Autonomic Nervous System Dysregulation Research Articles

Long-term neurodevelopment outcomes of hand, foot and mouth disease inpatients infected with EV-A71 or CV-A16, a retrospective cohort study

ABSTRACT Hand, foot and mouth disease (HFMD) is a common infectious disease in western Asia area and the full range of the long-term sequelae of HFMD remains poorly described. We conducted a retrospective hospital-based cohort study of HFMD patients with central nervous system (CNS) complications caused by EV-A71 or CV-A16 between 2010 and 2016. Patients were classified into three groups, including CNS only, autonomic nervous system (ANS) dysregulation, and cardiorespiratory failure. Neurologic examination, neurodevelopmental assessments, Magnetic Resonance Imaging (MRI) and lung function, were performed at follow up. Of the 176 patients followed up, 24 suffered CNS only, 133 ANS dysregulation, and 19 cardiorespiratory failure. Median follow-up period was 4.3 years (range [1.4–8.3]). The rate of neurological abnormalities was 25% (43 of 171) at discharge and 10% (17 of 171) at follow-up. The rates of poor outcome were significantly different between the three groups of complications in motor (28%, 38%, 71%) domain (p=0.020), but not for cognitive (20%, 24%, 35%), language (25%, 36%, 41%) and adaptive (24%, 16%, 26%) domains (p = 0.537, p = 0.551, p = 0.403). For children with ventilated during hospitalization, 41% patients (14 of 34) had an obstructive ventilatory defect, and one patient with scoliosis had mixed ventilatory dysfunction. Persistent abnormalities on brain MRI were 0% (0 of 7), 9% (2 of 23) and 57% (4 of 7) in CNS, ANS and cardiorespiratory failure group separately. Patients with HFMD may have abnormalities in neurological, motor, language, cognition, adaptive behaviour and respiratory function. Long-term follow-up programmes for children’s neurodevelopmental and respiratory function may be warranted.

Heart rate variability in psychiatric disorders: Implications for cardiovascular risk

Background: The autonomic nervous system (ANS) dysregulation is a major risk factor of adverse cardiovascular (CV) events. Aims and Objectives: The aim of the study was as follows: (1) To determine heart rate variability (HRV) in physically healthy patients with major depressive disorder (MDD) and generalized anxiety disorder (GAD) as a primary diagnosis and their comparison with healthy controls. (2) To compare HRV in patients with MDD versus patients with GAD. Materials and Methods: In this cross-sectional study, 120 volunteer subjects in the age group of 20–55 years comprising 80 patients, divided into two groups, 40 with MDD alone without comorbid illness and other 40 with GAD as a primary diagnosis along with 40 age- and sex-matched healthy controls were included using convenient sampling. Short-term electrocardiogram (

Brief Autonomic Assessment in Concussion Clinic

To examine the feasibility and tolerability of administering a brief autonomic assessment via capnometry and pupillometry in an outpatient concussion clinic. Both acute and chronic phases of concussion have been associated with autonomic nervous system (ANS) dysregulation. Few concussion clinics currently employ autonomic assessments, which could enhance diagnostic accuracy and treatment recommendations. Although less-studied in outpatient concussion clinics, pupillometry and capnometry are two well-validated, peripheral autonomic assessment approaches that together provide information about both sympathetic and parasympathetic responses. In addition to being objective measures, they are fast and non-invasive. In order to investigate the potential utility of these measures as an addition to clinic procedures, the present study sought to examine their feasibility and tolerability as an adjunctive assessment in clinic. This project employed a prospective, observational research design. Eight patients (ages 20-65, 4 females) diagnosed with concussion (>1 month post injury) underwent a 2-minute baseline capnometry that measured end-tidal CO2, respiration rate, pulse rate, and oxygen saturation. Their pupillary response to light was captured using a pupillometer. Tolerability and feasibility were measured via the following metrics: patient tolerability and comfort Likert scales and administration details (e.g., total duration, logistical difficulties, clinic flow variables). Average rating of comfort for the capnometer and pupillometer were between comfortable (4) to very comfortable (5) on a 5-point Likert scale. There were no difficulties due to participant discomfort or time limitations among all patients, and minimal issues with administration logistics were noted. Both measures were completed for all participants in <5 minutes. Capnometry and pupillometry were found to be both tolerable among patients and feasible to administer in a concussion clinic. Given the ease of administration, further studies should investigate the utility of these portable devices in concussion clinics to objectively identify those at risk for persistent post-concussion symptoms and for early treatment stratification.

