Home-Based Exercise Training in the Recovery of Multisystem Inflammatory Syndrome in Children: A Case Series Study.

OBJECTIVE: To assess the potential therapeutic role of exercise on health-related quality of life, assessed by the Pediatric Outcomes Data Collection Instrument (PODCI), coronary flow reserve (CFR), cardiac function, cardiorespiratory fitness, and inflammatory and cardiac blood markers in multisystemic inflammatory syndrome in children (MIS-C) patients. METHODS: This is a case series study of a 12-wk, home-based exercise intervention in children and adolescents after MIS-C diagnosis. From 16 MIS-C patients followed at our clinic, 6 were included (age: 7-16 years; 3 females). Three of them withdrew before the intervention and served as controls. The primary outcome was health-related quality of life, assessed PODCI. Secondary outcomes were CFR assessed by 13N-ammonia PET-CT imaging, cardiac function by echocardiography, cardiorespiratory fitness, and inflammatory and cardiac blood markers. RESULTS: In general, patients showed poor health-related quality of life, which seemed to be improved with exercise. Additionally, exercised patients showed improvements in coronary flow reserve, cardiac function, and aerobic conditioning. Non-exercised patients exhibited a slower pattern of recovery, particularly in relation to health-related quality of life and aerobic conditioning. CONCLUSIONS: Our results suggest that exercise may play a therapeutic role in the treatment of post-discharge MIS-C patients. As our design does not allow inferring causality, randomized controlled trials are necessary to confirm these preliminary findings.

Effects of exercise training on brain metabolism and cognitive functioning in sleep apnea.

Impaired glucose metabolism reflects neuronal/synaptic dysfunction and cognitive function decline in patients with obstructive sleep apnea (OSA). The study investigated the extent to which exercise training (ET) improves cerebral metabolic glucose rate (CMRgl) and cognitive function in patients with OSA. Patients with moderate to severe OSA were randomly assigned to ET (3 times/week, n = 23) or no intervention (control, n = 24). Echocardiography and apolipoprotein ε4 (APOEε4) genotyping were obtained at baseline. Both groups underwent cardiopulmonary exercise testing, polysomnography, cognitive tests, brain magnetic resonance imaging, and 18F-fluoro-2-deoxy-D-Glucose positron emission tomography (18FDG-PET) at baseline and study end. Compared with control, exercise-trained group had improved exercise capacity, decreased apnea-hypopnea index (AHI), oxygen desaturation and arousal index; increased attention/executive functioning, increased CMRgl in the right frontal lobe (P < 0.05). After ET an inverse relationships occurred between CMRgl and obstructive AHI (r = - 0.43, P < 0.05) and apnea arousal index (r = - 0.53, P < 0.05), and between the changes in CMRgl and changes in mean O2 saturation during sleep and non-rapid eye movement sleep (r = - 0.43, P < 0.05), desaturation during arousal (r = - 0.44, P < 0.05), and time to attention function testing (r = - 0.46, P < 0.05). ET improves OSA severity and CMRg in the frontal lobe, which helps explain the improvement in attention/executive functioning. Our study provides promising data that reinforce the growing idea that ET may be a valuable tool to prevent hypoxia associated with decreased brain metabolism and cognitive functioning in patients with moderate to severe OSA.Trial registration: NCT02289625 (13/11/2014).

Migraine and balance impairment: Influence of subdiagnosis, otoneurological function, falls, and psychosocial factors.

