Late lesion growth following endovascular therapy: is 24 hours too early to assess acute infarct size including the effects of secondary injury?

Introduction Stroke lesion volume on MRI or CT provides objective evidence of tissue injury as a consequence of ischemic stroke. Measurement of "final" lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome. The goals of this study were to quantify lesion growth during the first week after treatment, identify early predictors, and explore the association with clinical outcome. Methods This is a prospective study of stroke patients at two centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, and iii) had 3T MRI post-EVT at 24hr and 5-day. We defined "Early" and "Late" lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively. Complete reperfusion was defined as >90% reduction of the volume of tissue with perfusion delay (Tmax>6sec) between pre-EVT and 24hr post-EVT. Favorable clinical outcome was defined as modified Rankin scale (mRS) of 0-2 at 30 or 90 days. Results One hundred twelve patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 66% with M1 occlusion, and median baseline DWI volume 21.2mL. Successful recanalization was achieved in 87% and 68% had complete reperfusion, with an overall favorable clinical outcome rate of 53%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.3mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (64%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (87%: 46% mTICI 2b/ 41% mTICI 3). Late lesion growth patients had a 27.4mL change in Late lesion volume and 30.1mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome. Conclusion Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Most patients with no Early lesion growth had no Late lesion growth. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally, it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.

Post-ischemic hyperemia following endovascular therapy for acute stroke is associated with lesion growth.

A substantial proportion of acute stroke patients fail to recover following successful endovascular therapy (EVT) and injury to the brain and vasculature secondary to reperfusion may be a contributor. Acute stroke patients were included with: i) large vessel occlusion of the anterior circulation, ii) successful recanalization, and iii) evaluable MRI early after EVT. Presence of hyperemia on MRI perfusion was assessed by consensus using a modified ASPECTS. Three different approaches were used to quantify relative cerebral blood flow (rCBF). Sixty-seven patients with median age of 66 [59-76], 57% female, met inclusion criteria. Hyperemia was present in 35/67 (52%) patients early post-EVT, in 32/65 (49%) patients at 24 hours, and in 19/48 (40%) patients at 5 days. There were no differences in incomplete reperfusion, HT, PH-2, HARM, severe HARM or symptomatic ICH rates between those with and without early post-EVT hyperemia. A strong association (R2 = 0.81, p < 0.001) was found between early post-EVT hyperemia (p = 0.027) and DWI volume at 24 hours after adjusting for DWI volume at 2 hours (p < 0.001) and incomplete reperfusion at 24 hours (p = 0.001). Early hyperemia is a potential marker for cerebrovascular injury and may help select patients for adjunctive therapy to prevent edema, reperfusion injury, and lesion growth.

Association of Pediatric ASPECTS and NIH Stroke Scale, Hemorrhagic Transformation, and 12-Month Outcome in Children With Acute Ischemic Stroke.

OBJECTIVE: We aimed to determine whether a modified pediatric Alberta Stroke Program Early CT Score (modASPECTS) is associated with clinical stroke severity, hemorrhagic transformation, and 12-month functional outcomes in children with acute AIS. METHODS: Children (29 days to <18 years) with acute AIS enrolled in two institutional prospective stroke registries at Children's Hospital of Philadelphia and Royal Children's Hospital Melbourne, Australia were retrospectively analyzed to determine whether modASPECTS, in which higher scores are worse, correlated with acute Pediatric NIH Stroke Scale (PedNIHSS) scores (children ≥2 years of age), was associated with hemorrhagic transformation on acute MRI, and correlated with 12-month functional outcome on the Pediatric Stroke Outcome Measure (PSOM). RESULTS: 131 children were included; 91 were ≥2 years of age. Median days from stroke to MRI was 1 (interquartile range [IQR] 0-1). Median modASPECTS was 4 (IQR 3-7). ModASPECTS correlated with PedNIHSS (rho=0.40, P=0.0001). ModASPECTS was associated with hemorrhagic transformation (OR 1.13 95% CI 1.02-1.25, P=0.018). Among children with follow-up (N=128, median 12.2 months, IQR 9.5-15.4 months), worse outcomes were associated with higher modASPECTS (common OR 1.14, 95%CI 1.04-1.24, P=0.005). The association between modASPECTS and outcome persisted when we adjusted for age at stroke ictus and the presence of tumor or meningitis as stroke risk factors (common OR 1.14, 95%CI 1.03-1.25, P=0.008). CONCLUSIONS: ModASPECTS correlates with PedNIHSS scores, hemorrhagic transformation, and 12-month functional outcome in children with acute AIS. Future pediatric studies should evaluate its usefulness in predicting symptomatic intracranial hemorrhage and outcome after acute revascularization therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the modified pediatric ASPECTS on MRI is associated with stroke severity (as measured by the baseline pediatric NIH Stroke Scale), hemorrhagic transformation, and 12-month outcome in children with acute supratentorial ischemic stroke.