Maternal long-chain polyunsaturated fatty acid status during early pregnancy: Association with child behavioral problems and the role of autonomic nervous system activity

The prenatal environment, including availability of critical nutrients, has a profound impact on offspring development. The present study examined the association between maternal long-chain polyunsaturated fatty acid (LC-PUFA) status during pregnancy and later child behavioral problems at the age of 5-6 years. In light of evidence of autonomic nervous system (ANS) dysregulation in some behavioral problems, study further tested if the above association is statistically mediated by cardiac ANS activity. Data was collected as part of the Amsterdam Born Children and their Development-study and complete data were available for 1717 mothers and their offspring. Maternal LC-PUFA status was assessed during early pregnancy (mean gestation=12.7, SD=2.5 weeks) and quantified as levels of docosahexenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), as well as the ratio of n-6:n-3 fatty acids. Child emotional problems and peer problems (internalizing problems), as well as conduct problems and inattention/hyperactivity (externalizing problems), were assessed using the Strengths and Difficulties Questionnaire as rated by the mother and teacher at 5-6 years. Child cardiac respiratory sinus arrhythmia (RSA), pre-ejection period (PEP), and heart rate (HR) were utilized as measures of ANS activity at 5-6 years. The results confirmed an association between maternal LC-PUFA status and internalizing behavioral problems as rated by the mother, as shown for DHA (β=-0.11;p<0.01), EPA (β=-0.22;p<0.05), and n-6:n-3 LC-PUFA (β=0.17;p<0.01). Statistical mediation was only demonstrated for HR. No associations were observed between LC-PUFA status and externalizing behavioral problems. The present results are consistent with a role of maternal LC-PUFA status in internalizing behavioral problems as rated by the mother. These results were not observed when problem behavior was rated by the teacher. Analyses did not yield strong evidence supporting ANS activity as a possible mediator in this relationship.

Reduced Heart Rate Variability in Patients With Medically Unexplained Physical Symptoms: A Meta-Analysis of HF-HRV and RMSSD.

Medically unexplained physical symptoms (MUPS) and related syndromes are common and place a substantial burden on both patients and society. Chronic psychological distress and dysregulation of the autonomic nervous system may be common factors associated with MUPS, although previous studies have reported mixed results. The aims of this meta-analysis are to provide an updated synthesis of studies investigating heart rate variability (HRV) indices associated with autonomic nervous system functioning in three common MUPS syndromes and to explain inconsistencies in previous study findings. Literature search yielded 58 studies comparing HRV indices of reduced parasympathetic activity of healthy individuals with those of patients with chronic fatigue syndrome (npatients = 271), irritable bowel syndrome (npatients = 1005), and fibromyalgia (npatients = 534). Separate random-effects meta-analyses were conducted on studies measuring root mean square of successive differences (RMSSD) and high-frequency HRV (HF-HRV). Regardless of syndrome type, patients had significantly lower RMSSD (k = 22, Hedges g = -0.37 [-0.53 to -0.21], p < .001) and HF-HRV (k = 52, Hedges g = -0.69 [-1.03 to -0.36], p < .001) than did healthy individuals. Sample age and publication year explained a substantial variation in RMSSD, whereas controlling for confounders in statistical analyses explained variation in HF-HRV. Lower RMSSD and HF-HRV in patients with MUPS versus healthy controls indicates that autonomic nervous system dysregulation, particularly lower parasympathetic activity, may play a role in patients with these conditions. This conclusion may have important implications for the underlying mechanisms and treatment of MUPS and related syndromes.

