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Cervical artery dissection (CeAD) is a frequent cause of stroke among young patients. It is unclear how many CeADs occur asymptomatically or cause subtle and unspecific clinical symptoms. We hypothesize that CeAD remains often unrecognized. Accordingly, the incidence of CeAD might be higher and the stroke risk lower than generally assumed. Lack of CeAD-indicating clinical symptoms is regarded as the main cause of missed diagnoses. We further hypothesize that underrepresentation of asymptomatic and oligosymptomatic patients in CeAD studies may have biased the association between ischemia and local symptoms in CeAD patients as well as the associations of CeAD with risk factors or co-morbidities. We finally hypothesize that symptomatic CeAD may be preceded by an initial asymptomatic phase. According to this final hypothesis, the time of onset of CeAD should be considered uncertain. The issue of unrecognized CeAD is relevant, as it may affect the associations between CeAD and putative risk factors. Furthermore, the existence of clinically silent CeADs may explain why recurrent and familial CeAD have been rarely observed.

Objective:: Data on recurrence of vascular events and their prognostic factors in young (

Background: Cervical artery dissection (CAD) is the most common single etiology for stroke in young adults. Migraine, especially with aura (MA), is a known risk factor for ischemic stroke. The association between CAD and migraine was suggested based on a few small studies, but there are no large-scale case-control data, and the mechanisms are not yet clear. Methods: We compared the lifetime prevalence of migraine and migraine characteristics in 313 CAD patients with 313 healthy age- and sex-matched controls. We also analyzed clinical and radiological characteristics of CAD with respect to migraine subtypes to investigate whether clear phenotypical associations can be found that might help in the search for a possible shared genetic background for migraine and CAD. Results: Migraine was clearly more common in CAD patients than in controls (36 vs. 23%; OR 2.15; 95% CI 1.48–3.14), and the association was also highly significant for MA (23 vs. 12%; OR 2.41; 95% CI 1.53–3.80). Percentages of reported migraine history and MA of CAD patients vs. controls compared separately for both sexes were as follows: for women, migraine 54 vs. 35% (OR 2.30; 95% CI 1.28–4.13), MA 35 vs. 18% (OR 2.79; 95% CI 1.40–5.59); for men, migraine 27 vs. 16% (OR 2.02; 95% CI 1.23–3.31), MA 16 vs. 10% (OR 2.21; 95% CI 1.19–4.11). Over 60% of the CAD patients with still active migraine at the time of dissection reported later alleviation of migraine activity. Conclusion: Our observations suggest that patients with CAD are a significant link between ischemic stroke and migraine. This connection may represent a common pathophysiological or genetic background, or both. Migraine activity appears to be alleviated by CAD.

Background and Purpose— To characterize different forms of intracranial artery dissections (IADs), and to test the assumption that IADs are frequently associated with subarachnoid hemorrhage (SAH) and poor outcome, and that anticoagulant therapy is contraindicated in these patients. Methods— We studied 81 consecutive non-SAH IAD patients and 22 IAD patients with SAH, diagnosed between 1994 and 2004 and 1998 and 2004, respectively, and treated the former patients immediately with heparin, followed with at least 3 months of warfarin. Outcomes were recorded at 3 months. Results— Approximately one-third of all cervicocephalic artery dissections were identifiably either completely located intracranially or extended into the intracranial space. At 3 months, 64 of the 81 non-SAH patients (79%) had a favorable outcome (modified Rankin Scale, 0 to 2); 1 patient died of brain infarction in the acute stage. Only 1 aneurysm developed during follow-up in the non-SAH group, and no intracranial bleeding was observed during anticoagulant treatment. Those presenting with SAH formed ≈25% of all IADs, and 21 cases out of 22 (95%) were associated with ruptured fusiform dissecting aneurysm. This latter group displayed significantly worse outcomes: 7 died, and only 7 had modified Rankin Scale 0 to 2 at 3 months. Conclusions— Our results provide important information for clinical practice. IADs appear to polarize into 2 groups: (1) nonaneurysmatic IADs presenting without SAH that are associated with favorable outcomes and safe anticoagulant therapy; and (2) aneurysmatic IADs, characterized by SAH and poorer prognosis. Literature on IADs may have been biased toward group 2.

