Perinatal Stroke Research Articles

Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): a first-in-human, open-label intervention study

Perinatal arterial ischaemic stroke (PAIS) is an important cause of neurodevelopmental disabilities. In this first-in-human study, we aimed to assess the feasibility and safety of intranasally delivered bone marrow-derived allogeneic mesenchymal stromal cells (MSCs) to treat PAIS in neonates. In this open-label intervention study in collaboration with all neonatal intensive care units in the Netherlands, we included neonates born at full term (≥36 weeks of gestation) with MRI-confirmed PAIS in the middle cerebral artery region. All eligible patients were transferred to the neonatal intensive care unit of the Wilhelmina Children's Hospital. Neonates received one dose of 45-50 × 106 bone-marrow derived MSCs intranasally within 7 days of presenting signs of PAIS. The primary endpoints were acute and subacute safety outcomes, including vital signs, blood markers, and the occurrence of toxicity, adverse events, and serious adverse events. The occurrence of unexpected cerebral abnormalities by a repeat MRI at 3 months of age was a secondary endpoint. As part of standard clinical follow-up at Wilhelmina Children's Hospital, we assessed corticospinal tract development on MRI and performed motor assessments at 4 months of age. This study is registered with ClinicalTrials.gov, NCT03356821. Between Feb 11, 2020, and April 29, 2021, ten neonates were enrolled in the study. Intranasal administration of MSCs was well tolerated in all ten neonates. No serious adverse events were observed. One adverse event was seen: a mild transient fever of 38°C without the need for clinical intervention. Blood inflammation markers (C-reactive protein, procalcitonin, and leukocyte count) were not significantly different pre-administration versus post-administration and, although thrombocyte levels increased (p=0·011), all were within the physiological range. Follow-up MRI scans did not show unexpected structural cerebral abnormalities. All ten patients had initial pre-Wallerian changes in the corticospinal tracts, but only four (40%) patients showed asymmetrical corticospinal tracts at follow-up MRI. Abnormal early motor assessment was found in three (30%) infants. This first-in-human study demonstrates that intranasal bone marrow-derived MSC administration in neonates after PAIS is feasible and no serious adverse events were observed in patients followed up until 3 months of age. Future large-scale placebo-controlled studies are needed to determine the therapeutic effect of intranasal MSCs for PAIS. Netherlands Organization for Health Research and Development (ZonMw).

Perinatal stroke: modelling and the potential of neurovisualization

Perinatal stroke (PS), characterized by sudden disappearance or impairment of brain functions, is a socially significant form of pathology that leads to the death and/or disability of children. Depending on the extent of the lesion, the severity of the consequences of a PS varies from a slight lag in learning to lifelong disability and inability to independently take care of yourself. The most common complications are cerebral palsy and epilepsy. Since the possibilities of diagnosis and therapy in the acute period are extremely limited, the efforts of health care providers and scientists are aimed at improving approaches to the rehabilitation of such patients. The authors presented an overview of modern methods of modelling PS in various experimental conditions. It is established that the modelling of PS is continuously being improved, new ways of forming ischemic brain damage are being created, each of which is necessary for the development of new scientific criteria for its early diagnosis and prediction of outcomes in standardized conditions. It is shown that a special place in the diagnosis of ischemic brain damage is occupied by wide-field optical visualization, which allows determining the formation of neural networks and functional maps of the cortex of the developing brain, provides an opportunity to analyze the spatiotemporal activity of neurons in large areas of the cerebral cortex and the processes of restoring cortical functions in the post-traumatic period. With the advent of genetically encoded ion sensor proteins and technologies for obtaining transgenic animal lines that specifically express sensors directly in neurons, opportunities have been created for optical registration of neural activity by analyzing changes in spontaneous activity of calcium signals and other mechanisms, which allows us to study brain neuroplasticity at a new level and create new ways to correct ischemic brain damage.

