Diagnostic accuracy of telestroke consultation: a Louisiana based tele-network experience.

Background and purpose: Telestroke has grown significantly since its implementation. Despite growing utilization, there is a paucity of data regarding the diagnostic accuracy of telestroke to distinguish between stroke and its mimics. We aimed to evaluate diagnostic accuracy of telestroke consultations and explore the characteristics of misdiagnosed patients with a focus on stroke mimics. Methods: We conducted a retrospective study of all the consultations in our Ochsner Health's TeleStroke program seen between April 2015 and April 2016. Consultations were classified into one of three diagnostic categories: stroke/transient ischemic attack, mimic, and uncertain. Initial telestroke diagnosis was compared with the final diagnosis post review of all emergency department and hospital data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for diagnosis of stroke/TIA versus mimic were calculated. Area under receiver-operating characteristic curve (AUC) analysis to predict true stroke was performed. Bivariate analysis based on the diagnostic categories examined association with sex, age, NIHSS, stroke risk factors, tPA given, bleeding after tPA, symptom onset to last known normal, symptom onset to consult, timing in the day, and consult duration. Logistic regression was performed as indicated by bivariate analysis. Results: Eight hundred and seventy-four telestroke evaluations were included in our analysis. Accurate diagnosis through teleneurological consultation was seen in 85% of which 532 were strokes (true positives) and 170 were mimics (true negatives). Sensitivity, specificity, PPV, NPV were 97.8, 82.5, 93.7 and 93.4%, respectively. LR+ and LR- were 5.6 and 0.03. AUC (95% CI) was 0.9016 (0.8749-0.9283). Stroke mimics were more common with younger age and female gender and in those with less vascular risk factors. LR revealed OR (95% CI) of misdiagnosis for female gender of 1.9 (1.3-2.9). Lower age and lower NIHSS score were other predictors of misdiagnosis. Conclusion: We report high diagnostic accuracy of the Ochsner Telestroke Program in discriminating stroke/TIA and stroke mimics, with slight tendency towards over diagnosis of stroke. Female gender, younger age and lower NIHSS score were associated with misdiagnosis.

Noninvasive neuromonitoring with rheoencephalography: a case report.

Cerebral blood flow (CBF) autoregulation (AR) can be monitored using invasive modalities, such as intracranial pressure (ICP) and arterial blood pressure (ABP) to calculate the CBF AR index (PRx). Monitoring PRx can reduce the extent of secondary brain damage in patients. Rheoencephalography (REG) is an FDA-approved non-invasive method to measure CBF. REGx, a CBF AR index, is calculated from REG and arm bioimpedance pulse waves. Our goal was to test REG for neuromonitoring. 28 measurement sessions were performed on 13 neurocritical care patients. REG/arm bioimpedance waveforms were recorded on a laptop using a bioimpedance amplifier and custom-built software. The same program was used for offline data processing. Case #1: The patient's mean REGx increased from - 0.08 on the first day to 0.44 on the second day, indicating worsening intracranial compliance (ICC) (P < 0.0001, CI 0.46-0.58). Glasgow Coma Scale (GCS) was 5 on both days. Case #2: REGx decreased from 0.32 on the first recording to 0.07 on the last (P = 0.0003, CI - 0.38 to - 0.12). GCS was 7 and 14, respectively. Case #3: Within a 36-minute recording, REGx decreased from 0.56 to - 0.37 (P < 0.0001, 95%, CI - 1.10 to - 0.76). Central venous pressure changed from 14 to 9 mmHg. REG pulse wave morphology changed from poor ICC to good ICC morphology. Bioimpedance recording made it possible to quantify the active/passive status of CBF AR, indicate the worsening of ICC, and present it in real time. REGx can be a suitable, non-invasive alternative to PRx for use in head-injured patients.

Bilateral Cerebral Mucormycosis in an Immunocompetent Female.

Background: Mucormycosis is a serious angioinvasive fungal infection. Immunocompromised patients are more likely to be susceptible to mucormycosis than immunocompetent individuals. Cerebral mucormycosis has been reported, but cases have primarily been unilateral. We report a case of bilateral cerebral mucormycosis in an immunocompetent patient. Case Report: A 37-year-old female with no significant medical history was transferred to our tertiary center after cerebrospinal fluid profile following a lumbar puncture at an outside hospital suggested bacterial meningitis. Computed tomography of the head revealed hypodensity and cerebral edema in the left basal ganglia, and magnetic resonance imaging (MRI) brain showed increased T2 signal and mass-like configuration centered in the left basal ganglia. During her hospital stay, she had neurologic decompensation with respiratory failure. She was intubated and placed on mechanical ventilation. Repeat MRI brain revealed evolving cerebral edema signal and interval development of progression across the midline involving the right basal ganglia. Because of the aggressive nature of the lesion and cerebral edema, she underwent a biopsy with placement of an external ventricular drain. Despite medical and surgical interventions, she neurologically worsened and died. Histopathologic evaluation of the biopsied lesion revealed numerous fungal hyphae consistent with mucormycosis. Conclusion: Our patient was not immunocompromised, and this case highlights the clinical challenges in initiating immunosuppressive therapy in a patient with rapidly progressive central nervous system disease.

