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).

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.

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.

[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.

Mechanical arm trainer for the treatment of the severely affected arm after a stroke: a single-blinded randomized trial in two centers.

OBJECTIVE: To test whether training with a new mechanical arm trainer leads to better outcomes than electrical stimulation of the paretic wrist extensors in subacute stroke patients with severe upper limb paresis. Electrical stimulation is a standard and reimbursable form of therapy in Germany. DESIGN: Randomized controlled trial of 54 inpatients enrolled 4-8 wks from stroke onset, mean upper-extremity subsection of Fugl-Meyer assessment (0-66) at admission less than 18. In addition to standard care, all patients practiced 20-30 mins arm trainer or electrical stimulation every workday for 6 wks, totaling 30 sessions. Primary outcome was the Fugl-Meyer assessment, secondary outcomes were the Box and Block test, the Medical Research Council and the modified Ashworth scale, blindly assessed at enrollment, after 6 wks, and at 3-mo follow-up. RESULTS: Both groups were homogeneous at study onset. Shoulder pain occurred in two arm trainer patients. The primary Fugl-Meyer assessment outcome improved for both groups over time (P < 0.001), but this improvement did not differ between groups. The initial (terminal) mean Fugl-Meyer assessment scores were 8.8 +/- 4.8 (19.2 +/- 14.5) for the arm trainer and 8.6 +/- 3.5 (13.6 +/- 7.9) for the electrical stimulation group. No patient could transport a block initially, but at completion significantly more arm trainer patients were able to transport at least three blocks (five vs. zero, P = 0.023). No significant differences were observed between the groups on the secondary Box and Block outcome at follow-up (eight vs. four patients). All Box and Block responders had an initial Fugl-Meyer assessment > or =10. CONCLUSIONS: Arm trainer training did not lead to a superior primary outcome over electrical stimulation training. However, "good performers" on the secondary outcome seemed to benefit more from the arm trainer training.

Aerobic treadmill plus Bobath walking training improves walking in subacute stroke: a randomized controlled trial.

OBJECTIVE: To evaluate the immediate and long-term effects of aerobic treadmill plus Bobath walking training in subacute stroke survivors compared with Bobath walking training alone. DESIGN: Randomized controlled trial. SETTING: Rehabilitation unit. SUBJECTS: Fifty patients, first-time supratentorial stroke, stroke interval less than six weeks, Barthel Index (0-100) from 50 to 80, able to walk a minimum distance of 12 m with either intermittent help or stand-by while walking, cardiovascular stable, minimum 50 W in the bicycle ergometry, randomly allocated to two groups, A and B. INTERVENTIONS: Group A 30 min of treadmill training, harness secured and minimally supported according to patients' needs, and 30 min of physiotherapy, every workday for six weeks, speed and inclination of the treadmill were adjusted to achieve a heart rate of HR: (Hrmax-HRrest)*0.6+HRrest; in group B 60 min of daily physiotherapy for six weeks. MAIN OUTCOME MEASURES: Primary outcome variables were the absolute improvement of walking velocity (m/s) and capacity (m), secondary were gross motor function including walking ability (score out of 13) and walking quality (score out of 41), blindly assessed before and after the intervention, and at follow-up three months later. RESULTS: Patients tolerated the aerobic training well with no side-effects, significantly greater improvement of walking velocity and capacity both at study end (p =0.001 versus p =0.002) and at follow-up (p <0.001 versus p <0.001) in the experimental group. Between weeks 0 and 6, the experimental group improved walking speed and capacity by a mean of.31 m/s and 91 m, the control group by a mean of 0.16 m/s and 56 m. Between weeks 0 and 18, the experimental group improved walking speed and capacity by a mean of 0.36 m/s and 111 m, the control group by a mean of 0.15 m/s and 57 m. Gross motor function and walking quality did not differ at any time. CONCLUSIONS: Aerobic treadmill plus Bobath walking training in moderately affected stroke patients was better than Bobath walking training alone with respect to the improvement of walking velocity and capacity. The treatment approach is recommended in patients meeting the inclusion criteria. A multicentre trial should follow to strengthen the evidence.

[Development of a robotic walking simulator for gait rehabilitation]. / Entwicklung eines robotergestützten Laufsimulators zur Gangrehabilitation.

