Nazli Janjua

Cardiac Troponin Elevation, Cardiovascular Morbidity, and Outcome After Subarachnoid Hemorrhage

Background— Cardiac troponin I (cTI) release occurs frequently after subarachnoid hemorrhage (SAH) and has been associated with a neurogenic form of myocardial injury. The prognostic significance and clinical impact of these elevations remain poorly defined. Methods and Results— We studied 253 SAH patients who underwent serial cTI measurements for clinical or ECG signs of potential cardiac injury. These patients were drawn from an inception cohort of 441 subjects enrolled in the Columbia University SAH Outcomes Project between November 1998 and August 2002. Peak cTI levels were divided into quartiles or classified as undetectable. Adverse in-hospital events were prospectively recorded, and outcome at 3 months was assessed with the modified Rankin Scale. Admission predictors of cTI elevation included poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, and a composite score of physiological derangement (all P≤0.01). Peak cTI level was associated with an increased risk of echocardiographic left ventricular dysfunction (odds ratio [OR], 1.3 per quintile; 95% CI, 1.0 to 1.7; P=0.03), pulmonary edema (OR, 2.1 per quintile; 95% CI, 1.6 to 2.7; P<0.001), hypotension requiring pressors (OR, 1.9 per quintile; 95% CI, 1.5 to 2.3; P<0.001), and delayed cerebral ischemia from vasospasm (OR, 1.3 per quintile; 95% CI, 1.07 to 1.7; P=0.01). Peak cTI levels were predictive of death or severe disability at discharge after controlling for age, clinical grade, and aneurysm size (adjusted OR, 1.4 per quintile; 95% CI, 1.1 to 1.9; P=0.02), but this association was no longer significant at 3 months. Conclusions— cTI elevation after SAH is associated with an increased risk of cardiopulmonary complications, delayed cerebral ischemia, and death or poor functional outcome at discharge.

Phenytoin Exposure Is Associated With Functional and Cognitive Disability After Subarachnoid Hemorrhage

Background and Purpose— Phenytoin (PHT) is routinely used for seizure prophylaxis after subarachnoid hemorrhage (SAH), but may adversely affect neurologic and cognitive recovery. Methods— We studied 527 SAH patients and calculated a “PHT burden” for each by multiplying the average serum level of PHT by the time in days between the first and last measurements, up to a maximum of 14 days from ictus. Functional outcome at 14 days and 3 months was measured with the modified Rankin scale, with poor functional outcome defined as dependence or worse (modified Rankin Scale ≥4). We assessed cognitive outcomes at 14 days and 3 months with the telephone interview for cognitive status. Results— PHT burden was associated with poor functional outcome at 14 days (OR, 1.5 per quartile; 95% CI, 1.3 to 1.8; P<0.001), although not at 3 months (P=0.09); the effect remained (OR, 1.6 per quartile; 95% CI, 1.2 to 2.1; P<0.001) after correction for admission Glasgow Coma Scale, fever, stroke, age, National Institutes of Health Stroke Scale ≥10, hydrocephalus, clinical vasospasm, and aneurysm rebleeding. Seizure in hospital (OR, 4.1; 95% CI, 1.5 to 11.1; P=0.002) was associated with functional disability in a univariate model only. Higher quartiles of PHT burden were associated with worse telephone interview for cognitive status scores at hospital discharge (P<0.001) and at 3 months (P=0.003). Conclusions— Among patients treated with PHT, burden of exposure to PHT predicts poor neurologic and cognitive outcome after SAH.

Clinical trial of a novel surface cooling system for fever control in neurocritical care patients

Objective:To compare the efficacy of a novel water-circulating surface cooling system with conventional measures for treating fever in neuro-intensive care unit patients. Design:Prospective, unblinded, randomized controlled trial. Setting:Neurologic intensive care unit in an urban teaching hospital. Patients:Forty-seven patients, the majority of whom were mechanically ventilated and sedated, with fever ≥38.3°C for >2 consecutive hours after receiving 650 mg of acetaminophen. Interventions:Subjects were randomly assigned to 24 hrs of treatment with a conventional water-circulating cooling blanket placed over the patient (Cincinnati SubZero, Cincinnati OH) or the Arctic Sun Temperature Management System (Medivance, Louisville CO), which employs hydrogel-coated water-circulating energy transfer pads applied directly to the trunk and thighs. Measurements and Main Results:Diagnoses included subarachnoid hemorrhage (60%), cerebral infarction (23%), intracerebral hemorrhage (11%), and traumatic brain injury (4%). The groups were matched in terms of baseline variables, although mean temperature was slightly higher at baseline in the Arctic Sun group (38.8 vs. 38.3°C, p = .046). Compared with patients treated with the SubZero blanket (n = 24), Arctic Sun-treated patients (n = 23) experienced a 75% reduction in fever burden (median 4.1 vs. 16.1 C°-hrs, p = .001). Arctic Sun-treated patients also spent less percent time febrile (T ≥38.3°C, 8% vs. 42%, p < .001), spent more percent time normothermic (T ≤37.2°C, 59% vs. 3%, p < .001), and attained normothermia faster than the SubZero group median (2.4 vs. 8.9 hrs, p = .008). Shivering occurred more frequently in the Arctic Sun group (39% vs. 8%, p = .013). Conclusion:The Arctic Sun Temperature Management System is superior to conventional cooling-blanket therapy for controlling fever in critically ill neurologic patients.

