Retinal vessel diameters and microvascular abnormalities in patients with carotid stenosis before and 6 months after carotid endarterectomy: A prospective study.

PURPOSE: To assess retinal findings in patients with severe carotid stenosis (CS) before and after carotid endarterectomy (CEA) compared to those in controls. METHODS: This study is based on 70 patients (male 81%, mean age 69) scheduled for CEA in Helsinki University Hospital and 41 healthy nonmedicated controls (male 76%, mean age 68). Our examinations included fundus photographs. Semi-automated software (Vesselmap, Imedos) served for evaluation of central retinal arterial equivalent (CRAE) and venular equivalent (CRVE), and arterio-venous ratio (AVR) in both eyes. We assessed fundus photographs to subjectively grade microvascular abnormalities in the ipsilateral eyes including focal arteriolar narrowing and irregularities, arteriolar wall reflex, arterio-venous crossing signs and arteriolar and venular tortuosity in the macula. RESULTS: CRAE was similar in the ipsi-and contralateral eyes of our patients, and similar to that of the controls both pre- and postoperatively. Preoperatively, we observed higher CRVE in the patients' ipsilateral than in their contralateral eyes (222 vs. 217 µm, p = 0.009), and likewise higher than in controls' eyes (222 vs. 214 µm, p = 0.024). CRVE decreased postoperatively in the patients' ipsilateral eyes (222 vs. 217 µm, p = 0.037). Among the microvascular abnormalities, arteriolar and venular tortuosity in the macula showed higher grades in the patients than in the controls preoperatively (p = 0.035 and p = 0.043), but not postoperatively (p = 0.15 and p = 0.10). CONCLUSIONS: CRVE decreased after CEA, showing that venules constrict after the mechanical hindrance of blood flow is removed. Higher grades in arteriolar and venular tortuosity in the macula, a potential ocular biomarker of CS, subsided after CEA.

Comparison of the prognostic value of early-phase proton magnetic resonance spectroscopy and diffusion tensor imaging with serum neuron-specific enolase at 72 h in comatose survivors of out-of-hospital cardiac arrest-a substudy of the XeHypotheca trial.

PURPOSE: We compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA). METHODS: The predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3 - 6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory. RESULTS: The predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62-0.84), total N-acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68 - 0.88)), or NSE at 72 h (0.85 (0.76 - 0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80-0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85-0.98) vs 0.98 (0.96-1.00), p = 0.037). CONCLUSION: None of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use. TRIAL REGISTRATION: ClinicalTrials.gov NCT00879892, April 13, 2009.

Flicker-induced retinal vascular dilation in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy: a prospective study.

PURPOSE: Retinal vascular function was assessed in patients with carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) and in controls at a six-month interval. METHODS: We studied 68 patients (81% male, mean age 69) and 41 healthy non-medicated controls (77%, 68) from March 2015 to December 2018. Our ophthalmological examination included flicker-induced arteriolar and venular measurements with a Dynamic Vessel Analyser in both eyes. RESULTS: At baseline, flicker-induced arteriolar and venular dilation was reduced in the ipsilateral eyes of the patients compared with dilation in the controls (arteriolar 1.0% versus 2.6%, p = 0.001 and venular 2.2% versus 2.8%, p = 0.049). These differences subsided after CEA. In patients' ipsilateral eyes, flicker-induced arteriolar dilation was borderline postoperatively (preoperative 1.0% versus postoperative 1.6%, p = 0.06), whereas venular dilation increased (2.2% versus 2.8%, p = 0.025). We found various tentative associations with the change in flicker-induced dilations after CEA, but not with the preoperative dilations. CONCLUSIONS: Postoperative recovery of the reduced flicker-induced arteriolar and venular dilatation in the ipsilateral eye shows that, after CEA, the activity-dependent vascular reactivity of haemodynamically compromised retinal tissue can improve.

Ocular signs of carotid stenosis in ipsi- and contralateral eyes before and after carotid endarterectomy: a prospective study.

