Low-level stochastic vestibular stimulation (SVS) has been associated with improved postural responses in the medio-lateral (ML) direction, but its effect in improving balance function in both the ML and anterior-posterior (AP) directions has not been studied. In this series of studies, the efficacy of applying low amplitude SVS in 0–30 Hz range between the mastoids in the ML direction on improving cross-planar balance function was investigated. Forty-five (45) subjects stood on a compliant surface with their eyes closed and were instructed to maintain a stable upright stance. Measures of stability of the head, trunk, and whole body were quantified in ML, AP and combined APML directions. Results show that binaural bipolar SVS given in the ML direction significantly improved balance performance with the peak of optimal stimulus amplitude predominantly in the range of 100–500 μA for all the three directions, exhibiting stochastic resonance (SR) phenomenon. Objective perceptual and body motion thresholds as estimates of internal noise while subjects sat on a chair with their eyes closed and were given 1 Hz bipolar binaural sinusoidal electrical stimuli were also measured. In general, there was no significant difference between estimates of perceptual and body motion thresholds. The average optimal SVS amplitude that improved balance performance (peak SVS amplitude normalized to perceptual threshold) was estimated to be 46% in ML, 53% in AP, and 50% in APML directions. A miniature patch-type SVS device may be useful to improve balance function in people with disabilities due to aging, Parkinson’s disease or in astronauts returning from long-duration space flight.
Purpose: Ongoing post-stroke structural degeneration and neuronal loss preceding neuropsychological symptoms such as cognitive decline and depression are poorly understood. Various substructures of the limbic system have been linked to cognitive impairment. In this longitudinal study, we investigated the post-stroke macro- and micro-structural integrity of the limbic system using structural and diffusion tensor magnetic resonance imaging.Materials and Methods: Nineteen ischemic stroke patients (11 men, 8 women, average age 53.4 ± 12.3, range 18–75 years), with lesions remote from the limbic system, were serially imaged three times over 1 year. Structural and diffusion-tensor images (DTI) were obtained on a 3.0 T MRI system. The cortical thickness, subcortical volume, mean diffusivity (MD), and fractional anisotropy (FA) were measured in eight different regions of the limbic system. The National Institutes of Health Stroke Scale (NIHSS) was used for clinical assessment. A mixed model for multiple factors was used for statistical analysis, and p-values <0.05 was considered significant.Results: All patients demonstrated improved NIHSS values over time. The ipsilesional subcortical volumes of the thalamus, hippocampus, and amygdala significantly decreased (p < 0.05) and MD significantly increased (p < 0.05). The ipsilesional cortical thickness of the entorhinal and perirhinal cortices was significantly smaller than the contralesional hemisphere at 12 months (p < 0.05). The cortical thickness of the cingulate gyrus at 12 months was significantly decreased at the caudal and isthmus regions as compared to the 1 month assessment (p < 0.05). The cingulum fibers had elevated MD at the ipsilesional caudal-anterior and posterior regions compared to the corresponding contralesional regions.Conclusion: Despite the decreasing NIHSS scores, we found ongoing unilateral neuronal loss/secondary degeneration in the limbic system, irrespective of the lesion location. These results suggest a possible anatomical basis for post stroke psychiatric complications.
Background: First pass complete or near complete reperfusion defined as a modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3 is the target for endovascular thrombectomy (EVT). Here, we examine whether additional passes in patients who achieve a first pass mTICI 2b, in order to attain mTICI 2c/3, improve clinical outcomes. Methods: From our prospectively maintained institutional registry at 4 comprehensive stroke centers, we identified patients treated with EVT (11/2017-12/2021). Per-pass mTICI grades were recorded at the time of the procedure. The primary outcome was functional independence rates at 90 days (mRS 0-2) in first pass mTICI 2b patients compared with multiple passes mTICI 2c/3 patients. Results: A total of 857 EVT patients were identified in the study period. The median age was 68 [58-79], 49.7% were female, median NIHSS was 16 [11-21], median ASPECTS was 9 [7-10], and 64% had MCA occlusions. First pass mTICI 2c/3 (FP-mTICI 2c/3) was achieved in 342 (39.9%) cases and first pass mTICI 2b (FP-mTICI 2b) was achieved in 123 (14.4%) patients. Of the FP-mTICI 2b group, 27 (21.9%) patients received additional passes to reach complete reperfusion. Good functional outcome was observed in 159 patients (46.5%) of the FP-mTICI 2c/3 reperfusion group as compared to 27 patients (28.1%) in the FP-mTICI 2b group (p=0.002). The rate of good functional outcome was not significantly different for patients who achieved mTICI 2c/3 following additional passes after a first pass mTICI 2b (28.1 vs. 29.6%, first pass mTICI 2b vs. first pass mTICI 2b with final mTICI 2c/3, p=0.954). Adjusted for age, sex and NIHSS at presentation, patients with FP-mTICI 2c/3 had a better chance of good outcomes than patients with FP-mTICI 2b (OR 2.23, 95% CI [1.38-3.62]). In multivariable analysis adjusting for age, sex, and NIHSS at presentation, patients with FP-mTICI 2b reperfusion followed by improved reperfusion to mTICI 2c/3 did not have better outcomes than patients with FP-mTICI 2b reperfusion (OR 1.14, 95% CI [0.41-3.12]). Conclusions: Additional EVT passes to achieve mTICI 2c/3 following a first pass mTICI 2b does not lead to significant improvement in functional outcomes. This study suggests that EVT can be terminated if FP-mTICI 2b-3 is achieved.
