Scan without evidence of dopaminergic deficit: A 10-year retrospective study

123I-ioflupane SPECT is a powerful method to assess nigrostriatal dopamine system integrity. Several independent studies have shown that 1–15% of patients with suspected degenerative parkinsonism, mainly PD, have scans without evidence of dopaminergic deficit (SWEDD). It has been proposed that most SWEDD patients either present with a non-degenerative condition mimicking PD, such as atypical tremor or dystonia, or demonstrate an abnormal scan when repeated later. We here hypothesized that scan interpretation methods may also play a crucial yet underestimated role in this issue.Methods We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N = 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis.Results Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome.Conclusion SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned

Establishing on-site reference values for 123I-FP-CIT SPECT (DaTSCAN®) using a cohort of individuals with non-degenerative conditions

To overcome the issue of reference values for DaTSCAN® requiring healthy controls, we propose an original approach using scans from individuals with non- degenerative conditions performed at one single center following the same acquisition protocol. Procedures: From a cohort of 970 consecutive patients, we identified 182 patients with a clinical diagnosis of non-degenerative parkinsonism or tremor and a visually normal DATSCAN®. Caudate nucleus (C), putamen (P), and striatum (S) uptake values, C/P ratios, and asymmetry indexes (AI) were calculated using semi-quantitative methods. Outcomes were assessed according to age and gender, and reference limits were established using the percentile approach. Results: A significant negative linear effect of age was found upon striatal nuclei uptake of 0.21–0.22 per decade (6.8 %/decade for striatum), whereas a potential gender influence proved unclear. Inferior reference limits were established at the 5th percentile. C/P ratios and AIs were not influenced by age or gender, and superior reference limits were set at the 95th percentile. Conclusions: We here propose a convenient approach to calculate site-specific reference limits for DaTSCAN® outcomes not requiring scanning healthy controls. The method appears to yield robust values that range within nearly identical limits as those obtained in healthy subjects

Distinct spatiotemporal patterns for disease duration and stage in Parkinson’s disease

Purpose: To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson’s disease (PD).Methods: This retrospective study included 970 consecutive patients undergoing ¹²³I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 ± 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 ± 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.Results: Increasing disease stage was associated with an exponential decrease in ¹²³I-ioflupane uptake (R ²  = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p p R ²  = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001).Conclusion: We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 ¹²³I-ioflupane SPECT scans can be used for clinical and research applications

Attachment and Reflective Functioning in Women With Borderline Personality Disorder

Insecure attachment and impairments in reflective functioning (RF) are thought to play a critical role in borderline personality disorder (BPD). In particular, the mentalization-based model argues that insecure attachment indirectly accounts for increased BPD features, notably via disruption of RF capacities. Although the mediation relationship between attachment, RF, and BPD is supported by previous evidence, it remains to be directly tested in adults with BPD. In the current study, a sample of 55 female adult BPD patients and 105 female healthy controls completed a battery of self-report measures to investigate the interplay between attachment, RF capacities, and BPD clinical status. Overall, the results showed that BPD patients predominantly reported insecure attachment, characterized by negative internal working models of the self as unlovable and unimportant to others, and decreased RF abilities. Our findings further indicated that actual RF capacities mediated the relationships between adult insecure attachment and BPD clinical status

Self-reported interoceptive deficits in eating disorders: A meta-analysis of studies using the eating disorder inventory

