Increased common carotid artery wall thickness is associated with rapid progression of asymptomatic carotid stenosis.

BACKGROUND AND PURPOSES: This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis. METHODS: A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up. RESULTS: At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model). CONCLUSIONS: Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.

Efficacy of systemic thrombolysis within 4.5 h from stroke symptom onset: a single-centre clinical and diffusion-perfusion 3T MRI study.

PURPOSE: The efficacy of thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) within 3 h from stroke onset has been extensively supported by randomised placebo-controlled multicentre trials. In our single-centre study, we investigated the efficacy of intravenous (IV) administration of rt-PA within 4.5 h of stroke onset, in terms of clinical and radiological outcome, using a 3T magnetic resonance (MR) scanner in a cohort of patients similar to that of multicentre clinical trials. MATERIALS AND METHODS: Consecutive patients treated with IV rt-PA were compared with an historical cohort of untreated patients (controls). Inclusion criteria were: (1) infarction of the middle cerebral artery territory, (2) eligibility for IV rt-PA treatment, and (3) 3T perfusion- and diffusion-weighted MR imaging and MR angiography performed within 4.5 h and repeated after 5-7 days. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Growth of the DWI lesion, saved hypoperfused tissue, and clinical outcome was assessed and compared in treated patients and controls. RESULTS: Forty-three patients treated with rt-PA and 69 controls were eligible for the analysis. Treated patients showed higher percentages of saved hypoperfused tissue (75 vs. 40 %; p = 0.009), vessel recanalisation (65 vs. 27.5%; p = 0.003), and haemorrhagic transformation (21 vs. 7%; p = 0.004), without any clinically significant haemorrhages. Furthermore, treated patients had a significant improvement of NIHSS at 24 h (p < 0.001), at discharge (p ≤ 0.001), and at the 3-month clinical evaluation (p < 0.001), while similar rates of both treated patients and controls achieved a 3-month modified Rankin scale ≤ 2 (62 and 65%; p = 0.7). CONCLUSION: Treatment with IV rt-PA within 4.5 h of stroke onset preserves a significant amount of brain tissue from final infarction, and increases the possibility of early and late clinical improvement.

Intra-arterial thrombectomy versus standard intravenous thrombolysis in patients with anterior circulation stroke caused by intracranial arterial occlusions: a single-center experience.

BACKGROUND: Severely impaired patients with persisting intracranial occlusion despite standard treatment with intravenous (IV) administration of recombinant tissue plasminogen activator (rtPA) or presenting beyond the therapeutic window for IV rtPA may be candidates for interventional neurothrombectomy (NT). The safety and efficacy of NT by the Penumbra System (PS) were compared with standard IV rtPA treatment in patients with severe acute ischemic stroke (AIS) caused by large intracranial vessel occlusion in the anterior circulation. METHODS: Consecutive AIS patients underwent a predefined treatment algorithm based on arrival time, stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score, and site of arterial occlusion on computed tomographic angiography (CTA). NT was performed either after a standard dose of IV rtPA (bridging therapy [BT]) or as single treatment (stand-alone NT [SAT]). Rates of recanalization, symptomatic intracranial bleeding (SIB), mortality, and functional outcome in NT patients were compared with a historical cohort of IV rtPA treated patients (i.e., controls). Three-month favourable outcome was defined as a modified Rankin Scale (mRS) score ≤2. RESULTS: Forty-six AIS patients were treated with NT and 51 with IV rtPA. The 2 groups did not differ with regard to demographics, onset NIHSS score (18.5±4 v 17±5; P=.06), or site of intracranial occlusion. Onset-to-treatment time in the NT and IV rtPA groups was 230 minutes (±78) and 176.5 (±44) minutes, respectively (P=.001). NT patients had significantly higher percentages of major improvement (≥8 points NIHSS score change at 24 hours; 26% v 10%; P=.03) and partial/complete recanalization (93.5% v 45%; P<.0001) compared to controls. Treatment by either SAT or BT similarly improved the chance of early recanalization and early clinical improvement. No significant differences were observed in the rate of SIB (11% v 6%), 3-month mortality (24% v 25%), or favorable outcome (40% v 35%) between NT and IV rtPA patients. CONCLUSIONS: Despite significantly delayed time of intervention, NT patients had higher rates of recanalization and early major improvement, with no differences in symptomatic intracranial hemorrhages. Early NIHSS score improvement did not translate into better 3-month mortality or outcome. NT seems a safe and effective adjuvant treatment strategy for selected patients with severe AIS secondary to large intracranial vessel occlusion in the anterior circulation.

