Computed tomography-based quantification of lesion water uptake identifies patients within 4.5 hours of stroke onset: A multicenter observational study.

OBJECTIVE: Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours, the time window of thrombolysis. METHODS: Perfusion CT was used to identify ischemic brain tissue, and its density was measured in native CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. The optimal cutoff value of water uptake distinguishing stroke onset within and beyond 4.5 hours was calculated in patients with proximal middle cerebral artery occlusion (derivation cohort) with known time of symptom onset. The so-derived cutoff value was validated in a prospective cohort from other stroke centers. RESULTS: Of 178 patients of the derivation cohort, 147 (82.6%) had CT within 4.5 hours. Percentage water uptake was significantly lower in patients with stroke onset within compared to beyond 4.5 hours. The area under the receiver operating characteristic curve for distinguishing these patient groups according to percentage water uptake was 0.999 (95% confidence interval = 0.996-1.000, p < 0.001) with an optimal cutoff value of 11.5%. Applying this cutoff to the validation cohort of 240 patients, sensitivity was 98.6%, specificity 90.5%, positive predictive value 99.1%, and negative predictive value 86.4%. INTERPRETATION: Quantification of brain water uptake identifies stroke patients with symptom onset within 4.5 hours with high accuracy and may guide the decision to use thrombolysis in patients with unknown time of stroke onset. Ann Neurol 2016;80:924-934.

Diagnostic classification of unipolar depression based on resting-state functional connectivity MRI: effects of generalization to a diverse sample.

In small, selected samples, an approach combining resting-state functional connectivity MRI and multivariate pattern analysis has been able to successfully classify patients diagnosed with unipolar depression. Purposes of this investigation were to assess the generalizability of this approach to a large clinically more realistic sample and secondarily to assess the replicability of previously reported methodological feasibility in a more homogeneous subgroup with pronounced depressive symptoms. Two independent subsets were drawn from the depression and control cohorts of the BiDirect study, each with 180 patients with and 180 controls without depression. Functional connectivity either among regions covering the gray matter or selected regions with known alterations in depression was assessed by resting-state fMRI. Support vector machines with and without automated feature selection were used to train classifiers differentiating between individual patients and controls in the entire first subset as well as in the subgroup. Model parameters were explored systematically. The second independent subset was used for validation of successful models. Classification accuracies in the large, heterogeneous sample ranged from 45.0 to 56.1% (chance level 50.0%). In the subgroup with higher depression severity, three out of 90 models performed significantly above chance (60.8-61.7% at independent validation). In conclusion, common classification methods previously successful in small homogenous depression samples do not immediately translate to a more realistic population. Future research to develop diagnostic classification approaches in depression should focus on more specific clinical questions and consider heterogeneity, including symptom severity as an important factor.

MR imaging of the brain in large cohort studies: feasibility report of the population- and patient-based BiDirect study.

OBJECTIVES: To describe the implementation and protocol of cerebral magnetic resonance imaging (MRI) in the longitudinal BiDirect study and to report rates of study participation as well as management of incidental findings. METHODS: Data came from the BiDirect study that investigates the relationship between depression and arteriosclerosis and comprises 2258 participants in three cohorts: 999 patients with depression, 347 patients with manifest cardiovascular disease (CVD) and 912 population-based controls. The study program includes MRI of the brain. Reasons for non-participation were systematically collected. Incidental findings were categorized and disclosed according to clinical relevance. RESULTS: At baseline 2176 participants were offered MRI, of whom 1453 (67 %) completed it. Reasons for non-participation differed according to cohort, age and gender with controls showing the highest participation rate of 79 %. Patient cohorts had higher refusal rates and CVD patients a high prevalence of contraindications. In the first follow-up examination 69 % of participating subjects completed MRI. Incidental findings were disclosed to 246 participants (17 %). The majority of incidental findings were extensive white matter hyperintensities requiring further diagnostic work-up. CONCLUSIONS: Knowledge about subjects and sensible definition of incidental findings are crucial for large-scale imaging projects. Our data offer practical and concrete information for the design of future studies. KEY POINTS: • Willingness to participate in MRI is generally high, also in follow-up examinations. • Rates of refusal and prevalence of contraindications differ according to subject characteristics. • Extensive white matter hyperintensities considerably increase the disclosure rates of incidental findings. • MRI workflow requires continuous case-by-case handling by an interdisciplinary team.

