Characterizing Blunt Cerebrovascular Injuries and Stroke: A Single Center Retrospective Study.

OBJECTIVE: To highlight the occurrence of ischemic stroke after blunt cerebrovascular injuries and discuss the neurologist's role in preventing and managing ischemic strokes in this trauma population. METHODS: A retrospective chart review was performed and included data from 2016 to 2019 from a Level I trauma center. Demographics, injury mechanism, ischemic stroke occurrence, interventions, and neurology consultations were examined and descriptive statistics were utilized to characterize the nature of ischemic strokes and their management. RESULTS: A total of forty patients (81% male, average age 44) presented with blunt cerebrovascular injury, nine of whom later developed ischemic stroke. Eighteen patients had a carotid artery injury with six developing ischemic stroke. Twenty-seven patients had a vertebral artery injury with three developing ischemic stroke. Six of the nine ischemic strokes occurred on hospital day two, whereas neurology was generally consulted on hospital day four. CONCLUSIONS: A considerable portion of patients may go on to develop ischemic stroke following blunt cerebrovascular injuries. Polytrauma may interfere with prompt diagnosis which may contribute to delayed anti-thrombotic therapy for ischemic stroke prevention. Neurologists have the opportunity to reduce ischemic stroke burden in this trauma population and patients may benefit from earlier neurology consultation.

The Association Between Stroke Mortality and Time of Admission and Participation in a Telestroke Network.

OBJECTIVES: Acute ischemic stroke is one of the leading causes of death. Patient outcomes, such as in-patient mortality, may be impacted by the time of arrival to the hospital. Telestroke networks have been found to be effective and safe at treating acute ischemic strokes. This paper investigated the association between mortality and time of arrival and hospital's participation in a telestroke network. METHODS: Data were collected on ischemic stroke patients who arrived at 15 nonteaching hospitals in Georgia's Paul Coverdell Acute stroke registry from 2009 to 2016. After controlling for patient and hospital characteristics, multivariate logistic regression was conducted to assess whether time of arrival and telestroke participation was associated with in-hospital mortality. Subgroup analysis was conducted based on hospital bed size. RESULTS: Overall, a total of 19,759 admissions for acute ischemic stroke were included in this analysis. The odds of dying in the hospital when arriving during the nighttime are 1.22 times the odds of dying when arriving during the day (95% CI: 1.04-1.45) and the odds of dying at a telestroke hospital are 53% lower than at a nontelestroke hospital (OR .47, 95% CI .31-.71). The associations were more prominent in large hospitals. CONCLUSIONS: Our study found that the hour of arrival for acute ischemic stroke is linked with in-hospital mortality in large hospitals, with patients more likely to die if they arrive during the nighttime hours as compared to the daytime hours. Telestroke participation is linked with lower odds of hospital mortality in all hospitals.

Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke Mimics Evaluated Over Telestroke Networks.

BACKGROUND AND PURPOSE: Up to 30% of acute stroke evaluations are deemed stroke mimics, and these are common in telestroke as well. We recently published a risk prediction score for use during telestroke encounters to differentiate stroke mimics from ischemic cerebrovascular disease derived and validated in the Partners TeleStroke Network. Using data from 3 distinct US and European telestroke networks, we sought to externally validate the TeleStroke Mimic (TM) score in a broader population. METHODS: We evaluated the TM score in 1930 telestroke consults from the University of Utah, Georgia Regents University, and the German TeleMedical Project for Integrative Stroke Care Network. We report the area under the curve in receiver-operating characteristic curve analysis with 95% confidence interval for our previously derived TM score in which lower TM scores correspond with a higher likelihood of being a stroke mimic. RESULTS: Based on final diagnosis at the end of the telestroke consultation, there were 630 of 1930 (32.6%) stroke mimics in the external validation cohort. All 6 variables included in the score were significantly different between patients with ischemic cerebrovascular disease versus stroke mimics. The TM score performed well (area under curve, 0.72; 95% confidence interval, 0.70-0.73; P<0.001), similar to our prior external validation in the Partners National Telestroke Network. CONCLUSIONS: The TM score's ability to predict the presence of a stroke mimic during telestroke consultation in these diverse cohorts was similar to its performance in our original cohort. Predictive decision-support tools like the TM score may help highlight key clinical differences between mimics and patients with stroke during complex, time-critical telestroke evaluations.

Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial.

BACKGROUND AND PURPOSE: Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage. METHODS: This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile. RESULTS: A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (Tmax) of 1 hour for oral minocycline, the Tmax was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients. CONCLUSIONS: In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01805895.

