Agnieszka Zygmunt

Methods of evaluation of autonomic nervous system function

Disturbances of the autonomic nervous system play a crucial role in the pathogenesis and clinical course of many diseases. Recently, rapid development has occurred in the clinical assessment of autonomic function. Various procedures have been described as diagnostic tools to monitor autonomic dysfunction. Some of them are mostly used for research purposes. Many, however, have found their place in routine clinical evaluation. Our paper presents selected methods of assessment of the autonomic nervous system with particular emphasis on those that are useful in diagnosis and treatment of diseases of the cardiovascular system. We discuss multiple tests based on cardiovascular reflexes, methods of studying heart rate variability as well as direct catecholamine measurements. Moreover, we outline tests of sudomotor function and microneurography.

Heart rate variability in children with neurocardiogenic syncope.

Abstract.In order to characterize the autonomic profile of syncopal children, we have studied heart rate variability (HRV) of 73 children, ages 11–18, with neurocardiogenic syncope and a positive outcome of head-up tilt testing (HUT).HRV was calculated over a 24-hour period for the time-domain indices (SDNN, SDANNi, SDNN, rMSSD, pNN50), and over 5-minute segments from night and day for frequency-domain indices (LF, HF, LF/HF). The obtained results were compared to reference values calculated for Polish children. 55% of the children had mixed response to HUT, 41% vasodepressor and 4% cardioinhibitory. Patients with syncope had significantly lower values of rMSSD and pNN50 in comparison to healthy children. Moreover, in the frequency-domain analysis they exhibited significantly higher LF and lower HF values. The day-night rhythm of HRV and the age-related changes of HRV were, however, similar in syncopal and healthy children. In addition to this, we found a significantly lower SDNN value in children with cardioinhibitory response during HUT in comparison to children with mixed response. We concluded that 1) based on HRV analysis children with neurocardiogenic syncope had alterations in basal autonomic balance, which indicated an increased sympathetic modulation in these patients, 2) syncopal children had adequate circadian rhythm of autonomic activity, 3) the changes of HRV indices with age in these groups are not altered in comparison to healthy children, 4) syncopal children may exhibit differences in HRV indices values depending on the kind of vasovagal response observed during HUT.

Evaluation of efficacy of iodine prophylaxis in Poland based on the examination of schoolchildren living in Opoczno Town (Lodz Voivodship)

BackgroundIn 1997 a currently obligatory model of iodine prophylaxis, based on mandatory iodization of household salt with 30 mg KI/kg, was introduced. The aim of our study was to assess the iodine intake among school-age children living in Opoczno in 3 subsequent time points – in 1994, before establishment of currently operating model of iodine prophylaxis, in 1999 – 2 years after implementation of iodine prophylaxis and in 2010, – 14 years after its implementation.MethodsWe assessed goitre incidence and urine iodine concentration (UIC) in 104 children in 1994, 207 children in 1999 and 174 children in 2012. Age of examined children ranged from 6 to 15 years. The thyroid volumes evaluated by ultrasound were compared to reference values for thyroid volume proposed by Zimmermann at al. Moreover, we have introduced a new index – V/BSA ratio (comparison of thyroid volume to the body surface area), which to our belief allows for more accurate assessment of thyroid volume.ResultsThe median of UICs was 45.5 μg/L (1994), 101.1 μg/L (1999) and 100.6 μg/L (2010). The distribution of obtained results has changed as well – iodine concentrations below 50 μg/L were present in 59.1% children in 1994, in 12.6% children – in 1999 and in 7.1% children – in 2010.Although a significant decrease in goitre incidence with regard to age – 92.6% (1994) vs 18.5% (1999) and 15.8% (2010), as well as with regard to BSA – 95.4% (1994) vs 15.2% (1999) and 11.6% (2010) was observed, it still points to the iodine deficiency, which is in contradiction with UICs as they are within normal limits. V/BSA ratio avoids such discrepancy. The values of ratio V/BSA were higher in 1994 (7.079 ± 2.775) than in 1999 (2.935 ± 1.112) (p<0.05) and in 2010 (2.846 ± 1.029) (p<0.05).ConclusionsHitherto model of iodine prophylaxis has proved to be effective in eliminating the iodine deficiency. The iodine intake is now more even, homogenous, which translates into smaller scatter of UICs and less percentage of children, in whom UIC is less than 50 μg/L. However, the iodine intake only slightly exceeds the recommended values, so median of UICs oscillates around the lower limit of references values.

Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

Objectives Connective tissue diseases (CTD) are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA). Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patients clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS), it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods Data from 24 patients with CTD treated with tumor necrosis factor-α-blockers (etanercept, adalimumab, golimumab) and an interleukin-6 receptor blocker (tocilizumab) were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1%) during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS daily doses.

