PWV calculations. We foresee this technique will be valuable in protocols investigating early development of carotid atherosclerosis.

Reproducibility and interobserver variability of systolic blood flow velocity and 3D wall shear stress derived from 4D flow MRI in the healthy aorta.

PURPOSE: To investigate the reproducibility and interobserver variability of 3D aortic velocity vector fields and wall shear stress (WSS) averaged over five systolic timeframes derived from noncontrast 4D flow magnetic resonance imaging (MRI). MATERIALS AND METHODS: Fourteen controls underwent test-retest 4D flow MRI examinations separated by 16 ± 3 days (resolution = 3.0-3.6 × 2.3-2.6 × 2.5-2.7 mm(3) ; TE/TR/FA = 2.5/4.9 msec/7°; Venc = 150 cm/s). Two observers segmented the aorta, and WSS was calculated for both series of scans and both segmentations. Test-retest and interobserver velocity and WSS vectors were compared on a voxel-by-voxel basis in the aorta and on a regional basis by subdividing the aortas in six segments. RESULTS: Test-retest: voxel-by-voxel Bland-Altman analysis revealed small differences (-0.03/-0.02 m/s/Pa), limits of agreement (LOA) of 0.25 m/s/0.29 Pa, and coefficients of variation (CV) of 20% for velocity/WSS. Voxel-by-voxel orthogonal regression analysis showed moderate agreement (slope: 1.14/1.16, intraclass correlation coefficient [ICC]: 0.76/0.67 for velocity/WSS). The regional analysis revealed a CV of 9%/8% and ICC of 0.9/0.9 for velocity/WSS. Interobserver: voxel-by-voxel difference for WSS was 0, LOA: 0.17/0.19 Pa, CV: 12/13%, slope: 1.01/1.09, ICC: 0.87/0.85 for test/retest. The CV/ICC for WSS in the regional analysis was 4%/1.0 for test and 3%/1.0 for retest. CONCLUSION: Systolic velocity and WSS derived from 4D flow MRI are reproducible between consecutive visits, with low interobserver variability in healthy volunteers.

Age-related changes in aortic 3D blood flow velocities and wall shear stress: Implications for the identification of altered hemodynamics in patients with aortic valve disease.

PURPOSE: To investigate age-related changes in peak systolic aortic 3D velocity and wall shear stress (WSS) in healthy controls and to investigate the importance of age-matching for 3D mapping of abnormal aortic hemodynamics in bicuspid aortic valve disease (BAV). MATERIALS AND METHODS: 4D flow MRI (fields strengths = 1.5-3T; resolution = 2.2-3.9 × 1.7-2.6 × 2.2-4.0 mm(3) ; Venc = 150-250 cm/s; TE/TR/FA = 2.3-2.8/4.7-5.4msec/7-15°) was performed in 56 controls (age range: 19-78 years) and in two BAV patient groups each consisting of 10 subjects (group 1: 20-29 years, group 2: 52-57 years). Heat maps showing abnormal 3D velocity and WSS were created for the BAV patients by comparison with an age-matched and with an unmatched control group. The fraction of the aorta exposed to abnormal velocity/WSS was calculated relative to the total aortic volume/surface. RESULTS: Significant inverse relationships between age and healthy velocity/WSS were found (R(2) = 0.32/0.39, P < 0.001). For BAV group 1, abnormally elevated velocity/WSS was overestimated when compared with older controls (51-60 years) than when correctly age-matched (∼25 ± 14% vs. ∼8 ± 5%). For BAV group 2, abnormally decreased velocity/WSS was overestimated when compared with younger controls (21-30 years) than when correctly age-matched (∼9 ± 7% vs. 1 ± 1%). CONCLUSION: Significant correlations exist between age and peak systolic velocity and WSS. Therefore, robust age-matching is important when creating abnormal 3D aortic velocity and WSS maps for patients with BAV.

Long-Term Serial Follow-Up of Pulmonary Artery Size and Wall Shear Stress in Fontan Patients.

