[Nuclear medicine diagnostics in Wilson's disease]. / Nuklearmedizinische Diagnostik beim Morbus Wilson.

Wilson's disease is an autosomal recessive disorder of copper metabolism and is caused by a genetic defect on chromosome 13. Nuclear medicine methods can prove the metabolic defect and contribute to the assessment of central neurological deficits.With high specificity and sensitivity, the intravenous radiocopper test enables the diagnosis to be confirmed as the basis for initiating treatment. The oral radiocopper test is used to monitor zinc treatment.[123I]ß-CIT-SPECT and [123I]IBZM-SPECT provide functional information of the nigrostriatal system.[123I]ß-CIT-SPECT also allows the determination of SERT availability in the hypothalamus/brain stem as a surrogate parameter of depression.Metabolic parameters of the cortex, basal ganglia and cerebellum can be assessed by [18F]FDG-PET studies.SPECT and [18F]FDG-PET studies show significant differences between neurological and non-neurological Wilson patients. Overall, only noninvasive in vivo nuclear medicine enables a deeper insight into the pathophysiology of neurological processes in Wilson's disease.

Association of electroencephalogram trajectories during emergence from anaesthesia with delirium in the postanaesthesia care unit: an early sign of postoperative complications.

BACKGROUND: Postoperative delirium is associated with an increased risk of morbidity and mortality, especially in the elderly. Delirium in the postanaesthesia care unit (PACU) could predict adverse clinical outcomes. METHODS: We investigated a potential link between intraoperative EEG patterns and PACU delirium as well as an association of PACU delirium with perioperative outcomes, readmission and length of hospital stay. The risk factors for PACU delirium were also explored. Data were collected from 626 patients receiving general anaesthesia for procedures that would not interfere with frontal EEG recording. RESULTS: Of the 626 subjects enrolled, 125 tested positive for PACU delirium. Whilst age, renal failure, and pre-existing neurological disease were associated with PACU delirium in the univariable analysis, the multivariable analysis revealed the importance of information derived from the EEG, anaesthetic technique, anaesthesia duration, and history of stroke or neurodegenerative disease. The occurrence of EEG burst suppression during maintenance [odds ratio (OR)=1.86 (1.13-3.05)] and the type of EEG emergence trajectory may be predictive of PACU delirium. Specifically, EEG emergence trajectories lacking significant spindle power were strongly associated with PACU delirium, especially in cases that involved ketamine or nitrous oxide [OR=6.51 (3.00-14.12)]. Additionally, subjects with PACU delirium were at an increased risk for readmission [OR=2.17 (1.13-4.17)] and twice as likely to stay >6 days in the hospital. CONCLUSIONS: Specific EEG patterns were associated with PACU delirium. These findings provide valuable information regarding how the brain reacts to surgery and anaesthesia that may lead to strategies to predict PACU delirium and identify key areas of investigation for its prevention.

Emotional eating and in vivo norepinephrine transporter availability in obesity: A [11 C]MRB PET pilot study.

OBJECTIVE: Emotional eating (EE) has been linked to norepinephrine dysfunction. Therefore, we aimed to investigate the relationship between EE and norepinephrine transporter (NET) availability. METHOD: Ten severely obese individuals (body mass index (BMI) 42.4 ± 3.7 kg/m2 ) and ten non-obese, healthy controls (BMI 23.9 ± 2.5 kg/m2 ) matched for age and sex were studied using (S,S)-[11 C]-O-methylreboxetine ([11 C]MRB) positron emission tomography (PET). Kinetic modeling of regional tissue time activity curves was performed using multilinear reference tissue model 2 (MRTM2, with the occipital cortex as a reference region) to estimate binding potential based on individual PET-MR coregistration. To test for associations of EE and NET availability, participants completed the EE subscale of the Dutch Eating Behavior Questionnaire before scanning. RESULTS: Obese individuals and non-obese, healthy controls did not significantly differ regarding EE scores and regional NET availability. For obese individuals only, correlative data analyses pointed to a sinoidal distribution pattern as a higher degree of EE related to lower NET availability in the locus coeruleus and to higher NET availability in the left thalamus. DISCUSSION: These results indicate that central in vivo NET availability is altered in EE of individuals with obesity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:152-156).

