Cervical Artery Dissection Patients Research Articles

Peripheral inflammatory response in people after acute ischaemic stroke and isolated spontaneous cervical artery dissection.

The systemic inflammatory response following acute ischaemic stroke remains incompletely understood. We characterised the circulating inflammatory profile in 173 acute ischaemic stroke patients by measuring 65 cytokines and chemokines in plasma. Participants were grouped based on their inflammatory response, determined by high-sensitivity C-reactive protein levels in the acute phase. We compared stroke patients' profiles with 42 people experiencing spontaneous cervical artery dissection without stroke. Furthermore, variations in cytokine levels among stroke aetiologies were analysed. Follow-up samples were collected in a subgroup of ischaemic stroke patients at three and twelve months. Ischaemic stroke patients had elevated plasma levels of HGF and SDF-1α, and lower IL-4 levels, compared to spontaneous cervical artery dissection patients without stroke. Aetiology-subgroup analysis revealed reduced levels of nine cytokines/chemokines (HGF, SDF-1α, IL-2R, CD30, TNF-RII, IL-16, MIF, APRIL, SCF), and elevated levels of IL-4 and MIP-1β, in spontaneous cervical artery dissection (with or without ischaemic stroke as levels were comparable between both groups) compared to other aetiologies. The majority of cytokine/chemokine levels remained stable across the study period. Our research indicates that stroke due to large artery atherosclerosis, cardioembolism, and small vessel occlusion triggers a stronger inflammatory response than spontaneous cervical artery dissection.

Peripheral Blood Gene Expression Profiling Reveals Molecular Pathways Associated with Cervical Artery Dissection.

Cervical artery dissection (CeAD) is the primary cause of ischemic stroke in young adults. Monogenic heritable connective tissue diseases account for fewer than 5% of cases of CeAD. The remaining sporadic cases have known risk factors. The clinical, radiological, and histological characteristics of systemic vasculopathy and undifferentiated connective tissue dysplasia are present in up to 70% of individuals with sporadic CeAD. Genome-wide association studies identified CeAD-associated genetic variants in the non-coding genomic regions that may impact the gene transcription and RNA processing. However, global gene expression profile analysis has not yet been carried out for CeAD patients. We conducted bulk RNA sequencing and differential gene expression analysis to investigate the expression profile of protein-coding genes in the peripheral blood of 19 CeAD patients and 18 healthy volunteers. This was followed by functional annotation, heatmap clustering, reports on gene-disease associations and protein-protein interactions, as well as gene set enrichment analysis. We found potential correlations between CeAD and the dysregulation of genes linked to nucleolar stress, senescence-associated secretory phenotype, mitochondrial malfunction, and epithelial-mesenchymal plasticity.

Abstract 100: Impact of Dissection Location on Subsequent Stroke Risk: A Nationwide Analysis

Introduction: Cervical artery dissection (CAD) is a frequent cause of acute ischemic stroke (AIS) in young adults. We conducted a nationwide study to investigate potential predictors for subsequent AIS following CAD. Method: Adult patients diagnosed with non-traumatic CAD, and without any previous or concurrent stroke (2016-2020), were identified from the Nationwide Readmission Database using validated and standard ICD-10 CM codes. Significant demographic and clinical factors associated with 90-day AIS risk were identified through weighted survey univariate logistic regression followed by a multivariate Cox regression model. Result: Among 13,905 CAD patients (mean age 54.6±0.2, 54.8% female), 215 (1.5%) had subsequent AIS within 90 days of discharge with the median stroke occurrence on day 8. Patients with AIS were significantly older (58.3±1.3 vs. 54.5±0.2, P =0.026), and more commonly had vertebral artery dissection (51.6% vs. 41.0%, P =0.046), and coronary artery disease (24.7% vs. 15.6%, P =0.019). After including all these significant variables, the vertebral artery location of the dissection emerged as the sole significant predictor of subsequent AIS (adjusted HR 1.64, 95% CI 1.07-2.50, P =0.022). A Kaplan-Meier curve validated these findings, showing a higher AIS risk with vertebral versus carotid artery dissections (Figure). Notably, other risk factors such as hyperlipidemia and hypertension lacked significant association with AIS. Conclusion: Our study identifies vertebral artery dissection as a significant risk factor for 90-day AIS occurrence post CAD. This highlights the need for research into tailored management strategies for these patients to reduce stroke risk.

