Mare Lintrop

Acutely and Retrospectively Diagnosed Perinatal Stroke A Population-Based Study

Background and Purpose— There are not very many epidemiological studies on perinatal stroke, and many authors suggest that this may be an underdiagnosed condition. The aim of the study was to estimate the incidence of perinatal arterial ischemic and hemorrhagic stroke in Estonia, to study the first clinical signs and to identify possible differences in predisposing factors and outcome between acutely and retrospectively diagnosed cases of perinatal stroke. Methods— A retro- and prospective study of acutely (within the first month) and retrospectively diagnosed ischemic and hemorrhagic cases of perinatal stroke was conducted in a children population born in the eastern and southern regions of Estonia during the years 1994 to 2003. Patients were identified from a pilot study, hospital records, and an inquiry of child neurologists and general practitioners. The diagnosis was confirmed in 38 (12 were diagnosed acutely and 26 retrospectively) cases by neuroradiology (MRI or CT). Results— The incidence rate of perinatal stroke in Estonia is 63 per 100 000 live births. Main clinical findings in the neonatal period were seizures, abnormalities of muscular tone, and disturbed level of alertness. Previously identified risk factors occurred in 32% of cases. Children with early diagnosis had more often adverse events during pregnancy and delivery (P<0.05) and developed more severe stage of hemiparesis compared with children with late diagnosis (P<0.05). Conclusions— The incidence rate of 63 per 100 000 live birth is higher than previously reported. Detailed analysis of the first signs of perinatal stroke may improve the early diagnostics of perinatal stroke.

Cerebral blood-flow velocities in predicting outcome of asphyxiated newborn infants

Aim: To evaluate the role of early (up to 12h) changes in cerebral blood‐flow (CBF) velocity in predicting the severity of hypoxic‐ischaemic encephalopathy (HIE) and long‐term outcome in asphyxiated term infants. Methods: CBF velocities were investigated by colour Doppler ultrasonography in 81 healthy and 60 asphyxiated term infants at least three times during the first 5 d of life. The psychomotor development of infants was followed up to 18 mo. Results: No differences in CBF velocities were found at the age of 2–6 h between infants with severe and mild‐moderate HIE, mean CBF velocity [mean (95% CI of mean CBF velocity)] in anterior cerebral artery [14.9 (1.4–28.4) cm/s] and [13.9 (11.1–16.7) cm/s], respectively, and between infants with poor outcome (death or severe disability) and with normal development/mild impairments. By the age of 12 h infants with mild‐moderate HIE and infants with normal development/mild impairments had decreased CBF velocity in the anterior cerebral artery, and infants with severe HIE or poor outcome had increased mean CBF velocity in anterior, medial cerebral and basilar artery compared to the control group.

Missense single nucleotide polymorphism of the ADAM12 gene is associated with radiographic knee osteoarthritis in middle-aged Estonian cohort

OBJECTIVE One of the recognized candidate genes of osteoarthritis (OA) is the ADAM metallopeptidase domain 12 (meltrin alpha) gene. We investigated the potential role of two single nucleotide polymorphisms (SNP) of the ADAM12 gene in susceptibility to radiographic knee OA and its progression in an Estonian cohort. METHODS The rs3740199 and rs1871054 polymorphisms were genotyped according to restriction fragment polymorphism in a population-based cohort consisting of 189 subjects selected from the age group 32-55 years. The radiological features of OA were measured in the tibio- and patellofemoral joints (PFJ). The X-ray investigation was repeated 3 years later for estimation of OA progression. RESULTS We found statistically significant association between rs3740199 polymorphism and patellofemoral OA in male patients (P=0.014), genetic risk was mostly related to CC homozygosity. The same SNP also affected the presence of advanced grade (II+III) osteophytes in the whole group (P=0.042) and the occurrence of osteophytes on the patellar margins in the PFJ (P=0.046). In OA progression the most significant association was found between joint space narrowing of the tibiofemoral joint and rs3740199 SNP in women (P=0.018). The rs1871054 polymorphism was not related to OA susceptibility or to progression traits. In our study the haplotype GC (rs3740199/rs1871054) was associated with reduced risk for development of osteophytes in the PFJ (P=0.041). CONCLUSIONS We conclude that rs3740199 polymorphism may affect occurrence of knee OA and its progression. We also hypothesize that the genetic contribution of ADAM12 to OA is remarkably gender-dependent and anatomical site-specific.

