Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial.

BACKGROUND: With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial. METHODS: We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110-139 mm Hg versus 140-179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days. RESULTS: Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00-5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71-1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions. CONCLUSIONS: Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 ).

Pre-Existing Renal Failure Increases In-Hospital Mortality in Patients with Intracerebral Hemorrhage.

BACKGROUND: To determine the clinical outcome for intracerebral hemorrhage (ICH) patients with pre-existing renal failure in the United States. METHODS: We analyzed the data from Nationwide Inpatient Sample (2008-2012) for all ICH patients with or without pre-existing renal failure. Patients were identified using the International Classification of Disease, Ninth Revision, Clinical Modification codes. Baseline characteristics, in-hospital complications, and exposure to invasive procedures were compared between groups. Discharge outcomes (mortality, minimal disability, and moderate-to-severe disability) were compared between the two groups, before and after adjusting for the presence of other medical comorbidities, in-hospital complications, and exposure to invasive procedures. RESULTS: Of the 328,728 patients with ICH, 36,067 (11.8%) had pre-existing renal failure as a comorbidity. There were higher rates for in-hospital complications like myocardial infarction (3.5% versus 1.9%, P ≤ .0001), sepsis (5.4% versus 3.0%, P ≤ .0001), pneumonia (7.1% versus 5.3%, P ≤ .0001), deep venous thrombosis (1.6% versus 1.2%, P = .0041), urinary tract infections (16.9% versus 15.1%, P = .0101), and gastrointestinal bleeding (0.4% versus 0.2%, P ≤ .0154), longer hospital stay (9.4 ± 14.4 versus 7.7 ± 11.4; P < .0001), and higher mean hospital charges ($86497.9 ± 131708.1 versus $69583.4 ± 110629.1; P < .0001) in patients with pre-existing renal failure . The in-hospital mortality was also higher among patients with pre-existing renal failure as comorbidity in both univariate (26.4% versus 25.3 %, P = .0010) and multivariate analysis (odds ratio [OR] = 1.124 [1.042-1.213], P = .0025). There was no statistically significant difference for in terms of moderate to severe disability between 2 groups (OR = 1.030 [0.962-1.104], P value: .3953 in multivariate analysis when analysis was limited to alive patients. CONCLUSIONS: Patients with ICH, who present with pre-existing renal failure, have higher rates of in-hospital mortality but not for disability, the difference remained significant after adjusting for the presence of other medical comorbidities, in-hospital complications or exposure to invasive procedures.

Albumin-Induced Neuroprotection in Focal Cerebral Ischemia in the ALIAS Trial: Does Severity, Mechanism, and Time of Infusion Matter?

OBJECTIVE: To determine whether there is any differential benefit of albumin administration within 2 h of onset of ischemia and in settings (severe ischemia with reperfusion in cardioembolic strokes with National Institutes of Health Stroke Scale [NIHSS] ≥15), most representative of experimental models of cerebral ischemia in which albumin was effective in reducing neurological injury. BACKGROUND: High-dose intravenous (IV) albumin treatment for acute ischemic stroke (ALIAS) trial did not show overall clinical benefit in ischemic stroke patients in contrast to preclinical studies; however, models of preclinical studies were not completely followed. METHODS: A total of 1275 patients combined from ALIAS trials I and II were included in our analysis. We analyzed preclinical studies and selected patients with large ischemic stroke (NIHSS ≥15) related to cardioembolic etiology (n = 189). Outcomes were then studied including time from onset to IV albumin administration. RESULTS: The odds of excellent outcome (mRS 0-1) at 3 months was not different with high-dose IV albumin infusion (n = 100) compared with placebo (n = 89) ((odds ratio [OR]) 1.632 [0.719-3.708], p value 0.2419). When we further classified these subjects according to time of IV albumin administration, we observed significantly higher odds of excellent outcome at 3 months when patients received IV albumin within 2 h, OR 9.369 (CI 1.040-84.405), p value 0.0461, after adjusting for age, gender, baseline NIHSS score, and any therapeutic procedure. CONCLUSION: A trend for benefit is noted in ischemic stroke patients with large cardioembolic stroke (NIHSS ≥15) when high-dose albumin was initiated within 2 h, suggesting that certain ischemic stroke subgroups of patients most representative of preclinical settings may benefit from such a treatment. Additional clinical trials maybe needed to stratify subjects and treatment assignments according to NIHSS severity and timely randomization to evaluate this concept further.

