Reliability and validity of DTI-based indirect disconnection measures.

White matter connections enable the interaction within and between brain networks. Brain lesions can cause structural disconnections that disrupt networks and thereby cognitive functions supported by them. In recent years, novel methods have been developed to quantify the extent of structural disconnection after focal lesions, using tractography data from healthy controls. These methods, however, are indirect and their reliability and validity have yet to be fully established. In this study, we present our implementation of this approach, in a tool supplemented by uncertainty metrics for the predictions overall and at voxel-level. These metrics give an indication of the reliability and are used to compare predictions with direct measures from patients' diffusion tensor imaging (DTI) data in a sample of 95 first-ever stroke patients. Results show that, except for small lesions, the tool can predict fiber loss with high reliability and compares well to direct patient DTI estimates. Clinical utility of the method was demonstrated using lesion data from a subset of patients suffering from hemianopia. Both tract-based measures outperformed lesion localization in mapping visual field defects and showed a network consistent with the known anatomy of the visual system. This study offers an important contribution to the validation of structural disconnection mapping. We show that indirect measures of structural disconnection can be a reliable and valid substitute for direct estimations of fiber loss after focal lesions. Moreover, based on these results, we argue that indirect structural disconnection measures may even be preferable to lower-quality single subject diffusion MRI when based on high-quality healthy control datasets.

The impact of etiology in lesion-symptom mapping - A direct comparison between tumor and stroke.

INTRODUCTION: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. METHODS: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. RESULTS: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. CONCLUSION: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.

The course of post-stroke apathy in relation to cognitive functioning: a prospective longitudinal cohort study.

Apathy is common after stroke and has been associated with cognitive impairment. However, causality between post-stroke apathy and cognitive impairment remains unclear. We assessed the course of apathy in relation to changes in cognitive functioning in stroke survivors. Using the Apathy Scale (AS) and cognitive tests on memory, processing speed and executive functioning at six- and 15 months post-stroke we tested for associations between (1) AS-scores and (change in) cognitive scores; (2) apathy course (persistent/incident/resolved) and cognitive change scores. Of 117 included participants, 29% had persistent apathy, 13% apathy resolving over time and 10% apathy emerging between 6-15 months post-stroke. Higher AS-scores were cross-sectionally and longitudinally associated with lower cognitive scores. Relations between apathy and cognitive change scores were ambiguous. These inconsistent relations between apathy and changes in cognition over time suggest that post-stroke apathy does not directly impact cognitive performance. Both these sequelae of stroke require separate attention.

Mediating Mechanisms in Cognitive Behavioral Therapy for Childhood OCD: The Role of Dysfunctional Beliefs.

Reframing cognitions is assumed to play an important role in treatment for obsessive-compulsive disorder (OCD). However, there hardly is any empirical support for this assumption, especially for children. The aim of this study was to examine if changing dysfunctional beliefs is a mediating mechanism of cognitive behavioral therapy (CBT) for childhood OCD. Fifty-eight children (8-18 years) with OCD received CBT. Dysfunctional beliefs (OBQ-CV) and OCD severity (CY-BOCS) were measured pre-treatment, mid-treatment, post-treatment, and at 16-week follow-up. Results showed that OCD severity and dysfunctional beliefs decreased during CBT. Changes in severity predicted changes in beliefs within the same time interval. Our results did not support the hypothesis that changing dysfunctional beliefs mediates treatment effect. Future studies are needed to replicate these findings and shed more light on the role of explicit and implicit cognitions in treatment for childhood OCD.

Action blindsight and antipointing in a hemianopic patient.

Blindsight refers to the observation of residual visual abilities in the hemianopic field of patients without a functional V1. Given the within- and between-subject variability in the preserved abilities and the phenomenal experience of blindsight patients, the fine-grained description of the phenomenon is still debated. Here we tested a patient with established "perceptual" and "attentional" blindsight (c.f. Danckert and Rossetti, 2005). Using a pointing paradigm patient MS, who suffers from a complete left homonymous hemianopia, showed clear above chance manual localisation of 'unseen' targets. In addition, target presentations in his blind field led MS, on occasion, to spontaneous responses towards his sighted field. Structural and functional magnetic resonance imaging was conducted to evaluate the magnitude of V1 damage. Results revealed the presence of a calcarine sulcus in both hemispheres, yet his right V1 is reduced, structurally disconnected and shows no fMRI response to visual stimuli. Thus, visual stimulation of his blind field can lead to "action blindsight" and spontaneous antipointing, in absence of a functional right V1. With respect to the antipointing, we suggest that MS may have registered the stimulation and subsequently presumes it must have been in his intact half field.

