The aim of this study was to assess long-term outcomes in patients with different vascular types of childhood stroke. Methods: Data for children with childhood stroke (aged 29 days to 18 years) were collected from the Estonian Pediatric Stroke Database. Outcomes (death, recurrent stroke, epilepsy, neurodevelopmental outcome by pediatric stroke outcome measure (PSOM)) were assessed at a minimum of two years after stroke. Results: Long-term outcome data were available for 44 patients with childhood stroke (including three patients who died of stroke). According to the PSOM, based on gender, age, location of stroke and epilepsy, there were no differences in outcomes, but patients with a Pediatric NIH Stroke Scale (PedNIHSS) score of ≥6 had worse outcomes compared to patients with a score of <6. Children with arterial hemorrhagic stroke (AHS) were more likely to die, suffer from epilepsy and develop problems in the cognition/behavior PSOM subscale compared to children with arterial ischemic stroke (AIS). Combined poor outcomes (epilepsy, PSOM ≥ 1, recurrent stroke, mortality) occurred in 75% (33/44) of all patients with long-term outcome data. Conclusions: Combined poor outcomes occurred in 75% of the patients with childhood stroke. Patients with AHS showed higher mortality and worse long-term outcomes compared to patients with AIS in certain neurodevelopmental domains.

Diagnostic reference levels (DRLs) guide dose optimisation, yet paediatric computed tomography (CT) DRLs remain scarce, heterogeneous, largely anatomy-based. This study aimed to establish local paediatric DRLs for head, chest, and abdomen-pelvis CT according to European guidelines, compare them with European DRLs, and assess the feasibility of indication-based DRLs. This single-institution study included 604 of 829 CT acquisitions performed in children aged ⩽16 years in 2017 or 2022. DRLs, defined as the 75th percentiles of volumetric CT dose index (CTDIvol) and dose length product, were derived by age for head CT and by weight for body CT. Indication-based DRLs were explored for five indications. Local DRLs were compared with European and other recent values using 95% confidence intervals. Quantile regression was used to estimate DRL curves and identify predictors for cervical spine CT dose. Head CT DRLs were up to 33% lower than European levels (p< 0.05), and abdomen-pelvis CT DRLs up to 44% lower (p< 0.05), while chest CT DRLs did not differ significantly (p> 0.05). Compared with recent studies, head CT DRLs were lower (p< 0.05), whereas chest and abdomen-pelvis CT DRLs were higher for some groups. Higher doses were observed with older scanner. DRLs for craniosynostosis and chronic sinusitis CT were tenfold lower than those for head trauma or stroke CT. For cervical spine CT, weight was a stronger predictor of CTDIvol than age (pseudoR2= 0.72 vs 0.54). In conclusion, paediatric CT DRLs can be established at institutional level in accordance with European guidelines. The observed DRLs suggest successful implementation of optimisation strategies for head, whereas chest and abdomen-pelvis CT may offer further optimisation potential. Latest-generation scanners and paediatric protocols across the paediatric spectrum should be standard practice, and greater emphasis on indication-based DRLs can enable more precise and clinically relevant optimisation. Weight-based stratification is recommended for cervical spine CT DRLs.

Background: The annual incidence rate (IR) of childhood‐onset type 1 diabetes mellitus (T1DM) among Estonian children under 15 years of age was 12.6 cases per 100,000 between 1983 and 2006, with the highest IR occurring in the 10–14‐year‐old age group. Notably, the 0–4‐year‐old age group saw the most significant annual increase, at 9.3%. Objective: This study aims to determine the incidence and trends of T1DM among Estonian children from 1983 to 2022, focusing on the period from 2007 to 2022. Additionally, the study evaluates the impact of the COVID‐19 pandemic on the incidence of T1DM in this population. Subjects and Methods: This retrospective cohort study gathered data from 2007 to 2022 using population‐based registries from Estonia’s paediatric medical centers. Preceding data were sourced from previous publications. The subjects were divided into three age groups, and the study period was segmented into five time periods, each spanning 8 years. Results: From 2007 to 2022, 1104 new T1DM cases were diagnosed in children under 15 years in Estonia, with a crude IR of 32.9 per 100,000 persons per year (95% confidence interval [CI] 30.9–34.8). The highest incidence was in the 10–14‐year age group (40.5 per 100,000 per year) (95% CI 36.7–44.3). On average, the incidence grew by 1.6% during this time period for all age groups combined. The most significant growth was in the 5–9‐year‐old group, with an annual increase of 2.9% (relative risk [RR] 1.23, 95% CI 1.0–1.5). The highest IR ever recorded in Estonia was in 2021, during the highest fatality year of COVID‐19, at 45.8 per 100,000 (95% CI 26.9–54.8). Conclusions: The incidence of childhood‐onset T1DM in Estonia continues to rise, with a notable spike in 2021 during the peak of the COVID‐19 pandemic.

