Intracranial arterial and arteriovenous malformations presenting with infarction. Lausanne Stroke Registry study.

Cerebral aneurysms and arteriovenous malformations (AVMs) are well-known sources of intracranial hemorrhage, but can also manifest as other clinical symptoms or remain clinically asymptomatic. The aim was to document and analyze cases of aneurysm or AVM with brain infarction. Survey on 4804 stroke patients treated at the Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland between 1978 and 2000 using the Lausanne Stroke Registry. Twenty patients presented with cerebral aneurysm and 21 with cerebral AVM. Hemorrhage was present in 100% of the AVM and in 75% of the aneurysm patients; in one (5%) of the remaining aneurysm patients, aneurysm and infarction were located in different territories. Infarction associated with Sylvian artery aneurysm was found in three (15%), vertebrobasilar ischemia because of fusiform left vertebral artery aneurysm in one (5%), and dural fistula draining to the distal transversal and left sigmoid sinus associated with a stroke in the territory of the left anterior inferior cerebellar artery in one patient. Ischemic stroke is infrequent, but important, complication in unruptured intracranial aneurysms and AVMs. The early recognition and therapy of these vascular malformations in selected patients can avoid a major neurological deficit or death caused by their rupture.

Embolic strokes of undetermined source in the athens stroke registry: a descriptive analysis.

BACKGROUND AND PURPOSE: A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria. METHODS: The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients. ESUS was defined as a radiologically confirmed nonlacunar brain infarct in the absence of (a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the ischemic area, (b) major-risk cardioembolic source, and (c) any other specific cause of stroke. RESULTS: Among 2735 patients admitted between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity (median National Institute Health Stroke Scale score, 5). The most prevalent risk factor was arterial hypertension (64.7%), and 50.9% of patients were dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF) was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was detected after repeated ECG monitoring during follow-up. Also, covert AF was strongly suggested in 38 patients (13.8%) but never recorded. CONCLUSIONS: About 10% of patients with first-ever ischemic stroke met criteria for ESUS; covert paroxysmal AF seems to be a frequent cause of ESUS.

Factors affecting cognitive outcome in early pediatric stroke.

OBJECTIVE: We examined cognitive performance in children after stroke to study the influence of age at stroke, seizures, lesion characteristics, neurologic impairment (NI), and functional outcome on cognitive outcome. METHODS: This was a prospectively designed study conducted in 99 children who sustained an arterial ischemic stroke (AIS) between the age of 1 month and 16 years. All children underwent cognitive and neurologic follow-up examination sessions 2 years after the insult. Cognitive development was assessed with age-appropriate instruments. RESULTS: Although mean cognitive performance was in the lower normative range, we found poorer results in subtests measuring visuoconstructive skills, short-term memory, and processing speed. Risk factors for negative cognitive outcome were young age at stroke, seizures, combined lesion location (cortical and subcortical), as well as marked NI. CONCLUSIONS: We recommend that all children with a history of AIS undergo regularly scheduled neuropsychological assessment to ensure implementation of appropriate interventions and environmental adjustments as early as possible.