Eight-year follow-up of a randomized clinical trial comparing ultrasound-guided foam sclerotherapy with surgical stripping of the great saphenous vein.

BACKGROUND: This was an 8-year follow-up of an RCT comparing ultrasound-guided foam sclerotherapy (UGFS) with high ligation and surgical stripping (HL/S) of the great saphenous vein (GSV). METHODS: Patients were randomized to UGFS or HL/S of the GSV. The primary outcome was the recurrence of symptomatic GSV reflux. Secondary outcomes were patterns of reflux according to recurrent varices after surgery, Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification, Venous Clinical Severity Score (VCSS) and EuroQol Five Dimensions (EQ-5D™) quality-of-life scores. RESULTS: Of 430 patients originally randomized (230 UGFS, 200 HL/S), 227 (52·8 per cent; 123 UGFS, 103 HL/S) were available for analysis after 8 years. The proportion of patients free from symptomatic GSV reflux at 8 years was lower after UGFS than HL/S (55·1 versus 72·1 per cent; P = 0·024). The rate of absence of GSV reflux, irrespective of venous symptoms, at 8 years was 33·1 and 49·7 per cent respectively (P = 0·009). More saphenofemoral junction (SFJ) failure (65·8 versus 41·7 per cent; P = 0·001) and recurrent reflux in the above-knee GSV (72·5 versus 20·4 per cent; P = 0·001) was evident in the UGFS group. The VCSS was worse than preoperative scores in both groups after 8 years; CEAP classification and EQ-5D® scores were similar in the two groups. CONCLUSION: Surgical stripping had a technically better outcome in terms of recurrence of GSV and SFJ reflux than UGFS in the long term. Long-term follow-up suggests significant clinical progression of venous disease measured by VCSS in both groups, but less after surgery. Registration number: NCT02304146 (http://www.clinicaltrials.gov).

Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery for the incompetent great saphenous vein.

BACKGROUND: New minimally invasive treatment modalities, such as ultrasound-guided foam sclerotherapy (UGFS), are becoming more popular. In a multicentre randomized controlled non-inferiority trial, the effectiveness and costs of UGFS and surgery for treatment of the incompetent great saphenous vein (GSV) were compared. METHODS: Patients with primary great saphenous varicose veins were assigned randomly to either UGFS or surgical stripping with high ligation. Recurrence, defined as reflux combined with venous symptoms, was determined on colour duplex scans at baseline, 3 months, 1 year and 2 years after initial treatment. Secondary outcomes were presence of recurrent reflux (irrespective of symptoms), reduction of symptoms, health-related quality of life (EQ-5D(™)), adverse events and direct hospital costs. RESULTS: Two hundred and thirty patients were treated by UGFS and 200 underwent GSV stripping. The 2-year probability of recurrence was similar in the UGFS and surgery groups: 11·3 per cent (24 of 213) and 9·0 per cent (16 of 177) respectively (P = 0·407). At 2 years, reflux irrespective of venous symptoms was significantly more frequent in the UGFS group (35·0 per cent) than in the surgery group (21·0 per cent) (P = 0·003). Mean(s.d.) hospital costs per patient over 2 years were €774(344) per patient for UGFS and €1824(141) for stripping. CONCLUSION: At 2-year follow-up, UGFS was not inferior to surgery when reflux associated with venous symptoms was the clinical outcome of interest. UGFS has the potential to be a cost-effective approach to a common health problem. Registration numbers: NCT01103258 (http://www.clinicaltrials.gov) and NTR654 (http://www.trialregister.nl).

The posterior parietal paradox: Why do functional magnetic resonance imaging and lesion studies on episodic memory produce conflicting results?