Telemedicine Quality and Outcomes in Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: Telestroke is one of the most frequently used and rapidly expanding applications of telemedicine, delivering much-needed stroke expertise to hospitals and patients. This document reviews the current status of telestroke and suggests measures for ongoing quality and outcome monitoring to improve performance and to enhance delivery of care. METHODS: A literature search was undertaken to examine the current status of telestroke and relevant quality indicators. The members of the writing committee contributed to the review of specific quality and outcome measures with specific suggestions for metrics in telestroke networks. The drafts were circulated and revised by all committee members, and suggestions were discussed for consensus. RESULTS: Models of telestroke and the role of telestroke in stroke systems of care are reviewed. A brief description of the science of quality monitoring and prior experience in quality measures for stroke is provided. Process measures, outcomes, tissue-type plasminogen activator use, patient and provider satisfaction, and telestroke technology are reviewed, and suggestions are provided for quality metrics. Additional topics include licensing, credentialing, training, and documentation.

Telestroke: variations in intravenous thrombolysis by spoke hospitals.

BACKGROUND: Telestroke extends stroke expertise to underserved hospitals and facilitates treatment with tissue plasminogen activator (tPA). We investigated the variability in tPA treatment rates across 2 large telestroke networks-consisting of hubs at Georgia Regents Medical Center (GRMC) and Medical University of South Carolina (MUSC) and their affiliated spoke hospitals-to identify spoke-related factors predictive of greater tPA use. METHODS: Observational study of tPA treatment rate at 32 spoke hospitals within the GRMC and MUSC telestroke networks. Spokes were characterized by primary stroke center status, local stroke nurse coordinator, local neurology support, hospital size, post-tPA management strategy, whether the spoke hospitals paid to participate in the network, and whether the hub or the spoke hospital initially proposed the telemedicine linkage for consultations with a remote stroke specialist. Primary outcome was tPA treatment rate adjusted for emergency department (ED) volume. RESULTS: There was substantial variation in the adjusted tPA rate across spokes (range, .85-8.74 administrations/10(4) ED visits/year). Only spokes with a stroke nurse coordinator (4.75/10(4) ED visits/year versus 2.84/10(4) ED visits/year, P = .03) were associated with higher tPA use. CONCLUSIONS: The application of telestroke has variable results on tPA delivery in spoke hospitals. However, the presence of a stroke nurse coordinator at the spoke facilitated treatment of ischemic stroke cases with tPA.

Timeliness of intravenous thrombolysis via telestroke in Georgia.

BACKGROUND AND PURPOSE: Through 2-way live video and audio communication, telestroke enhances urgent treatment of patients with acute stroke in emergency departments (EDs) without immediate access to on-site specialists. To assess for opportunities to shorten the door to thrombolysis time, we measured multiple time intervals in a telestroke system. METHODS: We retrospectively analyzed 115 records of consecutive acute stroke patients treated with intravenous thrombolysis during a 20-month period via a statewide telestroke system in 17 EDs in Georgia. On the basis of times documented in the telestroke system, we calculated the time elapsed between the following events: ED arrival, telestroke patient registration, start of specialist consultation, head computed tomography, thrombolysis recommendation, and thrombolysis initiation. RESULTS: The most conspicuous delay was from ED arrival to telestroke patient registration (median, 39 minutes; interquartile range, 21-56). Median time from ED arrival to thrombolysis initiation was 88 minutes, interquartile range 75 to 105. Thrombolysis was initiated within 60 minutes from ED arrival in 13% of patients. CONCLUSIONS: The greatest opportunity to expedite acute thrombolysis via telestroke is by shortening the time from ED arrival to telestroke patient registration.

Effects of pendant ligand binding affinity on chain transfer for 1-hexene polymerization catalyzed by single-site zirconium amine bis-phenolate complexes.

