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.

Teleneurocritical care is associated with equivalent billable charges to in-person neurocritical care for patients with acute stroke.

INTRODUCTION: Teleneurocritical care (TNCC) provides virtual care for hospitals who do not have continuous neurointensivist coverage. It is not known if TNCC is cost effective nor which variables impact the total billed charges per patient encounter. We characterize cost, defined by charge characteristics of TNCC compared to in-person neurocritical care (NCC), for patients with acute ischemic or hemorrhagic stroke requiring ICU care. METHODS: We performed a retrospective review from 2018 to 2021 of prospectively collected multinstitutional databases from a large, integrated, not-for-profit health system with an in-person NCC and spoke TNCC sites. The primary outcome was the total billable charge per TNCC patient with acute ischemic or hemorrhagic stroke compared to in-person NCC. Secondary outcomes were functional outcome, transfer rate, and length of stay (LOS). RESULTS: A total of 1779 patients met inclusion criteria, 1062 at the hub in-person NCC hospital and 717 at spoke TNCC hospitals. Total billed patient charges of TNCC were similar to in-person NCC (median 104% of the cost per in-person NCC patient, 95% CI: 99%-108%). From 2018 to 2021, the charge difference between TNCC and NCC was not different (r2 = 0.71, p = 0.16). Both age and length stay were independently predictive of charges: for every year older the charge increased by US $6.3, and every day greater LOS the charge increased by $2084.3 (p < 0.001, both). TNCC transfer rates were low, and TNCC had shorter LOS and greater favorable functional outcome. DISCUSSION: TNCC was associated with similar patient financial charges as compared to in-person NCC. Standardization of care and the integrated hub-spoke value-focused operational procedures of TNCC may be applicable to other healthcare systems, however, further prospective study is needed.

Teleneurocritical Care for Patients with Large Vessel Occlusive Ischemic Stroke Treated by Thrombectomy.

BACKGROUND: Teleneurocritical care (TNCC) provides 24/7 virtual treatment of patients with neurological disease in the emergency department or intensive care unit. However, it is not known if TNCC is safe, effective, or associated with similar outcomes compared with in-person neurocritical care. We aim to determine the effect of daily inpatient consults from TNCC on the outcomes of patients with large vessel occlusive acute ischemic stroke treated by thrombectomy. METHODS: A multicenter, retrospective cohort of consecutive patients ≥ 18 years old with acute ischemic stroke from a large vessel occlusion treated by thrombectomy were identified from 2018 to 2021 within a telehealth network of an integrated not-for-profit health care system in the United States. The primary end point was good functional outcome, i.e., modified Rankin Scale 0-3, at the time of hospital discharge in patients receiving in-person neurocritical care versus TNCC. RESULTS: A total of 437 patients met inclusion criteria, 226 at the in-person hospital (median age 67, 53% women) and 211 at the two TNCC hospitals (median age 74, 49% women). The rate of successful endovascular therapy (modified Thrombolysis in Cerebral Infarction score 2b-3) was not different among hospitals. Good functional outcome at discharge was similar between in-person neurocritical care and TNCC (in-person 31.4% vs. TNCC 33.5%, odds ratio 0.88, 95% confidence interval 0.6-1.3; p = 0.64). Only National Institutes of Health stroke scale and age were multivariable predictors of outcome. There were no differences in mortality (9.3% vs. 13.2%, p = 0.19), intensive care unit length of stay (2.1 vs. 1.9 days, p = 0.39), or rate of symptomatic intracerebral hemorrhage (6.8% vs. 6.6%, p = 0.47) between in-person neurocritical care and TNCC. CONCLUSIONS: Teleneurocritical care allows for equivalent favorable functional outcomes compared with in-person neurocritical care for patients with acute large vessel ischemic stroke receiving thrombectomy. The standardized protocols used by TNCC in this study, specifically the comprehensive 24/7 treatment of patients in the intensive care unit for the length of their stay, may be relevant for other health systems with limited in-person resources; however, additional study is required.

Intravenous acetaminophen for postoperative supratentorial craniotomy pain: a prospective, randomized, double-blinded, placebo-controlled trial.