Neuroprotectin D1, a lipid anti-inflammatory mediator, in patients with intracerebral hemorrhage.

Little is known of the lipid anti-inflammatory mediators, docosanoids, in intracerebral hemorrhage (ICH). We aim to characterize the abundance of the docosanoid, Neuroprotectin D1 (NPD1), in ICH patients. Blood samples (whole blood in PAXgene-blood-RNA tubes and plasma) were collected from consecutive patients with acute spontaneous ICH within 48 h of admission. A liquid-liquid lipid extraction was used for liquid chromatography-mass spectrometry (LC-MS/MS) and analyzed using MassLynx Mass Spectrometry Software with results normalized to internal standards. RNA was extracted from PAXgene-blood-RNA tubes for 15-LOX-1 gene expression, a critical enzyme in NPD1 synthesis. Demographic and clinical data were collected. Outcome measures included 90-day modified-rankin-score. Sixteen patients were included in the study with a mean age of 62.5years (SD13.5). Three abundant isomers were detected and analyzed - NPD1, PDX, and an uncharacterized isomer designated as NPD1-C. NPD1 levels were higher in patients with 90-day MRS 0-3 (49.63pg/mL SD43.78 vs. 1.88pg/mL SD1.7 p = 0.0012). ROC-AUC analysis showed an NPD1 cutoff of 2.9pg/mL differentiated 90-day MRS 0-3 (sensitivity 100%, specificity 88.89%, AUC 0.98 p = 0.0002). A Spearman correlation demonstrated an inverse relationship with NPD1 and 90-day MRS (rho -7.392 p = 0.0011). 15-LOX-1 gene was almost undetectable in patients with MRS 4-6. Though not significant, NPD1 levels were higher in patients <65 years, ICH volume <30 ml, and non-whites. NPD1 was abundant and significantly higher in ICH patients with MRS 0-3.15-LOX-1 was significantly under-expressed in patients with MRS 4-6. Early synthesis and abundance of NPD1 is likely an important protective mediator in ICH pathophysiology.

Anti-inflammatory genes in PBMCs post-spontaneous intracerebral hemorrhage.

BACKGROUND: Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome. METHODOLOGY: Blood samples from ICH patients (n = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH. Data on hospital length of stay and modified Rankin score (MRS) were collected with 90-day MRS ≤ 3 as favorable outcome. Statistical analysis of clinical characteristics to temporal gene expression from early to delayed timepoints was compared for MRS groups (favorable vs unfavorable) and hematoma volume. PRINCIPLE FINDINGS AND RESULTS: IL10, SOD1, and REL expression were significantly higher at delayed timepoints in PBMCs of ICH patients with favorable outcome. PPARG and REL increased between timepoints in patients with favorable outcome. NFKB1 expression was not sustained, but significantly decreased from higher levels at early onset in patients with unfavorable outcome. IL10 expression showed a negative correlation in patients with high hematoma volume (>30 mL). CONCLUSIONS AND SIGNIFICANCE: Anti-inflammatory, pro-survival regulators were highly expressed at delayed time points in ICH patients with a favorable outcome, and IL10 expression showed a negative correlation to high hematoma volume.