Pulmonary arterial (PA) flow is abnormal after the Fontan operation and is marked by a lack of pulsatility. We assessed the effects of this abnormal flow on the size and function of the PA's in Fontan patients in long-term serial follow-up. Twenty-three Fontan patients with serial follow-up were included. Median age was 11.1 (9.5-16.0) years at baseline and 15.5 (12.5-22.7) years at follow-up. Median follow-up duration was 4.4 (4.0-5.8) years. Flow and size of the left pulmonary artery were determined using phase-contrast MRI. From this wall shear stress (WSS), distensibility and pulsatility were determined. A group of healthy peers was included for reference. Flow and pulsatility were significantly lower in patients than in controls (p < 0.001). Mean area was comparable in patients and controls, but distensibility was significantly higher in controls (p < 0.001). Mean and peak WSS were significantly lower in Fontan patients (p < 0.001). Between baseline and follow-up, there was a significant increase in normalized flow (15.1 (14.3-19.1) to 18.7 (14.0-22.6) ml/s/m(2), p = 0.023). Area, pulsatility, distensibility and WSS did not change, but there was a trend toward a lower mean WSS (p = 0.068). Multivariable regression analysis showed that flow, area and age were important predictors for WSS. WSS in Fontan patients is decreased compared to healthy controls and tends to decrease further with age. Pulsatility and distensibility are significantly lower compared to healthy controls. Pulmonary artery size, however, is not significantly different from healthy controls and long-term growth after Fontan operation is proportionate to body size.

A methodology to detect abnormal relative wall shear stress on the full surface of the thoracic aorta using four-dimensional flow MRI.

PURPOSE: To compute cohort-averaged wall shear stress (WSS) maps in the thoracic aorta of patients with aortic dilatation or valvular stenosis and to detect abnormal regional WSS. METHODS: Systolic WSS vectors, estimated from four-dimensional flow MRI data, were calculated along the thoracic aorta lumen in 10 controls, 10 patients with dilated aortas, and 10 patients with aortic valve stenosis. Three-dimensional segmentations of each aorta were coregistered by group and used to create a cohort-specific aortic geometry. The WSS vectors of each subject were interpolated onto the corresponding cohort-specific geometry to create cohort-averaged WSS maps. A Wilcoxon rank sum test was used to generate aortic P-value maps (P<0.05) representing regional relative WSS differences between groups. RESULTS: Cohort-averaged systolic WSS maps and P-value maps were successfully created for all cohorts and comparisons. The dilation cohort showed significantly lower WSS on 7% of the ascending aorta surface, whereas the stenosis cohort showed significantly higher WSS on 34% of the ascending aorta surface. CONCLUSIONS: The findings of this study demonstrated the feasibility of generating cohort-averaged WSS maps for the visualization and identification of regionally altered WSS in the presence of disease, compared with healthy controls.

Volumetric arterial wall shear stress calculation based on cine phase contrast MRI.

PURPOSE: To assess the accuracy and precision of a volumetric wall shear stress (WSS) calculation method applied to cine phase contrast magnetic resonance imaging (PC-MRI) data. MATERIALS AND METHODS: Volumetric WSS vectors were calculated in software phantoms. WSS algorithm parameters were optimized and the influence of spatial resolution and segmentation was evaluated. Subsequently, 2D cine PC-MRI data in the carotid and the aorta at varying spatial resolutions were obtained (n = 2) and compared with the simulations. Finally, volumetric WSS was calculated in 3D cine PC-MRI data of the carotid bifurcation and the aorta (n = 6). RESULTS: We found that at least 8 voxels across the diameter are required to obtain a WSS accuracy of 5% and a precision of 20% in software phantoms. Systematic WSS quantification errors up to 40% were found in the case of segmentation errors. The in vivo measurements using 2D cine PC-MRI exhibited WSS increase at increasing spatial resolutions, similar to the results in software phantoms. Volumetric WSS vectors were successfully calculated in three healthy carotid bifurcations and aortas. CONCLUSION: The effects of resolution and segmentation on the accuracy and precision of the WSS algorithm were quantified. We were able to calculate volumetric WSS in the carotid bifurcation and the aorta.

Wall shear stress calculations based on 3D cine phase contrast MRI and computational fluid dynamics: a comparison study in healthy carotid arteries.

