Lesion size and long-term cognitive outcome after pediatric stroke: A comparison between two techniques to assess lesion size.

BACKGROUND There is little consensus on how lesion size impacts long-term cognitive outcome after pediatric arterial ischemic stroke (AIS). This study, therefore, compared two techniques to assessed lesion size in the chronic phase after AIS and determined their measurement agreement in relation to cognitive functions in patients after pediatric stroke. METHODS Twenty-five patients after pediatric AIS were examined in the chronic phase (>2 years after stroke) in respect to intelligence, memory, executive functions, visuo-motor functions, motor abilities, and disease-specific outcome. Lesion size was measured using the ABC/2 formula and segmentation technique (3D Slicer). Correlation analysis determined the association between volumetry techniques and outcome measures in respect to long-term cognitive outcome. RESULTS The measurements from the ABC/2 and segmentation technique were strongly correlated (r = 0.878, p < .001) and displayed agreement in particular for small lesions. Lesion size from both techniques was significantly correlated with disease-specific outcome (p < .001) and processing speed (p < .005) after controlling for age at stroke and multiple comparison. CONCLUSION The two techniques showed convergent validity and were both significantly correlated with long-term outcome after pediatric AIS. Compared to the time-consuming segmentation technique, ABC/2 facilitates clinical and research work as it requires relatively little time and is easy to apply

Cognitive outcome is related to functional thalamo-cortical connectivity after paediatric stroke.

The thalamus has complex connections with the cortex and is involved in various cognitive processes. Despite increasing interest in the thalamus and the underlying thalamo-cortical interaction, little is known about thalamo-cortical connections after paediatric arterial ischaemic stroke. Therefore, the aim of this study was to investigate thalamo-cortical connections and their association with cognitive performance after arterial ischaemic stroke. Twenty patients in the chronic phase after paediatric arterial ischaemic stroke (≥2 years after diagnosis, diagnosed <16 years; aged 5-23 years, mean: 15.1 years) and 20 healthy controls matched for age and sex were examined in a cross-sectional study design. Cognitive performance (selective attention, inhibition, working memory, and cognitive flexibility) was evaluated using standardized neuropsychological tests. Resting-state functional magnetic resonance imaging was used to examine functional thalamo-cortical connectivity. Lesion masks were integrated in the preprocessing pipeline to ensure that structurally damaged voxels did not influence functional connectivity analyses. Cognitive performance (selective attention, inhibition, and working memory) was significantly reduced in patients compared to controls. Network analyses revealed significantly lower thalamo-cortical connectivity for the motor, auditory, visual, default mode network, salience, left/right executive, and dorsal attention network in patients compared with controls. Interestingly, analyses additionally revealed higher thalamo-cortical connectivity in some subdivisions of the thalamus for the default mode network (medial nuclei), motor (lateral nuclei), dorsal attention (anterior nuclei), and the left executive network (posterior nuclei) in patients compared with controls. Increased and decreased thalamo-cortical connectivity strength within the same networks was, however, found in different thalamic subdivisions. Thus, alterations in thalamo-cortical connectivity strength after paediatric stroke seem to point in both directions, with stronger as well as weaker thalamo-cortical connectivity in patients compared with controls. Multivariate linear regression, with lesion size and age as covariates, revealed significant correlations between cognitive performance (selective attention, inhibition, and working memory) and the strength of thalamo-cortical connectivity in the motor, auditory, visual, default mode network, posterior default mode network, salience, left/right executive, and dorsal attention network after childhood stroke. Our data suggest that the interaction between different sub-nuclei of the thalamus and several cortical networks relates to post-stroke cognition. The variability in cognitive outcomes after paediatric stroke might partly be explained by functional thalamo-cortical connectivity strength

Impact of Age at Pediatric Stroke on Long-term Cognitive Outcome.

OBJECTIVES To investigate the impact of age at pediatric arterial ischemic stroke on long-term cognitive outcome in order to identify patients particularly at risk for the development of cognitive long-term cognitive sequelae. METHODS This cross-sectional study included patients in the chronic phase of stroke (> 2 years after stroke) previously diagnosed with neonatal or childhood arterial ischemic stroke and a control group. Participants with active epilepsy, severe learning difficulties, or behavioral problems hindering the cognitive assessment were excluded. Several cognitive domains, including intelligence, executive functions (working memory, inhibition, and cognitive flexibility), processing speed, memory, letter fluency, and visual-motor skills were assessed with neuropsychological tests. Cognitive long-term outcome was compared across patients after neonatal stroke (stroke between 0 and 28 days of life), early childhood stroke (stroke between 29 days and < 6 years) and late childhood stroke (stroke between ≥ 6 and < 16 years). RESULTS 52 patients after neonatal or childhood arterial ischemic stroke (median age: 15.3 years, IQR = 10.6 - 18.7) and 49 healthy controls (median age: 13.6 years, IQR = 9.8 - 17.2) met the inclusion criteria. Cognitive outcome was significantly worse in the pediatric stroke group compared to the control group. A non-linear effect of age at stroke (irrespective of lesion size and lesion location) was found for cognitive flexibility, processing speed, and verbal learning with early childhood stroke (29 days to < 6 years) showing significantly worse cognitive outcome compared to neonatal or late childhood stroke (p < .05, FDR-corrected). CONCLUSION Age at stroke is an important factor for post-stroke recovery and modulates long-term cognitive outcome irrespective of lesion size and lesion location. Children after early childhood stroke are at particular risk for alterations of long-term cognitive functions

