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Background and purpose: Cognitive impairment is a common sequel of recent small subcortical infarction (RSSI) and might be negatively affected by preexisting cerebral small vessel disease (SVD). We investigated whether the course of cognitive function in patients with RSSI is influenced by the severity of white matter hyperintensities (WMH), an important imaging feature of SVD. Methods: Patients with magnetic resonance imaging (MRI)‐proven single RSSI were tested neuropsychologically concerning global cognition, processing speed, attention, and set‐shifting. Deep and periventricular WMH severity was assessed using the Fazekas scale, and total WMH lesion volume was calculated from T1‐weighted MRI images. We compared baseline function and course of cognition 15 months after the acute event in patients with absent, mild, and moderate‐to‐severe WMH. Results: The study cohort comprised 82 RSSI patients (mean age: 61 ± 10 years, 23% female). At baseline, 40% had cognitive impairment (1.5 standard deviations below standardized mean), and deficits persisted in one‐third of the sample after 15 months. After age correction, there were no significant differences in set‐shifting between WMH groups at baseline. However, although patients without WMH (deep: p < 0.001, periventricular: p = 0.067) or only mild WMH (deep: p = 0.098, periventricular: p = 0.001) improved in set‐shifting after 15 months, there was no improvement in patients with moderate‐to‐severe WMH (deep: p = 0.980, periventricular: p = 0.816). Baseline total WMH volume (p = 0.002) was the only significant predictor for attention 15 months poststroke. Conclusions: This longitudinal study demonstrates that preexisting moderate‐to‐severe WMH negatively affect the restoration of cognitive function after RSSI, suggesting limited functional reserve in patients with preexisting SVD. [ABSTRACT FROM AUTHOR]

Background and purpose: Guidelines on monogenic cerebral small‐vessel disease (cSVD) diagnosis and management are lacking. Endorsed by the Stroke and Neurogenetics Panels of the European Academy of Neurology, a group of experts has provided recommendations on selected monogenic cSVDs, i.e. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), autosomal dominant High Temperature Requirement A Serine Peptidase 1 (HTRA1), cathepsin‐A‐related arteriopathy with strokes and leukoencephalopathy (CARASAL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), Fabry disease, mitochondrial encephalopathy, lactic acidosis and stroke‐like episodes (MELAS) and type IV collagen (COL4)A1/2. Methods: We followed the Delphi methodology to provide recommendations on several unanswered questions related to monogenic cSVD, including genetic testing, clinical and neuroradiological diagnosis, and management. Results: We have proposed 'red‐flag' features suggestive of a monogenic disease. General principles applying to the management of all cSVDs and specific recommendations for the individual forms of monogenic cSVD were agreed by consensus. Conclusions: The results provide a framework for clinicians involved in the diagnosis and management of monogenic cSVD. Further multicentre observational and treatment studies are still needed to increase the level of evidence supporting our recommendations. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to investigate the clinical impact of the duration of artificial ventilation in stroke patients receiving mechanical thrombectomy (MT) under general anaesthesia. Methods: All consecutive ischaemic stroke patients who had been treated at our centre with MT for anterior circulation large vessel occlusion under general anaesthesia were identified over an 8‐year period. Ventilation time was analysed as a continuous variable and patients were grouped into extubation within 6 h ('early'), 6–24 h ('delayed') and >24 h ('late'). Favourable outcome was defined as modified Rankin Scale scores of 0–2 at 3 months post‐stroke. Pneumonia rate and reasons for prolonged ventilation were also assessed. Results: Amongst 447 MT patients (mean age 69.1 ± 13.3 years, 50.1% female), the median ventilation time was 3 h. 188 (42.6%) patients had a favourable 3‐month outcome, which correlated with shorter ventilation time (Spearman's rho 0.39, P < 0.001). In patients extubated within 24 h, early compared to delayed extubation was associated with improved outcome (odds ratio 2.40, 95% confidence interval 1.53–3.76, P < 0.001). This was confirmed in multivariable analysis (P = 0.01). A longer ventilation time was associated with a higher rate of pneumonia during neurointensive care unit/stroke unit stay (early/delayed/late extubation: 9.6%/20.6%/27.7%, P < 0.01). Whilst stroke‐associated complications represented the most common reasons for late extubation (>24 h), delayed extubation (6–24 h) was associated with admission outside of core working hours (P < 0.001). Conclusions: Prolonged ventilation time after stroke thrombectomy independently predicts unfavourable outcome at 3 months and is associated with increased pneumonia rates. Therefore, extubation should be performed as early as safely possible. [ABSTRACT FROM AUTHOR]