Wall shear stress (WSS) is involved in many pathophysiological processes related to cardiovascular diseases, and knowledge of WSS may provide vital information on disease progression. WSS is generally quantified with computational fluid dynamics (CFD), but can also be calculated using phase contrast MRI (PC-MRI) measurements. In this study, our objectives were to calculate WSS on the entire luminal surface of human carotid arteries using PC-MRI velocities (WSSMRI ) and to compare it with WSS based on CFD (WSSCFD ). Six healthy volunteers were scanned with a 3 T MRI scanner. WSSCFD was calculated using a generalized flow waveform with a mean flow equal to the mean measured flow. WSSMRI was calculated by estimating the velocity gradient along the inward normal of each mesh node on the luminal surface. Furthermore, WSS was calculated for a down-sampled CFD velocity field mimicking the MRI resolution (WSSCFDlowres ). To ensure minimum temporal variation, WSS was analyzed only at diastole. The patterns of WSSCFD and WSSMRI were compared by quantifying the overlap between low, medium and high WSS tertiles. Finally, WSS directions were compared by calculating the angles between the WSSCFD and WSSMRI vectors. WSSMRI magnitude was found to be lower than WSSCFD (0.62 ± 0.18 Pa versus 0.88 ± 0.30 Pa, p < 0.01) but closer to WSSCFDlowres (0.56 ± 0.18 Pa, p < 0.01). WSSMRI patterns matched well with those of WSSCFD. The overlap area was 68.7 ± 4.4% in low and 69.0 ± 8.9% in high WSS tertiles. The angles between WSSMRI and WSSCFD vectors were small in the high WSS tertiles (20.3 ± 8.2°), but larger in the low WSS tertiles (65.6 ± 17.4°). In conclusion, although WSSMRI magnitude was lower than WSSCFD , the spatial WSS patterns at diastole, which are more relevant to the vascular biology, were similar. PC-MRI-based WSS has potential to be used in the clinic to indicate regions of low and high WSS and the direction of WSS, especially in regions of high WSS.

Deep Brain Stimulation for Orthostatic Tremor: An Observational Study.

BACKGROUND: Primary orthostatic tremor (OT) can affect patients' life. Treatment of OT with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) is described in a limited number of patients. The Vim and posterior subthalamic area (PSA) can be targeted in a single trajectory, allowing both stimulation of the Vim and/or dentatorubrothalamic tract (DRT). In essential tremor this is currently often used with positive effects. OBJECTIVE: To evaluate the efficacy of Vim/DRT-DBS in OT-patients, based on standing time and Quality of Life (QoL), also on the long-term. Furthermore, to relate stimulation of the Vim and DRT, medial lemniscus (ML) and pyramidal tract (PT) to beneficial clinical and side-effects. METHODS: Nine severely affected OT-patients received bilateral Vim/DRT-DBS. Primary outcome measure was standing time; secondary measures included self-reported measures, neurophysiological measures, structural analyses, surgical complications, stimulation-induced side-effects, and QoL up to 56 months. Stimulation of volume of tissue activated (VTA) were related to outcome measures. RESULTS: Average maximum standing time increased from 41.0 s ± 51.0 s to 109.3 s ± 65.0 s after 18 months, with improvements measured in seven of nine patients. VTA (n = 7) overlapped with the DRT in six patients and with the ML and/or PT in six patients. All patients experienced side-effects and QoL worsened during the first year after surgery, which improved again during long-term follow-up, although remaining below age-related normal values. Most patients reported a positive effect of DBS. CONCLUSION: Vim/DRT-DBS improved standing time in patients with severe OT. Observed side-effects are possibly related to stimulation of the ML and PT.

Wall shear stress estimated with phase contrast MRI in an in vitro and in vivo intracranial aneurysm.

