Synthetic OCT-A blood vessel maps using fundus images and generative adversarial networks.

Vessel segmentation in fundus images permits understanding retinal diseases and computing image-based biomarkers. However, manual vessel segmentation is a time-consuming process. Optical coherence tomography angiography (OCT-A) allows direct, non-invasive estimation of retinal vessels. Unfortunately, compared to fundus images, OCT-A cameras are more expensive, less portable, and have a reduced field of view. We present an automated strategy relying on generative adversarial networks to create vascular maps from fundus images without training using manual vessel segmentation maps. Further post-processing used for standard en face OCT-A allows obtaining a vessel segmentation map. We compare our approach to state-of-the-art vessel segmentation algorithms trained on manual vessel segmentation maps and vessel segmentations derived from OCT-A. We evaluate them from an automatic vascular segmentation perspective and as vessel density estimators, i.e., the most common imaging biomarker for OCT-A used in studies. Using OCT-A as a training target over manual vessel delineations yields improved vascular maps for the optic disc area and compares to the best-performing vessel segmentation algorithm in the macular region. This technique could reduce the cost and effort incurred when training vessel segmentation algorithms. To incentivize research in this field, we will make the dataset publicly available to the scientific community.

Inpatient Teleneurology Follow-up Has Comparable Outcomes to In-Person Neurology Follow-up.

Background and Objectives: Community emergency departments often transfer patients for lack of neurology coverage, potentially burdening patients and accepting facilities. Telestroke improves access to acute stroke care, but there is a lack of data on inpatient teleneurology and telestroke care. Methods: From our prospective telestroke registry, we retrospectively reviewed 3702 consecutive patients who were seen via telestroke between September 2015 and December 2018. Patients who required transfer after initial telestroke evaluation or who were kept at hospitals without consistent neurology coverage were excluded from analysis. We compared baseline demographics, clinical characteristics, and hospital outcomes in patients who were subsequently followed remotely by a teleneurology neurohospitalist and those followed in person by a neurohospitalist. Results: There were 447 (23%) patients followed by a teleneurology neurohospitalist and 1459 (77%) patients followed in person by a neurohospitalist. Both groups presented with similar stroke severity. In multivariate analysis, there were no significant differences in discharge disposition, stroke readmission rates, or 90-day modified Rankin Scale (mRS) scores. Length of stay was shorter with teleneurology follow-up. In the subgroup of patients who received tissue plasminogen activator, patients showed no differences in outcomes and had similar complication rates. Teleneurology follow-up resulted in a 3% transfer rate for higher level of care after admission. There remained no difference in outcomes in a subanalysis without Comprehensive Stroke Centers. A higher proportion of non-Hispanic Black patients and a lower proportion of Hispanic patients in the teleneurology follow-up group were possibly due to spoke location demographics. Discussion: Teleneurology follow-up resulted in comparable outcomes to in-person neurology follow-up, with few transfers after admission. For select neurology and ischemic stroke patients, teleneurology follow-up provides an alternative to transfer for hospitals lacking neurology coverage.

Computed Tomography Angiography Quantification of Intracranial and Extracranial Vascular Narrowing in Ischemic Stroke: Differences Between Patients With and Without Illicit Drug Use.

OBJECTIVE: Previous studies have linked illicit drug consumption and stroke. The purpose of this study is to identify specific imaging findings depicted on computed tomography angiography on patients with illicit drug-associated stroke. METHODS: This is a retrospective case-control study that included ischemic stroke patients. Subjects who tested positive for cocaine or marijuana were considered as cases, while patients who tested negative were included as controls. Matching of the controls was carried out based on the presence of stroke risk factors. A previously validated scale was used to calculate narrowing scores through computed tomography angiography. Comparison between cases and matched controls was evaluated by paired t test for age and body mass index, and by Wilcoxon signed rank test for intracranial, extracranial, and total scores. RESULTS: One hundred seventy-four patients were included in the study, 87 subjects for each group. Because of matching, baseline status differed only on body mass index, with a greater proportion of obese subjects among controls ( P < 0.016). Subgroup analysis demonstrated that it is more likely to find any intracranial abnormality among cocaine consumers when compared with controls ( P = 0.041). CONCLUSIONS: By using computed tomography angiography, we found that stroke patients with history of cocaine consumption had a higher incidence of intracranial circulation narrowing compared with matched controls.