Hunger and disinhibition but not cognitive restraint are associated with central norepinephrine transporter availability.

The relationship between food-intake related behaviours measured by the Three-Factor Eating Questionnaire (TFEQ) and in vivo norepinephrine transporter (NET) availability has not been explored yet. We investigated ten obese individuals (body mass index (BMI) 42.4 ± 3.7 kg/m2) and ten normal-weight healthy controls (HC, BMI 23.9 ± 2.5 kg/m2) with (S,S)-[11C]-O-methylreboxetine ([11C]MRB) positron emission tomography (PET). All participants completed the TFEQ, which measures cognitive restraint, disinhibition and hunger. Image analysis required magnetic resonance imaging data sets onto which volumes-of-interests were drawn. Tissue time activity curves (TACs) were obtained from the dynamic PET data followed by kinetic modeling of these regional brain TACs applying the multilinear reference tissue model (2 parameters) with the occipital cortex as reference region. Obese individuals scored significantly higher on the hunger subscale of the TFEQ. Correlative data analysis showed that a higher degree of hunger correlated negatively with the NET availability of the insular cortex in both obese individuals and HC; however, this finding was more pronounced in obesity. Further, for obese individuals, a negative correlation between disinhibition and NET BPND of the locus coeruleus was detected. In conclusion, these initial data provide in vivo imaging support for the involvement of the central NE system in maladaptive eating behaviors such as susceptibility to hunger.

[Evaluation of practices in the management of scabies in children]. / Évaluation des pratiques dans la prise en charge de la gale chez les enfants.

BACKGROUND: Scabies has been on the rise in France in recent years and has posed therapeutic problems, mainly due to the withdrawal of benzyl benzoate. The objective of this study was to describe prescribing practices for scabies in children. METHODS: A national survey was conducted by means of a standardized questionnaire covering various clinical situations of scabies and the drugs used preferentially according to age, which was sent out between December 2014 and March 2015 to members of the clinical research group of the French Society of Paediatric Dermatology. RESULTS: Of the 38 experts contacted, 20 replied. For a typical case of scabies, 55% of the experts initially prescribed oral ivermectin for children aged 6 years, 15% prescribed ivermectin in children aged 2 years, and 5% in infants aged 3 months. Ivermectin was more widely prescribed after failure of prior treatment or recurrence of scabies, on skin lesions or impetigo, if precarious, especially for profuse hyperkeratotic scabies. A total of 35% of the experts reported no prescribing restrictions with regard to patient age or weight. Discrepancies were observed concerning the mode of administration and the time between consecutive doses. Esdepallethrin remained the preferred local treatment among the experts (38% of all topical prescriptions) except in asthmatic children, while permethrin was the least-prescribed topical agent. DISCUSSION: This study confirms the heterogeneity of our practices. Formal expert recommendations are awaited, particularly concerning the use of ivermectin in infants.

The central nervous norepinephrine network links a diminished sense of emotional well-being to an increased body weight.

OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress remain largely undiscovered. METHODS: In this pilot study, we combined positron emission tomography, using the norepinephrine transporter (NET) tracer [(11)C]-O-methylreboxetine, with functional connectivity magnetic resonance imaging, the Beck depression inventory (BDI), and the impact of weight on quality of life-Lite questionnaire (IWQOL-Lite), to investigate the role of norepinephrine in the severity of depression (BDI), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a small group of lean-to-morbidly obese individuals (n=20), we show that an increased body mass index (BMI) is related to a lowered NET availability within the hypothalamus, known as the brain's homeostatic control site. The hypothalamus displayed a strengthened connectivity in relation to the individual hypothalamic NET availability to the anterior insula/frontal operculum, as well as the medial orbitofrontal cortex, assumed to host the primary and secondary gustatory cortex, respectively (n=19). The resting-state activity in these two regions was correlated positively to the BMI and IWQOL-Lite scores, but not to the BDI, suggesting that the higher the resting-state activity in these regions, and hence the higher the BMI, the stronger the negative impact of the body weight on the individual's emotional well-being was. CONCLUSIONS: This pilot study suggests that the loss in emotional well-being with weight is embedded within the central norepinephrine network.