Background Stroke in patients with acute cervical artery dissection may be anticipated by initial transient ischemic or nonischemic symptoms. Aim Identifying risk factors for delayed stroke upon cervical artery dissection. Methods Cervical artery dissection patients from the multicenter Cervical Artery Dissection and Ischemic Stroke Patients study were classified as patients without stroke ( n = 339), with stroke preceded by nonstroke symptoms (delayed stroke, n = 244), and with stroke at onset ( n = 382). Demographics, clinical, and vascular findings were compared between the three groups. Results Patients with delayed stroke were more likely to present with occlusive cervical artery dissection ( P < 0·001), multiple cervical artery dissection ( P = 0·031), and vertebral artery dissection ( P < 0·001) than patients without stroke. No differences were observed in age, smoking, arterial hypertension, hypercholesterolemia, migraine, body mass index, infections during the last week, and trauma during the last month, but patients with delayed stroke had less often transient ischemic attack ( P < 0·001) and local signs (Horner syndrome and cranial nerve palsy; P < 0·001). Conclusions Occlusive cervical artery dissection, multiple cervical artery dissection, and vertebral artery dissection were associated with an increased risk for delayed stroke. No other risk factors for delayed stroke were identified. Immediate cervical imaging of cervical artery dissection patients without ischemic stroke is needed to identify patients at increased risk for delayed ischemia.

Erratum in: Familial occurrence and heritable connective tissue disorders in cervical artery dissection. [Neurology. 2016]; International audience; In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%-1.5%) from 17 families (0.9%, 0.5%-1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.

To study the prognostic importance of Horner syndrome (HS) in patients with internal carotid artery dissection (ICAD) or vertebral artery dissection (VAD).In this observational study, characteristics and outcome of patients with ICAD or VAD from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) database were analyzed. The presence of HS was systematically assessed using a standardized questionnaire. Patients with HS (HS+) were compared with HS- patients. Crude odds ratios (ORs) with 95% confidence intervals and ORs adjusted for age, sex, center, arterial occlusion, bilateral dissection, stroke severity, and type of antithrombotic treatment were calculated.We analyzed 765 patients (n = 496 with ICAD, n = 269 with VAD, n = 303 prospective, n = 462 retrospective). HS was present in 191 (38.5%) of the patients with ICAD and 36 (13.4%) of the patients with VAD (p0.001). HS+ ICAD patients presented less often with stroke or TIA (p0.001), less often had bilateral (p = 0.019) or occlusive (p = 0.001) dissections, and had fewer severe strokes (p = 0.041) than HS- ICAD patients. HS+ ICAD patients had a better functional 3-month outcome than those without HS (ORcrude = 4.0 [2.4-6.7]), and also after adjustment for outcome-relevant covariates (ORadjusted = 2.0 [1.1-4.0]). HS+ ICAD patients were less likely to have new strokes than HS- ICAD patients (p = 0.039). HS+ VAD patients more often had vessel occlusion (p = 0.014) than HS- patients but did not differ in any of the other aforementioned variables.In patients with ICAD, HS is an easily assessable marker that might indicate a more benign clinical course. HS had no prognostic meaning in patients with VAD.

Background: Little data is available on familial occurrence of cervical artery dissection (CEAD), a major cause of ischemic stroke in young adults. We aimed to examine the prevalence of family history of CEAD in a large multicenter cohort of CEAD patients and compare characteristics of CEAD patients with and without such a family history. Methods: Across 18 neurological departments in 8 countries, consecutive patients with a diagnosis of CEAD were included in the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) cohort study following a standardized protocol and using the same questionnaire. Results: Among 921 consecutive CEAD patients, 11 patients (1.2%, 95%CI:0.5-1.9%) from 9 families (1.0%, 0.3-1.6%) had a family history of CEAD, mostly in a first degree relative (64%). One patient without family history of CEAD had biologically confirmed vascular Ehlers-Danlos syndrome, while none of the patients with a family history of CEAD had a diagnosis of known inherited connective tissue disorder. Risk factors, baseline features, and 3-month outcome did not differ significantly between CEAD patients with and without a family history of CEAD. Conclusion: In the largest series of CEAD patients to date, family history of CEAD was very rare, although slightly higher than expected by chance given the low disease incidence.

The goal of this work was to explore age-dependent differences in cervical artery dissection (CeAD). This study is based on the Cervical Artery Dissection and Ischemic Stroke Patients population comprising 983 consecutive CeAD patients and 658 control patients with a non-CeAD ischemic stroke (IS), frequency-matched for age and gender. Patients were divided into three age categories: ≤33 (for CeAD, n = 150), 34-54 (n = 688), and ≥55 (n = 145) years, and the youngest and oldest groups were compared. The youngest patients were mostly women and the oldest men. The frequency of internal carotid artery dissection (ICAD) versus vertebral artery dissection (VAD) increased with age from 44 to 75 %. This age-related shift remained significant after adjustment for sex. The frequency of a transient ischemic event as the CeAD symptom declined from 33 % in the youngest age group, to 19 % in the oldest. Vascular risk factors increased in frequency with advancing age in both groups, but for hypertension the increase was steeper for non-CeAD IS patients. For CeAD patients, but not for patients with non-CeAD IS, preceding infection was more common in the oldest group. The youngest non-CeAD IS patients had better functional outcome (modified Rankin Scale 0-1) than the oldest, while the similar trend was not statistically significant among CeAD patients. Younger age seems to be associated with VAD and female gender, and older age with ICAD and male gender. Age-related changes in the frequencies of hypertension and recent infection were different between the CeAD and non-CeAD IS groups. Age does not seem to be an important outcome predictor in CeAD strokes.