PURPOSE: We describe hypoperfusion-related and embolic ocular signs of carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) in a CS population. METHODS: We enrolled prospectively 70 CEA patients (81% male, mean age 69) and 41 non-medicated control subjects (76%, 68), from March 2015 to December 2018, assessing intraocular pressure (IOP), best-corrected visual acuity (BCVA) in logMAR units and performing a bio-microscopy examination. RESULTS: Main index symptoms included amaurosis fugax (Afx) (29, 41%) and hemispheric TIA (17, 24%), and 17 (24%) were asymptomatic. Of the 70, 17 patients (24%, 95% CI 16-36) showed ocular signs of CS. Of four embolic (Hollenhorst plaques) findings, one small macular plaque disappeared postoperatively. Four had hypoperfusion, that is ocular ischaemic syndrome (OIS), requiring panretinal photocoagulation: one for multiple mid-peripheral haemorrhages, two for iris neovascularization and one for neovascular glaucoma (NVG); only the NVG proved irreversible. Nine (de novo in three) showed mild OIS, that is only few mid-peripheral haemorrhages, ranging pre- /postoperatively in ipsilateral eyes from one to eleven (median two)/ one to two (median one), and in contralateral eyes from three to nine (median five)/ one to six (median three). Pre- and postoperative median BCVA was 0 or better, and mean IOP was normal, except in the NVG patient. Temporary visual impairment from 0 to 0.3 occurred in one eye soon after CEA due to ocular hyperperfusion causing macular oedema. CONCLUSIONS: Ocular signs of CS are common in CEA patients, ranging from few mid-peripheral haemorrhages to irreversible NVG. Clinicians should be aware of these signs in detecting CS.

Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification.

Background: Long-term treatment with the vitamin K antagonist warfarin is widely used for the prevention of venous thrombosis and thromboembolism. However, vitamin K antagonists may promote arterial calcification, a phenomenon that has been previously studied in coronary and peripheral arteries, but not in extracranial carotid arteries. In this observational cohort study, we investigated whether warfarin treatment is associated with calcification of atherosclerotic carotid arteries. Methods: Overall, 500 consecutive patients underwent carotid endarterectomy, 82 of whom had received long-term warfarin therapy. The extent of calcification was assessed with preoperative computed tomography angiography, and both macroscopic morphological grading and microscopic histological examination of each excised carotid plaque were performed after carotid endarterectomy. Results: Compared with non-users, warfarin users had significantly more computed tomography angiography-detectable vascular calcification in the common carotid arteries (odds ratio 2.64, 95% confidence interval 1.51-4.63, P < 0.001) and even more calcification in the internal carotid arteries near the bifurcation (odds ratio 18.27, 95% confidence interval 2.53-2323, P < 0.001). Histological analysis revealed that the intramural calcified area in plaques from warfarin users was significantly larger than in plaques from non-users (95% confidence interval 3.36-13.56, P = 0.0018). Conclusions: Long-lasting warfarin anticoagulation associated with increased calcification of carotid atherosclerotic plaques, particularly in locations known to be the predilection sites of stroke-causing plaques. The clinical significance of this novel finding warrants further investigations.

Comatose With Basilar Artery Occlusion: Still Odds of Favorable Outcome With Recanalization Therapy.

Background: Around 30-60% of patients with basilar artery occlusion (BAO) present with coma, which is often considered as a hallmark of poor prognosis. Aim: To examine factors that will help predict outcomes in patients with BAO comatose on admission. Methods: A total of 312 patients with angiography-proven BAO were analyzed. Comas were assessed as Glasgow Coma Scale (GCS) of ≤8 or impaired level of consciousness ascertained in the medical records. Outcomes were evaluated with the modified Rankin Scale (mRS) over a phone call at 3 months. In our study, 53 patients were excluded due to inadequate data on the level of consciousness. Results: In total, 103/259 (39.8%) of BAO patients were comatose on admission. Factors associated with acute coma were higher age, coronary artery disease, convulsions, extent of early ischemia by posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) < 8, absence of patent posterior collateral vasculature, and occlusion over multiple segments of BA. A total of 21/103 (20.4%) of comatose patients had a favorable outcome (mRS 0-3), and 12/103 (11.7%) had a good outcome (mRS 0-2). Factors associated with a favorable outcome in comatose BAO patients were younger age (p = 0.010), less extensive baseline ischemia (p = 0.027), recanalization (p = 0.013), and avoiding symptomatic intracranial hemorrhage (sICH) (p = 0.038). Factors associated with the poorest outcome or death (mRS 5-6) were older age (p = 0.001), diabetes (p = 0.022), atrial fibrillation (p = 0.016), lower median GCS [4 (IQR 3.6) vs. 6 (5-8); p = 0.006], pc-ASPECTS < 8 (p = 0.003), unsuccessful recanalization (p = 0.006), and sICH (p = 0.010). Futile recanalization (mRS 4-6) was significantly more common in comatose patients (49.4 vs. 18.5%, p < 0.001). Conclusions: One in five BAO patients with acute coma had a favorable outcome. Older patients with cardiovascular comorbidities and already existing ischemic lesions before reperfusion therapies tended to have a poor prognosis, especially if no recanalization is achieved and sICH occurred.

