Clinical and neuroanatomical predictors of post-stroke fatigue.

INTRODUCTION: Post-stroke fatigue (PSF) has been described as early exhaustion with tiredness that develops during physical or mental activity and generally does not improve with rest. There are inconsistent findings on the relationship between the characteristics of the ischemic brain lesion and PSF. However, some studies suggest that specific neuroanatomical and neuroplastic changes could explain post-stroke fatigue. The aim was to evaluate the severity of PSF in relation to the location and the size of the ischemic lesion in acute stroke patients to establish possible predictors of PSF. PATIENTS AND METHODS: We performed a prospective observational study to establish potential early predictors of long-term PSF, which was assessed using the Fatigue Assessment Scale six months after ischemic stroke. After segmenting brain infarcts on Diffusion-Weighted Imaging (DWI) images, we studied the association with PSF using Voxel-Based Lesion-Symptom Mapping (VLSM). RESULTS: Out of 104 patients, 61 (59 %) reported PSF. Female sex and history of diabetes mellitus were associated with a greater risk of developing PSF. The association of PSF with female sex was confirmed in a replication cohort of 50 patients. The ischemic lesion volume was not associated with PSF, and VBLSM analysis did not identify any specific brain area significantly associated with PSF. CONCLUSIONS: PSF is frequent in stroke patients, especially women, even after six months. The absence of neuroanatomical correlates of PSF suggests that it is a multifactorial process with biological, psychological, and social risk factors that require further study.

Optimizing the Definition of Ischemic Core in CT Perfusion: Influence of Infarct Growth and Tissue-Specific Thresholds.

BACKGROUND AND PURPOSE: CTP allows estimating ischemic core in patients with acute stroke. However, these estimations have limited accuracy compared with MR imaging. We studied the effect of applying WM- and GM-specific thresholds and analyzed the infarct growth from baseline imaging to reperfusion. MATERIALS AND METHODS: This was a single-center cohort of consecutive patients (n = 113) with witnessed strokes due to proximal carotid territory occlusions with baseline CT perfusion, complete reperfusion, and follow-up DWI. We segmented GM and WM, coregistered CTP with DWI, and compared the accuracy of the different predictions for each voxel on DWI through receiver operating characteristic analysis. We assessed the yield of different relative CBF thresholds to predict the final infarct volume and an estimated infarct growth-corrected volume (subtracting the infarct growth from baseline imaging to complete reperfusion) for a single relative CBF threshold and GM- and WM-specific thresholds. RESULTS: The fixed threshold underestimated lesions in GM and overestimated them in WM. Double GM- and WM-specific thresholds of relative CBF were superior to fixed thresholds in predicting infarcted voxels. The closest estimations of the infarct on DWI were based on a relative CBF of 25% for a single threshold, 35% for GM, and 20% for WM, and they decreased when correcting for infarct growth: 20% for a single threshold, 25% for GM, and 15% for WM. The combination of 25% for GM and 15% for WM yielded the best prediction. CONCLUSIONS: GM- and WM-specific thresholds result in different estimations of ischemic core in CTP and increase the global accuracy. More restrictive thresholds better estimate the actual extent of the infarcted tissue.

Synthetic MRI in subarachnoid haemorrhage.

AIM: To evaluate the reliability of synthetic magnetic resonance imaging (SyMRI) for detecting complications associated with subarachnoid haemorrhage (SAH), such as ischaemic lesions, hydrocephalus, or bleeding complications. MATERIALS AND METHODS: Twenty patients with SAH, who underwent a conventional brain MRI and a SyMRI on a 3 T MRI machine. Comparable conventional and synthetic T2-weighted fluid attenuated inversion recovery (FLAIR) images were acquired. The presence of ischaemic lesions, hydrocephalus, extra-axial blood collections as well as the volumes of grey matter (GMv), white matter (WMv), and cerebrospinal (CSFv) were compared. The acquisition times of both sequences was also analysed. RESULTS: The concordance between the two techniques was excellent for the detection of ischaemic lesions and extra-axial collections (kappa = 0.80 and 0.88 respectively) and good for the detection of hydrocephalus (kappa = 0.69). No significant differences were detected in the number of ischaemic lesions (p=0.31) or in the Evans index (p=0.11). The WMv and CSFv measures were also similar (p=0.18 and p=0.94, respectively), as well as the volume of ischaemic lesions (p=0.79). Compared to conventional MRI, the SyMRI acquisition time was shorter regardless of the number of sections (32% and 6% time reduction for 4 or 3 mm section thickness, respectively). CONCLUSIONS: SyMRI allows the detection of potential complications of SAH in a similar way to conventional MRI with a shorter acquisition time.