Disturbances of Autonomic Regulation of Cardiovascular System at Different Working Regimes with Night Shifts

Aim To study temporal and spectral characteristics of heart rhythm variability (HRV) in night shift workers.Materials and methods Along with traditional risk factors, conditions of labor contribute to development of cardiovascular morbidity, including night shift work, which can be associated with disorders of the autonomic regulation detected by analysis of HRV. This study included 100 healthy men. 74 of them were engaged in shift work, including 53 men with rotating shift work, 21 men with fixed night shifts, and 26 men with day-time work. HRV was analyzed by data of 5-min electrocardiogram recording (background recording and orthostatic test).Results Night-shift workers had decreases in total power of regulation (ТР, SDNN) and in the parasympathetic branch (HF, pNN50). Rotating night-shift workers displayed significant decreases in SDNN and pNN50 and pronounced changes in the VLF / LF / HF ratio in the orthostatic test.Conclusion In work with night shifts, the type of autonomic regulation differs from the "standard" functioning of the autonomic nervous system (ANS). This study showed different effects of night work regimens on HRV indexes. With the rotating shift work, the ANS dysregulation was more profound and was evident by a significant decrease in the ANS total tone and parasympathetic activity (SDNN, pNN50) compared to night shifts with fixed working hours. The excessive weakening of the parasympathetic component in the passive orthostatic test can be considered as an early marker for ANS maladaptation.

Heritability and the Genetic Correlation of Heart Rate Variability and Blood Pressure in >29 000 Families: The Lifelines Cohort Study.

Dysregulation of the cardiac autonomic nervous system, as indexed by reduced heart rate variability (HRV), has been associated with the development of high blood pressure (BP). However, the underlying pathological mechanisms are not yet fully understood. This study aimed to estimate heritability of HRV and BP and to determine their genetic overlap. We used baseline data of the 3-generation Lifelines population-based cohort study (n=149 067; mean age, 44.5). In-house software was used to calculate root mean square of successive differences and SD of normal-to-normal intervals as indices of HRV based on 10-second resting ECGs. BP was recorded with an automatic BP monitor. We estimated heritabilities and genetic correlations with variance components methods in ASReml software. We additionally estimated genetic correlations with bivariate linkage disequilibrium score regression using publicly available genome-wide association study data. The heritability (SE) estimates were 15.6% (0.90%) for SD of normal-to-normal intervals and 17.9% (0.90%) for root mean square of successive differences. For BP measures, they ranged from 24.4% (0.90%) for pulse pressure to 30.3% (0.90%) for diastolic BP. Significant negative genetic correlations (all P<0.0001) of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (-0.20/-0.16) and with diastolic BP (-0.15/-0.13) were observed. LD score regression showed largely consistent genetic correlation estimates of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (range, -0.08 to -0.23) and diastolic BP (range, -0.20 to -0.27). Our study shows a substantial contribution of genetic factors in explaining the variance of HRV and BP measures in the general population. The significant negative genetic correlations between HRV and BP indicate that genetic pathways for HRV and BP partially overlap.

Stress, sleep, and autonomic function in healthy adolescent girls and boys: Findings from the NCANDA study