Fluid-Attenuated Inversion Recovery Hyperintense Ischemic Stroke Predicts Less Favorable 90-Day Outcome after Intravenous Thrombolysis.

INTRODUCTION: The absence of an ischemic lesion on MRI fluid-attenuated inversion recovery (FLAIR) is helpful in predicting stroke onset within 4.5 h. However, some ischemic strokes become visible on FLAIR within 4.5 h. We hypothesized that the early lesion visibility on FLAIR may predict stroke outcome 90 days after intravenous (IV) thrombolysis, independent of time. MATERIALS AND METHODS: We analyzed data from acute ischemic stroke patients presenting over the last 10 years who were screened with MRI and treated with IV thrombolysis within 4.5 h from onset. Three independent readers assessed whether ischemic lesions seen on diffusion-weighted imaging were also FLAIR positive based on visual inspection. Multivariable regression analyses were used to obtain an adjusted odds ratio of favorable clinical and radiological outcomes based on FLAIR positivity. RESULTS: Of 297 ischemic stroke patients, 25% had lesion visibility on initial FLAIR. The interrater agreement for the FLAIR positivity assessment was 84% (κ = 0.604, 95% CI: 0.557-0.652). Patients with FLAIR-positive lesions had more right hemispheric strokes (57 vs. 41%, p = 0.045), were imaged later (129 vs. 104 min, p = 0.036), and had less frequent favorable 90-day functional outcome (49 vs. 63%, p = 0.028), less frequent early neurologic improvement (30 vs. 58%, p = 0.001), and more frequent contrast extravasation to the cerebrospinal fluid space (44 vs. 26%, p = 0.008). CONCLUSIONS: Early development of stroke lesion on FLAIR within 4.5 h of onset is associated with reduced likelihood of favorable 90-day outcome after IV thrombolysis.

Practice Current: How do you manage mild cognitive impairment?

Mild cognitive impairment (MCI) is characterized by evidence of cognitive impairment with minimal disruption of instrumental activities of daily living and carries a substantial risk of progression of dementia. Whereas current guidelines support a relatively minimalistic workup to identify reversible or structural causes, the field has witnessed the rapid development of various sophisticated imaging, biomarker, and genetic investigations in the past few years. The role of these investigations in routine practice is uncertain. Similarly, although there are no approved treatments for MCI, neurologists may experience uncertainty about using cholinesterase inhibitors or other medications or supplements that have been studied in MCI with limited success, particularly when patients or families are keen to try pharmacologic options. Given these uncertainties, and the paucity of high-quality data in the literature, we sought expert opinion from around the globe on how to investigate and treat patients with MCI. Similar questions were posed to the rest of our readership in an online survey, the preliminary results of which are also presented.

Routine use of FLAIR-negative MRI in the treatment of unknown onset stroke.

BACKGROUND: Treatment of FLAIR-negative stroke in patients presenting in an unknown time window has been shown to be safe and effective. However, implementation can be challenging due to the need for hyper-acute MRI screening. The purpose of this study was to review the routine application of this practice outside of a clinical trial. METHODS: Patients presenting from 3/1/16 to 8/22/18 in a time window <4.5 h from symptom discovery but >4.5 h from last known normal were included if they had a hyper-acute MRI performed. Quantitative assessment based on the MR WITNESS trial and qualitative assessment based on the WAKE-UP trial were used to grade the FLAIR images. The MR WITNESS trial used a quantitative assessment of FLAIR change where the fractional increase in signal change had to be <1.15, whereas the WAKE-UP trial used a visual assessment requiring the absence of marked FLAIR signal changes. RESULTS: During the study period, 136 stroke patients presented and were imaged in the specified time window. Of these, 17 (12.5%) received IV tPA. Three patients had hemorrhage on 24-h MRI follow up; none had an increase in NIHSS ≥4. Of the 119 patients who were screened but not treated, 18 (15%) were eligible based on FLAIR quantitative assessment and 55 (46%) were eligible based on qualitative assessment. In all cases where patients were not treated, there was an identifiable exclusion based on trial criteria. During the study period, IV tPA utilization was increased by 5.6% due to screening and treating patients with unknown onset stroke. CONCLUSIONS: Screening stroke patients in an unknown time window with MRI is practical in a real-world setting and increases IV tPA utilization.