Stroke prevention: managing modifiable risk factors.

Prevention plays a crucial role in counteracting morbidity and mortality related to ischemic stroke. It has been estimated that 50% of stroke are preventable through control of modifiable risk factors and lifestyle changes. Antihypertensive treatment is recommended for both prevention of recurrent stroke and other vascular events. The use of antiplatelets and statins has been shown to reduce the risk of recurrent stroke and other vascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are indicated in stroke prevention because they also promote vascular health. Effective secondary-prevention strategies for selected patients include carotid revascularization for high-grade carotid stenosis and vitamin K antagonist treatment for atrial fibrillation. The results of recent clinical trials investigating new anticoagulants (factor Xa inhibitors and direct thrombin inhibitors) clearly indicate alternative strategies in stroke prevention for patients with atrial fibrillation. This paper describes the current landscape and developments in stroke prevention with special reference to medical treatment in secondary prevention of ischemic stroke.

Safety of early carotid artery stenting after systemic thrombolysis: a single center experience.

Background. Patients with acute ischemic stroke due to internal carotid artery (ICA) disease are at high risk of early stroke recurrence. A combination of IV thrombolysis and early carotid artery stenting (CAS) may result in more effective secondary stroke prevention. Objective. We tested safety and durability of early CAS following IV thrombolysis in stroke patients with residual stenosis in the symptomatic ICA. Methods. Of consecutive patients treated with IV rtPA, those with residual ICA stenosis ≥70% or <70% with an ulcerated plaque underwent early CAS (>24 hours). The protocol included pre-rtPA MRI and MR angiography, and post-rtPA carotid ultrasound and CT angiography. Stroke severity was assessed by the NIH Stroke Scale (NIHSS). Three- and twelve-month stent patency was assessed by ultrasound. Twelve-month functional outcome was assessed by the modified Rankin Scale (mRS). Results. Of 145 consecutive IV rtPA-treated patients, 6 (4%) underwent early CAS. Median age was 76 (range 67-78) years, median NIHSS at stroke onset was 12 (range 9-16) and 7 (range 7-8) before CAS. Median onset-to-CAS time was 48 (range 30-94) hours. A single self-expandable stent was implanted to cover the entire lesion in all patients. The procedure was uneventful in all patients. After 12 months, all patients had stent patency, and the functional outcome was favourable (mRS ≤ 2) in all but 1 patient experiencing a recurrent stroke for new-onset atrial fibrillation. Conclusion. This small case series of a single centre suggests that early CAS may be considered a safe alternative to CEA after IV rtPA administration in selected patients at high risk of stroke recurrence.

Cryptogenic cerebral ischemia: clinical usefulness of a flexible ultrasound diagnostic algorithm for detection of patent foramen ovale.

OBJECTIVES: Paradoxical thromboembolism across a patent foramen ovale (PFO) may be involved in the pathogenesis of cryptogenic strokes. We tested the feasibility and the clinical usefulness of an early screening for PFO combining different ultrasound techniques in patients with acute cerebral ischemia of undetermined cause. METHODS: Consecutive patients with acute ischemic stroke or transient ischemic attack with undetermined cause were selected. Contrast-enhanced transcranial Doppler ultrasound (c-TCD) for detection of right-to-left shunt was performed on admission. Patients with right-to-left shunt on c-TCD underwent contrast-enhanced transesophageal echocardiography (c-TEE) and/or contrast-enhanced transthoracic echocardiography (c-TTE) for PFO confirmation. We tested the feasibility of this ultrasound algorithm in patients with acute cerebral ischemia, as well as its impact on further treatment decision. RESULTS: Over 30 months, we admitted 154 of 674 (23%) patients with undetermined stroke cause. Right-to-left shunt was detected by c-TCD in 76 of 148 (51%) patients. Of them, five of 76 (7%) patients dropped out of the study, whereas 10 of 76 (13%) could not perform a c-TEE due to lack of compliance. In the remaining 61 patients, a PFO was detected by c-TEE in 49 (80%) patients. Additional c-TTE study extended the examination for PFO detection to 66 patients, with a total of 57 PFO diagnosis (86%). An alternative stroke cause (i.e. an ulcerated aortic plaque) was detected in four patients. CONCLUSION: A combined ultrasound approach based on a flexible diagnostic algorithm improved our ability to detect a PFO or alternative stroke cause in patients with acute cerebral ischemia of undetermined cause and to optimize secondary stroke prevention.

