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.

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.

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.

Preventive antibiotic therapy in acute stroke patients: A systematic review and meta-analysis of individual patient data of randomized controlled trials.

Introduction: Infection after stroke is associated with unfavorable outcome. Randomized controlled studies did not show benefit of preventive antibiotics in stroke but lacked power for subgroup analyses. Aim of this study is to assess whether preventive antibiotic therapy after stroke improves functional outcome for specific patient groups in an individual patient data meta-analysis. Patients and methods: We searched MEDLINE (1946-7 May 2021), Embase (1947-7 May 2021), CENTRAL (17th September 2021), trial registries, cross-checked references and contacted researchers for randomized controlled trials of preventive antibiotic therapy versus placebo or standard care in ischemic or hemorrhagic stroke patients. Meta-analysis was performed by a one-step and two-step approach. Primary outcome was functional outcome adjusted for age and stroke severity. Secondary outcomes were infections and mortality. Results: 4197 patients from nine trials were included. Preventive antibiotic therapy was not associated with a shift in functional outcome (mRS) at 3 months (OR1.13, 95%CI 0.98-1.31) or unfavorable functional outcome (mRS 3-6) (OR0.85, 95%CI 0.60-1.19). Preventive antibiotics did not improve functional outcome in pre-defined subgroups (age, stroke severity, timing and type of antibiotic therapy, pneumonia prediction scores, dysphagia, type of stroke, and type of trial). Preventive antibiotics reduced infections (276/2066 (13.4%) in the preventive antibiotic group vs. 417/2059 (20.3%) in the control group, OR 0.60, 95% CI 0.51-0.71, p < 0.001), but not pneumonia (191/2066 (9.2%) in the preventive antibiotic group vs. 205/2061 (9.9%) in the control group (OR 0.92 (0.75-1.14), p = 0.450). Discussion and conclusion: Preventive antibiotic therapy did not benefit any subgroup of patients with acute stroke and currently cannot be recommended.

Concomitant central venous sinus thrombosis and subdural hematoma in acute promyelocytic leukemia: middle meningeal artery embolization enables safe anticoagulation. Illustrative case.

BACKGROUND: Acute promyelocytic leukemia (APL) has long been associated with coagulation disorders. The proposed mechanism is a combination of fibrinolysis, proteolysis, platelet dysfunction, thrombocytopenia, and possibly disseminated intravascular coagulation. Hemorrhagic complications are prominent. OBSERVATIONS: In this case, a 25-year-old female with newly diagnosed APL developed extensive cerebral venous thrombosis (CVT) and was initiated on a protocol with idarubicin and all-trans retinoic acid. The general recommendation for treating CVT is anticoagulation to stabilize the existing thrombus and prevent propagation. The patient was initiated on a heparin drip, but her clinical course was complicated by subdural hemorrhage (SDH) and epidural hemorrhage in the setting of thrombocytopenia. Anticoagulation was held, and her CVT propagated on follow-up imaging. To restart anticoagulation for CVT with a limited risk of SDH, the authors pursued middle meningeal artery (MMA) embolization. The patient was transitioned to apixaban and discharged to home. LESSONS: MMA embolization enables safe anticoagulation in patients with concomitant CVT and SDH. The authors report the complex clinical course and effective management of this rare clinical scenario.

Outcomes of interfacility helicopter transportation in acute stroke care.

OBJECTIVE: To evaluate the long-term functional outcome of interhospital transfer of patients with stroke with suspected large vessel occlusion (LVO) using Helicopter Emergency Medical Services (HEMS). METHODS: Records of consecutive patients evaluated through 2 telestroke networks and transferred to thrombectomy-capable stroke centers between March 2017 and March 2018 were reviewed. Inverse probability of treatment weighting (IPTW) using the propensity score was performed to address confounding factors. Multivariate logistic regression analysis with IPTW was used to determine whether HEMS were associated with good long-term functional outcome (modified Rankin scale score ≤ 2). RESULTS: A total of 199 patients were included; median age was 67 years (interquartile range [IQR] 55-79 years), 90 (45.2%) were female, 120 (60.3%) were white, and 100 (50.3%) were transferred by HEMS. No significant differences between the 2 groups were found in mean age, sex, race, IV tissue plasminogen activator (tPA) receipt, and thrombectomy receipt. The median baseline NIH Stroke Scale score was 14 (IQR 9-18) in the helicopter group vs 11 (IQR 6-18) for patients transferred by ground (p = 0.039). The median transportation time was 60 minutes (IQR 49-70 minutes) by HEMS and 84 minutes (IQR 25-102 minutes) by ground (p < 0.001). After weighting baseline characteristics, the use of HEMS was associated with higher odds of good long-term outcome (OR 4.738, 95% CI 2.15-10.444, p < 0.001) controlling for transportation time, door-in-door-out time, and thrombectomy and tPA receipt. The magnitude of the HEMS effect was larger in thrombectomy patients who had successful recanalization (OR 1.758, 95% CI 1.178-2.512, p = 0.027). CONCLUSIONS: HEMS use was associated with better long-term functional outcome in patients with suspected LVO, independently of transportation time.