Non-contrast head CT-based thrombolysis for wake-up/unknown onset stroke is safe: A single-center study and meta-analysis.

BACKGROUND: Recent studies have shown that tPA can be safely administered past the standard 4.5 h 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 January 2015 to December 2018 receiving tPA within 4.5 h (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.

Towards Stroke Biomarkers on Fundus Retinal Imaging: A Comparison Between Vasculature Embeddings and General Purpose Convolutional Neural Networks.

Fundus Retinal imaging is an easy-to-acquire modality typically used for monitoring eye health. Current evidence indicates that the retina, and its vasculature in particular, is associated with other disease processes making it an ideal candidate for biomarker discovery. The development of these biomarkers has typically relied on predefined measurements, which makes the development process slow. Recently, representation learning algorithms such as general purpose convolutional neural networks or vasculature embeddings have been proposed as an approach to learn imaging biomarkers directly from the data, hence greatly speeding up their discovery. In this work, we compare and contrast different state-of-the-art retina biomarker discovery methods to identify signs of past stroke in the retinas of a curated patient cohort of 2,472 subjects from the UK Biobank dataset. We investigate two convolutional neural networks previously used in retina biomarker discovery and directly trained on the stroke outcome, and an extension of the vasculature embedding approach which infers its feature representation from the vasculature and combines the information of retinal images from both eyes.In our experiments, we show that the pipeline based on vasculature embeddings has comparable or better performance than other methods with a much more compact feature representation and ease of training.Clinical Relevance-This study compares and contrasts three retinal biomarker discovery strategies, using a curated dataset of subject evidence, for the analysis of the retina as a proxy in the assessment of clinical outcomes, such as stroke risk.

Thrombolytic Refusal Over Telestroke.

BACKGROUND: Tissue plasminogen activator (tPA) refusal is 4%-6% for acute ischemic stroke (AIS) in the emergency department. Telestroke (TS) has increased the use of tPA for AIS but is accompanied by barriers in communication that can affect tPA consent. We characterized the incidence of tPA refusal in our TS network and its associated reasons. METHODS: Patients with AIS who were offered tPA within 4.5 hours from symptom onset according to American Heart Association guidelines were identified within our Lone Star Stroke Consortium Telestroke Registry from September 2015 to December 2018. We compared baseline characteristics and clinical outcomes between patients who refused tPA and patients who accepted tPA. RESULTS: Among the 1,242 patients who qualified for tPA and were offered treatment, 8% refused tPA. Female and non-Hispanic Black patients and patients with a prior history of stroke were more likely to decline tPA. Patients who refused tPA presented with a lower NIHSS and were associated with a final diagnosis of stroke mimic (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.15-0.36). Good outcome (90-day modified Rankin Scale 0-2) was the same among patients who received tPA and those who refused (OR 0.80; 95% CI 0.42-1.54). The most common reasons for refusal were rapidly improving and mild/nondisabling symptoms and concern for potential side effects. CONCLUSION: tPA refusal over TS is comparable to previously reported rates; there was no difference in outcomes among patients who received tPA compared with those who refused. Sex and racial differences associated with an increased tPA refusal warrant further investigation in efforts to achieve equity/parity in tPA decisions.

Lack of Racial, Ethnic, and Sex Disparities in Ischemic Stroke Care Metrics within a Tele-Stroke Network.

