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Background: Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We sought to identify the onset of the neuroinflammatory cascade using a mobile stroke unit. Methods: The study is a proof-of-concept, cohort investigation of ultra-early blood- and extracellular vesicle–derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained, prehospital, on an mobile stroke unit. Outcomes were biomarker concentrations, modified Rankin Scale score, and National Institutes of Health Stroke Scale score. Results: Forty-one adults were analyzed, including 15 patients treated on the mobile stroke unit between August 2021 and April 2022, and 26 healthy controls to establish biomarker reference levels. Median patient age was 74 (range, 36–97) years, 60% were female, and 80% White. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely transient ischemic attack or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial National Institutes of Health Stroke Scale score was 11 (range, 4–19) and 6 (75%) received tPA (tissue-type plasminogen activator). Blood was obtained a median of 58 (range, 36–133) minutes after symptom onset. Within 36 minutes after stroke, plasma IL-6 (interleukin-6), neurofilament light chain, UCH-L1 (ubiquitin C-terminal hydrolase L1), and GFAP (glial fibrillary acidic protein) were elevated by as much as 10 times normal. In EVs, MMP-9 (matrix metalloproteinase-9), CXCL4 (chemokine (C-X-C motif) ligand 4), CRP (C-reactive protein), IL-6, OPN (osteopontin), and PECAM1 (platelet and endothelial cell adhesion molecule 1) were elevated. Inflammatory markers increased rapidly in the first 2 hours and continued rising for 24 hours. Conclusions: The neuroinflammatory cascade was found to be activated within 36 to 133 minutes after stroke and progresses rapidly. This is earlier than observed previously in humans and suggests injury from neuroinflammation occurs faster than had been surmised. These findings could inform development of acute immunomodulatory stroke therapies and lead to new diagnostic tools and improved outcomes.

Background: Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We used a mobile stroke unit (MSU) to identify the onset of the neuroinflammatory cascade within minutes of symptom onset. Methods: The study is a prospective, cohort investigation of ultra-early blood- and extracellular vesicle (EV)-derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained on the MSU with head CT, and from healthy controls. Plasma biomarkers were analyzed with ELISA, SIMOA and ECL. EVs were isolated with HSP pull down. Confirmed strokes, mimics and healthy controls were compared. Variables included demographics, mRS, NIHSS and discharge disposition. Results: Forty one adults were analyzed, including 15 patients treated on the MSU between August 2021 and April 2022, and 26 controls. For MSU patients, median age was 74 (range 36-97) years, 60% were female, and 80% white. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely TIA or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial NIHSS score was 11 (range 4-19) and 6 (75%) received tPA. Blood was obtained a median of 58 (range 36-133) minutes after symptom onset. Within 36 minutes after stroke, plasma interleukin-6 (IL-6), neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were elevated by as much as 10 times normal. In EVs, matrix metalloproteinase-9 (MMP-9), chemokine (C-X-C motif) ligand 4 (CXCL4), C-reactive protein (CRP), IL-6, osteopontin (OPN) and platelet and endothelial cell adhesion molecule 1 (PECAM1) were elevated. Inflammatory markers increased rapidly in the first two hours, and continued rising for 24 hours. Conclusions: This study found the inflammatory cascade is activated as early as 36 minutes after stroke, and progresses rapidly. This is earlier than observed previously in humans, and suggests injury from neuroinflammation may occur faster than had been surmised. The findings may inform development of immunomodulatory therapies for acute stroke, and lead to new diagnostic tools and improved outcomes.