Association of Perinatal and Childhood Ischemic Stroke With Attention-Deficit/Hyperactivity Disorder

Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts. To assess the risk of ADHD in children after pediatric ischemic stroke. Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021. Pediatric ischemic stroke. Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives. Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI ,1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]). This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD, particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.

Robotic mapping of motor cortex in children with perinatal stroke and hemiparesis.

Brain stimulation combined with intensive therapy may improve hand function in children with perinatal stroke‐induced unilateral cerebral palsy (UCP). However, response to therapy varies and underlying neuroplasticity mechanisms remain unclear. Here, we aimed to characterize robotic motor mapping outcomes in children with UCP. Twenty‐nine children with perinatal stroke and UCP (median age 11 ± 2 years) were compared to 24 typically developing controls (TDC). Robotic, neuronavigated transcranial magnetic stimulation was employed to define bilateral motor maps including area, volume, and peak motor evoked potential (MEP). Map outcomes were compared to the primary clinical outcome of the Jebsen–Taylor Test of Hand Function (JTT). Maps were reliably obtained in the contralesional motor cortex (24/29) but challenging in the lesioned hemisphere (5/29). Within the contralesional M1 of participants with UCP, area and peak MEP amplitude of the unaffected map were larger than the affected map. When comparing bilateral maps within the contralesional M1 in children with UCP to that of TDC, only peak MEP amplitudes were different, being smaller for the affected hand as compared to TDC. We observed correlations between the unaffected map when stimulating the contralesional M1 and function of the unaffected hand. Robotic motor mapping can characterize motor cortex neurophysiology in children with perinatal stroke. Map area and peak MEP amplitude may represent discrete biomarkers of developmental plasticity in the contralesional M1. Correlations between map metrics and hand function suggest clinical relevance and utility in studies of interventional plasticity.

Early, Intensive, Lower Extremity Rehabilitation Shows Preliminary Efficacy After Perinatal Stroke: Results of a Pilot Randomized Controlled Trial

Background Perinatal stroke injures motor regions of the brain, compromising movement for life. Early, intensive, active interventions for the upper extremity are efficacious, but interventions for the lower extremity remain understudied. Objective To determine the feasibility and potential efficacy of ELEVATE—Engaging the Lower Extremity Via Active Therapy Early—on gross motor function. Methods We conducted a single-blind, two-arm, randomized controlled trial (RCT), with the Immediate Group receiving the intervention while the Delay Group served as a 3-month waitlist control. A separate cohort living beyond commuting distance was trained by their parents with guidance from physical therapists. Participants were 8 months to 3 years old, with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. The intervention was play-based, focused on weight-bearing, balance and walking for 1 hour/day, 4 days/week for 12 weeks. The primary outcome was the Gross Motor Function Measure-66 (GMFM-66). Secondary outcomes included steps and gait analyses. Final follow-up occurred at age 4. Results Thirty-four children participated (25 RCT, 9 Parent-trained). The improvement in GMFM-66 over 12 weeks was greater for the Immediate than the Delay Group in the RCT (average change 3.4 units higher) and greater in younger children. Average step counts reached 1370-3750 steps/session in the last week of training for all children. Parent-trained children also improved but with greater variability. Conclusions Early, activity-intensive lower extremity therapy for young children with perinatal stroke is feasible and improves gross motor function in the short term. Longer term improvement may require additional bouts of intervention. Clinical trial registration This study was registered at ClinicalTrials.gov (NCT01773369).

The Effect of Constraint-Induced Movement Therapy Combined With Repetitive Transcranial Magnetic Stimulation on Hand Function in Preschool Children With Unilateral Cerebral Palsy: A Randomized Controlled Preliminary Study.

Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.

Erythropoietin as a Neuroprotective Drug for Newborn Infants: Ten Years after the First Use.