ObjectivesStarting in adolescence, female sex is a strong risk factor for the development of insomnia. Reasons for this are unclear but could involve altered stress reactivity and/or autonomic nervous system (ANS) dysregulation, which are strongly associated with the pathophysiology of insomnia. We investigated sex differences in the effect of stress on sleep and ANS activity in adolescents, using the first night in the laboratory as an experimental sleep-related stressor. DesignRepeated measures (first night vs. a subsequent night) with age (older/younger) and sex (males/females) as between factors. SettingRecordings were performed at the human sleep laboratory at SRI International. ParticipantsOne hundred six healthy adolescents (Age, mean ± SD: 15.2 ± 2.0 years; 57 boys). MeasuresPolysomnographic sleep, nocturnal heart rate (HR), and frequency-domain spectral ANS HR variability (HRV) indices. ResultsBoys and girls showed a first-night effect, characterized by lower sleep efficiency, lower %N1 and %N2 sleep, more wake after sleep onset and %N3 sleep, altered sleep microstructure (increased high-frequency sigma and Beta1 electroencephalographic activity), and reduced vagal activity (P < .05) on the first laboratory night compared to a subsequent night. The first night ANS stress effect (increases in HR and suppression in vagal HRV during rapid eye movement sleep) was greater in girls than boys (P < .05). ConclusionsSleep and ANS activity were altered during the first laboratory night in adolescents, with girls exhibiting greater ANS alterations than boys. Findings suggest that girls may be more vulnerable than boys to sleep-specific stressors, which could contribute to their increased risk for developing stress-related sleep disturbances.

Prevalence and Management of Severe Hand, Foot, and Mouth Disease in Xiangyang, China, From 2008 to 2013.

Therapeutic strategies for severe hand, foot, and mouth disease (HFMD) are currently either inconsequent or deficient in evidence. We retrospectively surveyed HFMD outbreaks in Xiangyang from June 2008 to December 2013. HFMD is staged from I to V according to clinical severity. Severe HFMD is defined as a case involving the central nervous system (CNS). We analyzed risk factors for fatality of severe cases and compared the efficiency and outcome of some therapies by binary logistic regression. The overall HFMD cases included 637 (1.26%) severe cases and 38 fatalities (0.075%). Analyses indicate that age (<3 years), enterovirus 71 (+), autonomic nervous system dysregulation, pulmonary edema/hemorrhage, C-reactive protein (CRP) (>40 mg/L), and cardiac troponin I (>0.04 ng/ml) are risk factors for fatality (all P < 0.05). Intravenous immunoglobulin (IVIG) and mechanical ventilation applied only in early stage IV significantly improved HFMD progression (both P < 0.05) with odds ratios of 0.24 (95% CI: 0.10–0.57) and 0.01 (95% CI: 0.00–0.10), respectively. Neither methylprednisolone nor milrinone administered in any stage made any significant difference on mortality (all P > 0.05). Precise recognition of the severe HFMD cases in early stage IV and prompt IVIG and mechanical ventilation application may reduce mortality. Mechanical ventilation training programs and dispatch of specialists to hospitals where there is no chance of transferring critical cases to the severe HFMD designated hospitals are two key measures to reduce fatality.

Non-linear analysis of the heart rate variability in characterization of manic and euthymic phases of bipolar disorder

Background– Bipolar Disorder (BD) has been associated with autonomic nervous system (ANS) dysregulation, with a consequent increase in mortality. Recent work highlights the non-linear analysis of ANS function. Our objective was to compare ANS modulation using recurrence plots (RP) and symbolic analysis (SA) in manic and euthymic phases of BD to controls. Methods– Eighteen male patients (33.1 ± 12.0 years) were assessed during mania and at discharge in the euthymic phase compared and to a healthy group matched by age (33.9 ± 10.8 years). Electrocardiographic series (1000 RR intervals, at rest, in supine position) were captured using Polar Advantage RS800CX equipment and Heart Rate Variability (HRV) was analysed using RP and SA. Statistical analysis was performed using ANOVA with Tukey's post-test. The threshold for statistical significance was set at P < 0.05 and Cohen's d effect size was also quantified considering d > 0.8 as an important effect. The study was registered into the Clinical Trials Registration (ClinicalTrials.gov: NCT01272518). ResultsManic group presented significantly higher linearity before treatment (P<0.05) compared to controls considering RP variables. Cohen's d values had a large effect size ranging from 0.888 to 1.227. In the manic phase, SA showed predominance of the sympathetic component (OV%) with reduction of the parasympathetic component (2LV% and 2UV%) with reversion post treatment including higher Shannon Entropy (SE) indicating higher complexity. Limitations- short follow-up (1 month) and small number of patients. Conclusions- Non-linear analyzes may be used as supplementary tools for understanding autonomic function in BD during mania and after drug treatment.