PURPOSE: To evaluate wall shear stress (WSS) estimations in an in vitro and in vivo intracranial aneurysm, WSS was estimated from phase contrast magnetic resonance imaging (PC-MRI) and compared with computational fluid dynamics (CFD). MATERIALS AND METHODS: First, WSS was estimated using a high-resolution in vitro PC-MRI measurement under steady and pulsatile flow conditions and compared with CFD simulations. Second, WSS was estimated in steady PC-MRI data acquired at different spatial resolutions. Third, WSS estimations in pulsatile in vivo data were compared with CFD. The direction and magnitude of WSS vectors were computed and compared. RESULTS: Quantitative agreement between PC-MRI and CFD-based WSS estimations was moderate for the phantom (Spearman ρ = 0.69). The WSS magnitude derived from PC-MRI data was lower than CFD for both the in vitro and in vivo case. However, there was qualitative agreement between PC-MRI and CFD, i.e. WSS vector direction was similar for both modalities. Circular WSS patterns were found both in vitro and in vivo for PC-MRI and CFD. Increasing PC-MRI resolution increased mean WSS magnitude and uncovered complex WSS patterns. CONCLUSION: WSS patterns can be estimated based on PC-MRI data in in vitro and in vivo aneurysm geometries. Similar WSS directions as CFD can be discerned.

Magnetoencephalography to measure the effect of contact point-specific deep brain stimulation in Parkinson's disease: A proof of concept study.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for disabling fluctuations in motor symptoms in Parkinson's disease (PD) patients. However, iterative exploration of all individual contact points (four in each STN) by the clinician for optimal clinical effects may take months. OBJECTIVE: In this proof of concept study we explored whether magnetoencephalography (MEG) has the potential to noninvasively measure the effects of changing the active contact point of STN-DBS on spectral power and functional connectivity in PD patients, with the ultimate aim to aid in the process of selecting the optimal contact point, and perhaps reduce the time to achieve optimal stimulation settings. METHODS: The study included 30 PD patients who had undergone bilateral DBS of the STN. MEG was recorded during stimulation of each of the eight contact points separately (four on each side). Each stimulation position was projected on a vector running through the longitudinal axis of the STN, leading to one scalar value indicating a more dorsolateral or ventromedial contact point position. Using linear mixed models, the stimulation positions were correlated with band-specific absolute spectral power and functional connectivity of i) the motor cortex ipsilateral tot the stimulated side, ii) the whole brain. RESULTS: At group level, more dorsolateral stimulation was associated with lower low-beta absolute band power in the ipsilateral motor cortex (p = .019). More ventromedial stimulation was associated with higher whole-brain absolute delta (p = .001) and theta (p = .005) power, as well as higher whole-brain theta band functional connectivity (p = .040). At the level of the individual patient, switching the active contact point caused significant changes in spectral power, but the results were highly variable. CONCLUSIONS: We demonstrate for the first time that stimulation of the dorsolateral (motor) STN in PD patients is associated with lower low-beta power values in the motor cortex. Furthermore, our group-level data show that the location of the active contact point correlates with whole-brain brain activity and connectivity. As results in individual patients were quite variable, it remains unclear if MEG is useful in the selection of the optimal DBS contact point.

Subhairline Electroencephalography for the Detection of Large Vessel Occlusion Stroke.

BACKGROUND: Endovascular thrombectomy is standard treatment for patients with anterior circulation large vessel occlusion stroke (LVO-a). Prehospital identification of these patients would enable direct routing to an endovascular thrombectomy-capable hospital and consequently reduce time-to-endovascular thrombectomy. Electroencephalography (EEG) has previously proven to be promising for LVO-a stroke detection. Fast and reliable electrode application, however, can remain a challenge. A potential alternative is subhairline EEG. We evaluated the diagnostic accuracy of subhairline EEG for LVO-a stroke detection. METHODS AND RESULTS: We included adult patients with a suspected stroke or known LVO-a stroke and symptom onset time <24 hours. A single 3-minute EEG recording was performed at the emergency department, before endovascular thrombectomy, using 9 self-adhesive electrodes placed on the forehead and behind the ears. We evaluated the diagnostic accuracies of EEG features quantifying frequency band power and brain symmetry (pairwise derived Brain Symmetry Index) for LVO-a stroke detection using receiver operating characteristic analysis. EEG data were of sufficient quality for analysis in 51/52 (98%) included patients. Of these patients, 16 (31%) had an LVO-a stroke, 16 (31%) a non-LVO-a ischemic stroke, 5 (10%) a transient ischemic attack, and 14 (27%) a stroke mimic. Median symptom-onset-to-EEG-time was 266 (interquartile range 130-709) minutes. The highest diagnostic accuracy for LVO-a stroke detection was reached by the pairwise derived Brain Symmetry Index in the theta frequency band (area under the receiver operating characteristic curve 0.90; sensitivity 86%; specificity 83%). CONCLUSIONS: Subhairline EEG could detect LVO-a stroke with high diagnostic accuracy and had high data reliability. These data suggest that subhairline EEG is potentially suitable as a prehospital stroke triage instrument.