OBJECTIVE: To assess the balance sensory organization among patients with migraine, considering the influence of migraine subdiagnosis, otoneurological function, falls, and psychosocial factors. BACKGROUND: Migraine has been associated with vestibular symptoms and balance dysfunction; however, neither comprehensive balance assessment nor associated factors for greater impairment have been addressed thus far. METHODS: Patients from a tertiary headache clinic with a diagnosis of episodic migraine with aura (MWA), without aura (MWoA), and chronic migraine (CM) were included for this cross-sectional study (30 patients per group). Thirty headache-free controls (CG) were recruited. Participants underwent a comprehensive evaluation protocol, including the Sensory Organization Test (SOT) and otoneurological examination. Questionnaires about fear of falls, dizziness disability, and kinesiophobia were administered. RESULTS: All migraine groups presented lower composite SOT scores than controls (CG: 82.4 [95% confidence interval (CI): 79.5-85.3], MWoA: 76.5 [95% CI: 73.6-79.3], MWA: 66.5 [95% CI: 63.6-69.3], CM: 69.1 [95% CI: 66.3-72.0]; p < 0.0001). Compared to controls and to MWoA, MWA and CM groups exhibited greater vestibular (CG: 75.9 [95% CI: 71.3-80.4], MWoA: 67.3 [95% CI: 62.7-71.8], MWA: 55.7 [95% CI: 51.2-60.3], CM: 58.4 [95% CI: 53.8-63.0]; p < 0.0001) and visual functional impairment (CG: 89.6 [95% CI: 84.2-94.9], MWoA: 83.2 [95% CI: 77.9-88.6], MWA: 68.6 [95% CI: 63.3-74.0], CM: 71.9 [95% CI: 66.5-77.2], p < 0.0001). Fall events during the assessment were documented more often among patients with migraine (CG: 0.0, interquartile range [IQR], 0.0, 0.0); MWoA: 1.0 [IQR: 1.0, 1.0], MWA: 2.0 [IQR: 1.8, 4.3], CM: 1.0 [IQR: 1.0, 2.0]; p = 0.001). The SOT scores correlated with fear of falls (r = -0.44), dizziness disability (r = -0.37), kinesiophobia (r = -0.38), and migraine frequency (r = -0.38). There was no significant influence of the vestibular migraine diagnosis in the study outcomes when used as a covariate in the analysis (composite score [F = 3.33, p = 0.070], visual score [F = 2.11, p = 0.149], vestibular score [F = 1.88, p = 0.172], somatosensory score [F = 0.00, p = 0.993]). CONCLUSIONS: Aura and greater migraine frequency were related to falls and balance impairment with sensory input manipulation, although no otoneurological alterations were detected. The diagnosis of vestibular migraine does not influence the balance performance. The vestibular/visual systems should be considered in the clinical examination and treatment of patients with migraine.

In-depth cardiovascular and pulmonary assessments in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: A case series study.

We assessed PET-CT myocardial blood flow (MBF) using N-13 ammonia, brachial flow-mediated dilation, and cardiopulmonary exercise test in five post-discarged MIS-C survivors. None of the patients (median age: 9, range: 7-18 years; 3 females; 2 males) had preexisting pediatric chronic conditions. At the follow-up visit, two patients exhibited severe perfusion defect developed in the left ventricular cavity, suggesting extensive myocardial ischemia (MBF <2.0) and one patient showed persistent mild pericardial effusion. Others two patients demonstrated endothelial dysfunction. Nevertheless, all patients had lower predicted values in the VO2peak , VO2VAT , OUES, and O2 Pulse (range: 35.2%-64.5%; 15.6%-38.2%; 1.0-1.3 L/min; 4-7 ml/beat), respectively. Our d suggested that previously health MIS-C patients had impaired MBF, endothelial dysfunction and lower cardiopulmonary capacity at follow-up analysis. Multidisciplinary further investigations should be conducted to reinforce these findings.

Home-Based Exercise Training in Childhood-Onset Takayasu Arteritis: A Multicenter, Randomized, Controlled Trial.

Introduction: Childhood-onset Takayasu Arteritis (c-TA) is a rare, large-vessel vasculitis seen in children that could predisposing patients to a high risk of mortality. Exercise has the potential to improve overall health in several diseases, but evidence remains scant in c-TA. The main objective of this study was to investigate the safety and potential therapeutic effects of exercise in c-TA. Methods: This was a 12-week, multicenter, randomized, controlled trial, to test the effects of a home-based, exercise intervention vs. standard of care in c-TA patients in remission. The primary outcomes were arterial inflammation, assessed by [18F] FDG- PET/MRI and systemic inflammatory markers. Secondary outcomes included, physical activity levels, functionality, body composition, disease-related parameters, and quality of life. Results: Thirty-seven patients were assessed for eligibility, which represents the total number of c-TA patients being followed by the three specialized medical ambulatory services in Sao Paulo. After exclusions, fourteen c-TA patients (71.4% females) aged 12-25 years were randomly allocated into exercised (n=5) and non-exercised groups (n=9). Exercise did not exacerbate arterial inflammation. In fact, exercised patients had a reduction in the frequency of vessel segments with severe inflammation, whereas the non-exercised patients had an opposite response (P=0.007). Greater improvements in visceral fat, steps per day, functionality and physical component SF-36 were observed in the exercised patients (P ≤ 0.05). Conclusions: Exercise is safe and may improve visceral fat, physical activity levels, functionality, and physical component SF-36 in c-TA patients. Thus, exercise arises as a novel, evidence-based intervention to improve general health in c-TA. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03494062?term=NCT03494062&draw=2&rank=1, identifier NCT03494062.

Preserved repetition in thalamic afasia. A pathophysiological hypothesis.