OBJECTIVE: Acute pain control after cranial surgery is challenging. Prior research has shown that patients experience inadequate pain control post-craniotomy. The use of oral medications is sometimes delayed because of postoperative nausea, and the use of narcotics can impair the evaluation of brain function and thus are used judiciously. Few nonnarcotic intravenous (IV) analgesics exist. The authors present the results of the first prospective study evaluating the use of IV acetaminophen in patients after elective craniotomy. METHODS: The authors conducted a randomized, double-blinded, placebo-controlled investigation. Adults undergoing elective, supratentorial craniotomies between September 2013 and June 2015 were randomized into two groups. The experimental group received 1000 mg/100 ml IV acetaminophen every 8 hours for 48 hours. The placebo group received 100 ml of 0.9% normal saline on the same schedule. Both groups were also treated with a standardized pain control algorithm. The study was powered to detect a 30% difference in the primary outcome measures: narcotic consumption (morphine equivalents, ME) at 24 and 48 hours after surgery. Patient-reported pain scores immediately postoperatively and 48 hours after surgery were also recorded. RESULTS: A total of 204 patients completed the trial. No significant differences were found in narcotic consumption between groups at either time point (in the treatment and placebo groups, respectively, at 24 hours: 84.3 ME [95% CI 70.2­98.4] and 85.5 ME [95% CI 73­97.9]; and at 48 hours: 123.5 ME [95% CI 102.9­144.2] and 134.2 ME [95% CI 112.1­156.3]). The difference in improvement in patient-reported pain scores between the treatment and placebo groups was significant (p < 0.001). CONCLUSIONS: Patients who received postoperative IV acetaminophen after craniotomy did not have significantly decreased narcotic consumption but did experience significantly lower pain scores after surgery. The drug was well tolerated and safe in this patient population.

Stroke Due to Cerebral Vasculitis in a Patient with Relentless Placoid Chorioretinitis.

PURPOSE: To report the first case of stroke in a patient with relentless placoid chorioretinitis. METHODS: Observational case report. RESULTS: A 20-year-old female with newly diagnosed relentless placoid chorioretinitis was urgently evaluated for unilateral paresthesias. She was found to have acute bilateral pontine strokes and cerebral vasculitis on magnetic resonance imaging of the brain and cerebral angiography. CONCLUSIONS: We report the first case of stroke due to cerebral vasculitis in a patient with relentless placoid chorioretinitis. This case emphasizes the need for timely evaluation of neurological symptoms in patients with this ocular diagnosis.

A pilot study of audiovisual family meetings in the intensive care unit.

PURPOSE: We hypothesized that virtual family meetings in the intensive care unit with conference calling or Skype videoconferencing would result in increased family member satisfaction and more efficient decision making. METHODS: This is a prospective, nonblinded, nonrandomized pilot study. A 6-question survey was completed by family members after family meetings, some of which used conference calling or Skype by choice. Overall, 29 (33%) of the completed surveys came from audiovisual family meetings vs 59 (67%) from control meetings. RESULTS: The survey data were analyzed using hierarchical linear modeling, which did not find any significant group differences between satisfaction with the audiovisual meetings vs controls. There was no association between the audiovisual intervention and withdrawal of care (P = .682) or overall hospital length of stay (z = 0.885, P = .376). CONCLUSIONS: Although we do not report benefit from an audiovisual intervention, these results are preliminary and heavily influenced by notable limitations to the study. Given that the intervention was feasible in this pilot study, audiovisual and social media intervention strategies warrant additional investigation given their unique ability to facilitate communication among family members in the intensive care unit.

The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae).

This study demonstrates that the polyketide toxin karlotoxin 2 (KmTx 2) produced by Karlodinium veneficum, a dinoflagellate associated with fish kills in temperate estuaries world-wide, alters vertebrate cell membrane permeability. Microfluorimetric and electrophysiological measurements were used to determine that vertebrate cellular toxicity occurs through non-selective permeabilization of plasma membranes, leading to osmotic cell lysis. Previous studies showed that KmTx 2 is lethal to fish at naturally-occurring concentrations measured during fish kills, while sub-lethal doses severely damage gill epithelia. This study provides a mechanistic explanation for the association between K. veneficum blooms and fish kills that has long been observed in temperate estuaries worldwide.

Therapeutic hypothermia for status epilepticus: A report, historical perspective, and review.

Refractory status epilepticus is a disease associated with high morbidity and mortality, which does not always respond to standard treatments, and when they fail, alternative modalities become crucial. Therapeutic hypothermia slows nerve conduction in vitro, and has been shown to abort seizures in animal models. Therapeutic hypothermia has been experimentally used in humans since 1963 for a variety of intracranial pathologies. More recently there have been multiple reports demonstrating the effectiveness of therapeutic hypothermia in treating refractory status epilepticus. We report a case of super-refractory status epilepticus successfully treated with therapeutic hypothermia, complimented by a historical and literature review of this modality. While there is limited evidence, and some risks associated with therapeutic hypothermia, it should be considered as a reasonable and potentially effective treatment option for refractory status epilepticus.

