Fetal development of complex autonomic control evaluated from multiscale heart rate patterns.

Development of the fetal autonomic nervous system's integrative capacity in relation to gestational age and emerging behavioral pattern is reflected in fetal heart rate patterns. Conventional indices of vagal and sympathetic rhythms cannot sufficiently reflect their complex interrelationship. Universal behavioral indices of developing complex systems may provide additional information regarding the maturating complex autonomic control. We investigated fetal magnetocardiographic recordings undertaken at 10-min intervals in active (n = 248) and quiet (n = 111) states between 22 and 39 wk gestational age. Standard deviation of heartbeat intervals, skewness, contribution of particular rhythms to the total power, and multiscale entropy were analyzed. The multiscale entropy methodology was validated for 10-min data sets. Age dependence was analyzed by linear regression. In the quiet state, contribution of sympathovagal rhythms and their complexity over a range of corresponding short scales increased with rising age, and skewness shifted from negative to positive values. In the active state, age dependencies were weaker. Skewness as the strongest parameter shifted in the same direction. Fluctuation amplitude and the complexity of scales associated with sympathovagal rhythms increased. We conclude that in the quiet state, stable complex organized rhythms develop. In the active state, however, increasing behavioral variability due to multiple internal coordinations, such as movement-related heart rate accelerations, and external influences develop. Hence, the state-selective assessment in association with developmental indices used herein may substantially improve evaluation of maturation age and early detection and interpretation of developmental problems in prenatal diagnosis.

Development of integrative autonomic nervous system function: an investigation based on time correlation in fetal heart rate patterns.

OBJECTIVE: To describe the development of the integrative capacity of the fetal autonomic nervous system (ANS) according to gestational age and emerging behavioral states, assuming that developing integrative ANS functions are reflected in increasing autocorrelation of fetal heart rate and fetal heart rate variability markers. METHODS: Magnetocardiograms of 114 healthy fetuses (21-40 weeks of gestation) were recorded. Level of fetal activity (quiet/active sleep) was estimated according to characteristic heart rate patterns. Autocorrelation functions of (i) fetal heart rate and (ii) time patterns of SDNN (standard deviation of normal-to-normal intervals) and RMSSD (root mean square of successive differences in normal-to-normal intervals) were calculated and autocorrelation was determined over different time scales. Age and activity related changes were examined using linear regression and non-parametric tests. RESULTS: During pregnancy, autocorrelation increased in fetal heart rate signals and time patterns of SDNN and RMSSD. Short-time correlation (0-20 s) changed between 21 and 31 gestational weeks. Long-time correlation (75-300 s) accelerated later in pregnancy and did not increase in quiet heart rate patterns. Strong state-dependent changes were found with time patterns of SDNN. CONCLUSIONS: Emerging integrative ANS functions are reflected in increasing autocorrelation of fetal heart rate fluctuations over increasing time scales. The period from 21 to 31 gestational weeks seems to be critical to ANS development. Increasing long-time correlation is specific to active sleep states.

From dizziness to severe ataxia and dysarthria: New cases of anti-Ca/ARHGAP26 autoantibody-associated cerebellar ataxia suggest a broad clinical spectrum.

In 2010, a novel anti-neuronal autoantibody, termed anti-Ca, was described in a patient with subacute cerebellar ataxia, and Rho GTPase-activating protein 26 (ARHGAP26) was identified as the target antigen. Recently, three additional cases of anti-Ca-positive cerebellar ataxia have been published. In addition to ataxia, cognitive decline and depression have been observed in some patients. Here, we report two new cases of anti-Ca-associated autoimmune cerebellar ataxia. Patient 1 presented with dizziness and acute yet mild limb and gait ataxia. Symptoms stabilized with long-term oral corticosteroid therapy but transiently worsened when steroids were tapered. Interestingly, both initial occurrence and worsening of the patient's neurological symptoms after steroid withdrawal were accompanied by spontaneous cutaneous hematomas. Patient 2 initially presented with an increased startle response and myoclonic jerks, and subsequently developed severe limb and gait ataxia, dysarthria, oculomotor disturbances, head and voice tremor, dysphagia, cognitive symptoms and depression. Steroid treatment was started five years after disease onset. The symptoms then responded only poorly to corticosteroids. At most recent follow-up, 19 years after disease onset, the patient was wheelchair-bound. These cases extend the clinical spectrum associated with anti-ARHGAP26 autoimmunity and suggest that early treatment may be important in patients with this rare syndrome.

Fetal autonomic brain age scores, segmented heart rate variability analysis, and traditional short term variability.

Disturbances of fetal autonomic brain development can be evaluated from fetal heart rate patterns (HRP) reflecting the activity of the autonomic nervous system. Although HRP analysis from cardiotocographic (CTG) recordings is established for fetal surveillance, temporal resolution is low. Fetal magnetocardiography (MCG), however, provides stable continuous recordings at a higher temporal resolution combined with a more precise heart rate variability (HRV) analysis. A direct comparison of CTG and MCG based HRV analysis is pending. The aims of the present study are: (i) to compare the fetal maturation age predicting value of the MCG based fetal Autonomic Brain Age Score (fABAS) approach with that of CTG based Dawes-Redman methodology; and (ii) to elaborate fABAS methodology by segmentation according to fetal behavioral states and HRP. We investigated MCG recordings from 418 normal fetuses, aged between 21 and 40 weeks of gestation. In linear regression models we obtained an age predicting value of CTG compatible short term variability (STV) of R (2) = 0.200 (coefficient of determination) in contrast to MCG/fABAS related multivariate models with R (2) = 0.648 in 30 min recordings, R (2) = 0.610 in active sleep segments of 10 min, and R (2) = 0.626 in quiet sleep segments of 10 min. Additionally segmented analysis under particular exclusion of accelerations (AC) and decelerations (DC) in quiet sleep resulted in a novel multivariate model with R (2) = 0.706. According to our results, fMCG based fABAS may provide a promising tool for the estimation of fetal autonomic brain age. Beside other traditional and novel HRV indices as possible indicators of developmental disturbances, the establishment of a fABAS score normogram may represent a specific reference. The present results are intended to contribute to further exploration and validation using independent data sets and multicenter research structures.

Fetal development assessed by heart rate patterns--time scales of complex autonomic control.

The increasing functional integrity of the organism during fetal maturation is connected with increasing complex internal coordination. We hypothesize that time scales of complexity and dynamics of heart rate patterns reflect the increasing inter-dependencies within the fetal organism during its prenatal development. We investigated multi-scale complexity, time irreversibility and fractal scaling from 73 fetal magnetocardiographic 30min recordings over the third trimester. We found different scale dependent complexity changes, increasing medium scale time irreversibility, and increasing long scale fractal correlations (all changes p<0.05). The results confirm the importance of time scales to be considered in fetal heart rate based developmental indices.