Síndrome dolorosa miofascial, função do sistema descendente da dor e eficácia da estimulação elétrica intramuscular : ensaio clínico randomizado duplo-cego sham controlado exploratório

A síndrome dolorosa miofascial (MPS) é uma das causas mais prevalentes de dor crônica na população, provocando altos graus de incapacidade, sem normalmente responder ao tratamento analgésico conservador. Embora sua fisiopatologia não esteja completamente esclarecida, vários processos ocorrem tanto no tecido periférico quanto no nível do sistema nervoso periferico e central, levando a um processamento de neuroplasticidade mal adaptativa nas redes neurais da neuromatriz da dor, o que resulta na amplificação de sua percepção e na alteração comportamental observada em seus portadores. Evidências sugerem que existem três sistemas neurais primariamente envolvidos na dor da MPS: (i) o sistema corticoespinal; (ii) o sistema modulador descendente da dor: e (iii) o sistema regulador da neuroplasticidade. A estimulação elétrica intramuscular (IMES) é uma forma de estimulação neuromuscular periférica que promove aumento do fluxo sanguíneo regional, ativa centros relacionados ao processamento da dor e, de forma ascendente, também ativa as vias modulatórias da dor (efeito bottom-up). Nesta tese buscamos avaliar duas perguntas que deram origem a dois artigos: (1) se a disrupção do sistema modulador descendente da dor, aferida pelo CPM-task, correlaciona-se com disfunção na condução corticoespinal e desinibição no nível cortical, acessados pela Estimulação Magnética Transcraniana (TMS), e nível sérico do BDNF; e (2) avaliar os efeitos neuromodulatórios de 10 sessões de IMES comparados a intervenção sham em 24 pacientes do sexo feminino com idade de 18 a 65 anos, com dor crônica de origem miofascial do complexo craniocervicomandibular. Nossa hipótese era de que: (i) a disrupção do sistema modulador descendente da dor correlacionava-se com disfunção na condução corticoespinal, desinibição no nível cortical, e nível sérico do BDNF; (ii) que os efeitos neuromodulatórios da IMES se manifestariam como melhora clínica nos escores de dor e funcionalidade; e (iii) seus efeitos terapêuticos envolvessem mecanismos neuroplásticos implicados na secreção de BDNF, alteração da excitabilidade cortical e corticoespinal e potencialização do sistema modulador descendente da dor. RESULTADOS: (1) A análise MANCOVA, após ajuste para comparações múltiplas por meio do Teste de Bonferroni, revelou que os pacientes com disrupção do sistema modulador descendente da dor apresentaram maior Facilitação Intracortical (ICF; média ± DP) 1,43 (0,3) vs. 1,11 (0,12), maior excitabilidade do sistema corticoespinal (MEP; μV) 1.93 (0,54) vs. 1,40 (0,27), e níveis séricos de BDNF mais elevados (pg/Ml) 32,56 (9,95) vs. 25,59 (10,24), (p < 0,05 para todos), e (2) a análise de variância num modelo de efeito misto demonstrou redução nos escores de dor de -73,02% (IC95% = -95,28 to -52,30), e diminuição da disfunção em -43,19% (IC95%, -57,23 a -29,39), diminuição da excitabilidade corticoespinal (p=0,02), potencialização do sistema modulador descendente da dor ( p=0,01) e aumento dos níveis séricos de BDNF (p<0,01). Além disso, a magnitude do aumento do BDNF foi preditora dos efeitos nos níveis de dor e disfunção a longo prazo (Beta = 0,67; IC95% = 0,07 a 1,26). Esses achados sugerem que o enfraquecimento do sistema descendente inibitório da dor está associado ao aumento da ICF, MEP e níveis séricos do BDNF e o efeito bottom–up induzido pela IMES diminuiu a dor e reduziu a disfunção nessa amostra de pacientes. Esses efeitos podem ser mediados por melhora de mecanismos inibitórios corticoespinais. Outros