Longer Cortical Silent Period Length Is Associated to Binge Eating Disorder: An Exploratory Study.

Introduction: Although binge eating disorder (BED) is an eating disorder and obesity is a clinical disease, it is known that both conditions present overlapped symptoms related to, at least partially, the disruption of homeostatic and hedonistic eating behavior pathways. Therefore, the understanding of neural substrates, such as the motor cortex excitability assessed by transcranial magnetic stimulation (TMS), might provide new insights into the pathophysiology of BED and obesity. Objectives: (i) To compare, among BED, obesity, ex-obese, and HC (healthy control) subjects, the cortical excitability indexed by TMS measures, such as CSP (cortical silent period; primary outcome), SICI (intracortical inhibition), and ICF (intracortical facilitation; secondary outcome). (ii) To explore the relationship of the CSP, eating behavior (e.g., restraint, disinhibition, and hunger), depressive symptoms, and sleep quality among the four groups (BED, obesity, ex-obese, and HC). Methods: Fifty-nine women [BED (n = 13), obese (n = 20), ex-obese (n = 12), and HC (n = 14)] comprise the total sample for this study. Assessments: cortical excitability measures (CSP, SICI, and ICF), inhibition response task by the Go/No-go paradigm, and instruments to assess the eating psychopathology (Three-Factor Eating Questionnaire, Eating Disorder Examination Questionnaire, and Binge Eating Scale) were used. Results: A MANCOVA analysis revealed that the mean of CSP was longer in the BED group compared with other three groups: 24.10% longer than the obesity group, 25.98% longer than the HC group, and 25.41% longer than the ex-obese group. Pearson's correlations evidenced that CSP was positively associated with both eating concern and binge eating scores. Conclusion: The findings point out that BED patients present longer CSP, which might suggest an upregulation of intracortical inhibition. Additionally, CSP was positively correlated with Binge Eating Scale and eating concern scores. Further studies are needed.

The Evaluation of Medication Adherence in Patients Infected With HCV Receiving Protease Inhibitors: A Pilot Study.

Adherence to treatment is essential for hepatitis C cure. Studies show the complexity of the treatment due to side effects, many pills, and rigor in the schedules. The aim of this study was to evaluate the adherence to treatment with protease inhibitor in patients with hepatitis C. It is a longitudinal, observational, prospective pilot study with patients with hepatitis C genotype 1. Bimonthly consultations and biweekly calls for 20 weeks were performed. Evaluation methods for adherence were Measure of Adherence to Treatment score, patient report, count pills, and sustained virological response. Twenty-two patients were enrolled. Mean age was 54.0 ± 8.72 years; 50% were men, educational level was 7.9 ± 3.89 years for the study, and intake of pills was 2.2 ± 1.60 per day. Adverse events reported were fatigue (90.9%), muscular pain (72.7%), and nausea (68.2%). In total, 71.4% of patients took 100% of medications and were classified as having a high degree of adherence to treatment. The sustained virological response was not significant in relation to the high or low adherence degree. Measure of Adherence to Treatment score is a good instrument to measure adherence to protease inhibitor treatment. The adherence of patients undergoing long-term and complex treatments improves when the multidisciplinary team follows up every 7-15 days. The patient's access to the team through additional phone calls or medical/nursing appointment is essential to improve adherence.

Differential Neuroplastic Changes in Fibromyalgia and Depression Indexed by Up-Regulation of Motor Cortex Inhibition and Disinhibition of the Descending Pain System: An Exploratory Study.