Neuroprotection in cerebral ischemia with XG-102, a new peptide inhibitor of JNK

Abstract Stroke or cerebrovascular accident, whose great majority is of ischemic nature, is the third leading cause of mortality and long lasting disability in industrialised countries. Resulting from the loss of blood supply to the brain depriving cerebral tissues of oxygen and glucose, it induces irreversible neuronal damages. Despite the large amount of research carried out into the causes and pathogenic features of cerebral ischemia the progress toward effective treatments has been poor. Apart the clot-busting drug tissue-type plasminogen activator (tPA) as effective therapy for acute stroke (reperfusion by thrombolysis) but limited to a low percentage of patients, there are currently no other approved medical treatments. The need for new therapy strategies is therefore imperative. Neuronal death in cerebral ischemia is among others due to excitotoxic mechanisms very early after stroke onset. One of the main involved molecular pathways leading to excitotoxic cell death is the c-Jun NH2-terminal kinase (JNK) pathway. Several studies have already shown the efficacy of a neuroprotective agent of a new type, a dextrogyre peptide synthesized in the retro inverso form (XG102, formerly D-JNKI1), which is protease-resistant and cell-penetrating and that selectively and strongly blocks the access of JNK to many of its targets. A powerful protection was observed with this compound in several models of ischemia (Borsello et al. 2003;Hirt et al. 2004). This chimeric compound, made up of a 10 amino acid TAT transporter sequence followed by a 20 amino acids JNK binding domain (JBD) sequence from JNK inhibitor protein (JIP) molecule, induced both a major reduction in lesion size and improved functional outcome. Moreover it presents a wide therapeutic window. XG-102 has proved its powerful efficacy in an occlusion model of middle cerebral artery in mice with intracérebroventricular (i.c.v.) injection but in order to be able to consider the development of this drug for human ischemic stroke it was therefore necessary to determine the feasibility of its systemic administration. The studies being the subject of this thesis made it possible to show a successful neuroprotection with XG-102 administered systemically after transient mouse middle cerebral artery occlusion (MCAo). Moreover our data. provided information about the feasibility to combine XG-102 with tPA without detrimental action on cell survival. By combining the benefits from a reperfusion treatment with the effects of a neuroprotective compound, it would represent the advantage of bringing better chances to protect the cerebral tissue. Résumé L'attaque cérébrale ou accident vasculaire cérébral, dont la grande majorité est de nature ischémique, constitue la troisième cause de mortalité et d'infirmité dans les pays industrialisés. Résultant de la perte d'approvisionnement de sang au cerveau privant les tissus cérébraux d'oxygène et de glucose, elle induit des dommages neuronaux irréversibles. En dépit du nombre élevé de recherches effectuées pour caractériser les mécanismes pathogènes de l'ischémie. cérébrale, les progrès vers des traitements efficaces restent pauvres. Excepté l'activateur tissulaire du plasminogène (tPA) dont le rôle est de désagréger les caillots sanguins et employé comme thérapie efficace contre l'attaque cérébrale aiguë (reperfusion par thrombolyse) mais limité à un faible pourcentage de patients, il n'y a actuellement aucun autre traitement médical approuvé. Le besoin de nouvelles stratégies thérapeutiques est par conséquent impératif. La mort neuronale dans l'ischémie cérébrale est entre autres due à des mécanismes excitotoxiques survenant rapidement après le début de l'attaque cérébrale. Une des principales voies moléculaires impliquée conduisant à la mort excitotoxique des cellules est la voie de la c-Jun NH2terminal kinase (JNK). Plusieurs études ont déjà montré l'efficacité d'un agent neuroprotecteur d'un nouveau type, un peptide dextrogyre synthétisé sous la forme retro inverso (XG-102, précédemment D-JNKI1) résistant aux protéases, capable de pénétrer dans les cellules et de bloquer sélectivement et fortement l'accès de JNK à plusieurs de ses cibles. Une puissante protection a été observée avec ce composé dans plusieurs modèles d'ischémie (Borsello et al. 2003;Hirt et al. 2004). Ce composé chimérique, construit à partir d'une séquence TAT de 10 acides aminés suivie par une séquence de 20 acides aminés d'un domaine liant JNK (JBD) issu de la molécule JNK protéine inhibitrice. (JIP), induit à la fois une réduction importante de la taille de lésion et un comportement fonctionnel amélioré. De plus il présente une fenêtre thérapeutique étendue. XG-102 a prouvé sa puissante efficacité dans un modèle d'occlusion de l'artère cérébrale moyenne chez la souris avec injection intracerebroventriculaire (i.c.v.) mais afin de pouvoir envisager le développement de ce composé pour l'attaque cérébrale chez l'homme, il était donc nécessaire de déterminer la faisabilité de son administration systémique. Les études faisant l'objet de cette thèse ont permis de montrer une neuroprotection importante avec XG-102 administré de façon systémique après l'occlusion transitoire de l'artère cérébrale moyenne chez la souris (MCAo). De plus nos données ont fourni des informations quant à la faisabilité de combiner XG-102 et tPA, démontrant une protection efficace par XG-102 malgré l'action nuisible du tPA sur la survie des cellules. En combinant les bénéfices de la reperfusion avec les effets d'un composé neurooprotecteur, cela représenterait l'avantage d'apporter des meilleures chances de protéger le tissu cérébral.

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

BACKGROUND AND PURPOSE: We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received IV thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. RESULTS: In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS: IV thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

Stroke initial severity and outcome relative to insurance status in a universal health care system in Switzerland.

