Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke.

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.

Genetic Imbalance in Patients with Cervical Artery Dissection.

BACKGROUND: Genetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed. Rare genic CNVs were equally frequent in CeAD-patients (16.4%; n=137) and in control subjects (17.0%; n=346) but differed with respect to their genetic content. Compared to control subjects, CNVs from CeAD patients were enriched for genes associated with muscle organ development and cell differentiation, which suggests a possible association with arterial development. CNVs affecting cardiovascular system development were more common in CeAD patients than in control subjects (p=0.003; odds ratio (OR) =2.5; 95% confidence interval (95% CI) =1.4-4.5) and more common in patients with a familial history of CeAD than in those with sporadic CeAD (p=0.036; OR=11.2; 95% CI=1.2-107). CONCLUSION: The findings suggest that rare genetic imbalance affecting cardiovascular system development may contribute to the risk of CeAD. Validation of these findings in independent study populations is warranted.

Characteristics and outcomes of patients with multiple cervical artery dissection.

BACKGROUND AND PURPOSE: Little is known about factors contributing to multiple rather than single cervical artery dissections (CeAD) and their associated prognosis. METHODS: We compared the baseline characteristics and short-term outcome of patients with multiple to single CeAD included in the multicenter Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study. RESULTS: Among the 983 patients with CeAD, 149 (15.2%) presented with multiple CeAD. Multiple CeADs were more often associated with cervical pain at admission (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.10-2.30), a remote history of head or neck surgery (OR, 1.87; 95% CI, 1.16-3.00), a recent infection (OR, 1.71; 95% CI, 1.12-2.61), and cervical manipulation (OR, 2.23; 95% CI, 1.26-3.95). On imaging, cervical fibromuscular dysplasia (OR, 3.97; 95% CI, 2.04-7.74) and the presence of a pseudoaneurysm (OR, 2.91; 95% CI, 1.86-4.57) were more often seen in patients with multiple CeAD. The presence of multiple rather than single CeAD had no effect on functional 3-month outcome (modified Rankin Scale score, ≥3; 12% in multiple CeAD versus 11.9% in single CeAD; OR, 1.20; 95% CI, 0.60-2.41). CONCLUSIONS: In the largest published series of patients with CeAD, we highlighted significant differences between multiple and single artery involvement. Features suggestive of an underlying vasculopathy (fibromuscular dysplasia) and environmental triggers (recent infection, cervical manipulation, and a remote history of head or neck surgery) were preferentially associated with multiple CeAD.

Association of vascular risk factors with cervical artery dissection and ischemic stroke in young adults.

BACKGROUND: Little is known about the risk factors for cervical artery dissection (CEAD), a major cause of ischemic stroke (IS) in young adults. Hypertension, diabetes mellitus, smoking, hypercholesterolemia, and obesity are important risk factors for IS. However, their specific role in CEAD is poorly investigated. Our aim was to compare the prevalence of vascular risk factors in CEAD patients versus referents and patients who suffered an IS of a cause other than CEAD (non-CEAD IS) in the multicenter Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study. METHODS AND RESULTS: The study sample comprised 690 CEAD patients (mean age, 44.2 ± 9.9 years; 43.9% women), 556 patients with a non-CEAD IS (44.7 ± 10.5 years; 39.9% women), and 1170 referents (45.9 ± 8.1 years; 44.1% women). We compared the prevalence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and obesity (body mass index ≥ 30 kg/m²) or overweightness (body mass index ≥ 25 kg/m² and <30 kg/m²) between the 3 groups using a multinomial logistic regression adjusted for country of inclusion, age, and gender. Compared with referents, CEAD patients had a lower prevalence of hypercholesterolemia (odds ratio 0.55; 95% confidence interval, 0.42 to 0.71; P<0.0001), obesity (odds ratio 0.37; 95% confidence interval, 0.26 to 0.52; P<0.0001), and overweightness (odds ratio 0.70; 95% confidence interval, 0.57 to 0.88; P=0.002) but were more frequently hypertensive (odds ratio 1.67; 95% confidence interval, 1.32 to 2.1; P<0.0001). All vascular risk factors were less frequent in CEAD patients compared with young patients with a non-CEAD IS. The latter were more frequently hypertensive, diabetic, and current smokers compared with referents. CONCLUSION: These results, from the largest series to date, suggest that hypertension, although less prevalent than in patients with a non-CEAD IS, could be a risk factor of CEAD, whereas hypercholesterolemia, obesity, and overweightness are inversely associated with CEAD.