Correlation properties of spontaneous motor activity in healthy infants: a new computer-assisted method to evaluate neurological maturation

Qualitative assessment of spontaneous motor activity in early infancy is widely used in clinical practice. It enables the description of maturational changes of motor behavior in both healthy infants and infants who are at risk for later neurological impairment. These assessments are, however, time-consuming and are dependent upon professional experience. Therefore, a simple physiological method that describes the complex behavior of spontaneous movements (SMs) in infants would be helpful. In this methodological study, we aimed to determine whether time series of motor acceleration measurements at 40-44weeks and 50-55weeks gestational age in healthy infants exhibit fractal-like properties and if this self-affinity of the acceleration signal is sensitive to maturation. Healthy motor state was ensured by General Movement assessment. We assessed statistical persistence in the acceleration time series by calculating the scaling exponent α via detrended fluctuation analysis of the time series. In hand trajectories of SMs in infants we found a mean α value of 1.198 (95% CI 1.167-1.230) at 40-44weeks. Alpha changed significantly (p=0.001) at 50-55weeks to a mean of 1.102 (1.055-1.149). Complementary multilevel regression analysis confirmed a decreasing trend of α with increasing age. Statistical persistence of fluctuation in hand trajectories of SMs is sensitive to neurological maturation and can be characterized by a simple parameter α in an automated and observer-independent fashion. Future studies including children at risk for neurological impairment should evaluate whether this method could be used as an early clinical screening tool for later neurological compromis

Cerebral blood flow and cognitive outcome after pediatric stroke in the middle cerebral artery.

Adaptive recovery of cerebral perfusion after pediatric arterial ischemic stroke (AIS) is sought to be crucial for sustainable rehabilitation of cognitive functions. We therefore examined cerebral blood flow (CBF) in the chronic stage after stroke and its association with cognitive outcome in patients after pediatric AIS. This cross-sectional study investigated CBF and cognitive functions in 14 patients (age 13.5 ± 4.4 years) after pediatric AIS in the middle cerebral artery (time since AIS was at least 2 years prior to assessment) when compared with 36 healthy controls (aged 13.8 ± 4.3 years). Cognitive functions were assessed with neuropsychological tests, CBF was measured with arterial spin labeled imaging in the anterior, middle, and posterior cerebral artery (ACA, MCA, PCA). Patients had significantly lower IQ scores and poorer cognitive functions compared to healthy controls (p < 0.026) but mean performance was within the normal range in all cognitive domains. Arterial spin labeled imaging revealed significantly lower CBF in the ipsilesional MCA and PCA in patients compared to healthy controls. Further, we found significantly higher interhemispheric perfusion imbalance in the MCA in patients compared to controls. Higher interhemispheric perfusion imbalance in the MCA was significantly associated with lower working memory performance. Our findings revealed that even years after a pediatric stroke in the MCA, reduced ipsilesional cerebral blood flow occurs in the MCA and PCA and that interhemispheric imbalance is associated with cognitive performance. Thus, our data suggest that cerebral hypoperfusion might underlie some of the variability observed in long-term outcome after pediatric stroke

Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland.

Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland. We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy. Improvements were reported in 59 (66%) study participants. The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young. What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders. What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting. • The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions

Trends in Outcomes of Major Intracerebral Haemorrhage in a National Cohort of Very Preterm Born Infants in Switzerland

Background: Major brain lesions, such as grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI) are among the main predictors for poor neurodevelopment in preterm infants. In the last decades advancements in neonatal care have led to a general decrease in adverse outcomes. Aim: To assess trends of mortality and neurodevelopmental impairment (NDI) in a recent Swiss cohort of very preterm infants with grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI). Methods: In this retrospective population-based cohort study, rates of mortality, and NDI at 2 years corrected age were reported in infants born at 24–29 weeks gestational age (GA) in Switzerland in 2002–2014, with G3-IVH and/or PVHI. Results: Out of 4956 eligible infants, 462 (9%) developed G3-IVH (n = 172) or PVHI (n = 290). The average mortality rates for the two pathologies were 33% (56/172) and 60% (175/290), respectively. In 2002–2014, no change in rates of mortality (G3-IVH, p = 0.845; PVHI, p = 0.386) or NDI in survivors (G3-IVH, p = 0.756; PVHI, p = 0.588) were observed, while mean GA decreased (G3-IVH, p = 0.020; PVHI, p = 0.004). Multivariable regression analysis showed a strong association of G3-IVH and PVHI for both mortality and NDI. Death occurred after withdrawal of care in 81% of cases. Conclusion: In 2002–2014, rates of mortality and NDI in very preterm born infants with major brain lesions did not change. The significant decrease in mean GA and changing hospital policies over this time span may factor into the interpretation of these results