Subfoveal choroidal thickness in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy: a prospective study.

PURPOSE: To compare subfoveal choroidal thickness (SFCT) and associated clinical variables in patients with carotid stenosis (CS) before and 6 months after carotid endarterectomy (CEA). METHODS: The prospective non-randomized Helsinki Carotid Endarterectomy Study - Brain and Eye Sub-sTudy included seventy patients (81% male, mean age 69 years) and 40 control subjects (77% male, 68 years), from March 2015 to December 2018. Ophthalmological examination included SFCT measured with enhanced-depth imaging-optical coherence tomography. Carotid stenosis (CS) was more severe (≥70% stenosis in 92%) ipsilateral to the CEA than contralaterally (<50% stenosis in 74%; p < 0.001). RESULTS: At baseline, patients had thinner mean SFCT than control subjects in both eyes (ipsilateral, 222 versus 257 µm and contralateral, 217 versus 258 µm, p ≤ 0.005). At follow-up, SFCT did not change in ipsi- and contralateral eyes compared to baseline in patients (p = 0.68 and p = 0.77), or in control subjects (p = 0.59 and p = 0.79). Patients with coronary artery disease had thinner mean SFCT versus those without it in ipsilateral eyes before CEA (200 versus 233 µm, p = 0.027). In ipsilateral eyes of patients before CEA, thinner SFCT and ocular signs of CS, plaque and hypoperfusion related findings combined, were associated (p = 0.036), and the best-corrected visual acuity, measured in logMAR, increased with increasing SFCT (r = -0.25; p = 0.046). CONCLUSIONS: Subfoveal choroidal thickness (SFCT) is thinner in patients with CS without association between SFCT and the grade of CS. Unchanged SFCT after CEA suggests, that choroidal vessels in severe CS are unable to react to increased blood flow. Bilaterally thin SFCT could be considered as yet another sign of CS.

Outcomes and long-term mortality after basilar artery occlusion-A cohort with up to 20 years' follow-up.

BACKGROUND: The data on long-term outcome after basilar artery occlusion (BAO) are scarce. Little is known about BAO survivors´ outcome over decades. AIM: We set out to investigate long-term survival and causes of death in BAO patients with up to two decades of follow-up. We also evaluated differences in outcome trends. METHODS: Two hundred and seven BAO patients treated with intravenous thrombolysis (IVT) at the Department of Neurology, Helsinki University Hospital, between 1995 and 2016, were analyzed. Short-term outcome was assessed by modified Rankin Scale (mRS) at 3 months. Long-term cumulative survival rate was analyzed using Kaplan-Meier analysis. Factors associated with mortality were analyzed with Cox regression. RESULTS: Moderate outcome (mRS 0-3) was achieved in 41.1% and good outcome (mRS 0-2) in 30.4% of patients at 3 months. Three-month mortality was 39.6%, of which 89% died within the first month. The median follow-up time in 3-month survivors was 8.9 years (maximum 21.8 years). Total mortality during follow-up was 52.2%. Cumulative mortality rate was 25.7%. Older age, coronary artery disease and more extensive ischemic changes on admission brain imaging were independently associated with long-term mortality. After the acute phase, the rate of other vascular causes of death increased in relation to stroke. CONCLUSIONS: The described evolution of a large, single-center BAO cohort shows a trend towards a higher rate of good and/or moderate outcome during later years in IVT-treated patients. Survivors showed relative longevity, and the rate of cardiac and other vascular causes of death increased in relation to stroke sequelae over the long term.

Predictive Factors for Pre-operative Recurrence of Cerebrovascular Symptoms in Symptomatic Carotid Stenosis.