Stroke units could be a valid alternative to intensive care units for patients with low-grade aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: According to current guidelines, patients with aneurysmal subarachnoid haemorrhage (aSAH) are mostly managed in intensive care units (ICUs) regardless of baseline severity. We aimed to assess the prognostic and economic implications of initial admission of patients with low-grade aSAH into a stroke unit (SU) compared to initial ICU admission. METHODS: We reviewed prospectively registered data from consecutive aSAH patients with a World Federation of Neurosurgery Societies grade <3, admitted to our Comprehensive Stroke Centre between April 2013 and September 2018. Clinical and radiological baseline traits, in-hospital complications, length of stay (LOS) and poor outcome at 90 days (modified Rankin Scale score > 2) were compared between the ICU and SU groups in the whole population and in a propensity-score-matched cohort. RESULTS: Of 131 patients, 74 (56%) were initially admitted to the ICU and 57 (44%) to the SU. In-hospital complication rates were similar in the ICU and SU groups and included rebleeding (10% vs. 7%; P = 0.757), angiographic vasospasm (61% vs. 60%; P = 0.893), delayed cerebral ischaemia (12% vs. 12%; P = 0.984), pneumonia (6% vs. 4%; P = 0.697) and death (10% vs. 5%; P = 0.512). LOS did not differ between groups (median [interquartile range] 22 [16-30] vs. 19 [14-26] days; P = 0.160). In adjusted multivariate models, the location of initial admission was not associated with long-term poor outcome either in the whole population (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.32-4.19; P = 0.825) or in the matched cohort (OR 0.98, 95% CI 0.24-4.06; P = 0.974). CONCLUSIONS: A dedicated SU, with care from a multidisciplinary team, might be an optimal alternative to ICU for initial admission of patients with low-risk aSAH.

Leukoaraiosis May Confound the Interpretation of CT Perfusion in Patients Treated with Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Leukoaraiosis frequently coexists in patients with acute stroke. We studied whether leukoaraiosis could confound the interpretation of CTP findings in patients treated with mechanical thrombectomy. MATERIALS AND METHODS: We analyzed 236 patients with stroke treated with mechanical thrombectomy and studied with CTP, of whom 127 (53.8%) achieved complete reperfusion. Periventricular white matter hyperintensities on MR imaging and hypodensities on NCCT were assessed through the Fazekas score. CTP-predicted nonviable tissue was defined as relative CBF <30%, and final infarct volume was quantified in DWI. We estimated mean MTT, CBV, and CBF in the asymptomatic hemisphere. In patients achieving complete reperfusion, we assessed the accuracy of nonviable tissue to predict final infarct volume using the intraclass correlation coefficient across periventricular hyperintensity/hypodensity Fazekas scores and variable relative CBF cutoffs. RESULTS: MTT was longer (Spearman ρ = 0.279, P < .001) and CBF was lower (ρ = -0.263, P < .001) as the periventricular hyperintensity Fazekas score increased, while CBV was similar across groups (ρ = -0.043, P = .513). In the subgroup of patients achieving complete reperfusion, nonviable tissue-final infarct volume reliability was excellent in patients with periventricular hyperintensity Fazekas score grade 0 (intraclass correlation coefficient, 0.900; 95% CI, 0.805-0.950), fair in patients with periventricular hyperintensity Fazekas scores 1 (intraclass correlation coefficient, 0.569; 95% CI, 0.327-0.741) and 2 (intraclass correlation coefficient, 0.444; 95% CI, 0.165-0.657), and poor in patients with periventricular hyperintensity Fazekas score 3 (intraclass correlation coefficient, 0.310; 95% CI, -0.359-0.769). The most accurate cutoffs were relative CBF <30% for periventricular hyperintensity Fazekas score grades 0 and 1, relative CBF <25% for periventricular hyperintensity Fazekas score 2, and relative CBF <20% for periventricular hyperintensity Fazekas score 3. The reliability analysis according to periventricular hypodensity Fazekas score grades on NCCT was similar to that in follow-up MR imaging. CONCLUSIONS: In patients with stroke, the presence of leukoaraiosis confounds the interpretation of CTP despite proper adjustment of CBF thresholds.