National outcomes of in-hospital cardiopulmonary resuscitation in patients with acute kidney injury: years 2005 - 2011
.

BACKGROUND: There is paucity of data on the outcomes of in-hospital cardiopulmonary resuscitation (CPR) in patients with acute kidney injury (AKI). We analyzed the impact of acute kidney injury on in-hospital CPR-related outcomes. MATERIALS AND METHODS: We analyzed data from Nationwide Inpatient Sample (NIS 2005 - 2011) including patients with and without AKI who had undergone in-hospital CPR. Baseline characteristics, in-hospital complications and discharge outcomes were compared between the two groups. We determined the effect of AKI on length of hospital stay, discharge destination, hospital mortality, survival trends, and discharge to home. RESULTS: 180,970 patients with primary or secondary diagnosis of AKI underwent in-hospital CPR compared to 323,620 patients without AKI. Unadjusted in-hospital mortality rates were higher in the AKI group (78.2 vs. 71.8%, p < 0.0001). After adjusting for age, sex, and potential confounders, patients in the AKI group had higher odds of mortality with odds ratio 1.3, 95% confidence interval 1.2 - 1.4, p < 0.0001. Survivors in the AKI group were more likely to be discharged to nursing homes and had higher mean hospitalization charges. In 2011 compared with 2005, there was an improved survival after CPR and higher rates of discharges to home. There was no significant change in the mean length of hospital stay between these time periods (p = 0.4). CONCLUSION: AKI independently increases the odds of in-hospital mortality and nursing home placement after in-hospital CPR. These data may facilitate CPR discussions and decision-making in critically ill patients.
.

Are There Disparities in Thrombolytic Treatment and Mortality in Acute Ischemic Stroke in the Hispanic Population Living in Border States versus Nonborder States?

BACKGROUND: Recent studies have found an underutilization of hospital in-patient care for coronary artery disease in Hispanics living in border states. OBJECTIVE: To identify acute treatment disparities in acute ischemic stroke Hispanic patients and determine the effect of such disparity on patient outcomes. METHODS: We identified Hispanic and non-Hispanic acute ischemic stroke patients from the Nationwide Inpatient Sample-2011 data files. We determined the rate of utilization of thrombolytics and outcomes according to patient's demographic and clinical characteristics and whether or not they lived in a border state (defined as California, Arizona, New Mexico, and Texas). RESULTS: A total of 34,904 Hispanic patients were admitted with ischemic stroke; of those 21,130 were admitted in border states and 13,774 in nonborder states. There was a significantly lower rate of thrombolytic use in Hispanic patients (1013 (4.8%) and non-Hispanics (5326 (5.7%, p=0.05)). After adjusting for age, gender, and other confounding risk factors, Hispanics were 30% more likely to suffer in-hospital mortality versus there non-Hispanic counterparts in border states [OR 1.3 (1.1-1.6) p=0.009], which was not apparent in the non-border states [OR 1.0 (0.8-1.2) p=0.9]. CONCLUSIONS: There was an underutilization of thrombolytics and higher mortality in the Hispanic population admitted in border states but not in nonborder states. Further studies are warranted to better understand the associated factors.

Outcomes of In-Hospital Cardiopulmonary Resuscitation in Patients with CKD.