ObjectiveEpilepsy develops in one third of the patients after perinatal stroke. It is still unclear which vascular syndrome of ischemic stroke carries higher risk of epilepsy. The aim of the current study was to evaluate the risk of epilepsy according to the vascular syndrome of perinatal stroke.MethodsThe study included 39 children with perinatal arterial ischemic stroke (13 with anterior or posterior trunk of the distal middle cerebral artery occlusion, 23 with proximal or distal M1 middle cerebral artery occlusion and three with lenticulostriate arteria infarction), and 44 children with presumed perinatal venous infarction. Magnetic resonance imaging obtained at the chronic stage was used to evaluate the vascular syndrome of stroke.ResultsThe median follow-up time was 15.1 years (95% CI: 12.4-16.5 years), epilepsy developed in 19/83 (22.9%) patients. The cumulative probability to be without epilepsy at 15 years was 75.4% (95% CI: 65.8-86.4). The probability of having epilepsy was higher in the group of proximal or distal M1 artery occlusion compared to patients with periventricular venous infarction (HR 7.2, 95% CI: 2.5-26, p = .0007). Patients with periventricular venous infarction had significantly more often status epilepticus or spike-wave activation in sleep >= 85% of it compared to patients with anterior or posterior trunk of the distal middle cerebral artery occlusion (OR = 81; 95% CI: 1.3-5046, p = .029).SignificanceThe emphasis of this study is placed on classifying the vascular syndrome of perinatal stroke and on the targeted follow-up of patients for epilepsy until young adulthood. The risk for having epilepsy after perinatal stroke is the highest in children with proximal or distal M1 middle cerebral artery occlusion. Patients with periventricular venous infarction have a more severe course of epilepsy.

Objectives: To analyse changes in the use of paediatric (<= 16 years) CT over the past decade and to evaluate the appropriateness of CT examinations at a tertiary teaching hospital. Methods: Data from 290 paediatric CTs were prospectively collected in 2022 and compared with data from 2017 (358 cases) and 2012 (538 cases). The justification of CTs was evaluated with regard to medical imaging referral guidelines and appropriateness rates were calculated. Results: Paediatric CTs decreased 39.4% over the 10 years, contrasting with a 27.6% increase in overall CTs. Paediatric CTs as the share of overall CTs dropped from 2.5% in 2012 to 1.1% in 2022 (P < .0001), with a concurrent rise in paediatric MRIs (P < .0001). Notable reductions in CT use occurred for head trauma (P = .0003), chronic headache (P < .0001), epilepsy (P = .037), hydrocephalus (P = .0078), chest tumour (P = .0005), and whole-body tumour (P = .0041). The overall appropriateness of CTs improved from 73.1% in 2017 to 79.0% in 2022 (P = .0049). In 15.4% of the cases, no radiological examination was deemed necessary, and in 8.7% of the cases, another modality was more appropriate. Appropriateness rates were the highest for the head and neck angiography (100%) and the chest (96%) and the lowest for the neck (66%) and the head (67%). Conclusions: Justification of CT scans can be improved by regular educational interventions, increasing MRI accessibility, and evaluating the appropriateness of the requested CT before the examination. Interventions for a more effective implementation of referral guidelines are needed. Advances in knowledge: The focus for improvement should be CTs for head and cervical spine trauma, accounting for the majority of inappropriate requests in the paediatric population.