Recent functional magnetic resonance imaging (fMRI) studies addressing healthy subjects point towards posterior parietal cortex (PPC) involvement in episodic memory tasks. This is noteworthy, since neuropsychological studies usually do not connect parietal lesions to episodic memory impairments. Therefore an inventory of the possible factors behind this apparent paradox is warranted. This review compared fMRI studies which demonstrated PPC activity in episodic memory tasks, with findings with studies of patients with PPC lesions. A systematic evaluation of possible explanations for the posterior parietal paradox indicates that PPC activation in fMRI studies does not appear to be attributable to confounding cognitive/psychomotor processes, such as button pressing or stimulus processing. What may be of more importance is the extent to which an episodic memory task loads on three closely related cognitive processes: effort and attention, self-related activity, and scene and image construction. We discuss to what extent these cognitive processes can account for the paradox between lesion and fMRI results. They are strongly intertwined with the episodic memory and may critically determine in how far the PPC plays a role in a given memory task. Future patient studies might profit from specifically taking these cognitive factors into consideration in the task design.

Device therapy in children: current indications.

The implantable cardioverter defibrillator has achieved increasing acceptance in paediatric cardiologic practice. Concurrent with technological advances which have made the devices more versatile, easier to implant and to program, there has been a fundamental breakthrough in our understanding of genetic and inherited arrhythmia syndromes in the last decade. This in turn has led to investigations into risk stratification, with the aim of choosing high risk candidates for timely device therapy. The second group of young patients with a risk of sudden death are those who have had a previous repair of a structural heart defect. Given that sudden arrhythmic death is the commonest cause of mortality in this population, it behoves the practising paediatric cardiologist to be aware of the current recommendations for device implantation in this population. In this manuscript, we summarise the current state of our understanding of the risk factors for sudden death, and identify possible candidates for ICD implantation.

Paediatric electrophysiologic studies: how and what with?

Catheter ablation of arrhythmias in children has become standard practice virtually worldwide. Successful and safe ablation has been made possible by a combination of factors. These include increased operator experience, a better understanding of the natural history of a wide variety of arrhythmias, advances in technology such as smaller catheters, the routine use of various three-dimensional mapping systems, and the development of alternative energy sources. It is also not uncommon to perform multiple catheter intervention procedures (ablation +/- intravascular stent implantation +/- device closure of residual shunts +/- elective pacemaker or device implantation) during a single session. It is important to bear in mind that arrhythmia recurrence is commoner in children in general, and that this is particularly the case with postoperative (scar-related arrhythmias). Despite acute success, long-term follow-up is mandated for this subgroup of patients.

Acute neglect rehabilitation using repetitive prism adaptation: a randomized placebo-controlled trial.

PURPOSE: At present, prism adaptation is probably the most promising rehabilitation procedure for hemi-neglect. However, randomised controlled trials are lacking and no data are available on the effectiveness of prism adaptation in the treatment of acute neglect. METHODS: We followed sixteen neglect patients using a randomised controlled design in which six patients received four-day-in-a-row placebo treatment (CG) and ten patients received four-day-in-a row experimental treatment with 10 degrees rightward deviating prisms (EG) during their stay on the stroke unit. We examined whether patients in the EG improved faster than the CG by administering three neglect tasks (Schenkenberg Line Bisection, Letter Cancellation, Gainotti Scene Copying) immediately before and after each treatment. Second, we examined whether patients in the EG demonstrated a better long-term outcome at one month post-treatment (Behavioural Inattention Test). RESULTS: Patients in the EG improved faster on spatial tasks (line bisection, cancellation) than the CG but not on visuo-construction. Patients in the EG showed no differences with the CG in neglect outcome at one month post-treatment. CONCLUSIONS: Four consecutive prism sessions produced beneficial effects in patients with acute neglect. However, prism effects were either short-term, or placebo treatment with repeated pointing and/or repeated neglect testing was more helpful than we anticipated. Our results emphasize the importance of a placebo condition and a follow-up in rehabilitation studies.

Perception of facial expressions in obsessive-compulsive disorder: a dimensional approach.

The study examined the perception of facial expressions of different emotional intensities in obsessive-compulsive disorder (OCD) subtypes. Results showed that the High Risk Assessment and Checking subtype was more sensitive in perceiving the emotions fear and happiness. This suggests that altered affective processing may underlie the clinical manifestation of OCD.

Hearing a voice in the noise: auditory hallucinations and speech perception.

