Impact of Local Tailoring on Acute Stroke Care in 21 Disparate Emergency Departments: A Prospective Stepped Wedge Type III Hybrid Effectiveness-Implementation Study.

BACKGROUND: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system. METHODS: Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers. RESULTS: A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes. CONCLUSIONS: A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers.

Extended Window Thrombolytics for Ischemic Stroke: A Telestroke versus In-person Experience.

Background and Purpose: Telestroke evaluation of patients with acute ischemic stroke is supported by American Heart and Stroke Association Guidelines. However, there is no data on outcomes or safety of administering IV thrombolytic stroke therapy using extended window criteria (>4.5 h since onset of symptoms with a hyperacute MRI diffusion T2/FLAIR mismatch) via telestroke. Here, we report adverse events and outcomes of extended-window thrombolysis by telestroke vs in-person care. Methods: We performed a retrospective cohort review from 2020 to 2022 of prospectively collected multinstitutional databases from a large, not-for-profit health system with both in-person stroke and telestroke care. The primary outcome was frequency of symptomatic intracranial hemorrhage (sICH). Secondary outcomes were favorable functional outcome at hospital discharge (modified Rankin Scale, mRS, 0-3) and discharge disposition. Results: A total of 33 patients were treated with extended-window thrombolysis (n = 20 in-person, n = 13 telestroke). The median NIH stroke scale was 6, and time since last known normal was similar (median [95% CI]: in-person 13 h [11-15 h] vs telestroke 12 h [9-16 h], P = .33). The sICH frequency was low and occurred in one patient (4.8% in-person vs 0% by telestroke). Favorable outcome at discharge was not different between in-person and telestroke care (median mRS [95% CI]: 2 [1-3] vs 1 [0-2], OR .0 [.0-1.8], P = .27), and discharge deposition was also similar. Conclusions: In patients eligible for extended window acute stroke treatment with thrombolytics, there was no difference in adverse events between telestroke and in-person care.

Voltage-gated calcium channel autoimmune cerebellar degeneration: Case and study of cytotoxicity.

OBJECTIVES: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures. METHODS: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies. RESULTS: A 53-year-old man developed progressive incoordination with ataxic speech. Laboratory evaluation revealed VGCC autoantibodies without other antineuronal autoantibodies. Whole-body PET scans 6 and 12 months after presentation detected no malignancy. The patient improved significantly with IV immunoglobulin G (IgG), prednisone, and mycophenolate mofetil, but worsened after IV IgG was halted secondary to aseptic meningitis. He subsequently developed weakness with electrodiagnostic evidence of LEMS. The patient's IgG bound to Purkinje cells in rat cerebellar slice cultures, followed by neuronal death. Reactivity of the patient's autoantibodies with VGCCs was confirmed by blocking studies with defined VGCC antibodies. CONCLUSIONS: Autoimmune cerebellar degeneration associated with VGCC autoantibodies may precede onset of LEMS and may improve with immunosuppressive treatment. Binding of anti-VGCC antibodies to Purkinje cells in cerebellar slice cultures may be followed by cell death. Patients with anti-VGCC autoantibodies may be at risk of irreversible neurologic injury over time, and treatment should be initiated early.

Two children with both arm ischemia and arterial ischemic stroke during the perinatal period.

It is rare for both limb ischemia and arterial ischemic stroke to occur in the same child during the perinatal period. Two children who appear to have had perinatal emboli to both an arm and a middle cerebral artery territory are presented here. One child required amputation of the ischemic limb below the shoulder, and the other required skin grafts to the distal ischemic fingers. Each of these children later received cerebral magnetic resonance imaging for evaluation of developmental delay and was found to have what appeared to be old perinatal arterial ischemic stroke. Both children were homozygous for the methylenetetrahydrofolate reductase C677T gene variant. Eight other children with perinatal limb ischemia and stroke were found on literature review; several also had delayed diagnosis of perinatal stroke. This report examines the approach to diagnosis and treatment in each of these and makes suggestions for the similar cases in the future.

Chick embryonic Schwann cells migrate anodally in small electrical fields.

Little is known about the cues that guide migrating neural crest derivatives to their targets. This lack of understanding is especially significant in the case of Schwann cells, which have been transplanted into the central nervous system in an effort to promote axonal myelination after injury or disease. We have investigated the response of Schwann cells, cultured from the peripheral nerves of E7/8 chick embryos, to applied electrical fields. We find that they respond by migrating to the anode, and show a significant anodal bias in directionality at 3 mV mm(-1). This is the smallest electrical field that has been shown to affect cellular movement or growth in culture, and the anodal direction is surprising given the known cathodal responses of neural crest cells. The effective fields are considerably smaller than endogenous electrical fields that have been measured in embryonic tissues.