BACKGROUND AND OBJECTIVES: Advance care planning, including code/resuscitation status discussion, is an essential part of the medical care of patients with CKD. There is little information on the outcomes of cardiopulmonary resuscitation in these patients. We aimed to measure cardiopulmonary resuscitation outcomes in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study is observational in nature. We compared the following cardiopulmonary resuscitation-related outcomes in patients with CKD with those in the general population by using the Nationwide Inpatient Sample (2005-2011): (1) survival to hospital discharge, (2) discharge destination, and (3) length of hospital stay. All of the patients were 18 years old or older. RESULTS: During the study period, 71,961 patients with CKD underwent in-hospital cardiopulmonary resuscitation compared with 323,620 patients from the general population. Unadjusted in-hospital mortality rates were higher in patients with CKD (75% versus 72%; P<0.001) on univariate analysis. After adjusting for age, sex, and potential confounders, patients with CKD had higher odds of mortality (odds ratio, 1.24; 95% confidence interval, 1.11 to 1.34; P≤0.001) and length of stay (odds ratio, 1.11; 95% confidence interval, 1.07 to 1.15; P=0.001). Hospitalization charges were also greater in patients with CKD. There was no overall difference in postcardiopulmonary resuscitation nursing home placement between the two groups. In a separate subanalysis of patients ≥75 years old with CKD, higher odds of in-hospital mortality were also seen in the patients with CKD (odds ratio, 1.10; 95% confidence interval, 1.02 to 1.17; P=0.01). CONCLUSIONS: In conclusion, we observed slightly higher in-hospital mortality in patients with CKD undergoing in-hospital cardiopulmonary resuscitation.

Clinical Outcomes among Transferred Children with Ischemic and Hemorrhagic Strokes in the Nationwide Inpatient Sample.

INTRODUCTION: Children with ischemic stroke (IS) and hemorrhagic stroke (HS) may require interfacility transfer for higher level of care. We compared the characteristics and clinical outcomes of transferred and nontransferred children with IS and HS. METHODS: Children aged 1-18 years admitted to hospitals in the United States from 2008 to 2011 with a primary discharge diagnosis of IS and HS were identified from the National Inpatient Sample database by ICD-9 codes. Using logistic regression, we estimated the odds ratios (OR) and 95% confidence intervals (CI) for in-hospital mortality and discharge to nursing facilities (versus discharge home) between transferred and nontransferred patients. RESULTS: Of the 2815 children with IS, 26.7% were transferred. In-hospital mortality and discharge to nursing facilities were not different between transferred and nontransferred children in univariable analysis or in multivariable analysis that adjusted for age, sex, and confounding factors. Of the 6879 children with HS, 27.1% were transferred. Transferred compared to nontransferred children had higher rates of both in-hospital mortality (8% versus 4%, P = .003) and discharge to nursing facilities (25% versus 20%, P = .03). After adjusting for age, sex, and confounding factors, in-hospital mortality (OR 1.5, 95% CI 1.1-2.4, P = .04) remained higher in transferred children, whereas discharge to nursing facilities was not different between the groups. CONCLUSION: HS but not IS was associated with worse outcomes for children transferred to another hospital compared to children who were not transferred. Additional study is needed to understand what factors may contribute to poorer outcomes among transferred children with HS.

Weekend Effect in Children With Stroke in the Nationwide Inpatient Sample.

BACKGROUND AND PURPOSE: Studies have demonstrated differences in clinical outcomes in adult patients with stroke admitted on weekdays versus weekends. The study's objective was to determine whether a weekend impacts clinical outcomes in children with ischemic stroke and hemorrhagic stroke. METHODS: Children aged 1 to 18 years admitted to US hospitals from 2002 to 2011 with a primary discharge diagnosis of ischemic stroke or hemorrhagic stroke were identified by International Classification of Disease, 9th Revision, codes. Logistic regression estimated odds ratios and 95% confidence intervals for in-hospital mortality and discharge to a nursing facility among children admitted on weekends (Saturday and Sunday) versus weekdays (Monday to Friday), adjusting for potential confounders. RESULTS: Of 8467 children with ischemic stroke, 28% were admitted on a weekend. Although children admitted on weekends did not have a higher in-hospital mortality rate than those admitted on weekdays (4.1% versus 3.3%; P=0.4), children admitted on weekends had a higher rate of discharge to a nursing facility (25.5% versus 18.6%; P=0.003). After adjusting for age, sex, and confounders, the odds of discharge to a nursing facility remained increased among children admitted on weekends (odds ratio, 1.5; 95% confidence interval, 1.1-1.9; P=0.006). Of 10 919 children with hemorrhagic stroke, 25.3% were admitted on a weekend. Children admitted on weekends had a higher rate of in-hospital mortality (12% versus 8%; P=0.006). After adjusting for age, sex, and confounders, the odds of in-hospital mortality remained higher among children admitted on weekends (odds ratio, 1.4; 95% confidence interval, 1.1-1.9; P=0.04). CONCLUSIONS: There seems to be a weekend effect for children with ischemic and hemorrhagic strokes. Quality improvement initiatives should examine this phenomenon prospectively.