Phantom-based standardization of CT angiography images for spot sign detection.

PURPOSE: The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance. METHODS: A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%. RESULTS: A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p < 0.001). All spot signs identified in the non-calibrated analysis remained positive after calibration. Calibrated CTA images had higher sensitivity for ICH expansion (76 vs 52%) but inferior specificity (35 vs 63%) compared with uncalibrated images. CONCLUSION: Normalization of CTA images using phantom data is a feasible strategy to obtain consistent image quantification for spot sign analysis across different sites and may improve sensitivity for identification of ICH expansion.

Risk of Ischemic Stroke in High Risk Atrial Fibrillation Patients during Periods of Warfarin Discontinuation for Surgical Procedures.

IMPORTANCE: The risk of ischemic stroke during periods of warfarin discontinuation for surgical procedures is recognized but not well characterized. OBJECTIVE: The study aimed to quantitate the risk of ischemic stroke associated with high risk atrial fibrillation during periods of warfarin discontinuation. DESIGN, SETTING AND PARTICIPANTS: A cohort of 4,060 patients (mean follow-up period of 3.5 ± 1.3 years) were randomized into the Atrial Fibrillation Follow-Up Investigation of Rhythm Management study. Patients enrolled in the study had atrial fibrillation plus at least one other risk factor for stroke or death: age ≥65 years', systemic hypertension, diabetes mellitus, congestive heart failure, transient ischemic attack, prior stroke, left atrium >50 mm, left ventricular fractional shortening <25% or left ventricular ejection fraction <40%. EXPOSURE: Warfarin discontinuation for procedure. MAIN OUTCOME AND MEASURES: The association of warfarin discontinuation with the incidence of ischemic stroke using pooled repeated measures and Cox proportional hazards analyses during follow-up after adjusting for age, gender, obesity, diabetes mellitus, hypercholesterolemia, cigarette smoking and study period. RESULTS: Warfarin discontinuation for procedure occurred in 265 (0.4%) of the 71,355 person observations. Compared with those without warfarin discontinuation, the rate of ischemic stroke was higher among participants with surgery-related warfarin discontinuation (1.1% of 265 person observations vs. 0.2% of 71,090 person observations, p = 0.001). Warfarin discontinuation was associated with an increased risk for ischemic stroke (relative risk 5.8; 95% CI 1.8-18.4) after adjusting for potential confounders. The population-attributable risk associated with surgery-related warfarin discontinuation was estimated to be 23.1% (95% CI 15.2-30.9%) for ischemic stroke. CONCLUSIONS AND RELEVANCE: The 6-fold higher risk of ischemic stroke associated with discontinuation of warfarin for surgical procedures must be recognized in high risk atrial fibrillation patients and considered in the risk-benefit analysis of any procedure.

A Population-Based Study of the Incidence of Acute Spinal Cord Infarction.

BACKGROUND: There is a paucity of reliable data regarding incidence of acute spinal cord infarction in population-based studies. OBJECTIVES: To determine the incidence of acute spinal cord infarction using a population-based design. METHODS: Medical records and neuroimaging data of all patients with acute spinal cord infarction from Stearns and Benton Counties, Minnesota, between January 1, 2010 and May 31, 2014 were reviewed. Patients with a first-time diagnosis of spinal cord infarction were categorized as primary or secondary depending upon underlying etiology identified. We calculated the incidences of primary and secondary spinal cord infarction adjusted for age and sex based on the 2010 US census (189,093 resident populations). RESULTS: The age- and sex-adjusted incidence of spinal cord infarction was 3.1 [95% confidence interval (CI) 1.6-7.2] per100,000 person-years. The age- and sex-adjusted incidence of primary and secondary spinal cord infarction was 1.5 [95% CI 0.6-3.6] and 1.6 [95% CI 0.6-3.6] per 100,000 person-years, respectively. The age-adjusted incidences among men and women were 1.5 [95%CI 0.6-3.7] and 4.6 [95% CI 2.2-8.7] per 100,000 person-years, respectively. No case fatality was observed at one month. CONCLUSION: We provide incidence rates for acute spinal cord infarction to assist in future studies and resource allocation.

