Brain compensatory mechanisms in depression and memory complaints in fibromyalgia: The role of theta oscillatory activity.

BACKGROUND: The different clinical presentations of fibromyalgia (FMS) may play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in this population. Understanding how these clinical presentations are associated with FMS's clinical and neurophysiological aspects is important when developing effective treatments. AIM: To explore the relationship between memory complaints and depressive symptoms, and the different clinical and neurophysiological characteristics of FMS. METHODS: Cross-sectional data analysis from a randomized clinical trial. Baseline demographics, physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) data from 63 FMS subjects were used. Multiple linear and logistic association models were constructed. RESULTS: Final regression models including different sets of predictions were statistically significant (p < 0.001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poor sleep quality, lower motor threshold, and higher relative theta power in the central area, are more likely to have clinical depression. Higher anxiety, pain and theta power were associated with an increase memory complaint. CONCLUSION: Depression symptoms seem to be associated with TMS-indexed motor threshold and psychosocial variables, while memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms may be catalyzed and/or triggered by some behavioral and clinical features such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment for FMS.

The role of symptoms severity, heart rate, and central sensitization for predicting sleep quality in patients with fibromyalgia.

BACKGROUND: Clinical predictors of sleep quality in patients with fibromyalgia syndrome (FMS) are still unknown. By identifying these factors, we could raise new mechanistic hypotheses and guide management approaches. We aimed to describe the sleep quality of FMS patients and to explore the clinical and quantitative sensory testing (QST) predictors of poor sleep quality and its subcomponents. METHODS: This study is a cross-sectional analysis of an ongoing clinical trial. We performed linear regression models between sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and demographic, clinical, and QST variables, controlling for age and gender. Predictors for the total PSQI score and its seven subcomponents were found using a sequential modeling approach. RESULTS: We included 65 patients. The PSQI score was 12.78 ± 4.39, with 95.39% classified as poor sleepers. Sleep disturbance, use of sleep medications, and subjective sleep quality were the worst subdomains. We found poor PSQI scores were highly associated with symptom severity (FIQR score and PROMIS fatigue), pain severity, and higher depression levels, explaining up to 31% of the variance. Fatigue and depression scores also predicted the subjective sleep quality and daytime dysfunction subcomponents. Heart rate changes (surrogate of physical conditioning) predicted the sleep disturbance subcomponent. QST variables were not associated with sleep quality or its subcomponents. CONCLUSIONS: Symptom severity, fatigue, pain, and depression (but no central sensitization) are the main predictors of poor sleep quality. Heart rate changes independently predicted the sleep disturbance subdomain (the most affected one in our sample), suggesting an essential role of physical conditioning in modulating sleep quality in FMS patients. This underscores the need for multidimensional treatments targeting depression and physical activity to improve the sleep quality of FMS patients.

Temporal Summation in Fibromyalgia Patients: Comparing Phasic and Tonic Paradigms.

Introduction: Fibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables. Materials and Methods: In this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity. Results: Fifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = -0.5, p = 0.009). Conclusion: Our results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.

Motor cortex inhibition as a fibromyalgia biomarker: a meta-analysis of transcranial magnetic stimulation studies.