Background: Major depressive disorder (MDD) and fibromyalgia (FM) present overlapped symptoms. Although the connection between these two disorders has not been elucidated yet, the disruption of neuroplastic processes that mediate the equilibrium in the inhibitory systems stands out as a possible mechanism. Thus, the purpose of this cross-sectional exploratory study was: (i) to compare the motor cortex inhibition indexed by transcranial magnetic stimulation (TMS) measures [short intracortical inhibition (SICI) and intracortical facilitation (ICF)], as well as the function of descending pain modulatory systems (DPMS) among FM, MDD, and healthy subjects (HS); (ii) to compare SICI, ICF, and the role of DPMS evaluated by the change on Numerical Pain Scale (NPS) during the conditioned pain modulation test (CPM-test) between FM and MDD considering the BDNF-adjusted index; (iii) to assess the relationship between the role of DPMS and the BDNF-adjusted index, despite clinical diagnosis. Patients and Methods: A cohort of 63 women, aged 18 to 75 years [FM (n = 18), MDD (n = 19), and HC (n = 29)]. Results: The MANCOVA analysis revealed that the mean of SICI was 53.40% larger in FM compared to MDD [1.03 (0.50) vs. 0.55 (0.43)] and 66.99% larger compared to HC [1.03 (0.50) vs. 0.34 (0.19)], respectively. The inhibitory potency of the DPMS assessed by the change on the NPS during CPM-test was 112.29 % lower in the FM compared to MDD [0.22 (1.37) vs. -0.87 (1.49)]. The mean of BDNF from FM compared to MDD was 35.70% higher [49.82 (16.31) vs. 14.12 (8.86)]. In FM, the Spearman's coefficient between the change in the NPS during CPM-test with the SICI was Rho = -0.49, [confidence interval (CI) 95%; -0.78 to -0.03]. The BDNF-adjusted index was positively correlated with the disinhibition of the DPMS. Conclusion: These findings support the hypothesis that in FM a deteriorated function of cortical inhibition, indexed by a higher SICI parameter, a lower function of the DPMS, together with a higher level of BDNF indicate that FM has different pathological substrates from depression. They suggest that an up-regulation phenomenon of intracortical inhibitory networks associated with a disruption of the DPMS function occurs in FM.

Intramuscular electrical stimulus potentiates motor cortex modulation effects on pain and descending inhibitory systems in knee osteoarthritis: a randomized, factorial, sham-controlled study.

BACKGROUND: Neuroplastic changes in nociceptive pathways contribute to severity of symptoms in knee osteoarthritis (KOA). A new look at neuroplastic changes management includes modulation of the primary motor cortex by transcranial direct current stimulation (tDCS). OBJECTIVES: We investigated whether tDCS combined with intramuscular electrical stimulation (EIMS) would be more efficacious than a sham (s) intervention (s-tDCS/s-EIMS) or a single active(a)-tDCS/s-EIMS intervention and/or s-tDCS/a-EIMS in the following domains: pain measures (visual analog scale [VAS] score and descending pain modulatory system [DPMS], and outcomes, and analgesic use, disability, and pain pressure threshold (PPT) for secondary outcomes. REGISTRATION: The trial is registered in Clinicaltrials.gov: NCT01747070. METHODS: Sixty women with KOA, aged 50-75 years old, randomly received five sessions of one of the four interventions (a-tDCS/a-EIMS, s-tDCS/s-EIMS, a-tDCS/s-EIMS, and s-tDCS/a-EIMS). tDCS was applied over the primary motor cortex (M1), for 30 minutes at 2 mA and the EIMS paraspinal of L1-S2. RESULTS: A generalized estimating equation model revealed the main effect of the a-tDCS/a-EIMS in the VAS pain scores at end treatment compared with the other three groups (P<0.0001). There existed a significant effect of time and a significant interaction between group and time (P<0.01 for both). The delta-(Δ) pain score on VAS in the a-tDCS/a-EIMS group was -3.59, 95% CI: -4.10 to -2.63. The (Δ) pain scores on VAS in the other three groups were: a-tDCS/s-EIMS=-2.13, 95% CI: -2.48 to -1.64; s-tDCS/a-EIMS=-2.25, 95% CI: -2.59 to -1.68; s-tDCS/s-EIMS MR =-1.77, 95% CI: -2.08 to -1.38. The a-tDCS/a-EIMS led to better effect in DPMS, PPT, analgesic use, and disability related to pain. CONCLUSION: This study provides additional evidence regarding additive clinical effects to improve pain measures and descending pain inhibitory controls when the neuromodulation of the primary motor cortex with tDCS is combined with a bottom-up modulation with EIMS in KOA. Also, it improved the ability to walk due to reduced pain and reduced analgesic use.

