Rabinstein, Alejandro A.

Objective: To determine trends in tPA utilization, treatment outcomes and predictors of mortality for pediatric patients with acute ischemic stroke. Materials and Methods: Using the Nationwide Inpatient Sample (NIS) from 2001-2010, pediatric patients (age < 18 years) with the primary diagnosis of ischemic stroke were identified. We studied time trends of utilization of intravenous rtPA and outcomes after thrombolysis. We also analyzed the associations of demographic factors, comorbidities, and complications of acute ischemic stroke with in-hospital mortality. Results: A total of 7,379 patients were included in this study. In-hospital mortality was 4.5%. The co-morbidities associated with the highest rates of in-hospital mortality were mitochondrial disorders (19.5%, P<0.0001) and hypercoagulable states (10.9%, p<0.0001). The main complications associated with increased mortality were intracranial hemorrhage (19.9%, p<0.0001), sepsis (13.2%, p<0.0001) and pneumonia (9.3%, p=0.0007). tPA utilization rate was 1.3% (99 patients). tPA utilization increased from 0.9% of patients in 2001-2005 to 1.9% of patients in 2006-2010 (P<0.0001). While patients who received tPA did not have higher mortality rates than non-tPA patients (0.0% versus 5.5%, P=0.06), there was an increased discharge-to-long-term-facilities rate in the tPA group (50.8% versus 12.1%, P<0.0001). Conclusion: Acute ischemic stroke in the pediatric population is associated with a higher mortality rate when related to mitochondriopathies or hypercoagulability. Patients suffering complications such as intracranial hemorrhage, sepsis and pneumonia have higher mortality. rtPA utilization is increasing in pediatric patients with acute ischemic stroke. Pediatric patients receiving tPA have a low risk of fatal hemorrhage. Although patients receiving rtPA have higher rates of morbidity, this may be related to worse stroke severity in these cases.

Background and Purpose- IV rt-PA has become a widely accepted treatment for a select group of patients with acute ischemic stroke. Quantifying the costs of hospitalization is important for understanding the economic impact of these patients on the hospitals that care for them. We evaluated recent data to determine costs associated with hospitalization for acute ischemic stroke patients treated with intravenous thrombolysis, including subgroup analysis to determine the effects of age and discharge status on hospital costs. Methods- Using the National Inpatient Sample, we evaluated the costs for hospitalization for patients treated with intravenous thrombolysis for acute ischemic stroke in the United States from 2001-2008. The primary endpoint examined in this study was total hospital costs, and these were correlated with clinical outcome. Costs were compared with 2008 Medicare reimbursement for intravenous thrombolysis without complication, and intravenous thrombolysis with major complication. Results- A total of 63472 patients received intravenous thrombolysis for acute ischemic stroke. 24094 patients were <65 years old and 40780 patients were ≥65 years old. Median hospital costs in 2008 dollars were $14102 (IQR $9987-$20819) for patients with good outcome, $18856 (IQR $13145-$30423) for patients with severe disability, and $19129 (IQR $11966-$30781) for patients with mortality. Average 2008 Medicare payments were $10,098 for intravenous thrombolysis without complication and $13,835 for intravenous thrombolysis with major complication. Conclusions- Our study of the NIS shows that hospitalization costs in the United States for ischemic stroke patients treated with intravenous thrombolysis are rather high. Medicare payments have not been adequate reimbursement for these hospitalizations. Hopefully, future reconciliation of costs with payments will be feasible, so that hospitals can afford to provide proper care for ischemic stroke patients treated with intravenous thrombolysis.

Background and Objective Hyperdense middle cerebral artery (HDMCA) sign is an early sign seen on CT head after acute ischemic stroke indicating acute arterial thrombosis. We aimed to measure HDMCA sign objectively. Methods We conducted a retrospective analysis of prospectively collected data from 151 cases of acute ischemic stroke eligible for IV rt-PA by time criteria, admitted to Mayo Clinic from March, 2002 through June, 2011. Admission CT Head was studied to identify HDMCA sign. All patients had either 24 hour CT head or MRI head to confirm the stroke in the same vessel territory. MCA was measured in Hounsfield units and was compared to the contralateral MCA. Receiver Operating Characteristic (ROC) curve analysis was performed to calculate sensitivity and specificity. Results Mean admission NIHSS score was 11±7. HDMCA sign was seen in 93 (62%) patients. ROC curve analysis for ipsilateral MCA Hounsfield units had an area under the curve 0.88 (p<0.001, CI 0.83-0.94) which showed 50 HU or more had 48% sensitivity and 98% specificity. Ratio of ipsilateral to contralateral MCA HU had an area under the curve 0.94 (p<0.001, CI 0.90-0.98) which showed ratio of 1.23 had 67% sensitivity and 98% specificity. A combination of either ipsilateral HU more than equal to 50 or a ratio of ipsilateral to contralateral MCA HU more than equal to 1.23 had 77% sensitivity, 95% specificity, 96% positive predictive value and 72% negative predictive value. Conclusion A combination of ipsilateral HU more than equal to 50 or a ratio of ipsilateral to contralateral MCA HU more than equal to 1.23 can objectively identify HDMCA sign with good sensitivity and high specificity.