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.

Door in door out and transportation times in 2 telestroke networks.

BACKGROUND: Inter-hospital transfer is important in the treatment of acute stroke. We sought to assess door in to door out (DIDO) time at spoke sites, and transportation time between spoke sites and thrombectomy-capable stroke center (TSC) in 2 large, rural telestroke networks. METHODS: Records of patients treated with tissue plasminogen activator through 2 telestroke networks between March 2017 and December 2017 were reviewed. Mann-Whitney test was used to compare median times, and a generalized linear regression model was used to predict the total time of care controlling for transportation distance. RESULTS: Eighty-five patients were included with median NIH stroke scale on presentation of 13 (interquartile range [IQR] 7-17), median door to needle time 49 minutes (IQR 40-62), and median DIDO 111 minutes (IQR 92-157). Eighteen patients (21%) underwent computed tomography angiography (CTA) at spoke prior to transportation. Median DIDO was 169 minutes for patients who received CTA before transfer, compared with 107 minutes for patients who did not (p = 0.0004). Median door-to-groin time at TSC was 68 minutes for the CTA group and 85 minutes in the non-CTA group (p = 0.832). Controlling for distance, the predicted time of care from spoke door in time to groin puncture at TSC (sDTG) is 93.68 minutes longer for patients who receive CTA prior to transport (p = 0.034). CONCLUSION: In the included telestroke networks, the sDTG time is longer when CTA is conducted at spoke site prior to transportation to TSC. New strategies are urgently needed to decrease sDTG when CTA is done prior to transfer to TSC.

Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke. METHODS: Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models. RESULTS: We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0-2) (RR = 1.31; 95% CI 0.98-1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI - 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0-2 (RR = 1.59; 95% CI 1.19-2.12, p = 0.002; I2 = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3-month NIHSS (MD - 2.84; 95% CI - 5.55, - 0.13; p = 0.04; I2 = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion. CONCLUSIONS: Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.

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.

Expansion Of Telestroke Services Improves Quality Of Care Provided In Super Rural Areas.

Telestroke is a telemedicine intervention that facilitates communication between stroke centers and lower-resourced facilities to optimize acute stroke management. Using administrative claims data, we assessed trends in telestroke use among fee-for-service Medicare beneficiaries with acute ischemic stroke and the association between providing telestroke services and intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy use, mortality, and medical expenditures, by urban versus rural county of residence in the period 2008-15. The proportion of ischemic stroke cases receiving telestroke increased from 0.4 to 3.8 per 1,000 cases, with usage highest among younger, male, non-Hispanic white, and patients in rural or super rural areas (super rural is the bottom quartile of rural areas. Compared with patients receiving usual care, those receiving telestroke had greater IV tPA and mechanical thrombectomy use regardless of county type, while those in super rural counties had lower thirty-day all-cause mortality. Despite increased telestroke use, rural patients remained less likely than urban patients to receive IV tPA. The findings suggest that telestroke service expansion efforts have increased, especially in rural and super rural counties, and have improved outcomes.

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.

IgG4-related leptomeningitis: a reversible cause of rapidly progressive cognitive decline.

Immunoglobulin G4-related diseases (IgG4-RD) are a newly recognized category of diseases. CNS involvement in IgG4-RD includes hypophysitis(1) and intracranial or spinal manifestations of hypertrophic pachymeningitis.(2,3) We present a unique case of rapid cognitive decline due to IgG4-related leptomeningitis.

A double-blind placebo-controlled clinical evaluation of MultiStem for the treatment of ischemic stroke.

BACKGROUND: There is growing interest in neurorestorative and reparative therapies after acute stroke. MultiStem is an allogeneic cell therapy treatment comprising a population of multipotent adherent bone marrow cells that has shown safety in clinical trials of myocardial infarction and graft vs. host disease, as well as preclinical evidence of activity in stroke and other neurological damage models. MultiStem is now being evaluated in a clinical trial in patients that have suffered an ischemic stroke, in which the product is administered intravenously 24-36 h after the ischemic event. METHODS: The Phase 2 randomized, double-blind, placebo-controlled, multicenter dose-escalation trial will consist of three treatment cohorts, including a placebo group, and two treatment groups involving dose tiers of either 400 million or 1200 million cells per patient. Patients will be treated at 24-36 h after stroke. The two primary objectives are to determine the highest well-tolerated and safe single dose of MultiStem up to a maximum of 1200 million total cells in subjects with ischemic stroke and to determine the efficacy of MultiStem on functional outcome in subjects with stroke as measured by the modified Rankin Scale at 90 days. Patients will also be evaluated using the National Institutes of Health Stroke Scale and Barthel Index. The study will explore other aspects including, uniquely, the measurement of spleen size after stroke by magnetic resonance imaging or computed tomography imaging. CONCLUSIONS AND FUTURE DIRECTION: If MultiStem is safe and there is a signal of efficacy, a late stage phase IIb-III trial is planned.