Neuroplasticity changes in knee osteoarthritis (KOA) indexed by event-related desynchronization/synchronization during a motor inhibition task.

PURPOSE: Event-related desynchronisation (ERD) and event-related synchronisation (ERS) reflect pain perception and integration of the nociceptive sensory inputs. This may contribute to the understanding of how neurophysiological markers of Knee Osteoarthritis (KOA) patients can differ from control individuals, which would improve aspects such as prediction and prognosis. We performed a cross-sectional analysis of our cohort study (DEFINE cohort), KOA arm, with 71 patients, compared with 65 control participants. The study aimed to examine possible differences between ERD and ERS in control participants compared to Knee Osteoarthritis (KOA) patients when adjusting for important covariates. MATERIALS AND METHODS: We performed independent multivariate regression models considering as dependent variables the power value related to ERD and ERS for four different sensorimotor tasks (Motor Execution, Motor Imagery, Active Observation and Passive Observation) and four sensorimotor oscillations (Alpha, Beta, Low Beta, and High Beta), each model, controlled by age and sex. RESULTS: We demonstrate that the differences between KOA and healthy subjects are frequency specific, as most differences are in the beta bandwidth range. Also, we observed that subjects in the KOA group had significantly higher ERD and ERS. This may be correlated to the amount of lack of brain organisation and a subsequent attempt at compensation induced by KOA. CONCLUSIONS: Our findings strengthen the notion that subjects with KOA have a higher degree of brain plasticity changes that are also likely correlated to the degree of compensation and behavioural dysfunction.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

S1 Guidelines on Bone Impairment in Spinal Cord Injury.

During the acute and chronic phase of spinal cord injury (SCI) bone turnover and structure are affected. Bone mineral density of lower limbs is decreased up to 28%-50% below that of age-matched peers at 12-18 mo post injury. Coexisting secondary etiologies of osteoporosis may be present, and during ageing additional loss of bone occurs. All these compose a complex canvas of bone impairment after spinal cord injury and make the therapeutical approach challenging. The risk of fragility fractures is increased after the 2nd decade post SCI affecting the functionality and quality of life of individuals with SCI. Diagnostic flaws, lack of a ranking system to categorize the degree of bone impairment similar to the one of World Health Organization, and evidence-based clinical guidelines for management in SCI requires interdisciplinary cooperation and appropriate planning of future research and interventions. Spinal Cord Section of Hellenic Society of Physical Rehabilitation Medicine convened an expert panel working group on bone and spinal cord injury at the Pan-Hellenic Congress 2018 of PRM in Athens Greece, to establish an evidence-based position statement for bone loss in individuals with SCI of traumatic or non-traumatic etiology. This was reviewed by an International Task Force and used to create S1 Guidelines. This first version S1 guideline will work towards to provide help with prophylactic basic osteoporosis therapy diagnostic and therapeutic decisions in acute and chronic phase and rehabilitation countermeasures against osteoporosis related with spinal cord injury.

Post-discharge mortality in patients with traumatic spinal cord injury in a Brazilian hospital: a retrospective cohort.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate the survival outcomes in patients with traumatic spinal cord injury (TSCI). SETTING: A teaching hospital in Brazil. METHODS: A total of 434 patients diagnosed with TSCI (2004-2014) were included. Overall survival, standardized mortality ratios (SMR), and causes of death were assessed by Student's t-test, χ2 test, Kaplan-Meier analysis, and Cox proportional-hazards regression. RESULTS: The mean follow-up was 4.8 years (±3.3 years). Individuals with tetraplegia had a median survival of 11 years, with participants in the paraplegia group not reaching median survival. The overall mortality rate was 37 per 1000 person-years. Age-adjusted SMR was 28.8 (95% CI: 22.8-36). There were 77 deaths with 56 defined causes, of which pneumonia was the most frequent (35.7%). Combined infectious etiologies caused 55.3% of deaths. Multivariate analysis revealed higher mortality among individuals with tetraplegia vs. paraplegia in the first 2 years post injury (HR = 8.28, 95% CI: 2.76-24.80), after 2 years post injury (HR = 2.35, 95% CI: 1.31-4.24), and in all years combined (HR = 3.36, 95% CI: 2.04-5.52). CONCLUSION: Mortality among patients with TSCI was 28.8 times higher than in the reference population. In more than half of the cases, the cause of death was linked to infectious diseases. Pneumonia caused two times more deaths in individuals with tetraplegia than in individuals with paraplegia, with a higher impact in the first 2 years post injury. Reported findings indicate the need for a surveillance and prevention program with emphasis on vaccination and respiratory rehabilitation.