The kinetics of 1-hexene polymerization using a family of five zirconium amine bis-phenolate catalysts, Zr[tBu-ON(X)O]Bn2 (where X = THF (1), pyridine (2), NMe2 (3), furan (4), and SMe (5)), has been investigated to uncover the mechanistic effect of varying the pendant ligand X. A model-based approach using a diverse set of data including monomer consumption, evolution of molecular weight, and end-group analysis was employed to determine each of the reaction specific rate constants involved in a given polymerization process. The mechanism of polymerization for 1-5 was similar and the necessary elementary reaction steps included initiation, normal propagation, misinsertion, recovery from misinsertion, and chain transfer. The latter reaction, chain transfer, featured monomer independent ß-H elimination in 1-3 and monomer dependent ß-H transfer in 4 and 5. Of all the rate constants, those for chain transfer showed the most variation, spanning 2 orders of magnitude (ca. (0.1-10) × 10(-3) s(-1) for vinylidene and (0.5-87) × 10(-4) s(-1) for vinylene). A quantitative structure-activity relationship was uncovered between the logarithm of the chain transfer rate constants and the Zr-X bond distance for catalysts 1-3. However, this trend is broken once the Zr-X bond distance elongates further, as is the case for catalysts 4 and 5, which operate primarily through a different mechanistic pathway. These findings underscore the importance of comprehensive kinetic modeling using a diverse set of multiresponse data, enabling the determination of robust kinetic constants and reaction mechanisms of catalytic olefin polymerization as part of the development of structure-activity relationships.

Simplified modified Rankin Scale questionnaire correlates with stroke severity.

OBJECTIVE: To further validate the simplified modified Rankin Scale questionnaire (smRSq), we compare it here to a well-established predictor of functional outcome after stroke, the initial stroke severity. DESIGN: Retrospective correlation analysis. PARTICIPANTS: Forty patients identified from a registry of stroke patients treated with intravenous tissue plasminogen activator. SETTING: Community and 17 hospital Emergency Departments within a web-based telestroke network throughout the state of Georgia, USA. MEASURES: Five certified raters assessed the initial stroke severities with the National Institutes of Health Stroke Scale (NIHSS) via the telestroke system. Over a 20 month period, one certified rater, unaware of the NIHSS scores, attempted to contact each patient in the registry to assess their functional outcomes with the smRSq via telephone. We analyzed patients who had the smRSq assessment at least three months after stroke. RESULTS: Forty of 120 registered patients were contacted and qualified for this study. The baseline clinical characteristics of the 40 analyzed and the 80 disqualified patients were similar. The correlation between the initial NIHSS and the smRSq was good (r = 0.69, R(2) = 0.47, P < 0.001). CONCLUSIONS: The good correlation of the smRSq with the initial stroke severity further confirms the smRSq validity in assessing functional outcome after stroke.

Stroke size correlates with functional outcome on the simplified modified Rankin Scale questionnaire.

BACKGROUND: Acute stroke size is one of the factors impacting functional outcome. To further validate the simplified modified Rankin Scale questionnaire (smRSq), we tested its correlation with stroke size. METHODS: We screened 60 ischemic stroke patients with acute brain images available for stroke volume measurement who were enrolled in 2 smRSq reliability studies. Inclusion criteria were acute ischemic stroke visible on computed tomography (CT) or magnetic resonance imaging (MRI) and the smRSq scored at least 3 months after stroke. We excluded patients with disabilities from a previous stroke. One investigator who was blinded to the functional outcomes measured stroke volumes with a specialized computer program (Analyze). We used MRI when both MRI and CT were available. We classified strokes into 2 size categories: lacunar type measuring ≤ 6.28 cm(3), which corresponds to a cylinder with a maximum diameter and height of 2.00 cm, or strokes >6.28 cm(3). The Spearman correlation analysis compared the smRSq between the lacunar type and the larger strokes. RESULTS: Thirty-two patients qualified for this analysis with a mean age of 59 ± 15 years, and 17 (53%) were men. Lacunar stroke volumes (n = 17) ranged from 0.03 to 4.58 cm(3), and the larger stroke volumes (n = 15) ranged from 11.52 to 250.02 cm(3). Lacunar strokes were associated with lower smRSq scores (median 1) than the larger strokes (median 4; r = 0.68; R(2) = 0.46; P < .001). CONCLUSIONS: Acute stroke size correlates well with the smRSq, supporting its validity in assessing functional outcome after stroke.

Serendipitous recanalization of basilar artery occlusion.

OBJECTIVE: To describe a case of recanalization of a basilar artery occlusion with intravenous (IV) tenecteplase. CASE: A 74-year-old man with a history of cardiomyopathy presented to an outside hospital with acute vertigo, dysarthria, gaze deviation, and ataxia. Computerized tomography arteriography demonstrated occlusion of the proximal basilar artery. IV tissue plasminogen activator was ordered; however, the patient received a cardiac dose of IV tenecteplase. The patient was transferred to our facility, whereby symptoms resolved, and repeat computerized tomography arteriography displayed recanalization of the basilar artery. CONCLUSIONS: Tenecteplase has enhanced biochemical and pharmacokinetic properties that may be ideal for treatment of basilar artery occlusion and should be further investigated in a randomized clinical trial.