Protective strategies against perinatal brain injury represent a major challenge for modern neonatology. Erythropoietin (Epo) enhances endogenous mechanisms of repair and angiogenesis. In order to analyse the newest evidence on the role of Epo in prematurity, hypoxic ischemic encephalopathy (HIE) and perinatal stroke, a critical review using 2020 PRISMA statement guidelines was conducted. This review uncovered 26 clinical trials examining the use of Epo for prematurity and brain injury-related outcomes. The effects of Epo on prematurity were analysed in 16 clinical trials. Erythropoietin was provided until 32–35 weeks of corrected postnatal age with a dosage between 500–3000 UI/kg/dose. Eight trials reported the Epo effects on HIE term newborn infants: Erythropoietin was administered in the first weeks of life, at different multiple doses between 250–2500 UI/kg/dose, as either an adjuvant therapy with hypothermia or a substitute for hypothermia. Two trials investigated Epo effects in perinatal stroke. Erythropoietin was administered at a dose of 1000 IU/kg for three days. No beneficial effect in improving morbidity was observed after Epo administration in perinatal stroke. A positive effect on neurodevelopmental outcome seems to occur when Epo is used as an adjuvant therapy with hypothermia in the HIE newborns. Administration of Epo in preterm infants still presents inconsistencies with regard to neurodevelopmental outcome. Clinical trials show significant differences mainly in target population and intervention scheme. The identification of specific markers and their temporal expression at different time of recovery after hypoxia-ischemia in neonates might be implemented to optimize the therapeutic scheme after hypoxic-ischemic injury in the developing brain. Additional studies on tailored regimes, accounting for the risk stratification of brain damage in newborns, are required.

The Incidence and Characteristics of Perinatal Stroke in Beijing: A Multicenter Study.

ObjectiveTo assess the incidence, risk factors, and clinical characteristics of perinatal stroke in Beijing.MethodsThis multicenter prospective study included all the live births from 17 representative maternal delivery hospitals in Beijing from March 1, 2019 to February 29, 2020. Neonates with a stroke were assigned to the study group. Clinical data, including general information, clinical manifestations, and risk factors, were collected. Up until 18 months after birth, neonates were routinely assessed according to the Ages and Stages Questionnaire (ASQ) and/or the Bayley scale. Statistical analysis was done using the chi-squared, t-tests, and logistic regression analysis using SPSS version 26.0.OutcomesIn total, 27 cases were identified and the incidence of perinatal stroke in Beijing was 1/2,660 live births, including 1/5,985 for ischemic stroke and 1/4,788 for hemorrhagic stroke. Seventeen cases (62.96%) of acute symptomatic stroke and convulsions within 72 h (10 cases, 37.04%) were the most common presentations. Ten patients showed no neurological symptoms and were found to have had a stroke through routine cranial ultrasonography after being hospitalized for non-neurological diseases. The risk factors include primiparity, placental or uterine abruption/acute chorioamnionitis, intrauterine distress, asphyxia, and severe infection. In the study group, 11.1% (3/27) of patients had adverse neurodevelopmental outcomes. The patients in the study group had lower scores for the ASQ than those in the control group in the communication, gross, and fine motor dimensions.ConclusionThe incidence of perinatal stroke in Beijing was consistent with that in other countries. Routine neuroimaging of infants with risk factors may enable identification of asymptomatic strokes in more patients. Patients who have suffered from a stroke may have neurological sequelae; therefore, early detection, treatment, and regular follow-ups are beneficial for improving their recovery outcomes.

Language lateralization and outcome in perinatal stroke patients with different vascular types

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.

Risk of Autism After Pediatric Ischemic Stroke: A Nationwide Cohort Study.