Fibromyalgia (FM) is a common and refractory chronic pain condition with multiple clinical phenotypes. The current diagnosis is based on a syndrome identification which can be subjective and lead to under or over-diagnosis. Therefore, there is a need for objective biomarkers for diagnosis, phenotyping, and prognosis (treatment response and follow-up) in fibromyalgia. Potential biomarkers are measures of cortical excitability indexed by transcranial magnetic stimulation (TMS). However, no systematic analysis of current evidence has been performed to assess the role of TMS metrics as a fibromyalgia biomarker. Therefore, this study aims to evaluate evidence on corticospinal and intracortical motor excitability in fibromyalgia subjects and to assess the prognostic role of TMS metrics as response biomarkers in FM. We conducted systematic searches on PubMed/Medline, Embase, and Cochrane Central databases for observational studies and randomized controlled trials on fibromyalgia subjects that used TMS as an assessment. Three reviewers independently selected and extracted the data. Then, a random-effects model meta-analysis was performed to compare fibromyalgia and healthy controls in observational studies. Also, to compare active versus sham treatments, in randomized controlled trials. Correlations between changes in TMS metrics and clinical improvement were explored. The quality and evidence certainty were assessed following standardized approaches. We included 15 studies (696 participants, 474 FM subjects). The main findings were: (1) fibromyalgia subjects present less intracortical inhibition (mean difference (MD) = -0.40, 95% confidence interval (CI) -0.69 to -0.11) and higher resting motor thresholds (MD = 6.90 µV, 95% CI 4.16 to 9.63 µV) when compared to controls; (2) interventions such as exercise, pregabalin, and non-invasive brain stimulation increased intracortical inhibition (MD = 0.19, 95% CI 0.10 to 0.29) and cortical silent period (MD = 14.92 ms, 95% CI 4.86 to 24.98 ms), when compared to placebo or sham stimulation; (3) changes on intracortical excitability are correlated with clinical improvements - higher inhibition moderately correlates with less pain, depression, and pain catastrophizing; lower facilitation moderately correlates with less fatigue. Measures of intracortical inhibition and facilitation indexed by TMS are potential diagnostic and treatment response biomarkers for fibromyalgia subjects. The disruption in the intracortical inhibitory system in fibromyalgia also provides additional evidence that fibromyalgia has some neurophysiological characteristics of neuropathic pain. Treatments inducing an engagement of sensorimotor systems (e.g., exercise, motor imagery, and non-invasive brain stimulation) could restore the cortical inhibitory tonus in FM and induce clinical improvement.

Recruitment characteristics and non-adherence associated factors of fibromyalgia patients in a randomized clinical trial: A retrospective survival analysis.

INTRODUCTION: Fibromyalgia is a complex pain condition that affects mostly women. Given the disease's lack of understanding, patients report poor adherence to medication and mistrust of medical services. This study aims to describe the recruitment characteristics and non-adherence associated factors of fibromyalgia patients to an RCT. METHODS: We performed a retrospective longitudinal analysis with data from our ongoing RCT. We investigated characteristics of subjects recruited, consented, and randomized. Adherence was studied using survival analysis techniques, and its associated factors were identified using Cox proportional hazards regression model. RESULTS: 524 subjects were contacted, 269 were eligible, 61 consented and 40 subjects were randomized. Thirty-eight percent were non-adherent to the protocol with a median of visits of five. The recruitment survey reported that 90% would likely participate in RCTs, 52% had previous participation, and 19% were aware of RCTs by their physicians. Some barriers were investigator-related (staff's friendliness and receiving the results of their trial participation) and center-related (privacy-confidentiality issues and the institution's reputation), without difference between adherent and non-adherent participants. We report significant factors for non-adherence as VAS anxiety score of 5 or more (5.3 HR, p = 0.01), Body Mass Index (BMI) (0.91 HR, p = 0.041) and Quality of Life (QoL) - Personal development subdomain (0.89 HR, p = 0.046). CONCLUSION: Recruitment and adherence of fibromyalgia patients is a challenge; however, they seem eager to participate in RCTs. We recommend creating a comfortable, friendly and trusting environment to increase the recruitment rate. Higher anxiety, lower BMI and lower quality of life were associated with a higher attrition rate.

Barriers and facilitators for clinical trial participation of underrepresented and non-underrepresented fibromyalgia patients: A cross-sectional internet survey.

BACKGROUND: There is a need of well-powered randomized clinical trials in fibromyalgia. However, challenges for recruitment are presented. This study aims to describe and assess the perception of barriers and facilitators and the associated factors for the participation of underrepresented and non-underrepresented fibromyalgia patients. METHODS: We performed an online survey through REDCap (Research Electronic Data Capture) targeting fibromyalgia patients from April 7 to July 3, 2020 during the COVID-19 stay home mandate and it was restricted to the United States of America. We described and compared the survey characteristics between underrepresented and non-underrepresented participants, and we performed logistic regression models to assess the associated factors with clinical trial participation. RESULTS: In total, 481 completed the survey including 168 underrepresented fibromyalgia patients. Only (1) 11.09 % reported previous participation in clinical trials and the significant perceived barriers were investigator-related (lack of friendliness of research staff and the opportunity to receive the results) and center-related (privacy and confidentiality policies, and the institution's reputation); (2) the participation rate and perceived barriers and facilitators were similar between underrepresented and non-underrepresented patients; and was positively associated with low income, higher age, and clinical trial awareness from their physician; and negatively associated with the perception of investigator-related barriers; and (4) for the underrepresented population, the presence of emotional support. CONCLUSION: Our findings suggest low rates of participation, regardless of underrepresented population status. Strategies as involving their physician as liaison to increase the awareness of clinical trials, as well as improving patient-researcher communication should be considered in this population.

