Anneli Kolk

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.

Neurocognitive development of children with congenital unilateral brain lesion and epilepsy

The aim of this study was to specify the neuropsychological deficits characteristic of children with unilateral non-progressive brain lesion. In order to assess these specific functions, we used a comprehensive model of congenital hemiparesis with partial epilepsy and newly diagnosed partial epilepsy without hemiparesis. The neuropsychological examination was performed using the NEPSY test battery on 44 children aged from 4 to 9 years. The children were divided into three groups: 18 children suffering from congenital hemiparesis with chronic partial epilepsy, 12 children with newly diagnosed partial epilepsy prior to anti-epileptic treatment, and 14 healthy controls matched by sex, age, and socioeconomic status. Children with congenital hemiparesis and epilepsy had a more clearly expressed cognitive dysfunction, especially in language, visuo-perceptual and memory tasks, than children with newly diagnosed partial epilepsy. The profile of cognitive weakness appears to be diffuse and quite similar in both groups, and it did not demonstrate a clear effect of lateralization, according to the side of epileptic electroencephalogram discharges. Children within both groups are likely to have a high risk of developing attention, phonological, visuo-perceptual, and memory deficits in their life. Especially interesting and surprising was the fact that the newly diagnosed epilepsy group demonstrated impairment not only in attention, visuo-perceptual and short-term memory skills, but also in auditory perception, lexical function, and the comprehension of speech. Therefore, it is recommended that children with epilepsy would undergo neuropsychological examination in order to assess their cognitive abilities.

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

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.

Long-Term Cognitive Outcomes After Pediatric Stroke

This study assessed neurocognitive and neurologic outcomes of children with neonatal and childhood strokes. Twenty-one children with neonatal (mean age, 6.86 years) and 10 children with childhood (mean age, 8.21 years) strokes, identified via the Estonian Pediatric Stroke Database (1995-2006), participated. A developmental neuropsychologic assessment was used for neurocognitive outcomes, and the Paediatric Stroke Outcome Measure for neurologic outcomes. Neuromotor impairment was evident in 62% of children with neonatal strokes, and in 70% of children with childhood strokes. Compared with control subjects, children with strokes exhibited worse attention, language, memory, and sensorimotor functions. The sensorimotor domain comprised the most impaired neurocognitive area, whereas executive functions remained intact in both stroke groups. A well-preserved executive function may account for the normal range of intelligence in children with strokes. More severe impairment in neurocognitive skills was evident after neonatal strokes, and the visuospatial domain was more impaired than in children from the childhood group. Prognoses were worse after left hemisphere strokes associated with epilepsy. Our results on emerging neurocognitive deficits in several areas underline the importance of neuropsychologic testing and the follow-up of children with pediatric strokes.

The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition

BACKGROUND Deletions and duplications of the 16p11.2 BP4-BP5 locus are prevalent copy number variations (CNVs), highly associated with autism spectrum disorder and schizophrenia. Beyond language and global cognition, neuropsychological assessments of these two CNVs have not yet been reported. METHODS This study investigates the relationship between the number of genomic copies at the 16p11.2 locus and cognitive domains assessed in 62 deletion carriers, 44 duplication carriers, and 71 intrafamilial control subjects. RESULTS IQ is decreased in deletion and duplication carriers, but we demonstrate contrasting cognitive profiles in these reciprocal CNVs. Deletion carriers present with severe impairments of phonology and of inhibition skills beyond what is expected for their IQ level. In contrast, for verbal memory and phonology, the data may suggest that duplication carriers outperform intrafamilial control subjects with the same IQ level. This finding is reminiscent of special isolated skills as well as contrasting language performance observed in autism spectrum disorder. Some domains, such as visuospatial and working memory, are unaffected by the 16p11.2 locus beyond the effect of decreased IQ. Neuroimaging analyses reveal that measures of inhibition covary with neuroanatomic structures previously identified as sensitive to 16p11.2 CNVs. CONCLUSIONS The simultaneous study of reciprocal CNVs suggests that the 16p11.2 genomic locus modulates specific cognitive skills according to the number of genomic copies. Further research is warranted to replicate these findings and elucidate the molecular mechanisms modulating these cognitive performances.

Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Children and Youth Aged 0-19 Years: Data from the Global and Regional Burden of Stroke 2013

Background: There is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management. Objectives: To estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013. Conclusions: Globally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries. There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care.

Epidemiology of Childhood Stroke in Estonia

We investigated the incidence and 30-day case-fatality of childhood stroke in Estonia, and clinical signs and risk factors of childhood stroke. A retrospective (1995-2003) and prospective study (2004-2006) of childhood stroke (arterial ischemic, hemorrhagic, and sinovenous thrombosis) and transient ischemic attack was conducted. Stroke-incidence calculation was based on the prospective study. Clinical diagnoses of stroke were confirmed by neuroradiology. The incidence rate of childhood stroke in Estonia was 2.73/100,000 person-years for children aged 30 days to 18 years: 1.61/100,000 for arterial ischemic stroke, 0.87/100,000 for hemorrhagic stroke, 0.25/100,000 for sinovenous thrombosis, and 0.37/100,000 for transient ischemic attack. No arterial ischemic stroke patients died within 30 days, but case-fatality for intracerebral hemorrhage was 46%. Focal signs occurred in 100% of arterial ischemic strokes and 64% of intracerebral hemorrhage cases. Risk factors were identified in 35/48 (73%) children with cerebrovascular attacks. Six children with arterial ischemic stroke (6/24, 25%) manifested more than one risk factor. The incidence rate of childhood stroke in Estonia is similar to that in earlier data.

Factor V Leiden and prothrombin 21210G>A mutation and paediatric ischaemic stroke: a case–control study and two meta‐analyses

Aim:  To determine whether factor V Leiden (FVL) and prothrombin (PT) 20210G>A mutation are associated with paediatric ischaemic stroke.

Different Plasticity Patterns of Language Function in Children With Perinatal and Childhood Stroke

Plasticity of language function after brain damage can depend on maturation of the brain. Children with left-hemisphere perinatal (n = 7) or childhood stroke (n = 5) and 12 controls were investigated using functional magnetic resonance imaging. The verb generation and the sentence comprehension tasks were employed to activate the expressive and receptive language areas, respectively. Weighted laterality indices were calculated and correlated with results assessed by neuropsychological test battery. Compared to controls, children with childhood stroke showed significantly lower mean scores for the expressive (P < .05) and receptive (P = .05) language tests. On functional magnetic resonance imaging they showed left-side cortical activation, as did controls. Perinatal stroke patients showed atypical right-side or bilateral language lateralization during both tasks. Negative correlation for stroke patients was found between scores for expressive language tests and laterality index during the verb generation task. (Re)organization of language function differs in children with perinatal and childhood stroke and correlates with neurocognitive performance.

The incidence of childhood traumatic brain injury in Tartu and Tartu County in Estonia.

Background: Traumatic brain injury (TBI) is a major health problem in childhood. Estonia and other Baltic states have the highest trauma-related mortality in the European Union. There are no data on the incidence and causes of TBI for children in Estonia. The aim of this study was to estimate the incidence, structure and main causes of TBI in Tartu and Tartu County. Methods: The study was carried out at Tartu University Hospital, between January 1, 2001, and December 31, 2005. For inclusion in the study the following criteria had to be fulfilled: age 0–14 years, documented brain trauma and neurological symptoms and residency in Tartu or Tartu County. Over the study period the inclusion criteria were fulfilled in 478 cases [272 boys (57%) and 206 girls (43%)]. Results: The incidence of TBI in childhood in Tartu and Tartu County was 369:100,000 (405:100,000 for boys, 330:100,000 for girls). The incidence was highest among children from 0 to 4 years of age – 566:100,000. The main cause of TBI in all age groups was falling – 63.6%. According to severity, 82% of the cases were mild and 18% were moderate and severe. Conclusions: There is an urgent need for governmental prevention programs for TBI in children in Estonia.