BACKGROUND: It has recently been suggested that auditory hallucinations are the result of a criterion shift when deciding whether or not a meaningful signal has emerged. The approach proposes that a liberal criterion may result in increased false-positive identifications, without additional perceptual deficit. To test this hypothesis, we devised a speech discrimination task and used signal detection theory (SDT) to investigate the underlying cognitive mechanisms. METHOD: Schizophrenia patients with and without auditory hallucinations and a healthy control group completed a speech discrimination task. They had to decide whether a particular spoken word was identical to a previously presented speech stimulus, embedded in noise. SDT was used on the accuracy data to calculate a measure of perceptual sensitivity (Az) and a measure of response bias (beta). Thresholds for the perception of simple tones were determined. RESULTS: Compared to healthy controls, perceptual thresholds were higher and perceptual sensitivity in the speech task was lower in both patient groups. However, hallucinating patients showed increased sensitivity to speech stimuli compared to non-hallucinating patients. In addition, we found some evidence of a positive response bias in hallucinating patients, indicating a tendency to readily accept that a certain stimulus had been presented. CONCLUSIONS: Within the context of schizophrenia, patients with auditory hallucinations show enhanced sensitivity to speech stimuli, combined with a liberal criterion for deciding that a perceived event is an actual stimulus.

Accuracy of body mass index in predicting pre-eclampsia: bivariate meta-analysis.

OBJECTIVE: The objective of this study was to determine the accuracy of body mass index (BMI) (pre-pregnancy or at booking) in predicting pre-eclampsia and to explore its potential for clinical application. DESIGN: Systematic review and bivariate meta-analysis. SETTING: Medline, Embase, Cochrane Library, MEDION, manual searching of reference lists of review articles and eligible primary articles, and contact with experts. POPULATION: Pregnant women at any level of risk in any healthcare setting. METHODS: Reviewers independently selected studies and extracted data on study characteristics, quality, and accuracy. No language restrictions. MAIN OUTCOME MEASURES: Pooled sensitivities and specificities (95% CI), a summary receiver operating characteristic curve, and corresponding likelihood ratios (LRs). The potential value of BMI was assessed by combining its predictive capacity for different prevalences of pre-eclampsia and the therapeutic effectiveness (relative risk 0.90) of aspirin. RESULTS: A total of 36 studies, testing 1,699,073 pregnant women (60,584 women with pre-eclampsia), met the selection criteria. The median incidence of pre-eclampsia was 3.9% (interquartile range 1.4-6.8). The area under the curve was 0.64 with 93% of heterogeneity explained by threshold differences. Pooled estimates (95% CI) for all studies with a BMI > or = 25 were 47% (33-61) for sensitivity and 73% (64-83) for specificity; and 21% (12-31) and 92% (89-95) for a BMI > or = 35. Corresponding LRs (95% CI) were 1.7 (0.3-11.9) for BMI > or = 25 and 0.73 (0.22-2.45) for BMI < 25, and 2.7 (1.0-7.3) for BMI > or = 35 and 0.86 (0.68-1.07) for BMI < 35. The number needed to treat with aspirin to prevent one case of pre-eclampsia ranges from 714 (no testing, low-risk women) to 37 (BMI > or = 35, high-risk women). CONCLUSIONS: BMI appears to be a fairly weak predictor for pre-eclampsia. Although BMI is virtually free of cost, noninvasive, and ubiquitously available, its usefulness as a stand-alone test for risk stratification must await formal cost-utility analysis. The findings of this review may serve as input for such analyses.

Cognitions in children with OCD. A pilot study for age specific relations with severity.

Cognitive theory, postulates that dysfunctional cognitions play a maintaining or even aetiological role in obsessive-compulsive disorder (OCD). In this study it was hypothesised that if distorted cognitions play a central role in OCD, there should be a relation between cognitive measures and the severity of the obsessive-compulsive symptoms in a childhood OCD sample. A group of 39 children and adolescents with a primary diagnosis OCD was measured on the CY-BOCS, and on the cognitive questionnaires the MTQ, and the CATS. The findings suggest no relation between the severity of the OCD and magical thinking. In the younger group aged 8-12 years (n = 18) no relations with any negative thoughts were found. In the older group, aged 13-18 years (n = 21), relations between the CY-BOCS Obsession scale and the CATS subscales Physical Threat, Social Threat and Personal Failure were found. Compared to a previously published community sample, the MTQ scores in the present sample are lower. The CATS scores for the OCD sample were found to be lower than most clinical comparison groups, which is especially true for the CATS Hostility subscale. Issues about criterion contamination and explanatory hypothesis about the age specific relation are addressed.

Predictors of course in obsessive-compulsive disorder: logistic regression versus Cox regression for recurrent events.

