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OBJECTIVE: Epidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent. METHODS AND RESULTS: In the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non-CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke-free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke-free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37-1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74-3.34), without aura (OR = 2.67, 95% CI = 2.15-3.32), and family history of vascular disease in first-degree relatives (OR = 1.69, 95% CI = 1.39-2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47-0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62-0.91), and obese (OR = 0.41, 95% CI = 0.31-0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47-2.22) in comparison with patients with non-CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti-migraine preventive medications, especially beta-blockers, compared with the other groups. INTERPRETATION: The risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta-blockers. ANN NEUROL 2023;94:585-595.
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Enxaqueca sem Aura , Acidente Vascular Cerebral , Dissecação da Artéria Vertebral , Masculino , Adulto Jovem , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Dissecação da Artéria Vertebral/complicações , Dissecação da Artéria Vertebral/epidemiologia , Acidente Vascular Cerebral/complicações , ArtériasRESUMO
OBJECTIVE: To explore the impact of antithrombotic therapy discontinuation in the postacute phase of cervical artery dissection (CeAD) on the mid-term outcome of these patients. METHODS: In a cohort of consecutive patients with first-ever CeAD, enrolled in the setting of the multicentre Italian Project on Stroke in Young Adults Cervical Artery Dissection, we compared postacute (beyond 6 months since the index CeAD) outcomes between patients who discontinued antithrombotic therapy and patients who continued taking antithrombotic agents during follow-up. Primary outcome was a composite of ischaemic stroke and transient ischaemic attack. Secondary outcomes were (1) Brain ischaemia ipsilateral to the dissected vessel and (2) Recurrent CeAD. Associations with the outcome of interest were assessed by the propensity score (PS) method. RESULTS: Of the 1390 patients whose data were available for the outcome analysis (median follow-up time in patients who did not experience outcome events, 36.0 months (25th-75th percentile, 62.0)), 201 (14.4%) discontinued antithrombotic treatment. Primary outcome occurred in 48 patients in the postacute phase of CeAD. In PS-matched samples (201 vs 201), the incidence of primary outcomes among patients taking antithrombotics was comparable with that among patients who discontinued antithrombotics during follow-up (5.0% vs 4.5%; p(log rank test)=0.526), and so was the incidence of the secondary outcomes ipsilateral brain ischaemia (4.5% vs 2.5%; p(log rank test)=0.132) and recurrent CeAD (1.0% vs 1.5%; p(log rank test)=0.798). CONCLUSIONS: Discontinuation of antithrombotic therapy in the postacute phase of CeAD does not appear to increase the risk of brain ischaemia during follow-up.
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Isquemia Encefálica , Acidente Vascular Cerebral , Dissecação da Artéria Vertebral , Artérias , Isquemia Encefálica/complicações , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/complicações , Dissecação da Artéria Vertebral/complicações , Dissecação da Artéria Vertebral/tratamento farmacológico , Dissecação da Artéria Vertebral/epidemiologia , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. METHODS: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD-). RESULTS: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13-2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06-18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26-0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58-7.31] and 2.07 [95% CI, 1.06-4.03], respectively) in multivariable Cox proportional hazards analysis. CONCLUSIONS: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.
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Displasia Fibromuscular/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Dissecação da Artéria Vertebral/epidemiologia , Adolescente , Adulto , Artérias Carótidas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Prevalência , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco , Adulto JovemRESUMO
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.
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Acidente Vascular Cerebral , Dissecação da Artéria Vertebral , Adolescente , Artérias , Estudos de Coortes , Dissecação , Feminino , Humanos , Itália/epidemiologia , Estudos Multicêntricos como Assunto , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
INTRODUCTION: To describe clinical, neuroimaging, and laboratory features of a large cohort of Italian patients with reversible cerebral vasoconstriction syndrome. METHODS: In the setting of the multicenter Italian Project on Stroke at Young Age (IPSYS), we retrospectively enrolled patients with a diagnosis of definite reversible cerebral vasoconstriction syndrome according to the International Classification of Headache Disorders (ICHD)-3 beta criteria (6.7.3 Headache attributed to reversible cerebral vasoconstriction syndrome, imaging-proven). Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of reversible cerebral vasoconstriction syndrome without typical causes ("idiopathic reversible cerebral vasoconstriction syndrome") were compared with those of reversible cerebral vasoconstriction syndrome related to putative causative factors ("secondary reversible cerebral vasoconstriction syndrome"). RESULTS: A total of 102 patients (mean age, 47.2 ± 13.9 years; females, 85 [83.3%]) qualified for the analysis. Thunderclap headache at presentation was reported in 69 (67.6%) patients, and it typically recurred in 42 (60.9%). Compared to reversible cerebral vasoconstriction syndrome cases related to putative etiologic conditions (n = 21 [20.6%]), patients with idiopathic reversible cerebral vasoconstriction syndrome (n = 81 [79.4%]) were significantly older (49.2 ± 13.9 vs. 39.5 ± 11.4 years), had more frequently typical thunderclap headache (77.8% vs. 28.6%) and less frequently neurological complications (epileptic seizures, 11.1% vs. 38.1%; cerebral infarction, 6.1% vs. 33.3%), as well as concomitant reversible brain edema (25.9% vs. 47.6%). CONCLUSIONS: Clinical manifestations and putative etiologies of reversible cerebral vasoconstriction syndrome in our series are slightly different from those observed in previous cohorts. This variability might be partly related to the coexistence of precipitating conditions with a putative etiologic role on disease occurrence.