IntroductionEpilepsy develops in one third of children after perinatal stroke. Both epilepsy and stroke may be risk factors for impaired cognitive abilities. How the development of epilepsy is related to the cognitive profile of children with perinatal stroke is still unclear. The aim of the study was to evaluate general and specific cognitive functions in children with epilepsy and children without epilepsy after perinatal ischemic stroke.MethodsThe study group consisted of 51 children with perinatal ischemic stroke confirmed by magnetic resonance imaging: 27 (53%) children with arterial ischemic stroke and 24 (47%) with periventricular venous infarction. Magnetic resonance imaging and electroencephalography were performed in all patients after the neonatal period. Epilepsy was diagnosed if the child had at least two unprovoked seizures occurring >24 h apart or one unprovoked seizure with a high recurrence risk. Cognitive assessments were performed using the Kaufman Assessment Battery for Children, Second Edition, at the age of ≥7 years. General ability (Fluid Crystallized Index, Mental Processing Index, Non-verbal Index) and specific cognitive functions (sequential processing, simultaneous processing, learning, planning, knowledge) were evaluated.ResultsAt the median age of 19.3 years (interquartile range 14.0–22) at the time of follow-up for epilepsy, 14 (27.5%) patients had developed epilepsy, and 37 (72.5%) patients were without epilepsy. All general cognitive ability scores were lower in children with epilepsy compared to children without epilepsy. Among specific cognitive functions, simultaneous processing, planning, and knowledge were lower in children with epilepsy compared to children without epilepsy: simultaneous processing mean [78.5, 95% CI: [69.8, 87.2], vs. 96.9, 95% CI [90, 103.9], p = 0.0018]; planning mean [82.5, 95% CI: [73, 92], vs. 96.2, 95% CI: [88.7, 103.6], p = 0.026]; knowledge median (25th, 75th percentile): 80.5 (75, 87) vs. 92 (84, 108), p = 0.023.ConclusionChildren with epilepsy after perinatal ischemic stroke have lower general cognitive abilities compared to children without epilepsy. The profile of the subscales indicates lower verbal abilities and executive functions in children with epilepsy. Children with post-stroke epilepsy need targeted cognitive monitoring for early aimed rehabilitation and for establishing an adapted learning environment.

BackgroundEpilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy.MethodsThe follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens.ResultsDuring a median follow-up time of 12.8 years [interquartile range (IQR): 10.8-17.3] in the AIS group and 12.5 years (IQR: 9.3-14.8) in the PVI group (p = 0.32), epilepsy developed in 10 children (34.5%) with AIS and in 4 (12.1%) children with PVI, p = 0.036 [odds ratio (OR) = 3.8, 95%, confidence interval (CI): 1.04-14]. Epilepsy and interictal epileptiform discharges (IEDs) without clinical seizures were more often expressed in children with AIS (n = 16, 55%) than in children with PVI (n = 7, 21.2%), p = 0.0057 (OR = 3.8 95% CI: 1.04-14). In the AIS group, the ipsilesional and contralesional thalamus, ipsilesional caudate nucleus, and nucleus accumbens were significantly smaller in children with epilepsy compared to children without epilepsy. In the PVI group, the ipsilesional thalamus, caudate nucleus, and nucleus accumbens were smaller in the pooled group of epilepsy plus IED alone compared to children without epilepsy.ConclusionIn children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.

INTRODUCTION:The aim of this study was to evaluate genetic risk factors in term-born children with antenatal periventricular hemorrhagic infarction (PVHI), presumed antenatal periventricular venous infarction and periventricular hemorrhagic infarction in preterm neonates.METHODS:Genetic analysis and magnetic resonance imaging were performed in 85 children: term-born children (≥36 gestational weeks) with antenatal periventricular hemorrhagic infarction (n = 6) or presumed antenatal (n = 40) periventricular venous infarction and preterm children (<36 gestational weeks) with periventricular hemorrhagic infarction (n = 39). Genetic testing was performed using exome or large gene panel (n = 6700 genes) sequencing.RESULTS:Pathogenic variants associated with stroke were found in 11 of 85 (12.9%) children with periventricular hemorrhagic infarction/periventricular venous infarction. Among the pathogenic variants, COL4A1/A2 and COL5A1 variants were found in 7 of 11 (63%) children. Additionally, 2 children had pathogenic variants associated with coagulopathy, whereas 2 other children had other variants associated with stroke. Children with collagenopathies had significantly more often bilateral multifocal stroke with severe white matter loss and diffuse hyperintensities in the white matter, moderate to severe hydrocephalus, moderate to severe decrease in size of the ipsilesional basal ganglia and thalamus compared to children with periventricular hemorrhagic infarction/periventricular venous infarction without genetic changes in the studied genes (P ≤ .01). Severe motor deficit and epilepsy developed more often in children with collagenopathies compared to children without genetic variants (P = .0013, odds ratio [OR] = 233, 95% confidence interval [CI]: 2.8-531; and P = .025, OR = 7.3, 95% CI: 1.3-41, respectively).CONCLUSIONS:Children with periventricular hemorrhagic infarction/periventricular venous infarction have high prevalence of pathogenic variants in collagene genes (COL4A1/A2 and COL5A1). Genetic testing should be considered for all children with periventricular hemorrhagic infarction/periventricular venous infarction; COL4A1/A2 and COL5A1/A2 genes should be investigated first.