Background: Recent studies have shown that tPA can be safely administered past the standard 4.5hr window with good outcomes when selected with multi-model imaging, which is often lacking outside of comprehensive stroke centers. Aim: We aim to analyze the safety and outcomes of wake up/unknown onset (WUS/UNK) patients treated based on non-contrast head CT (NCCT) at our institution and in the literature. Methods: Suspected stroke patients from 01/2015-12/2018 receiving tPA within 4.5 hours (standard window-SW) and with WUS/UNK based on NCCT and clinical-imaging mismatch were identified. We compared baseline characteristics, tPA metrics, and outcome data, with primary outcome as symptomatic intracerebral hemorrhage (sICH). A meta-analysis was performed evaluating NCCT-based treatment of WUS/UNK patients. Results: Of 1827 patients treated at our hub or through telestroke, 93 underwent WUS/UNK-based treatment. There was no statistical difference in sICH between WUS/UNK and SW: 1% vs 4% (OR 0.3; 95% confidence interval 0.0-1.9). 90-day modified Rankin scale outcomes were similar between SW and WUS/UNK treated patients. Seven studies encompassing 485 WUS/UNK patients were included in a pooled analysis with a 2.1% incidence of sICH. In our meta-analysis, three studies compared NCCT-based treated WUS/UNK patients with SW patients with no difference in rate of hemorrhage: 2.1% vs 3.4% (OR 1.01; 95% confidence interval 0.45-2.28). Interpretation: Our single-center analysis and meta-analysis suggest that tPA can be safely administered based on NCCT with comparable rates of sICH for select WUS/UNK stroke patients.
Introduction: Recent studies support tPA for acute ischemic stroke (AIS) patients presenting beyond 4.5 hours from last known well (LKW), if established infarct is not evident on advanced imaging. Many community hospitals, where AIS patients may be managed via telestroke (TS), lack advanced imaging capability and hesitate to administer off-label tPA. In our TS network, physicians adhere to an extended window tPA (EW) protocol also used in the hub emergency room; eligibility includes NIHSS≤25, <1/3 MCA territory hypodensity on CT brain, and off-label tPA consent. Here, we characterize patients receiving EW via TS and investigate safety. Methods: We identified 1,150 AIS patients who received tPA via TS (9/2015-12/2018). We compared baseline characteristics between patients who received EW (arrival >4.5 hrs) and those who received standard window tPA (SW, arrival ≤4.5 hrs). We explored clinical outcomes and describe incidence of adverse effects from tPA. Results: Forty patients received EW, with median ASPECTS of 9 (Q1-Q3: 9-10). Median LKW to arrival time was 491 mins with EW and 66 mins with SW (p<0.0001, Table 1). EW led to few tPA complications; symptomatic intracranial hemorrhage incidence was 2%. EW was given for more severe stroke than SW (median NIHSS 10 vs 7, p=0.011). Both groups had comparable baseline characteristics, except a higher rate of tobacco use with EW. EW patients had longer length of stay (median 5 vs 3, p=0.023) and were more likely to be discharged to rehab than home (OR: 2.05 (1.01 4.15), p=0.046), however a small number of EW patients precludes in-depth comparative outcomes analysis. Conclusions: Our data suggest that EW is safe via TS for select patients with favorable CT, in settings that may lack advanced imaging capability. A specified mismatch between NIHSS and acute ischemia on plain CT is not part of our EW protocol, however EW is more likely given for severe stroke in our TS network. Small sample size warrants further study on clinical outcomes.