Decreased neural inhibitory state in fibromyalgia pain: A cross-sectional study.

OBJECTIVES: Chronic pain is one of the most common and challenging symptoms in fibromyalgia (FM). Currently, self-reported pain is the main criterion used by clinicians assessing patients with pain. However, it is subjective, and multiple factors can affect pain levels. In this study, we investigated the neural correlates of FM pain using conditioned pain modulation (CPM), electroencephalography (EEG), and transcranial magnetic stimulation (TMS). METHODS: In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 36 patients with fibromyalgia were included. We analyzed CPM, EEG variables and TMS measures and their correlation with pain levels as measured by a visual analog scale. Univariate and multivariate linear regression analyses were performed to identify the predictors of pain severity. RESULTS: We found: (1) no association between pain levels and CPM; (2) an association between reduced alpha and beta power over the central region in resting-EEG and higher pain levels; (3) an association between smaller event-related desynchronization (ERD) responses in theta and delta bands over the central region and higher pain levels; (4) an association between smaller ERD responses in theta and delta bands and smaller intracortical inhibition and higher intracortical facilitation ratios; (5) an association between smaller ERD responses in delta band and reduced CPM. CONCLUSIONS: Our results do not support CPM as a biomarker for pain intensity in FM. However, our specific EEG findings showing the relationship between pain, CPM and TMS measures suggest that FM leads to a disruption of inhibitory neural modulators and thus support CPM as a likely predictive marker of disrupted pain modulation system. These neurophysiological markers need to be further explored in potential future trials as to find novel targets for the treatment of FM.

Brain perfusion during manic episode and at 6-month follow-up period in bipolar disorder patients: Correlation with cognitive functions.

BACKGROUND: Patterns of altered cerebral perfusion and cognitive dysfunction have been described in Bipolar Disorder (BD) acute episodes and euthymia. Knowledge of the relationship between cognitive function and perfusion in a manic state and status when followed up is still limited. OBJECTIVE: To describe brain perfusion alterations and its relationship with cognitive impairment in patients with BD during manic episodes and after 6 months. METHODS: Observational-prospective study in 10 type I BD adults during moderate-severe manic episodes. We assessed sociodemographic data and clinical variables as well as cognitive function through Screening for Cognitive Impairment in Psychiatry (SCIP-S). Finally, we performed a Brain Perfusion SPECT using a Tc99m-ethyl cysteine dimer. RESULTS: During manic episodes, patients showed cognitive impairment with a mean SCIP-S score of 63.8 ± 17.16. This was positively correlated with perfusion measured as relative reuptake index (RRI) at the right temporal pole (ρ = 0.65 p = .0435) and negatively correlated with right the orbitofrontal cortex (ρ = -0.70 p = .0077) and the right subgenual cingulate cortex (ρ = -0.70 p = .0256). Episode severity measured by the Young Mania Rating Scale (YMRS) positively correlated with RRI at the right temporal pole (ρ = 0.75, p = .01). At follow-up, six patients were taking treatment and were euthymic, we found a negative correlation with the YMRS and RRI at the bilateral orbitofrontal cortex (ρ = -0.8827, p = .019). They did not show significant improvement in cognitive performance at SCIP-S, and there was negative correlation with the following of the SCIP-S subscales; processing speed with the bilateral dorsolateral prefrontal, the bilateral medial prefrontal, the left temporal pole cortex RRI, and verbal fluency with the bilateral anterior cingulate cortex RRI. CONCLUSION: Cognitive impairment was correlated with brain perfusion patterns at baseline and follow-up. Large sample size studies with longer follow-up are needed to describe the changes in perfusion and cognitive functions in BD.

Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol.

INTRODUCTION: Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control. METHODS AND ANALYSIS: A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)-primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study-CPM and TSPS-and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables. ETHICS AND DISSEMINATION: This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications. TRIAL REGISTRATION NUMBER: NCT03371225.