Introduction: The study was designed to assess the prevalence of pregnancy and delivery associated risk factors in children suffering from neonatal or presumed periventricular venous infarction. Methods: Antenatal records and pregnancy outcome data were retrospectively assessed in children with presumed periventricular venous infarction (n = 43, born ≥36 gestational weeks) or neonatal periventricular venous infarction (n = 86, born <36 gestational weeks) and compared to a matched control group (n = 2168, ≥36 gestational weeks) from a prospective study. Results: Children with presumed periventricular venous infarction had significantly more maternal bacterial infections compared to the control group (47% vs 20%, respectively, P < .001), whereas no difference was found compared to the neonatal periventricular venous infarction group (49%, P = .80). Mothers with bacterial infection in the presumed periventricular venous infarction group had significantly more often pyelonephritis compared to the control group (50% vs 3.4%, respectively, P < .001). Conclusions: Our data show an increased risk for developing periventricular venous infarction in the case of maternal bacterial infections, especially between gestational weeks 21 and 31.

Perinatal stroke affects child's language development and can change language lateralization. Language generation and comprehension tasks in functional magnetic resonance imaging were used to determine language lateralization in term born children with perinatal left-side arterial ischemic stroke (AIS) (n = 9, mean age (SD) 13.4 (3.1) y.) and periventricular venous infarction (PVI) (n = 12, 11.8 (2.8) y.), and in healthy right-handed controls (n = 30, 11.6 (2.6) y.). Lateralization index was calculated for the Broca and Wernicke areas and correlated with language and cognitive outcomes measured by the Kaufman Assessment Battery for Children II ed. Language outcome in children with perinatal stroke is poorer compared to healthy controls. Children with small AIS lesions and most children with PVI showed left-side language activation. Most children with large AIS lesions and one child with large PVI had language activation reorganized to the right hemisphere. Language reorganization to the unlesioned right hemisphere did not ensure normal language outcome.

Abstract Background Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge. Aims To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls. Methods Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS). Results Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p < 0.005). Affected hand function in children with AIS was correlated with smaller ipsilesional thalamus, putamen, globus pallidus, hippocampus, amygdala and contralesional amygdala (r > 0.5; p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < − 0.5; p < 0.05). In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p ≤ 0.001) and hippocampus (p < 0.03) was smaller compared to controls. Smaller volume of the ipsi- and contralesional thalami and ipsilesional caudate nucleus was correlated with affected hand function (r > 0.55; p < 0.05) in children with PVI. Conclusions Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.

Poster: EuroSafe Imaging 2020 / ESI-04239 / Optimization and dose reduction in paediatric CT: experience from Estonian teaching hospital by: Langemets1, P. Ilves2, P. Kool1, M. Rajas3, L. Kargenberg4, A. Borkvel1, K. Kepler5, A. Aavik1; 1 Tartu/EE, 2Tartu University Tartu/EE, 3Radioloogia kliinik Tartu/EE, 4Radiology department Tartu/EE, 5University of Tartu Tartu/EE

Purpose: To investigate the differences in the pattern of changes in serum inflammatory cytokines measured annually over a 24-month period, between less active and more active overweight boys. Participants/Methods: In total, 25 pubertal overweight boys were divided by their moderate to vigorous physical activity (MVPA) levels into 2 groups: less active group (LAG; n = 10; MVPA < 60 min/d) and more active group (MAG; n = 15; MVPA > 60 min/d). Physical activity was measured by 7-day accelerometry. Serum concentration of 13 inflammatory cytokines [interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, vascular endothelial growth factor, interferon-γ, tumor necrosis factor-α, monocyte chemotactic protein-1, epidermal growth factor, and C-reactive protein] was measured at baseline (T0), after 12 months (T1), and after 24 months (T2) from fasting blood samples. Results: Serum IL-6 level was significantly higher [LAG: 1.27 (0.86, 1.98) pg/mL; MAG: 0.80 (0.52, 0.84) pg/mL] at T0 and IL-8 level [LAG: 10.26 (8.80, 11.64) pg/mL; MAG: 7.42 (6.10, 9.54) pg/mL] at T2 in LAG compared with MAG. The changes over the study period varied between different inflammatory markers. None of the slopes of any measured markers were statistically different between the LAG and MAG, although the slopes of interferon-γ and IL-10 tended to be different between the groups. Conclusions: The pattern of changes over the study period varied between different inflammatory markers, but these changes were not different between the MVPA groups. More longitudinal studies are needed to investigate whether IL-6, IL-8, IL-10, and interferon-γ would be the choice of inflammatory markers to study the associations between obesity and physical activity in future.