Massage for low-back pain.

BACKGROUND: Low-back pain (LBP) is one of the most common and costly musculoskeletal problems in modern society. It is experienced by 70% to 80% of adults at some time in their lives. Massage therapy has the potential to minimize pain and speed return to normal function. OBJECTIVES: To assess the effects of massage therapy for people with non-specific LBP. SEARCH METHODS: We searched PubMed to August 2014, and the following databases to July 2014: MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Index to Chiropractic Literature, and Proquest Dissertation Abstracts. We also checked reference lists. There were no language restrictions used. SELECTION CRITERIA: We included only randomized controlled trials of adults with non-specific LBP classified as acute, sub-acute or chronic. Massage was defined as soft-tissue manipulation using the hands or a mechanical device. We grouped the comparison groups into two types: inactive controls (sham therapy, waiting list, or no treatment), and active controls (manipulation, mobilization, TENS, acupuncture, traction, relaxation, physical therapy, exercises or self-care education). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures and followed CBN guidelines. Two independent authors performed article selection, data extraction and critical appraisal. MAIN RESULTS: In total we included 25 trials (3096 participants) in this review update. The majority was funded by not-for-profit organizations. One trial included participants with acute LBP, and the remaining trials included people with sub-acute or chronic LBP (CLBP). In three trials massage was done with a mechanical device, and the remaining trials used only the hands. The most common type of bias in these studies was performance and measurement bias because it is difficult to blind participants, massage therapists and the measuring outcomes. We judged the quality of the evidence to be "low" to "very low", and the main reasons for downgrading the evidence were risk of bias and imprecision. There was no suggestion of publication bias. For acute LBP, massage was found to be better than inactive controls for pain ((SMD -1.24, 95% CI -1.85 to -0.64; participants = 51; studies = 1)) in the short-term, but not for function ((SMD -0.50, 95% CI -1.06 to 0.06; participants = 51; studies = 1)). For sub-acute and chronic LBP, massage was better than inactive controls for pain ((SMD -0.75, 95% CI -0.90 to -0.60; participants = 761; studies = 7)) and function (SMD -0.72, 95% CI -1.05 to -0.39; 725 participants; 6 studies; ) in the short-term, but not in the long-term; however, when compared to active controls, massage was better for pain, both in the short ((SMD -0.37, 95% CI -0.62 to -0.13; participants = 964; studies = 12)) and long-term follow-up ((SMD -0.40, 95% CI -0.80 to -0.01; participants = 757; studies = 5)), but no differences were found for function (both in the short and long-term). There were no reports of serious adverse events in any of these trials. Increased pain intensity was the most common adverse event reported in 1.5% to 25% of the participants. AUTHORS' CONCLUSIONS: We have very little confidence that massage is an effective treatment for LBP. Acute, sub-acute and chronic LBP had improvements in pain outcomes with massage only in the short-term follow-up. Functional improvement was observed in participants with sub-acute and chronic LBP when compared with inactive controls, but only for the short-term follow-up. There were only minor adverse effects with massage.

Ultrasonography in myofascial neck pain: randomized clinical trial for diagnosis and follow-up.