Background and Objective Hyperdense MCA (HDMCA) sign is an early sign seen on CT head after acute ischemic stroke indicating acute arterial thrombosis. It has been reported as a predictor of stroke morbidity and mortality. The relationship of size of hyperdense middle cerebral artery (MCA) sign with stroke volume and functional outcome has not been sufficiently studied. Methods We did a retrospective analysis of prospectively collected data from 206 cases of acute ischemic stroke eligible for IV rt-PA by time criteria, admitted to Mayo Clinic from March, 2002 through June, 2011. Admission CT Head was studied to identify HDMCA sign which was further subcategorized according to size. CT head at 24 hours after intravenous tissue plasminogen activator was used to calculate Alberta Stroke Program Early CT Score (ASPECTS) to measure ischemic damage area. Functional outcome was assessed using the modified Rankin score at 3 months and dichotomized into less than equal to 2 (good outcome) and more than 2 (bad outcome). Univariate analysis including t-test, Chi-square, and Fisher Exact test was used when appropriate. Results Mean admission NIHSS score was 11±7. HDMCA sign was seen in 99 (48%) patients: 100% MCA occlusion (7) 76-100% M1 (17), 50-75% M1 (17), less than 50% M1 (6), MCA dot sign (23), sylvian dot sign (21) and sylvian MCA sign, defined as any sylvian MCA occlusion bigger than a dot (8). Univariate analysis showed statistically significant associations between our HDMCA classification and ASPECTS at 24 hours (p<0.001) and modified Rankin score at 3 months (p<0.001). Smaller infarctions (ASPECTS >8) were observed more often with lower MCA clot burden; MCA dot (48%), less than 50% MCA (80%), sylvian dot (57%) and sylvian MCA (38%), 50-75% M1 (6%), 75-100% M1 (0%) and 100% MCA (0%). Good outcome (mRS≤2 at 3 months) was seen more often with lower MCA clot burden; MCA dot (52%), less than 50% MCA (67%), sylvian dot (67%) and sylvian MCA (63%). Conversely, larger HDMCA size was associated with poor outcome (mRS>2); 50-75% M1 (100%), 75-100% (88%) and 100% MCA (100%). Conclusion The size of the HDMCA sign size is an important predictor of ischemic stroke mortality and morbidity. HDMCA should be measured upon admission as it may help refine prognostication and identify patients who could benefit from endovascular rescue therapy after intravenous thrombolysis.

Background: Whether a significant proportion of cryptogenic stroke (CS) is caused by under-detected paroxysmal atrial fibrillation (PAF) is not known. Prolonged ambulatory cardiac monitoring may detect episodes of PAF in patients with stroke of unknown cause (cryptogenic stroke, CS). However, it is unclear whether PAF is more common in patients wtih CS compared with patients with stroke of known cause (SKC). We performed a case control study to compare the rates of detection of PAF in CS vs SKC using prolonged ambulatory cardiac rhythm monitoring. Methods and Results: We prospectively enrolled 132 patients within 3 months of a stroke (66 with CS and 66 with SKC) to undergo 3-week ambulatory cardiac rhythm monitoring using the CardioNet MCOT system. Stroke group was assigned by consensus between two vascular neurologists upon enrollment based on the Causative Classification of Stroke system. Primary endpoint was detection of PAF of any duration independently confirmed by two cardiologists blinded to the stroke group. The groups were well balanced except that patients with CS tended to be older and to have less hypertension and diabetes. Four patients (2 in each group) were excluded because of insufficient stroke evaluation or early discontinuation of monitoring. Episodes of PAF were detected in 16/64 (25%) patients with CS and 9/64 (14%) patients with SKC (p=0.12). Only 5 patients had episodes of PAF lasting > 30 seconds (3 with CS and 2 with SKC). Six of the 9 patients from the SKC group with PAF had small subcortical infarctions; the other 3 had cortical strokes ascribed to artery-to-artery embolism (2 with complex aortic plaques, 1 with severe vertebrobasilar stenosis). In patients under age 65, episodes of PAF were more common in the CS group (22% vs 3; p=0.07) while in patients age 65 or older the rates of detection were very similar (29% in CS vs 28% in SKC; p=0.9). Conclusions: Very short episodes of PAF are relatively common in patients with CS and with SKC, and their pathogenic significance is unclear. However, considering only patients under 65, a greater proportion of cryptogenic stroke patients had PAF, suggesting it might be pathogenic.