INTRODUCTION: Differences in access to stroke care and compliance with standard of care stroke management among patients of varying racial and ethnic backgrounds and sex are well-characterized. However, little is known on the impact of telestroke in addressing disparities in acute ischemic stroke care. METHODS: We conducted a retrospective review of acute ischemic stroke patients evaluated over our 17-hospital telestroke network in Texas from 2015-2018. Patients were described as Non-Hispanic White (NHW) male or female, Non-Hispanic Black (NHB) male or female, or Hispanic (HIS) male or female. We compared frequency of tPA and mechanical thrombectomy (MT) utilization, door-to-consultation times, door-to-tPA times, and time-to-transfer for patients who went on to MT evaluation at the hub after having been screened for suspected large vessel occlusion at the spoke. RESULTS: Among 3873 patients (including 1146 NHW male (30%) and 1134 NHW female (29%), 405 NHB male (10%) and 491 NHB female (13%), and 358 HIS male (9%) and 339 HIS female (9%) patients), we did not find any differences in door-to consultation time, door-to-tPA time, time-to-transfer, frequency of tPA administration, or incidence of MT utilization. CONCLUSION: We did not find racial, ethnic, and sex disparities in ischemic stroke care metrics within our telestroke network. In order to fully understand how telestroke alleviates disparities in stroke care, collaboration among networks is needed to formulate a multicenter telestroke database similar to the Get-With-The Guidelines.

Training in Neurology: Adoption of resident teleneurology training in the wake of COVID-19: Telemedicine crash course.

The coronavirus disease 2019 pandemic has changed the way we engage patient care, with a move toward telemedicine-based health care encounters. Teleneurology is now being rapidly embraced by neurologists in clinics and hospitals nationwide but for many, this paradigm of care is unfamiliar. Exposure to telemedicine in neurology training programs is scarce despite previous calls to expand teleneurology education. Programs that provide a teleneurology curriculum have demonstrated increased proficiency, accuracy, and post-training utilization among their trainees. With the current changes in health care, broad incorporation of teleneurology education in resident and fellow training after this pandemic dissipates will only serve to improve trainee preparedness for independent practice.

Mobile Stroke Unit Computed Tomography Angiography Substantially Shortens Door-to-Puncture Time.

Background and Purpose- Endovascular thrombectomy (ET) door-to-puncture time (DTPT) is a modifiable metric. One of the most important, yet time-consuming steps, is documentation of large vessel occlusion by computed tomography angiography (CTA). We hypothesized that obtaining CTA on board a Mobile Stroke Unit and direct alert of the ET team shortens DTPT by over 30 minutes. Methods- We compared DTPT between patients having CTA onboard the Mobile Stroke Unit then subsequent ET from September 2018 to November 2019 and patients in Mobile Stroke Unit from August 2014 to August 2018, when onboard CTA was not yet being used. We also correlated DTPT with change in National Institutes of Health Stroke Scale between baseline and 24 hours. Results- Median DTPT was 53.5 (95% CI, 35-67) minutes shorter with onboard CTA and direct ET team notification: 41 minutes (interquartile range, 30.0-63.5) versus 94.5 minutes (interquartile range, 69.8-117.3; P<0.001). Median on-scene time was 31.5 minutes (interquartile range, 28.8-35.5) versus 27.0 minutes (interquartile range, 23.0-31.0) (P<0.001). Shorter DTPT correlated with greater improvement of National Institutes of Health Stroke Scale (correlation=-0.2, P=0.07). Conclusions- Prehospital Mobile Stroke Unit management including on-board CTA and ET team alert substantially shortens DTPT. Registration- URL: https://clinicaltrials.gov; Unique identifier: NCT02190500.

Hepatic Encephalopathy Mimicking Acute Dominant Middle Cerebral Artery Ischemic Stroke: A Case Report.