Splenic rupture associated with primary CMV infection, AMSAN, and IVIG.

Splenic rupture is a rare complication of primary cytomegalovirus infection, but has not been reported after administration of intravenous immunoglobulin or in the setting of the Guillain-Barré syndrome and its many variants, which often lead to treatment with intravenous immunoglobulin. There is strong evidence that intravenous immunoglobulin causes sequestration of erythrocytes in the spleen and extravascular hemolytic anemia. This may result in a two-hit scenario that clinicians should be aware of, where a patient who is at risk for splenic rupture due to primary cytomegalovirus infection receives intravenous immunoglobulin as treatment for the cytomegalovirus-associated Guillain-Barré syndrome, further increasing their risk of rupture.

Reproducibility of ABC/2 method to determine infarct volume and mismatch percentage with CT perfusion.

BACKGROUND: Our aim is to implement a simple, rapid, and reliable method using computed tomography perfusion imaging and clinical judgment to target patients for reperfusion therapy in the hyper-acute stroke setting. We introduce a novel formula (1-infarct volume [CBV]/penumbra volume [MTT] × 100%) to quantify mismatch percentage. METHODS: Twenty patients with anterior circulation strokes who underwent CT perfusion and received intravenous tissue plasminogen activator (IV tPA) were analyzed retrospectively. Nine blinded viewers determined volume of infarct and ischemic penumbra using the ABC/2 method and also the mismatch percentage. RESULTS: Interrater reliability using the volumetric formula (ABC/2) was very good (intraclass correlation [ICC] = .9440 and ICC = .8510) for hemodynamic parameters infarct (CBV) and penumbra (MTT). ICC coefficient using the mismatch formula (1-MTT/CBV × 100%) was good (ICC of .635). CONCLUSIONS: The ABC/2 method of volume estimation on CT perfusion is a reliable and efficient approach to determine infarct and penumbra volumes. The 1-CBV/MTT × 100% formula produces a mismatch percentage assisting providers in communicating the proportion of salvageable brain and guides therapy in the setting of patients with unclear time of onset with potentially salvageable tissue who can undergo mechanical retrieval or intraarterial thrombolytics.

Pathophysiology of acute coma and disorders of consciousness: considerations for diagnosis and management.

Disorders of consciousness are due to failure of the arousal system. In this review, the authors introduce the spectrum of disorders of consciousness and describe the structures, projections, and neurotransmitters involved in the generation and maintenance of arousal. Next, they discuss the neurologic diseases frequently associated with arousal failure. Evaluation of patients with disorders of arousal is summarized, including the neurologic exam, electrophysiological studies, biochemical testing, and imaging modalities. Finally, they review treatment options, including therapeutic hypothermia, medications, and deep brain and spinal cord stimulation.

Effective treatment of refractory intracranial hypertension after traumatic brain injury with repeated boluses of 14.6% hypertonic saline.

OBJECT: Normal intracranial pressure (ICP) and cerebral perfusion pressure (CPP) have been identified as favorable prognostic factors in the outcome of patients with traumatic brain injuries (TBIs). Osmotic diuretics and hypertonic saline (HTS) are commonly used to treat elevated ICP in patients with TBI; however, sustained effects of repeated high-concentration HTS boluses for severely refractory ICP elevation have not been studied. The authors' goal in this study was to determine whether repeated 14.6% HTS boluses were efficacious in treating severely refractory intracranial hypertension in patients with TBI. METHODS: In a prospective cohort study in a neurocritical care unit, adult TBI patients with sustained ICP > 30 mm Hg for more than 30 minutes after exhaustive medical and/or surgical therapy received repeated 15-minute boluses of 14.6% HTS over 12 hours through central venous access. RESULTS: Response to treatment was evaluated in 11 patients. Within 5 minutes of bolus administration, mean ICP decreased from 40 to 33 mm Hg (30% reduction, p < 0.05). Intracranial pressure-lowering effects were sustained for 12 hours (41% reduction, p < 0.05) with multiple boluses (mean number of boluses 7 ± 5.5). The mean CPP increased 22% and 32% from baseline at 15 and 30 minutes, respectively (p < 0.05). The mean serum sodium level (SNa) at baseline was 155 ± 7.1 mEq/L, and after multiple boluses of 14.6% HTS, S(Na) at 12 hours was 154 ± 7.1 mEq/L. The mean heart rate, systolic blood pressure, blood urea nitrogen, and creatinine demonstrated no significant change throughout the study. CONCLUSIONS: The subset of TBI patients with intracranial hypertension that is completely refractory to all other medical therapies can be treated effectively and safely with repeated boluses of 14.6% HTS rather than a one-time dose.