Vertebral Artery Origin Stent Placement Using the Dual Lumen Qureshi-Jiao Guidecatheter.

OBJECTIVE: We report the first experience with a new dual lumen guide catheter with lumen A with curved tip designed for delivery of stent and angioplasty catheters and lumen B with side exit for coaxial placement of stiff 0.014 inch wire. METHODS: We prospectively determined technical success, intended procedure (stent delivery at target lesion and a final residual stenosis <30%) completed without a need for a different catheter, and technical ease, intended procedure completed without ≥3 unsuccessful attempts in patients with symptomatic vertebral artery origin stenosis. Vertebral artery origin was classified as type A if originated from ascending segment and type B if originated from an arch or horizontal segment of subclavian artery. RESULTS: The mean age of the four treated patients was 66.2 years (range 64-68 years). The mean percentage of vertebral artery origin stenosis was 82.7% (range 60-92%). The origin of vertebral artery from subclavian artery was classified as type A and type B origins in two patients each. The dual lumen catheter was advanced over an exchange length of 0.035 inch glide wire in one patient and directly through transfemoral insertion in three patients. Technical success and technical ease was achieved in all four procedures. Post procedure residual stenosis was 6% (range 5-7%). The primary operator rated the performance of guide catheter as superior compared with another catheter used in such procedures. CONCLUSION: The present study demonstrates the feasibility of performing stent placement for vertebral artery origin stenosis by using a dual lumen catheter with superior performance.

Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion.

OBJECTIVE: To validate various noncontrast CT (NCCT) predictors of hematoma expansion in a large international cohort of ICH patients and investigate whether intensive blood pressure (BP) treatment reduces ICH growth and improves outcome in patients with these markers. METHODS: We analyzed patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized controlled trial. Participants were assigned to intensive (systolic BP <140 mm Hg) vs standard (systolic BP <180 mm Hg) treatment within 4.5 hours from onset. The following NCCT markers were identified: intrahematoma hypodensities, black hole sign, swirl sign, blend sign, heterogeneous hematoma density, and irregular shape. ICH expansion was defined as hematoma growth >33% and unfavorable outcome was defined as modified Rankin Scale score >3 at 90 days. Logistic regression was used to identify predictors of ICH expansion and explore the association between NCCT signs and clinical benefit from intensive BP treatment. RESULTS: A total of 989 patients were included (mean age 62 years, 61.9% male), of whom 186/869 experienced hematoma expansion (21.4%) and 361/952 (37.9%) had unfavorable outcome. NCCT markers independently predicted ICH expansion (all p < 0.01) with overall accuracy ranging from 61% to 78% and good interrater reliability (k > 0.6 for all markers). There was no evidence of an interaction between NCCT markers and benefit from intensive BP reduction (all p for interaction >0.10). CONCLUSIONS: NCCT signs reliably identify ICH patients at high risk of hematoma growth. However, we found no evidence that patients with these markers specifically benefit from intensive BP reduction. CLINICALTRIALSGOV IDENTIFIER: NCT01176565.

Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The computed tomographic angiography (CTA) spot sign is associated with intracerebral hemorrhage (ICH) expansion and may mark those patients most likely to benefit from intensive blood pressure (BP) reduction. Objective: To investigate whether the spot sign is associated with ICH expansion across a wide range of centers and whether intensive BP reduction decreases hematoma expansion and improves outcome in patients with ICH and a spot sign. Design, Setting, and Participants: SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized clinical trial. Participants included consecutive patients with primary ICH who underwent a CTA within 8 hours from onset at 59 sites from May 15, 2011, through December 19, 2015. Data were analyzed for the present study from July 1 to August 31, 2016. Main Outcomes and Measures: Patients in ATACH-II were randomized to intensive (systolic BP target, <140 mm Hg) vs standard (systolic BP target, <180 mm Hg) BP reduction within 4.5 hours from onset. Expansion of ICH was defined as hematoma growth of greater than 33%, and an unfavorable outcome was defined as a 90-day modified Rankin Scale score of 4 or greater (range, 0-6). The association among BP reduction, ICH expansion, and outcome was investigated with multivariable logistic regression. Results: A total of 133 patients (83 men [62.4%] and 50 women [37.6%]; mean [SD] age, 61.9 [13.1] years) were included. Of these, 53 (39.8%) had a spot sign, and 24 of 123 without missing data (19.5%) experienced ICH expansion. The spot sign was associated with expansion with sensitivity of 0.54 (95% CI, 0.34-0.74) and specificity of 0.63 (95% CI, 0.53-0.72). After adjustment for potential confounders, intensive BP treatment was not associated with a significant reduction of ICH expansion (relative risk, 0.83; 95% CI, 0.27-2.51; P = .74) or improved outcome (relative risk of 90-day modified Rankin Scale score ≥4, 1.24; 95% CI, 0.53-2.91; P = .62) in spot sign-positive patients. Conclusions and Relevance: The predictive performance of the spot sign for ICH expansion was lower than in prior reports from single-center studies. No evidence suggested that patients with ICH and a spot sign specifically benefit from intensive BP reduction. Trial Registration: clinicaltrials.gov Identifier: NCT01176565.

Lumbar Catheter Placement Using Paramedian Approach Under Fluoroscopic Guidance.

BACKGROUND: Lumbar catheter placement under fluoroscopic guidance may reduce the rate of technical failures and associated complications seen with insertion guided by manually palpable landmarks. METHODS: We reviewed our experience with 43 attempted lumbar catheter placements using paramedian approach under fluoroscopic guidance and ascertained rates of technical success, and clinical events. RESULTS: Among the 43 patients, 18, 1, and 1 patients were on aspirin (with dipyrimadole in 2), clopidogrel, and combination of both, respectively. Lumbar catheter placement was successful in 42 of 43 attempted placements. Floroscopic guidance was critical in three patients; one patient had severe cerebrospinal fluid (CSF) depletion (empty thecal sac phenomenon) following pituitary surgery leading to no cerebrospinal fluid return despite correct placement confirmation under fluoroscopy. Two patients had spinal needle placement at the junction between epidural and cerebrospinal fluid spaces (junctional position) leading to cerebrospinal fluid return but inability to introduce the lumbar catheter. After confirmation of position by the injection of contrast or radiographic landmarks the needle was advanced by indenting the subcutaneous tissue or reinserting at a spinal level above the first insertion. The lumbar catheter remained in position over a mean period (±standard deviation) of 4.1(±2.3) days. Improvement in hydrocephalus was seen in two patients with intracranial mass lesions. One patient developed cerebrospinal fluid leakage through the insertion track following removal of catheter and required skin suturing at the site of insertion. CONCLUSIONS: We observed a high technical success rate with low rate of complications even in patients with intracranial mass lesions, those on ongoing antiplatelet medications or in whom insertion would not be possible guided by manually palpable landmarks.

Human Immunodeficiency Viral Infection and Status Epilepticus in United States (2002-2009).

OBJECTIVE: To determine the association between human immunodeficiency virus (HIV) infection and status epilepticus and compare the outcomes of patients with status epilepticus with or without underlying HIV infection. METHODS: Patients with primary diagnosis of status epilepticus (cases) and status asthmaticus (controls) were identified from the 2002-2009 Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. We performed logistic regression analysis adjusting for age, gender, co-morbid conditions, including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and opportunistic infections. We compared the in hospital outcomes among patients admitted with status epilepticus in strata defined by underlying HIV infection. RESULTS: The rate of concurrent status epilepticus and HIV has increased over the last 7 years in hospitalized patients with status epilepticus in United States (0.14%-0.27% p<0.0001). The HIV infection was significantly associated with status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8-2.6; p<0.0001)) after adjusting for age, gender, opportunistic infections, and cardiovascular risk factors. The in-hospital mortality was significantly higher while discharge with none or minimal disability was significantly lower in status epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and (50.4% vs. 63.3%, p<0.0001), respectively. CONCLUSIONS: Our study suggests that there is a direct association between HIV infection and status epilepticus. The proportion of patients admitted with concurrent status epilepticus and HIV infections is increasing and such patients have higher rates of poor discharge outcomes.