OBJECTIVE: Across stroke subtypes, carotid artery stroke carries the highest risk of recurrence. Despite initiation of best medical therapy (BMT), some patients suffer recurrent neurological events before undergoing carotid endarterectomy (CEA). The aim was to identify clinical predictors of early recurrent events in patients with symptomatic carotid stenosis (sCS) awaiting CEA on modern BMT. METHODS: The Helsinki Carotid Endarterectomy Study 2 (HeCES2) is a cross sectional, longitudinal, prospective, and consecutive cohort study, which enrolled 500 symptomatic or asymptomatic patients with carotid stenosis scheduled for CEA in a tertiary stroke centre. Symptomatic patients were included for this analysis (n = 324). RESULTS: Of all 324 patients with sCS, 39 (12%) had a recurrent cerebrovascular event at a median of six days after the index symptom: four had an ischaemic stroke (1.2%), 16 a hemispheric transient ischaemic attack (TIA; 4.9%), and 19 amaurosis fugax (AFX; 5.9%). The recurrence rate was 4.0 % (n = 13) within 48 h and 9.9% (n = 32) within two weeks. None of the patients (n = 108) presenting with ocular symptoms (AFX or retinal artery occlusion) suffered recurrent hemispheric TIA or stroke. In Cox regression analysis, comorbid hypertension (hazard ratio [HR] 6.58, 95% confidence interval [CI] 1.33-32.47), hemispheric TIA as the index symptom (HR 3.42, 95% CI 1.70-6.90), the number of prior attacks (HR 1.12, 95% CI 1.08-1.15), and high low density lipoprotein/high density lipoprotein ratio (HR 1.51, 95% CI 1.09-2.11) were independently associated with an increased risk of recurrent event, while a history of major cardiovascular event (HR 0.33, 95% CI 0.11-0.96) and high serum fibrinogen level (HR 0.59, 95% CI 0.41-0.86) were associated with a decreased risk. CONCLUSION: More than every tenth patient with sCS experienced an early recurrent cerebrovascular event prior to scheduled CEA, despite optimal medication. However, stroke recurrence was lower than in earlier observational studies, which could be explained by improved care pathways, more aggressive medication, and expedited CEA. All recurrent strokes occurred in patients initially presenting with minor stroke.

Morphology and histology of silent and symptom-causing atherosclerotic carotid plaques - Rationale and design of the Helsinki Carotid Endarterectomy Study 2 (the HeCES2).

INTRODUCTION: Every fifth ischemic stroke is caused by thromboembolism originating from an atherosclerotic carotid artery plaque. While prevention is the most cost-effective stroke therapy, antiplatelet and cholesterol-lowering drugs have a ceiling effect in their efficacy. Therefore, discovery of novel pathophysiologic targets are needed to improve the primary and secondary prevention of stroke. This article provides a detailed study design and protocol of HeCES2, an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis. MATERIALS AND METHODS: Recruitment and carotid endarterectomies of the study patients with carotid atherosclerosis were performed from October 2012 to September 2015. After brain and carotid artery imaging, endarterectomised carotid plaques (CPs) and blood samples were collected from 500 patients for detailed biochemical and molecular analyses. Findings to date: We developed a morphological grading for macroscopic characteristics within CPs. The dominant macroscopic CP characteristics were: smoothness 62%, ulceration 61%, intraplaque hemorrhage 60%, atheromatous gruel 59%, luminal coral-type calcification 34%, abundant (44%) and moderate (39%) intramural calcification, and symptom-causing "hot spot" area 53%. Future plans: By combining clinically oriented and basic biomedical research, this large-scale study attempts to untangle the pathophysiological perplexities of human carotid atherosclerosis. Key Messages This article is a rationale and design of the HeCES2 study that is an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis. The HeCES2 study strives to develop diagnostic algorithms including radiologic imaging to identify carotid atherosclerosis patients who warrant surgical treatment. In addition, the study aims at finding out new tools for clinical risk stratification as well as novel molecular targets for drug development.

Recognizing subtle near-occlusion in carotid stenosis patients: a computed tomography angiographic study.