Hepatic encephalopathy and hyperammonemia are common in the setting of liver disease and have been associated with both generalized and focal neurological deficits. We report a case of hepatic encephalopathy with transaminitis in the setting of hyperammonemia clinically mimicking acute dominant middle cerebral artery (MCA) syndrome. A 59-year-old right-handed woman had new-onset expressive aphasia, left gaze deviation, and right hemiparesis consistent with MCA stroke. Her symptoms began 12 h after transarterial chemoembolization, a procedure to embolize blood supply and provide cytotoxic agents to a hepatocellular carcinoma tumor. Thrombocytopenia and age-indeterminate hypodensities on brain CT precluded intravenous thrombolytic administration. MRI revealed predominantly dominant hemisphere subcortical restricted diffusion with no cortical involvement. Due to a mismatch between the MRI findings and the neurological symptoms, she underwent digital subtraction cerebral angiography to assess candidacy for intra-arterial thrombectomy, which revealed completely patent MCAs with intact filling of the distal branches. Liver enzymes and ammonia were elevated. The patient was treated with lactulose and intravenous fluids. After normalization of liver enzymes, the patient's neurological deficits resolved. Reversal of this patient's focal symptoms with medical management could potentially be explained by the recovery of blood flow-metabolic demand mismatch caused by worsening liver dysfunction and hyperammonemia. As acute stroke therapies and interventions increase in utility for large artery acute ischemic stroke, it is vital to recognize hepatic encephalopathy and liver failure as part of the differential diagnosis for patients presenting with MCA syndrome.

Variability and Delay in Telestroke Physician Alert among Spokes in a Telestroke Network: A Need for Metric Benchmarks.

INTRODUCTION: Telestroke has increased access to acute management of ischemic stroke in areas that lack stroke care expertise, yet delays persist in evaluation and treatment. We describe variation in time to alert a telestroke physician of suspected acute ischemic stroke patients potentially eligible for acute stroke therapies among community hospitals in our telestroke network, and explore demographic and spoke-related characteristics associated with delays. METHODS: From our telestroke registry, we identified suspected acute ischemic stroke patients who arrived within 6 hours of symptom onset and underwent video consultation at 1 of 17 community hospitals in our hub-and-spoke network. We compared time between patient arrival to telestroke alert (door-to-page-time) and to tissue plasminogen activator (tPA) administration for eligible patients (door-to-needle-time). We identified factors associated with prolonged metrics. RESULTS: Of 1020 cases between 9/2015 and 3/2017, 47% received tPA. Sixty percent had door-to-page-time more than 15 minutes (median 19.5; IQR, 11-34). Door-to-page-time more than 15 minutes was associated with an 8-fold increase in likelihood of door-to-needle-time more than 60 minutes. Patients with severe stroke experienced faster door-to-page-times. Hospitals with more beds had prolonged door-to-page-time. Full time in-house neurology presence, even when not covering emergent consultations, was associated with faster door-to-page-time over telestroke. Seventy-one percent of patients underwent CT brain prior to the telestroke physician alert; this scenario delayed door-to-page and door-to-needle times. CONCLUSIONS: Door-to-page-time varied considerably among spokes. Awaiting CT scan prior to alerting the telestroke consultant of a stroke code delayed metrics. Telestroke physician alert standards are needed, as are educational initiatives on acute ischemic stroke management and workflow.

Emergency Department Door-to-Puncture Time Since 2014.

Background and Purpose- The impact of a mobile stroke unit (MSU) on access to intraarterial thrombectomy (IAT) is a prespecified BEST-MSU substudy (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). On the MSU, IAT decision-making steps, such as computed tomography, neurological exam, and tPA (tissue-type plasminogen activator) treatment are completed before emergency department arrival. We hypothesized that such pre-ED assessment of potential IAT patients on an MSU improves the time from ED arrival to skin puncture time (door-to-puncture-time, DTPT). Methods- BEST-MSU is a prospective comparative effectiveness study of MSU versus standard management by emergency medical services (EMS). We compared ED DTPT among the following groups of MSU and EMS patients: all IAT patients, IAT patients post-tPA, and IAT patients post-tPA meeting thrombolytic adjudication criteria over the first 4 years of the study. Results- From August 2014 to July 2018, a total of 161 patients underwent IAT. Ninety-four patients presented to the ED via the MSU and 67 by EMS. One hundred forty patients received tPA before IAT, 85 in the MSU arm, and 55 in the EMS arm. One hundred twenty-six patients received tPA within thrombolytic adjudication criteria: 76 MSU and 50 EMS. DTPT in minutes was shorter for MSU patients (all IAT MSU versus EMS 89 versus 99, P=0.01; IAT post-tPA MSU versus EMS 93 versus 100, P=0.03; and IAT post-tPA within adjudicated criteria MSU versus EMS 93 versus 99.5, P=0.03). From 2014 to 2018, DTPT decreased at a faster rate for EMS compared with MSU-managed patients, improving by about an hour. Conclusions- Pre-ED IAT evaluation on an MSU results in faster DTPT compared with arrival by EMS. Since 2014, dramatic improvement in ED IAT metrics has attenuated this difference. However, DTPT in all groups indicates substantial room for improvement.