Correlation properties of spontaneous motor activity in healthy infants: a new computer-assisted method to evaluate neurological maturation

Qualitative assessment of spontaneous motor activity in early infancy is widely used in clinical practice. It enables the description of maturational changes of motor behavior in both healthy infants and infants who are at risk for later neurological impairment. These assessments are, however, time-consuming and are dependent upon professional experience. Therefore, a simple physiological method that describes the complex behavior of spontaneous movements (SMs) in infants would be helpful. In this methodological study, we aimed to determine whether time series of motor acceleration measurements at 40-44 weeks and 50-55 weeks gestational age in healthy infants exhibit fractal-like properties and if this self-affinity of the acceleration signal is sensitive to maturation. Healthy motor state was ensured by General Movement assessment. We assessed statistical persistence in the acceleration time series by calculating the scaling exponent α via detrended fluctuation analysis of the time series. In hand trajectories of SMs in infants we found a mean α value of 1.198 (95 % CI 1.167-1.230) at 40-44 weeks. Alpha changed significantly (p = 0.001) at 50-55 weeks to a mean of 1.102 (1.055-1.149). Complementary multilevel regression analysis confirmed a decreasing trend of α with increasing age. Statistical persistence of fluctuation in hand trajectories of SMs is sensitive to neurological maturation and can be characterized by a simple parameter α in an automated and observer-independent fashion. Future studies including children at risk for neurological impairment should evaluate whether this method could be used as an early clinical screening tool for later neurological compromise

Performance of the German version of the PARCA-R questionnaire as a developmental screening tool in two-year-old very preterm infants.

To validate and test a German version of the revised Parent Report of Children's Abilities questionnaire (PARCA-R). Multicentre cross-sectional study. Parents of infants born &lt;32 gestational weeks, completed the PARCA-R within three weeks before the follow-up assessment of their child at age two years. Infants were assessed using the Mental Development Index (MDI) of the Bayley Scales of Infant Development 2nd edition (BSID-II). Pearson correlation between the Parent Report Composite (PRC) of the PARCA-R and MDI was tested. The optimal PRC cut-off for predicting moderate-to-severe mental delay, defined as MDI&lt;70, was identified through the receiver operating characteristic (ROC) curve. PARCA-R and BSID-II data were collected from 154 consecutive infants [51% girls, mean (SD) gestational age 29.0 (2.0) weeks, birth weight 1174 (345) grams] at 23.2 (1.6) months of corrected age. The PRC score [70.5 (31.1)] correlated with the MDI [92.2 (17.3); R = 0.54; p &lt; 0.0001]. The optimal PRC cut-off for identifying mental delay was 44 with 0.81 (0.54-0.96) sensitivity (95%-CI), 0.81 (0.74-0.87) specificity, area under the ROC curve of 0.840 (0.729-0.952). The German version of the PARCA-R had good validity with the BSID-II and PCR scores &lt; 44 proved optimal discriminatory power for the identification of mental delay at two years of corrected age

Cohort profile: the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) cohort study.

BACKGROUND Cerebral Palsy (CP) is a group of permanent disorders of movement and posture that follow injuries to the developing brain. It results in motor dysfunction and a wide variety of comorbidities like epilepsy; pain; speech, hearing and vision disorders; cognitive dysfunction; and eating and digestive difficulties. Central data collection is essential to the study of the epidemiology, clinical presentations, care, and quality of life of patients affected by CP. CP specialists founded the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) in 2017. This paper describes the design, structure, aims and achievements of Swiss-CP-Reg and presents its first results. METHODS Swiss-CP-Reg records patients of any age diagnosed with CP who are born, are treated, or live in Switzerland. It collects data from medical records and reports, from questionnaires answered by patients and their families, and from data linkage with routine statistics and other registries. The registry contains information on diagnosis, clinical presentation, comorbidities, therapies, personal information, family history, and quality of life. RESULTS From August 2017 to August 2021, 546 participants (55% male, mean age at registration 8 years [interquartile range IQR: 5-12]), were enrolled in Swiss-CP-Reg. Most had been born at term (56%), were less than two years old at diagnosis (73%, median 18 months, IQR: 9-25), and were diagnosed with spastic CP (76%). Most (59%) live with a mild motor impairment (Gross Motor Function Classification System [GMFCS] level I or II), 12% with a moderate motor impairment (GMFCS level III), and 29% with a severe motor impairment (GMFCS level IV or V). In a subset of 170 participants, we measured intelligence quotient (IQ) and saw lower IQs with increasing GMFCS level. Swiss-CP-Reg has a strong interest in research, with four nested projects running currently, and many more planned. CONCLUSIONS Swiss-CP-Reg collects and exchanges national data on people living with CP to answer clinically relevant questions. Its structure enables retrospective and prospective data collection and knowledge exchange between experts to optimise and standardise treatment and to improve the health and quality of life of those diagnosed with CP in Switzerland