OBJECTIVE: A definitive diagnosis of chronic neck pain (CNP) is sometimes not possible. The aim of this study was to understand the possible role of the deep fasciae in CNP and the utility of the ultrasonography in the diagnosis of myofascial neck pain. METHODS: The morphometric and clinical data of 25 healthy subjects and 28 patients with CNP were compared. For all subjects, the active and passive cervical range of motion (ROM) was analyzed and the neck pain disability questionnaire (NDPQ) was administered. The fascial thickness of the sternal ending of the sternocleidomastoid and medial scalene muscles was also analyzed by ultrasonography. RESULTS: There were significant differences between healthy subjects and patients with CNP in the thickness of the upper side of the sternocleidomastoid fascia and the lower and upper sides of the right scalene fascia both at the end of treatment as during follow-up. A significant decrease in pain and thickness of the fasciae were found. Analysis of the thickness of the sub-layers showed a significant decrease in loose connective tissue, both at the end of treatment and during follow-up. CONCLUSIONS: The data support the hypothesis that the loose connective tissue inside the fasciae may plays a significant role in the pathogenesis of CNP. In particular, the value of 0.15 cm of the SCM fascia was considered as a cut-off value which allows the clinician to make a diagnosis of myofascial disease in a subject with CNP. The variation of thickness of the fascia correlated with the increase in quantity of the loose connective tissue but not with dense connective tissue.

Factors associated with pain pressure threshold in both local and remote sites in knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent condition, and its most frequent symptom is pain that often leads to disability. Pain sensitization is a core feature of KOA, and it can be measured through quantitative sensory testing protocols such as pain pressure threshold (PPT). However, there is a lack of understanding about the factors that may influence changes in PPTs in the KOA population. OBJECTIVE: To explore the clinical and functional factors associated with PPTs in a sample of people with chronic KOA pain and to compare models of local (knees) and remote (thenar regions) sites. DESIGN: Cross-sectional analysis of a prospective cohort. SETTING: Primary care in public institution. PARTICIPANTS: 113 adults with KOA. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Multivariable regression analyses evaluating demographic, clinical, and functional variables that could be associated with local and remote PPTs (main outcomes) were performed. RESULTS: Both thenar region (adjusted-R2 : 0.29) and knee (adjusted-R2 : 0.45) models had the same significant negative association with being a female, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain levels (thenar: ß: -0.15, p = .002; knee: ß: -0.2, p < .001), and the 10-Meter Walking Test (thenar: ß: -0.05, p = .038; knee: ß: -0.08, p = .004). A small significant positive association with depressive symptoms was identified in both models, which acted as a confounder for WOMAC pain and was likely affected by unmeasured confounders. CONCLUSIONS: PPTs in KOA pain are associated with functional outcomes such as the 10-Meter Walking Test and activity-related pain intensity; thus more disability is associated with smaller pain thresholds. Similarity between models may suggest central sensitization.

Memory complaints after COVID-19: a potential indicator of primary cognitive impairment or a correlate of psychiatric symptoms?

Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV-2 infection or with symptoms of psychiatric conditions. A total of 608 COVID-19 survivors were evaluated in-person 6-11 months after hospitalization, with 377 patients assigned to a "no subjective memory complaint (SMC)" group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores. Follow-up evaluations included an objective cognitive battery and scale-based assessments of anxiety, depression, and post-traumatic stress symptoms. We found the perception of memory impairment in COVID-19 survivors to be more strongly associated to core symptoms of psychiatric conditions rather than to primary objective cognitive impairment. Univariate analysis indicated significant differences between the "no SMC" and SMC groups, both for the psychiatric symptom evaluations and for the cognitive evaluations (p < 0.05); however, the psychiatric symptoms all had large partial eta-squared values (ranging from 0.181 to 0.213), whereas the cognitive variables had small/medium partial eta-squared values (ranging from 0.002 to 0.024). Additionally, multiple regression analysis indicated that only female sex and depressive and post-traumatic stress symptoms were predictors of subjective memory complaints. These findings may help guide clinical evaluations for COVID-19 survivors presenting with memory complaints while also serving to expand our growing understanding of the relationship between COVID-19, subjective memory complaints, and the risk of cognitive decline.

The Endogenous Pain Modulatory System as a Healing Mechanism: A Proposal on How to Measure and Modulate It.