Outcomes Among Patients With Ischemic Stroke Treated With Intravenous tPA (Tissue-Type Plasminogen Activator) via Telemedicine.

Background and Purpose- Telemedicine is increasingly utilized for intravenous tPA (tissue-type plasminogen activator) delivery. The comparative safety of leaving tPA-treated patients at a presenting (spoke) hospital (drip-and-stay) or transferring patients to a central treating (hub) hospital (drip-and-ship) is not established. We sought to compare outcomes between drip-and-ship and drip-and-stay patients treated with tPA via telemedicine. We hypothesized that there would be no differences in short-term outcomes of in-hospital mortality, length of stay, or discharge disposition or in 90-day outcomes between groups. Methods- We retrospectively identified patients treated with tPA at 17 spoke hospitals between September 2015 and December 2016. Demographic, clinical, and outcome data were obtained from a prospective telemedicine registry. We used negative binomial, multinomial, and logistic regression analyses to evaluate length of stay, discharge disposition, and inpatient mortality, respectively. We compared the proportion of patients with 90-day modified Rankin Scale score <2 by group. Results- Among 430 tPA-treated patients, 232 (53.9%) were transferred to the hub after treatment. The median arrival National Institutes of Health Stroke Scale score was higher for drip-and-ship (10; interquartile range, 5-18) compared with drip-and-stay patients (6; interquartile range, 4-10; P<0.001). Unadjusted length of stay was longer in drip-and-stay patients (incidence rate ratio, 0.82; 95% CI, 0.71-0.95). There were no significant differences in adjusted length of stay, hospital mortality, or discharge disposition. Among the 64% of patients with complete 90-day modified Rankin Scale score, the proportion with good outcomes (modified Rankin Scale score <2) did not differ between groups. Conclusions- We found no differences in measured outcomes between drip-and-ship and drip-and-stay patients treated in our network, although our study may be underpowered to detect small differences.

Benchmarking Telestroke Proficiency: Page-to-Needle Time Among Neurovascular Fellows and Attendings.

BACKGROUND AND PURPOSE: Formal telestroke training for neurovascular fellows (NVFs) is necessary because of growing use of telestroke technologies in the management of acute ischemic stroke; yet, educational approaches and training benchmarks are not formalized. Time between telestroke consultant page and tissue-type plasminogen activator administration (page-to-needle time, PTNT) can provide an objective measure of proficiency. We compared PTNT between NVFs and neurovascular attendings (NVAs) and evaluated changes in PTNT with experience. METHODS: We identified suspected acute ischemic stroke patients in our telestroke registry from July 2013 to December 2015 who received tissue-type plasminogen activator. Using multivariable quantile regression, we estimated the difference and 95% confidence interval in median PTNT between NVFs and NVAs. We also report the coefficient of change in PTNT over increasing number of telestroke consults. RESULTS: NVFs evaluated 53.7% of 618 tissue-type plasminogen activator cases over telestroke. NVAs had significantly shorter PTNT compared with NVFs, with a difference in median PTNT of -9 minutes (95% confidence interval, -12.3 to -5.7). This difference persisted when adjusted for relative tissue-type plasminogen activator contraindications. For each additional telestroke consult, PTNT decreased by 0.07 minutes for NVFs or NVAs (P=0.02 and <0.01, respectively). CONCLUSIONS: PTNT improves by ≈1 minute for every 14 consults for both NVFs and NVAs. Our findings support the importance of integrating telestroke training into supervised neurovascular fellowships to increase proficiency prior to independent practice and suggest that PTNT can be a benchmark for tracking proficiency.