Sex differences in serotonin-hypothalamic connections underpin a diminished sense of emotional well-being with increasing body weight.

BACKGROUND/OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress related to weight remain largely unknown. PARTICIPANTS/METHODS: Here we combined positron emission tomography, using the serotonin transporter (5-HTT) radiotracer [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, with functional connectivity magnetic resonance imaging, the Beck Depression Inventory (BDI-II) and the Impact of Weight on Quality of Life-Lite questionnaire (IWQOL-Lite) to investigate the role of central serotonin in the severity of depression (BDI-II), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a group of lean to morbidly obese individuals (n=28), we found sex differences in the 5-HTT availability-related connectivity of the hypothalamus. Males (n=11) presented a strengthened connectivity to the lateral orbitofrontal cortex, whereas in females (n=17) we found strengethened projections to the ventral striatum. Both regions are known as reward regions involved in mediating the emotional response to food. Their resting-state activity correlated positively to the body mass index (BMI) and IWQOL-Lite scores, suggesting that each region in both sexes also underpins a diminished sense of emotional well-being with body weight. Contrarily to males, we found that in females also the BDI-II positively correlated with the BMI and by trend with the activity in ventral striatum, suggesting that in females an increased body weight may convey to other mood dimensions than those weight-related ones included in the IWQOL-Lite. CONCLUSIONS: This study suggests sex differences in serotonin-hypothalamic connections to brain regions of the reward circuitry underpinning a diminished sense of emotional well-being with an increasing body weight.

[Therapeutic failure in scabies: An observational study]. / Gales en échec de traitement : étude observationnelle.

BACKGROUND: Several sources suggest an escalation of scabies in France. AIM: To describe a population of patients continuing to present with scabies despite multiple treatments in order to identify factors associated with persistence of infection. PATIENTS AND METHODS: A descriptive cross-sectional study in adults and children consulting for persistent scabies despite at least one previous treatment. A standardized questionnaire explored potential sources of treatment failure. RESULTS: Thirty-one patients were analyzed. Initial symptoms were noted to have started between two and 52 weeks earlier (mean: 19 weeks). The mean number of prior consultations with a general practitioner was 3.1 (0-10) and 1.7 with a dermatologist (0-7). The mean number of patients per household was 3.5 (1-9). At least one dose of oral ivermectin (maximum of 6 doses per household) was prescribed for 84 % of patients (29 % of whom were not fasted at the time). Further, 74 % of patients received at least one local application of esdepallethrin and piperonyl butoxide (maximum: 5 courses), four received benzyl benzoate and two received permethrin; however, 58 % did not reapply the substance after hand washing. All households bought the prescribed treatments despite the costs. Close contacts of patients were treated in 58 % of households. Decontamination of bedding and clothing was carried out properly in 90 % of households. DISCUSSION: Persistence of infection appears to be linked to: (1) insufficient treatment of close contacts; (2) absence of a second treatment between days 7 and 14; (3) insufficient efficacy of the available treatments, doubtless due to multiple factors (intrinsic resistance of Sarcoptes, failure to repeat treatment, poor explanation of methods for dosing and application, and oral intake of treatments). Access to non-reimbursed treatments was not identified as a problem and decontamination of bedding and clothing was correctly performed in most cases. CONCLUSION: Though certain fundamental aspects of scabies treatment must be better known, longer consultations and provision of efficacious treatments are also a priority.

[Skin tumors in children]. / Les tumeurs cutanées de l'enfant.

The presence of a congenital or acquired cutaneous lesion is a frequent reason for consultation in pediatric plastic surgery unit. The management of these lesions requires a good knowledge of specific diagnoses in children. This step is sometimes difficult because of the multiplicity of possible diagnosis. Some skin tumors may be the external sign of a general disease or an underlying malformation; those can change the overall prognosis and management and require to be properly identified. The decision of surgical excision depends on various criteria, including diagnosis but also the reconstruction possibilities. The timing of surgical treatment depends on the medical emergency of the tumor resection (benign tumor, spontaneously regressive tumor, risk of degeneration into malignancy), on the cosmetic and psychological impact but also on the growth or learning steps in child life. This article first provides an aid in the diagnosis of the most common or more characteristic skin tumors. The algorithm is principally based on the pigmentation aspect of the tumor. The age and conditions of the surgical management are specified for each type of tumor. Cutaneous hemangiomas and vascular malformations, and congenital cysts and fistulas are not reported in this article.