Developmental Changes in Cerebral and Visceral Blood Flow Velocity in Healthy Neonates and Infants

The purpose of this study was to evaluate the changes in Doppler blood flow velocity (BFV) in cerebral and visceral arteries during infancy.

Low cerebral blood flow velocity and head circumference in infants with severe hypoxic ischemic encephalopathy and poor outcome.

Aims: To evaluate long‐term changes in cerebral blood flow velocity (CBFV) and head circumference in asphyxiated infants.

Diagnostic and prognostic value of bone biomarkers in progressive knee osteoarthritis: a 6-year follow-up study in middle-aged subjects

OBJECTIVE To determine the value of bone markers in early-stage progressive knee osteoarthritis (OA), a population-based cohort of middle-aged subjects with chronic knee complaints was followed over 6 years (two consecutive two 3-year periods). METHODS Tibiofemoral (TF) and patellofemoral (PF) radiographs were graded in 128 subjects (mean age at baseline 45 ± 6.2 years) in 2002, 2005 and 2008. Bone formation was assessed by the serum concentration of procollagen type I amino-terminal propeptide (sPINP); bone resorption by the level of the C-terminal cross-linked telopeptides of type I collagen (sCTx-I); and bone mineralization by the values of osteocalcin (sOC) by electrochemiluminescence immunoassay. A novel marker of bone resorption, urinary osteocalcin midfragments (uMidOC), was assayed using enzyme linked immunosorbent assay (ELISA). RESULTS Several diagnostic associations were found between the bone markers (PINP, OC, MidOC) and progressive OA expressed by TF osteophytosis. The increasing output of MidOC demonstrated several-fold higher risk for progressive TF osteophytosis [odds ratio (OR) 5.32; 95% confidence interval (CI) 1.41-20.06, P = 0.014] than other bone markers. The values of PINP had prognostic value for subsequent more severely expressed knee OA progression [r(s) = 0.460, P = 0.005]. CONCLUSIONS Bone metabolism is activated in early-stage knee OA. OA progression was preceded by the enhanced bone formation (by PINP) and accompanied by the activation of bone formation (by PINP), non-collagenous bone resorption (by MidOC), as well as by changes in mineralization (by OC). All three bone markers had diagnostic value, and one of them, PINP, had also a predictive value for knee OA progression, especially for progressive osteophytosis.

Changes in Cerebral and Visceral Blood Flow Velocities in Asphyxiated Term Neonates With Hypoxic-Ischemic Encephalopathy

Objective. The purpose of this study was to evaluate changes in the Doppler blood flow velocity (BFV) in the cerebral and visceral arteries in asphyxiated term neonates. Methods. The BFV was measured in 47 asphyxiated and 37 healthy term neonates in the anterior cerebral artery, middle cerebral artery, basilar artery, internal carotid artery, celiac artery (CA), superior mesenteric artery (SMA), and renal artery (RA) up to the age of 60 to 149 days. Results. At the age of 12 to 120 hours after asphyxia, the mean BFV had increased, and the resistive index (RI) had decreased (P < .05) in all cerebral arteries in neonates with severe hypoxic‐ischemic encephalopathy (HIE) compared with the control group. In neonates with severe HIE, the mean BFV in the RA had significantly decreased at the age of 3 to 240 hours, and the RI had increased at the age of 24 to 240 hours, normalizing by the age of 21 to 59 days compared with the control group (P < .05). In the SMA, a decreased mean BFV was found in neonates with severe HIE compared with those with mild to moderate HIE only at the age of 24 to 36 hours. In neonates with mild to moderate HIE, the mean BFV had increased in the SMA and CA compared with the control group at the age of 2 to 11.9 hours. Conclusions. A severe alteration of the cerebral and visceral BFV takes place during the first days after asphyxia in neonates with different severities of HIE.

Predictive value of clinical and radiological findings in inflicted traumatic brain injury.