Cerebral vasospasm after subarachnoid hemorrhage

Purpose of reviewTo summarize new pathophysiologic insights and recent advances in the diagnosis and treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Recent findingsImportant, newly recognized mediators of cerebral arterial spasm after subarachnoid hemorrhage include superoxide free radicals, ferrous hemoglobin (which acts as a nitric oxide scavenger), endothelins, protein kinase C, and &rgr; kinase. Microvascular dysfunction and autoregulatory failure also has been an area of increasing research focus in recent years. New diagnostic modalities include measures of cerebral blood flow such as single-photon emission computed tomography and perfusion computed tomography, magnetic resonance imaging, intracranial brain oxygen tension probes, and jugular venous oxygen saturation monitors. Proton magnetic resonance spectroscopy and microdialysis can detect tissue biochemical abnormalities, but these techniques have not found their way into routine clinical practice as of yet. In addition to nimodipine and hypertensive hypervolemic therapy, promising new treatments for vasospasm or its ischemic complications include magnesium sulfate, fasudil hydrochloride, tirilazad mesylate, erythropoietin, and induced hypothermia. Balloon angioplasty has emerged as the primary weapon for treating medically refractory ischemia from vasospasm and in many centers is being used as a first-line treatment or even prophylactically. SummaryThe neurointensive care management of vasospasm after subarachnoid hemorrhage has evolved significantly over the past 10 years, with many new diagnostic modalities and promising treatments now available. Clinical trials are needed to evaluate the efficacy of these new techniques and to further define the optimal management of this often devastating complication.

Thrombolysis for Ischemic Stroke in Children: Data From the Nationwide Inpatient Sample

Background and Purpose— Few pediatric reports of thrombolysis exist. We sought to determine national rates of thrombolysis among pediatric ischemic stroke patients using a national database. Methods— Patients between the ages of 1 and 17 years, entered in the Nationwide Inpatient Sample between 2000 and 2003, with International Classification of Diseases codes for ischemic stroke were included in the study. Differences in mean age, gender distribution, ethnicity, secondary diagnoses, medical complications, associated procedure rates, modes of discharge, and hospital costs between pediatric stroke patients receiving and not receiving thrombolysis were estimated. Results— In the United States, between 2000 and 2003 an estimated 2904 children were admitted with ischemic stroke, of which 46 children (1.6%) received thrombolytic therapy. Children who received thrombolysis were on the average older (11 versus 9 years), more likely to be male (100% versus 53.8%), with significantly higher hospital costs (

Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study.

81 800 versus

Intra-arterial reteplase and intravenous abciximab in patients with acute ischemic stroke: An open-label, dose-ranging, phase I study

38 700). These children were also less likely to be discharged home with higher rates of death and dependency, although differences in clinical severity between the 2 groups was not known. Conclusion— Thrombolysis, though not indicated for patients <18 years of age, is currently being administered to children, with unclear benefit. Larger studies are needed to evaluate the safety and efficacy of this treatment for children.

Intra-Arterial Recanalization Techniques for Patients 80 Years or Older with Acute Ischemic Stroke: Pooled Analysis from 4 Prospective Studies