Comparative Outcomes of Carotid Artery Stent Placement and Carotid Endarterectomy in Patients with Chronic Kidney Disease and End-Stage Renal Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have a high prevalence of carotid artery stenosis but are excluded from clinical trials. We sought to determine the clinical characteristics and outcomes related to carotid endarterectomy (CEA) and carotid artery stenting (CAS) in ESRD and CKD patients. METHODS: We determined the frequency of CAS and CEA performed in patients with ESRD and CKD and associated in-hospital outcomes using data from the nationwide inpatient sample data files from 2005 to 2011. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. RESULTS: Of the 43,875 CKD patients who underwent CEA, 3888 (8.8%) were ESRD patients. After adjusting for age, gender, race, presence of hypertension, congestive heart failure (CHF), dyslipidemia, nicotine dependence and alcohol abuse, CEA performed in ESRD patients was associated with higher rates of in-hospital mortality (odds ratio [OR] 4.3, 95% confidence interval [CI] 2.1-9.0; P ≤ .0001) and moderate to severe disability (OR 1.4, 95% CI 1.1-1.8; P = .009). Of the 8148 CKD patients who underwent CAS, 693 (8.5%) were ESRD patients. After adjusting for age, gender, race/ethnicity, presence of dyslipidemia, CHF, and hypertension, CAS performed in ESRD patients was associated with higher rates of in-hospital mortality (OR 3.7, 95% CI 1.0-13.9; P = .04) and moderate to severe disability (OR 1.7, 95% CI 1.0-3.3; P = .05). CONCLUSIONS: Both CAS and CEA were associated with 4-folds higher odds of in-hospital mortality in ESRD patients and such observations raise concerns regarding the risk : benefit ratio of carotid revascularization in these patients.

Hypertension is Associated With Increased Mortality in Children Hospitalized With Arterial Ischemic Stroke.

BACKGROUND: Recently a single-center study suggested that hypertension after stroke in children was a risk factor for mortality. Our goal was to assess the association between hypertension and outcome after arterial ischemic stroke in children from a large national sample. METHODS: Using the Healthcare Cost and Utilization Project Kids' Inpatient Database, children (1-18 years) with a primary diagnosis of ischemic stroke (International Classification of Diseases, Ninth Revision [ICD-9] codes 433-437.1) who also had a diagnosis of elevated blood pressure (ICD-9 code 796.2) or hypertension (ICD-9 codes 401 and 405) from 2003, 2006, and 2009 were identified. Clinical characteristics, discharge outcomes, and length of stay were assessed. Multivariable logistic regression was used to assess the relationship between hypertension and in-hospital mortality or discharge outcomes. RESULTS: Of 2590 children admitted with arterial ischemic stroke, 156 (6%) also had a diagnosis of hypertension. Ten percent of children with hypertension also had renal failure. Among patients with arterial ischemic stroke, hypertension was associated with increased mortality (7.4% vs. 2.8%; P = 0.01) and increased length of stay (mean 11 ± 17 vs. 7 ± 12 days; P = 0.004) compared with those without hypertension. After adjusting for age, sex, intubation, presence of a fluid and electrolyte disorder, and renal failure, children with hypertension had an increased odds of in-hospital death (odds ratio 1.2, 95% confidence interval [1.1-3.3, P = 0.04]). CONCLUSION: Hypertension was associated with an increased risk of in-hospital death for children presenting with arterial ischemic stroke. Further prospective study of blood pressure in children with stroke is needed.

Outcomes of transient ischemic attack in maintenance dialysis patients and those with chronic kidney disease.