Outcome After Thrombectomy and Intravenous Thrombolysis in Patients With Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, randomized trials showed a better functional outcome after endovascular therapy with new-generation thrombectomy devices compared with medical treatment, including intravenous thrombolysis. However, effects on mortality and the generalizability of results to routine clinical practice are uncertain. METHODS: In a prospective observational register-based study patients with ischemic stroke treated either with thrombectomy, intravenous thrombolysis, or their combination were included. Primary outcome was the modified Rankin scale score (0 [no symptoms] to 6 [death]) at 3 months. Ordinal logistic regression was used to estimate the common odds ratio as treatment effects (shift analysis). Propensity score matching was applied to compare patients treated either with intravenous thrombolysis alone or with intravenous thrombolysis plus thrombectomy. RESULTS: Among 2650 recruited patients, 1543 received intravenous thrombolysis, 504 underwent thrombectomy, and 603 received intravenous thrombolysis in combination with thrombectomy. Later time-to-treatment was associated with worse outcomes among patients treated with thrombectomy plus thrombolysis. In 241 pairs of propensity score-matched patients with a proximal intracranial occlusion, thrombectomy plus thrombolysis was associated with improved functional outcome (common odds ratio, 1.84; 95% confidence interval, 1.32-2.57), and reduced mortality (15% versus 33%; P<0.0001) compared with intravenous thrombolysis alone. Results were similar in various sensitivity analyses accounting for missing outcome data and different analytic methods. CONCLUSIONS: Results from this large prospective registry show that also in routine clinical care thrombectomy plus thrombolysis compared with thrombolysis alone improved functional outcome and reduced mortality in patients with ischemic stroke. Earlier treatment was associated with better outcomes.

Major depressive disorder: Findings of reduced homotopic connectivity and investigation of underlying structural mechanisms.

Depression has been associated with various alterations in magnetic resonance imaging (MRI) derived resting-state functional connectivity. Recently, homotopic connectivity, defined as functional connectivity between homotopic regions across hemispheres, has been reported to be reduced in patients with major depressive disorder (MDD). However, little is known about structural factors underlying alterations of homotopic connectivity, which would contribute to the understanding of the altered neurophysiological architecture in patients with MDD. We compared 368 patients with MDD and 461 never-depressed controls regarding voxel-mirrored homotopic connectivity (VMHC) and potential underlying mechanisms such as the structural connectivity of the corpus callosum, measured by DTI-derived fractional anisotropy (FA), and left-right symmetries in homotopic gray matter volumes. Compared to controls, patients with MDD exhibited reduced VMHC in the cuneus, putamen, superior temporal gyrus, insula, and precuneus. Within these regions, no differences in left-right symmetries in homotopic gray matter volumes were evident across cohorts. FA of the corpus callosum correlated with VMHC in the entire sample. However, patients with MDD and controls did not differ with regard to callosal FA. The findings indicate that MDD is associated with a loss of interhemispheric synchrony in regions known to be implicated in self-referential and reward processing. They also suggest that additional mechanisms are implicated in altered homotopic connectivity of patients with MDD, other than direct callosal fiber pathways or asymmetries in homotopic gray matter volumes.

Diagnostic criteria for Susac syndrome.

BACKGROUND: Susac syndrome is characterised by the triad of encephalopathy with or without focal neurological signs, branch retinal artery occlusions and hearing loss. Establishment of the diagnosis is often delayed because the triad is complete only in a minority of patients at disease onset. This leads to a critical delay in the initiation of appropriate treatment. Our objective was to establish criteria for diagnosis of either definite or probable Susac syndrome. METHOD: The establishment of diagnostic criteria was based on the following three steps: (1) Definition of a reference group of 32 patients with an unambiguous diagnosis of Susac syndrome as assessed by all interdisciplinary experts of the European Susac Consortium (EuSaC) team (EuSaC cohort); (2) selection of diagnostic criteria, based on common clinical and paraclinical findings in the EuSaC cohort and on a review of the literature; and (3) validation of the proposed criteria in the previously published cohort of all Susac cases reported until 2012. RESULTS: Integrating the clinical presentation and paraclinical findings, we propose formal criteria and recommend a diagnostic workup to facilitate the diagnosis of Susac syndrome. More than 90% of the cases in the literature fulfilled the proposed criteria for probable or definite Susac syndrome. We surmise that more patients could have been diagnosed with the recommended diagnostic workup. CONCLUSIONS: We propose diagnostic criteria for Susac syndrome that may help both experts and physicians not familiar with Susac syndrome to make a correct diagnosis and to prevent delayed treatment initiation.