Restoration of gait is a major concern of rehabilitation after stroke or spinal cord injury. Modern concepts of motor learning favour a task-specific repetitive approach, i.e. "whoever wants to learn to walk again must walk." However, the physical demands this places on the therapist, is a limiting factor in the clinical routine setting. This article describes a robotic walking simulator for gait training that enables wheelchair-bound subjects to freely carry out repetitive practicing of an individually adapted gait pattern under simulation of the manual guidance of an experienced therapist. The technical principle applied makes use of programmable footplates with permanent foot/machine contact in combination with compliance control. The solution chosen comprises a planar parallel-serial hybrid kinematic system with three degrees of freedom that moves the feet in the sagittal plane. Gait analysis while floor walking and stair climbing, clinical practicability and safety aspects were the basis for the design. A variable compliance control enables man-machine interaction, ranging from purely position controlled movement to full compliance during swing phase above a virtual ground profile. In full compliance mode the robotic walking simulator behaves like a haptic device. The concept presented offers new prospects for individualized gait rehabilitation.

Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate whether the combined approach of botulinum toxin type A (BtxA) and electrical stimulation was more effective than the toxin alone in the treatment of chronic upper limb spasticity after stroke. DESIGN: Randomized, placebo-controlled study with four treatment groups: 1000 units BtxA (Dysport) + electrical stimulation (A), 1000 units BtxA (B), placebo + electrical stimulation (C) and placebo (D). SETTING: A neurological rehabilitation clinic. SUBJECTS: Twenty-four stroke patients with chronic upper limb spasticity after stroke, six patients in each treatment group. INTERVENTIONS: Intramuscular injection of either toxin or placebo into six upper imb flexor muscles. In group A and C additional electrical stimulation of the injected muscles with surface electrodes, three times half an hour each day for three days. MAIN OUTCOME MEASURES: Muscle tone rated with the modified Ashworth score, limb position at rest and difficulties encountered during three upper limb motor tasks assessed before and 2, 6 and 12 weeks after injection. RESULTS: Most improvements were observed in patients of group A. Cleaning the palm (p = 0.004) differed across groups. Pairwise comparison for this target variable showed that group A differed from group B and D (p <0.01), but not from C. Indicative across-group differences were obtained for elbow spasticity reduction (p = 0.011), and improvement of putting the arm through a sleeve (p = 0.020). CONCLUSIONS: The placebo-controlled trial favours the concept that electrical stimulation enhances the effectiveness of BtxA in the treatment of chronic upper limb flexor spasticity after stroke.

[Plasma tryptophan bioavailability during chronic urticaria]. / Biodisponibilité plasmatique du tryptophane au cours de l'urticaire chronique.

OBJECTIVES: Chronic idiopathic urticaria is known to have psychogenic component with a triggering or favoring effect. Different tests or evaluation scales have been unable to identify a specific psychological profile. Erythrocyte-specific membrane transport of tyrptophan (TRP), the main plasma precursor of cerebral serotonin synthesis, controls, by a erythrocyte-specific storage and release mechanism, circulating TRP homeostasis. Bioavailability of circulating TRP is a factor controlling serotonin synthesis in the brain. An evaluation of the rate of TRP transfer could be a biochemical approach to chronic urticaria more informative than psychological tests. PATIENTS AND METHODS: A kinetic study of L-TRP influx into circulating erythrocytes was conducted in 17 patients with chronic urticaria with no detectable cause and in 35 healthy controls. Blood samples were marked with 3H-TRP. Maximum L-TRP-specific influx (Vmax) was expressed in mumol/cell/min. The urticaria patients also underwent psychological testing to determine anxiety and depression scores using standardized scales (Hamilton). RESULTS: Mean Vmax was not significantly difference between the two groups. Vmax values were quite similar in all the control subjects but showed wide dispersion in the urticaria group. Three subgroups were found in the urticaria patients depending on Vmax: those with Vmax equivalent in control levels (+2 SD), those with Vmax less then 2 SD (29% of the patients) and those with Vmax greater than 2 SD of control levels (23% of the patients). Thus more than 50% of the urticaria patients had perturbed erythrocyte-specific L-TRP influx. The anxiety and depression scores obtained from the psychological evaluation were not correlated with Vmax. DISCUSSION: Erythrocyte-specific TRP membrane transport, evaluated by Vmax. Would not appear to be perturbed in chronic urticaria. Even though the urticaria patients could be divided into three groups according to their Vmax, the mean value was not significantly different from that in controls. These findings do not allow a conclusion concerning a perturbation of bioavailability of plasmatic TRP and any possible central serotoninergic dysfunction in chronic urticaria.

[Value of functional electrostimulation in patients with paraplegia]. / Stellenwert der funktionellen Elektrostimulation bei Patienten mit Querschnittlähmung.