achados sugerem que a magnitude do aumento do BDNF gerado pela IMES predizeram o impacto nos efeitos clínicos, ao longo de doze semanas, nessa população de pacientes.Myofascial pain syndrome (MPS) is one of the most prevalent causes of chronic pain in the population, causing high degrees of disability without normally responding to conservative analgesic treatment. Although its pathophysiology is not completely understood, several processes occur at both peripheral tisue and central and peripheral nervous system levels, leading to a maladaptive neuroplasticity processing in the pain neuromatrix networks, which results in the amplification of their perception and in the behavioral change observed in its carriers. Evidence suggests that there are three neural systems primarily involved in MPS pain: (i) the corticospinal system; (ii) the descending pain modulating system; and (iii) the neuroplasticity regulating system. Intramuscular electrical stimulation (IMES) is a form of peripheral neuromuscular stimulation that promotes increased regional blood flow, activates centers related to pain processing, and upwardly activates pain modulatory pathways (botton-up effect). In this thesis we aimed to evaluate two questions that gave rise to two articles: (1) if the disruption of the descending pain modulator system, measured by the CPM-task, correlates with corticospinal conduction dysfunction and cortical disinhibition, accessed by Magnetic Stimulation. Transcranial (TMS), and BDNF serum level; and (2) to evaluate the neuromodulatory effects of 10 IMES sessions compared to sham intervention in 24 female patients aged 18 to 65 years with chronic myofascial pain of the craniocervicomandibular complex. Our hypothesis was that: (i) disruption of the descending pain modulatory system was correlated with dysfunction in corticospinal conduction and disinhibition at cortical level and serum BDNF level; (ii) that the neuromodulatory effects of IMES would manifest as clinical improvement in pain scores and functionality; and (iii) its therapeutic effects involved neuroplastic mechanisms involving BDNF secretion, alteration of cortical and corticospinal excitability, and potentiation of the descending pain modulating system. RESULTS: (1) The MANCOVA analysis, after adjustment for multiple comparisons by the Bonferroni Test, revealed that patients with disruption of the descending pain modulatory system had higher Intracortical Facilitation (ICF; mean ± SD) 1.43 (0.3) vs. 1.11 (0.12), greater corticospinal system excitability (MEP; μV) 1.93 (0.54) vs. 1.40 (0.27), and higher serum BDNF levels (pg / Ml) 32.56 (9.95) vs. 25.59 (10.24), (P <0.05 for all), and (2) analysis of variance in a mixed-effect model showed a reduction in pain scores of -73.02% (95% CI = -95.28 to -52.30), and decreased dysfunction by -43,19% (95% CI, -57.23 to -29.39), decreased corticospinal excitability (p = 0.02), potentiation of the descending pain modulating system (p = 0.01) and increased levels BDNF serum levels (p <0.01). In addition, the magnitude of the increase in BDNF leves was predictive of long-term effects on pain and dysfunction levels (Beta = 0.67; 95% CI = 0.07 to 1.26). These findings suggest that the weakening of the descending pain inhibitory system is associated with increased ICF, MEP, and BDNF serum levels, and the IMES-induced bottom-up effect improved pain and reduced dysfunction in this patient population. These effects may be mediated by improvement of corticospinal inhibitory mechanisms. Other findings suggest that the magnitude of the increase in IMES-generated BDNF predicted the long-term impact on clinical effects in this patient population