Feasibility platform for stroke studies: an online tool to improve eligibility criteria for clinical trials.

BACKGROUND AND PURPOSE: Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial. METHODS: We identified relevant inclusion and exclusion criteria of acute stroke trials. Based on these criteria and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3 stroke centers, we developed a web portal feasibility platform for stroke studies (FePASS) to estimate proportions of eligible patients for acute stroke trials. We applied the FePASS resource to calculate the proportion of patients eligible for 4 recent stroke studies. RESULTS: Sixty-one eligibility criteria were derived from 30 trials on acute ischemic stroke. FePASS, publicly available at http://fepass.uni-muenster.de, displays the proportion of patients in percent to assess the effect of varying values of relevant eligibility criteria, for example, age, symptom onset time, National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale, on this proportion. The proportion of eligible patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations of the inclusion criteria could substantially increase the proportion of eligible patients. CONCLUSIONS: FePASS is an open access online resource to assess the effect of inclusion and exclusion criteria on the proportion of eligible patients for a stroke trial. FePASS can help to design stroke studies, optimize eligibility criteria, and to estimate the potential recruitment rate.

Associations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect Study.

BACKGROUND: Depression is supposed to be associated with an unhealthy lifestyle including poor diet. The objective of this study was to investigate differences in diet quality between patients with a clinical diagnosis of depression and population-based controls. Additionally, we aimed to examine effects of specific depression characteristics on diet by analyzing if diet quality varies between patients with distinct depression subtypes, and if depression severity is associated with diet quality. METHODS: The study included 1660 participants from the BiDirect Study (n = 840 patients with depression, n = 820 population-based controls). The psychiatric assessment was based on clinical interviews and a combination of depression scales in order to provide the classification of depression subtypes and severity. Diet quality scores, reflecting the adherence to a healthy dietary pattern, were calculated on the basis of an 18-item food frequency questionnaire. Using analysis of covariance, we calculated adjusted means of diet quality scores and tested differences between groups (adjusted for socio-demographic, lifestyle-, and health-related factors). RESULTS: We found no differences in diet quality between controls and patients with depression if depression was considered as one entity. However, we did find differences between patients with distinct subtypes of depression. Patients with melancholic depression reported the highest diet quality scores, whereas patients with atypical depression reported the lowest scores. Depression severity was not associated with diet quality. CONCLUSIONS: Previous literature has commonly treated depression as a homogeneous entity. However, subtypes of depression may be associated with diet quality in different ways. Further studies are needed to enlighten the diet-depression relationship and the role of distinct depression subtypes.

Establishing the bidirectional relationship between depression and subclinical arteriosclerosis--rationale, design, and characteristics of the BiDirect Study.

BACKGROUND: Depression and cardiovascular diseases due to arteriosclerosis are both frequent and impairing conditions. Depression and (subclinical) arteriosclerosis appear to be related in a bidirectional way, and it is plausible to assume a partly joint causal relationship. However, the biological mechanisms and the behavioral pathways that lead from depression to arteriosclerosis and vice versa remain to be exactly determined. METHODS/DESIGN: This study protocol describes the rationale and design of the prospective BiDirect Study that aims at investigating the mutual relationship between depression and (subclinical) arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of individuals ((i) patients with acute depression (N = 999), (ii) patients after an acute cardiac event (N = 347), and (iii) reference subjects from the general population (N = 912)). Over the course of 12 years, four personal examinations are planned to be conducted. The core examination program, which will remain identical across follow-ups, comprises a personal interview (e.g. medical diagnoses, health care utilization, lifestyle and risk behavior), a battery of self-administered questionnaires (e.g. depressive symptoms, readiness to change health behavior, perceived health-related quality of life), sensory (e.g. olfaction, pain) and neuropsychological (e.g. memory, executive functions, emotional processing, manual dexterity) assessments, anthropometry, body impedance measurement, a clinical work-up regarding the vascular status (e.g. electrocardiogram, blood pressure, intima media thickness), the taking of blood samples (serum and plasma, DNA), and structural and functional resonance imaging of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces processing). The present report includes BiDirect-Baseline, the first data collection wave. DISCUSSION: Due to its prospective character, the integration of three distinct cohorts, the long follow-up time window, the diligent diagnosis of depression taking depression subtypes into account, the consideration of relevant comorbidities and risk factors, the assessment of indicators of (subclinical) arteriosclerosis in different vascular territories, and the structural and functional brain imaging that is performed for a large number of participants, the BiDirect Study represents an innovative approach that combines population-based cohorts with sophisticated clinical work-up methods and that holds the potential to overcome many of the drawbacks characterizing earlier investigations.