Intrathecal Baclofen therapy in Germany: Proceedings of the IAB-Interdisciplinary Working Group for Movement Disorders Consensus Meeting.

Continuous intrathecal Baclofen application (ITB) through an intracorporeal pump system is widely used in adults and children with spasticity of spinal and supraspinal origin. Currently, about 1200 new ITB pump systems are implanted in Germany each year. ITB is based on an interdisciplinary approach with neurologists, rehabilitation specialists, paediatricians and neurosurgeons. We are presenting the proceedings of a consensus meeting organised by IAB-Interdisciplinary Working Group for Movement Disorders. The ITB pump system consists of the implantable pump with its drug reservoir, the refill port, an additional side port and a flexible catheter. Non-programmable pumps drive the Baclofen flow by the reservoir pressure. Programmable pumps additionally contain a radiofrequency control unit, an electrical pump and a battery. They have major advantages during the dose-finding phase. ITB doses vary widely between 10 and 2000 µg/day. For spinal spasticity, they are typically in the order of 100-300 µg/day. Hereditary spastic paraplegia seems to require particularly low doses, while dystonia and brain injury require particularly high ones. Best effects are documented for tonic paraspasticity of spinal origin and the least effects for phasic muscle hyperactivity disorders of supraspinal origin. Oral antispastics are mainly effective in mild spasticity. Botulinum toxin is most effective in focal spasticity. Myotomies and denervation operations are restricted to selected cases of focal spasticity. Due to its wide-spread distribution within the cerebrospinal fluid, ITB can tackle wide-spread and severe spasticity.

An early botulinum toxin A treatment in subacute stroke patients may prevent a disabling finger flexor stiffness six months later: a randomized controlled trial.

OBJECTIVE: The study asked whether an early botulinum toxin A (BTX-A) injection in subacute stroke patients may prevent a disabling finger flexor stiffness six months later. DESIGN: Single-blind, randomized pilot study. SETTING: Inpatient rehabilitation centre. SUBJECTS: Eighteen stroke patients, interval 4-6 weeks, non-functional arm, Fugl-Meyer arm score (0-66) <20, beginning elevated finger flexor tone, randomly allocated to group A or B. INTERVENTIONS: In group A patients 150 units BTX-A (Xeomin) injected into the deep and superficial finger (100 units) and wrist flexors (50 units), no injection in group B patients. Comprehensive rehabilitation in both groups. MAIN MEASURES: Primary variable was the Modified Ashworth Scale score (0-5) of the finger flexors; secondary variables were whole arm muscle tone with REPAS (a summary rating scale for resistance to passive movement), its motor control with the Fugl-Meyer arm score, and a disability scale, blindly assessed at T0 (start), T1 (four weeks) and T6 (six months). RESULTS: Homogeneous groups at T0. Significantly less finger flexor stiffness in the BTX-A group at T1 and T6, the mean (SD) Modified Ashworth Scale scores in group A (B) were: 1.7 ± 0.5 (1.6 ± 0.5) at T0; 0.4 ± 0.5 (1.9 ± 0.7) at T1; and 1.4 ± 0.7 (2.4 ± 0.9) at T6. Among the secondary measures, the disability score, namely the items pain and passive nail trimming, was lower in group A at T1 and T6. CONCLUSIONS: The results indicate an effect of early BTX-A injection on finger flexor stiffness six months later, presumably attributable to a reduced contracture development. Effect size calculation suggests inclusion of at least 17 patients per group excluding drop-outs in a warranted placebo-controlled trial.

[Mental distress and quality of life in tinnitus patients]. / Psychische Belastung und Lebensqualität bei Tinnituspatienten.