OBJECTIVE: Two methods for predicting remissions in obsessive-compulsive disorder (OCD) treatment are evaluated. Y-BOCS measurements of 88 patients with a primary OCD (DSM-III-R) diagnosis were performed over a 16-week treatment period, and during three follow-ups. METHOD: Remission at any measurement was defined as a Y-BOCS score lower than thirteen combined with a reduction of seven points when compared with baseline. Logistic regression models were compared with a Cox regression for recurrent events model. RESULTS: Logistic regression yielded different models at different evaluation times. The recurrent events model remained stable when fewer measurements were used. Higher baseline levels of neuroticism and more severe OCD symptoms were associated with a lower chance of remission, early age of onset and more depressive symptoms with a higher chance. CONCLUSION: Choice of outcome time affects logistic regression prediction models. Recurrent events analysis uses all information on remissions and relapses. Short- and long-term predictors for OCD remission show overlap.

Cognitive disorders in acute stroke: prevalence and clinical determinants.

BACKGROUND: Although cognitive impairment early after stroke is a powerful predictor of long-term functional dependence and dementia, little is known about the characteristics and determinants of cognitive dysfunction in acute stroke. METHODS: We administered a neuropsychological examination covering 7 cognitive domains to 190 patients within 3 weeks after a first stroke. We also assembled lesion characteristics, clinical factors at admission, demographic characteristics and vascular risk factors. Multivariate logistic regression adjusted for age, gender and education was performed to examine determinants of acute cognitive impairment. RESULTS: Overall, 74% of patients with a cortical stroke, 46% with a subcortical stroke and 43% with an infratentorial stroke demonstrated acute cognitive impairment. Disorders in executive functioning (39%) and visual perception/construction (38%) were the most common. The prevalence and severity of deficits in executive functioning, language, verbal memory and abstract reasoning was more pronounced following left compared to right cortical stroke (all p < 0.05). Intracerebral haemorrhage (OR = 5.6; 95% CI = 1.2-25.4) and cortical involvement of the stroke (OR = 3.6; 95%, CI = 1.3-9.9) were independent determinants of acute cognitive impairment, whereas premorbid moderate alcohol consumption exerted a protective effect (OR = 0.4; 95% CI = 0.1-1.1). CONCLUSIONS: Cognitive impairment is common in the first weeks after stroke, with executive and perceptual disorders being the most frequent. Intracerebral haemorrhage, cortical involvement of the lesion and premorbid moderate alcohol consumption are independently associated with acute cognitive impairment.

Type 2 diabetes, cognitive function and dementia: vascular and metabolic determinants.

Type 2 diabetes is a common metabolic disease with a rising global prevalence. It is associated with slowly progressive end-organ damage in the eyes and kidneys, but also in the brain. The latter complication is often referred to as "diabetic encephalopathy" and is characterized by mild to moderate impairments in cognitive functioning. It is also associated with an increased risk of dementia. To date, its pathogenetic mechanisms are largely unclear. Cognitive impairments in patients with type 2 diabetes have been associated both with vascular risk factors, such as hypertension and dyslipidemia, and with diabetes-related factors, such as glycemic control, duration of the disease and treatment modality. Studies that address these associations generally focus on statistical (in)dependence of certain risk factors in the association between type 2 diabetes and cognitive decline rather than the causality of the association, which, from a mechanistic point of view, is more relevant. In this review we describe the association between type 2 diabetes and cognitive dysfunction and dementia. Furthermore, potential determinants of impaired cognition in type 2 diabetes are addressed both from the perspective of statistical associations and from a mechanistic point of view.

Visual information processing in high-functioning individuals with autism spectrum disorders and their parents.

The authors assessed visual information processing in high-functioning individuals with pervasive developmental disorders (PDD) and their parents. The authors used tasks for contrast sensitivity, motion, and form perception to test visual processing occurring relatively early and late in the magnocellular-dorsal and parvocellular-ventral pathways. No deficits were found in contrast sensitivity for low or high spatial frequencies or for motion or form perception between individuals with PDD in comparison with a matched control group. Individuals with PDD performed equally with or better than controls on motion detection tasks. In addition, the authors did not find differences on any of the tasks between parents of the PDD group and matched control parents. These results indicate that high-functioning individuals with PDD and their parents are able to process visual stimuli that rely on early or late processing in the magnocellular-dorsal and parvocellular-ventral pathways as well as controls.