INTRODUCTION: Near-occlusion of the internal carotid artery (ICA) is a significant luminal diameter (LD) reduction beyond a tight atherosclerotic carotid stenosis (CS). Recognition of even subtle near-occlusions is essential to prevent underestimation of the stenosis degree. Our goal was to investigate the prevalence of near-occlusion among CS patients using a single standard criterion to facilitate its recognition, even when distal ICA LD reduction is not visually evident in computed tomography angiography (CTA). METHODS: We analysed carotid artery CTAs of 467 patients with moderate-to-severe CS scheduled for endarterectomy. We performed measurements of the bilateral distal ICA LDs from thin axial source images and utilized a 1.0 mm intra-individual side-to-side distal ICA LD difference to distinguish near-occlusions, based on a previous study, aware of the vagaries of measurement. For analysis stratification, we excluded cases with significant carotid pathology affecting LD measurements. RESULTS: We discovered 126 near-occlusions fulfilling our criterion of ipsilateral near-occlusion: the mean LD side-to-side difference (mm) with 95% confidence interval being 1.8 (1.6, 1.9) and a standard deviation of 0.8 mm. Among the 233 cases not meeting our near-occlusion criterion, we found 140 moderate (50-69%) and 93 severe (70-99%) ipsilateral stenoses. CONCLUSION: The utilization of 1.0 mm cut-off value for the intra-individual distal ICA LD side-to-side difference to distinguish atherosclerotic ICA near-occlusion leads to a relatively high incidence of near-occlusion. In CTA, recently suggested to be used for near-occlusion diagnosis, a discriminatory 1.0 mm cut-off value could function as a pragmatic tool to enhance the detection of even subtle near-occlusions.

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS: Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES: The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS: Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE: Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00879892.

Recanalization treatments in basilar artery occlusion-Systematic analysis.

BACKGROUND AND AIMS: Basilar artery occlusion is a most devastating form of stroke, and the current practice is to reverse it with revascularization therapies. Pharmacological thrombolysis, intravenous or intraarterial, has been adjuncted or replaced with invasive, endovascular thrombectomy procedures. The preferred approach remains unknown and many recanalizations are futile with no clinical benefit. We sought to determine reasons for futility and weigh the existing reports to find whether endovascular mechanical interventions provide superior outcomes over pharmacological thrombolysis alone. METHODS: After analyzing systematically the reports of outcomes produced by variable basilar artery occlusion recanalization protocols, information was retrieved and reconciled from 15 reports published from year 2005 comprising 803 patients in 17 cohorts. In the largest single-center cohort (162, Helsinki), predictors of futile recanalization (three-month modified Rankin Scale score 4 to 6) were determined. RESULTS: Good outcome was reported by mechanical approaches either alone or on demand more frequently than by pharmacological, intravenous or intraarterial thrombolysis protocols (35.5% versus 24.4%, p < 0.001), accompanied by higher recanalization rates (84.1% versus 70.9%, p < 0.001). Along with superior recanalization rate at 91%, good outcome was reached by primary thrombectomy in 36% at the cost of substantial futile recanalization rate at 60%, which was lower when using modern stentrievers only (52.8%). In the Helsinki cohort, the single most significant predictor was extensive baseline ischemia, increasing the odds of futility 20-fold (95%CI 4.39-92.29, p < 0.001). Other attributes of futility were ventilation support and history of atrial fibrillation or previous stroke. CONCLUSIONS: Endovascular mechanical approaches have been reported to provide superior outcomes over pharmacological thrombolysis in basilar artery occlusion. Stricter patient selection, most notably to exclude victims of already extended ischemia, would assist in translating excellent recanalization rates into improved clinical outcomes and more acceptable futility rates.

Comparative Burden of Influenza A/H1N1, A/H3N2 and B Infections in Children Treated as Outpatients.

BACKGROUND: Few studies have directly compared the clinical impact of different types and subtypes of influenza viruses in children. METHODS: In a prospective study of respiratory infections in preenrolled cohorts of children ≤13 years of age, we compared the clinical features and the overall burden of illness between outpatient children with A/H1N1, A/H3N2 and B infections. The data were derived from structured medical records filled out by study physicians and from daily symptom diaries filled out by the parents throughout the follow-up period. RESULTS: Of 358 children included in the analyses, 203 (57%) had influenza A/H1N1, 96 (27%) had A/H3N2, and 59 (16%) had influenza B infection. Children with influenza A/H3N2 were significantly younger (median, 3.2 years) than those with A/H1N1 (median, 4.8 years) or B (median, 5.1 years) infections (P < 0.0001). When adjusted for age, children 3-6 years of age with A/H3N2 infection had a higher frequency of fever ≥39.0°C (67% vs. 38%; P = 0.002), longer duration of fever (median, 4 vs. 3 days; P = 0.02) and more antibiotic treatments (43% vs. 20%; P = 0.004) than did children with A/H1N1 infections. Overall, the clinical presentation, duration of illness, frequency of complications, children's absenteeism from day care or school and parental work absenteeism were comparable between children with A/H1N1, A/H3N2 and B infections. CONCLUSIONS: Adjusted for age, the clinical manifestations and the burden of illness are largely comparable between children with influenza A/H1N1, A/H3N2 and B infections.