Prevalence and Management of Severe Hand, Foot, and Mouth Disease in Xiangyang, China from 2008-2013.

Therapeutic strategies for severe hand, foot, and mouth disease (HFMD) are currently either inconsequent or deficient in evidence. We retrospectively surveyed HFMD outbreaks in Xiangyang from June 2008 to December 2013. HFMD is staged form I to V according to clinical severity and the case with central nervous system involvement is defined as a severe one. We analyzed risk factors for fatality of severe cases and compared the efficiency and outcome of some therapies by binary logistic regression. The overall HFMD cases included 637 (1.26%) severe cases, 38 fatalities (0.75‰). Analysis indicates that age (<3 y), enterovirus 71 (+), autonomic nervous system dysregulation, pulmonary edema/hemorrhage, CRP (>40 mg/L) and cardiac troponin I (>0.04 ng/mL) are risk factors for fatality (all P < 0.05). Intravenous immunoglobulin (IVIG) and mechanical ventilation applied only in early stage IV significantly improved HFMD progression (both P < 0.05) with odds ratios of 0.24 (95% CI: 0.10-0.57) and 0.01 (95% CI: 0.00-0.10), respectively. Neither methylprednisolone nor milrinone administered in any stage made any significant difference on mortality (all P > 0.05). Precise recognition of the severe HFMD cases in early stage IV and prompt IVIG and mechanical ventilation application may decrease mortality. Mechanical ventilation training programs and dispatching specialists to county-level or district hospitals when there is no chance of transfer critical HFMD cases to a superior hospital are two key successful administrative initiatives. This article is protected by copyright. All rights reserved.

Neurocognitive functioning in individuals with congenital central hypoventilation syndrome

BackgroundCongenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by respiratory system abnormalities, including alveolar hypoventilation and autonomic nervous system dysregulation. CCHS is associated with compromised brain development and neurocognitive functioning. Studies that evaluate cognitive skills in CCHS are limited, and no study has considered cognitive abilities in conjunction with psychosocial and adaptive functioning. Moreover, the roles of pertinent medical variables such as genetic characteristics are also important to consider in the context of neurocognitive functioning.MethodsSeven participants with CCHS ranging in age from 1 to 20 years underwent neuropsychological evaluations in a clinic setting.ResultsNeurocognitive testing indicated borderline impaired neurocognitive skills, on average, as well as relative weaknesses in working memory. Important strengths, including good coping skills and relatively strong social skills, may serve as protective factors in this population.ConclusionCCHS was associated with poor neurocognitive outcomes, especially with some polyalanine repeat expansion mutations (PARMS) genotype. These findings have important implications for individuals with CCHS as well as medical providers for this population.

Evaluation of TP-E Interval and TP-E/QT Ratio in Panic Disorder.

Background and Objectives: The autonomic nervous system (ANS) is involved in panic disorders. ANS dysfunction has been shown to be associated with ventricular arrhythmia and increased heterogeneity of ventricular repolarization. However, there remains limited evidence of the relationship between panic disorders and ventricular depolarization markers, including the Tp-e interval and Tp-e/QT ratio. This study aimed to evaluate ventricular repolarization parameters in patients with panic disorder. Materials and Methods: In total, 40 patients with panic disorder, diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, were included in the study group. The control group comprised of 50 age- and sex-matched healthy individuals. A standard 12 lead electrocardiogram was recorded on all participants, and heart rate, QT interval, QRS duration, Tp-e interval, and Tp-e/QT ratio were measured. Results: QRS durations and QT intervals were similar in the study and control groups. Compared to the control group, QTd, Tp-e, and cTp-e intervals as well as Tp-e/QT and Tp-e/QTc ratios were significantly increased in patients with panic disorder (p < 0.05 for all). In the study group, the Severity Measure for Panic Disorder—Adult score had a significant positive correlation with the Tp-e interval (r = 0.369, p < 0001), cTp-e interval (r = 0.531, p < 0.001), Tp-e/QT ratio (r = 0.358, p = 0.001), and Tp-e/QTc ratio (r = 0.351, p = 0.001). Conclusion: These findings indicate that panic disorders are associated with increased ventricular repolarization heterogeneity, which may be attributed to ANS dysregulation.