BACKGROUND:  Socioeconomic status is thought to have a significant influence on stroke incidence, risk factors and outcome. Its influence on acute stroke severity, stroke mechanisms, and acute recanalisation treatment is less known. METHODS:  Over a 4-year period, all ischaemic stroke patients admitted within 24 h were entered prospectively in a stroke registry. Data included insurance status, demographics, risk factors, time to hospital arrival, initial stroke severity (NIHSS), etiology, use of acute treatments, short-term outcome (modified Rankin Scale, mRS). Private insured patients (PI) were compared with basic insured patients (BI). RESULTS:  Of 1062 consecutive acute ischaemic stroke patients, 203 had PI and 859 had BI. They were 585 men and 477 women. Both populations were similar in age, cardiovascular risk factors and preventive medications. The onset to admission time, thrombolysis rate, and stroke etiology according to TOAST classification were not different between PI and BI. Mean NIHSS at admission was significantly higher for BI. Good outcome (mRS ≤ 2) at 7 days and 3 months was more frequent in PI than in BI. CONCLUSION:  We found better outcome and lesser stroke severity on admission in patients with higher socioeconomic status in an acute stroke population. The reason for milder strokes in patients with better socioeconomic status in a universal health care system needs to be explained.

Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Rupture of a concealed aneurysm after intravenous thrombolysis of a thrombus in the parent middle cerebral artery.

BACKGROUND: Management of ischemic stroke in the presence of aneurysmal brain disease is controversial. Recent retrospective evidence suggests that in selected patients, intravenous thrombolysis (IVT) remains a safe approach for reperfusion. METHODS: We document a case of post-thrombolysis aneurysmal rupture. Supported by additional scientific literature we postulate that acute aneurysmal thrombosis leading to stroke in the culprit artery may be an ominous sign of rupture and should be considered separately from fortuitously discovered distant aneurysmal disease. RESULTS: A 71-year-old female presented with an acute right middle cerebral artery stroke syndrome. IVT allowed vessel reperfusion and revealed a previously concealed, juxtaposed non-giant M1 segment saccular aneurysm. Secondary aneurysmal rupture ensued. The aneurysm was secured by surgical clipping. Postoperative course was uneventful. CONCLUSIONS: This case shows that despite reports of thrombolysis safety in the presence of brain aneurysms, thrombolysis remains potentially hazardous and hints toward an increased risk when the stroke arises on the parent vessel itself.

Coagulation factor Xa activates thrombin in ischemic neural tissue.

Thrombin is involved in mediating neuronal death in cerebral ischemia. We investigated its so far unknown mode of activation in ischemic neural tissue. We used an in vitro approach to distinguish the role of circulating coagulation factors from endogenous cerebral mechanisms. We modeled ischemic stroke by subjecting rat organotypic hippocampal slice cultures to 30-min oxygen (5%) and glucose (1 mmol/L) deprivation (OGD). Perinuclear activated factor X (FXa) immunoreactivity was observed in CA1 neurons after OGD. Selective FXa inhibition by fondaparinux during and after OGD significantly reduced neuronal death in the CA1 after 48 h. Thrombin enzyme activity was increased in the medium 24 h after OGD and this increase was prevented by fondaparinux suggesting that FXa catalyzes the conversion of prothrombin to thrombin in neural tissue after ischemia in vitro. Treatment with SCH79797, a selective antagonist of the thrombin receptor protease-activated receptor-1 (PAR-1), significantly decreased neuronal cell death indicating that thrombin signals ischemic damage via PAR-1. The c-Jun N-terminal kinase (JNK) pathway plays an important role in excitotoxicity and cerebral ischemia and we observed activation of the JNK substrate, c-Jun in our model. Both the FXa inhibitor, fondaparinux and the PAR-1 antagonist SCH79797, decreased the level of phospho-c-Jun Ser73. These results indicate that FXa activates thrombin in cerebral ischemia, which leads via PAR-1 to the activation of the JNK pathway resulting in neuronal death.

Temporal distribution and magnitude of the vulnerability period around stroke depend on stroke subtype.

Background: We aimed to analyze the rate and time distribution of pre- and post-morbid cerebrovascular events in a single ischemic stroke population, and whether these depend on the etiology of the index stroke. Methods: In 2,203 consecutive patients admitted to a single stroke center registry (ASTRAL), the ischemic stroke that led to admission was considered the index event. Frequency distribution and cumulative relative distribution graphs of the most recent and first recurrent event (ischemic stroke, transient ischemic attack, intracranial or subarachnoid hemorrhage) were drawn in weekly and daily intervals for all strokes and for all stroke types. Results: The frequency of events at identical time points before and after the index stroke was mostly reduced in the first week after (vs. before) stroke (1.0 vs. 4.2%, p < 0.001) and the first month (2.7 vs. 7.4%, p < 0.001), and then ebbed over the first year (8.4 vs. 13.1%, p < 0.001). On daily basis, the peak frequency was noticed at day -1 (1.6%) with a reduction to 0.7% on the index day and 0.17% 24 h after. The event rate in patients with atherosclerotic stroke was particularly high around the index event, but 1-year cumulative recurrence rate was similar in all stroke types. Conclusions: We confirm a short window of increased vulnerability in ischemic stroke and show a 4-, 3- and 2-fold reduction in post-stroke events at 1 week, 1 month and 1 year, respectively, compared to identical pre-stroke periods. This break in the 'stroke wave' is particularly striking after atherosclerotic and lacunar strokes.

