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      D-dimer for the exclusion of cerebral venous thrombosis: a meta-analysis of low risk patients with isolated headache

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          Abstract

          Background

          Patients with isolated headache may have cerebral venous thrombosis (CVT). D-dimers are proven sensitive in excluding deep venous thrombosis (DVT) and pulmonary embolism (PE) in low risk patients. We aimed to determine whether D-dimer may play the same role in low risk CVT patients with isolated headache.

          Methods

          We included consecutive patients suspected of CVT from our teaching hospital with isolated headache, a normal neurological examination and normal standard head CT in whom D-dimer was determined. Additionally we did a systematic review on articles describing consecutive patients suspected of CVT with isolated headache and their D-dimer values. CVT was investigated with CT or MR venography in all patients.

          Results

          A total of 636 consecutive patients were collected from our own data and the literature search. Of 45 CVT patients one had a negative D-dimer (7.5 %). Sensitivity of D-dimer for diagnosing CVT was 97.8 % (95 % CI: 88.2–99.6 %), specificity was 84.9 % (95 % CI: 81.8–87.7 %), positive predictive value was 33.1 % (95 % CI: 25.2–41.7 %), negative predictive value was 99.8 % (95 % CI: 98.9–100 %). Another 56 isolated headache CVT patients were identified in literature, lacking consecutive isolated headache controls. Sensitivity of D-dimer for diagnosing CVT including these patients was 87.1 % (95 % CI: 79.0–93.0 %).

          Conclusions

          D-dimers have a high negative predictive value in patients with isolated headache for excluding CVT. Sensitivity is lower but comparable to the values accepted in PE and DVT. Low risk patients were defined as headache patients with a normal neurological examination, normal standard head CT and absence of risk factors such as pregnancy or puerperium. Normal D-dimers in these patients may reduce unnecessary imaging, making it a potential valuable marker.

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          Most cited references23

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          Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).

          The natural history and long-term prognosis of cerebral vein and dural sinus thrombosis (CVT) have not been examined previously by adequately powered prospective studies. We performed a multinational (21 countries), multicenter (89 centers), prospective observational study. Patients were followed up at 6 months and yearly thereafter. Primary outcome was death or dependence as assessed by modified Rankin Scale (mRS) score >2 at the end of follow-up. From May 1998 to May 2001, 624 adult patients with CVT were registered. At the end of follow-up (median 16 months), 356 patients (57.1%) had no symptom or signs (mRS=0), 137 (22%) had minor residual symptoms (mRS=1), and 47 (7.5%) had mild impairments (mRS=2). Eighteen (2.9%) were moderately impaired (mRS=3), 14 (2.2%) were severely handicapped (mRS=4 or 5), and 52 (8.3%) had died. Multivariate predictors of death or dependence were age >37 years (hazard ratio [HR]=2.0), male sex (HR=1.6), coma (HR=2.7), mental status disorder (HR=2.0), hemorrhage on admission CT scan (HR=1.9), thrombosis of the deep cerebral venous system (HR=2.9), central nervous system infection (HR=3.3), and cancer (HR=2.9). Fourteen patients (2.2%) had a recurrent sinus thrombosis, 27 (4.3%) had other thrombotic events, and 66 (10.6%) had seizures. The prognosis of CVT is better than reported previously. A subgroup (13%) of clinically identifiable CVT patients is at increased risk of bad outcome. These high-risk patients may benefit from more aggressive therapeutic interventions, to be studied in randomized clinical trials.
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            Acute pulmonary embolism.

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              Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases.

              Headache is the most frequent symptom in cerebral venous thrombosis (CVT), and usually the first. However, it has rarely been reported as the only symptom of CVT. To study the characteristics of patients in whom headache was the only presentation of CVT in the absence of intracranial hypertension, subarachnoid haemorrhage (SAH), meningitis, or other intracranial lesion. From a prospective study of 123 consecutive patients with CVT only those with isolated headache and normal brain computed tomography (CT) scan and cerebrospinal fluid (CSF) examination were included in the present study. All patients underwent an extensive systematic aetiological work-up and were given intravenous heparin followed by oral anticoagulants. A detailed description of the headache was obtained. Headache was only sign of CVT in 17 patients. The lateral sinus was the most frequently involved sinus (n = 15). Onset of headache was progressive in 11, acute in 3, and thunderclap in 3 patients. Once established, the headache was continuous in 15, diffuse in four and unilateral in 13, usually ipsilateral to the occluded lateral sinus. No specific risk factor or cause was found. All had a favourable evolution. The pathogenesis of isolated headache in CVT in the absence of intracranial hypertension, SAH, meningitis or intracerebral lesion is unknown but may involve changes in the walls of the occluded sinus. Hence MRI/MRV should be used to look for signs of CVT in all patients with recent headache (progressive or thunderclap) even when the CT scan and CSF examination are normal.
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                Author and article information

                Contributors
                0031 (0)70 330 2000 , mandaalons@hotmail.com
                k.jellema@mchaaglanden.nl
                m.j.h.wermer@lumc.nl
                a.algra@umcutrecht.nl
                Journal
                BMC Neurol
                BMC Neurol
                BMC Neurology
                BioMed Central (London )
                1471-2377
                28 July 2015
                28 July 2015
                2015
                : 15
                : 118
                Affiliations
                [ ]Department of Neurology, MCH Westeinde, Lijnbaan 32, 2501 CK The Hague, The Netherlands
                [ ]Department of Neurology, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
                [ ]Department of Clinical Epidemiology, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
                [ ]Department of Neurology and Neurosurgery, Brain Center Rudolph Magnus, UMC, Utrecht, The Netherlands
                [ ]Julius Center for Health Sciences and Patient Care, UMC, Utrecht, The Netherlands
                Article
                389
                10.1186/s12883-015-0389-y
                4517419
                26215857
                f5fd0625-95b9-40ca-9a77-abda7307438a
                © Alons et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 March 2015
                : 21 July 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Neurology
                cerebral sinus thrombosis,d-dimer,isolated headache,diagnostic marker,meta-analysis
                Neurology
                cerebral sinus thrombosis, d-dimer, isolated headache, diagnostic marker, meta-analysis

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