Floating carotid thrombus treated by intravenous heparin and endarterectomy.

Among different subtypes of ischemic stroke, atherosclerotic stroke carries the greatest risk (30%) of worsening and recurrence during the acute phase of hospitalization with a 7.9% risk ≤ 30 days. Causes of this high risk include plaque rupture leading to thrombus formation, thrombus propagation with consequent vessel occlusion, and distal embolism. In this context, emergent endarterectomy or anticoagulation, followed by deferred endarterectomy, are both controversial. We report a patient with an ischemic stroke caused by thromboembolism from an ulcerated plaque with floating thrombus of the internal carotid artery (ICA). A controversial use of heparin is discussed.

Short-Term and Two-Year Rate of Recurrent Cerebrovascular Events in Patients with Acute Cerebral Ischemia of Undetermined Aetiology, with and without a Patent Foramen Ovale.

Purpose. We investigated stroke recurrence in patients with acute ischemic stroke of undetermined aetiology, with or without a patent foramen ovale (PFO). Methods. Consecutive stroke patients underwent to Transcranial Doppler and Transesophageal Echocardiography for PFO detection. Secondary stroke prevention was based on current guidelines. Results. PFO was detected in 57/129 (44%) patients. The rate of recurrent stroke did not significantly differ between patients with and without a PFO: 0.0% versus 1.4% (1 week), 1.7% versus 2.7% (1 month), and 3.5% versus 4.2% (3 months), respectively. The 2-year rates were 10.4% (5/48) in medically treated PFO and 8.3% (6/72) in PFO-negative patients (P = 0.65), with a relative risk of 1.25. No recurrent events occurred in 9 patients treated with percutaneous closure of PFO. Conclusion. PFO was not associated with increased rate of recurrent stroke. Age-related factors associated with stroke recurrence in cryptogenic stroke should be taken into account when patients older than 55 years are included in PFO studies.

Is stroke history reliably reported by elderly with cognitive impairment? A community-based study.

BACKGROUND/AIMS: Self-reported history of stroke has been questioned in the elderly due to the high prevalence of cognitive impairment. We tested the validity of response to a stroke questionnaire versus clinical diagnosis of stroke among elderly people with and without cognitive impairment. METHODS: Community-dwelling participants to the phase 1 Canadian Study of Health and Aging were screened for self-reported stroke. Physician-diagnosed stroke was set as the gold standard. The positive predictive value (PPV), sensitivity and specificity were determined. RESULTS: 1,536/ 1,659 (93%) participants aged 65 years and over had stroke information from both sources. Among stroke positive responders, the PPV was 81% overall: 76% for cognitively normal, 84% for cognitively impairment with no dementia (CIND), and 82% for demented. Among stroke diagnosed by physicians, history of stroke was reported by 38% cognitively normal, 54% CIND, and 55% demented. The specificity was over 97% in all cognitive categories. CONCLUSION: Among community-dwelling elderly people, any cognitive impairment did not imply inaccurate self-reported history of stroke. High prevalence of stroke and frequent contacts with health services among cognitively-impaired elderly may increase the awareness of stroke symptoms and signs. Stroke increases the risk of developing dementia in both cognitively normal and CIND, and efforts to accomplish stroke prevention are justified, especially in these categories.

Changes in cerebrovascular reactivity following low-frequency repetitive transcranial magnetic stimulation.