BACKGROUND: Chronic pain is highly burdening and multifactorial in etiology. The endogenous-pain-healing system restores body tissue to a non-painful state after an injury leading to pain, and its disruption could represent a relevant mechanism, especially for nursing interventions. AIM: To review the literature and summarize the results that support this hypothesis. METHODS: We hypothesized that the mechanism behind this system mainly depends on the endogenous pain modulatory system (EPMS), which is responsible for inhibiting pain after tissue healing is complete and facilitating it when tissue damage is still present. Different biomarkers can quantify EPMS functioning. We reviewed the literature and included relevant information regarding this hypothesis. RESULTS: First, conditioned pain modulation (CPM) measures pain inhibition and is a possible predictor for pain chronification. Second, motor cortex excitability measures the cortical control of the EPMS, which can be assessed through transcranial magnetic stimulation (using intracortical inhibition) or electroencephalography. Modifiable factors disrupt its functioning, such as sleep deprivation, medication overuse, and mental health status, but could be protective, such as exercise, certain medications, mind-body techniques, and non-invasive neuromodulation therapies. The acquisition of neurophysiological knowledge of how the chronicity of pain occurs and the EPMS involvement in this process may allow for better management of these patients. CONCLUSIONS: We raised the hypothesis that the impairment of the EPMS (altered cortical excitability and descendent pain modulation pathways) seems to be related to the disruption of the pain healing process and its chronicity. Further longitudinal studies evaluating the relationship between these biomarkers and chronic pain development are necessary.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported. Methods: In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment. Results: SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1ß serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Neurophysiological biomarkers of motor improvement from Constraint-Induced Movement Therapy and Robot-Assisted Therapy in participants with stroke.

Background: The mechanism of stroke recovery is related to the reorganization of cerebral activity that can be enhanced by rehabilitation therapy. Two well established treatments are Robot-Assisted Therapy (RT) and Constraint-Induced Movement Therapy (CIMT), however, it is unknown whether there is a difference in the neuroplastic changes induced by these therapies, and if the modifications are related to motor improvement. Therefore, this study aims to identify neurophysiological biomarkers related to motor improvement of participants with chronic stroke that received RT or CIMT, and to test whether there is a difference in neuronal changes induced by these two therapies. Methods: This study included participants with chronic stroke that took part in a pilot experiment to compare CIMT vs. RT. Neurophysiological evaluations were performed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), pre and post rehabilitation therapy. Motor function was measured by the Wolf Motor Function Test (WMFT) and Fugl-Meyer Assessment Upper Limb (FMA-UL). Results: Twenty-seven participants with chronic stroke completed the present study [mean age of 58.8 years (SD ± 13.6), mean time since stroke of 18.2 months (SD ± 9.6)]. We found that changes in motor threshold (MT) and motor evoked potential (MEP) in the lesioned hemisphere have a positive and negative correlation with WMFT improvement, respectively. The absolute change in alpha peak in the unlesioned hemisphere and the absolute change of the alpha ratio (unlesioned/lesioned hemisphere) is negatively correlated with WMFT improvement. The decrease of EEG power ratio (increase in the lesioned hemisphere and decrease in the unlesioned hemisphere) for high alpha bandwidths is correlated with better improvement in WMFT. The variable "type of treatment (RT or CIMT)" was not significant in the models. Conclusion: Our results suggest that distinct treatments (RT and CIMT) have similar neuroplastic mechanisms of recovery. Moreover, motor improvements in participants with chronic stroke are related to decreases of cortical excitability in the lesioned hemisphere measured with TMS. Furthermore, the balance of both EEG power and EEG alpha peak frequency in the lesioned hemisphere is related to motor improvement.

A model for personalized diagnostics for non-specific low back pain: the role of the myofascial unit.