Recurrent ischemic events in young adults after first-ever ischemic stroke.

OBJECTIVE: Data on recurrence of vascular events and their prognostic factors in young (<50 years of age) stroke patients are not well defined. METHODS: We assessed the occurrence of arterial thrombotic events in consecutive first-ever ischemic stroke patients aged 15 to 49 years entered into the Helsinki Young Stroke Registry (January 1994-October 2004) within 5-year follow-up. Follow-up was conducted with a structured telephone interview or letter, and review of all patient records; mortality data came from Statistics Finland. Primary outcomes were (1) nonfatal or fatal recurrent ischemic stroke; (2) nonfatal or fatal myocardial infarct, other arterial thrombotic event, or revascularization procedure; and (3) any combination of these, whichever occurred first (composite endpoint). We used Kaplan-Meier analysis to estimate cumulative risks and Cox proportional hazard model-adjusted for age, gender, relevant risk factors, and stroke subtype-for identifying predictors of recurrence. RESULTS: In the 807 patients followed (mean age, 41.5 ± 7.4 years; 62.9% male), cumulative 5-year recurrence rate was 9.4% (95% confidence interval [CI], 7.3-11.5%) for nonfatal or fatal ischemic stroke, 2.4% (95% CI, 1.3-3.5%) for nonfatal or fatal myocardial infarct or other arterial endpoint, and 11.5% (95% CI, 9.2-13.7%) for the composite endpoint. Independent predictors of the composite endpoint were type 1 diabetes mellitus (hazard ratio [HR], 4.39; 95% CI, 2.28-8.45), large-artery atherosclerosis underlying the index stroke (HR, 2.82; 95% CI, 1.36-5.83), heart failure (HR, 2.96; 95% CI, 1.17-7.50), previous transient ischemic attack (HR, 2.33; 95% CI, 1.40-3.88), and increasing age (HR, 1.05; 95% CI, 1.01-1.10). INTERPRETATION: Despite their young age, these individuals were at marked risk of recurrent arterial events, predicted by mostly modifiable baseline factors.

Thrombolysis in young adults with ischemic stroke.

BACKGROUND AND PURPOSE: No exclusive systematic data exist on the safety and outcomes of thrombolytic treatment in young patients with ischemic stroke. METHODS: We evaluated all 48 patients aged 16 to 49 years with hemispheric ischemic stroke treated with intravenous alteplase in Helsinki University Central Hospital from 1994 to 2007. For comparison of outcome, we selected, blinded to outcome data, 96 control subjects (1:2) with ischemic stroke not treated with alteplase matched by age, gender, and admission stroke severity (National Institutes of Health Stroke Scale). We selected similarly 96 older alteplase-treated gender and arrival National Institutes of Health Stroke Scale score-matched patients (aged, 50 to 79 years) for comparison of outcome and hemorrhage rate. A 3-month favorable outcome was defined as modified Rankin Scale score of 0 to 1. Symptomatic intracerebral hemorrhage was defined according to the Safe Implementation of Thrombolysis in Stroke Monitor Study. RESULTS: Young alteplase-treated patients (67% males; mean age, 38.8+/-9.1 years) more often recovered completely (27% versus 10%, P=0.010) and achieved a favorable outcome (40% versus 22%, P=0.025) compared with their age-matched control subjects not treated with alteplase. In alteplase-treated patients, unfavorable outcome was more frequent in males and in those with carotid artery dissection. We observed no difference in outcome between cases and older control subjects treated with alteplase. However, none of the cases had symptomatic intracerebral hemorrhage versus 3 (3%) in the older control group (P=0.551). Mortality rate was 2% (P=0.552) in age-matched control subjects and 7% (P=0.095) among older control subjects, whereas none of the case patients died during the 3-month follow-up. CONCLUSIONS: Young adults with acute hemispheric ischemic stroke benefited from intravenous thrombolysis with good safety.

Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry.

BACKGROUND AND PURPOSE: To analyze trends in occurrence, risk factors, etiology, and neuroimaging features of ischemic stroke in young adults in a large cohort. METHODS: We evaluated all 1008 consecutive ischemic stroke patients aged 15 to 49 admitted to Helsinki University Central Hospital, 1994 to 2007. Etiology was classified by Trial of Org 10172 in Acute Stroke Treatment criteria. Comparisons were done between groups stratified by gender and age. RESULTS: Estimated annual occurrence was 10.8/100,000 (range 8.4 to 13.0), increasing exponentially with aging. Of our 628 male and 380 female (ratio 1.7:1) patients, females were preponderant among those <30, whereas male dominance rapidly increased around age of 44. The most frequent risk factors were dyslipidemia (60%), smoking (44%), and hypertension (39%). Males and patients >44 clearly had more risk factors. Cardioembolism (20%) and cervicocerebral artery dissection (15%) were the most frequent etiologic subgroups. Proportions of large-artery atherosclerosis (8%) and small-vessel disease (14%) began to enlarge at age 35, whereas frequency of undetermined etiology (33%) decreased along aging. Posterior circulation infarcts were more common among patients <45 years of age. Left hemisphere infarcts were more frequent in general. There were 235 (23%) patients with multiple and 126 (13%) with silent infarcts, and 55 (5%) patients had leukoaraiosis. CONCLUSIONS: The frequency of ischemic stroke increases sharply at age 40. Etiology and risk factors start resembling those seen in the elderly in early midlife but causes defined in younger patients still are frequent in those aged 45 to 49. Subclinical infarcts were surprisingly common in the young.

Compound nerve conduction velocity- a reflection of proprioceptive afferents?

OBJECTIVE: To gather the required sample size to compare compound nerve conduction velocities (CV) to cutaneous sensory CVs and motor CVs to find out if there are statistically significant differences between these nerve fibre populations. METHODS: We report age, height, and temperature standardized CVs for cutaneous sensory, motor, and compound nerve fibres measured by electroneuromyography (ENMG) for 109 median nerves in 74 people from different age groups with no known neuropathy (age 50.4, median 49, range 21-87). RESULTS: In the region of the forearm, mean CVs were 63.6m/s (CI=62.6-64.7) for compound nerve fibres, 61.3m/s (CI=60.1-62.5) for cutaneous sensory fibres, and 56.3m/s (CI=55.1-57.6) for motor fibres (for all p<0.001). Age explained most of the variation of CVs (Pearson's coefficients -0.394, -0,538, and -0.443, respectively, for all p

Prognosis and safety of anticoagulation in intracranial artery dissections in adults.

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 approximately 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.

Observation of the main phase transition of dinervonoylphosphocholine giant liposomes by fluorescence microscopy.