This document is the Accepted Manuscript version of the following article: Paul M. Jenkinson, Lauren Taylor, Keith R. Laws, ‘Self-reported interoceptive deficits in eating disorders: A meta-analysis of studies using the eating disorder inventory’, Journal of Psychosomatic Research, Vol. 110: 38-45, July 2018, under embargo until 19 April 2019. The Version of Record is available online at DOI: https://doi.org/10.1016/j.jpsychores.2018.04.005Objective: An impairment of the ability to sense the physiological condition of the body – interoception – has long been proposed as central to the onset and maintenance of eating disorders. More recent attention to this topic has generally indicated the presence of interoceptive deficits in individuals with an eating disorder diagnosis; however, possible links with specific diagnosis, BMI, age, illness duration, depression, and alexithymia remain unclear from individual studies. This meta-analysis aimed to provide a necessary quantitative overview of self-reported interoceptive deficits in eating disorder populations, and the relationship between these deficits and the previously mentioned factors. Methods: Using a random effects model, our meta-analysis assessed the magnitude of differences in interoceptive abilities as measured using the Eating Disorder Inventory in 41 samples comparing people with eating disorders (n=4308) and healthy controls (n=3459). Follow-up and moderator analysis was conducted, using group comparisons and meta-regressions. Results: We report a large pooled effect size of 1.62 for eating disorders with some variation between diagnostic groups. Further moderator analysis showed that BMI, age and alexithymia were significant predictors of overall effect size. Conclusion: This meta-analysis is the first to confirm that large interoceptive deficits occur in a variety of eating disorders and crucially, in those who have recovered. These deficits may be useful in identifying and distinguishing eating disorders. Future research needs to consider both objective and subjective measures of interoception across different types of eating disorders and may fruitfully examine interoception as a possible endophenotype and target for treatment.Peer reviewe

Systemic effects of epidural methylprednisolone injection on glucose tolerance in diabetic patients

ABSTRACT: BACKGROUND: Several studies have shown that in diabetic patients, the glycemic profile was disturbed after intra-articular injection of corticosteroids. Little is known about the impact of epidural injection in such patients. The goal of this study was double, at first comparing the glycaemic profile in diabetic patients after a unique injection of 80 mg of acetate methylprednisolone either intra-articular or epidural and secondly to compare the amount of systemic diffusion of the drug after both procedures. METHODS: Seventeen patients were included. Glycemic changes were compared in 9 diabetic patients following intra-articular (4 patients) and epidural injections (5 patients). Epidural injections were performed using the sacral route under fluoroscopic control in patients with lumbar spinal stenosis. Diabetes control had to stable for more than 10 days and the renal function to be preserved. Blood glucose was monitored using a validated continuous measuring device (GMS, Medtronic) the day before and for two days following the injection. Results were expressed in the form of daily glycemic profiles and as by mean, peak and minimal values +/ SD. The urinary excretion of methylprednisolone after the 2 routes of injection was analyzed in 8 patients (4 in each group). Urine samples were cropped one hour before the injections, then 4 times during the first day and 3 times a week for 2 weeks. The measurements included the free and conjugated fraction RESULTS: The glycaemic profile remains unchanged with no significant changes in the group of the 5 diabetic patients receiving epidural injections. On the other end, the average peak and mean values were enhanced up to 3 mmol/l above baseline two days after the infiltration in the groups of the 4 diabetic patients infiltrated intra-articular. The mean urinary excretion of the steroid was about ten times higher in the intra-articular versus epidural group: 7000 ng/ml versus 700 ng/ml. Looking at each individual there were marked differences especially after intra-articular injections. CONCLUSION: This is the first study to show that a single epidural steroid injection of 80 mg depot methylprednisolone had no effect on the glycemic control in diabetic patients. The absence of glycemic control changes correlated well with the very low urinary excretion of the drug after epidural injection. Trial registration NCT01420497

Brain activity underlying negative self- and other-perception in adolescents: The role of attachment-derived self-representations

One of teenagers' key developmental tasks is to engage in new and meaningful relationships with peers and adults outside the family context. Attachment-derived expectations about the self and others in terms of internal attachment working models have the potential to shape such social reorientation processes critically and thereby influence adolescents' social-emotional development and social integration. Because the neural underpinnings of this developmental task remain largely unknown, we sought to investigate them by functional magnetic resonance imaging. We asked n = 44 adolescents (ages 12.01-18.84 years) to evaluate positive and negative adjectives regarding either themselves or a close other during an adapted version of the well-established self-other trait-evaluation task. As measures of attachment, we obtained scores reflecting participants' positive versus negative attachment-derived self- and other-models by means of the Relationship Questionnaire. We controlled for possible confounding factors by also obtaining scores reflecting internalizing/externalizing problems, schizotypy, and borderline symptomatology. Our results revealed that participants with a more negative attachment-derived self-model showed increased brain activity during positive and negative adjective evaluation regarding the self, but decreased brain activity during negative adjective evaluation regarding a close other, in bilateral amygdala/parahippocampus, bilateral anterior temporal pole/anterior superior temporal gyrus, and left dorsolateral prefrontal cortex. These findings suggest that a low positivity of the self-concept characteristic for the attachment anxiety dimension may influence neural information processing, but in opposite directions when it comes to self- versus (close) other-representations. We discuss our results in the framework of attachment theory and regarding their implications especially for adolescent social-emotional development and social integration