Aims:  The aim of this study is to evaluate the value of early radiological investigations in predicting the long‐term neurodevelopmental outcome of infants with inflicted traumatic brain injury (ITBI).

105 KNEE OSTEOARTHRITIS PROGRESSION DURING 6 YEARS FOLLOW-UP: THE PROGNOSTIC VALUE OF BONE AND CARTILAGE BIOMARKERS

Purpose: To investigate the prognostic value of bone-cartilage biomarkers in predicting knee OA progression during 6 years follow-up. Methods: A population cohort aged 35-55 years (n=141) was investigated at baseline and after 3 and 6 years follow-up. Tibiofemoral (TF) and patellofemoral (PF) radiographs were graded for OA. Progression was documented if presence of osteophytes and/or joint space narrowing (JSN) was described in subjects with no previous radiographic changes or in case of radiographic deterioration during 6 years. At baseline and at 3 years follow-up, biomarkers of bone resorption (CTx-I), formation (PINP), osteocalcin (OC) were assessed by ECLIA and cartilage oligomeric matrix protein (COMP) by ELISA. Specific markers of cartilage degradation (U-CTx-II) and synthesis (PIIANP) were assayed by ELISA only at 3-years follow-up. For statistics nonparametric methods were used. Results: Within 6 years follow-up, progression in TF joint was observed in 38% of cases, mostly from OA grade 0 to 1. At 3 years follow-up we documented radiographic OA progression in 16 men and 38 women out of 141, and at 6 years follow-up in 21 men and 49 women out of 131. In women, the progression in TF osteophytes during 6 year follow-up was related to higher levels of COMP compared to non-progressors (p=0.011). The higher COMP, OC and U-CTx-II levels in case of TF osteophyte progression was found already at 3 years follow-up. The women who developed TF JSN progression had lower PINP and higher PIIANP levels compared to non-progressors (p levels 0.030 and 0.031, respectively). Progression in PF JSN was related to higher COMP and U-CTx-II values (p levels 0.047 and 0.003, respectively). Increased U-CTx-II levels was found in women who had progression in TFOA and PFOA simultaneously (p=0.030). Baseline PINP levels were higher in those who developed TFOA and PFOA during 6 years follow-up (p=0.007). Baseline CTx-I levels were higher in case of PF osteophyte progression (p=0.037). In men, the progression in TF and PF osteophytes was related to higher levels of COMP (p levels 0.003 and 0.025, respectively). The progression in PF osteophytes during 6 years was related to the increase in PIIANP (p=0.019). The progression in JSN was associated with lower OC levels (p=0.045). Conclusions: • The 6 years follow-up demonstrated changes in radiographic stage as well as in the levels of the set of biomarkers. • The pattern of biomarkers differed by gender. • In both genders, S-COMP levels that reflect the status of several soft joint tissues was associated with the development of TF osteophytes. • In women, increased degradation of articular cartilage based on U-CTx-II associated with progression in PF JSN. The same process was found in cases when TFOA and PFOA progression was combined. • Increased synthesis of articular cartilage based on S-PIIANP was related to progression in TF JSN that might refer to enhanced reparative process. • The activation of bone metabolism was demonstrated in future knee OA progressors already at baseline by the increase in osteoblast-related biomarkers S-OC and S-PINP. This study is supported by ECTS/Czech Society Young Investigator Grant. 106

Inflicted traumatic brain injury (ITBI) or shaken baby syndrome (SBS) in Estonia: Inflicted brain injury in infants

Background: Inflicted traumatic brain injury (ITBI) or shaken baby syndrome (SBS) is recognized as a major cause of disability and death in the paediatric population. Aim: To find out the incidence of ITBI in Estonia. Methods: 26 cases of ITBI were recognized: four children died, 22 survived. Results: Of 26 children, 20 (77%) were boys and six (23%) were girls. Median age at admission to hospital was 3.9 mo, and the boys were younger than the girls. Conclusion: The overall incidence of ITBI was 28.7 per 100 000 infants. In the prospective group the incidence was 40.5 per 100 000, and in retrospective group 13.5 per 100 000. ITBI is not rare but not always a recognized form of child abuse. Healthcare professionals should be more aware of this condition.