This 1-year follow-up study included 17 patients with spinal cord injuries who participated in a functional electrical stimulation (FES) program for restoration of the ability to stand and walk. Four tetraplegic patients reached a mean FES-assisted standing duration of 6.8 min after 6 weeks. After 1 year three patients had stopped FES-assisted standing due to orthostatic problems and only used the system for cyclic stimulation of quadriceps muscles while lying down. Ten paraplegic patients had a mean standing duration of 22.6 min. The gait velocity (gait distance) of seven patients ranged from 2.9 to 24.2 m/min (from 4 to 335 m) in seven patients. Due to flexor spasm in two and unrealistic expectations in seven cases, four patients stopped the program and five only practiced FES-assisted standing. One patient continued FES walking after 1 year. Three patients with an incomplete cervical lesion who had been able to walk a short distance before treatment achieved constant improvement their gait ability. Their gait velocity/walking distance without FES improved for a mean of +33.3%/+163.8%, after 6 weeks. Assuming that FES is used according to the level of impairment, the results favor broader application of the method in the rehabilitation of patients with spinal cord injuries.

Immediate effects of therapeutic facilitation on the gait of hemiparetic patients as compared with walking with and without a cane.

OBJECTIVES: Although the neurodevelopmental technique (Bobath) is the most widely used approach in the gait rehabilitation of hemiparetic subjects in Europe, there is little neurophysiological evidence for its presumed effects on gait symmetry and facilitation of paretic muscles during the therapeutic intervention. The study, therefore, investigated the immediate effects of gait entrainment by a physical therapist on the gait of hemiparetic subjects. METHODS: Cycle parameters, gait symmetry, hip joint movement and the electromyographic activity of several lower limb muscles were assessed in 22 patients during a classic intervention by five Bobath therapists and while walking with and without a cane. RESULTS: Multivariate statistics revealed that, while being assisted by the therapist, patients walked faster (P = 0.022), with a longer relative stance period of the affected leg (P = 0.005), a higher symmetry (P = 0.002), larger hip extension (P = 0.001) and more activation (P = 0.026) of the Mm. triceps surae, vastus lateralis, biceps femoris and gluteus medius as compared to walking with and without a cane. Extensor spasticity of the plantar-flexor tended to increase (n.s.). In five subjects, no after-effect could be documented 1 h after a gait training of 30 min. CONCLUSIONS: The study confirmed a more balanced walking pattern in conjunction with facilitation of various weight bearing muscles during the therapeutic intervention. A prolonged single stance period of the affected leg, an unobstructed hip movement, enhanced weight acceptance and a faster gait seemed to be responsible for the observed immediate effects of the therapeutic intervention.

Short-term electrical stimulation enhances the effectiveness of Botulinum toxin in the treatment of lower limb spasticity in hemiparetic patients.

The study tested the spasmolytic effect of Botulinum toxin A in two groups of hemiparetic patients with lower limb spasticity: in the first group (n = 5) 2000 U Dysport were injected into the soleus, tibialis posterior and both heads of gastrocnemius muscles alone; the second (n = 5) received additional repetitive alternating electrical stimulation of M. tibialis anterior and plantar flexors for 30 min six times per day during the 3 days following the injection. Muscle tone, rated by the Ashworth spasticity score, and gait analysis including recording of vertical ground reaction forces, were assessed before and 4 weeks after injection. The combined treatment proved to be more effective with respect to the clinically assessed reduction of muscle tone, gait velocity, stride length, stance- and swing-symmetry (P < 0.05). The result is discussed with reference to animal experiments demonstrating enhanced toxin uptake and accelerated onset of its paralytic effect by electrical stimulation.

Restoration of gait by combined treadmill training and multichannel electrical stimulation in non-ambulatory hemiparetic patients.

Functional electrical stimulation and treadmill training with partial body weight support through suspension by a parachute harness were combined for gait restoration in 11 chronic non-ambulatory hemiparetic patients. Individually adjusted multichannel stimulation of the trunk and of upper and lower limb muscles, as well as a motor driven treadmill, induced functional gait within 3 to 6 weeks. The improvement of gait ability was assessed by the Functional Ambulation Category test. Other motor functions were rated by the Rivermead Motor Score. The leg muscle strength, stride length, cadence, gait velocity and gait pattern were recorded. In seven of the patients, we did a single case research A-B-A study that showed that this combined approach had advantages, in regard to gait restoration and walking velocity (p <0.05) as compared with our common physiotherapeutic programme.