BACKGROUND: In-hospital outcomes of transient ischemic attack (TIA) in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) requiring maintenance dialysis are largely unknown. We evaluated TIA-related in-hospital outcomes in these patients using a national database. METHODS: Our study is observational in nature. Data from all adult (≥ 18 years) patients admitted to US hospitals between 2005 and 2011 with a primary discharge diagnosis of TIA and secondary diagnosis of CKD and ESRD were included using the Nationwide In-Patient Sample. We aimed to compare the following TIA-related outcomes between CKD and ESRD patients: (i) degree of disability (mainly functional status) derived from discharge destination, (ii) length of stay, (iii) charges of hospitalization, and (iv) mortality. The comparisons of TIA-related mortality and discharge outcomes between CKD and ESRD were analyzed after adjusting for potential confounders using logistic regression analysis. We adjusted for age, sex, co-morbidities, hospital size and hospital teaching status. RESULTS: A total of 18 316 dialysis and 67 256 CKD patients were admitted with TIA in the study period (2005-11). On univariate analysis, there was no difference in the rates of moderate-to-severe disability (20.5% versus 20.2%, P = 0.7) and in-hospital mortality (0.4% versus 0.2%, P = 0.07) in ESRD patients compared with those with CKD. After adjusting for age, sex and potential confounders, ESRD patients with TIA had higher odds of moderate-to-severe disability at discharge [odds ratio (OR): 1.53, 95% confidence interval (CI): 1.37-1.71, P ≤ 0.0001] and in-hospital death (OR: 2.87, 95% CI: 1.29-6.37, P = 0.009). CONCLUSION: ESRD patients with TIA have significantly higher rates of moderate-to-severe disability at discharge and in-hospital mortality when compared with the patients of other stages of CKD who are not dialysis-dependent.

CT Evolution of Hematoma and Surrounding Hypodensity in a Cadaveric Model of Intracerebral Hemorrhage.

BACKGROUND: The evolution of intracerebral hematoma and perihematoma edema in the ultra-early period on computed tomographic (CT) scans in patients with intracerebral hemorrhage (ICH) is not well understood. We aimed to investigate hematoma and perihematoma changes in "neutral brain" models of ICH. METHODS: One human and five goat cadaveric heads were used as "neutral brains" to provide physical properties of brain without any biological activity or new bleeding. ICH was induced by slow injection of 4 ml of fresh human blood into the right basal ganglia of the goat brains. Similarly, 20 ml of fresh blood was injected deep into the white matter of the human cadaver head in each hemisphere. Serial CT scans of the heads were obtained immediately after hematoma induction and then 1, 3, and 5 hours afterward. Analyze software (AnalyzeDirect, Overland Park, KS, USA) was used to measure hematoma and perihematoma hypodensity volumes in the baseline and follow-up CT scans. RESULTS: The initial hematoma volumes of 11.6 ml and 10.5 ml in the right and left hemispheres of the cadaver brains gradually decreased to 6.6 ml and 5.4 ml at 5 hours, showing 43% and 48% retraction of hematoma, respectively. The volume of the perihematoma hypodensity in the right and left hemisphere increased from 2.6 ml and 2.2 ml in the 1-hour follow-up CT scans to 4.9 ml and 4.4 ml in the 5-hour CT scan, respectively. Hematoma retraction was also observed in all five goat brains ICH models with the mean ICH volume decreasing from 1.49 ml at baseline scan to 1.01 ml at the 5-hour follow-up CT scan (29.6% hematoma retraction). Perihematoma hypodensity was visualized in 70% of ICH in goat brains, with an increasing mean hypodensity volume of 0.4 ml in the baseline CT scan to 0.8 ml in the 5-hour follow-up CT scan. CONCLUSION: Our study demonstrated that substantial hematoma retraction and perihematoma hypodensity occurs in ICH in the absence of any new bleeding or biological activity of surrounding brain. Such observations suggest that active bleeding is underestimated in patients with no or small hematoma expansion and our understanding of perihematoma hypodensity needs to be reconsidered.

Risk of In-Hospital Cardiac Arrest Among Medicare Beneficiaries Undergoing Video Electroencephalographic Monitoring.

PURPOSE: Sudden cardiac death is the dominant reason of sudden unexpected death in epilepsy (SUDEP). Anecdotal reports have documented cardiac arrest during video electroencephalographic (EEG) monitoring. We performed this study to determine the rate of cardiac arrest and need for cardiac resuscitation during video EEG monitoring. METHODS: We used inpatient data from the Centers for Medicare and Medicaid Services (CMS)'s Linkable 2008-2010 Medicare Data Entrepreneur's Synthetic Public Use File. Using the International Classification of Diseases 9th revision (ICD-9) primary diagnosis codes, we identified patients with epilepsy. We used the primary or secondary ICD-9 procedure codes to identify patients who underwent video EEG during admission. For primary endpoints, we identified patients who suffered cardiac arrest and those who underwent cardiorespiratory resuscitation (CPR). RESULTS: A total of 6,087 patients (mean age 76±12 years; 3,354 women) were included; 5,597 patients had a primary diagnosis of epilepsy and no video EEG, 240 patients had a primary diagnosis of epilepsy and underwent video EEG, and 250 patients underwent a video EEG without any diagnosis of epilepsy. A total of 12 patients (0.2%, 95% CI: 0.7-0.8) suffered a cardiac arrest during their admission. Three patients (0.1%) underwent CPR during their admission. There was no in-hospital mortality. None of the patients in those undergoing video EEG suffered cardiac arrest or underwent CPR. CONCLUSION: While the risk of cardiac arrest during video EEG monitoring may exist, the rate of such events was negligible in our study comprising of elderly Medicare patients.