The normal internal carotid artery: a computed tomography angiographic study.

INTRODUCTION: Systematic computed tomography angiographic (CTA) studies investigating variation in internal carotid artery (ICA) luminal diameters (LDs) are scarce. Knowledge of the normal intra-individual LD variability would provide a cut-off value for detection of more subtle collapses. In addition, low intra-individual variability would allow using contralateral LD as a reference for estimation of stenosis degree in cases where ipsilateral measurement is hampered. Therefore, our aim was to investigate intra-individual LD variation of normal ICA. METHODS: We retrospectively collected multidetector high-speed CTAs of 104 patients younger than 40 years who were considered not to have carotid pathology. We carried out independent measurements of the common carotid artery (CCA) and ICA LDs bilaterally from axial source images by two observers, analysing side-to-side LD differences from averaged double measurements with a paired t test. RESULTS: We discovered no significant side-to-side LD differences. In the female group, the mean differences (mm) with 95% confidence intervals were 0.08 (0.00, 0.17) for CCA and 0.03 (-0.04, 0.11) for ICA, with ICA LD standard deviation of 0.4 mm. In the male group, these were: 0.06 (-0.04, 0.17), 0.02 (-0.07, 0.11) and 0.4 mm, respectively. We detected no ICA agenesis. CONCLUSION: The intrinsic intra-individual variation of the LD of normal ICA is minimal. This uniformity may serve as the basis for detection of subtle grades of side-to-side variation caused by pathology.

Predictors of early mortality in young adults after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Patient and radiological characteristics of intracerebral hemorrhage (ICH), surgical treatment, and outcome after ICH are interrelated. Our purpose was to define whether these characteristics or surgical treatment correlate with mortality among young adults. METHODS: We retrospectively reviewed clinical and imaging data of all first-ever nontraumatic patients with ICH between 16 and 49 years of age treated in our hospital between January 2000 and March 2010 and linked these data with national causes of death registry. A logistic regression analysis of factors associated with 3-month mortality and a propensity score comparison between patients treated conservatively and operatively was performed. RESULTS: Among the 325 eligible patients (59.4% men), factors associated with 3-month mortality included higher National Institutes of Health Stroke Scale score, infratentorial location, hydrocephalus, herniation, and multiple hemorrhages. Adjusted for these factors, as well as demographics, ICH volume, and the underlying cause, surgical evacuation was associated with lower 3-month mortality (odds ratio, 0.06; 95% confidence interval, 0.02-0.21). In propensity score-matched analysis, 3-month case fatality rates were 3-fold in those treated conservatively (27.5% versus 7.8%; P<0.001). CONCLUSIONS: The predictors of short-term case fatality are alike in young and elderly patients with ICH. However, initial hematoma evacuation was associated with lower 3-month case fatality in our young patients with ICH.

Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study.

Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.

Intravenous thrombolysis of basilar artery occlusion: thrombus length versus recanalization success.

BACKGROUND AND PURPOSE: In middle cerebral artery occlusion, probability of recanalization after intravenous tissue-type plasminogen activator thrombolysis (IVT) was reported to drop <1% for thrombi exceeding 8 mm. We aimed to evaluate the effect of thrombus length and location on success of recanalization after IVT in basilar artery occlusion. METHODS: We evaluated 164 consecutive patients with angiography-proven basilar artery occlusion and available thrombus length. We excluded 24 patients who underwent endovascular treatment. All included patients (n=140) received IVT. Thrombolysis in myocardial infarction 2 to 3 was considered as successful recanalization. RESULTS: Of the 140 included patients, 37 (26.4%) lacked post-treatment angiography, mostly because of early death. Of the remaining 103 patients, those with recanalization had shorter thrombi (median, 5.5 mm and mean, 9.7 mm) when compared with those with nonrecanalized (median, 15.0 mm and mean, 16.6 mm; P<0.001). Thrombi shorter than 10 mm had 70% to 80% probability of recanalization, whereas 10 to 20 mm, 20 to 30 mm, and >30 mm long thrombi had probabilities of 50% to 70%, 30% to 50%, and 20% to 30%, respectively. Patients with thrombi <10 mm (n=52) and recanalization had more frequently top-of-the basilar (92.5%) and less frequently caudal or midbasilar (7.5%) clot location (P=0.01). In multivariable analysis, thrombus length was independently associated with recanalization (P=0.001). Their relationship remained linear across all lengths. CONCLUSIONS: Although recanalization of basilar artery occlusion with IVT depends on thrombus length, its probability even in patients with thrombi >30 mm (20%-30%) was substantially higher than minimal recanalization of middle cerebral artery thrombi exceeding 8 mm. There was no threshold length, beyond which basilar artery occlusion recanalization with IVT could ad hoc be deemed hopeless.