OBJECTIVES: Repetitive Transcranial Magnetic Stimulation (rTMS) potential therapeutic uses have been explored in many conditions including stroke. However, its potential effects on cerebral hemodynamics have not been deeply considered. Transcranial Doppler ultrasonography (TCD) is a promising tool in detecting focal changes of cerebral blood flow velocity (CBFV) and cerebrovascular reactivity (CRV) induced by rTMS. We evaluated possible changes in CBFV and CVR in healthy volunteers. METHODS: Low-frequency (1 Hz) and Sham rTMS were applied over the motor cortex (M1) of the left hemisphere of healthy volunteers. CBFV and CVR were evaluated in the ipsilateral middle cerebral artery (MCA). CVR to hypercapnia was derived from the breath-holding index (BHI). Subjects were randomly assigned to real or sham stimulation. RESULTS: Maximal CBFV of MCA tended to decrease after 1 Hz M1 rTMS. Low-frequency 1Hz M1 rTMS increased BHI (measured in MCA) immediately after rTMS, and the observed effect vanished after 15 min when applied over M1. We did not observe any significant change in Pulsatility Index (PI) and Resistance Index (RI) measures in all conditions. No significant changes of above mentioned parameters were observed in the sham stimulation group. CONCLUSIONS: Low-frequency rTMS induces a significant modulation of CVR in healthy subjects. This effect should be relevant in acute stroke patients with impaired cerebral autoregulation.

The Canadian Neurological Scale and the NIHSS: development and validation of a simple conversion model.

BACKGROUND: The Canadian Neurological Scale (CNS) and the National Institutes of Health Stroke Scale (NIHSS) are among the most reliable stroke severity assessment scales. The CNS requires less extensive neurological evaluation and is quicker and simpler to administer. OBJECTIVE: Our aim was to develop and validate a simple conversion model from the CNS to the NIHSS. METHODS: A conversion model was developed using data from a consecutive series of acute-stroke patients who were scored using both scales. The model was then validated in an external dataset in which all patients were prospectively assessed for stroke severity using both scales by different observers which consisted of neurology residents or stroke fellows. RESULTS: In all, 168 patients were included in the model development, with a median age of 73 years (20-94). Men constituted 51.8%. The median NIHSS score was 6 (0-31). The median CNS score was 8.5 (1.5-11.5). The relationship between CNS and NIHSS could be expressed as the formula: NIHSS = 23 - 2 x CNS. A cohort of 350 acute-stroke patients with similar characteristics was used for model validation. There was a highly significant positive correlation between the observed and predicted NIHSS score (r = 0.87, p < 0.001). The predicted NIHSS score was on average 0.61 higher than the observed NIHSS score (95% CI = 0.31-0.91). CONCLUSIONS: The CNS can be reliably converted to the NIHSS using a simple conversion formula: NIHSS = 23 - 2 x CNS. This finding may have a practical impact by permitting reliable comparisons with NIHSS-based evaluations and simplifying the routine assessment of acute-stroke patients in more diverse settings.

Ultrasound evaluation of early changes in arterial dissection.

We show magnetic resonance imaging, computed tomography-angiography, and ultrasound images of internal carotid artery dissection in a patient with acute ischemic stroke. Arterial changes occurring during the first few days were detected by serial ultrasound examinations. Neurologic and functional outcome are provided and therapeutic options discussed.

Vascular cognitive impairment (VCI): progress towards knowledge and treatment / Comprometimento cognitivo vascular (CCV): progresso do conhecimento e tratamento