Impact of primary stroke center certification on location of acute ischemic stroke care in Georgia.

BACKGROUND AND PURPOSE: Primary stroke centers (PSCs) are associated with greater rates of tissue plasminogen activator use and improved outcomes. The American Stroke Association has advocated for the preferential transport of stroke patients to PSCs. We investigated the impact of PSC certification on hospital stroke discharge patterns in Georgia communities with a choice between PSC and non-PSC. METHODS: We analyzed data from the Georgia Discharge Data System before (2004) and after stroke certification (2009). Only Metropolitan Statistical Areas containing ≥1 PSC and ≥1 non-PSC were included in the analysis. We calculated the odds of acute stroke discharge from a PSC in 2009 compared with 2004. RESULTS: In Georgia Metropolitan Statistical Areas with at least 1 PSC and 1 non-PSC hospital, the percent of patients discharged from a subsequently designated PSC increased from 50.2% to 56.6% between 2004 and 2009 (OR, 1.29; P<0.0001). In 4 Metropolitan Statistical Areas, the proportion of stroke discharges from PSCs increased, whereas in 2 Metropolitan Statistical Areas, there was no significant increase, and in 1, there was a trend toward less stroke discharges from PSCs. CONCLUSIONS: Although there has been an overall increase in stroke discharges from PSCs, the impact of stroke certification on patient destination was small and inconsistent across the state suggesting that local factors influence the location of hospitalization.

Clinical experience with three-factor prothrombin complex concentrate to reverse warfarin anticoagulation in intracranial hemorrhage.

BACKGROUND AND PURPOSE: The effectiveness of prothrombin complex concentrate (PCC) products available in the United States that contain low levels of factor VII (3-factor PCC) has not been tested. The purpose of this study was to review our experience with 3-factor PCC (Profilnine) in the setting of warfarin-associated intracranial hemorrhage (wICH). METHODS: In November 2007, we implemented a protocol for reversal of anticoagulation in wICH using Profilnine. Additional treatment with fresh-frozen plasma was at the discretion of the treating physician. Medical records of all patients receiving PCC for wICH between November 1, 2007, and December 7, 2011 were reviewed. Correction of the international normalized rate (INR) was defined as an INR <1.4. RESULTS: Seventy wICH patients were treated with Profilnine, including 46 (66%) with intraparenchymal hemorrhage, 22 (31%) with subdural hemorrhage, and 2 (3%) with subarachnoid hemorrhage. Mean INR was reduced from 3.36 to 1.96, and in 44 (62.9%) patients the INR corrected to <1.4. Baseline INR ≥3.0 decreased the likelihood of INR correction. Concomitant administration of fresh-frozen plasma (mean, 2.6 U) did not increase the likelihood of INR correction. Seven (10%) patients had serious adverse events during their hospital course, including 2 sudden deaths from suspected pulmonary embolism. CONCLUSIONS: Reversal of coagulopathy in wICH with Profilnine was incomplete and associated with serious adverse events. In the absence of available 4-factor PCC, options for urgent reversal of anticoagulation in wICH remain limited.

Overcoming challenges to sustain a telestroke network.

Our objectives are to identify and help overcome obstacles to telestroke practice, to present tips for sustaining a telestroke network, to suggest strategies for obtaining buy-in from clinicians and administrative leadership and providers, and to identify and engage champions and stakeholders of telestroke.

Measured neurological improvements correlate with self-perceived improvements after stroke.

BACKGROUND: Important advantages of neurologic impairment scales after stroke include measurements of within-subject changes over time starting at baseline. We compared percent improvement on the National Institutes of Health stroke scale (NIHSS) to stroke outcome that seems tangible to patients and caregivers: their perceived percent improvement. METHODS: We prospectively measured improvement on the NIHSS between baseline and 3 to 6 months in consecutive patients with acute stroke presenting within 48 hours after onset. Unaware of the measured result, patients and caregivers were asked to estimate their perceived overall improvement since baseline assessment at the time of enrollment. We excluded patients with baseline NIHSS <3, clear improvement before screening, coma, brain herniation, or intraventricular hemorrhage. RESULTS: Of 40 enrolled patients, 9 died, 5 could not return for reevaluation, and the remaining 26 were reevaluated and analyzed. Median time from stroke onset to enrollment was 19.5 hours (range 2-45) and the median baseline NIHSS score was 8 (range 3-31). The measured improvements on the NIHSS ranged between 12.5% and 100% and correlated moderately (Spearman rank coefficient 0.54) and significantly (P = .005) with the patient- and caregiver-perceived percent improvement. CONCLUSIONS: Percent improvement on the NIHSS after stroke correlates moderately and significantly with patient and caregiver perceived overall improvement and appears to be a useful addition to the current functional outcome measures.