Validation of the DRAGON Score in 12 Stroke Centers in Anterior and Posterior Circulation.

BACKGROUND AND PURPOSE: The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0-2) and miserable (modified Rankin scale score, 5-6) outcomes. RESULTS: Area under the receiver operating characteristic curve was 0.84 (0.82-0.85) for miserable outcome and 0.82 (0.80-0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83-0.86) and 0.82 (0.78-0.87), respectively. No sex-related difference in performance was observed (P=0.25). CONCLUSIONS: The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

Cerebral infarction in diabetes: Clinical pattern, stroke subtypes,and predictors of in-hospital mortality

Background: To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke.Methods: Diabetes was diagnosed in 393 (21.3%) of 1,840 consecutive patients with cerebral infarction included in a prospective stroke registry over a 12-year period. Demographic characteristics, cardiovascular risk factors, clinical events, stroke subtypes, neuroimaging data, and outcome in ischemic stroke patients with and without diabetes were compared. Predictors of in-hospital mortality in diabetic patients with ischemic stroke were assessed by multivariate analysis. Results: People with diabetes compared to people without diabetes presented more frequently atherothrombotic stroke (41.2% vs 27%) and lacunar infarction (35.1% vs 23.9%) (P < 0.01). The in-hospital mortality in ischemic stroke patients with diabetes was 12.5% and 14.6% in those without (P = NS). Ischemic heart disease, hyperlipidemia, subacute onset, 85 years old or more, atherothrombotic and lacunar infarcts, and thalamic topography were independently associated with ischemic stroke in patients with diabetes, whereas predictors of in-hospital mortality included the patient's age, decreased consciousness, chronic nephropathy, congestive heart failure and atrial fibrillation. Conclusion: Ischemic stroke in people with diabetes showed a different clinical pattern from those without diabetes, with atherothrombotic stroke and lacunar infarcts being more frequent. Clinical factors indicative of the severity of ischemic stroke available at onset have a predominant influence upon in-hospital mortality and may help clinicians to assess prognosis more accurately.

Early mobilization out of bed after ischaemic stroke reduces severe complications but not cerebral blood flow: a randomized controlled pilot trial.

OBJECTIVE: To evaluate whether early mobilization after acute ischaemic stroke is better than delayed mobilization with regard to medical complications and if it is safe in relation to neurological function and cerebral blood flow. DESIGN: Randomized controlled pilot trial of early versus delayed mobilization out of bed with incidence of severe complications as the primary outcome. SETTING: Acute stroke unit in the neurology department of a University Hospital. PARTICIPANTS: Fifty patients after ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score >6 were recruited. INTERVENTION: All patients were treated with physiotherapy immediately after their admission. In the early protocol patients were mobilized out of bed after 52 hours, in the delayed protocol after seven days. RESULTS: Eight out of 50 randomized patients were excluded from the per-protocol analysis because of early transfer to other hospitals. There were 2 (8%) severe complications in the 25 early mobilization patients and 8 (47%) in the 17 delayed mobilization patients (P < 0.006). There were no differences in the total number of complications or in clinical outcome. In the 26 patients (62%) who underwent serial transcranial Doppler ultrasonography, no blood flow differences were found. CONCLUSION: We found an apparent reduction in severe complications and no increase in total complications with an early mobilization protocol after acute ischaemic stroke. No influence on neurological three-month outcomes or on cerebral blood flow was seen. These results justify larger trials comparing mobilization protocols with possibly even faster mobilization out of bed than explored here.

Diagnostic pitfalls: posterior ischemic optic neuropathy mimicking optic neuritis.

In young people, the most frequent cause of isolated monocular visual loss due to an optic neuropathy is optic neuritis. We present the case of a 27 year old woman who presented monocular visual loss, excruciating orbital pain and unusual temporal headache. The initial diagnosis of optic neuritis revealed later to be a posterior ischemic optic neuropathy (PION). In this case, PION was the first unique presentation of a non-traumatic carotid dissection, and it was followed 24h later by an ischemic stroke. Sudden monocular visual loss associated with a new-onset headache are clinical symptoms that should immediately prompt to a carotid dissection.