Potency of descending pain modulatory system is linked with peripheral sensory dysfunction in fibromyalgia: An exploratory study.

Fibromyalgia (FM) is characterized by chronic widespread pain whose pathophysiological mechanism is related to central and peripheral nervous system dysfunction. Neuropathy of small nerve fibers has been implicated due to related pain descriptors, psychophysical pain, and neurophysiological testing, as well as skin biopsy studies. Nevertheless, this alteration alone has not been previously associated to the dysfunction in the descending pain modulatory system (DPMS) that is observed in FM. We hypothesize that they associated, thus, we conducted a cross-sectional exploratory study.To explore small fiber dysfunction using quantitative sensory testing (QST) is associated with the DPMS and other surrogates of nociceptive pathways alterations in FM.We run a cross-sectional study and recruited 41 women with FM, and 28 healthy female volunteers. We used the QST to measure the thermal heat threshold (HTT), heat pain threshold (HPT), heat pain tolerance (HPT), heat pain tolerance (HPTo), and conditional pain modulation task (CPM-task). Algometry was used to determine the pain pressure threshold (PPT). Scales to assess catastrophizing, anxiety, depression, and sleep disturbances were also applied. Serum brain-derived neurotrophic factor (BDNF) was measured as a marker of neuroplasticity. We run multivariate linear regression models by group to study their relationships.Samples differed in their psychophysical profile, where FM presented lower sensitivity and pain thresholds. In FM but not in the healthy subjects, regression models revealed that serum BDNF was related to HTT and CPM-Task (Hotelling Trace = 1.80, P < .001, power = 0.94, R = 0.64). HTT was directly related to CPM-Task (B = 0.98, P = .004, partial-η = 0.25), and to HPT (B = 1.61, P = .008, partial η = 0.21), but not to PPT. Meanwhile, BDNF relationship to CPM-Task was inverse (B = -0.04, P = .043, partial-η = 0.12), and to HPT was direct (B = -0.08, P = .03, partial-η = 0.14).These findings high spot that in FM the disinhibition of the DPMS is positively correlated with the dysfunction in peripheral sensory neurons assessed by QST and conversely with serum BDNF.

Home-Based Transcranial Direct Current Stimulation Device Development: An Updated Protocol Used at Home in Healthy Subjects and Fibromyalgia Patients.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation (NIBS) method, which modulates the membrane potential of neurons in the cerebral cortex by a low-intensity direct current. tDCS is a low-cost technique with minimal adverse effects and easy application. This neurostimulation method has a promising future to improve pain therapy, treatment of neuropsychiatric disorders, and physical rehabilitation. Current studies demonstrate the benefits of using tDCS over consecutive multiple sessions. However, the daily displacement to the specialized centers, travel costs, and disruptions to daily activities are some of the difficulties faced by patients. Thus, to be more comfortable, easy-to-use, and not disrupt daily commitments, a home-based tDCS was designed. Therefore, the objective of this study was to evaluate the feasibility of a portable tDCS device for home use in healthy subjects and fibromyalgia patients. Despite increased tDCS use and a reasonably large body of research on the effects across a range of clinical conditions, there is a limited amount of research on developing secure devices that guarantee the dose and contain a block system to avoid excessive use. Therefore, we used a tDCS device with a security system to permit daily use for 20 minutes with a minimal interval of 12 hours between sessions. A programmer preconfigures the equipment, which has a neoprene cap that allows the electrode positions in any assembly, according to individualized protocols for treatments or research. After, researchers can assess the effectiveness of treatment, and its adherence using information kept in the device software. Results suggest that the device is feasible for home use, with proper monitoring of adherence and contact impedance. There were reports of a few adverse effects, which do not differ from those reported in the literature in studies with the treatment under direct supervision.

Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential.

The association of oral lichen planus (OLP) lesions with malignant transformation risk has remained a controversial topic and is of clinical importance. Therefore, the present study evaluated the expression levels of p16, Ki-67, budding uninhibited by benzimidazoles 3 (Bub-3) and sex-determining region Y-related high mobility group box 4 (SOX4), and their roles as precancerous biomarkers in OLP. A retrospective study was performed, in which tissue blocks of OLP, oral dysplasia (OD), cutaneous lichen planus (CLP) and oral fibrous hyperplasia (OFH) were used (n=120). A positivity index (PI) for p16, BUB3, Ki-67 and SOX4 expression was calculated in each group. The PI for p16 was 20.65% for OLP, 7.85% for OD, 86.59% for CLP and 11.8% for OFH, and the difference between these groups was statistically significant (P<0.001). PIs of Ki-67 were indicated as 11.6% for OLP, 14.4% for OD, 8.24% for CLP and 5.5% for OFH, and a statistically significant difference was observed between the groups (P<0.001). Notably, the expression levels of BUB3 were not statistically different among groups. The highest expression levels of SOX4 were identified in CLP (P<0.001 vs. OLP/CLP; P=0,001 vs. CLP/OD). The determined expression levels of p16 and Ki-67 suggest that specific OLP lesions may have an intermediate malignant potential and should be carefully followed up. The intense SOX4 staining in CLP indicated a different proliferation pattern of epithelium compared with oral mucosa cells. These findings suggest that SOX4 expression may also be associated with the different clinical courses of OLP and CLP.

Descending Control of Nociceptive Processing in Knee Osteoarthritis Is Associated With Intracortical Disinhibition: An Exploratory Study.

Based on the hypothesis that an imbalance in excitatory and inhibitory input is a central mechanism of knee osteoarthritis chronic pain (KOACP), this exploratory study had the following aims: to compare whether the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system indexed by the motor-evoked potential (MEP) and the cortical salient period (CSP) in patients with severe osteoarthritis (OA) and healthy controls; and to determine if there is correlation between the measures of intracortical inhibition (CSP, MEP) with changes on the numerical pain scale (NPS [0-10]) in KOACP during a conditioned pain modulation (CPM)-task considering the effect of self-reported function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and analgesic use.In a cross-sectional study, we included females (n = 21), with disability by pain or stiffness due to KOACP and healthy controls (n = 10), aged 19 to 75 years. The motor cortex excitability parameters (MEP and CSP) were assessed using the transcranial magnetic stimulation. We assessed the pain and disability by the WOMAC, and change on NPS (0-10) during CPM-task.A Multivariate analysis of covariance revealed that the adjusted mean (SD) on the MEP amplitude was 13.53% higher in the OA than in healthy subjects (1.33 [0.49] vs 1.15 [0.13]), respectively (P = 0.16). The adjusted mean (SD) on the CSP observed in OA patients was 23.43% lower than in healthy subjects (54.54 [16.10] vs 70.94 [22.87]), respectively (P = 0.01). The function of the descending pain modulatory system assessed by change on NPS (0-10) during a CPM-task was negatively correlated with the cortical excitability parameter indexed by the CSP (P = 0.001). Also, the CSP was negatively correlated with the pain and disability assessed by the WOMAC index.These findings support the hypothesis that the change in cortical plasticity in KOACP is associated with less intracortical inhibition, as measured by the CSP. These results show that the neural change in the motor cortex in KOACP is associated with pain and disability levels, and also with decreased activation of the endogenous pain-modulating system by a CPM-task.