Wernicke's encephalopathy and cranial nerve VII palsy in a 24-year-old patient with COVID-19.

BACKGROUND: Many documented secondary neurologic manifestations are associated with COVID-19, including mild peripheral and central nervous system disorders (such as hypo/anosmia, hypo/ageusia, and cranial nerve VII palsy) and severe problems (such as ischemic stroke, Guillain-Barré syndrome, and encephalitis). The list is growing. A new addition is non-alcohol Wernicke's encephalopathy. CASE PRESENTATION: We present the case of a 24-year-old male with no past medical history who developed stroke-like symptoms two days after testing positive for COVID-19. MRI of his brain showed T2 FLAIR hyperintensity in the splenium of the corpus collosum, mamillary bodies, periaqueductal gray matter, tectum, and ventral and dorsal medulla, an MRI signal concerning for non-alcohol Wernicke's encephalopathy. Our patient had no risk factors for Wernicke's encephalopathy. He was admitted and started on thiamine for Wernicke's encephalopathy and steroids for his cranial VII nerve palsy. Both his symptoms and imaging improved. He was discharged on oral thiamine. Follow-up in the Neurology Clinic has confirmed his continued stable state. CONCLUSIONS: This case is one of three documented cases of Wernicke's encephalopathy believed to be caused by COVID-19 in patients without risk factors or chronic alcohol use. Ours is also the first case in which Wernicke's encephalopathy presents with a concomitant cranial nerve VII palsy. While Emergency Medicine doctors must maintain a high index of suspicion for stroke in younger patients with COVID-19, our patient's case augments the correlation between COVID-19 and Wernicke's encephalopathy in patients without other risk factors for developing the syndrome.

Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study in Georgia, USA.

Background: As the coronavirus disease 2019 (COVID-19) pandemic continues, there has been a growing interest in the chronic sequelae of COVID-19. Neuropsychiatric symptoms are observed in the acute phase of infection, but there is a need for accurate characterization of how these symptoms evolve over time. Additionally, African American populations have been disproportionately affected by the COVID-19 pandemic. The COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia (CONGA) was established to investigate the severity and chronicity of these neurologic findings over the five-year period following infection. Methods: The CONGA study aims to recruit COVID-19 positive adult patients in Georgia, United States from both the inpatient and outpatient setting, with 50% being African American. This paper reports our preliminary results from the baseline visits of the first 200 patients recruited who were on average 125 days since having a positive COVID-19 test. The demographics, self-reported symptoms, comorbidities, and quantitative measures of depression, anxiety, smell, taste, and cognition were analyzed. Cognitive measures were compared to demographically matched controls. Blood and mononuclear cells were drawn and stored for future analysis. Results: Fatigue was the most reported symptom in the study cohort (68.5%). Thirty percent of participants demonstrated hyposmia and 30% of participants demonstrated hypogeusia. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety. The study cohort performed worse on cognitive measures compared to demographically matched controls, and African American patients scored lower compared to non-Hispanic White patients on all quantitative cognitive testing. Conclusion: Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infection. Our results suggest that self-reported neurologic symptoms do not appear to correlate with associated quantitative dysfunction, emphasizing the importance of quantitative measurements in the complete assessment of deficits. Self-reported symptoms are associated with depression and anxiety. COVID-19 infection appears to be associated with worse performance on cognitive measures, though the disparity in score between African American patients and non-Hispanic White patients is likely largely due to psychosocial, physical health, and socioeconomic factors.

Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke.

BACKGROUND AND PURPOSE: Plasma matrix metalloproteinase-9 levels predict posttissue plasminogen activator (tPA) hemorrhage. METHODS: The authors investigated the effect of minocycline on plasma matrix metalloproteinase-9 in acute ischemic stroke in the Minocycline to Improve Neurological Outcome in Stroke (MINOS) trial and a comparison group. RESULTS: Matrix metalloproteinase-9 level decreased at 72 hours compared with baseline in MINOS (tPA, P=0.0022; non-tPA, P=0.0066) and was lower than in the non-MINOS comparison group at 24 hours (tPA, P<0.0001; non-tPA, P=0.0019). CONCLUSIONS: Lower plasma matrix metalloproteinase-9 was seen among tPA-treated subjects in the MINOS trial. Combining minocycline with tPA may prevent the adverse consequences of thrombolytic therapy through suppression of matrix metalloproteinase-9 activity.