Mechanical Thrombectomy in Cervical Artery Dissection-Related Stroke

Cervical artery dissection (CeAD) causing a large vessel occlusion (LVO) stroke might represent a procedural challenge for mechanical thrombectomy (MT) impacting on its effects. The aim of the present study was to analyze safety, reperfusion rates and clinical outcome of CeAD patients treated by MT and compare these results with those obtained in non-CeAD patients. All consecutive LVO stroke patients undergoing MT between June 2015 and June 2021 at our University Stroke Center were analyzed. Baseline and procedural characteristics, recanalization rates, adverse events, and functional outcome of CeAD patients were compared with non-CeAD patients. MT was performed on 375 patients, 20 (5.3%) were diagnosed with CeAD. These patients were younger (52.9±7.8 vs 72.5±12.9 years, p<0.001), and showed lower rates of cardiovascular risk factors. In CeAD patients, tandem occlusions were more frequent (65.0% vs 14.4%, p<0.001), groin to reperfusion time was longer (93.6 ± 34.9 vs 68.3 ± 50.2 minutes, p=0.01) and general anesthesia was more frequently utilized (70.0% vs 27.9%, p<0.001). Recanalization rates (TICI 2b-3: 100.0% vs 88.5%) and MT-related adverse events (10.0% vs 10.7%) did not differ between the groups, while functional outcome was better in CeAD patients (mRS 0-2 at 3 months: 85.0% vs 62.0%, p=0.038). Although CeAD represents a procedural challenge, MT constitutes a safe and effective treatment for CeAD patients with LVO stroke.

Extracranial Internal Carotid and Vertebral Dissecting Pseudoaneurysms: Clinical Features and Long‐Term Outcomes

Background The formation of dissecting pseudoaneurysms (dPSAs) is a common sequela of cervical artery dissection, which has been suggested to increase thrombotic risk in previous studies. This study reported clinical features and long‐term outcomes of cervical internal carotid (cICA) and vertebral artery (cVA) dPSAs. Methods We performed a retrospective chart review over a 10‐year period (January 2012–December 2021). Baseline demographics and clinical characteristics, medical and endovascular treatments, and long‐term outcomes were reported for cICA and cVA dPSA groups separately. Nonparametric tests were used to compare group differences. Results In our cohort, 120 (12%) of 999 cervical artery dissection patients had dPSA, with 85% occurring in the cICA and 15% in the cVA. Most dPSAs occurred spontaneously or in association with minor trauma. Compared with cICA dPSA, patients with cVA dPSA were younger (median age [range]=34.5 [24–70] versus 52 [30–77]; P &lt;0.01), had a smaller dPSA size (median size [range]=4.5 mm [2–17] versus 8 mm [1.2–32]; P &lt;0.01), and were more likely to reduce in size at follow‐up (median size change [range]=−2.8 mm [−17;0] versus 0 [−24;10.8]). Antithrombotic therapy was predominately aspirin monotherapy. No patients with cVA dPSA experienced recurrent strokes and only 3% of patients with cICA dPSA developed new/recurrent stroke in the territory of dPSA while on an antithrombotic regimen requiring endovascular intervention, and none of the dPSAs ruptured. A total of 98% of the patients had an excellent outcome (modified Rankin scale 0–2 at final follow‐up). Conclusion Most cICA and cVA dPSAs have a benign prognosis with medical therapy alone. Further prospective randomized clinical trials are needed to provide high quality evidence on the necessity of additional endovascular therapy at diagnosis in addition to medical therapy alone.

Vertebral Artery Tortuosity and Morphometric Characteristics of Patients with Recurrent Cervical Artery Dissection