Effect of Carotid Revascularization Endarterectomy Versus Stenting Trial Results on the Performance of Carotid Artery Stent Placement and Carotid Endarterectomy in the United States.

BACKGROUND: CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) results, published in 2010, showed no difference in the rates of composite outcome (stroke, myocardial infarction, or death) between carotid artery stent placement (CAS) and carotid endarterectomy (CEA). OBJECTIVE: To identify any changes in use and outcomes of CAS and CEA subsequent to the CREST results. METHODS: We estimated the frequency of CAS and CEA procedures in the years 2009 (pre-CREST period) and 2011 (post-CREST period), using data from the National Inpatient Sample (NIS). Demographic and clinical characteristics and in-hospital outcomes of pre- and post-CREST CAS-treated and post-CREST CEA-treated patients were compared with pre-CREST CEA-treated patients. RESULTS: A total of 225,191 patients underwent CEA or CAS in the pre- and post-CREST periods. The frequency of CAS among carotid revascularization procedures did not change after publication of the CREST results (12.3% vs. 12.7%, P = .9). In the pre-CREST period, the CAS group (compared with the CEA group) had higher rates of congestive heart failure (P < .001), coronary artery disease (P < .001), and renal failure (P < .001). The post-CREST CAS group had a higher frequency of atrial fibrillation (P = .003), congestive heart failure (P < .0001), coronary artery disease (P < .0001), and renal failure (P = .0001). Discharge with moderate to severe disability (P < .0001) and postprocedure neurological complications (P = .005) were more frequently reported in the post-CREST CAS group. After adjusting for age, sex, and risk factors, the odds ratio (OR) for moderate to severe disability was 1.0 (95% confidence interval [CI]: 0.8-1.2) in the pre-CREST CAS group and 1.4 (95% CI: 1.1-1.7) in the post-CREST CAS group compared with the reference group. The adjusted OR for neurological complications in the pre-CREST CAS group was 1.6 (95% CI: 1.2-2.1, P = .002), and 1.5 (95% CI: 1.1-2.0, P = .01) in the post-CREST CAS group. CONCLUSION: The frequency of CAS and CEA for carotid artery stenosis has not changed after publication of the CREST. The demographics, pretreatment comorbidity profile, and in-hospital complication rates remained unchanged during the 2 time periods.

Hematoma Enlargement Among Patients with Traumatic Brain Injury: Analysis of a Prospective Multicenter Clinical Trial.

Observational studies suggest that hematomas continue to enlarge during hospitalization in patients with traumatic brain injury (TBI). There is limited data regarding factors associated with hematoma enlargement and on whether hematoma enlargement contributes directly to death and disability in patients with TBI. We analyzed data collected as part of the Resuscitation Outcomes Consortium Hypertonic Saline and TBI Study. Hematoma enlargement was ascertained and collected as a predefined safety endpoint. We evaluated the effect of hematoma enlargement on the risk of death and disability at 6 months based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4) using stepwise logistic regression analysis. We adjusted for age (continuous variable), admission GCS score (dichotomized at >5 and ≤5), and computed tomography (CT) scan classification (Marshall grades entered as a categorical variable). Of the 1200 patients with severe TBI analyzed, 238 (19.8%) patients were reported to have hematoma enlargement as an adverse event. The proportion of patients who reached favorable outcome at 6 months was significantly lower (defined by GOSE of >4) among patients with hematoma enlargement (29.0% vs. 40.1%, p<.0001). The proportion of patients who died within 6 months was significantly higher among patients with hematoma enlargement (31.9% vs. 20.7%, p<.0001). After adjusting for age, admission GCS score, and initial injury score, the odds of favorable outcome was lower in patients with hematoma enlargement (odds ratio 0.7, 95% confidence interval [CI]; 0.5-0.97). Our results suggest that hematoma enlargement may be a direct contributor to death and disability in patients with TBI at 6 months. Future clinical trials must continue to evaluate new therapeutic interventions aimed at reducing hematoma enlargement with a favorable risk benefit ratio in patients with TBI.