Características de los factores de riesgo cardiovascular en una población urbana y rural de la selva peruana, julio - 2014 / Characteristics of cardiovascular risk factors in an urban and rural population of the Peruvian jungle - July, 2014

Objetivo: Determinar las características del lugar de residencia y los factores de riesgo cardiovascular en una población de la selva peruana en julio 2014. Materiales y métodos: Estudio descriptivo transversal realizado en individuos entre 30 y 74 años sin diagnóstico ni tratamiento de enfermedad cardiovascular en una población urbana y una rural del distrito de Yantaló. La muestra se obtuvo a partir del programa Power Analysis and Sample Size Software (PASS) y estuvo conformada por 268 personas (152 habitantes urbanos y 116 rurales). Los factores estudiados fueron hipertensión arterial (HTA), diabetes mellitus (DM), índice de masa corporal (IMC), índice cintura-cadera (ICC) y tabaquismo. Resultados: La población urbana presentó un mayor porcentaje de HTA (18,4%), mientras que los otros factores de riesgo no presentaron diferencias significativas. Conclusiones: El único factor de riesgo que mostró asociación significativa con el lugar de residencia fue la HTA. En contraste, los otros factores de riesgo del estudio no presentaron diferencias entre ambas poblaciones, lo que demostraría que el distrito de Yantaló se encuentra inmerso en un proceso de transición epidemiológica debido a la urbanización.

Objective: To determine the characteristics of the place of residence and the cardiovascular risk factors in a Peruvian jungle population in July 2014. Materials and methods: A descriptive cross-sectional study conducted in individuals between 30 and 74 years old without a diagnosis of or treatment for a cardiovascular disease in an urban and rural population of the district of Yantaló. The sample was obtained using the Power Analysis and Sample Size Software (PASS) program, and consisted of 268 people (152 urban and 116 rural residents). The studied factors were hypertension (HBP), diabetes mellitus (DM), body mass index (BMI), waist-hip ratio (WHR) and smoking. Results: The urban population had higher rates of hypertension (18.4%), while the other risk factors showed no significant differences between the two populations. Conclusions: The only risk factor that showed a significant association with the place of residence was hypertension. In contrast, the other risk factors of the study showed no differences between the two populations, which demonstrates that the district of Yantaló is involved in a process of epidemiological transition due to urbanization.

Determinación de riesgo cardiovascular y edad vascular según el score de Framingham en pacientes del Hospital Nacional Arzobispo Loayza / Determination of cardiovascular risk and vascular age by the Framingham score in patients at the Arzobispo Loayza Hospital

Las enfermedades cardiovasculares ocupan el cuarto lugar de carga de enfermedad en Perú, y en los últimos 7 años, la población de alto riesgo cardiovascular se ha incrementado. OBJETIVO: Determinar el riesgo cardiovascular y edad vascular según el score de Framingham de los pacientes del Hospital Nacional Arzobispo Loayza así como determinar su factor de riesgo más prevalente. Y las características clínicas de los pacientes con mediano y alto riesgo. MATERIAL Y MÉTODOS: Estudio descriptivo, observacional, transversal. Se encuestaron a 238 pacientes hospitalizados en el Servicio de Medicina Interna del hospital. Se consideró: edad, género, diabetes, tabaquismo, IMC y presión arterial. Los datos fueron analizados con el programa SPSS v.21. RESULTADOS: Se encontró que el mayor porcentaje de la población de estudio presentó mediano y alto riesgo, siendo el factor más prevalente la diabetes y la mayoría hombres. La diferencia entre la edad cronológica y la edad vascular fue en promedio 6,9 años. CONCLUSIÓN: La población estudiada tuvo mediano y alto riesgo por lo que se deberían tomar medidas de prevención primaria y secundaria.

Cardiovascular diseases rank fourth place of disease burden in Peru, and in the last 7 years, the population of high cardiovascular risk has increased. OBJECTIVE: Determine the cardiovascular risk and vascular age according to the Framingham score in patients attending the "Hospital Nacional Arzobispo Loayza", as well as to determine the most prevalent factor. Furthermore, to determine the clinical characteristics of patients with mild and high risk. MATERIAL AND METHODS: This is a descriptive, observational, cross-sectional study. 238 hospitalized patients in internal medicine wards were surveyed. Variables such as age, gender, diabetes, smoking, BMI and blood pressure were considered. The data were analyzed using SPSS v.21. RESULTS: The highest percentage of the population was found within the mild and high risk categories, with diabetes being the most prevalent factor. The average difference between chronological age and vascular age was 6.9 years. CONCLUSION: The majority of the population has mild and high risk, thus primary and secondary prevention measures should be taken. (Horiz Med 2015; 15(2): 27-34)