Sepsis-Induced Myocardial Dysfunction (SIMD): the Pathophysiological Mechanisms and Therapeutic Strategies Targeting Mitochondria.

Sepsis is a lethal syndrome with multiple organ failure caused by an inappropriate host response to infection. Cardiac dysfunction is one of the important complications of sepsis, termed sepsis-induced myocardial dysfunction (SIMD), which is characterized by systolic and diastolic dysfunction of both sides of the heart. Mechanisms that contribute to SIMD include an excessive inflammatory response, altered circulatory, microvascular status, nitric oxide (NO) synthesis impairment, endothelial dysfunction, disorders of calcium regulation, cardiac autophagy anomaly, autonomic nervous system dysregulation, metabolic reprogramming, and mitochondrial dysfunction. The role of mitochondrial dysfunction, which is characterized by structural abnormalities, increased oxidative stress, abnormal opening of the mitochondrial permeability transition pore (mPTP), mitochondrial uncoupling, and disordered quality control systems, has been gaining increasing attention as a central player in the pathophysiology of SIMD. The disruption of homeostasis within the organism induced by mitochondrial dysfunction may also be an important aspect of SIMD development. In addition, an emerging therapy strategy targeting mitochondria, namely, metabolic resuscitation, seems promising. The current review briefly introduces the mechanism of SIMD, highlights how mitochondrial dysfunction contributes to SIMD, and discusses the role of metabolic resuscitation in the treatment of SIMD.

Comorbid Obesity and Depressive Symptoms in Childhood Asthma: A Harmful Synergy

Overweight/obesity (OV/OB) and depression have each been separately associated with worsened childhood asthma severity and control. Pathways by which these factors may jointly affect childhood asthma have not been elucidated. To examine the interrelationship of OV/OB and depressive symptoms with childhood asthma and explore associated psychobiologic pathways. The present study investigated whether comorbid OV/OB and depressive symptoms are associated with impaired baseline lung function and increased airway resistance during emotional stress, and to assess whether such effects may be mediated by autonomic nervous system (ANS) dysregulation, specifically through predominance of vagal over sympathetic reactivity (vagal bias). A total of 250 children with asthma, aged 7 to 17, were assessed for OV/OB using body mass index, depressive symptoms using the Children's Depression Inventory (CDI), and asthma severity using National Asthma Education and Prevention Program Expert Panel Report 3 criteria. Baseline pulmonary function (forced expiratory volume in 1 second [FEV1]) was assessed. The film "E.T. the Extra-Terrestrial" was used in a laboratory paradigm to evoke emotional stress/arousal. Airway resistance (Rint) was measured before and after the film to determine changes in airway function. ANS reactivity was assessed by measuring parasympathetic/vagal and sympathetic reactivity throughout the film. In OV/OB children with asthma, depressive symptoms predicted lower baseline FEV1 (β=-0.67, standard error [SE]= 0.24, P= .008), CDI predicted vagal bias under emotion stress/arousal (β= 0.27, SE= 0.09, P= .009), and vagal bias predicted increased Rint (β= 3.55, SE= 1.54, P= .023). This study is the first to link OV/OB and depressive symptoms in their relationship to childhood asthma. In OV/OB children with asthma, depression may potentiate airway compromise, mediated by vagal bias. Use of antidepressant and anticholinergic therapies should be studied in this subgroup of patients.

Brief Report: Reduced Heart Rate Variability in Children with Autism Spectrum Disorder.