Sustained Low-Efficiency Dialysis is Associated with Worsening Cerebral Edema and Outcomes in Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVES: We postulated that renal replacement therapy (RRT) in ICH patients with advanced chronic kidney disease (CKD) is associated with increased frequency and size of perihematomal edema (PHE) expansion and worse patient outcomes. METHODS: The Get With the Guidelines-Stroke Registry was queried for all patients admitted with ICH (N = 1089). Secondary causes, brainstem ICH, and initial HV < 7 cc were excluded. We identified patients with advanced CKD with and without RRT following admission for ICH. ABC/2 formula was used to measure hematoma volume (HV) and PHE. Patient outcomes were 30-day mortality, 90-day modified Rankin Scale score, and discharge disposition. We used propensity scores and optimal matching to adjust for multiple covariates. RESULTS: At 48 h post-ICH, PHE expansion was a significant predictor of poor patient outcomes in our cohort. Patients with CKD who received sustained low-efficacy dialysis (SLED) treatment had larger 48 h PHE growth compared to both untreated CKD group (average treatment effect (ATE), 11.5; 95% CI, 4.9-18.1; p < 0.01) and all untreated patients (ATE, 7.43; 95% CI, 4.7-10.2; p < 0.01). Moreover, patients with RRT had significantly worse functional and mortality outcomes. CONCLUSIONS: SLED treatment in ICH patients with CKD was associated with significant increase in rate and frequency of PHE expansion. Absolute increase in PHE during 48-h post-ICH was associated with increased mortality and worse functional outcomes. Further prospective and multicenter evaluation is needed to differentiate the effects of RRT on hematoma dynamics and patient outcomes from those attributed to CKD.

Secondary hypothermia in patients with super-refractory status epilepticus managed with propofol and ketamine.

BACKGROUND: Therapeutic hypothermia as a potent nonpharmacologic antiseizure therapy has been investigated experimentally in animal models and humans. Although induced hypothermia has been shown to be neuroprotective in acute convulsive status epilepticus, whether its use will translate into improved outcomes for patients with super-refractory nonconvulsive status epilepticus (SRNCSE) has been debated. No clinical data are available on the occurrence and prognostic impact of secondary hypothermia (s-HT) in patients with SRNCSE. With the possibility of core to periphery redistribution of heat with propofol and a centrally mediated dose-dependent fall in body temperature with ketamine, we aimed to investigate the incidence of s-HT events in patients with SRNCSE managed with propofol and ketamine and their impact on clinical outcomes. METHODS: We performed a retrospective observational analysis of consecutive patients with SRNCSE managed with propofol and/or ketamine in a single-center neurological intensive care unit between December 1, 2012 and December 31, 2015. Patients were divided according to the occurrence of hypothermia (temperature < 35.0 °C) into an s-HT group and a nonhypothermia (n-HT) group. Patients who received targeted temperature management therapy were excluded. We compared the demographics, comorbidities, treatment characteristics, and outcomes between groups. RESULTS: Ninety-nine consecutive patients with SRNCSE managed with propofol and/or ketamine were identified during the study period. Twenty patients who received targeted temperature management were excluded, leaving a total of 79 patients for analysis. Hypothermia was observed in 52% (41/79) of the study population. Ketamine was used in 63/79 patients (80%). Ketamine infusion rates were higher and of longer duration among patients who developed s-HT compared with those who did not (mean dosage: 57.35 ±â€¯26.6 mcg/kg/min vs 37.17 ±â€¯15 mcg/kg/min, P = 0.001; duration: 116.36 ±â€¯81.9 h vs 88 ±â€¯89.7 h, P = 0.048). Propofol was used in 78/79 patients (99%), with no significant differences in characteristics between groups (mean dosage: 46.44 ±â€¯20.2 mcg/kg/min vs 36.9 ±â€¯12.9 mcg/kg/min, P = 0.058; duration: 125.43 ±â€¯96.4 h vs 102.3 ±â€¯87.1 h, P = 0.215). No significant differences in demographics, comorbidities, status epilepticus duration and resolution rates, and outcomes were observed between groups. CONCLUSION: In this single-center retrospective analysis of patients whose SRNCSE is being treated, higher doses and longer durations of ketamine were associated with the occurrence of s-HT. Further investigation is warranted to clarify the thermogenic effects of ketamine and its effect on status epilepticus outcomes.

MicroRNA Regulatory Network as Biomarkers of Late Seizure in Patients with Spontaneous Intracerebral Hemorrhage.

Approximately 15% of patients experience seizures after spontaneous intracerebral hemorrhage (ICH). The pathogenesis of seizures post-ICH is not well-known; however, iron deposition-related neuronal injury following hemoglobin breakdown may contribute. Profiling known miRNAs to identify biomarkers for post-ICH late seizures, we found 64 differentially expressed miRNA: 32 upregulated and 32 downregulated in seizure vs. non-seizure. Functional classification of upregulated miRNA for KEGG pathways and biological processes identified enrichment for cell cycle, protein modifications, and FoxO neurotrophin signaling pathways. No significant enrichment was found for downregulated miRNA. Molecular functions Gene Ontology (GO) terms enriched for upregulated miRNA are numerous, while downregulated miRNAs were associated with ion channel activity. RT-PCR confirmed two miRNAs, 4317 and 4325, were differentially expressed in patients who developed seizures at 1 year. MiR-4317 regulates SLC38A1, a glutamine-glutamate transporter. Integrated miRNA-mRNA network analysis identified COMMD6, APOBEC2, and RASSF6-involved in NF-kB regulation. Two miRNAs (miR-4317 and 4325) differentiated post-ICH late seizures vs. non-seizures at 1 year. The results suggest functional and miRNA-mRNA networks as potential biomarkers for post-ICH late seizures.