Medial premotor cortex shows a reduction in inhibitory markers and mediates recovery in a mouse model of focal stroke.

BACKGROUND AND PURPOSE: Motor recovery after ischemic stroke in primary motor cortex is thought to occur in part through training-enhanced reorganization in undamaged premotor areas, enabled by reductions in cortical inhibition. Here we used a mouse model of focal cortical stroke and a double-lesion approach to test the idea that a medial premotor area (medial agranular cortex [AGm]) reorganizes to mediate recovery of prehension, and that this reorganization is associated with a reduction in inhibitory interneuron markers. METHODS: C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke in the caudal forelimb area. The mice were then retrained and inhibitory interneuron immunofluorescence was assessed in prechosen, anatomically defined neocortical areas. Mice then underwent a second photocoagulation-induced stroke in AGm. RESULTS: Focal caudal forelimb area stroke led to a decrement in skilled prehension. Training-associated recovery of prehension was associated with a reduction in parvalbumin, calretinin, and calbindin expression in AGm. Subsequent infarction of AGm led to reinstatement of the original deficit. CONCLUSIONS: We conclude that with training, AGm can reorganize after a focal motor stroke and serve as a new control area for prehension. Reduced inhibition may represent a marker for reorganization or it is necessary for reorganization to occur. Our mouse model, with all of the attendant genetic benefits, may allow us to determine at the cellular and molecular levels how behavioral training and endogenous plasticity interact to mediate recovery.

Boomerang sign on MRI.

INTRODUCTION: Altered mental status and more subtle cognitive and personality changes after traumatic brain injury (TBI) are pervasive problems in patients who survive initial injury. MRI is not necessarily part of the diagnostic evaluation of these patients. METHODS: Case report with relevant image and review of the literature. RESULTS: Injury to the corpus callosum is commonly described in traumatic brain injury; however, extensive lesions in the splenium are not well described. This image shows an important pattern of brain injury and demonstrates a common clinical syndrome seen in patients with corpus callosum pathology. CONCLUSION: Injury to the splenium of the corpus callosum due to trauma may be extensive and can cause significant neurologic deficits. MRI is important in the diagnostic evaluation of patients with cognitive changes after TBI.

Sleep rounds: a multidisciplinary approach to optimize sleep quality and satisfaction in hospitalized patients.

BACKGROUND: Poor sleep has adverse affects on heath, yet few studies have addressed the goal of improving sleep among hospitalized patients. We evaluated the effectiveness of a sleep-promoting intervention on the quality and quantity of sleep among inpatients. METHODS: This study was conducted on a neurological ward in a large, tertiary care hospital. Sleep quality, quantity, and disruptors were assessed using questionnaires completed by patients during their hospital stay and Press Ganey surveys completed retrospectively. Room noise was also measured using noise meters. Data from each of 4 chronological phases of the study (baseline, basic intervention, "washout," and deluxe intervention) were analyzed. In the intervention phases, nurses conducted "Sleep Rounds" at bedtime, during which sleep-promoting practices were implemented, including lights out, television off, temperature adjustment, and a final restroom usage. RESULTS: Patients reported 5 (interquartile range [IQR] 3) hours of sleep per night, awoke 3 (IQR 3) times nightly, and reported a median sleep latency of 11 to 15 minutes. Pain, staff interruptions, and roommates were the most significant barriers to good sleep. Noise levels were adequately low (35-40 dB) at night but were not positively impacted by our sleep-promoting interventions. Patients perceived noise on the unit to be worse during phases of the study in which there was no intervention. CONCLUSIONS: Patient perception of sleep experience improved during the phases in which Sleep Rounds were implemented, despite the fact that there was no measurable improvement in sleep or sleep-disrupting factors.

Repetitive use of intra-arterial verapamil in the treatment of reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) typically presents with recurrent thunderclap headaches and neurological deficits that are usually self-limiting. The intra-arterial (IA) use of vasodilators for RCVS has been reported for severe cases. Patients with RCVS have the potential for serious and permanent neurological deficits. It is a rare disorder, with a recent surge in the number of reports, and probably continues to be under-diagnosed. We report two patients with RCVS with severe neurological sequelae, treated in a large tertiary hospital. Both patients received high-dose cortico steroids due to the possibility of angiitis of the central nervous system, but they deteriorated neurologically, which suggests that steroids may have a deleterious effect in RCVS. Treatment with IA verapamil resulted in reversal of vasoconstriction, but multiple treatments were necessary. Therefore, IA administration of verapamil is a possible treatment for severe RCVS, but there is only limited sustained improvement in vasodilation that may require repetitive treatments with a currently undetermined optimal treatment interval.