Dysregulation of the autonomic nervous system (ANS), which can be indexed by heart rate variability (HRV), has been posited to contribute to core features of autism spectrum disorder (ASD). However, the relationship between ASD and HRV remains uncertain. We assessed tonic and phasic HRV of 21 children with ASD and 21 age- and IQ-matched typically developing (TD) children and examined (1) group differences in HRV and (2) associations between HRV and ASD symptomatology. Children with ASD showed significantly lower tonic HRV, but similar phasic HRV compared to TD children. Additionally, reduced tonic HRV was associated with atypical attentional responsivity in ASD. Our findings suggest ANS dysregulation is present in ASD and may contribute to atypical attentional responses to sensory stimulation.

Neuroscience in the heart: Recent advances in neurocardiac communication and its role in cardiac arrhythmias.

Autonomic nervous system dysregulation is involved in the pathophysiology of multiple cardiac arrhythmias, and therefore modulating sympathetic or parasympathetic input to the heart provides novel therapeutic options for arrhythmia management. Examples include decreasing intrinsic cardiac neuron communication, patterned vagal nerve stimulation, denervation, and blockade of post-ganglionic neurons. However, lessons from ventricular arrhythmias, where increased sympathetic activity and vagal rebound activity both amplify arrhythmia risk, stress the importance of understanding the regulatory mechanisms that modulate the balance and levels of sympathetic and parasympathetic activity. Of critical need is an increased understanding of plasticity mechanisms in the autonomic nervous system, to a level similar to what is known in the central nervous system, in order to develop safe and effective neuromodulatory therapies.

Multidisciplinary intervention in the treatment of mixed anxiety and depression disorder

Depression and anxiety disorders are one of the main limiting psychopathologies in the world today. This pathology is linked to an inflammatory state and a dysregulation of both neurotransmitters and autonomic nervous system. Various treatments from psychiatric and psychological areas have shown different degrees of efficacy in their treatment, being Cognitive Behavioral Therapy one of the most successful. In addition, various interventions from other areas of knowledge are showing significant improvements in this pathology. This research aimed to analyze the psychological and physiological modifications of a multidisciplinary intervention that combines psychological treatment (Cognitive Behavioral Therapy), physical activity and nutritional intervention in a mixed anxiety and depression disorder (DSM-V). We analyzed modifications in the HAM-D depression, STAI anxiety questionnaire, subjective perceptions of anxiety, happiness, sleep and motivation and the autonomous modulation before and after a 6 multidisciplinary sessions of cognitive behavioral therapy, aerobic physical activity and nutritional intervention in a subject with a mixed anxiety and depression disorder. The results showed a reduction in the values of depression in HAM-D until the classification of non-depression, a reduction in both state and trait anxiety, an increase in the subjective perceptions of sleep, happiness and motivation and a greater parasympathetic modulation after the six intervention sessions. The combination of psychological therapy with aerobic physical activity and nutritional recommendations to treat mixed anxiety and depression disorder produced an increased parasympathetic tone and a decreased anxiety and depression symptoms in six sessions. This is a novel research that allows us to open the study of a new multidisciplinary field in the treatment of this disease that is highly present today.

Two males with sick sinus syndrome in a family with 0.6 kb deletions involving major domains in MECP2

Mutations in methyl-CpG-binding protein 2 (MECP2) in males can lead to various phenotypes, ranging from neonatal encephalopathy to intellectual disability. In this study, using Nord's method of next-generation sequencing in three siblings, we identified a 0.6 kb deletion involving the transcriptional repression domain (TRD). Two males and one female had intellectual disability and apnea, but none met the criteria of Rett syndrome. Both males had sick sinus syndrome and severe tracheomalacia that resulted in early death. The mother, with skewed X-inactivation, had no symptoms. Therefore, this mutation is pathological for both males and females, resulting in sick sinus syndrome and severe tracheomalacia with strong reproducibility in males. Deletions involving major domains in MECP2 can result in a severe phenotype, and deletion of the TRD domain can cause severe autonomic nervous system dysregulation in males in these cases.

Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease

BackgroundBrainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension).MethodsDuring a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death.ResultsBetween June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used.ConclusionAlthough we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen.Trial registrationClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013).Trial sponsor: University of Oxford