Background and Purpose-Several factors have been held responsible for the development of atherosclerosis. To avoid the masking effect of age, we evaluated correlates of carotid atherosclerosis in patients Ͻ55 years of age. Methods-Plasma lipids, oxidative resistance of low-density lipoprotein, homocysteine, inflammatory markers, plasma viscosity, and red cell deformability were measured in fasting blood samples of 100 subjects: 45 patients with Ͼ30% stenosis of the internal carotid artery, 20 patients with carotid occlusion, and 35 control subjects. Stenosis and intima-media thickness (IMT) of the carotid artery were evaluated by duplex ultrasound. Results-White blood cell (WBC) count, plasma fibrinogen, C-reactive protein (CRP), and lipoprotein(a) levels were significantly higher in patients than in control subjects, and patients had increased IMT (PϽ0.01 for all comparisons). There was a tendency for higher homocysteine levels in patients. Smokers had higher WBC, fibrinogen, and CRP levels. After the effect of smoking was controlled for, WBC count, natural logarithmic transform of homocysteine, and online-measured IMT remained significantly higher in patients than in control subjects. WBC, fibrinogen, and CRP levels were highest in the highest IMT quartile (Pϭ0.012, Pϭ0.007, and Pϭ0.036, respectively). Conclusions-Inflammatory markers and homocysteine have a more important role than lipid factors in early-onset carotid atherosclerosis. We cannot recommend the measurement of low-density lipoprotein peroxidation as a routine screening test to identify high-risk patients for early-onset carotid atherosclerosis. The confounding effect of smoking on inflammatory markers should be considered in studies on atherosclerosis.

Objectives The aim of this study was to determine a safe and effective dose of gadopiclenol, a new high relaxivity macrocyclic gadolinium-based contrast agent. Based on the contrast-to-noise ratio (CNR) as primary criterion, this new agent was compared with gadobenate dimeglumine in patients with contrast-enhancing central nervous system lesions. Methods and Materials This phase IIb international, multicenter, double-blind, randomized, controlled, parallel dose groups, and cross-over study included adult patients with known or highly suspected lesions with disrupted blood-brain barrier. Patients were randomized to 1 of 4 doses of gadopiclenol (0.025, 0.05, 0.1, 0.2 mmol/kg) and to 1 series of 2 magnetic resonance imaging scans: gadopiclenol then gadobenate dimeglumine at 0.1 mmol/kg or vice versa. The qualitative and quantitative efficacy evaluations were performed by 3 independent off-site blinded readers. Adverse events were monitored up to 1 day after second magnetic resonance imaging. Results The study population included 272 patients (58.5% females) with a mean (SD) age of 53.8 (13.6) years. The superiority of gadopiclenol over gadobenate dimeglumine was statistically demonstrated at 0.2 and 0.1 mmol/kg for all readers with an increase in CNR of more than 30% (P ≤ 0.0007). At 0.05 mmol/kg, gadopiclenol showed a CNR of similar magnitude as gadobenate dimeglumine at 0.1 mmol/kg, with no statistically significant difference. Similar results were obtained for lesion-to-brain ratio and contrast enhancement percentage, as secondary criteria. The relationship between CNR and dose of gadopiclenol was linear for all readers. Mean scores for lesion visualization variables, particularly lesion contrast enhancement, tended to be higher with gadopiclenol at 0.1 and 0.2 mmol/kg compared with gadobenate dimeglumine. All 3 readers mainly expressed an overall diagnostic preference for images with gadopiclenol at 0.1 mmol/kg (45.3%, 50.9%, or 86.8% of images) or expressed no preference (49.1%, 49.1%, or 9.4%, respectively), whereas preference for images with gadobenate dimeglumine was reported by 2 readers for 3.8% and 5.7% of the images. Predominantly, no preference was expressed when comparing images with gadopiclenol at 0.05 mmol/kg to those with gadobenate dimeglumine. Rates of adverse reactions were comparable for gadopiclenol (11.7%) and gadobenate dimeglumine (12.1%). Changes from baseline of more than 25% in serum creatinine and estimated glomerular filtration rate occurred in less than 2% of patients equally for gadopiclenol and gadobenate dimeglumine. Changes from baseline for the values of blood urea nitrogen and cystatin C were also similar between gadopiclenol and gadobenate dimeglumine. No safety concerns were detected on centralized electrocardiography readings. Conclusions Between the doses of 0.025 and 0.2 mmol/kg of gadopiclenol, the increase in CNR is linear. Compared with gadobenate dimeglumine at 0.1 mmol/kg, the doses of 0.05 and 0.1 mmol/kg of gadopiclenol gave similar or significantly greater contrast enhancement, respectively, and thus both doses can be considered for future phase III studies.

Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome (GBS), is characterized by ophthalmoplegia, ataxia, and areflexia. The annual incidence is around one patient per one million population. The antiganglioside anti-GQ1b IgG antibody has a role in the pathogenesis of the syndrome, especially of ophthalmoplegia. The presence of this antibody in the serum can be identified in over 80% of the patients, peaking in the first week, whereas albuminocytological dissociation in the cerebrospinal fluid (CSF) appears later. The most consistent electrophysiological findings in MFS are reduced sensory nerve action potentials and absent H reflexes. More variability is seen with F waves and various investigations involving cranial structures. Although there are usually no abnormalities in MFS by routine neuroimaging, in a few cases, contrast enhancement of nerve roots and signs of central nervous system involvement were described supporting the hypothesis of an anti-GQ1b-syndrome, a continuum involving GBS, MFS, and Bickerstaff's brainstem encephalitis. Owing to the lack of randomized trials, treatments used for GBS (intravenous immunoglobulin and plasmapheresis) are usually applied, although from retrospective analyses, the outcome was similar between treated and untreated subjects. The outcome of MFS is usually good with case fatality of < 5%. In the few autopsy cases, macroscopic abnormalities were generally not seen in the nervous system. Microscopic examination of the peripheral nervous system (including cranial nerves) showed segmental demyelination with minimal perivascular infiltration with normal spinal cord and brain stem.

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Background and purpose: The incidence of hospitalizations, treatment and case fatality of ischaemic stroke were assessed utilizing a comprehensive multinational database to attempt to compare the healthcare systems in six European countries, aiming also to identify the limitations and make suggestions for future improvements in the between-country comparisons. Methods: National registers of hospital discharges for ischaemic stroke identified by International Classification of Diseases codes 433-434 (ICD-9) and code I63 (ICD-10), medication purchases and mortality were linked at the patient level in each of the participating countries and regions: Finland, Hungary, Italy, the Netherlands, Scotland and Sweden. Patients with an index admission in 2007 were followed for 1 year. Results: In all, 64 170 patients with a disease code for ischaemic stroke were identified. The number of patients registered per 100 000 European standard population ranged from 77 in Scotland to 407 in Hungary. Large differences were observed in medication use. The age-and sex-adjusted all-cause case fatality amongst hospitalized patients at 1 year from stroke was highest in Hungary at 31.0% (95% confidence interval 30.5-31.5). Regional differences in age-and sex-adjusted 1-year case fatality within countries were largest in Hungary (range 23.6%-37.6%) and smallest in the Netherlands (20.5%-27.3%). Conclusions: It is feasible to link population-wide register data amongst European countries to describe incidence of hospitalizations, treatment patterns and case fatality of ischaemic stroke on a national level. However, the coverage and validity of administrative register data for ischaemic stroke should be developed further, and population-based and clinical stroke registers should be created to allow better control of case mix.

Stroke is the second-leading cause of death and a leading cause of serious long-term disability worldwide, with an increasing global burden due to the growing and aging population. However, strict eligibility criteria for current treatment opportunities make novel therapeutic approaches desirable. Oxidative stress plays a pivotal role during cerebral ischemia, eventually leading to neuronal injury and cell death. The significant correlation between redox imbalance and ischemic stroke has led to various treatment strategies targeting the endogenous antioxidant system in order to ameliorate the adverse prognosis in patients with cerebral infarction. One of the most extensively investigated cellular defense pathway in this regard is the Nrf2-heme oxygenase-1 (HO-1) axis. In this review, our aim is to focus on the potential clinical relevance of targeting the HO-1 pathway in ischemic stroke.

Our findings demonstrate the influence of geographical and ethnic variations on blood pressure. Acceptance and use of non-population-specific blood pressure distributions may lead to under- or overdiagnosis of adolescent hypertension. The use of geographically more relevant data should be encouraged.