The Polish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Polish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 154 JIA patients (10.4% systemic, 50.0% oligoarticular, 24.7% RF-negative polyarthritis, 14.9% other categories) and 91 healthy children, were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Polish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Comparison of uveitis in the course of juvenile idiopathic arthritis with isolated uveitis in children – own experiences

Objectives Uveitis and juvenile idiopathic arthritis (JIA) relatively often coexist. Inflammatory changes in the anterior segment of the eye are the most common extra-articular symptom in children with JIA, and JIA is, in turn, the main systemic cause of anterior uveitis in children. The aim of our study was to compare the course of anterior uveitis accompanying JIA and isolated uveitis. Material and methods We analyzed 25 children with JIA and uveitis (group I) and 28 children with isolated uveitis (group II). The study population was retrospectively selected from the patients treated in our center in the years 1998–2016 through a search of the hospital database. All data were presented as descriptive statistics. Results In group I there was a higher percentage of girls than in group II (64% vs. 50%) and uveitis occurred at a significantly younger age (8.7 years vs. 11.6). Patients from group I more often presented with immunological abnormalities (positive antinuclear antibodies or HLA-B27 antigen). The majority of children from group I developed uveitis prior to (44%) or simultaneously with (20%) arthritis. In patients who first presented with uveitis, arthritis appeared on average after 28 months (median 12 months). In children in whom arthritis developed first, uveitis appeared on average after 51 months (median 36 months). In some patients the time interval between the involvement of these two organs was as long as 9–10 years. Four children from group I and three from group II were qualified for biological treatment. Conclusions The results of our analysis indicate the need for constant cooperation between the pediatric rheumatologist and the ophthalmologist. Although the risk of uveitis in JIA decreases with the disease duration, in some cases this complication can develop after many years. Children with present antinuclear antibodies, at younger age and of female gender should be subject to particularly close observation.

Evaluation of the effectiveness of iodine prophylaxis in Poland based on over 20 years of observations of iodine supply in school-aged children in the central region of the country

Introduction Due to the mild-to-moderate iodine deficiency in Poland, in 1997 iodine prophylaxis based on obligatory salt iodization was introduced. We attempted to evaluate the effectiveness of such prophylaxis, based on over 20 years of observations of iodine supply in school-aged children in Opoczno district (Central Poland). Material and methods A group of 603 children (316 girls and 287 boys), aged 6–14, was examined at 4 time points: in the years 1994, 1999, 2010 and 2016. The children were tested for urine iodine concentration (UIC) and in each child the thyroid volume was measured ultrasonographically. Results The median UIC in 1994 (45.5 μg/l) indicated moderate iodine deficiency, while after introducing prophylaxis it corresponded to adequate values (1999 – 101.1 μg/l, 2010 – 100.6 μg/l, 2016 – 288.3 μg/l); however, the last value was higher than the previous two. The thyroid size, assessed by ultrasonography and presented as volume/body surface area (V/BSA), in 1994 was 6.55 × 10–6 m; this value was higher than at other time points (2.73 × 10–6 m in 1999, 2.73 × 10–6 m in 2010, and 2.70 × 10–6 m in 2016). Conclusions Iodine prophylaxis has proved effective in eliminating iodine deficiency. In recent years, the diversification of iodine sources, despite the reduction of salt consumption, has led to an increase in median UIC to values close to the upper limit of UIC, accepted as normal. Further increase in iodine supply may be unfavourable for health; therefore constant monitoring of iodine prophylaxis is required.

The Influence of the Manner of Performing the Thyroid Ultrasound Examination on the Reliability of the Assessment of the Thyroid Size in School-Aged Children

Background/Aims: Goitre incidence in school-aged children evaluated using ultrasonography is one of the essential indicators of iodine intake in a given area. The aim of the study was to examine what the difference is between the volume of the thyroid gland measured in the supine and sitting position and to determine the intra-observer, inter-observer, and inter-position variations. Methods: The survey was conducted among 87 children (56 girls and 31 boys aged 7–13 years, mean age 10.44 ± 1.72 years). Results: The thyroid volume measured in a sitting position was significantly lower than that measured in the supine position. The intra-observer variations for the total thyroid volume equalled 9.56–9.65%. The inter-observer variations were significantly higher and amounted to 34.5–35.7%. Conclusions: The way in which ultrasound evaluation is performed is important for the analysis of the results. It is crucial to aim for the smallest inter-observer variation, which can be achieved by strictly defining the methods of the thyroid measurement and comparing one’s measuring techniques with the reference method. The use of standards in ultrasound evaluation performed in the supine position, as well as the use of standards without a strict determination of the study method, can lead to erroneous conclusions.

Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl.

Mixed connective tissue disease (MCTD) is a systemic inflammatory disease affecting connective tissue with the underlying autoimmunological mechanism. The core of MCTD is an appearance of symptoms of several other inflammatory diseases of connective tissue – systemic lupus erythematosus, systemic scleroderma, poly- or dermatomyositis, rheumatoid arthritis at the same time, accompanied by a high level of anti-ribonucleoprotein antibodies (anti-U1RNP). The disease was described more than 40 years ago by Sharp et al. During recent years, many efforts to better understand clinical and serological features of MCTD have been made. Diagnosis of MCTD can be difficult. Obligatory international diagnostic criteria are required to be fulfilled. Several versions of such criteria have been proposed, but the most widely used one was described by Kasukawa. There is no consensus about treatment – a choice of drugs depends on symptoms. We present a case of a 10-year-old girl with sclerodactyly and trophic damages of fingers accompanied by symptoms of Raynauds phenomenon. After an almost 2-year course of the disease, a diagnosis of MCTD has been established.