Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study.

BACKGROUND: In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting. METHODS: Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview. RESULTS: Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p < 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age > 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test < 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression. CONCLUSIONS: Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department. TRIAL REGISTRATION: Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov.

Etiological classifications of transient ischemic attacks: subtype classification by TOAST, CCS and ASCO--a pilot study.

BACKGROUND: In patients with transient ischemic attacks (TIA), etiological classification systems are not well studied. The Trial of ORG 10172 in Acute Stroke Treatment (TOAST), the Causative Classification System (CCS), and the Atherosclerosis Small Vessel Disease Cardiac Source Other Cause (ASCO) classification may be useful to determine the underlying etiology. We aimed at testing the feasibility of each of the 3 systems. Furthermore, we studied and compared their prognostic usefulness. METHODS: In a single-center TIA registry prospectively ascertained over 2 years, we applied 3 etiological classification systems. We compared the distribution of underlying etiologies, the rates of patients with determined versus undetermined etiology, and studied whether etiological subtyping distinguished TIA patients with versus without subsequent stroke or TIA within 3 months. RESULTS: The 3 systems were applicable in all 248 patients. A determined etiology with the highest level of causality was assigned similarly often with TOAST (35.9%), CCS (34.3%), and ASCO (38.7%). However, the frequency of undetermined causes differed significantly between the classification systems and was lowest for ASCO (TOAST: 46.4%; CCS: 37.5%; ASCO: 18.5%; p < 0.001). In TOAST, CCS, and ASCO, cardioembolism (19.4/14.5/18.5%) was the most common etiology, followed by atherosclerosis (11.7/12.9/14.5%). At 3 months, 33 patients (13.3%, 95% confidence interval 9.3-18.2%) had recurrent cerebral ischemic events. These were strokes in 13 patients (5.2%; 95% confidence interval 2.8-8.8%) and TIAs in 20 patients (8.1%, 95% confidence interval 5.0-12.2%). Patients with a determined etiology (high level of causality) had higher rates of subsequent strokes than those without a determined etiology [TOAST: 6.7% (95% confidence interval 2.5-14.1%) vs. 4.4% (95% confidence interval 1.8-8.9%); CSS: 9.3% (95% confidence interval 4.1-17.5%) vs. 3.1% (95% confidence interval 1.0-7.1%); ASCO: 9.4% (95% confidence interval 4.4-17.1%) vs. 2.6% (95% confidence interval 0.7-6.6%)]. However, this difference was only significant in the ASCO classification (p = 0.036). Using ASCO, there was neither an increase in risk of subsequent stroke among patients with incomplete diagnostic workup (at least one subtype scored 9) compared with patients with adequate workup (no subtype scored 9), nor among patients with multiple causes compared with patients with a single cause. CONCLUSION: In TIA patients, all etiological classification systems provided a similar distribution of underlying etiologies. The increase in stroke risk in TIA patients with determined versus undetermined etiology was most evident using the ASCO classification.

Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.

BACKGROUND: There is insufficient evidence regarding which clinical features are best suited to distinguish between transient ischemic attack (TIA) and disorders mimicking TIA (TIA mimics). METHODS: We compared the frequency, clinical characteristics and outcome of patients with TIA and TIA mimics in a prospective, single-center emergency department cohort over 2 years. RESULTS: Of 303 patients, 248 (81.8%) had a TIA and 55 (18.2%) had TIA mimics. Epileptic seizures (26/55; 43.7%) and migraine attacks (13/55; 23.6%) were the most common TIA mimics. In patients presenting with unilateral paresis, TIA mimics were less likely than in patients without unilateral paresis [odds ratio (OR) 0.35, 95% confidence interval (CI) 0.17-0.68]. Memory loss (OR 9.17, 95% CI 2.89-32.50), headache (OR 3.71, 95% CI 1.07-12.78) and blurred vision (OR 2.48, 95% CI 0.90-6.59) increased the odds of TIA mimics. Once these clinical features were taken into account, neither aphasia, dysarthria, sensory loss, blood pressure values nor the duration of symptoms were found to improve explanation of the underlying status. At 3 months, stroke, recurrent TIA and myocardial infarction were absent in patients with TIA mimics but occurred in 13 (5.2%), 20 (8.1%) and 3 (1.2%) TIA patients, respectively. CONCLUSIONS: About 1 in every 5 patients with suspected TIA had a TIA mimic. Paresis suggested TIA, while other clinical variables used in risk assessment scores after TIA were not shown to distinguish between the two entities. Patients with TIA mimics had a better short-term prognosis.