Oral contraceptive use and incident stroke in women with sickle cell disease.

OBJECTIVE: Oral contraceptives increase the risk of ischemic stroke among women. However, the effect is not studied in the stroke prone sickle cell disease (SCD) population. We want to determine the rate of incident stroke among women with SCD enrolled in a large cohort with longitudinal follow-up. STUDY DESIGN: A total of 1257 women aged ≥15 and <45years, enrolled in Phase 1 of Cooperative Study of SCD, underwent a baseline examination for assessment of demographics, prior medical history, laboratory assessments, and clinical data. The effects of active oral contraceptive use at baseline interview on incident ischemic and hemorrhagic strokes were assessed after adjusting for potential confounders using Cox Proportional Hazards analysis. RESULTS: A total of 178 (14.2%) of 1257 women with SCD reported use of oral contraceptives. The age adjusted annual incidence of incident stroke was four folds higher among women who reported active oral contraceptive use than those who did not report use (1.6/100 person-years versus 0.4/ 100 person-years, p=0.03). After adjusting for age, cigarette smoking status, history of exchange transfusions, alcohol use, body weight, systolic blood pressure, and heart rate, oral contraceptive use was not significantly associated with rate of ischemic stroke (hazards ratio [HR], 3.6 95% confidence interval [CI] 0.8-16.5, p=0.09) or hemorrhagic stroke (HR, 1.2 95% CI 0.2-5.7, p=0.8). CONCLUSIONS: The four fold higher risk of incident stroke associated with use of oral contraceptives in women with SCD can be mitigated by controlling other cardiovascular risk factors. IMPLICATIONS: Our results are expected to increase the awareness, among both medical practitioners and patients, regarding the four fold higher risk of incident stroke associated with use of oral contraceptives in women with SCD. Our results also identify the confounding effect of other cardiovascular risk factors such as cigarette smoking on the observed relationship and thus identify potential targets for prevention.

Incident cancer in a cohort of 3,247 cancer diagnosis free ischemic stroke patients.

BACKGROUND: Subclinical cancer can manifest as a thromboembolic event and may be detected at a later interval in ischemic stroke survivors. We determined the rate of incident cancer and effect on cardiovascular endpoints in a large cohort of ischemic stroke survivors. METHODS: An analysis of 3,680 adults with nondisabling cerebral infarction who were followed for two years within the randomized, double-blinded VISP trial was performed. The primary intervention was best medical/surgical management plus a daily supplementation of vitamin B6, vitamin B12, and folic acid. We calculated age-adjusted rates of incidence of cancer among ischemic stroke survivors and standardized incidence ratios (SIR) with 95% confidence intervals (CI) based on comparison with age-adjusted rates in the general population. The significant variables from univariate analysis were entered in a Cox Proportional Hazards analysis to identify the association between various baseline factors and incident cancer after adjusting age, gender, and race/ethnicity. A logistic regression analysis evaluated the association between incident cancer and various endpoints including stroke, coronary heart disease, myocardial infarction, and death after adjusting age, gender, and race/ethnicity. RESULTS: A total of 3,247 patients (mean age ± SD of 66 ± 11; 2,013 were men) were cancer free at the time of enrollment. The incidence of new cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 months, 1 year, and 2 years, respectively. The age-adjusted annual rate of cancer in patients with ischemic stroke was higher than in persons in the general population at 1 year (581.8/100,000 persons vs. 486.5/100,000 persons, SIR 1.2, 95% CI 1.16-1.24) and 2 years (1,301.7/100,000 vs. 911.5/100,000, SIR 1.4, 95% CI 1.2-1.6) after recruitment. There was a higher risk for death (odds ratio (OR) 3.1, 95% CI 1.8-5.4), and composite endpoint of stroke, coronary heart disease, and/or death (OR 1.4, 95% CI 1.0-2.2) among participants who developed incident cancer compared with those who were cancer free after adjusting for potential confounders. CONCLUSIONS: The annual rate of age-adjusted cancer incidence was higher among ischemic stroke patients compared with those in the general population. The odds of mortality were three folds higher among stroke survivors who developed incident cancer.