Dorsal subthalamic nucleus targeting in deep brain stimulation: microelectrode recording versus 7-Tesla connectivity.

Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson's disease. It remains unclear whether deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 patients with Parkinson's disease, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus or non-motor-connected subthalamic nucleus, respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III) and microelectrode recording characteristics of multi- and single-unit activities were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared with electrodes placed in the non-motor-connected subthalamic nucleus (80% versus 52%, P < 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus (P < 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7-Tesla MRI subthalamic nucleus motor segment produced a superior clinical outcome; however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus.

Prehospital Detection of Large Vessel Occlusion Stroke With EEG.

BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is standard treatment for anterior large vessel occlusion stroke (LVO-a stroke). Prehospital diagnosis of LVO-a stroke would reduce time to EVT by allowing direct transportation to an EVT-capable hospital. We aim to evaluate the diagnostic accuracy of dry electrode EEG for the detection of LVO-a stroke in the prehospital setting. METHODS: ELECTRA-STROKE was an investigator-initiated, prospective, multicenter, diagnostic study, performed in the prehospital setting. Adult patients were eligible if they had suspected stroke (as assessed by the attending ambulance nurse) and symptom onset <24 hours. A single dry electrode EEG recording (8 electrodes) was performed by ambulance personnel. Primary endpoint was the diagnostic accuracy of the theta/alpha frequency ratio for LVO-a stroke (intracranial ICA, A1, M1, or proximal M2 occlusion) detection among patients with EEG data of sufficient quality, expressed as the area under the receiver operating characteristic curve (AUC). Secondary endpoints were diagnostic accuracies of other EEG features quantifying frequency band power and the pairwise derived Brain Symmetry Index. Neuroimaging was assessed by a neuroradiologist blinded to EEG results. RESULTS: Between August 2020 and September 2022, 311 patients were included. The median EEG duration time was 151 (interquartile range [IQR] 151-152) seconds. For 212/311 (68%) patients, EEG data were of sufficient quality for analysis. The median age was 74 (IQR 66-81) years, 90/212 (42%) were women, and the median baseline NIH Stroke Scale was 1 (IQR 0-4). Six (3%) patients had an LVO-a stroke, 109/212 (51%) had a non-LVO-a ischemic stroke, 32/212 (15%) had a transient ischemic attack, 8/212 (4%) had a hemorrhagic stroke, and 57/212 (27%) had a stroke mimic. AUC of the theta/alpha ratio was 0.80 (95% CI 0.58-1.00). Of the secondary endpoints, the pairwise derived Brain Symmetry Index in the delta frequency band had the highest diagnostic accuracy (AUC 0.91 [95% CI 0.73-1.00], sensitivity 80% [95% CI 38%-96%], specificity 93% [95% CI 88%-96%], positive likelihood ratio 11.0 [95% CI 5.5-21.7]). DISCUSSION: The data from this study suggest that dry electrode EEG has the potential to detect LVO-a stroke among patients with suspected stroke in the prehospital setting. Toward future implementation of EEG in prehospital stroke care, EEG data quality needs to be improved. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT03699397. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that prehospital dry electrode scalp EEG accurately detects LVO-a stroke among patients with suspected acute stroke.

Detection of large vessel occlusion stroke with electroencephalography in the emergency room: first results of the ELECTRA-STROKE study.