Executive performance is related to regional gray matter volume in healthy older individuals.

Individual differences in executive functioning and brain morphology are considerable. In this study, we investigated their interrelation in a large sample of healthy older individuals. Digit span, trail-making, and Stroop tasks were used to assess different executive subfunctions in 367 nondemented community-dwelling individuals (50-81 years). Task performance was analyzed relative to brain structure using voxel-based morphometry, corrected for age and sex. Improved task performance was associated with increased local gray matter volume in task-specific patterns that showed partial, but not complete overlap with known task-specific functional imaging patterns. While all three tasks showed associations with prefrontal gray matter volume as expected for executive functioning, the strongest overlap between the three tasks was found in insular cortex, suggesting that it has a previously underestimated role for executive functions. The association between the insular cortex and executive functioning was corroborated using stereological region-of-interest measurement of insular volume in a subgroup of 93 subjects. Quantitatively, the volume of the single most strongly related region explained 2.4 ± 1.1% of the variance in executive performance over and above the variance explained by age, which amounted to 7.4 ± 4.1%. The age-independent peak associations between executive performance and gray matter described here occurred in regions that were also strongly affected by age-related gray matter atrophy, consistent with the hypothesis that age-related regional brain volume loss and age-related cognitive changes are linked.

Successful regeneration after experimental stroke by granulocyte-colony stimulating factor is not further enhanced by constraint-induced movement therapy either in concurrent or in sequential combination therapy.

BACKGROUND AND PURPOSE: Both application of granulocyte-colony stimulating factor (G-CSF) and constraint-induced movement therapy (CIMT) have been shown to improve outcome after experimental stroke. The aim of the present study was to determine whether concurrent or sequential combination of both therapies will further enhance therapeutic benefit and whether specific modifications in the abundance of various neurotransmitter receptors do occur. METHODS: Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to the following treatment groups (n=20 each): (1) ischemic control (saline); (2) CIMT (CIMT between poststroke Days 2 and 11; (3) G-CSF (10 µg/kg G-CSF daily between poststroke Days 2 and 11; (4) combined concurrent group (CIMT plus 10 µg/kg G-CSF daily between poststroke Days 2 and 11; and (5) combined sequential group (CIMT between poststroke Days 2 and 11 and 10 µg/kg G-CSF daily between poststroke Days 12 and 21, respectively). Rats were functionally tested before and up to 4 weeks after ischemia. Quantitative receptor autography was performed for N-methyl-d-aspartate, AMPA, and GABA(A) receptors. RESULTS: Significant improvement of functional outcome was seen in all groups treated with G-CSF alone and in either combination with CIMT, whereas CIMT alone failed to enhance recovery. Infarct sizes and remaining cortical tissue did not differ in the various treatment groups. Failure of significant benefit in the CIMT group was associated with a shift toward inhibition in perilesional and remote cortical regions. CONCLUSIONS: Our findings disclose G-CSF as the major player for enhanced recovery after experimental stroke, preventing a shift toward inhibition as seen in the CIMT group.

Continuous positive airway pressure ventilation for acute ischemic stroke: a randomized feasibility study.