Introduction: The relationship between pass number during endovascular therapy (EVT) and outcomes in anterior circulation large vessel occlusion (LVO) acute ischemic stroke (AIS) has been well studied. However, the association between number of thrombectomy attempts and outcomes for patients with posterior circulation LVO remains undetermined. Methods: From our prospective multi-institutional registry including 4 comprehensive stroke centers in the Houston area, we identified consecutive LVO AIS patients who underwent EVT (01/2018-06/2021). The number of thrombectomy passes and per-pass reperfusion grades (TICI) were recorded at time of the EVT procedure. The primary outcome was the effect of number of passes on functional independence (modified Rankin Scale 0-2) at 90 days. Secondary outcomes included likelihood of attaining substantial reperfusion (TICI ≥2b). Results: Among 894 LVO AIS patients who underwent EVT, median age was 68 [IQR 58-78], 49% were female, and median NIHSS was 16 [IQR 11-21]. Of this cohort, 86 had posterior circulation LVO including 65 with basilar artery occlusion and 9 vertebral artery. The diminishing benefit on reperfusion and functional outcome after additional EVT passes was similar for anterior and posterior circulation AIS (Figure 1). Among patients with posterior circulation LVO, successful reperfusion with fewer passes was associated with greater likelihood of good outcomes (41.9% vs 6.7% mRS 0-2 with 1-2 vs ≥3, p=0.012). The likelihood of good outcomes with 1-2 passes for patients with posterior circulation LVO was comparable to patients with anterior circulation LVO (41.9% vs 40.2%, p=0.164). Conclusions: Similar to patients with anterior circulation LVO, patients with posterior circulation LVO undergoing EVT are more likely to achieve functional independence with successful reperfusion in fewer EVT attempts. Overall clinical outcomes are significantly better with fewer passes regardless of occlusion location.
Introduction: Endovascular therapy (ET) in acute ischemic stroke (AIS) care has established clear improvements in clinical outcome. However, a large percentage of treated patients still do poorly, and the rate of good outcome remains relatively low, even in patients who achieve substantial reperfusion. While the importance of time and rapid reperfusion have been well described in AIS, the recent prominence of imaging-alone based selection criteria has brought the relevance of time into question. We hypothesize that ischemic time even in patients with comparable infarct cores at presentation still plays an important role in modifying outcome in patients with AIS and large vessel occlusion (LVO) treated with ET. Method: From our prospectively collected institutional registry across 4 comprehensive stroke centers, we identified consecutive patients with LVO AIS treated with ET from 1/2017 to 1/2020. Patients were included if they had anterior circulation LVO, successful reperfusion TICI 2b/3, and witnessed time of symptom onset. Propensity score analysis used among patients matched by age, NIHSS, occlusion location, ASPECTS, TICI score and infarct core to evaluate if time from onset to arrival affect the likelihood of mRS 0-2 at 90 days. Data are presented as median [IQR] or mean±SD. Results: Among 242 patients that met inclusion criteria, mean age was 67±13.8, 50% were female, median NIHSS was 16 [10], and mean time from symptom onset to arrival (SOA) was 4.17±0.19 (hrs.min). The most common locations of the occlusion included M1 47.1%, ICA 20.2 %, M2 13.2% and A1 1.2%. In univariable analysis, fewer patients in the late time window (SOA > 6 hrs) achieved 90d mRS 0-2 compared to patients in the early window, but this difference was not statistically significant (66%% vs 34%%, early vs. late, P=0.1, Fisher’s exact). Propensity score analysis showed that among matched patients, later SOA was associated with decreased likelihood of mRS 0-2 at 90 days (coef: -0.22 [0.37-0.60], P=0.007). Conclusion: In patients with successful endovascular reperfusion, those presenting in later time windows had worse outcomes compared to those presenting earlier, even after accounting for differences in presentation infarct core.
Introduction: Evaluation of infarct core by advanced neuroimaging has facilitated patient selection for endovascular stroke therapy (EST), however the accuracy of machine-learning analysis compared to these modalities remains unexplored. We test the performance of computed tomography-Alberta Stroke Program Early Computed Tomography Score (CT- ASPECTS) vs. Computed Tomography Perfusion (CTP)-RAPID, vs. an extension of our novel machine-learning model, Deep Symmetry-sensitive Network (DeepSymNet [ref]), using the final infarct volume (FIV) in patients with rapid and successful endovascular reperfusion as the gold standard. Methods and Materials: We identified consecutive patients with large vessel occlusion acute ischemic stroke that underwent EST with TICI 2b/3 reperfusion. FIV was determined by volumetric measurements on 24-48h DWI MRI. The DeepSymNet algorithm combines symmetric and absolute brain representations and had been trained to predict CTP-RAPID core size from CTA source images acquired at presentation. Performance at predicting FIV was determined by Pearson’s correlation for CT- ASPECTS, CTP-RAPID, and DeepSymNet. Data are presented as median [IQR]. Results: Among the 76 patients that met inclusion criteria, 55.2% were male, the median age was 68 years [54-77], and 32.8% were White. 71% of the patients demonstrated an MCA occlusion, and 55% of all occlusions were left-sided. Median ASPECTS on presentation was 8 [7-8.5] and the median FIV was 10 mL [2-37]. ASPECTS, CTP-RAPID and DeepSymNet all correlated with FIV, with comparable performances from ASPECTS (R 2 =-0.398) and CTP-RAPID (R 2 =0.403) and superior performance by DeepSymNet (R 2 =-0.606)(Table). Conclusions: The DeepSymNet machine learning model analyzing CTA source images demonstrated superior performance to ASPECTS and CTP-RAPID in FIV prediction. These findings suggest machine learning models may provide improved predictions of infarct core and selection for EST.
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