The phase heterogeneity of giant unilamellar dinervonoylphosphocholine (DNPC) vesicles in the course of the main phase transition was investigated by confocal fluorescence microscopy observing the fluorescence from the membrane incorporated lipid analog, 1-palmitoyl-2-(N-4-nitrobenz-2-oxa-1,3-diazol)aminocaproyl-sn-glycero-3-phosphocholine (NBDPC). These data were supplemented by differential scanning calorimetry (DSC) of DNPC large unilamellar vesicles (LUV, diameter approximately 0.1 and 0.2 microm) and multilamellar vesicles (MLV). The present data collected upon cooling reveal a lack of micron-scale gel and fluid phase coexistence in DNPC GUVs above the temperature of 20.5 degrees C, this temperature corresponding closely to the heat capacity maxima (T(em)) of DNPC MLVs and LUVs (T(em) approximately 21 degrees C), measured upon DSC cooling scans. This is in keeping with the model for phospholipid main transition inferred from our previous fluorescence spectroscopy data for DMPC, DPPC, and DNPC LUVs. More specifically, the current experiments provide further support for the phospholipid main transition involving a first-order process, with the characteristic two-phase coexistence converting into an intermediate phase in the proximity of T(em). This at least macroscopically homogenous intermediate phase would then transform into the liquid crystalline state by a second-order process, with further increase in acyl chain trans-->gauche isomerization.

Characterization of the main transition of dinervonoylphosphocholine liposomes by fluorescence spectroscopy.

The structural dynamics of the main phase transition of large unilamellar dinervonoylphosphocholine (DNPC) vesicles was investigated by steady state and time-resolved fluorescence spectroscopy of the membrane incorporated fluorescent lipid analog, 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC). These data were supplemented by differential scanning calorimetry (DSC) and fluorescence anisotropy measured for 1-palmitoyl-2-(3-(diphenylhexatrienyl) propanoyl)-sn-glycero-3-phosphocholine (DPHPC). The collected data displayed several discontinuities in the course of the main transition and the pretransition. The discontinuities seen in the fluorescence properties may require modification of the existing models for phospholipid main transition as a first order process. From our previous study on dipalmitoylphosphocholine (DPPC), we concluded the transition to involve a first-order process resulting in the formation of an intermediate phase, which then converts into the liquid crystalline state by a second order process. Changes in the physical properties of the DNPC matrix influencing probe behavior were similar to those reported previously for PPDPC in DPPC. In gel state DNPC [(T-T(m))<-10] the high values for excimer/monomer emission ratio (I(e)/I(m)) suggest enrichment of the probe in clusters. In this temperature range, excimer fluorescence for PPDPC (mole fraction X(PPDPC)=0.02) is described by two formation times up to (T-T(m)) approximately -10, with a gradual disappearance of the fractional intensity (I(R1)) of the shorter formation time (tau(R1)) with increasing temperature up to (T-T(m)) approximately -10. This would be consistent with the initiation of the bilayer melting at the PPDPC clusters and the subsequent dispersion of the one population of PPDPC domains. A pronounced decrement in I(e) starts at (T-T(m))=-10, continuing until T(m) is reached. No decrease was observed in fluorescence quantum yield in contrast to our previous study on DPPC/PPDPC large unilamellar vesicles (LUVs) [J. Phys. Chem., B 107 (2003) 1251], suggesting that a lack of proper hydrophobic mismatch may prevent the formation of the previously reported PPDPC superlattice. With further increase in temperature and starting at (T-T(m)) approximately -1, I(e), tau(R2), and excimer decay times (tau(D)) reach plateaus while increment in trans-->gauche isomerization continues. This behavior is in keeping with an intermediate phase existing in the temperature range -1<(T-T(m))<4 and transforming into the liquid disordered phase as a second order process, the latter being completed when (T-T(m))-->4 and corresponding to approximately 50% of the total transition enthalpy.

Predictors of delayed stroke in patients with cervical artery dissection.

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.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Clinical import of Horner syndrome in internal carotid and vertebral artery dissection.

OBJECTIVE: To study the prognostic importance of Horner syndrome (HS) in patients with internal carotid artery dissection (ICAD) or vertebral artery dissection (VAD). METHODS: 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. RESULTS: 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 (p < 0.001). HS+ ICAD patients presented less often with stroke or TIA (p < 0.001), 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. CONCLUSION: 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.

Familial occurrence and heritable connective tissue disorders in cervical artery dissection.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cervical artery dissection goes frequently undiagnosed.

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.

Antiplatelets versus anticoagulants for the treatment of cervical artery dissection: Bayesian meta-analysis.

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.