Original Article

Prevalence and prognostic value of headache on early mortality in acute stroke: The Dijon Stroke Registry

Cephalalgia 2014, Vol. 34(11) 887–894 ! International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102414523340 cep.sagepub.com

Victor Abadie, Agne`s Jacquin, Benoit Daubail, Anne-Laure Vialatte, Claire Lainay, Je´roˆme Durier, Guy-Victor Osseby, Maurice Giroud and Yannick Be´jot Abstract Objective: To evaluate the prevalence of headache at onset and its association with 1-month mortality in stroke patients. Methods: All patients with stroke in Dijon, France (2006–2011), were prospectively identified using a populationbased registry. Cox regression models were used to evaluate the association between headache and 30-day all-cause mortality. Results: Among 1411 stroke patients, data about headache were obtained for 1391 (98.6%) of whom 1185 had an ischemic stroke (IS), 201 had an intracerebral hemorrhage (ICH) and five had a stroke of undetermined etiology. Headache was found in 253 (18.2%) patients and was more frequent in those with ICH than in those with IS (46.3% vs 13.5%, p < 0.001). Overall 30-day mortality was 11.7%, and was greater for patients with than those without headache (17.0% vs 10.5%, unadjusted HR 1.70; 95% CI 1.20–2.41, p ¼ 0.003). In multivariable analysis, an association between headache and 30-day mortality was observed (HR 1.51; 95% CI 1.02–2.25, p ¼ 0.042). In stratified analyses, headache was associated with 30-day mortality in ICH (HR 2.09; 95% CI 1.18–3.71, p ¼ 0.011) but not in IS (HR 1.01; 95% CI 0.53–1.92, p ¼ 0.97). Conclusion: Headache at stroke onset is associated with a higher risk of early mortality in patients with ICH. Keywords Epidemiology, headache, mortality, outcome, registry, stroke Date received: 20 August 2013; revised: 14 October 2013; 30 October 2013; 28 November 2013; 20 December 2013; accepted: 18 January 2014

Introduction Although headache is considered a classical clinical feature of stroke, the exact prevalence of this symptom is controversial. Hence, the reported frequency of stroke-related headache ranges from 7% to 65% according to various studies (1–8). Several factors, such as the hospital-based setting of studies, which resulted in large differences in recruited patients, and the absence of differentiation between stroke subtypes probably contributed to the divergent findings. In addition, the clinical relevance of headache in terms of prognosis in stroke patients has not been fully investigated (5–8). Therefore, this population-based study aimed to evaluate the prevalence of headache at onset and its association with 1-month mortality in stroke patients.

Methods Study population and case-ascertainment procedures The study population included all patients with stroke that occurred between 1 January 2006 and 31

Dijon Stroke Registry, Department of Neurology, University Hospital and Medical School of Dijon, University of Burgundy, France Corresponding author: Yannick Be´jot, Dijon Stroke Registry, EA4184, Department of Neurology, CHU, 3 Rue du Faubourg Raines, 21000 Dijon, France. Email: [email protected]

888 December 2011, who were prospectively identified among residents of the city of Dijon, France (2007 census: 151,543 inhabitants) from the Dijon Stroke Registry. This population-based registry complies with the criteria recommended for the running of high-quality stroke incidence studies (9,10), and casecollection procedures have been described elsewhere (11,12). Briefly, multiple overlapping sources of information were used to identify fatal and non-fatal stroke in hospitalized and non-hospitalized patients: (a) a review of medical records from the emergency rooms, and all the clinical and radiological departments of Dijon University Hospital, with a diagnosis of stroke made by one of the neurologists of the department of neurology, where the Stroke Registry is located; (b) a review of medical records from the emergency rooms and all of the clinical departments of the three private hospitals of the city and its suburbs, with diagnosis made by neurologists working in these establishments; (c) a review of computerized hospital diagnostic codes of Dijon University Hospital. The International Classification of Diseases, tenth revision (ICD-10) was used. The following codes are initially searched for: I60 (subarachnoid hemorrhage), I61 (intracerebral hemorrhage), I62 (non-traumatic intracranial hemorrhage), I63 (ischemic stroke), I64 (non-determined stroke), G45 (vascular syndromes), G46 (transient ischemic attack) G81 (hemiplegia). Study investigators then consulted the medical records of identified patients to confirm or not the reported diagnosis or to reclassify the patients if a misclassification was noted; (d) a review of computerized hospital diagnostic codes of the private hospitals with the same procedure as described above; (e) collaboration with the general practitioners to identify stroke patients managed at home or in nursing homes, with the diagnosis assessed by public or private neurologists from outpatient clinics; (f) a review of the medical records of patients identified from a computer-generated list of all requests for imaging to the private radiological and Doppler ultrasound centers of the city and its suburbs; (g) and regular checking of death certificates obtained from the local social security bureau that is responsible for the registration of deaths in the community particularly fatal strokes outside hospital. The quality and the completeness of the registry are certified every 4 years by an audit from the National Institute for Health and Medical Research and the National Public Health Institute. Stroke was defined according to World Health Organization recommendations (13). We distinguished between ischemic stroke (IS), spontaneous intracerebral hemorrhage (ICH) and undermined stroke. For this study, subarachnoid hemorrhage was excluded.