BACKGROUND AND PURPOSE: Sleep-related breathing disorders occur frequently after stroke. We assessed the feasibility of continuous positive airway pressure (CPAP) treatment initiated in the first night after stroke. METHODS: In this open-label, parallel-group trial, 50 patients were randomly assigned to the CPAP therapy or to the control group. All patients underwent polysomnography in the fourth night. Intervention patients received CPAP therapy for 3 nights starting the first night after stroke onset and for an additional 4 nights when polysomnography revealed an apnea-hypopnea index >10/hour. The primary end point was feasibility defined as apnea-hypopnea index reduction under CPAP treatment, nursing workload, and CPAP adherence. RESULTS: The apnea-hypopnea index under CPAP treatment was significantly reduced (32.2±25.3-9.8±6.6, P=0.0001). Nursing workload did not significantly differ between the CPAP (n=25) and the control group (n=25; P=0.741). Ten patients (40.0%) had excellent CPAP use, 14 patients (56.0%) had some use, and 1 patient (4.0%) had no use. There was a trend toward greater National Institutes of Health Stroke Scale score improvement until Day 8 in patients on CPAP (2.00 versus 1.40, P=0.092) and a significantly greater National Institutes of Health Stroke Scale score improvement in patients with excellent CPAP use when compared with control patients (2.30 versus 1.40, P=0.022). CONCLUSIONS: CPAP therapy initiated in the first night after stroke seems to be feasible and was not associated with neurological deterioration. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT00151177.

Generation of a probabilistic arterial cerebrovascular atlas derived from 700 time-of-flight MRA datasets.

The cerebral vasculature is a complex vessel network with high variations among human subjects. Although the coarse structure and spatial relationships of the main cerebrovascular branches are well known, not much knowledge about inter-individual vessel variability of humans at a finer level is available. The aim of this work is to present a probabilistic atlas of cerebral arterial vascular structures derived from 700 Time-of-Flight (TOF) magnetic resonance angiography (MRA) datasets of healthy subjects. Therefore, the cerebrovascular system was automatically segmented in each TOF datasets. In a following step, each TOF dataset and corresponding segmentation was registered to the MNI brain atlas. The registered datasets were then used for generation of a probabilistic cerebrovascular atlas. The generated atlas was evaluated with respect to three possible applications. The results suggest that the atlas is especially helpful to obtain knowledge about the cerebrovascular anatomy and its variations in terms of vessel occurrence probability. Furthermore, it appears useful for initialization of automatic cerebrovascular segmentation methods while an application for detection of vessel pathologies seems only feasible for large malformations.

Prediction of malignant middle cerebral artery infarction using computed tomography-based intracranial volume reserve measurements.

BACKGROUND AND PURPOSE: Early decompressive surgery in patients with malignant middle cerebral artery (MCA) infarction improves outcome. Elevation of intracranial pressure depends on both the space occupying brain edema and the intracranial volume reserve (cerebrospinal fluid [CSF]). However, CSF volume was not investigated as a predictor of malignant infarction so far. We hypothesize that assessment of CSF volume in addition to admission infarct size improves early prediction of malignant MCA infarction. METHODS: Stroke patients with carotid-T or MCA main stem occlusion and ischemic lesion (reduced cerebral blood volume [CBV]) on perfusion CT were considered for the analysis. The end point malignant MCA infarction was defined by clinical signs of herniation. Volumes of CSF and CBV lesion were determined on admission. Receiver-operator characteristics analysis was used to calculate predictive values for radiological and clinical measurements. RESULTS: Of 52 patients included, 26 (50%) developed malignant MCA infarction. Age, a decreased level of consciousness on admission, CBV lesion volume, CSF volume, and the ratio of CBV lesion volume to CSF volume were significantly different between malignant and nonmalignant groups. The best predictor of a malignant course was the ratio of CBV lesion volume to CSF volume with a cut-off value of 0.92 (96.2% sensitivity, 96.2% specificity, 96.2% positive predictive value, and 96.2% negative predictive value). CONCLUSIONS: Based on admission native CT and perfusion CT measurements, the ratio of ischemic lesion volume to CSF volume predicts the development of malignant MCA infarction with higher accuracy than other known predictors, including ischemic lesion volume or clinical characteristics.

Impact of the extended thrombolysis time window on the proportion of recombinant tissue-type plasminogen activator-treated stroke patients and on door-to-needle time.