BackgroundCervical Artery Dissection is an important cause of stroke in the young. Data on incidence and associations of recurrence in patients with cervical artery dissection are lacking. Increased Vertebral Artery Tortuosity Index has been reported in patients with cervical artery dissection and associated with earlier age of arterial dissection in patients with connective tissue disease. ObjectiveTo test the hypothesis that increased vertebral artery tortuosity is associated with recurrent cervical artery dissection. MethodsWe reviewed data from a single-center registry of cervical artery dissection patients enrolled between 2011-2021. CT angiography was reviewed for neck length, vertebral artery dominance, and vertebral artery tortuosity index. Incidence rate of recurrent dissection was calculated using Poisson regression. Differences between groups were analyzed using the Kruskal-Wallis rank sum test and Fisher's exact test. ResultsThe cohort included 155 patients: women (56%), mean (SD) age 42 (±10) years, and 116 single and 39 multiple artery dissections. Eleven (7.1%) had a recurrence with an incidence rate (95% CI) of 1.91 (1.06, 3.44) per 100 person-years. Vertebral artery tortuosity did not differ significantly between single and recurrent groups (median (IQR) 46.81 (40.85, 53.91) vs 44.97 (40.68, 50.62) p = 0.388). Morphometric characteristics of height, neck length, and BMI were not associated with recurrence. There was no difference in vertebral artery tortuosity by dissection location (carotid vs vertebral). ConclusionIn this single center cohort of patients with cervical artery dissection, there was no difference in VTI between single and recurrent groups.

Abstract TP103: Vertebral Artery Tortuosity And Morphometric Characteristics In Recurrent Cervical Artery Dissection

Background: Cervical Artery Dissection (CeAD) is an important cause of stroke in the young. Data on incidence and associations of recurrent CeAD are lacking. Increased Vertebral Artery Tortuosity Index (VTI) has been reported in patients with CeAD and associated with earlier age of arterial dissection in patients with connective tissue disease. We hypothesized that VTI may be associated with recurrent CeAD. Methods: We reviewed data from a large single-center registry of CeAD patients enrolled between 2011-2021. CT angiography (CTA) was reviewed for neck length, vertebral artery length (VAL), linear distance from the vertebral artery origin to the vertebrobasilar junction (VOBJ), and VTI [((VAL/VOBJ)–1)*100]. Recurrence was defined as radiographic diagnosis of a new dissection during a follow-up period between initial CTA imaging and July 1, 2021. Incidence rate of recurrent dissection was calculated using Poisson regression. Differences between groups were analyzed using the Kruskal-Wallis rank sum test and Fisher’s exact test. Results: The cohort included 155 patients: women (56%), mean (SD) age 42 (±10) years, and 116 single (carotid or vertebral) and 39 multiple artery dissections. Eight (5%) had a recurrence with a 10 year incidence rate (95% CI) of 1.23 events (0.53, 2.38) per 100 person-years. The recurrent group had a lower mean VTI than the nonrecurrent group (39.2 vs. 45.8; p = 0.024) and trended towards a lower mean age (34.6 vs. 42.3; p = 0.058). Participants with vertebral artery dissection were younger than those with carotid artery dissection with mean ages of 38.5 and 45.1 respectively (p &lt; 0.001) and did not differ in mean VTI (46.0 vs. 44.9; p = 0.747). Morphometric characteristics of height, neck length, and BMI were not associated with recurrence. Conclusion: In this single center cohort of patients with CeAD, greater VTI was associated with a decreased risk of recurrent dissection. This finding is hypothesis generating as adults with recurrent dissections may have distinct mechanistic or genetic factors contributing to their risk of dissection. This study is limited by relatively small sample size and the retrospective analysis. Further study of VTI and risk of incident CeAD in larger independent cohorts is warranted.

Disparities between guideline statements on acute and post-acute management of cervical artery dissection.

Even though cervical artery dissection is one of the main reasons for ischemic stroke in young patients, acute management and post-acute primary or secondary prevention of cerebral ischemia differ significantly in different centers and countries. These discrepancies are reflected by the differences in guideline recommendations of major stroke societies. Our narrative review aims to shed light on the different recommendations in guideline-statements of stroke societies and to give an overview of the current literature concerning acute management and post-acute treatment of cervical artery dissection patients. In general, intravenous thrombolysis and mechanical thrombectomy are recommended, irrespective of stroke etiology, if administered within the label. Secondary prevention of cerebral ischemia can be achieved by antiplatelet intake or anticoagulation, with, to date, neither treatment establishing superiority over the other. Duration of antithrombotic treatment, statin use as well as optimal endovascular approach are still up for debate and need further evaluation. Additionally, it is still unknown, whether the recommendations given in any of the guideline statements are similarly relevant in spontaneous and traumatic cervical artery dissection, as none of the stroke societies differentiates between the two.