Background and ObjectivesIschemic stroke increases the risk of neurodevelopmental disorders; however, the risk of autism is not thoroughly explored. Our aim was to evaluate risk of autism and risk factors for autism in children with pediatric ischemic stroke and in their first-degree relatives.MethodsIn this cohort study, individuals with ischemic stroke from 1969 to 2016, <18 years of age, alive 1 week after stroke, and without prior autism were identified in Swedish national registers. Ten matched controls per index individual and all first-degree relatives of index individuals and controls were identified. Conditional Cox regression was used to calculate the risk of autism. Unconditional logistic regression was performed to analyze sex, gestational age, age at stroke diagnoses, comorbid adverse motor outcome, comorbid epilepsy, and a sibling with autism as risk factors for autism in children with ischemic stroke.ResultsOf the 1,322 index individuals, 46 (3.5%) were diagnosed with autism compared to 161 (1.2%) controls (adjusted hazard ratio [aHR] 3.02, 95% CI 2.15–4.25). There was no significant difference in risk of autism according to age at stroke: perinatal (aHR 2.69, 95% CI 1.44–5.03) and childhood stroke (aHR 3.18, 95% CI 2.12–4.78). The increased risk remained after exclusion of children born preterm or small for gestational age (aHR 3.78, 95% CI 2.55–5.60) and when children with stroke diagnosed from 1997 to 2014 were analyzed (aHR 2.91, 95% CI = 1.95–4.35). Compared to controls, the risk of autism was increased in individuals with ischemic stroke and comorbid epilepsy (aHR 7.05, 95% CI 3.74–13.30), as well as adverse motor outcome (aHR 4.28, 95% CI 2.44–7.51). When individuals with adverse motor outcome and epilepsy were censored, the risk of autism was still increased (aHR 2.37, 95% CI 1.45–3.85). Sex, gestational age, and having a sibling with autism were not associated with autism in individuals with pediatric ischemic stroke.DiscussionAn increased risk of autism was seen after pediatric ischemic stroke, particularly in individuals with comorbid epilepsy, and could not be explained by being born preterm or small for gestational age. The risk was increased also in individuals free from epilepsy and adverse motor outcome, implying that all children with ischemic stroke should be readily screened for autism if the disorder is suspected.

Study Protocol: Multimodal Longitudinal Assessment of Infant Brain Organization and Recovery in Perinatal Brain Injury.

Perinatal brain injury is a primary cause of cerebral palsy, a condition resulting in lifelong motor impairment. Infancy is an important period of motor system development, including development of the corticospinal tract (CST), the primary pathway for cortical movement control. The interaction between perinatal stroke recovery, CST organization, and resultant motor outcome in infants is not well understood. Here, we present a protocol for multimodal longitudinal assessment of brain development and motor function following perinatal brain injury using transcranial magnetic stimulation and magnetic resonance imaging to noninvasively measure CST functional and structural integrity across multiple time points in infants 3 to 24 months of age. We will further assess the association between cortical excitability, integrity, and motor function. This protocol will identify bioindicators of motor outcome and neuroplasticity and subsequently inform early detection, diagnosis, and intervention strategies for infants with perinatal stroke, brain bleeds, and related diagnoses.

Structural connectivity of the sensorimotor network within the non-lesioned hemisphere of children with perinatal stroke

Perinatal stroke occurs early in life and often leads to a permanent, disabling weakness to one side of the body. To test the hypothesis that non-lesioned hemisphere sensorimotor network structural connectivity in children with perinatal stroke is different from controls, we used diffusion imaging and graph theory to explore structural topology between these populations. Children underwent diffusion and anatomical 3T MRI. Whole-brain tractography was constrained using a brain atlas creating an adjacency matrix containing connectivity values. Graph theory metrics including betweenness centrality, clustering coefficient, and both neighbourhood and hierarchical complexity of sensorimotor nodes were compared to controls. Relationships between these connectivity metrics and validated sensorimotor assessments were explored. Eighty-five participants included 27 with venous stroke (mean age = 11.5 ± 3.7 years), 26 with arterial stroke (mean age = 12.7 ± 4.0 years), and 32 controls (mean age = 13.3 ± 3.6 years). Non-lesioned primary motor (M1), somatosensory (S1) and supplementary motor (SMA) areas demonstrated lower betweenness centrality and higher clustering coefficient in stroke groups. Clustering coefficient of M1, S1, and SMA were inversely associated with clinical motor function. Hemispheric betweenness centrality and clustering coefficient were higher in stroke groups compared to controls. Hierarchical and average neighbourhood complexity across the hemisphere were lower in stroke groups. Developmental plasticity alters the connectivity of key nodes within the sensorimotor network of the non-lesioned hemisphere following perinatal stroke and contributes to clinical disability.