Background and purpose: Information on the prevalence and course of post‐stroke cognitive impairment in young stroke patients is limited. The aim was to assess a consecutive sample of acute young ischaemic stroke patients (18–55 years) for the presence and development of neuropsychological deficits. Methods: Patients prospectively underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, flexibility/executive function and word fluency within the first 3 weeks after hospital admission (median assessment at day 6) and at a 3 months' follow‐up (FU). Cognitive dysfunction was defined in comparison to age‐standardized published norms. Results: At baseline (N = 114), deficits were highly prevalent in processing speed (56.0%), flexibility/executive function (49.5%), attention (46.4%) and general cognitive function (42.1%). These frequencies were comparable for those with FU assessment (N = 87). In most domains, cognitive performance improved within 3 months, except for word fluency. However, in about one‐third of patients, cognitive deficits (as defined by 1.5 standard deviations below the standardized mean) were still present 3 months after stroke. At FU, 44.0% were impaired in the domain flexibility/executive function, 35.0% in processing speed and 30.0% in attention. Conclusions: The high prevalence of cognitive deficits in acute young patients with ischaemic stroke highlights the importance of early post‐stroke cognitive assessment to capture a patient's dysfunction in a comprehensive manner and to offer adequate rehabilitation. The role of factors which promote neuropsychological deficits needs further exploration. [ABSTRACT FROM AUTHOR]

Background and purpose Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. Methods The sifap1 study prospectively recruited a multinational European cohort ( n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. Results The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas ( n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27−2.91], dysarthria (OR 2.17, 95% CI 1.38−3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42−4.15; OR 2.41, 95% CI 1.02−5.69, respectively). Conclusions In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA. [ABSTRACT FROM AUTHOR]

We performed a prospective multi-centre study using functional magnetic resonance imaging (fMRI) to better characterize the relationships between clinical expression and brain function in patients with multiple sclerosis (MS) at eight European sites (56 MS patients and 60 age-matched, healthy controls). Patients showed greater task-related activation bilaterally in brain regions including the pre- and post-central, inferior and superior frontal, cingulate and superior temporal gyri and insula ( P < 0.05, all statistics corrected for multiple comparisons). Both patients and healthy controls showed greater brain activation with increasing age in the ipsilateral pre-central and inferior frontal gyri ( P < 0.05). Patients, but not controls, showed greater brain activation in the anterior cingulate gyrus and the bilateral ventral striatum ( P < 0.05) with less hand dexterity. An interaction between functional activation changes in MS and age was found. This large fMRI study over a broadly selected MS patient population confirms that movement for patients demands significantly greater cognitive ‘resource allocation’ and suggests age-related differences in brain responses to the disease. These observations add to evidence that brain functional responses (including potentially adaptive brain plasticity) contribute to modulation of clinical expression of MS pathology and demonstrate the feasibility of a multi-site functional MRI study of MS. [ABSTRACT FROM AUTHOR]