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Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/patologia , Adulto , Feminino , Transtornos da Cefaleia Primários/etiologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SíndromeRESUMO
BACKGROUND: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. METHODS: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. RESULTS: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. CONCLUSION: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy.
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Redes Comunitárias/estatística & dados numéricos , Doença de Moyamoya , Neuroimagem , Acidente Vascular Cerebral/complicações , Adolescente , Adulto , Idoso , Isquemia Encefálica/complicações , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/genética , Fenótipo , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Transorbital sonography (TOS) has been proven to be able to non-invasively detect elevated intracranial pressure. In this condition TOS shows an increase in optic nerve sheath diameter (ONSD). It has been suggested that internal jugular vein valve insufficiency (IJVVI) may represent a factor contributing to the pathogenesis of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate whether patients with IIH or secondary IH have higher ONSD values and higher frequency of IJVVI compared to subjects without IH. METHODS: Twenty-one patients with newly diagnosed IIH or secondary IH were prospectively evaluated and compared with 21 age, gender and BMI-matched controls. Experienced vascular sonographers used B-mode TOS to evaluate ONSD, optic nerve diameter (OND) and IJVVI. CSF opening pressures were also measured. RESULTS: ONSD values were significantly higher in patients (6.50 ± 0.67) than controls (5.73 ± 0.66; p < 0.0001). No differences were found in OND values between patients (2.99 ± 0.26) and controls (2.93 ± 0.41; p = 0.574). No correlation was demonstrated between ONSD and CSF opening pressure (r = 0,086) (p = 0.73). No difference in frequency of IJVVI between patients (11/42 valves, 26 %) and controls (9/42, 21 %) was observed (p = 0.777). CONCLUSIONS: Increased ONSD values detected by TOS support the diagnosis of IH. Our results do not support the hypothesis of a venous congestion as a potential factor contributing to the pathogenesis of IIH. TRIAL REGISTRATION: Not applicable. Observational, non-interventional study.
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Hipertensão Intracraniana/diagnóstico por imagem , Veias Jugulares/diagnóstico por imagem , Nervo Óptico/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana/métodos , Adulto , Estudos de Viabilidade , Feminino , Humanos , Hipertensão Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Órbita , Pseudotumor Cerebral/diagnóstico por imagem , Pseudotumor Cerebral/etiologiaRESUMO
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary cerebral small vessel disease, is caused by mutations in the NOTCH3 gene on chromosome 19. Clinical manifestations of CADASIL include recurrent transient ischemic attacks, strokes, cognitive defects, epilepsy, migraine and psychiatric symptoms. Parkinsonian features have variably been reported in CADASIL patients, but only a few patients showed a clear parkinsonian syndrome. We studied two patients, a pair of monozygotic twins, carrying the R1006C mutation of the NOTCH3 gene and affected by a parkinsonian syndrome. For the first time in CADASIL patients, we used transcranial sonography (TCS) to assess basal ganglia abnormalities. TCS showed a bilateral hyperechogenic pattern of substantia nigra in one twin, and a right hyperechogenic pattern in the other. In both patients, lenticular nuclei showed a bilateral hyperechogenic pattern, and the width of the third ventricle was slightly increased. The TCS pattern found in our CADASIL patients is characteristic neither for Parkinson's disease, nor for vascular parkinsonism and seems to be specific and related to the disease-specific pathological features.
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CADASIL/diagnóstico por imagem , Mutação/genética , Doença de Parkinson , Receptor Notch3/genética , Ultrassonografia Doppler Transcraniana/métodos , Idoso , Arginina/genética , CADASIL/complicações , CADASIL/genética , Cisteína/genética , Humanos , Masculino , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Gêmeos MonozigóticosRESUMO
In the present report, we describe two cases of right-sided M1 segment middle cerebral artery dissection in a 51-year-old Asian female and in a 28-year-old Caucasian male patient with no previous history of ischemic stroke or known intracranial atherosclerosis presenting with acute unilateral headache progressing to severe multifocal hemispheric infarction with nearly complete one-sided motor paralysis. In both patients, a middle cerebral artery dissection was detected on angiography; they were given exclusively medical therapy: patient 1 was not eligible to reperfusive therapies and was treated with a three-month course of acetylsalicylic acid and clopidogrel combined with low-dose enoxaparin, while patient 2 was initially treated with intravenous alteplase with no hemorrhagic complications and was later shifted to single antiplatelet therapy. Despite an initial worsening of clinical severity and an extensive ischemic lesion in both patients, neurologic function improved over time, eventually allowing recovery of unaided gait. Therefore, in the absence of signs of hemorrhage, intravenous thrombolysis or dual antiplatelet regimens could be considered in strokes related to middle cerebral artery dissection.