Perinatal Stroke; Risk Factors and Outcome. A Study from Aga Khan University Hospital Karachi

Objective: To determine the frequency, risk factors and the outcomes of a perinatal stroke.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Neonatal Intensive Care Unit, Department of Pediatrics, Aga Khan University Hospital, Karachi Pakistan, from Jan to Dec 2019.&#x0D; Methodology: Neonates with perinatal stroke confirmed on the neuroimaging, were included in the study. The primary outcomes were risk factors, divided into 3 groups, maternal, placental and neonatal. The secondary outcome was the condition at the time of the discharge.&#x0D; Results: A total of 58 patients were included in the study. Maternal risk factors identified in the study, were intrauterine infections 10 (17.2%), anti-phospholipid syndrome, gestational diabetes 8 (13.8%) and preeclampsia 7 (12.1%). Chorioamnionitis 9 (15.5%), antepartum hemorrhage 6 (10.3%), and placenta previa 4 (6.9%) were the placental risk factors. Neonatal risk factors were birth asphyxia 35 (60.3%), sepsis/meningitis 8 (13.8%), premature birth 6 (10.3%) and fetal bradycardia 4 (6.9%). Resuscitation was needed in 35 (60.3%) neonates with birth asphyxia. Haemorrhagic stroke was observed in 38 (65.5%) cases, ischemic stroke in 14 (24.1%) cases and mixed type of stroke was found in 6 (10.3%) patients. The total mortality rate in our study was13.8%.&#x0D; Conclusion: Haemorrhagic stroke was more common than ischemic or mixed stroke among the patients of perinatal stroke at our healthcare facility. Patients with low APGAR score at 5 minutes, birth asphyxia and male gender, were most affected.

Cognitive development after perinatal unilateral infarctions: No evidence for preferential sparing of verbal functions.

Even children with extensive perinatal left-sided lesions have been reported to show normal language functions based on right-hemispheric language reorganization. This reorganization can lead to deficits in originary right hemispheric functions ("crowding hypothesis"). In a previous study, however, we identified epilepsy (even when well-controlled), and not language reorganization, as the major risk factor for impaired nonverbal functions. Here, we asked whether verbal and nonverbal functions develop differently, and whether they share the same risk factors. We investigated 23 patients (11f, Md=12.56 years) with perinatal strokes (16 left-sided, 8 with epilepsy), and 23 healthy age-matched controls (8 f, Md=12.42years). Language functions were assessed using the Potsdam Illinois Test of Psycholinguistic Abilities, nonverbal intelligence with the Test of Nonverbal Intelligence, language lateralization with functional MRI, and lesion size with MRI-based volumetry. We found no systematic difference between verbal and nonverbal skills in our patients or controls [median difference Z(PITPA)-Z(TONI): patients=-0.03, controls=-0.06]. Accordingly, verbal and nonverbal functions were strongly correlated in patients (r=0.80) and in controls (r=0.74). Language ability correlated significantly with epilepsy. Furthermore, in patients with epilepsies, verbal skills were significantly lower than in controls. In our cohort, we found no evidence for a differential effect of perinatal strokes on the development of verbal versus nonverbal functions, and, specifically, no evidence for a preferential sparing of verbal functions. Epilepsy, even when well-controlled, was confirmed as a single key risk factor for verbal functions.

Bimanual performance in children with unilateral perinatal arterial ischaemic stroke or periventricular haemorrhagic infarction.