BACKGROUND AND PURPOSE: The European Cooperative Acute Stroke Study (ECASS) III extended the thrombolysis time window for patients with stroke from 3 to 4.5 hours after symptom onset. We investigated the effect of the extended thrombolysis time window on the proportion of recombinant tissue-type plasminogen activator-treated stroke patients and on the time of treatment initiation after hospital arrival. METHODS: The present study was based on a prospective database of 93 hospitals of the Stroke Register of Northwestern Germany, which included 91 805 patients with ischemic stroke admitted between January 2007 and December 2009. Main outcome measures were the use of recombinant tissue-type plasminogen activator among patients with stroke and the door-to-needle time before and after the publication of ECASS III in September 2008 and subsequent changes of the German guidelines in May 2009. RESULTS: Overall, 9262 patients (10.1%) were treated with recombinant tissue-type plasminogen activator. The proportion of thrombolyzed patients increased from 8.6% in 2007 to 11.7% in 2009. This increase was pronounced for patients admitted between 3 and 6 hours after symptom onset after the third quarter of 2008 (OR, 1.88; 95% CI, 1.24 to 2.85) and after the second and third quarters of 2009 (OR, 2.50; 95% CI, 1.69 to 3.69 and OR, 3.02; 95% CI, 2.07 to 4.41) compared with the first half year 2007. The proportion of patients with stroke with a door-to-needle time<60 minutes increased after publication of ECASS III (OR, 1.49; 95% CI, 1.37 to 1.63). CONCLUSIONS: Results of ECASS III were rapidly implemented in routine stroke care. Concerns of a delay in recombinant tissue-type plasminogen activator treatment initiation after the extension of the thrombolysis time window were not confirmed.

Erythropoietin for stroke treatment: dead or alive?

Endothelial progenitor cell (EPC) mobilization from the bone marrow was considered to improve outcome after ischemic stroke. Erythropoietin (EPO) might be a potential candidate stroke drug that increases the number of circulating EPCs. In the previous issue of Critical Care, Yip and colleagues investigated the effect of EPO in stroke patients on both clinical outcome and EPC stimulation. Although beneficial effects of EPO were observed, several issues regarding EPO's suitability as a stroke drug remain.

The impact of lesion location and lesion size on poststroke infection frequency.

OBJECTIVES: Infections in patients with stroke are common and significantly affect outcome. Various predictors of poststroke infections were determined, such as degree of neurological impairment and implementation of therapeutic interventions. The authors investigated whether stroke location and stroke size are independent risk factors for poststroke infections. METHODS: 591 patients with acute stroke who were treated on our stroke unit were included in a prospective observational study. Predefined endpoints were pneumonia, urinary-tract infection (UTI) and other infections. The OR of infections was calculated for various stroke locations, stroke lateralisation and three categories of stroke size. Logistic regression models were used to adjust for factors significantly associated with poststroke infections in a single-factor analysis. RESULTS: In the single-factor analysis, the left anterior cerebral artery territory was associated with pneumonia. After adjustment for relevant covariates, this association was no longer statistically significant. Stroke lateralisation showed no association with infection frequency. The largest stroke size was positively associated with pneumonia (OR 3.5, p<0.001). The smallest lesion size was significantly less associated with the occurrence of UTI (OR 0.4, p<0.01). CONCLUSION: In this study, lesion size is an independent risk factor for the development of poststroke infection. Particular brain regions associated with infections could not be determined.

Case report of MR perfusion imaging in sinking skin flap syndrome: growing evidence for hemodynamic impairment.

BACKGROUND: The syndrome of the sinking skin flap (SSSF) with delayed sensorimotor deficits after craniectomy is not well known and often neglected. Among various postulated causes, there is evidence that disturbed brain perfusion may be related to the observed symptoms, and that cranioplasty reliably alleviates these symptoms. We report a case of sinking skin flap syndrome (SSFS) with recovery from neurological sensorimotor deficits after cranioplasty correlated with pre- and postsurgical MR brain perfusion studies. CASE PRESENTATION: A 42-year-old woman presented with slowly progressive sensorimotor paresis of her left arm after decompressive extensive craniectomy due to subarachnoid hemorrhage four months ago. Her right cranium showed a "sinking skin flap". After cranioplastic repair of her skull defect, the patient fully recovered from her symptoms. Before cranioplasty, reduced brain perfusion in the right central cortical region was observed in MR-perfusion images. After cranioplasty, a marked increase in brain perfusion was observed which correlated with objective clinical recovery. CONCLUSION: There is increasing evidence that impaired blood flow is responsible for delayed motor deficits in patients with sinking skin flap syndrome in the area of compressed brain regions. Symptoms should be evaluated by brain perfusion imaging complementing surgical decision-making.

Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy.

AIMS: To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain. METHODS AND RESULTS: We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37-84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (ß = -0.115, P < 0.01) as well as attention and executive functions (ß = -0.105, P < 0.01) compared with subjects without AF. There was also a trend (P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups. CONCLUSION: Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.