The ability to repeat words is almost always preserved in thalamic aphasia. The pathophysiology of both thalamic aphasia and preservation of repetition are not fully understood. In a case of severe aphasia with preserved repetition after a left thalamic hemorrhage, MRI disclosed left thalamic lesion and loss of fractional anisotropy in the left centrum semiovale. FDG-PET showed severe hypometabolism in the left cerebral hemisphere, except for superior and transverse temporal gyri, calcarine fissure and frontopolar regions. Primary sensory function may be less functionally dependent on thalamic connections than heteromodal and paralimbic areas, which have connections with several thalamic nuclei. The extensive cortical hypometabolism due to diaschisis may have been responsible for the severity of the aphasia, whereas the less severe reduction of metabolism in the superior and transverse temporal gyri, and also, albeit less evident, in Broca's area, might explain the preservation of repetition.

A capacidade de repetir palavras é quase sempre preservada na afasia talâmica. A fisiopatologia da afasia talâmica assim como a da preservação da repetição não são totalmente compreendidas. Em um caso de afasia grave com repetição preservada após hemorragia talâmica esquerda, a RM revelou lesão talâmica esquerda e perda de anisotropia fracionada no centro semioval. O FDG-PET revelou hipometabolismo grave no hemisfério cerebral esquerdo, exceto nos giros temporais superiores e transversos, fissura calcarina e regiões frontopares. A função sensorial primária pode ser menos funcionalmente dependente das conexões talâmicas do que as áreas heteromodais e paralímbicas, que têm conexões com vários núcleos talâmicos. O hipometabolismo cortical extenso devido à diasquise pode ter sido responsável pela gravidade da afasia, enquanto a redução menos severa do metabolismo nos giros temporal superior e transverso, e também, embora menos evidente, na área de Broca, poderia explicar a preservação da repetição.

Preserved repetition in thalamic afasia. A pathophysiological hypothesis / Preservação da repetição na afasia talâmica. Uma hipótese fisiopatológica

ABSTRACT. The ability to repeat words is almost always preserved in thalamic aphasia. The pathophysiology of both thalamic aphasia and preservation of repetition are not fully understood. In a case of severe aphasia with preserved repetition after a left thalamic hemorrhage, MRI disclosed left thalamic lesion and loss of fractional anisotropy in the left centrum semiovale. FDG-PET showed severe hypometabolism in the left cerebral hemisphere, except for superior and transverse temporal gyri, calcarine fissure and frontopolar regions. Primary sensory function may be less functionally dependent on thalamic connections than heteromodal and paralimbic areas, which have connections with several thalamic nuclei. The extensive cortical hypometabolism due to diaschisis may have been responsible for the severity of the aphasia, whereas the less severe reduction of metabolism in the superior and transverse temporal gyri, and also, albeit less evident, in Broca's area, might explain the preservation of repetition.

RESUMO. A capacidade de repetir palavras é quase sempre preservada na afasia talâmica. A fisiopatologia da afasia talâmica assim como a da preservação da repetição não são totalmente compreendidas. Em um caso de afasia grave com repetição preservada após hemorragia talâmica esquerda, a RM revelou lesão talâmica esquerda e perda de anisotropia fracionada no centro semioval. O FDG-PET revelou hipometabolismo grave no hemisfério cerebral esquerdo, exceto nos giros temporais superiores e transversos, fissura calcarina e regiões frontopares. A função sensorial primária pode ser menos funcionalmente dependente das conexões talâmicas do que as áreas heteromodais e paralímbicas, que têm conexões com vários núcleos talâmicos. O hipometabolismo cortical extenso devido à diasquise pode ter sido responsável pela gravidade da afasia, enquanto a redução menos severa do metabolismo nos giros temporal superior e transverso, e também, embora menos evidente, na área de Broca, poderia explicar a preservação da repetição.

Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study.

Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrated that melatonin supplementation and a short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in patients with melatonin deficiency (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for 3 months. All four studied patients presented increased BAT volume and activity measured by positron emission tomography-MRI. We also found an improvement in total cholesterol and triglyceride blood levels without significant effects on body weight, liver fat, and HDL and LDL levels. Albeit not statistically significant, fasting insulin levels and HOMA of insulin resistance decreased in all four patients. The present results show that oral melatonin replacement increases BAT volume and activity and improves blood lipid levels in patients with melatonin deficiency, suggesting that melatonin is a possible BAT activator. Future studies are warranted because hypomelatoninemia is usually present in aging and appears as a result of light-at-night exposure and/or the use of ß-blocker drugs.