BACKGROUND: Tinnitus is a disease with a high prevalence that is often combined with psychiatric comorbidity. The aim of this study was to identify the dimensions of quality of life in which tinnitus patients are especially affected, and how these affections change during a therapy, including a hyperbaric oxygen therapy. MATERIAL AND METHODS: 120 patients suffering from tinnitus were examined at 3 time points: at the beginning (t1) and the end (t2) of a 2-week hyperbaric oxygen therapy, and 4 weeks later (t3). The following questionnaires were adopted: Hospital Anxiety and Depression Scale, Multidimensional Fatigue Inventory, and the quality of life instrument EORTC QLQ-C30. RESULTS: Compared with the general population, tinnitus patients were impaired in all areas of quality of life. The greatest differences were found in the scales Social, Cognitive, Emotional and Role Functioning and in the field of financial difficulties with effect sizes of about 1.5. During the therapy, the scores improved, reaching roughly the middle between the initial patients' scores and the values of the general population. The directly assessed subjective improvement due to the therapy was only marginally correlated with the differences in the questionnaires. CONCLUSION: Since there was no control group without hyperbaric oxygen therapy, the results do not justify conclusions about the effectiveness of this therapy. However, the findings document multiple impairments of the patients (especially psycho-social disturbances) and show hints for supportive offers.

Anisotropic interface magnetoresistance in Pt/Co/Pt sandwiches.

We report on an effect of reduced dimensionality on the magnetotransport in cobalt layers sandwiched by platinum. In a current in-plane geometry it is found that the resistivity depends on the magnetization orientation within the plane perpendicular to the current direction. The resistivity shows a symmetry adapted cos(2) dependence on the angle to the surface normal, with the maximum along the surface normal. The Co thickness dependence of the effect in Pt/Co/Pt sandwiches clearly points out that the mechanism behind this effect originates at the Co/Pt interfaces and is disparate to the texture induced geometrical size effect.

Comparison of an intermittent high-intensity vs continuous low-intensity physiotherapy service over 12 months in community-dwelling people with stroke: a randomized trial.

OBJECTIVE: This study compared two modes of physiotherapy service over 12 months in community-dwelling people with stroke, either following a train-wait train paradigm by providing bouts of intense physiotherapy, or a continuous less intense programme. DESIGN: Randomized trial. SETTING: Community-dwelling people with stroke. INTERVENTIONS: Fifty patients, first-time stroke, discharged home, following inpatient rehabilitation, allocated to two groups, A and B. Over 12 months, Group A (n = 25) received three two-month blocks of therapy at home, each block contained four 30 to 45 minute sessions per week, totalling 96 sessions. Group B (n = 25) continuously received two 30 to 45 minute sessions per week, totalling 104 sessions. MAIN OUTCOME MEASURES: Primary Rivermead Mobility Index (0-15), secondary upper- and lower-limb motor functions, Activities of Daily Living competence, tone and number of falls. RESULTS: Both groups were comparable at onset, the mean age in Group A (B) was 62.4 (61.9) years. A and B patients equally improved functions over time, between group differences did not occur. The initial (terminal) Rivermead Mobility Index was 9.4 ± 2.8 (12.2 ± 2.1) in Group A, and 8.5 ± 3.5 (11.2 ± 2.7) in Group B. More Group B patients fell seriously (7 versus 1). CONCLUSIONS: The intermittent high-intensity and continuous low-intensity therapy protocols were equally effective, the sheer intensity seems more important than the time-mode of application. The relatively young patients functionally improved in the first year after stroke, the reduced risk of serious falls in the intermittent high-intensity group should be validated.

IBZM SPECT and FDG PET in the differential diagnosis of Parkinsonian syndromes: comparison with respect to inter-rater agreement.