Until recently, the study of cognitive impairment as a manifestation of cerebrovascular disease (CVD) has been hampered by the lack of common standards for assessment. The term vascular cognitive impairment (VCI) encompasses all levels of cognitive decline associated with CVD from mild deficits in one or more cognitive domains to crude dementia syndrome. VCI incorporates the complex interactions among classic vascular risk factors (i.e. arterial hypertension, high cholesterol, and diabetes), CVD subtypes, and Alzheimer Disease (AD) pathology. VCI may be the earliest, commonest, and subtlest manifestation of CVD and can be regarded as a highly prevalent and preventable syndrome. However, cognition is not a standardized outcome measure in clinical trials assessing functional ability after stroke. Furthermore, with the exception of anti-hypertensive medications, the impact of either preventive or acute stroke treatments on cognitive outcome is not known. Although clinical, epidemiological, neuroimaging, and experimental data support the VCI concept, there is a lack of integrated knowledge on the role played by the most relevant pathophysiological mechanisms involved in several neurological conditions including stroke and cognitive impairment such as excitotoxicity, apoptosis, mitochondrial DNA damage, oxidative stress, disturbed neurotransmitter release, and inflammation. For this reason, in 2006 the National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) defined a set of data elements to be collected in future studies aimed at defining VCI etiology, clinical manifestations, predictive factors, and treatment. These recommendations represent the first step toward developing diagnostic criteria for VCI based on sound knowledge rather than on hypotheses. The second step will be to integrate all studies using the agreed methodologies. This is likely to accelerate the search for answers.

Até recentemente, o estudo do comprometimento cognitivo como manifestação de doença cerebrovascular (DCV) tem sido comprometido pela falta de métodos de abordagem. O termo comprometimento cognitivo vascular (CCV) inclui todos os níveis de declínio cognitivo associados à DCV, de déficites discretos em um ou mais domínios cognitivos a uma síndrome demencial inequívoca. CCV incorpora interações complexas entre fatores de risco vasculares clássicos (i.e. hipertensão arterial, colesterol elevado e diabetes), subtipos de DCV e patologia de Doença de Alzheimer (DA). CCV pode ser a mais precoce, comum e sutil manifestação de DCV e pode ser encarada como uma demência altamente prevalente e prevenível. Todavia, a cognição não é uma medida de desfecho em ensaios clínicos que avaliam habilidades funcionais após acidente vascular cerebral (AVC). Além disso, com exceção de medicações anti-hipertensivas, o impacto tanto de medidas preventivas quanto tratamento agudo de AVC em desfecho cognitivo não é conhecido. A despeito de que dados clínicos, epidemiológicos, de neuroimagem e experimentais suportam o conceito de CCV, há falta de conhecimento integrado no papel desempenhado pelos mecanismos patofisiológicos mais relevantes envolvidos em muitas condições neurológicas incluindo AVC e comprometimento cognitivo, como excitotoxicidade, apoptose, dano ao DNA mitocondrial, stress oxidativo, distúrbios na liberação de neurotransmissores e inflamação. Por esta razão, em 2006 o National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) definiram um conjunto de dados a serem coletados em estudos futures auxiliando na definição da etiologia, manifestações clínicas, fatores preditivos e tratamento. Estas recomendações representam o primeiro degrau para o desenvolvimento dos critérios diagnósticos para CCV baseados em conhecimentos mais do que em hipóteses. O segundo degrau seria integrar todos os estudos usando metodologias aceitas, o que aceleraria a busca por respostas.

Cilostazol in the management of atherosclerosis.

The burden of atherosclerosis is particularly high in western countries in terms of mortality and disability. The cerebral arteries (stroke or transient ischemic attack [TIA]), coronary arteries (myocardial infarction [MI]) and peripheral arteries (intermittent claudication [IC], ischemic limb) can be affected. Atherosclerosis may involve different mechanisms such as inflammation, platelet activation, endothelial damage, balance between proliferation and apoptosis of smooth muscle cells and oxidative stress. Research is focused to counteract each of these aspects. Many antithrombotic drugs are currently available and most of them act as inhibitors of platelet function. Aspirin, ticlopidine, clopidogrel and the combination of aspirin plus dipyridamole are widely used for primary (in high-risk patients) and secondary prevention of atherosclerotic diseases. Research of new pharmacological strategies is driven by the need to reduce the risk of bleeding associated with the use of antiplatelet drugs. In this context cilostazol, a type III phosphodiesterase inhibitor, has demonstrated antiplatelet and vasodilator effects with low rate of bleeding complications. This review will focus on the pharmacological properties of cilostazol and its use in the management of atherothrombotic vascular diseases.