Cephalalgia 34(11)

Data collected The following vascular risk factors were systematically collected (11,12): hypertension (high blood pressure noted in a patient’s medical history or patients on antihypertensive treatment), diabetes mellitus (glucose level 7.8 mmol/l reported in the medical record or patients on insulin or oral hypoglycemic agents), hypercholesterolemia (total cholesterol level 5.7 mmol/l reported in the medical history or patients treated with lipid-lowering therapy), atrial fibrillation, history of coronary heart disease, heart failure, peripheral artery disease (PAD), alcohol intake (3 units a day in men and 2 in women), smoking, cancer, and previous stroke or TIA. Treatments prior to the stroke, including antiplatelet agents, anticoagulants, antihypertensive treatments and statins were recorded. We also collected information on pre-stroke residence in a nursing home as a proxy of dependency and thrombolysis for IS patients. Headache at stroke onset was defined as cephalic pain appearing just before or after other stroke symptoms. We assessed headache in all patients with a routine neurological questionnaire that was completed by the emergency medical dispatchers at the call center for emergencies and/or at admission for patients hospitalized or during clinical consultations for outpatients. Relatives were asked about the history of headache at stroke onset either by the emergency medical dispatchers or at the time of the first examination if the patients were unconscious, confused or aphasic. Stroke severity was quantified by the means of the National Institutes of Health Stroke Scale (NIHSS) score either obtained at the first clinical examination or estimated on the basis of the review of medical records and charts when patients were identified retrospectively, as previously validated in the literature (14). The etiological classification of IS patients was derived from the TOAST classification (15) as follows: large artery IS, cardioembolic IS, lacunar IS, IS from other identified cause, IS from undetermined cause and IS from multiple possible causes. The ICH locations were reported according to the findings of CT scans except for one patient in whom only MRI was performed. For this study, all brain imaging data were blindly reviewed by three investigators (VA, YB, MG) to confirm the location of the ICH. We considered the following locations, as previously reported: lobar, deep infratentorial (11). Intraventricular extension of bleeding was reported. In cases of uncertainty about the ICH location, especially for patients with large ICH, the most probable origin was discussed by the investigators. ICH location was classified as undetermined either when the origin could not be reliably identified, including cases of hemorrhage that overlapped two territories, or unreported data or lost files.

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Abadie et al. All-cause mortality at 30 days was systematically assessed using death certificates.

Statistical analysis Proportions and mean values of baseline characteristics were compared between groups using the chi-square test, and the Wilcoxon–Mann–Whitney test when appropriate. Person-days were calculated from the date of onset until death, the last contact date and the end of follow-up at 1 month. Survival curves were obtained using Kaplan–Meier analysis, and the logrank test was used for comparisons between groups. Cox regression models were used to estimate hazard ratios (HRs) of 1-month mortality and their 95% confidence intervals (CIs). In the first series of multivariable analyses concerning all stroke patients, we introduced into the models headache, age, gender, stroke subtype, and baseline characteristics with p < 0.20 in unadjusted models. Backward selection was done using the likelihood-ratio test to obtain the final model, which included the significant confounders. Stratifications by stroke subtypes (IS and ICH) were then done. In a second series of multivariable analyses concerning IS patients, we generated new models into which we introduced headache, age, gender, IS subtypes and thrombolysis, and baseline characteristics with p < 0.20 in unadjusted models. In a third series of multivariable analyses concerning ICH patients only, we generated new models into which we introduced headache, age, gender, ICH location, intraventricular extension of bleeding, and baseline characteristics with p < 0.20 in unadjusted models. For each analysis, interaction terms were added to the models to test the modifying effect of confounding variables on the association between headache and 1month all-cause mortality, using the likelihood-ratio test. We used a dummy indicator for smoking status to prevent the deletion of data for 3.8% of the patients with missing values. The corresponding proportion for other variables was less than 1%. A p value

Prevalence and prognostic value of headache on early mortality in acute stroke: the Dijon Stroke Registry.

To evaluate the prevalence of headache at onset and its association with 1-month mortality in stroke patients...
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