Neuroimaging and Neurological Outcomes in Perinatal Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Prediction of outcomes in perinatal arterial ischemic stroke (PAIS) is challenging. We performed a systematic review and meta-analysis to determine whether infarct characteristics can predict outcomes in PAIS. METHODS: A systematic search was conducted using five databases in January 2023. Studies were included if the sample included children with neonatal or presumed PAIS; if infarct size, location, or laterality was indicated; and if at least one motor, cognitive, or language outcome was reported. The level of evidence and risk of bias were evaluated using the Risk of Bias in Non-Randomized Studies of Interventions tool. Meta-analyses were conducted comparing infarct size or location with neurological outcomes when at least three studies could be analyzed. RESULTS: Eighteen full-text articles were included in a systematic review with nine included in meta-analysis. Meta-analyses revealed that small strokes were associated with a lower risk of cerebral palsy/hemiplegia compared with large strokes (risk ratio [RR] = 0.263, P = 0.001) and a lower risk of epilepsy (RR = 0.182, P < 0.001). Middle cerebral artery (MCA) infarcts were not associated with a significantly different risk of cerebral palsy/hemiplegia compared with non-MCA strokes (RR = 1.220, P = 0.337). Bilateral infarcts were associated with a 48% risk of cerebral palsy/hemiplegia, a 26% risk of epilepsy, and a 58% risk of cognitive impairment. CONCLUSIONS: Larger stroke size was associated with worse outcomes across multiple domains. Widely heterogeneous reporting of infarct characteristics and outcomes limits the comparison of studies and the analysis of outcomes. More consistent reporting of infarct characteristics and outcomes will be important to advance research in this field.

An international perspective on young stroke incidence and risk factors: a scoping review.

BACKGROUND: Stroke among younger age groups is increasing globally. While there is a focus on research conducted on people under 65 years who have had a stroke, there is a paucity of data on the incidence and risk factors of stroke among younger people (≤ 30 years). This scoping review examines evidence on incidence and risk factors for perinatal, paediatric and young adult stroke globally. METHODS: The review was guided by the Joanna Briggs Institute's scoping review methodology. A systematic search was conducted on 23rd March 2022 across Medline Ovid, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The eligibility criteria included all study designs providing information on the incidence and risk factors of stroke among young people (≤ 30 years) in the last ten years. RESULTS: A total of 5750 articles were identified. After screening, 471 articles (224 cohort studies (47.6%), 164 case studies/case series (34.8%), 35 reviews (7.4%), 30 case-control (6.4%) and 18 combinations of designs (3.8%) were included. There was data from 50 different countries, 199 studies were from high-income countries, upper and middle income (n = 38), lower middle-income (n = 39), low-income (n = 3) countries, international study (n = 7) and a further 185 articles did not state the country of research. Most of the studies (63%) focused on risk factors while incidence constituted 37%. Incidence data were reported heterogeneously across studies, leading to an inability to synthesise data. The three most frequently reported risk factors for perinatal stroke were infections, cardiac conditions, and intrapartum factors. Vasculopathies, infection and cardiac conditions accounted for most reported risk factors for paediatric stroke, while chronic conditions such as diabetes mellitus, vasculopathies and cardiac conditions accounted for the most reported risk factors among young adults. CONCLUSION: This review has highlighted different stroke risk factors for each age cohort of people under 30 years. The low number of epidemiological studies suggests that further research of this type is needed to fully understand the incidence and risk factors in young stroke. A standardised reporting of age groupings of incidence data is imperative to enable the comparison of data from different geographical locations.

Vascular syndrome predicts the development and course of epilepsy after perinatal stroke.

OBJECTIVE: Epilepsy 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. METHODS: The 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. RESULTS: The 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). SIGNIFICANCE: The 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.

The long-term negative impact of childhood stroke on language.