Comparison of spectral gradient acoustic reflectometry and tympanometry for detection of middle-ear effusion in children.

BACKGROUND: Spectral gradient acoustic reflectometry (SGAR) and tympanometry are handy methods to aid in the diagnostics of middle-ear diseases, but no prior studies have directly assessed the correlation between SGAR and tympanometry readings in children. METHODS: We compared SGAR and tympanometry in 2152 otoscopic examinations among 600 children aged 0.6-14 years, who were examined for signs and symptoms of respiratory infection in a primary care setting; 677 (31.5%) of the ear examinations were in children <3 years of age. We further determined the test characteristics of these methods for the detection of middle-ear effusion (MEE) using pneumatic otoscopy as the gold standard. All examinations were performed by trained physicians. RESULTS: SGAR and tympanometry indicated probable absence of MEE in 1896 (88.1%) and 1937 (90.0%) of the 2152 ears, respectively. SGAR levels 1-2 were observed in 95.7% of ears with type A/As tympanogram and in 58.1% of ears with type B tympanogram. The frequency of type B tympanogram increased with increasing SGAR levels, from 4.8% at SGAR level 1 to 67.7% at SGAR level 5. The observed agreement between the 2 methods was 86%. The test characteristics of SGAR and tympanometry for the detection of MEE diagnosed by pneumatic otoscopy were comparable. CONCLUSIONS: The high specificities and negative predictive values of SGAR and tympanometry make them useful aids particularly in ruling out MEE in children with respiratory infections. The low cost, easy portability and absence of need for an airtight seal support the use of SGAR also for screening purposes at home.

Thrombolysis of basilar artery occlusion: impact of baseline ischemia and time.

OBJECTIVE: To evaluate the impact of extensive baseline ischemic changes on functional outcome after thrombolysis of basilar artery occlusion (BAO), and to study the effect of time to treatment in the absence of such findings. METHODS: We prospectively evaluated 184 consecutive patients with angiography-proven BAO. The majority of patients received intravenous alteplase and concomitant full-dose heparin. Extensive baseline ischemia was defined as posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) < 8. Onset-to-treatment time (OTT) was evaluated both as a continuous and as a categorical variable (0-6 hours, 6-12 hours, 12-24 hours, and 24-48 hours). Successful recanalization means thrombolysis in myocardial infarction (TIMI) = 2 to 3. Symptomatic intracranial hemorrhage (sICH) was evaluated with National Institute of Neurological Disorders and Stroke, European Cooperative Acute Stroke Study II, and Safe Implementation of Thrombolysis in Stroke criteria. Poor 3-month outcome was defined as modified Rankin Scale score of 3 to 6. RESULTS: The majority (96%) of patients with baseline pc-ASPECTS < 8 had poor 3-month outcome, and a similar number (94%) was observed in those of them with confirmed recanalization (51.5%). In contrast, half of the patients with pc-ASPECTS ≥ 8 and successful recanalization (73.2%) achieved good outcome. In these patients, OTT was associated with poor outcome neither as a continuous nor as a categorical variable. Factors independently associated with poor outcome were greater age and baseline National Institutes of Health Stroke Scale, lack of recanalization, history of atrial fibrillation, and sICH. In the model including the whole cohort (patients with any pc-ASPECTS), pc-ASPECTS < 8 was independently associated with poor outcome (odds ratio = 5.83, 95% confidence interval = 1.09-31.07). INTERPRETATION: In the absence of extensive baseline ischemia, recanalization of BAO up to 48 hours was seldom futile and produced good outcomes in 50% of patients, which was independent of time to treatment.