The pronounced susceptibility effect of macrovessels in MR bolus-tracking studies induces spots of artificially high blood flow and volume in perfusion parameter images. These high-intensity regions impede the detection of perfusion changes and lead to elevated perfusion parameters in adjacent tissues. The purpose of this work was to explore postprocessing methods to reduce the influence of macrovessel signal in dynamic MRI. After data reduction was performed with the use of a principal component analysis (PCA), an independent component analysis (ICA) was applied to separate signal components of different compartments. Based on this decomposition, the dynamic time series were reconstructed with minimized contributions of macrovessel signal and noise. The influence of the temporal resolution and signal-to-noise ratio (SNR) of the source data were investigated by means of a simulation study. A region-of-interest (ROI)-based analysis of corrected and uncorrected in vivo data demonstrated that the influence of arteries and veins was reduced at least by 50%, while gray matter (GM) and white matter (WM) tissues were nearly unaffected by the correction process. Hemodynamic parameter images of the cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated from corrected and uncorrected scans. The corrected parameter images showed a clearly reduced macrovessel signal and an improved perceptibility of microvascular perfusion changes compared to the uncorrected ones. Magn Reson Med 57:278-288, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Acute transverse myelitis (ATM) not related to systemic disease may present in a relapsing manner. Data in the literature about this condition are scarce. We describe three patients suffering from relapsing myelitis in whom no association with systemic disease, i.e. infectious or connective tissue disease was found. Magnetic resonance imaging (MRI) findings were also distinctly different from multiple sclerosis and consistent with a necrotizing type of inflammation. Despite various treatment strategies, all patients became severely disabled. Relapsing ATM not related to systemic disease appears to be a specific entity which accounts for severe disability and currently lacks effective treatment. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy, frequencies and reasons for treatment interruption of fingolimod, dimethyl fumarate (DMF) or teriflunomide in a nationwide observational cohort using prospectively collected data., Materials and Methods: Two cohorts of patients with relapsing-remitting multiple sclerosis (RRMS) starting treatment with fingolimod, dimethyl fumarate or teriflunomide documented in the Austrian MS Treatment Registry (AMSTR) since 2014 and either staying on therapy for at least 12 months (12m cohort) or having at least one follow-up visit (total cohort). The 12m cohort included 664 RRMS patients: 315 in the fingolimod, 232 in the DMF and 117 in the teriflunomide group. Multinomial propensity scores were used for inverse probability weighting to correct for the bias of this non-randomised registry study., Results: Estimated mean annualized relapse rates (ARR) over 12 months were 0.21 for fingolimod, 0.20 for DMF and 0.19 for teriflunomide treatment, causing an incidence rate ratio (IRR) of 1.01 for fingolimod vs DMF (P = 0.96) and 0.92 for teriflunomide vs DMF (P = 0.84). No differences were found regarding the probability for experiencing a relapse, EDSS change, EDSS progression and EDSS regression, except regarding less sustained EDSS progression for 12 weeks concerning DMF vs fingolimod (P = 0.02). The hazard ratio for treatment interruption comparing fingolimod vs DMF was 1.03 (P = 0.86) and 1.07 comparing teriflunomide vs DMF (P = 0.77)., Conclusions: In the AMSTR, there was no difference concerning ARR, probability for a relapse, EDSS change, treatment interruption, EDSS progression or regression between oral DMTs, except regarding less sustained EDSS progression for 12 weeks concerning DMF vs fingolimod., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To compare the efficacy of natalizumab or fingolimod in a nationwide observational cohort using prospectively collected data., Materials and Methods: We included all patients starting treatment with natalizumab or fingolimod documented in the Austrian MS Treatment Registry (AMSTR) from 2011 and staying on therapy for at least 24 months. We used propensity scores for several matching methods and as a covariate in multivariate models to correct for the bias of this non-randomized registry study., Results: The study cohort includes 588 patients with RRMS. Ten patients did not produce a propensity score in the common support region, thus leaving 578 cases for final analyses, 332 in the fingolimod and 246 in the natalizumab group. Mean annualized relapse rates (ARR) during the 24 months observation period were 0.19 under fingolimod and 0.12 under natalizumab treatment (P = .005). No statistical significant differences were found analysing the log-transformed ARR, probability for experiencing a relapse, EDSS progression and EDSS regression. The hazard ratio for switching treatment from fingolimod comparing with natalizumab was 0.36 (95% CI: 0.247-0.523), P < .001., Conclusions: The generalized linear model (GLM) for relapse count as Poisson distributed dependent variable and propensity score as covariate showed a statistically significant reduction for the mean relapse count in the natalizumab group compared with fingolimod. This effect was smaller in the analyses of log-transformed ARR with propensity score matching, loosing statistical significance although showing the same direction for the effect. We assume that the GLM was the more sensitive model analysing this question., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this multicentre study involving eight European centres, we characterized the spatial pattern of functional connectivity (FC) in the sensorimotor network from 61 right-handed patients with multiple sclerosis (MS) and 74 age-matched healthy subjects assessed with the use of functional magnetic resonance imaging (fMRI) and a simple motor task of their right dominant hand. FC was investigated by using: (i) voxel-wise correlations between the left sensorimotor cortex (SMC) and any other area in the brain; and (ii) bivariate correlations between time series extracted from several regions of interest (ROIs) belonging to the sensorimotor network. Both healthy controls and MS patients had significant FC between the left SMC and several areas of the sensorimotor network, including the bilateral postcentral and precentral gyri, supplementary motor area, middle frontal gyri, insulae, secondary somatosensory cortices, thalami, and right cerebellum. Voxel-wise assessment of FC revealed increased connectivity between the left SMC and the right precentral gyrus, right middle frontal gyrus (MFG) and bilateral postcentral gyri in MS patients as compared with controls. ROI analysis also showed a widespread pattern of altered connectivity, characterized by increased FC between the right MFG, the left insula and the right inferior frontal gyrus in comparison with many regions of the sensorimotor network. These results provide further evidence for increased bihemispheric contributions to motor control in patients with MS relative to healthy controls. They further suggest that multicentre fMRI studies of FC changes are possible, and provide a potential imaging biomarker for use in experimental therapeutic studies directed at enhancing adaptive plasticity in the disease., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)