Decompressive hemicraniectomy in the management of subcortical spontaneous intracerebral hemorrhage.

BACKGROUND: The benefit of decompressive hemicraniectomy in patients with malignant acute ischemic stroke is well established, however its role in supratentorial intracerebral hemorrhages is unclear and evolving. Prior studies combined cortical and subcortical hemorrhages in their analysis despite their different natural history. Subcortical hematoma is associated with worse outcomes due to mechanical compression of subcortical structures. We describe outcomes of a matched comparison of patients with spontaneous subcortical hemorrhage managed with hemicraniectomy versus medical management alone. METHODS: Using our "Get-with-the-guideline stroke" database, patients with spontaneous subcortical hematoma managed with hemicraniectomy were identified. Using age, gender, and hematoma volume (categorized as 0-30, 30-60, >60ml), patients managed with hemicraniectomy were matched with medical management alone. Outcomes included hospital length of stay, discharge disposition, and Glasgow outcome score. RESULTS: Eight patients with subcortical hematoma managed with hemicraniectomy were matched with 22 medically managed patients. Other than use of antithrombotics, clinical characteristics did not differ between groups. On comparing outcomes, hospital length of stay in the hemicraniectomy group (26.5 vs 12.5 days p = 0.006) was significantly longer. Discharge disposition did not differ between groups (75% vs 36.4% p = 0.101). Despite a higher frequency of Glasgow outcome score ≥ 3 at 90 days amongst hemicraniectomy cases, there was no significant difference between groups (71.3% vs 54.5% p = 0.535). CONCLUSION: Hemicraniectomy for subcortical hematoma was associated with a prolonged hospital stay. Despite improving survival and favorable discharge disposition, there was no statistically significant difference between groups. Further studies on the benefit of hemicraniectomy in subcortical hematoma are needed.

Transgenic expression of HuR increases vasogenic edema and impedes functional recovery in rodent ischemic stroke.

BACKGROUND AND PURPOSE: Ischemic stroke produces significant morbidity and mortality, and acute interventions are limited by short therapeutic windows. Novel approaches to neuroprotection and neurorepair are necessary. HuR is an RNA-binding protein (RBP) which modulates RNA stability and translational efficiency of genes linked to ischemic stroke injury. METHODS: Using a transgenic (Tg) mouse model, we examined the impact of ectopic HuR expression in astrocytes on acute injury evolution after transient middle cerebral artery occlusion (tMCAO). RESULTS: HuR transgene expression was detected in astrocytes in perilesional regions and contralaterally. HuR Tg mice did not improve neurologically 72h after injury, whereas littermate controls did. In Tg mice, increased cerebral vascular permeability and edema were observed. Infarct volume was not affected by the presence of the transgene. CONCLUSIONS: Ectopic expression of HuR in astrocytes worsens outcome after transient ischemic stroke in mice in part by increasing vasogenic cerebral edema. These findings suggest that HuR could be a therapeutic target in cerebral ischemia/reperfusion.

Description of a novel telemedicine-enabled comprehensive system of care: drip and ship plus drip and keep within a system of stroke care delivery.

United States (US) and worldwide telestroke programs frequently focus only on emergency room hyper-acute stroke management. This article describes a comprehensive, telemedicine-enabled, stroke care delivery system that combines "drip and ship" and "drip and keep" models with a comprehensive stroke center primary hub at Ochsner Medical Center in New Orleans, advanced stroke-capable regional hubs, and geographically-aligned, "stroke-ready" spokes. The primary hub provides vascular neurology expertise via telemedicine and monitors care for patients remaining at regional hubs and spokes using a multidisciplinary team approach. By 2014, primary hub telestroke consults grew to ≈1000/year with 16 min average door to consult initiation and 20 min to completion, and 29% of ischemic stroke patients received recombinant tissue-type plasminogen activator (rtPA), increasing 275%. Most patients remained in hospitals close to home, but neurointensive care and interventional procedures were common reasons for primary hub transfer. Given the time sensitivity and expert consultation needed for complex acute stroke care delivery paradigms, telestroke programs are effective for fulfilling unmet care needs. Combining drip and ship and drip and keep management allows more patients to stay "local," limiting primary hub transfer unless more advanced services are required. Post admission telestroke management at spokes increases personnel efficiency and can positively impact stroke outcomes.