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The aim of this paper is to discuss the use of transcranial doppler in the pre-hospital management of stroke. In the pre-hospital organization, neurological defect scales are used, but they are often indicative of the occlusions of anterior circulation and not of the posterior circulation. Patients with posterior circulation stroke are sometimes not diagnosed and clinically treated. In the pre-hospital phase, the transcranial doppler may identify an occlusion of the large cerebral vessels and be useful for stroke patients, in particular those with posterior occlusions, for a more precise diagnosis and consequently for adequate treatment in the excellence centers for stroke.
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Acidente Vascular Cerebral , Ultrassonografia Doppler Transcraniana , Hospitais , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Ultrassonografia Doppler em CoresRESUMO
BACKGROUND: The objective of our description is to shed light on some new hemodynamic and clinical characteristics in the unstable cerebral aneurysm Case: We describe a 54 year old woman who presented a tension headache, that increasing for several days. A CT scan performed in ER suggests a possible arterial ectasia at the level of the circle of Willis. The patient is hospitalized. An angio CT shows an aneurysm of the anterior communicating artery, without signs of fixation and/or other instability. A subsequent TCCD examination with venous study shows clear congestion at the level of the spheno-parietal sinus. The Valsalva maneuver determines an increase in local congestion. In the light of the ultrasound picture, the patient was quickly received in Neurosurgery with success. CONCLUSION: we describe a clinical case where the worsening tension headache was not secondary to the increase of volume of the aneurysm but was an epiphenomenon of venous congestion, explored with TCCD. The mass effect of the aneurysm determined venous sinus compression and changed the hemodynamic of the cerebral venous flow. We believe that venous outflow obstruction and a high intracranial venous pressure gradient may be a cerebral aneurysm rupture factor.
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Alteplase is the main pharmacological treatment available for intravenous thrombolysis in patients with acute ischemic stroke. Endovascular treatment alone or add-on to intravenous thrombolysis is a valid approach in acute ischemic stroke with cerebral large vessel disease. The most common serious adverse reaction related to alteplase is the development of spontaneous intracerebral hemorrhage and the presence of cerebral small vessel disease may increase this risk, particularly in cocaine users, even if only few data have been published on this topic. Here we reviewed in cocaine users with acute ischemic stroke the efficacy and safety of thrombolytic therapy.
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Isquemia Encefálica/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína , Cocaína/efeitos adversos , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Hemorragia CerebralRESUMO
INTRODUCTION: We describe the case of a 79-year-old Caucasian Italian woman with a transient basilar occlusion monitored by transcranial Doppler, with subsequent recanalization and clinical shrinking deficit. This is the first case of transient basilar occlusive disease diagnosed and monitored by transcranial Doppler. This case is important and needs to be reported because transient basilar occlusion may be easily diagnosed if transcranial Doppler is performed. CASE PRESENTATION: A 79-year-old woman affected by chronic atrial fibrillation and not treated with oral anticoagulants, cardioverted to sinus rhythm during a gastric endoscopy. She then showed a sudden-onset loss of consciousness, horizontal and vertical gaze palsy, tetraparesis and bilateral miosis and coma. Two hours later, the symptoms resolved quickly, leaving no residual neurologic deficits. Transcranial Doppler examination showed a dampened flow in the basilar artery in the emergency examination and a restored flow when the symptoms resolved. CONCLUSION: This is the first case of transient basilar occlusive disease diagnosed and monitored by transcranial Doppler. We believe that transcranial Doppler should be performed in all cases of unexplained acute loss of consciousness, in particular, if associated with signs of brainstem dysfunctions.
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AIMS OF THE STUDY: to identify with echo color Doppler ultrasound of the supra-aortic vessels and transcranial color-coded duplex sonography (TCCD) various patterns of vessel occlusion within 3 h from stroke onset, to compare each group defined at the admission with clinical findings and outcome, and to study the recanalization process, independent of therapy. METHODS: We enrolled 89 consecutive patients (mean age 68.9 years). Ultrasound evaluation was done within 3 h from stroke onset, and was repeated at 3-6 and 24-36 h, at day 5, and at 3 months. At admission, patients were divided into the following groups: internal carotid artery occlusions and stenoses (<50%, 50-69%, > or =70%, near occlusion), middle cerebral artery stenoses and occlusions, tandem occlusions and T occlusions. Vascular recanalization in each group was evaluated. Subgroups were compared for NIH Stroke Scale (NIHSS) and the outcome measures mortality, Barthel index (BI) and modified Rankin scale (mRS). Favorable outcome was defined as mRS < or =2 and BI > or =90. RESULTS: Each subgroup differed significantly for baseline NIHSS (p < 0.0001), 3-month mortality (p = 0.0235), BI at day 5 (p = 0.0458) and mRS at 3 months (p = 0.0028), even after adjustment for treatment. T and tandem occlusions were the subgroups with the highest NIHSS scores and the poorest outcomes, and the same subgroups had the worst recanalization rates. CONCLUSIONS: TCCD in the acute setting of stroke patients allows identification of the presence and site of clots, prediction of outcome and study of the dynamic process of vessel recanalization, in both the acute phase and follow-up.