Introduction: A Mobile Stroke Unit (MSU) has served Aurora, CO since 2016. This service is activated by 911 for stroke-like symptoms. We sought to characterize the population served by this MSU to determine whether it differed from the area’s population and to design targeted community-based interventions for the future. Methods: A retrospective study of the MSU transport cases in Aurora, CO was performed; self-identified variables such as age, race/ethnicity, preferred language, and activation zipcode were recorded and compared to frequencies from the Aurora census using Chi-squared tests. NIHSS and time from last known well (LKW) to dispatch were collected and analyzed with ANOVA type models. Tukey-Kramer and omnibus F-tests were utilized for testing adjustments. Results: A total of 320 MSU patients were included from 2016 to 2021. English speakers comprised 89.3% (vs. 68.2% of the population) and Spanish speakers 7.2% (vs. 21.1%); analysis of preferred language between MSU patients and the Aurora population demonstrated a significant difference (p = 1.75 x 10 -13 ). English-speaking MSTU patients were older than Spanish-speaking patients (67.7 ± 15.9 years vs. 59.3± 17.3 years). Analysis of race/ethnicity demonstrated significant differences (p = Conclusion: There was an increased representation of English-speaking patients with stroke-like symptoms who activated the MSU in Aurora, compared to the general population. Time from LKW to dispatch was significantly longer for English speakers than Spanish-speaking patients, a difference perhaps attributable to age differences. The differences observed through this analysis emphasize the need to develop and deliver educational stroke programing to non-English speakers and older individuals, to maximize the impact of the MSU in Aurora.

Background: Stroke mimics are often difficult to distinguish from true ischemic and hemorrhagic cerebrovascular accidents, and present a challenge for appropriate delivery of rapid stroke treatment. This is particularly true in ultra-early stroke care with Mobile Stroke Units (MSU), which administer tPA in the field, within minutes of symptom onset. We sought to evaluate and characterize stroke mimics during prehospital care with an MSU at a Comprehensive Stroke Center. Methods: The study compared patient and stroke characteristics, neurologic evaluation, and treatment between confirmed strokes and stroke mimics treated during a one-year pilot period on the MSU at a large urban medical center. Variables included patient demographics, NIHSS score, tPA administration, final diagnosis, and discharge disposition. Results: Between Jan. 15, 2016 and Jan. 9, 2017, 47 patients received prehospital management on the MSU, and 44 were admitted to UC hospital and had an available final diagnosis. Of these, 12 (27%) were stroke mimics. Mimics were younger [median age 60 (IQR 54-71) years, mimics vs. 68 (IQR 60-77) years, strokes], and were more often female (58%, mimics vs. 47%, strokes). Initial NIHSS score was lower for confirmed strokes [median 3 (IQR 2-10) strokes, vs. 6 (IQR 4-12) mimics], but severe strokes with a NIHSS score >17, were more common in strokes (16%, strokes vs. 0%, mimics). Of mimics, 6 (50%) were seizures, 2 (17%) migraine, 2 (17%) conversion, 1 (8%) encephalopathy, and 1 (8%) delirium. Thirteen (30%) of all patients were treated with IV tPA on the MSU, of whom 4 (31%) were mimics. Of mimics given tPA, 2 were seizures, 1 migraine and 1 conversion. Mimics were more likely to be discharged to home (64%, mimics vs. 46%, strokes) while strokes more likely received rehabilitation (23%, strokes vs. 9%, mimics). Conclusions: One third of patients treated on the MSU were stroke mimics, and among these the most common diagnosis was seizures. These results suggest vigilance is warranted for seizure, as well as further study of rapid EEG technologies to guide appropriate treatment for presentations that appear to be stroke, including antiepileptic drugs, in ultra-early MSU care of suspected CVA.

Introduction: Most clinical research stopped during COVID due to possible impact on data quality and personnel safety. We aimed to assess the impact of COVID on study conduct at sites that continued to enroll patients during the pandemic. Methods: BEST-MSU is an ongoing study of Mobile Stroke Units (MSU) vs standard management of tPA eligible acute stroke patients in the pre-hospital setting. MSU personnel include a vascular neurologist via telemedicine, and a nurse, CT tech, and medics on board using appropriate PPE. During COVID, consent, 90 d mRS and EQ5D could be obtained by phone instead of in person, otherwise management was the same. We compared patient demographics, study metrics, and infection of study personnel during intra- vs pre-COVID eras. Results: Four of 6 BEST-MSU sites continued to enroll during COVID. There was no difference in intra- (n= 41) vs pre- (n= 763) COVID enrolled tPA eligible patients’ age, sex, race (45% vs 41% Black), ethnicity (23% vs 19% Hispanic), or NIHSS (12 vs 12). MSU alert frequency did not change, but percent of screened patients enrolled and treated with tPA declined to 12% from 23% (p Conclusion: Clinical research in the pre-hospital setting can be carried out accurately and safely during a pandemic. Study enrollment and tPA treatment rates declined, but otherwise there was no difference in patient demographics, deterioration of study processes, or serious infection of study staff.