ObjectiveSerum inflammatory markers could help to identify those boys with overweight (OWB) who gain weight more extensively during puberty. This study aimed to examine the longitudinal changes in different serum inflammatory markers through puberty in boys with different BMI values and increments.MethodsTwenty‐six OWB and 29 normal‐weight boys (NWB) were followed yearly for 3 years to measure changes in BMI and serum concentrations of 12 inflammatory markers.ResultsOWB had higher (P < 0.033) baseline interleukin (IL)‐6, IL‐8, interferon gamma (IFN‐γ), tumor necrosis factor alpha (TNF‐α), and IL‐1α concentrations in comparison with NWB. Over the 3‐year period, IFN‐γ (P = 0.0001) and TNF‐α (P = 0.0042) decreased more in OWB compared to NWB. Serum IL‐8, monocyte chemoattractant protein (MCP)‐1, and leptin increased further in those OWB who gained BMI more extensively through puberty compared to OWB who gained weight at slower rates (P < 0.033).ConclusionsSerum IFN‐γ and TNF‐α levels decreased more during pubertal years in OWB compared to NWB, indicating that pubertal maturation itself may have a favorable impact on the inflammation of obesity. Serum IL‐8, MCP‐1, and leptin could help to identify OWB who gain BMI more extensively during pubertal years.

The aim of this 3-year prospective study was to examine changes in bone mineral characteristics during pubertal maturation in boys with different BMI values at the beginning of puberty and with different BMI increments during puberty. 26 boys with overweight and obesity (OWB) and 29 normal weight boys (NWB) were studied yearly for 3 years from the age of 11 years to measure the changes in different bone mineral characteristics. The OWB group was further divided into two subgroups according to extensive or non-extensive BMI increment during 3-year period. OWB had higher (P < 0.01) baseline total body (TB) bone mineral density (BMD), TB bone mineral content (BMC), TB BMC for height, lumbar spine (LS) BMD, and LS BMC compared to NWB. Throughout the study period, OWB gained more TB BMD (P = 0.0001), TB BMC (P = 0.0048), TB BMC for height (P = 0.0124), LS BMD (P = 0.0029), and LS BMC (P = 0.0022) compared to NWB. Also during the study period, TB BMD (P = 0.0065), TB BMC (P = 0.0141), TB BMC for height (P = 0.0199), LS BMD (P = 0.0066), LS apparent volumetric BMD (BMAD) (P = 0.0075), and LS BMC (P = 0.017) increased significantly less in those OWB whose BMI increased more extensively. Extensive BMI gain is associated with lower increments in bone mineral characteristics in boys with overweight and obesity. Unfavorable increment in total body fat mass and percentage during pubertal years could be one reason for that.

Background: During the last several decades the prevalence of coeliac disease (CD) has increased worldwide.Aim: To compare the cumulative incidence of CD between Estonian and Finnish children and to identify the risk factors.Materials and methods: Children were recruited as part of the DIABIMMUNE Study. In the birth cohort (BC) 258 children from Estonia and 305 from Finland, and in the young children's cohort (YCC) 1363 and 1384 children were followed up, respectively. The diagnosis of CD was made in accordance with the ESPGHAN guidelines-the presence of IgA-tTG antibodies and small bowel villous atrophy.Results: During the study period 29 children developed CD. The cumulative incidence of CD was significantly higher in Finland (0.77% vs 0.27%; P = 0.01). No difference was seen between the children with CD and the controls in the duration of breastfeeding or the age at cereal introduction. The BC children with CD had had significantly more episodes of infections with fever by the age of 12 months compared to the controls (3.4 vs 1.4; P = 0.04).Conclusion: The 5-year cumulative incidence of childhood CD is significantly higher in Finland than in Estonia. Sequential infections early in life may increase the risk for developing CD. (C) 2016 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.