Low back pain (LBP) is the leading cause of disability worldwide. Most LBP is non-specific or idiopathic, which is defined as symptoms of unknown origin without a clear specific cause or pathology. Current guidelines for clinical evaluation are based on ruling out underlying serious medical conditions, but not on addressing underlying potential contributors to pain. Although efforts have been made to identify subgroups within this population based on response to treatment, a comprehensive framework to guide assessment is still lacking. In this paper, we propose a model for a personalized mechanism-based assessment based on the available evidence that seeks to identify the underlying pathologies that may initiate and perpetuate central sensitization associated with chronic non-specific low back pain (nsLBP). We propose that central sensitization can have downstream effects on the "myofascial unit", defined as an integrated anatomical and functional structure that includes muscle fibers, fascia (including endomysium, perimysium and epimysium) and its associated innervations (free nerve endings, muscle spindles), lymphatics, and blood vessels. The tissue-level abnormalities can be perpetuated through a vicious cycle of neurogenic inflammation, impaired fascial gliding, and interstitial inflammatory stasis that manifest as the clinical findings for nsLBP. We postulate that our proposed model offers biological plausibility for the complex spectrum of clinical findings, including tissue-level abnormalities, biomechanical dysfunction and postural asymmetry, ecological and psychosocial factors, associated with nsLBP. The model suggests a multi-domain evaluation that is personalized, feasible and helps rule out specific causes for back pain guiding clinically relevant management. It may also provide a roadmap for future research to elucidate mechanisms underlying this ubiquitous and complex problem.

OPRM1 and BDNF polymorphisms associated with a compensatory neurophysiologic signature in knee osteoarthritis patients.

OBJECTIVE: The present study investigated the relationship between three genetic polymorphisms of OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) and EEG-measured brain oscillations in Knee Osteoarthritis (KOA) patients. MATERIALS AND METHODS: We performed a cross-sectional analysis of a cohort study (DEFINE cohort), KOA arm, with 66 patients, considering demographic (age, sex, and education), clinical (pain intensity and duration), OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) genotypes, and electrophysiological measures. Brain oscillations relative power from Delta, Theta, Alpha, Low Alpha, High Alpha, Beta, Low Beta and High Beta oscillations were measured during resting state EEG. Multivariate regression models were used to explore the main brain oscillation predictors of the three genetic polymorphisms. RESULTS: Our findings demonstrate that Theta and Low Beta oscillations are associated with the variant allele of OPRM1-rs1799971 (A118G) on left frontal and left central regions, respectively, while Alpha brain oscillation is associated with variant genotypes (CT/TT) of BDNF-rs6265 on frontal (decrease of oscillation power) and left central (increase of oscillation power) regions. No significant model was found for OPRM1-rs1799972 (C17T) in addition to the inclusion of pain intensity as a significant predictor of this last model. CONCLUSION: One potential interpretation for these findings is that polymorphisms of OPRM1 - that is involved with endogenous pain control - lead to increased compensatory oscillatory mechanisms, characterized by increased theta oscillations. Along the same line, polymorphisms of the BDNF lead to decreased alpha oscillations in the frontal area, likely also reflecting the disruption of resting states to also compensate for the increased injury associated with knee OA. It is possible that these polymorphisms require additional brain adaption to the knee OA related injury.

Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study.

Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (ß: -0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (ß: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (ß: -3.11) and central area (ß: -3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race.

Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain.

Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population.

Post-acute sequelae of SARS-CoV-2 associates with physical inactivity in a cohort of COVID-19 survivors.

The aim of this study was to determine whether Post-acute Sequelae of SARS-CoV-2 Infection (PASC) are associated with physical inactivity in COVID-19 survivors. This is a cohort study of COVID-19 survivors discharged from a tertiary hospital in Sao Paulo, Brazil. Patients admitted as inpatients due to laboratory-confirmed COVID-19 between March and August 2020 were consecutively invited for a follow-up in-person visit 6 to 11 months after hospitalization. Ten symptoms of PASC were assessed using standardized scales. Physical activity was assessed by questionnaire and participants were classified according to WHO Guidelines. 614 patients were analyzed (age: 56 ± 13 years; 53% male). Frequency of physical inactivity in patients exhibiting none, at least 1, 1-4, and 5 or more symptoms of PASC was 51%, 62%, 58%, and 71%, respectively. Adjusted models showed that patients with one or more persistent PASC symptoms have greater odds of being physically inactive than those without any persistent symptoms (OR: 1.57 [95% CI 1.04-2.39], P = 0.032). Dyspnea (OR: 2.22 [1.50-3.33], P < 0.001), fatigue (OR: 2.01 [1.40-2.90], P < 0.001), insomnia (OR: 1.69 [1.16-2.49], P = 0.007), post-traumatic stress (OR: 1.53 [1.05-2.23], P = 0.028), and severe muscle/joint pain (OR: 1.53 [95% CI 1.08-2.17], P = 0.011) were associated with greater odds of being physically inactive. This study suggests that PASC is associated with physical inactivity, which itself may be considered as a persistent symptom among COVID-19 survivors. This may help in the early identification of patients who could benefit from additional interventions tailored to combat inactivity (even after treatment of PASC), with potential beneficial impacts on overall morbidity/mortality and health systems worldwide.