Alteração de nervos cranianos como preditor de mortalidade em pacientes com infecção vertical pelo HIV

05

Insights about the neuroplasticity state on the effect of intramuscular electrical stimulation in pain and disability associated with Chronic Myofascial Pain Syndrome (MPS) : a double-blind, randomized, sham-controlled trial

Background: There is limited evidence concerning the effect of intramuscular electrical stimulation (EIMS) on the neural mechanisms of pain and disability associated with chronic Myofascial Pain Syndrome (MPS). Objectives: To provide new insights into the EIMS long-term effect on pain and disability related to chronic MPS (primary outcomes). To assess if the neuroplasticity state at baseline could predict the long-term impact of EIMS on disability due to MPS we examined the relationship between the serum brain-derived-neurotrophic-factor (BDNF) and by motor evoked potential (MEP). Also, we evaluated if the EIMS could improve the descending pain modulatory system (DPMS) and the cortical excitability measured by transcranial magnetic stimulation (TMS) parameters. Methods: We included 24 right-handed female with chronic MPS, 19-65 years old. They were randomically allocated to receive ten sessions of EIMS, 2 Hz at the cervical paraspinal region or a sham intervention (n = 12). Results: A mixed model analysis of variance revealed that EIMS decreased daily pain scores by -73.02% [95% confidence interval (CI) = -95.28 to -52.30] and disability due to pain -43.19 (95%CI, -57.23 to -29.39) at 3 months of follow up. The relative risk for using analgesics was 2.95 (95% CI, 1.36 to 6.30) in the sham group. In the EIMS and sham, the change on the Numerical Pain Scale (NPS0-10) throughout CPM-task was -2.04 (0.79) vs. -0.94 (1.18), respectively, (P = 0.01). EIMS reduced the MEP -28.79 (-53.44 to -4.15), while improved DPMS and intracortical inhibition. The MEP amplitude before treatment [(Beta = -0.61, (-0.58 to -0.26)] and a more significant change from pre- to post-treatment on serum BDNF) (Beta = 0.67; CI95% = 0.07 to 1.26) were predictors to EIMS effect on pain and disability due to pain. Conclusion: These findings suggest that a bottom-up effect induced by the EIMS reduced the analgesic use, improved pain, and disability due to chronic MPS. This effect might be mediated by an enhancing of corticospinal inhibition as seen by an increase in IC and a decrease in MEP amplitude. Likewise, the MEP amplitude before treatment and the changes induced by the EIMS in the serum BDNF predicted it's long-term clinical impact on pain and disability due MPS. The trial is recorded in ClinicalTrials.gov: NCT02381171

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Síndrome dolorosa miofascial, função do sistema descendente da dor e eficácia da estimulação elétrica intramuscular : ensaio clínico randomizado duplo-cego sham controlado exploratório