OBJECTIVE:Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which exhibit beneficial cerebrovascular effects by modulating inflammation and nitric oxide production, have not been evaluated in acute aneurysmal subarachnoid hemorrhage (SAH) patients. The effect of prior statin use on 14-day functional outcome and on prevention of vasospasm-induced delayed cerebral ischemia (DCI) or stroke during hospitalization was analyzed. METHODS:We conducted a 1:2 matched (age, admission Hunt and Hess grade, vascular disease/risk history) cohort study of 20 SAH patients on statins and 40 SAH controls. The primary outcome was functional outcome at 14 days (Modified Lawton Physical Self-Maintenance Scale and Barthel Index scale scores). Secondary outcomes were 14-day mortality, Modified Rankin Scale score, DCI, DCI supported by angiography/transcranial Doppler [TCD], cerebral infarctions of any type, and TCD highest mean velocity elevation. RESULTS:Statin users demonstrated a significant protective effect on 14-day Barthel Index scale and Modified Lawton Physical Self-Maintenance Scale scores (77 ± 10 versus 39 ± 8, P = 0.003; 12 ± 7 versus 19 ± 9, P = 0.03, respectively). Moreover, statin users demonstrated a significantly lower incidence of DCI and DCI supported by angiography/TCD (10% versus 43%, P = 0.02; 5% versus 35%, P = 0.01, respectively), cerebral infarctions of any type (25% versus 63%, P = 0.01), and baseline-to-final TCD highest mean velocity change of 50 cm/s or greater (18% versus 51%, P = 0.03). CONCLUSION:SAH statin users demonstrated significant improvement in 14-day functional outcome, a significantly lower incidence of DCI and cerebral infarctions of any type, as well as prevention of TCD highest mean velocity elevation. However, we did not find a significant statin impact on mortality or global outcome (Modified Rankin Scale) in this small sample. This study provides clinical evidence for the potential therapeutic benefit of statins after acute SAH.

Is IV tissue plasminogen activator beneficial in patients with hyperdense artery sign

OBJECTIVE:New approaches are focusing on using a combination of medication that lyse fibrin and prevent aggregation of platelets to achieve higher rates of recanalization and improved clinical outcomes. METHODS:A prospective, nonrandomized, open-label trial evaluated the safety of an escalating dose of reteplase in conjunction with intravenous abciximab (platelet glycoprotein IIb/IIIa inhibitor) in patients with acute ischemic stroke (3–6 h after symptom onset). The primary endpoint was symptomatic intracerebral hemorrhage at 24 to 72 hours, and secondary endpoints were partial or complete recanalization (≥ one grade improvement), early neurological improvement (decrease in National Institutes of Health Stroke Scale ≥ 4 at 24 h), and favorable outcome at 1 month (defined by modified Rankin scale ≤ 2). RESULTS:A total of 20 patients (mean age, 65 yr; 13 men) were recruited. Five patients were recruited in each of the escalating tiers of intra-arterial reteplase (0.5, 1, 1.5, and 2 units). Intravenous abciximab (0.25 mg/kg bolus followed by 0.125 &mgr;g/kg/min) was successfully administered in 18 out of 20 patients. The safety stopping rule was not activated in any of the tiers. One symptomatic intracerebral hemorrhage was observed in one of the 20 patients (in the 1-unit tier). Partial or complete recanalization was observed in 13 of the 20 patients. Thirteen patients demonstrated early neurological improvement, and favorable outcome at 1 month was observed in six patients. CONCLUSION:In this study, a combination of intra-arterial reteplase and intravenous abciximab was safely administered to patients with ischemic stroke presenting between 3 and 6 hours after symptom onset.

Demand-supply of neurointerventionalists for endovascular ischemic stroke therapy

BACKGROUND AND PURPOSE: Previous studies have demonstrated limited benefit with endovascular procedures such as stent placement in octogenarians. We evaluated the safety and effectiveness of intra-arterial recanalization techniques to treat ischemic stroke in patients 80 years or older presenting within 6 hours of symptom onset. MATERIALS AND METHODS: We pooled the data from 4 prospective studies by evaluating intra-arterial recanalization techniques for treatment of ischemic stroke. Clinical and radiologic evaluations were performed before treatment and at 24 hours, 7 to 10 days, and 1 to 3 months after treatment. We performed multivariate analyses to evaluate the effect of ages 80 years and older on angiographic recanalization, favorable outcome (modified Rankin scale of 0–2), and mortality rate at 1 to 3 months. RESULTS: A total of 101 patients were treated in the 4 protocols. Of these, 24 were 80 years or older. There was no significant difference between the 2 age groups in sex, initial stroke severity, time to treatment, site of vascular occlusion, and rate of symptomatic and asymptomatic intracranial hemorrhage (ICH). In logistic regression analysis, age 80 years or older was associated with a lower likelihood of a favorable outcome (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.13–1.2; P = .11) and recanalization (OR, 0.36; 95% CI, 0.12–1.1; P = .07) and with higher mortality rate (OR, 3.17; 95% CI, 1.05–9.55; P = .04) after adjusting for study protocol. After adjusting for recanalization in addition to study protocol, the older age group still had a lower likelihood of favorable outcomes (OR, 0.34; 95% CI, 0.1–1.1; P = .07) and higher mortality rates (OR, 3.62; 95% CI, 1.15–11.36; P = .027). CONCLUSIONS: Our study demonstrates that patients 80 years and older are at higher risk for poor outcome at 1 to 3 months following intra-arterial recanalization techniques. This relationship is independent of recanalization rate and symptomatic ICH supporting the role of other mechanisms.