Objective: To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site. Methods: We analyzed 982 consecutive patients with CEAD included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection [ICAD], n = 327 with vertebral artery dissection [VAD], n = 36 with ICAD and VAD). Results: Patients with ICAD were older ( p p = 0.006), more frequently had a recent infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09–2.31]), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 [0.56–1.007]) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 [1.01–1.84]) but less frequently complained of cervical pain (OR = 0.36 [0.27–0.48]) or had cerebral ischemia (OR = 0.32 [0.21–0.49]) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12–1.22]). Aneurysmal dilatation was more common (OR = 1.80 [1.13–2.87]) and bilateral dissection less frequent (OR = 0.63 [0.42–0.95]) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 [2.32–6.88]), but this was no longer significant after adjusting for baseline NIHSS score. Conclusion: In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.

Response: We thank Dr Arnold et al for their interest in our recent article.1 In their Letter,2 Arnold et al suggest that (1) the present data are not sufficient to conclude the safety of anticoagulation in intracranial artery dissection (IAD) patients presenting without subarachnoidal hemorrhage (SAH), and a routine lumbar puncture (LP) is necessary to exclude CT or MRI negative SAH, and (2) a filiform stenosis is not a reliable marker of dissection and more strict diagnostic criteria, ie, pathognomonic signs only, should be used for reliable diagnosis of IAD. Apparently, Arnold and his coauthors themselves2 use anticoagulation treatment in (some) IAD patients after routinely performing a LP to exclude SAH, as some patients may have a normal CT but blood in cerebrospinal fluid. In contrast to their …

OBJECTIVE To compare the effects of antiplatelets and anticoagulants on stroke and death in patients with acute cervical artery dissection. DESIGN Systematic review with Bayesian meta-analysis. DATA SOURCES The reviewers searched MEDLINE and EMBASE from inception to November 2012, checked reference lists, and contacted authors. STUDY SELECTION Studies were eligible if they were randomised, quasi-randomised or observational comparisons of antiplatelets and anticoagulants in patients with cervical artery dissection. DATA EXTRACTION Data were extracted by one reviewer and checked by another. Bayesian techniques were used to appropriately account for studies with scarce event data and imbalances in the size of comparison groups. DATA SYNTHESIS Thirty-seven studies (1991 patients) were included. We found no randomised trial. The primary analysis revealed a large treatment effect in favour of antiplatelets for preventing the primary composite outcome of ischaemic stroke, intracranial haemorrhage or death within the first 3 months after treatment initiation (relative risk 0.32, 95% credibility interval 0.12 to 0.63), while the degree of between-study heterogeneity was moderate (τ(2) = 0.18). In an analysis restricted to studies of higher methodological quality, the possible advantage of antiplatelets over anticoagulants was less obvious than in the main analysis (relative risk 0.73, 95% credibility interval 0.17 to 2.30). CONCLUSION In view of these results and the safety advantages, easier usage and lower cost of antiplatelets, we conclude that antiplatelets should be given precedence over anticoagulants as a first line treatment in patients with cervical artery dissection unless results of an adequately powered randomised trial suggest the opposite.

Cervicocerebral artery dissection (CAD) is “a common rare disease,” with an annual incidence of 2.6 to 2.9 patients per 100 000 people. In adults younger than 50 years of age, ∼15% of all ischaemic strokes are caused by CAD, while cardioembolism, representing a wider spectrum of pathological conditions, explain ∼20% of cases. Arnold et al 1 report the results of two studies, contributing to our understanding of the characteristics of CAD (see page 171) . They …

We read with great interest the article by Uyttenboogaart and co-workers on the association of serum glucose level with outcome in acute ischaemic stroke. In their multivariate analysis hyperglycaemia (glucose >8 mmol/l) was associated with worse functional outcome in a concentration-dependent manner in non-lacunar stroke, whereas in lacunar stroke hyperglycaemia was associated with favourable outcome, this beneficial effect diminishing with more severe hyperglycaemia (>12 mmol/l). Although Uyttenboogart and colleagues creditably discuss the potential neuroprotective effect of lactate produced by astrocytes, they fail in their conclusions stating that ‘hyperglycaemia has a detrimental effect in non-lacunar stroke, but moderate hyperglycaemia …