Introduction: Timing of clinical grading has not been fully studied in patients with aneurysmal subarachnoid hemorrhage (aSAH). Our primary objective was to identify at which time point the clinical assessment using the World Federation of Neurological Surgeons Scale (WFNS) and the Glasgow Coma Scale (GCS) is most predictive of poor functional outcome. Methods: Retrospective cohort study on the association of clinical grading determined at presentation, nadir and post-resuscitation, and poor outcome. Poor functional outcome was defined as Glasgow Outcome Scale score of 1-3 at 6 months. The study was approved by our Institutional Review Board. Results: We identified 186 consecutive patients admitted to a teaching hospital between January 2002 and June 2008. Patients’ mean age was 56.9±13.7 years and 63% of the patients were women. Twenty-four percent had poor functional outcome (mortality was 17%). On univariable logistic regression analyses, GCS determined at presentation (OR=0.80; p<0.0001), nadir (OR=0.73; p<0.0001) and post-resuscitation (OR=0.53; p<0.0001), modified Fisher Scale (OR=2.21;p=0.0013), WFNS assessed at presentation (OR=1.92;p<0.0001), nadir (OR=3.51; <0.0001) and post-resuscitation (OR=3.91; <0.0001), intracerebral hematoma on initial CT (OR=4.55;p<0.0002), acute hydrocephalus (OR=2.29;p=0.0375), and cerebral infarction (OR=4.84; <0.0001) were associated with poor outcome. On multivariable logistic regression analysis, only cerebral infarction (OR=5.80; 0.0013) and WFNS grade post-resuscitation (OR=3.43;<0.0001) were associated with poor outcome. Receiving operating characteristics/area under the curve (AUC) analysis demonstrated that WFNS determined post-resuscitation had a stronger association with poor outcome (AUC=0.90) than WFNS assessed upon admission or at nadir. Conclusions: Timing of WFNS assessment affects its prognostic value. Outcome after aSAH is best predicted by rating WFNS after neurological resuscitation.

Introduction: Long-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS). But occult AF is also found in some normal individuals and patients with stroke of known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal versus incidental. Methods: Through systematic search, we identified all case-control and cohort studies applying identical long-term monitoring techniques to both CS and KS patients. We performed a random-effects meta-analyses across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients, and across age subgroups. We then applied Bayes’ theorem (method of Alsheikh-Ali et al, Stroke 2009) to determine the probability that occult AF is causal or incidental. Results: The systematic search identified 3 case-control and cohort studies enrolling 575 patients (337 CS, 238 KS). Methods of long-term monitoring were implantable loop recorder in 191 (33.2%), extended mobile external cardiac monitor in 277 (48.2%), and patch/event/Holter monitoring in 107 (18.6%). In formal meta-analysis, the summary odds ratio for occult AF in CS vs KS in all patients was 1.72 (95%CI 0.91-3.25) (Figure). With application of Bayes theorem, the corresponding probabilities indicated that, when present, occult AF in CS patients is causal in 44.4% and incidental in 55.6%. Only one study reported age-specific subgroup data: these suggested occult AF in CS patients was causal in 93% of patients <65y vs 5.6% of patients ≥65y, but estimates had limited precision. Conclusions: In patients with cryptogenic stroke, when occult AF is found, it is likely causal in about 44% of patients, who may benefit from anticoagulation, and likely incidental in about 56% of patients, who may not benefit from anticoagulation. Figure

Introduction: Selection criteria for endovascular thrombectomy (EVT) for emergent large-vessel occlusion (ELVO) stroke increasingly rely on CT perfusion (CTP) findings at presentation. While perfusion imaging is used to estimate the likelihood of deriving long-term functional benefit from EVT, there is comparatively little data on how perfusion deficits relate to domains of neurological function. Here, we investigated region-specific hypoperfusion as a driver of neurological dysfunction through correspondence between NIHSS items and CTP. Methods: We included 169 patients with ELVO presenting to Mayo Clinic Rochester or Jacksonville, who had baseline CTP and itemised NIHSS data. Perfusion was quantified as mean transit time using e-CTP (Brainomix Ltd., Oxford, UK) and thresholded to ≥5 s for lesion masking. Voxel-wise lesion-symptom mapping (VLSM) was performed using sparse canonical correlations analysis (Lesymap package, R). Results: Total NIHSS was most strongly predicted by left MCA territory hypoperfusion, corresponding to language-eloquent cortical areas and dominant hemisphere motor tracts (figure 1). Contralateral limb motor deficits (NIHSS 5 and 6) were mainly associated with subcortical and white matter hypoperfusion; there was an additional strong signal for left frontal cortex in language function (NIHSS 9). The remaining NIHSS items were less well localised. Conclusions: Expanding on previous pilot data, our results provide further evidence for the feasibility of hypoperfusion-to-symptom mapping in ELVO. This could allow for more nuanced clinical-imaging mismatch determination, and selection of patients based on specific neurological deficits that may be reversible.

AbstractTelemedicine is a rapidly growing field of medicine due to a combination of high-speed global telecommunication systems and accessibility of small, fast mobile computing platforms with bidirectional audiovisual camera capabilities. Teleneurology is a subset of telemedicine. TeleNeuroICU, one form of teleneurology, is the practice of virtually consulting on patients in the ICU setting with neurological and neurosurgical conditions. Given the current and future shortage of neurologists and neurointensivists, there is a high demand for TeleNeuroICU services around the globe and this is expected to increase in the future. This review summarizes the state of the art around the TeleNeuroICU practice for practitioners in the field, emerging research in this area, and new technologies and integrations that enhance the value of TeleNeuroICU to health care systems.