Comparison of machine learning and semi-quantification algorithms for (I123)FP-CIT classification: the beginning of the end for semi-quantification?

Background Semi-quantification methods are well established in the clinic for assisted reporting of (I123) Ioflupane images. Arguably, these are limited diagnostic tools. Recent research has demonstrated the potential for improved classification performance offered by machine learning algorithms. A direct comparison between methods is required to establish whether a move towards widespread clinical adoption of machine learning algorithms is justified. This study compared three machine learning algorithms with that of a range of semi-quantification methods, using the Parkinson’s Progression Markers Initiative (PPMI) research database and a locally derived clinical database for validation. Machine learning algorithms were based on support vector machine classifiers with three different sets of features: Voxel intensities Principal components of image voxel intensities Striatal binding radios from the putamen and caudate. Semi-quantification methods were based on striatal binding ratios (SBRs) from both putamina, with and without consideration of the caudates. Normal limits for the SBRs were defined through four different methods: Minimum of age-matched controls Mean minus 1/1.5/2 standard deviations from age-matched controls Linear regression of normal patient data against age (minus 1/1.5/2 standard errors) Selection of the optimum operating point on the receiver operator characteristic curve from normal and abnormal training data Each machine learning and semi-quantification technique was evaluated with stratified, nested 10-fold cross-validation, repeated 10 times. Results The mean accuracy of the semi-quantitative methods for classification of local data into Parkinsonian and non-Parkinsonian groups varied from 0.78 to 0.87, contrasting with 0.89 to 0.95 for classifying PPMI data into healthy controls and Parkinson’s disease groups. The machine learning algorithms gave mean accuracies between 0.88 to 0.92 and 0.95 to 0.97 for local and PPMI data respectively. Conclusions Classification performance was lower for the local database than the research database for both semi-quantitative and machine learning algorithms. However, for both databases, the machine learning methods generated equal or higher mean accuracies (with lower variance) than any of the semi-quantification approaches. The gain in performance from using machine learning algorithms as compared to semi-quantification was relatively small and may be insufficient, when considered in isolation, to offer significant advantages in the clinical context

Distortions of perceived volume and length of body parts

We experience our body as a 3D, volumetric object in the world. Measures of our conscious body image, in contrast, have investigated the perception of body size along one or two dimensions at a time. There is, thus, a discrepancy between existing methods for measuring body image and our subjective experience of having 3D body. Here we assessed in a sample of healthy adults the perception of body size in terms of its 1D length and 3D volume. Participants were randomly assigned to two groups using different measuring units (other body part and non-body object). They estimated how many units would fit in a perceived size of body segments and the whole body. The patterns of length and volume misperception across judged segments were determined as their perceived size proportional to their actual size. The pattern of volume misperception paints the representation of 3D body proportions resembling those of a somatosensory homunculus. The body parts with a smaller actual surface area relative to their volume were underestimated more. There was a tendency for body parts underestimated in volume to be overestimated in length. Perceived body proportions thus changed as a function of judgement type while showing a similarity in magnitude of the absolute estimation error, be it an underestimation of volume or overestimation of length. The main contribution of this study is assessing the body image as a 3D body representation, and thus extending beyond the conventional ‘allocentric’ focus to include the body on the inside. Our findings highlight the value of studying the perceptual distortions “at the baseline”, i.e. in healthy population, so as to advance the understanding of the nature of perceptual distortions in clinical conditions