Treadmill training with partial body weight support compared with physiotherapy in nonambulatory hemiparetic patients.

BACKGROUND AND PURPOSE: Treadmill training with partial body weight support is a new and promising therapy in gait rehabilitation of stroke patients. The study intended to investigate its efficiency compared with gait training within regular physiotherapy in nonambulatory patients with chronic hemiparesis. METHODS: An A-B-A single-case study design compared treadmill training plus partial body weight support (A) with physiotherapy based on the Bobath concept (B) in seven nonambulatory hemiparetic patients. The minimum poststroke interval was 3 months, and each treatment phase lasted 3 weeks. Variables were gait ability assessed by the Functional Ambulation Category, other motor functions tested by the Rivermead Motor Assessment, muscle strength assessed by the Motricity Index, muscle tone rated by the Modified Ashworth Spasticity Scale, and gait cycle parameters. RESULTS: Treadmill training was more effective with regard to restoration of gait ability (P < .05) and walking velocity (P < .05). Other motor functions improved steadily during the study. Muscle strength did not change, and muscle tone varied in an unsystematic way. The ratio of cadence to stride length did not alter significantly. CONCLUSIONS: Treadmill training offers the advantages of task-oriented training with numerous repetitions of a supervised gait pattern. It proved powerful in gait restoration of nonambulatory patients with chronic hemiparesis. Treadmill training could therefore become an adjunctive tool to regain walking ability in a shorter period of time.

Restoration of gait by functional electrical stimulation in paraplegic patients: a modified programme of treatment.

Restoration of standing and of gait by functional electrical stimulation in clinically complete paraplegic patients was modified in the course of treatment and in the stimulation parameters. By substituting an initial cyclic muscle strengthening with an active stimulated standing, four patients with T3-11 lesions started walking with electrical stimulation in 10-17 days. They walked without ankle-foot orthoses. With a satisfactory stride length of 0.75-0.97 m, their gait velocity ranged from very slow to that of a leisurely healthy gait. Already established stimulation of the quadriceps muscles for standing and of the peroneal nerves for lower limb flexion during the swing phase of gait was applied. Diminished limb flexion after several weeks was restored by an increase of the stimulation frequency of the peroneal nerve from 20 to 60 Hz. EMG and kinesiological measurements displayed an improved direct response of the ankle as well as of the reflex mediated hip, knee and ankle flexion response. At the same time stimulation frequency was reduced to 16 Hz for the quadriceps muscles in order to reduce fatigue.

Restoration of standing, weight-shift and gait by multichannel electrical stimulation in hemiparetic patients.

The effects of multichannel electrical stimulation of standing, weight-shift and gait were studied in hemiparetic patients. The ground reaction forces under both feet were assessed by two force plates during standing and weight-shift of 11 patients with and without three-channel stimulation of the pelvic and knee muscles. Stance symmetry and rate of the weight-shift significantly improved (p = 0.05) for 11.4% and 50.8% respectively during the stimulation. The gait of three hemiparetic patients was treated by adaptable, individually fitted four-channel stimulation. Besides peroneal nerve, knee extensor and flexor, hip extensor and abductor muscles, a shoulder-arm stimulation was introduced to elevate a depressed shoulder, initiate arm swing and erect the trunk. Gait parameters including symmetry improved consistently after the 25 stimulation sessions: velocity 33%, cadence 5%, stride length 26%, stance symmetry ratio from 0.62 to 0.97. Moreover the gait pattern was restored in all patients. The study investigated a possibility of neurophysiologically based treatment by the stimulation of standing, weight-shift and gait.

Effect of urapidil on the performance of ischaemic myocardium in anaesthetized dogs.

The effect of urapidil on the ischaemic myocardium was studied in eight anaesthetized dogs. Stenosis of the left descending coronary artery reduced blood flow and systolic contraction of the post-stenotic myocardium by about 50%; the end-diastolic length of the post-stenotic myocardium and the end-diastolic pressure increased, while aortic pressure slightly decreased. Subsequent administration of urapidil (0.25 + 0.25 + 0.5 + 1.0 mg/kg intravenously) did not affect the systolic shortening and end-diastolic length of the myocardium supplied by the left circumflux coronary artery, while the stroke volume and the systolic shortening of the ischaemic myocardium increased. The latter was correlated with a decrease in the heart rate (r = -0.92), but not with the reduction in aortic pressure. Urapidil by itself does not impair the performance of the ischaemic myocardium, but might be beneficial in decreasing the heart rate or suppressing reflex tachycardia during reduction of the afterload.