The Novel Methods for Analysis of Exosomes Released from Endothelial Cells and Endothelial Progenitor Cells.

Exosomes (EXs) are cell-derived vesicles that mediate cell-cell communication and could serve as biomarkers. Here we described novel methods for purification and phenotyping of EXs released from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads and fluorescence quantum dots (Q-dots®) techniques. EXs from the culture medium of ECs and EPCs were isolated and detected with cell-specific antibody conjugated microbeads and second antibody conjugated Q-dots by using nanoparticle tracking analysis (NTA) system. The sensitivities of the cell origin markers for ECs (CD105, CD144) and EPCs (CD34, KDR) were evaluated. The sensitivity and specificity were determined by using positive and negative markers for EXs (CD63), platelets (CD41), erythrocytes (CD235a), and microvesicles (Annexin V). Moreover, the methods were further validated in particle-free plasma and patient samples. Results showed that anti-CD105/anti-CD144 and anti-CD34/anti-KDR had the highest sensitivity and specificity for isolating and detecting EC-EXs and EPC-EXs, respectively. The methods had the overall recovery rate of over 70% and were able to detect the dynamical changes of circulating EC-EXs and EPC-EXs in acute ischemic stroke. In conclusion, we have developed sensitive and specific microbeads/Q-dots fluorescence NTA methods for EC-EX and EPC-EX isolation and detection, which will facilitate the functional study and biomarker discovery.

Analyses of Endothelial Cells and Endothelial Progenitor Cells Released Microvesicles by Using Microbead and Q-dot Based Nanoparticle Tracking Analysis.

Accurate analysis of specific microvesicles (MVs) from biofluids is critical and challenging. Here we described novel methods to purify and detect MVs shed from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads with fluorescence quantum dots (Q-dots) coupled nanoparticle tracking analysis (NTA). In the in vitro screening systems, we demonstrated that 1) anti-CD105 (EC marker) and anti-CD34 (EPC marker) conjugated-microbeads had the highest sensitivity and specificity for isolating respective MVs, which were confirmed with negative controls, CD41 and CD235a; 2) anti-CD144 (EC marker) and anti-KDR (EPC marker) conjugated-Q-dots exhibited the best sensitivity and specificity for their respective MV NTA detection, which were confirmed with positive control, anti-Annexin V (MV universal marker). The methods were further validated by their ability to efficiently recover the known amount of EC-MVs and EPC-MVs from particle-depleted plasma, and to detect the dynamical changes of plasma MVs in ischemic stroke patients, as compared with traditional flow cytometry. These novel methods provide ideal approaches for functional analysis and biomarker discovery of ECs- and EPCs- derived MVs.

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke.

Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17ß-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke.

Propofol-ketamine combination therapy for effective control of super-refractory status epilepticus.

Retrospective analysis was conducted of patients with SRSE who were treated simultaneously with propofol and ketamine. Sixty-seven patients were identified from 2012 to 2015, and outcomes documented were resolution and mortality. The duration of combined ketamine and propofol use ranged from 1 to 28 days (mean - 3.6 days). Infusion rates ranged up to 145 and 175 mcg/kg/min. Vasopressors were used in 53 patients (79%), and were given within the first 5 days of the ICU admission in 48 (91%) patients. The overall SRSE resolution rate was 91%, and the overall mortality including patients with anoxic brain injury was 39%. Of the 13 patients with SRSE as a result of anoxic brain injury, SRSE was controlled in 5 (56%). The primary determinant of mortality was family withdrawing care related to the presence of severe medical/neurological diseases.

Macroglossia associated with brainstem injury.

BACKGROUND: Macroglossia has been reported in patients undergoing posterior fossa neurosurgical procedures and is thought to be as a result of venous engorgement from intubation or mechanical positioning during these prolonged procedures. METHODS: We report three patients who developed macroglossia and dysautonomia of central neurogenic origin following brainstem injury. RESULTS: The three patients developed macroglossia and dysautonomia with wide hemodynamic fluctuations in the setting of posterior fossa injury of the lower brainstem structures, necessitating tracheostomy placement. Macroglossia was managed with dexamethasone and there was complete resolution of dysautonomia while treated with beta-blockers and gabapentin. CONCLUSIONS: Neurointensivists should be aware of macroglossia with dysautonomia complicating brainstem injury, which may have perilous consequences in the setting of cerebral edema or intracranial hypertension.