Objectives: This study aims to investigate the long-term language outcome in children with unilateral childhood stroke in comparison to those with perinatal strokes and typically developing individuals and to explore the impact of lesion-specific modifiers. Methods: We examined nine patients with childhood stroke, acquired between 0;2 and 16;1 years (CHILD; 3 female, median = 13.5 years, 6 left-sided), 23 patients with perinatal strokes (PERI; 11 female, median = 12.5 years, 16 left-sided), and 33 age-matched typically developing individuals (CONTROL; 15 female, median = 12.33 years). The language outcome was assessed using age-appropriate tasks of the Potsdam Illinois Test of Psycholinguistic Abilities (P-ITPA) or the Peabody Picture Vocabulary Test (PPVT). For group comparisons, study-specific language z-scores were calculated. Non-verbal intelligence was assessed using the Test of Non-verbal Intelligence (TONI-4), language lateralization with functional MRI, and lesion size with MRI-based volumetry. Results: All four patients with childhood stroke who initially presented with aphasic symptoms recovered from aphasia. Patients with childhood stroke showed significantly lower language scores than those in the control group, but their scores were similar to those of the patients with perinatal stroke, after adjusting for general intelligence (ANCOVA, language z-score CHILD = -0.30, PERI = -0.38, CONTROL = 0.42). Among the patients with childhood stroke, none of the possible modifying factors, including lesion side, correlated significantly with the language outcome. Conclusion: Childhood stroke, regardless of the affected hemisphere, can lead to chronic language deficits, even though affected children show a "full recovery." The rehabilitation of children and adolescents with childhood stroke should address language abilities, even after the usually quick resolution of clear aphasic symptoms.

Identification and treatment of surgically-remediable causes of infantile epileptic spasms syndrome.

INTRODUCTION: Infantile epileptic spasms syndrome (IESS) is a common developmental and epileptic encephalopathy with poor long-term outcomes. A substantial proportion of patients with IESS have a potentially surgically remediable etiology. Despite this, epilepsy surgery is underutilized in this patient group. Some surgically remediable etiologies, such as focal cortical dysplasia and malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), are under-diagnosed in infants and young children. Even when a surgically remediable etiology is recognised, for example, tuberous sclerosis or focal encephalomalacia, epilepsy surgery may be delayed or not considered due to diffuse EEG changes, unclear surgical boundaries, or concerns about operating in this age group. AREAS COVERED: In this review, the authors discuss the common surgically remediable etiologies of IESS, their clinical and EEG features, and the imaging techniques that can aid in their diagnosis. They then describe the surgical approaches used in this patient group, and the beneficial impact that early epilepsy surgery can have on developing brain networks. EXPERT OPINION: Epilepsy surgery remains underutilized even when a potentially surgically remediable cause is recognized. Overcoming the barriers that result in under-recognition of surgical candidates and underutilization of epilepsy surgery in IESS will improve long-term seizure and developmental outcomes.

Investigating the Impact on Long-Term Outcomes and the Necessity of Hereditary Thrombophilia Screening in Presumed or Perinatal Arterial Ischemic Stroke.

This study aimed to investigate the influence of prothrombotic risk factors on long-term outcomes of patients with perinatal arterial ischemic stroke. The study was conducted through an analysis of monitoring results that were regularly maintained for approximately 20 years at a tertiary stroke-monitoring center. The study assessed prothrombotic risk factors, radiological area of involvement, clinical presentation, treatments, clinical outcomes, and long-term outcomes of the 48 patients included in the study, with a mean monitoring time of 77.6 ± 45.7 months (range: 6-204). Our results showed that the presence of prothrombotic risk factors did not affect long-term outcomes. However, patients with middle cerebral artery infarction had the highest risk of developing cerebral palsy, whereas those with presumed stroke had the highest risk of developing epilepsy. This study suggests that prothrombotic risk factors should not be evaluated during the acute stage unless there is a strong suspicion of the patient's history, and prevention or early diagnosis of presumed stroke patients will positively impact their long-term prognosis.

Hand function after neonatal stroke: A graph model based on basal ganglia and thalami structure.