Perfusion Deficits and Mismatch in Patients with Acute Lacunar Infarcts Studied with Whole-Brain CT Perfusion.

BACKGROUND AND PURPOSE: The incidence and significance of perfusion abnormalities on brain imaging in patients with lacunar infarct are controversial. We studied the diagnostic yield of CTP and the type of perfusion abnormalities in patients presenting with a lacunar syndrome and in those with MR imaging-confirmed lacunar infarcts. MATERIALS AND METHODS: A cohort of 33 patients with lacunar syndrome underwent whole-brain CTP on admission. Twenty-eight patients had an acute ischemic lesion at follow-up MR imaging; 16 were classified as lacunar infarcts. Two independent readers evaluated NCCT and CTP to compare their diagnostic yield. In patients with DWI-confirmed lacunar infarcts and visible deficits on CTP, the presence of mismatch tissue was measured by using different perfusion thresholds. RESULTS: The symptomatic acute lesion was seen on CTP in 50% of patients presenting with a lacunar syndrome compared with only 17% on NCCT, and in 62% on CTP compared with 19% on NCCT, respectively, in patients with DWI-confirmed lacunar infarcts. CTP was more sensitive in supratentorial than in infratentorial lesions. In the nonblinded analysis, a perfusion deficit was observed in 12/16 patients with DWI-confirmed lacunar infarcts. The proportion of mismatch tissue was similar in patients with lacunar infarcts or nonlacunar strokes (32% versus 36%, P = .734). CONCLUSIONS: Whole-brain CTP is superior to NCCT in identifying small ischemic lesions, including lacunar infarcts, in patients presenting with a lacunar syndrome. Perfusion deficits and mismatch are frequent in lacunar infarcts, but larger studies are warranted to elucidate the clinical significance of these CTP findings.

Modelling gene flow between oilseed rape and wild radish. I. Evolution of chromosome structure.

The assessment of gene flow from crop species to weeds has found a new emphasis over the last years because of the marketing of transgenic crops and the possible selective advantage that crop (trans)gene may confer to the weeds. Several studies focused on the F1 interspecific hybrid production but few data are available on the factors affecting the genetic structure of advanced generations. It depends on the genomic structure of the species concerned as well as on the degree of their genome homology that affect the occurrence of intergenomic recombination. Oilseed rape (Brassica napus, AACC, 2n = 38)-wild radish (Raphanus raphanistrum, RrRr, 2n = 18), a distantly related weed, is a good model to address such questions. From seven male sterile oilseed rape lines carrying an herbicide tolerance transgene, F1 interspecific hybrids and four advanced generations were produced under field conditions with wild radish as pollinator. Observation of hybrid chromosome numbers across four generations revealed a high variability, especially in the "BC1" generation. A regression model was fitted in order to describe the relationship between parent and offspring chromosome numbers. The effects of generation, transgenic line and selection pressure on the mean relationship were investigated. The first two factors had an influence on the rate of decrease of chromosome numbers, whereas selection pressure resulted in the presence of an additional chromosome in the herbicide treated plants. The model provided a convenient framework for analysing how chromosome numbers evolve over successive hybridization events and it may prove useful as a basis for simulation-based approaches.

[Brooke-Spiegler syndrome: an heterogeneous entity]. / Síndrome de Brooke-Spiegler: una entidad heterogénea.

The Brooke-Spiegler syndrome is a rare, autosomally dominant disease with a predisposition to develop different adnexal tumors. Clinically it is characterized by the presence of multiple cylindromas, trichoepitheliomas, and occasionally, spiradenomas. Although Brooke-Spiegler syndrome, familial cylindromatosis and multiple familial trichoepithelioma were initially described as separate entities, the recently identified identical mutations in the gene of cylindromatosis suggest that they represent fenotypic variations of the same entity. In this article we present the case of a woman and her daughter, both affected by this rare genodermatosis.