Transforming growth factor beta in patients with cervical artery dissection

To evaluate transforming growth factor beta (TGF-β) in patients with cervical artery dissection (CeAD). TGF-β was studied by enzyme immunoassay in 74 of 336 patients with CeAD observed at the Research Center of Neurology (Moscow) from 2000 to 2021. The average patient's age at the time of TGF-β study was 41.6±9.8 years; the proportion of women was 51%. TGF-β was studied in the first month of the disease (n=9), for 2-3 months (n=12) and at a later period (mean - 4.3±5.03 years) (n=53). The control group consisted of 20 healthy volunteers, matched for age and sex. Dissection occurred in internal carotid artery (ICA) (n=42), vertebral artery (VA) (n=29), ICA+VA (n=3) and involved 1 artery (n=58) or 2-3 arteries (n=16). Clinical manifestations included ischemic stroke (IS) (n=49), isolated cervical-cephalic headache (n=23), lower cranial nerve palsy (n=2). Pathological CeAD tortuosity was detected by angiography in 13 patients, and a dissecting aneurysm in 15 patients. TGF-β1 and TGF-β2 were elevated in patients with CeAD patients compared with the control: TGF-β1 - 4990 [3950; 7900] pg/ml vs. 3645 [3230; 4250] pg/ml, p=0.001; TGF-β2 - 6120 [4680; 7900] pg/ml vs. 3155 [2605; 4605] pg/ml, p=0.001. The highest TGF-β1 and TGF-β2 levels were noted at 2-3 months of the disease. There was no correlation between the TGF-β level and various clinical and angiographic parameters. Increased TGF-β level confirms that CeAD patients have connective tissue disorder that underlies the arterial wall weakness. A higher TGF-β level at 2-3 months of CeAD seems to be connected with an active reparative process in arterial wall after dissection. TGF-β can be used as a biomarker of connective tissue dysplasia in patients with CeAD.

Cervical Artery Dissection and Sports.

Cervical artery dissection (CeAD) occurring in the context of sports is a matter of concern for CeAD patients. They seek advice on the role of sports in CeAD and on the safety of resuming sports after CeAD. The scarcity of studies and guidelines addressing these issues poses a challenge. We aimed at summarizing the current knowledge about CeAD and sports in order to provide an informed, comprehensive opinion for counseling CeAD patients. We took into account pathophysiological considerations, observations of cases reports, series, and registries, and conclusions by analogy from aortic dissection or inherited connective tissue syndromes. In summary, practicing active sports as the cause of CeAD seems uncommon. It seems recommendable to refrain from any kind of sports activities for at least 1 month, which can be extended in case of an unfavorable clinical or neurovascular course. We recommend starting with sport activities at low intensity—preferably with types of endurance sports—and to gradually increase the pace in an individually tailored manner, taking into circumstances of the occurrences of the CeAD in the individual patient (particularly in relation to sports), the meaning of sports activities for the individual well-being, the presence or absence of comorbidities and of neurological sequela, neurovascular findings, and whether there are signs of an underlying connective tissue alteration. Major limitations and several forms of bias are acknowledged. Still, in the absence of any better data, the summarized observations and considerations might help clinicians in advising and counseling patients with CeAD in clinical practice.

Low penetrance COL5A1 variants in a young patient with intracranial aneurysm and very mild signs of Ehlers-Danlos syndrome

Spontaneous cervical artery dissection (CeAD) is a major cause of ischemic stroke in young adults, whose genetic susceptibility factors are still largely unknown. Nevertheless, subtle ultrastructural connective tissue alterations (especially in the collagen fibril morphology) are recognized in a large proportion of CeAD patients, in which recent genetic investigations reported an enrichment of variants in genes associated with known connective tissue disorders. In this regard, COL5A1 variants have been reported in a small subset of CeAD patients, with or without classical Ehlers-Danlos syndrome (cEDS) features.We investigated a 22-year-old patient with intracranial aneurysm and mild connective tissue manifestations reminiscent of EDS. Whole-exome sequencing identified two COL5A1 missense variants in trans configuration: NM_000093.5:c.[1588G>A];[4135C>T], NP_000084.3:p.[(Gly530Ser)];[(Pro1379Ser)]. Functional assays demonstrated a significant decrease of collagen α1(V) chain expression in both heterozygous parents compared to control cells, and an additive effect of these two variants in the proband. Interestingly, both parents manifested very subtle EDS signs, such as atrophic scars, recurrent bone fractures, colonic diverticulosis, varicose veins, and osteoarthritis.Our findings emphasize the involvement of COL5A1 in the predisposition to vascular phenotypes and provide novel insights on the c.1588G>A variant, whose functional significance has not been definitely established. In fact, it was previously reported as both “disease modifying”, and as a biallelic causative mutation (with heterozygous individuals showing subtle clinical signs of cEDS). We speculated that the c.1588G>A variant might lead to overt phenotype in combination with additional genetic “hits” lowering the collagen α1(V) chain expression below a hypothetical disease threshold.