Long term outcome data on bimanual performance in children with perinatal arterial ischaemic stroke (PAIS) and periventricular haemorrhagic infarction (PVHI) with and without unilateral spastic cerebral palsy (USCP) is sparse. To assess bimanual performance in children with PAIS or PVHI with and without USCP and to explore the relationship with unilateral hand function and full-scale IQ (FSIQ) in a cross-sectional study. Fifty-two children with PAIS (n=27) or PVHI (n=25) participated at a median age of 12 years and 1 month (range 6-20 years). The Bruininks Oseretsky Test of Motor Proficiency-2 (bimanual precision and dexterity subtest), Assisting Hand Assessment, Purdue Pegboard Test and Wechsler Intelligence scale were administered. Bimanual dexterity was worse in children with USCP (p<0.02) without a difference for the pathology groups. In children without USCP (n=21), those with PAIS showed a better bimanual precision compared to children with PVHI (p<0.04). The AHA score and the Purdue Pegboard score of the dominant hand explained 51% of the variance in bimanual precision and dexterity in children with USCP. In absence of USCP, FSIQ together with AHA scores explained 66% of the variance in bimanual precision and FSIQ together with the Purdue Pegboard Test score of the dominant hand, 71% of the variance in bimanual dexterity. Children with PAIS without USCP have a more favourable bimanual hand function compared to children with PVHI. This difference appears to be associated with a preserved FSIQ.

Grappling with uncertainty – Experiences of parents of infants following perinatal stroke

BackgroundThe term perinatal stroke describes focal damage to the developing brain due to cerebrovascular disease and occurring either before or shortly after birth. Aetiology, presentation and evolution differ from stroke in adults. AimsWe aimed to explore early parental experiences related to having a child with perinatal stroke, including how parental psychological wellbeing had been impacted, to consider how support for families could be improved. Methods and proceduresWe undertook a qualitative research study, using in-depth interviews of parents of infants with perinatal stroke when the infants were 5–6 months corrected gestational age. Sixteen parents (11 female, 5 male) of 11 infants with perinatal stroke took part. Thematic analysis was used in data interpretation. Outcomes and resultsParents described distress related to the lack of information regarding likely outcome following perinatal stroke, as well as confusion around the term ‘stroke’. Guilt and self-blame were expressed, with increased emotional sensitivity. Seeking information about stroke to reduce uncertainty was a useful strategy for some, but overwhelming for others. Conclusions and implicationsThe diagnosis of perinatal stroke led to psychological distress in parents. Uncertainty following diagnosis produced significant emotional difficulties. Recommendations for practice include providing timely, paced information and psychological support.

Childhood stroke.

Stroke is an important cause of neurological morbidity in children; most survivors have permanent neurological deficits that affect the remainder of their life. Stroke in childhood, the focus of this Primer, is distinguished from perinatal stroke, defined as stroke before 29 days of age, because of its unique pathogenesis reflecting the maternal-fetal unit. Although approximately 15% of strokes in adults are haemorrhagic, half of incident strokes in children are haemorrhagic and half are ischaemic. The causes of childhood stroke are distinct from those in adults. Urgent brain imaging is essential to confirm the stroke diagnosis and guide decisions about hyperacute therapies. Secondary stroke prevention strongly depends on the underlying aetiology. While the past decade has seen substantial advances in paediatric stroke research, the quality of evidence for interventions, such as the rapid reperfusion therapies that have revolutionized arterial ischaemic stroke care in adults, remains low. Substantial time delays in diagnosis and treatment continue to challenge best possible care. Effective primary stroke prevention strategies in children with sickle cell disease represent a major success, yet barriers to implementation persist. The multidisciplinary members of the International Pediatric Stroke Organization are coordinating global efforts to tackle these challenges and improve the outcomes in children with cerebrovascular disease.

Precise control of embolic stroke with magnetized red blood cells in mice

Precise embolism control in immature brains can facilitate mechanistic studies of brain damage and repair after perinatal arterial ischemic stroke (PAIS), but it remains a technical challenge. Microhemorrhagic transformation is observed in one-third of infant patients who have suffered PAIS, but the underlying mechanism remains elusive. Building on an established approach that uses magnetic nanoparticles to induce PAIS, we develop a more advanced approach that utilizes magnetized erythrocytes to precisely manipulate de novo and in situ embolus formation and reperfusion in perinatal rodent brains. This approach grants spatiotemporal control of embolic stroke without any transarterial delivery of pre-formed emboli. Transmission electron microscopy revealed that erythrocytes rather than nanoparticles are the main material obstructing the vessels. Both approaches can induce microbleeds as an age-dependent complication; this complication can be prevented by microglia and macrophage depletion. Thus, this study provides an animal model mimicking perinatal embolic stroke and implies a potential therapeutic strategy for the treatment of perinatal stroke.