Health-related quality of life and functionality in primary caregiver of surviving pediatric COVID-19.

Objectives: To prospectively assess health-related quality of life (HRQoL), global functionality, and disability in primary caregivers of surviving children and adolescents after COVID-19. Methods: A longitudinal observational study was carried out on primary caregivers of surviving pediatric post-COVID-19 patients (n = 51) and subjects without COVID-19 (n = 60). EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 12-question WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) were answered for both groups. The univariate regression analysis was carried out using SPSS (v 20) and significance was established at 5%. Results: The median duration between COVID-19 diagnosis in children and adolescents and longitudinal follow-up visits was 4.4 months (0.8-10.7). The median age of children and adolescents caregivers with laboratory-confirmed COVID-19 was similar to primary caregivers of subjects without laboratory-confirmed COVID-19 [43.2 (31.6-60.9) vs. 41.5 (21.6-54.8) years, p = 0.08], as well as similar female sex (p = 1.00), level of schooling (p = 0.11), social assistance program (p = 0.28), family income/month U$ (p = 0.25) and the number of household's members in the residence (p = 0.68). The frequency of slight to extreme problems (level ≥ 2) of the pain/discomfort domain according to EQ-5D-5L score was significantly higher in the former group [74% vs. 52.5%, p = 0.03, OR = 2.57 (1.14-5.96)]. The frequency of disability according to WHODAS 2.0 total score was similar to those without disability and unknown (p = 0.79); however, with a very high disability in both groups (72.5% and 78.3%). Further analysis of primary caregivers of children and adolescents with post-COVID-19 condition (PCC) [n = 12/51 (23%)] compared to those without PCC [n = 39/51(77%)] revealed no differences between demographic data, EQ-5D-5L and WHODAS 2.0 scores in both groups (p > 0.05). Conclusion: We longitudinally demonstrated that pain/discomfort were predominantly reported in approximately 75% of primary caregiver of COVID-19 patients, with high disability in approximately three-quarters of both caregiver groups. These data emphasized the prospective and systematic caregiver burden evaluation relevance of pediatric COVID-19.

Nociplastic Pain in Multiple Sclerosis Spasticity: Dermatomal Evaluation, Treatment with Intradermal Saline Injection and Outcomes Assessed by 3D Gait Analysis: Review and a Case Report.

Nociplastic pain has been introduced by the IASP as a third category of pain, distinct from nociceptive and neuropathic pain. Pathogenetically, it is considered to be a continuum of these two types of pain after becoming chronic. Repetitive peripheral painful stimulation causes a central sensitization with hypersensitivity of the corresponding spinal metamer or brain region. Therefore, signs of altered nociception, such as allodynia, may be found on the tissues of the related dermatome, myotome and sclerotome, and characterize nociplastic pain. This kind of pain was found in over 20% of people with multiple sclerosis (pwMS), a demyelinating autoimmune disease that affects the central nervous system. Nociplastic pain may be an amplifier of spasticity, the main pyramidal symptom that affects about 80% of pwMS. This article details the case of a 36-year-old woman with multiple sclerosis who was affected by spasticity and non-specific pain of the lower limbs, disabling on walking. Previous analgesic and muscle relaxant treatment had no benefits. The diagnosis of nociplastic pain on the cutaneous tissue of the anterolateral region of the left thigh and its treatment with intradermal normal saline injection on the painful skin area showed immediate and lasting effects on pain and spasticity, improving significantly the patient's balance and walking, as assessed by a 3D motion analysis and rating scales.