Recurrent versus first cervical artery dissection - a retrospective study of clinical and vascular characteristics.

Most recurrent cervical artery dissection (CeAD) events occur shortly after the acute first CeAD. This study compared the characteristics of recurrent and first CeAD events and searched for associations between subsequent events of an individual person. Cervical artery dissection patients with a new CeAD event occurring during a 3-6month follow-up were retrospectively selected in seven specialized stroke centers. Clinical and vascular characteristics of the initial and the recurrent CeADs were compared. The study sample included 76 patients. Recurrent CeADs were occlusive in one (1.3%) patient, caused cerebral ischaemia in 13 (17.1%) and were asymptomatic in 39 (51.3%) patients, compared to 29 (38.2%) occlusive, 42 (55.3%) ischaemic and no asymptomatic first CeAD events. In 52 (68.4%) patients, recurrent dissections affected both internal carotid arteries or both vertebral arteries, whilst 24 (31.6%) patients had subsequent dissections in both types of artery. Twelve (28.6%) of 42 patients with an ischaemic first dissection had ischaemic symptoms due to the recurrent CeADs, too. However, only one (1.3%) of 34 patients with a non-ischaemic first CeAD suffered ischaemia upon recurrence. Recurrent CeAD typically affects the same site of artery. It causes ischaemic events less often than the first CeAD. The risk that patients who presented with solely non-ischaemic symptoms of a first CeAD will have ischaemic symptoms in the case of a recurrent CeAD seems very small.

Biomarkers and antithrombotic treatment in cervical artery dissection - Design of the TREAT-CAD randomised trial.

The type of antithrombotic treatment in cervical artery dissection patients is still a matter of debate. Most physicians prefer anticoagulants over antiplatelet agents for stroke prevention. However, this approach is not evidence-based and antiplatelets might be as safe and as effective. The 'Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection' ('TREAT-CAD') trial (clinicaltrials.gov: NCT02046460) compares Aspirin to oral anticoagulants (vitamin K antagonists) with regard to efficacy and safety by using both clinical and imaging surrogate outcome measures. TREAT-CAD tests the hypothesis, that aspirin is as safe and effective as vitamin K antagonists. TREAD-CAD is a Prospective, Randomised controlled, Open-labelled, multicentre, non-inferiority trial with Blinded assessment of outcome Events (PROBE-design). Key eligibility criteria are (i) clinical symptoms attributable to cervical artery dissection and (ii) verification of the cervical artery dissection diagnosis by established magnetic resonance imaging criteria. Patients are randomised to receive either Aspirin 300 mg daily or vitamin K antagonists for 90 days. Primary outcomes are assessed at 14 ± 10 days (magnetic resonance imaging and clinical examination) and at 90 ± 30 days (clinical examinations). The primary endpoint is a composite outcome measure - labelled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) - and includes (i) occurrence of any stroke (including retinal infarction), (ii) new ischaemic lesions on diffusion-weighted magnetic resonance imaging, (iii) any major extracranial haemorrhage, (iv) any symptomatic intracranial haemorrhage, (v) any new haemorrhagic lesion visible on paramagnetic-susceptible sequences and (vi) death. After database closure, (i) central verification of cervical artery dissection diagnosis will be done by two experienced raters, (ii) adjudication of outcome events will be performed by independent adjudication committees, separately for clinical and imaging outcomes. The primary analysis will be done on the per protocol data set. The targeted sample size consists of 169 evaluable patients in the per protocol data set. TREAT-CAD is testing the non-inferiority of Aspirin versus vitamin K antagonists treatment in patients with symptomatic cervical artery dissection by combined clinical and magnetic resonance imaging outcomes.