OBJECTIVE This study aimed at investigating the role of IGF1 and IGF binding protein 3 (IGFBP3) in the development of β-cell autoimmunity. METHODS Five hundred and sixty-three subjects with HLA-conferred susceptibility to type 1 diabetes (T1D) were monitored for signs of seroconversion to positivity for insulin and/or GAD, IA2, and zinc transporter 8 autoantibodies by the age of 3 years. In 40 subjects who developed at least one autoantibody, IGF1 and IGFBP3 plasma concentrations were measured and compared with 80 control subjects who remained negative for autoantibodies, and were matched for age, sex, country of origin, and HLA genotype. The increments of IGF1, IGFBP3, and IGF1/IGFBP3 molar ratio before and after seroconverison were compared with corresponding time intervals in controls. RESULTS The IGF1 concentrations at the age of 12 months and the IGF1/IGFBP3 ratio at the age of 24 months were lower in the autoantibody-positive children (P<0.05). The increase in circulating IGFBP3 was significantly higher in the autoantibody-positive children before seroconversion than in the corresponding time intervals in controls (0.43 mg/l; 95% CI 0.29-0.56 vs 0.22 mg/l; 95% CI 0.10-0.34 mg/l; P<0.01). Children carrying the high-risk HLA genotype had lower plasma IGF1 and IGFBP3 concentrations at the age of 24 months than those with low-risk genotypes (P<0.05 and < 0.01 respectively). CONCLUSIONS Circulating IGF1 and IGFBP3 appear to have a role in early development of β-cell autoimmunity. The decreased IGF1 concentrations in children with the high-risk HLA genotype may contribute to the reduced growth previously described in such children.

Background Human leukocyte antigen (HLA) genotypes associated with increased risk for type 1 diabetes mellitus (T1D) have been reported to be associated with increased birth weight. We set out to investigate the association between HLA haplotypes conferring risk for T1D and birth weight and search for possible differences in the strength of these associations among populations with contrasting incidence of T1D. Methods As a part of the EU-funded DIABIMMUNE study, genotyping for the HLA haplotypes associated with T1D was performed in 8369 newborn infants from Estonia, Finland and Russian Karelia. Infants born before 35 gestational weeks, from mothers with diabetes, and multiple pregnancies were excluded. Relative birth weight, expressed in standard deviation scores, was estimated for each gestational week, sex and country. The standard deviation scores were calculated internally using the actual population studied. According to their HLA haplotypes, participants were divided into risk groups, and the distribution of birth weight between quartiles was analysed. Results We did not find any direct association between various HLA risk-associated genotypes (HLA DR3-DQ2/DR4-DQ8, DR3-DQ2/X or DR4-DQ8/X) and birth weight. We observed a significant relationship between increased relative birth weight and the protective HLA-DR2-DQ6 and DR13-DQ6 haplotypes. This association was significant only when these haplotypes were found together with the DR4-DQ8 haplotype. Conclusions The previously reported association between HLA-risk haplotypes for T1D and an increased birth weight was not confirmed. This suggests that the mechanisms behind the association between high birth weight and risk for T1D may be not directly HLA related. Copyright (c) 2012 John Wiley & Sons, Ltd.

The hereditary spastic paraplegias (HSPs) are neu-rodegenerative disorders of the motor system. The information about the prevalence of the cognitive dysfunction in HSP is inconsistent. The aim of the study was to describe the prevalence of cognitive dysfunction and the cognitive profiles of persons with HSP (pwHSP) compared to healthy controls. Subjects. Participating in the cognition study were 48 persons with HSP from the epidemiological study and 48 healthy controls. Of those with HSP, 81% (39/48) had pure and 19% (9/48) had complex forms. Among pwHSP, 20.8% (10/48) had pathogenic and 14.6% (7/48) had non-pathogenic mutations in the SPAST gene. There were no mutations detected in 31 persons with the SPAST gene. Methods. Neuropsychological test battery, MMSE Results. The results of the neuropsychological tests were significantly lower in persons with HSP than in the controls (Bonferroni correction, p < 0.00625). There were statistically significant differences in subtests measuring consistent long term retrieval (p < 0.001), later recall (p = 0.004) in verbal memory and symbol digit modalities (p = 0.0015). Five persons with HSP had an MMSE score of 24 or less. Conclusions. Our results demonstrate that cognitive dysfunction is present in 16.7 to 33.3% of persons with HSP, depending on the criteria applied. There was cognitive dysfunction in 30% of persons with a known pathogenic mutation in the SPAST gene. The most frequently damaged functions in HSP are consistent long term retrieval and later recall in verbal memory and symbol digit modalities tests that discriminate between controls and pwHSP with dysfunction (1.5 SD) in three or more domains. Dementia in HSP is rare.