AIM: Both IBZM SPECT and FDG PET may be used for differentiation between Parkinson's disease (PD) and atypical neurodegenerative parkinsonian syndromes (APS). However, there are only very limited data of both modalities in the same subjects. The present study compared both modalities with respect to inter-rater agreement in 30 patients with neurodegenerative parkinsonian syndromes (PS) confirmed by FP-CIT SPECT. METHODS: IBZM SPECT and FDG PET were categorized as PD or APS by visual inspection of standardized report pages and statistical parametric maps (SPMs). Categorization was performed independently by five readers. Inter-rater agreement was quantified using Cohen's kappa kappa. RESULTS: IBZM SPECT resulted in PD and APS in 11 and 19 cases, respectively (majoritarian categorization). Inter-rater agreement was kappa=0.64+/-0.10. FDG PET resulted in PD and APS in 12 and 18 cases, respectively (majoritarian categorization). Inter-rater agreement was kappa=0.68+/-0.07. Majoritarian diagnosis disagreed between IBZM SPECT and FDG PET in 13 cases (43%). Semi-quantitative analysis of IBZM SPECT using the striatum-to-reference distribution volume ratio was in good agreement with visual categorization (area under ROC curve 0.92). CONCLUSION: In neurodegenerative PS, inter-rater agreement of visual analysis is substantial in both IBZM SPECT and FDG PET. Furthermore, (I) visual analysis of IBZM SPECT is reliable if adequate standardized image display is used, (II) visual analysis of FDG SPMs allows unique categorization as either PD or APS in most subjects, and (III) IBZM SPECT and FDG PET are discordant in a significant fraction of cases.

[Juvenile hyaline fibromatosis]. / Fibromatose hyaline juvénile.

BACKGROUND: Juvenile hyaline fibromatosis and infantile systemic hyalinosis are two rare autosomal recessive diseases arising from mutation in the capillary morphogenesis factor-2 gene. They are characterized by accumulation of hyaline material, in the skin in the first instance and in other organs in the second. We describe a case of juvenile hyaline fibromatosis. CASE REPORT: A 2-year-old girl presented gingival hyperplasia, skin papules, subcutaneous nodules and joints and bones lesion. A diagnosis of juvenile hyaline fibromatosis was suggested and this was confirmed by histopathology and genetic analyses. The patient presented frequent episodes of diarrhoea, which is evocative of infantile systemic hyalinosis. DISCUSSION: This case clearly illustrates the wide phenotypic range of juvenile hyaline fibromatosis. Diagnosis must be made as soon as possible to avoid cosmetic and functional handicap.

Video-oculography in multiple sclerosis: Links between oculomotor disorders and brain magnetic resonance imaging (MRI).

BACKGROUND: Eye movement abnormalities (EMA) are common in multiple sclerosis (MS). However, type and severity according to the MS stage are poorly known, especially in Radiologically Isolated Syndrome (RIS) and in Clinically Isolated Syndrome (CIS). Although MRI has been included in the MS diagnostic criteria, there may be clinical-radiological dissociation. OBJECTIVE: To analyze by video-oculography (VOG) prevalence of EMA in different MS phenotypes and study correlations with brain and cervical cord MRI T2 lesions location. METHODS: 76 participants were prospectively recruited (12 RIS, 10 CIS, 11 relapsing-remitting-MS, 10 secondary progressive-MS, 10 primary progressive MS and 23 gender and age-matched healthy controls). We analyzed fixations, anti-saccades, horizontal and vertical reflex saccades and smooth pursuit. RESULTS: EMA were frequent and of gradual severity from RIS to progressive forms. Internuclear ophthalmoplegia (INO) and centripetal hypermetria were strong arguments for the diagnosis of a demyelinating disorder versus a control population. Some EMA were linked to infratentorial T2 lesion location, but others like INO were not. CONCLUSION: This study confirm that EMA are common in all MS phenotypes, even at the earliest stages. VOG can be useful to detect demyelinating process at preclinical stage by highlighting subclinical EMA even in absence of characteristic lesions visible on MRI.

Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8.

Selective events during T cell repertoire development in the thymus include both the positive selection of cells whose receptors recognize self-major histocompatibility complex (MHC) molecules and negative selection (tolerance) of cells whose interaction with self-MHC is of high affinity. The affinity of T cell interactions with class I MHC molecules includes contributions by both the T cell receptor and the CD8 coreceptor. Therefore, by decreasing the affinity of the interaction with CD8, T cells whose receptors have relatively high affinities for self-MHC may survive negative selection. Such T cells were generated and those T cells reactive with self-MHC plus antigen also displayed low affinity for self.