Cervical Artery Dissections with and without stroke, risk factors and prognosis: a Chilean prospective cohort

We aimed to characterize spontaneous cervical artery dissection (CeAD) patients with and without stroke and describe risk factors for cerebrovascular complications in a Chilean prospective cohort.Methods: Consecutive CeAD patients admitted to a Chilean center confirmed by neuroimaging. Logistic regression was used.Results: 168 patients were included, median follow-up time was 157 days. Stroke occurred in 49 (29.2%) cases, 4 (2%) patients died, all of whom had a stroke, and 10 (6%) presented CeAD recurrence. In univariate analyses, men (odds ratio [OR] 3.97, 95% confidence interval [CI] 1.97–8.00, P < 0.001), internal carotid artery CeAD (OR 2.82, 95% CI 1.38–5.78, P = 0.005) and vessel occlusion (OR 4.45, 95% CI 1.38–14.38, P = 0.035) increased stroke risk. Conversely, vertebral artery dissection (OR 0.35, 95% CI 0.16–0.74, P = 0.006) and longer symptom onset to admission (O–A) time (OR 0.79, 95% CI 0.70–0.90, P < 0.001) were associated to decreased stroke risk. After multivariate analysis, men (OR 2.88, 95% CI 1.32-6.27, P = 0.008) and O–A time (OR 0.80, 95% CI 0.69–0.92, P = 0.002) remained independently associated with stroke.Conclusion: CeAD presented commonly as a non-stroke entity, with favorable prognosis. Albeit to a higher frequency of CeAD in women, stroke occurred predominantly in men, who were admitted earlier.

Long-term outcome of cervical artery dissection : IPSYS CeAD: study protocol, rationale, and baseline data of an Italian multicenter research collaboration.

Long-term consequences of cervical artery dissection (CeAD), a major cause of ischemic stroke in young people, have been poorly investigated. The Italian Project on Stroke at Young Age - Cervical Artery Dissection (IPSYS CeAD) project is a multicenter, hospital-based, consecutively recruiting, observational, cohort study aimed to address clinically important questions about long-term outcome of CeAD patients, which are not covered by other large-scale registries. Patients with radiologically diagnosed CeAD were consecutively included in the registry. Baseline demographic and clinical variables, as well as information on risk factors, were systematically collected for each eligible patient. Follow-up evaluations were conducted between 3 and 6 months after the initial event (t1) and then annually (t2 at 1 year, t3 at 2 years , and so on), in order to assess outcome events (long-term recurrent CeAD, any fatal/nonfatal ischemic stroke, transient ischemic attack (TIA), or other arterial thrombotic event, and death from any cause). Between 2000 and 2019, data from 1530 patients (age at diagnosis, 47.2 ± 11.5 years; women, 660 [43.1%]) have been collected at 39 Italian neurological centers. Dissection involved a single vessel in 1308 (85.5%) cases and caused brain ischemia in 1303 (85.1%) (190 TIA/1113 ischemic stroke). Longitudinal data are available for 1414 (92.4%) patients (median follow-up time in patients who did not experience recurrent events, 36.0 months [25th to 75th percentile, 63.0]). The collaborative IPSYS CeAD effort will provide novel information on the long-term outcome of CeAD patients. This could allow for tailored treatment approaches based on patients' individual characteristics.

Clinical Usefulness of Serial Duplex Ultrasound in Cervical Artery Dissection Patients