Long-term neurodevelopmental outcome of neonates born at term with perinatal haemorrhagic stroke: A population-based study.

AimTo assess the long‐term neurodevelopmental outcome of neonates born at term diagnosed with perinatal haemorrhagic stroke (PHS) and investigate the associations among brain territorial involvement, clinical risk factors, and neurodevelopmental outcomes.MethodWe conducted a population‐based study enrolling 55 neonates born at term with PHS confirmed by magnetic resonance imaging born between 2007 and 2017. Long‐term neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition, the Brunet–Lézine test, and the Stanford–Binet Intelligence Scales, Fifth Edition.ResultsFollow‐up was available in 50 (91%) of the infants, at a median age of 60 months (interquartile range 35–88). Forty per cent of the infants developed according to population norms, and developmental disabilities were diagnosed less frequently among neonates with frontal lobe PHS. In a multivariable model, parietal lobe PHS increased the risk for cerebral palsy (odds ratio [OR] 6.7; 95% confidence interval [CI] 1.1–41.4) and cognitive impairment (OR: 23.6; 95% CI: 2.9–194.9), while the involvement of the thalamus and/or basal ganglia was associated with epilepsy (OR: 7.0; 95% CI: 1.3–37.7). Seizures on admission were associated with epilepsy (OR: 10.8; 95% CI: 1.8–64.3). Patients with PHS affecting multiple lobes had poor prognosis.InterpretationParietal lobe haemorrhage, the involvement of the thalamus/basal ganglia, PHS affecting multiple lobes, and seizures were independent predictors of chronic neurodevelopmental sequelae, suggesting that the stroke territorial involvement and clinical risk factors influence the outcome of PHS.

Abstract TMP87: Higher Prevalence Of Autism Spectrum Disorder In Children With Perinatal Ischemic Stroke

Introduction: Perinatal stroke leads to significant morbidity over a child’s lifetime. Following perinatal stroke, children are more likely to be diagnosed with attention-deficit/hyperactivity disorder, intellectual disability, and language disorders. However, to our knowledge, studies examining the prevalence of autism spectrum disorder (ASD) in children with perinatal stroke do not exist. Methods: We retrospectively examined all children seen in the Stroke and Cerebrovascular Center at Boston Children’s Hospital from August 2008 through April 2021. All children with a history of perinatal ischemic stroke, either arterial or venous, aged ≥15 months old at the time of last follow-up were considered for inclusion. We classified patients as having ASD if their medical record included an ASD diagnosis by a neurologist, neuropsychologist, clinical psychologist, or developmental pediatrician. Multivariable logistic regression was performed to examine association between stroke type and ASD. Results: Among 285 children with perinatal stroke, 22 children (7.71%) also had ASD. Males had 8 times higher odds of ASD compared to females (OR= 8.07, p=0.007). Children with perinatal venous stroke had 2.5 times higher odds of ASD compared to those with arterial stroke (OR=2.58, p=0.05), which approached significance. There was not a significant difference in odds of autism in children diagnosed with presumed perinatal stroke compared to neonatal stroke. Conclusion: In our perinatal stroke population, the prevalence of ASD is 4 times higher than the prevalence of ASD in the general U.S. population (1.85%) as per the CDC in 2020. Boys had higher odds of autism, similar to what has been found in the general population. Interestingly, patients with venous stroke had higher odds of autism compared to those with arterial stroke. In conclusion, prospective studies are needed to further investigate the role of perinatal stroke in ASD development.