Acute lung injury in critical neurological illness.

OBJECTIVE: Acute lung injury and acute respiratory distress syndrome have been reported in a significant proportion of patients with critical neurologic illness. Our aim was to identify risk factors for acute lung injury/acute respiratory distress syndrome in this population. DESIGN: Prospective, observational study. SETTING: A 22-bed, adult neurosciences critical care unit at a tertiary care hospital. PATIENTS: Primary neurologic disorder, mechanical ventilation >48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 192 patients were enrolled with a range of neurologic disorders. Among these, 68 (35%) were diagnosed with acute lung injury/acute respiratory distress syndrome. In a multivariate logistic regression analysis, independent risk factors for acute lung injury/acute respiratory distress syndrome were pneumonia (odds ratio [95% confidence interval] 3.12 [1.5-6.0], p = .002), circulatory shock (2.2 [1.07-4.57], p = .03), and absence of a gag or cough reflex (3.41 [1.34-8.68], p = .01). Neither neurologic diagnosis nor neurologic severity, assessed with the Glasgow Coma Scale, was significantly associated with the development of acute lung injury/acute respiratory distress syndrome. CONCLUSION: Acute lung injury/acute respiratory distress syndrome occurred in more than one third of mechanically ventilated neurosciences critical care unit patients. Loss of the cough or gag reflex is strongly predictive of acute lung injury/acute respiratory distress syndrome, while neurologic diagnosis and Glasgow Coma Scale are not. Lower brainstem dysfunction, a clinical marker of neurologic injury not captured by the Glasgow Coma Scale, is a risk factor for acute lung injury/acute respiratory distress syndrome and could inform decisions regarding airway protection and mechanical ventilation.

Post-cardiac arrest encephalopathy.

Brain injury continues to be a leading cause of mortality and morbidity in patients resuscitated after cardiac arrest. During periods of hypoxia and ischemia, numerous mechanisms contribute to the initial and secondary injury of the brain. Though many drugs and therapies have been evaluated for neuroprotection, only therapeutic hypothermia has been proven to be effective. Accurate prognostication after cardiac arrest is essential, and can be achieved with careful neurologic examination and several ancillary tests utilizing neurophysiology, neuroimaging, and biochemistry. Practice guidelines are now available for prognostication and postresuscitation care, with emphasis on improving survival and quality of life. Also reviewed are a wide spectrum of postarrest neurologic complications and their targeted treatments.

A case of postpartum cerebral angiopathy with subarachnoid hemorrhage.

BACKGROUND: A 33-year-old woman experienced a thunderclap headache immediately postpartum. The headache recurred over the next 10 days, and the patient also developed generalized tonic-clonic seizures. A subarachnoid hemorrhage was demonstrated on a head CT scan. INVESTIGATIONS: Physical examination, laboratory tests, brain CT scan, brain MRI scan, brain magnetic resonance angiogram, brain magnetic resonance venogram, cerebral angiography, transcranial Doppler ultrasound, EEG. DIAGNOSIS: Postpartum cerebral angiopathy. MANAGEMENT: NSAIds and opioid analgesics administered on postpartum day 3 provided partial headache relief. The next day, a blood patch was performed and intravenous caffeine, fluid and opioid analgesia were given to treat a suspected dural puncture headache. Following diagnosis of postpartum cerebral angiopathy on postpartum day 10, nimodipine was initiated to treat the vasospasm, and the headache was treated with opioid analgesics and toradol, followed by naproxen. The patient also received a 3-day course of intravenous magnesium sulfate.

Coma after global ischemic brain injury: pathophysiology and emerging therapies.

Cardiac arrest is a major cause of death and morbidity in the United States, and neurological injury contributes significantly to this. Neurological complications associated with global cerebral ischemia include disorders of responsiveness, such as coma and the vegetative state, seizures, motor deficits, and brain death. Coma, complete unresponsiveness, is the most pervasive of these. Therapies that improve neurological outcomes in general after cardiac arrest and therapies that stimulate arousal from coma could have enormous clinical impact. The authors review the physiology of arousal and describe the biochemical and pathophysiological derangements that develop after global cerebral ischemia. We then describe the potential therapeutic mechanisms of hypothermia and deep brain stimulation, which provide hope for better neurological outcomes after global cerebral ischemia.