Purpose: To study the clinical usefulness of serial color-coded duplex ultrasound (DUS) examinations in cervical artery dissection (CeAD) patients. Methods: Single-center, CeAD registry-based re-review of serial, routine DUS exams in consecutive CeAD patients treated at the Stroke Center Basel, Switzerland (2009–2015). Two experienced raters reassessed all DUS for the occurrence of new arterial findings during follow-up, that is. (i) recanalization of the dissected artery (if occluded at baseline), (ii) delayed occlusion of a patent dissected artery, and (iii) recurrent CeAD. We studied whether these new arterial findings were associated with clinical symptoms. Results: In 94 CeAD patients (n = 40 female [42.6%], median age 46 years [interquartile range (IQR) 36.2–53]), 506 DUS examinations were reviewed covering a median length of follow-up of 54.1 weeks (IQR 30.5–100.5). In total, 105 dissected arteries were detected, of which 27 (25.7%) were occluded. In 28/94 patients (29.8%), 31 new arterial findings were recorded, which were associated with clinical symptoms in 9/31 (30%) patients. Recanalization of occluded CeAD was observed in 22/27 (81.5%) arteries and occurred in 20/22 arteries within 3 months. In 4/22 patients (18.2%), recanalization was associated with clinical symptoms (ischemic events [n = 2], pure local symptoms [n = 2]). Delayed occlusions were observed in 4/78 (5.1%) dissected arteries patent at baseline. All were clinically asymptomatic and occurred within 14 days from baseline. Recurrent CeAD (all symptomatic) occurred in 5 previously non-dissected arteries. Conclusion: In CeAD patients, follow-up DUS identified new arterial findings, of which several were associated with clinical symptoms: we found that about 1 of 5 recanalizations were associated with clinical symptoms, of whom half were ischemic symptoms. Further, delayed occlusions occurred in patients with no or mild stenosis at baseline and were asymptomatic. This study emphasizes the potential importance of repeated DUS in CeAD particularly in the early phase of up to 4 weeks.

Abstract 49: Male Sex is Associated With Cervical Artery Dissection in Patients With Fibromuscular Dysplasia

Background: Cervical artery dissection (CeAD) is one of the most frequent manifestations of fibromuscular dysplasia (FMD). However, the risk factors for CeAD are unknown. We investigated factors associated with CeAD in the ARCADIA (Assessment of Renal and Cervical Artery Dysplasia) registry and performed a pooled analysis of published and unpublished data. Methods: Patients included were women and men ≥18 years, diagnosed with renal, cervical, or intracranial artery FMD, prospectively recruited at 16 university hospitals in France and Belgium. Diagnosis of CeAD was established by stroke specialists in each participating center, according to standard diagnostic criteria. Associations between CeAD and potential determinants were assessed by calculations of crude and adjusted odds ratios. Results: Among 469 patients (415 women) with FMD, 68 (14.5%) had CeAD. CeAD patients were younger, more likely to be men and to have a history of migraine, and less likely to have a history of hypertension, than non-CeAD patients. In the multivariate analysis, male sex (OR=2.75 ; CI95% 1.39-5.46), history of migraine (OR=1.93 ; 1.08-3.44), age &gt;50 years (OR=0.41 ; 0.23-0.74), history of hypertension (OR=0.35 ; 0.19-0.63), and the number of vascular beds involved by FMD &gt;=3 (OR=2.46 ; 1.13-5.35) remained significantly associated with CeAD. We collected data from 2 published studies and unpublished data from the US and the European Registries. There was no overlap between studies. In a pooled analysis (289 CeAD in 1933 patients), male sex was significantly associated with CeAD (pooled OR=2.04 ; 1.41-2.95, I2=0%, Figure). Conclusion: In patients with FMD, male sex and multisite involvement are associated with of CeAD, in addition to other previous known risk factors.

Triple and quadruple cervical artery dissections: a systematic review of individual patient data

Background and purposeSimultaneous dissection of three or four cervical arteries rarely occurs. As a result, limited information is available on clinical characteristics, underlying causes, treatment, and outcome of these patients.MethodsWe performed a systematic review of individual patient data on triple and quadruple cervical artery dissection (CeAD). We included all cases for whom, at minimum, data on age, sex and affected cervical arteries were available.ResultsOut of 1396 publications identified in the initial search, 52 were included, with data available on 96 patients. Mean age was 42 years and 66% were women. 63% had triple CeAD. The most common manifestations were headache (69%), neck pain (44%), motor deficit (36%), and Horner syndrome (34%). 57% had an ischemic stroke, in the majority of these patients the stroke was confined to the vascular territory of a single artery. 83% were managed medically (antiplatelets or anticoagulants) and 11% underwent endovascular treatment. An underlying disease or triggering event was identified in 71%, most commonly trauma (35%, cervical manipulative therapy in 13%), infection (18%), fibromuscular dysplasia (16%), and hereditary connective tissue disorder (8%). In-hospital mortality was 1%. 80% of patients had a good functional outcome (mRS 0–1) at follow-up. Two recurrences (3%) were reported.ConclusionsTriple or quadruple CeAD mostly affected young women, and underlying disease or triggering event could be identified in more than two-thirds of patients. Less than two-thirds of triple or quadruple CeAD patients suffered ischemic stroke. Most patients were managed medically and the majority had a favorable outcome.