BACKGROUND: Prehospital detection of large vessel occlusion stroke of the anterior circulation (LVO-a) would enable direct transportation of these patients to an endovascular thrombectomy (EVT) capable hospital. The ongoing ELECTRA-STROKE study investigates the diagnostic accuracy of dry electrode electroencephalography (EEG) for LVO-a stroke in the prehospital setting. To determine which EEG features are most useful for this purpose and assess EEG data quality, EEG recordings are also performed in the emergency room (ER). Here, we report data of the first 100 patients included in the ER. METHODS: Patients presented to the ER with a suspected stroke or known LVO-a stroke underwent a single EEG prior to EVT. Diagnostic accuracy for LVO-a stroke of frequency band power, brain symmetry and phase synchronization measures were evaluated by calculating receiver operating characteristic curves. Optimal cut-offs were determined as the highest sensitivity at a specificity of ≥ 80%. RESULTS: EEG data were of sufficient quality for analysis in 65/100 included patients. Of these, 35/65 (54%) had an acute ischemic stroke, of whom 9/65 (14%) had an LVO-a stroke. Median onset-to-EEG-time was 266 min (IQR 121-655) and median EEG-recording-time was 3 min (IQR 3-5). The EEG feature with the highest diagnostic accuracy for LVO-a stroke was theta-alpha ratio (AUC 0.83; sensitivity 75%; specificity 81%). Combined, weighted phase lag index and relative theta power best identified LVO-a stroke (sensitivity 100%; specificity 84%). CONCLUSION: Dry electrode EEG is a promising tool for LVO-a stroke detection, but data quality needs to be improved and validation in the prehospital setting is necessary. (TRN: NCT03699397, registered October 9 2018).

ELECTRA-STROKE: Electroencephalography controlled triage in the ambulance for acute ischemic stroke-Study protocol for a diagnostic trial.

Background: Endovascular thrombectomy (EVT) is the standard treatment for large vessel occlusion stroke of the anterior circulation (LVO-a stroke). Approximately half of EVT-eligible patients are initially presented to hospitals that do not offer EVT. Subsequent inter-hospital transfer delays treatment, which negatively affects patients' prognosis. Prehospital identification of patients with LVO-a stroke would allow direct transportation of these patients to an EVT-capable center. Electroencephalography (EEG) may be suitable for this purpose because of its sensitivity to cerebral ischemia. The hypothesis of ELECTRA-STROKE is that dry electrode EEG is feasible for prehospital detection of LVO-a stroke. Methods: ELECTRA-STROKE is an investigator-initiated, diagnostic study. EEG recordings will be performed in patients with a suspected stroke in the ambulance. The primary endpoint is the diagnostic accuracy of the theta/alpha ratio for the diagnosis of LVO-a stroke, expressed by the area under the receiver operating characteristic (ROC) curve. EEG recordings will be performed in 386 patients. Discussion: If EEG can be used to identify LVO-a stroke patients with sufficiently high diagnostic accuracy, it may enable direct routing of these patients to an EVT-capable center, thereby reducing time-to-treatment and improving patient outcomes. Clinical trial registration: ClinicalTrials.gov, identifier: NCT03699397.

SSEP amplitudes add information for prognostication in postanoxic coma.

OBJECTIVE: To investigate whether somatosensory evoked potential (SSEP) amplitude adds information for prediction of poor outcome in postanoxic coma. METHODS: In this retrospective cohort study we included adult patients admitted after cardiac arrest between January 2010 and June 2018 who remained in coma and had SSEP recorded for prognostication. Outcome was dichotomized in poor (Cerebral Performance Category (CPC) 4-5) and good (CPC 1-3) at ICU discharge. Sensitivity of bilaterally absent N20 potential was calculated. In case the N20 potential was not bilaterally absent, the amplitude contralateral to stimulation side (baseline-N20, N20-P25, and maximum) was determined. At a specificity of 100%, SEPP amplitude sensitivities were determined for poor outcome. RESULTS: SSEP recordings were performed in 197 patients of whom 57 had bilaterally absent N20 potentials. From 140 patients, 16 (11%) had a good outcome. The sensitivity for poor outcome of bilaterally absent N20 was 31%. At a specificity of 100%, contralateral amplitude thresholds were 0.34 µV (baseline-N20), 0.99 µV (N20-P25) and 1.0 µV (maximum), corresponding to a sensitivity for poor outcome of 38%, 44% and 40%. Combination of bilaterally absent N20 and a N20-P25 threshold below 0.99 µV yielded a sensitivity of 62%. CONCLUSIONS: Our results confirm that very low cortical SSEP amplitudes are highly predictive of poor outcome in patients with postanoxic coma. Adding 'N20-P25 threshold amplitude' to the 'bilaterally absent N20' criterion, increased sensitivity substantially.