A síndrome dolorosa miofascial (MPS) é uma das causas mais prevalentes de dor crônica na população, provocando altos graus de incapacidade, sem normalmente responder ao tratamento analgésico conservador. Embora sua fisiopatologia não esteja completamente esclarecida, vários processos ocorrem tanto no tecido periférico quanto no nível do sistema nervoso periferico e central, levando a um processamento de neuroplasticidade mal adaptativa nas redes neurais da neuromatriz da dor, o que resulta na amplificação de sua percepção e na alteração comportamental observada em seus portadores. Evidências sugerem que existem três sistemas neurais primariamente envolvidos na dor da MPS: (i) o sistema corticoespinal; (ii) o sistema modulador descendente da dor: e (iii) o sistema regulador da neuroplasticidade. A estimulação elétrica intramuscular (IMES) é uma forma de estimulação neuromuscular periférica que promove aumento do fluxo sanguíneo regional, ativa centros relacionados ao processamento da dor e, de forma ascendente, também ativa as vias modulatórias da dor (efeito bottom-up). Nesta tese buscamos avaliar duas perguntas que deram origem a dois artigos: (1) se a disrupção do sistema modulador descendente da dor, aferida pelo CPM-task, correlaciona-se com disfunção na condução corticoespinal e desinibição no nível cortical, acessados pela Estimulação Magnética Transcraniana (TMS), e nível sérico do BDNF; e (2) avaliar os efeitos neuromodulatórios de 10 sessões de IMES comparados a intervenção sham em 24 pacientes do sexo feminino com idade de 18 a 65 anos, com dor crônica de origem miofascial do complexo craniocervicomandibular. Nossa hipótese era de que: (i) a disrupção do sistema modulador descendente da dor correlacionava-se com disfunção na condução corticoespinal, desinibição no nível cortical, e nível sérico do BDNF; (ii) que os efeitos neuromodulatórios da IMES se manifestariam como melhora clínica nos escores de dor e funcionalidade; e (iii) seus efeitos terapêuticos envolvessem mecanismos neuroplásticos implicados na secreção de BDNF, alteração da excitabilidade cortical e corticoespinal e potencialização do sistema modulador descendente da dor. RESULTADOS: (1) A análise MANCOVA, após ajuste para comparações múltiplas por meio do Teste de Bonferroni, revelou que os pacientes com disrupção do sistema modulador descendente da dor apresentaram maior Facilitação Intracortical (ICF; média ± DP) 1,43 (0,3) vs. 1,11 (0,12), maior excitabilidade do sistema corticoespinal (MEP; μV) 1.93 (0,54) vs. 1,40 (0,27), e níveis séricos de BDNF mais elevados (pg/Ml) 32,56 (9,95) vs. 25,59 (10,24), (p < 0,05 para todos), e (2) a análise de variância num modelo de efeito misto demonstrou redução nos escores de dor de -73,02% (IC95% = -95,28 to -52,30), e diminuição da disfunção em -43,19% (IC95%, -57,23 a -29,39), diminuição da excitabilidade corticoespinal (p=0,02), potencialização do sistema modulador descendente da dor ( p=0,01) e aumento dos níveis séricos de BDNF (p<0,01). Além disso, a magnitude do aumento do BDNF foi preditora dos efeitos nos níveis de dor e disfunção a longo prazo (Beta = 0,67; IC95% = 0,07 a 1,26). Esses achados sugerem que o enfraquecimento do sistema descendente inibitório da dor está associado ao aumento da ICF, MEP e níveis séricos do BDNF e o efeito bottom–up induzido pela IMES diminuiu a dor e reduziu a disfunção nessa amostra de pacientes. Esses efeitos podem ser mediados por melhora de mecanismos inibitórios corticoespinais. Outros achados sugerem que a magnitude do aumento do BDNF gerado pela IMES predizeram o impacto nos efeitos clínicos, ao longo de doze semanas, nessa população de pacientes.Myofascial pain syndrome (MPS) is one of the most prevalent causes of chronic pain in the population, causing high degrees of disability without normally responding to conservative analgesic treatment. Although its pathophysiology is not completely understood, several processes occur at both peripheral tisue and central and peripheral nervous system levels, leading to a maladaptive neuroplasticity processing in the pain neuromatrix networks, which results in the amplification of their perception and in the behavioral change observed in its carriers. Evidence suggests that there are three neural systems primarily involved in MPS pain: (i) the corticospinal system; (ii) the descending pain modulating system; and (iii) the neuroplasticity regulating system. Intramuscular electrical stimulation (IMES) is a form of peripheral neuromuscular stimulation that promotes increased regional blood flow, activates centers related to pain processing, and upwardly activates pain modulatory pathways (botton-up effect). In this thesis we aimed to evaluate two questions that gave rise to two articles: (1) if the disruption of the descending pain modulator system, measured by the CPM-task, correlates with corticospinal conduction dysfunction and cortical disinhibition, accessed by Magnetic Stimulation. Transcranial (TMS), and BDNF serum level; and (2) to evaluate the neuromodulatory effects of 10 IMES sessions compared to sham intervention in 24 female patients aged 18 to 65 years with chronic myofascial pain of the craniocervicomandibular complex. Our hypothesis was that: (i) disruption of the descending pain modulatory system was correlated with dysfunction in corticospinal conduction and disinhibition at cortical level and serum BDNF level; (ii) that the neuromodulatory effects of IMES would manifest as clinical improvement in pain scores and functionality; and (iii) its therapeutic effects involved neuroplastic mechanisms involving BDNF secretion, alteration of cortical and corticospinal excitability, and potentiation of the descending pain modulating system. RESULTS: (1) The MANCOVA analysis, after adjustment for multiple comparisons by the Bonferroni Test, revealed that patients with disruption of the descending pain modulatory system had higher Intracortical Facilitation (ICF; mean ± SD) 1.43 (0.3) vs. 1.11 (0.12), greater corticospinal system excitability (MEP; μV) 1.93 (0.54) vs. 1.40 (0.27), and higher serum BDNF levels (pg / Ml) 32.56 (9.95) vs. 25.59 (10.24), (P <0.05 for all), and (2) analysis of variance in a mixed-effect model showed a reduction in pain scores of -73.02% (95% CI = -95.28 to -52.30), and decreased dysfunction by -43,19% (95% CI, -57.23 to -29.39), decreased corticospinal excitability (p = 0.02), potentiation of the descending pain modulating system (p = 0.01) and increased levels BDNF serum levels (p <0.01). In addition, the magnitude of the increase in BDNF leves was predictive of long-term effects on pain and dysfunction levels (Beta = 0.67; 95% CI = 0.07 to 1.26). These findings suggest that the weakening of the descending pain inhibitory system is associated with increased ICF, MEP, and BDNF serum levels, and the IMES-induced bottom-up effect improved pain and reduced dysfunction in this patient population. These effects may be mediated by improvement of corticospinal inhibitory mechanisms. Other findings suggest that the magnitude of the increase in IMES-generated BDNF predicted the long-term impact on clinical effects in this patient population

Alteração de nervos cranianos como preditor de mortalidade em pacientes com infecção vertical pelo HIV

05