Recurrence of cervical artery dissection: An underestimated risk.

To explore the recurrence of cervical artery dissection (CeAD). A single-center consecutive series of 282 CeAD patients was prospectively recruited during first admission from 1995 to 2012. Patients with a follow-up of at least 1 year (n = 238) were eligible for the current analysis. All patients with clinical symptoms or signs of recurrent CeAD on ultrasound were examined by MRI. Dermal connective tissue morphology was studied in 108 (45.4%) patients. Median follow-up was 52 months (range 12-204 months). In all, 221 (92.8%) patients presented with monophasic CeAD, including 188 (79.0%) patients with a single CeAD event, 11 (4.6%) with simultaneous dissections in multiple cervical arteries, and 22 (9.2%) with subsequent events within a single phase of 4 weeks. Seventeen patients (7.1%) had late (>1 month after the initial event) recurrent CeAD events, including 5 (2.1%) with multiple recurrences. Patients with late recurrences were younger (37.5 ± 6.9 years) than those without (43.8 ± 9.9; p = 0.011). Ischemic stroke occurred in 164 (68.9%) patients at first diagnosis, but only 4 of 46 (8.7%) subsequent events caused stroke (p < 0.0001), while 19 (41.3%) were asymptomatic. Connective tissue abnormalities were found in 54 (56.3%) patients with monophasic and 8 (66.7%) with late recurrent dissections (p = 0.494). Twenty-two (9.2%) patients had new CeAD events within 1 month and 17 (7.1%) later recurrences. The risk for new events was significantly higher (about 60-fold) during the acute phase than during later follow-up. Connective tissue abnormalities were not more frequent in patients with late recurrent events than in those with monophasic CeAD.

Abstract WP187: Diagnostic Significance of Connective Tissue Dysplasia Signs in Patients With Cervical Artery Dissection

Introduction: Cervical artery dissection (CeAD) is the most frequent cause of ischemic stroke in young adults. It is suggested that connective tissue dysplasia (CTD) underlies in the arterial wall weakness predisposing to dissection. The aim : to elucidate CTD signs that have prognostic and diagnostic significance for CeAD. Methods: We examined 80 patients (mean age 38,5±13,5; 49 females, 61,2%) with CeAD, verified by MRI/MRA and 20 healthy volunteers (mean age 30,3±6,7; 12 females 60%). We assessed 48 signs selected from criteria of the vascular type of Ehlers-Danlos syndrome, Marfan syndrome, Beighton criteria of joint hypermobility and other. In addition we estimated arterial hypotension (≤100/70 mm Hg), and headache in the past history. Each sign was counted as present or absent, resulting in an individual CTD score. On the basis of linear regression analysis these signs were divided into major and minor signs. Results: CTD signs were found more frequently in CeAD patients than in the control (mean score 7,9 ± 3,6 vs 4,6 ± 2,5; p&lt;0.0039). The following CTD signs were significantly more often in patients than in control: arterial hypotension (51% vs 20%, Р=0,018), extensive bruising (40% vs 10%, Р=0,016), widened atrophic scars (23% vs 0%, Р=0,02), headache in the past history (60% vs 35%, p=0,027) - major signs; translucent skin (29% vs 5%, Р=0,037), hight palate (20% vs 0%, Р=0,037), nasal bleeding (34% vs 15%, Р=0,044), blue sclera (20% vs 5%, Р=0,05), propensity to constipation (30% vs 0%, Р=0,05) - minor signs. If there were 4 major and 2 small signs logistic regression model gave 75% predictive value of dissection. The reliability of these signs was confirmed by ROC analysis (AUC 0,90 [95% CI 0,84-0,96], sensitivity - 86%, specificity - 85%). Conclusion: CTD signs are highly prevalent in patients with CeAD that is in accordance with our morphological data that arterial wall dysplasia is a main cause of spontaneous dissection. The presence of 4 major and 2 minor signs may be used to estimate the predisposition to CeAD and in some cases as additional argument at clinical diagnosis.