Síndrome de Brooke-Spiegler: una entidad heterogénea / Brooke-Spiegler syndrome: an heterogeneous entity

El síndrome de Brooke-Spiegler es una genodermatosis infrecuente, de transmisión autosómica dominante, que predispone a la aparición de diferentes neoplasias anexiales. Clínicamente se caracteriza por la presencia de múltiples cilindromas, tricoepiteliomas y, ocasionalmente, espiradenomas. Aunque el síndrome de Brooke-Spiegler, la cilindromatosis familiar y el tricoepitelioma múltiple familiar fueron inicialmente descritos como entidades distintas, recientemente se han identificado idénticas mutaciones en el gen de la cilindromatosis, por lo que se ha sugerido que representan variaciones fenotípicas de una misma entidad. En este artículo presentamos el caso de una mujer y su hija, ambas afectas por esta rara genodermatosis

The Brooke-Spiegler syndrome is a rare, autosomally dominant disease with a predisposition to develop different adnexal tumors. Clinically it is characterized by the presence of multiple cylindromas, trichoepitheliomas, and occasionally, spiradenomas. Although Brooke-Spiegler syndrome, familial cylindromatosis and multiple familial trichoepithelioma were initially described as separate entities, the recently identified identical mutations in the gene of cylindromatosis suggest that they represent fenotypic variations of the same entity. In this article we present the case of a woman and her daughter, both affected by this rare genodermatosis

A review of 685 rhytidectomies: a new method of analysis based on digitally processed photographs with computer-processed data.

It is the aim of this work to present a simple method to assess the surgery used for facial aging (face-neck lift), based on a digital computerized analysis of images, and to include an evaluation of the results obtained from its use on 685 cases of face lift, which our team resolved from January of 1990 to December of 1997. To this end, we reviewed 4110 preoperative and postoperative slides of these patients and processed them using a computer, obtaining the results presented herein. It is worthy of note that in this new method of analysis that we have used, data, measurements, or aspects of facial aging have revealed the most homogeneity and reliability when comparing the results obtained with the reality observed by both the surgeon and the patient. Likewise, we rejected other analyzed data, as they gave different or unreal results when compared with the reality.

Some statistical improvements for estimating population size and mutation rate from segregating sites in DNA sequences.

In population genetics, under a neutral Wright-Fisher model, the scaling parameter straight theta=4Nmu represents twice the average number of new mutants per generation. The effective population size is N and mu is the mutation rate per sequence per generation. Watterson proposed a consistent estimator of this parameter based on the number of segregating sites in a sample of nucleotide sequences. We study the distribution of the Watterson estimator. Enlarging the size of the sample, we asymptotically set a Central Limit Theorem for the Watterson estimator. This exhibits asymptotic normality with a slow rate of convergence. We then prove the asymptotic efficiency of this estimator. In the second part, we illustrate the slow rate of convergence found in the Central Limit Theorem. To this end, by studying the confidence intervals, we show that the asymptotic Gaussian distribution is not a good approximation for the Watterson estimator.

Variations of plasma immunoreactive motilin, pancreatic polypeptide, gastrin and somatostatin along the duodenal motility cycle in the pig.

The peripheral plasma concentrations of immunoreactive motilin, pancreatic polypeptide (PP), somatostatin and gastrin were measured in 7 pigs fasted to 24 h and subsequently fed a standard meal. Plasma motilin peaked during the last part of phase II activity of the migrating myoelectric complex (MMC) sequence (25.2 +/- 2.3 pM), the lowest value being recorded during phase I (10.6 +/- 1.5 pM) after a 24 h fast. Plasma motilin remained at a low level during the digestive pattern of duodenal activity, no fluctuation occurring when the first postprandial MMC recurred. At variance analysis, gastrin and PP were not released phasically with MMC in the fasting state, while at autocovariance both peptides tended to fluctuate during the MMC sequence with positive and negative peaks at regular intervals along MMC cycles. No variation of plasma somatostatin was observed in the fasting animals. These findings argue against a major role of circulating PP, gastrin and somatostatin-like components in the control of fasted and post absorptive duodenal motility in pigs while the role of motilin remains equivocal.

Echocardiographic changes after successful renal transplantation in young nondiabetic patients.

Eighteen young nondiabetic patients with chronic renal failure were studied by M-mode echocardiography before and three to 67 weeks after a successful renal transplant. Left ventricular mass (LVM), cardiac output (CO), and stroke work, which were increased before the operation, decreased afterward, in some cases to normal values. Both regression of the LVM and normalization of CO were detected as early as three weeks postoperatively and probably resulted from changes in the end-diastolic volume, mean systemic blood pressure, and hematocrit as a consequence of normal renal function. Because all the patients had normal left ventricular function and only moderate dilatation of the left ventricle, it is not known whether these striking beneficial changes after SRT also will occur in patients with significant dilatation or dysfunction of the left ventricle.