INTRODUCTION: Neonatal arterial ischemic stroke (NAIS) is a common model to study the impact of a unilateral early brain insult on developmental brain plasticity and the appearance of long-term outcomes. Motor difficulties that may arise are typically related to poor function of the affected (contra-lesioned) hand, but surprisingly also of the ipsilesional hand. Although many longitudinal studies after NAIS have shown that predicting the occurrence of gross motor difficulties is easier, accurately predicting hand motor function (for both hands) from morphometric MRI remains complicated. The hypothesis of an association between the structural organization of the basal ganglia (BG) and thalamus with hand motor function seems intuitive given their key role in sensorimotor function. Neuroimaging studies have frequently investigated these structures to evaluate the correlation between their volumes and motor function following early brain injury. However, the results have been controversial. We hypothesize the involvement of other structural parameters. METHOD: The study involves 35 children (mean age 7.3 years, SD 0.4) with middle cerebral artery NAIS who underwent a structural T1-weighted 3D MRI and clinical examination to assess manual dexterity using the Box and Blocks Test (BBT). Graphs are used to represent high-level structural information of the BG and thalami (volumes, elongations, distances) measured from the MRI. A graph neural network (GNN) is proposed to predict children's hand motor function through a graph regression. To reduce the impact of external factors on motor function (such as behavior and cognition), we calculate a BBT score ratio for each child and hand. RESULTS: The results indicate a significant correlation between the score ratios predicted by our method and the actual score ratios of both hands (p < 0.05), together with a relatively high accuracy of prediction (mean L1 distance < 0.03). The structural information seems to have a different influence on each hand's motor function. The affected hand's motor function is more correlated with the volume, while the 'unaffected' hand function is more correlated with the elongation of the structures. Experiments emphasize the importance of considering the whole macrostructural organization of the basal ganglia and thalami networks, rather than the volume alone, to predict hand motor function. CONCLUSION: There is a significant correlation between the structural characteristics of the basal ganglia/thalami and motor function in both hands. These results support the use of MRI macrostructural features of the basal ganglia and thalamus as an early biomarker for predicting motor function in both hands after early brain injury.

Periventricular hemorrhagic infarction in preterm neonates: Etiology and time of development.

BACKGROUND: To find the obstetrical and delivery associated risk factors of antenatal and postnatal grade III intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI) in preterm neonates. METHODS: A retrospective study of obstetric and delivery associated risk factors included neonates (<35 gestational weeks) with severe IVH/PVHI (n = 120) and a prospectively collected control group (n = 50). The children were divided into: (1) antenatal onset group (n = 27) with insult visible on cerebral ultrasonography within the first 12 hours of birth or periventricular cystic changes visible in PVHI within the first 3 days; (2) neonatal onset group (n = 70) with insult diagnosed after initial normal findings or I-II grade IVH, and (3) unknown time-onset group (n = 23) with insult visible at > 12 h of age. RESULTS: The mothers of the antenatal onset group had significantly more bacterial infections before delivery compared to the neonatal onset group: 20/27 (74.1%) versus 23/69 (33.3%), (odds ratio (OR) 5.7 [95% confidence interval 2.1-16]; p = 0.0008) or compared to the control group (11/50 (22%); OR 11 [2.8-42]; p = 0.0005). Placental histology revealed chorioamnionitis more often in the antenatal compared to the neonatal onset group (14/21 (66.7%) versus 16/42 (38.1%), respectively; OR 3.7 [1.18-11]; p = 0.025). Neonates with neonatal development of severe IVH/PVHI had significantly more complications during delivery or intensive care. CONCLUSIONS: Bacterial infection during pregnancy is an important risk factor for development of antenatal onset severe IVH or PVHI. In neonates born to mothers with severe bacterial infection during pregnancy, cerebral ultrasonography is indicated for early detection of severe IVH or PVHI.

Executive functioning, ADHD symptoms and resting state functional connectivity in children with perinatal stroke.

Perinatal stroke describes a group of focal, vascular brain injuries that occur early in development, often resulting in lifelong disability. Two types of perinatal stroke predominate, arterial ischemic stroke (AIS) and periventricular venous infarction (PVI). Though perinatal stroke is typically considered a motor disorder, other comorbidities commonly exist including attention-deficit hyperactivity disorder (ADHD) and deficits in executive function. Rates of ADHD symptoms are higher in children with perinatal stroke and deficits in executive function may also occur but underlying mechanisms are not known. We measured resting state functional connectivity in children with perinatal stroke using previously established dorsal attention, frontoparietal, and default mode network seeds. Associations with parental ratings of executive function and ADHD symptoms were examined. A total of 120 participants aged 6-19 years [AIS N = 31; PVI N = 30; Controls N = 59] were recruited. In comparison to typically developing peers, both the AIS and PVI groups showed lower intra- and inter-hemispheric functional connectivity values in the networks investigated. Group differences in between-network connectivity were also demonstrated, showing weaker anticorrelations between task-positive (frontoparietal and dorsal attention) and task-negative (default mode) networks in stroke groups compared to controls. Both within-network and between-network functional connectivity values were highly associated with parental reports of executive function and ADHD symptoms. These results suggest that differences in functional connectivity exist both within and between networks after perinatal stroke, the degree of which is associated with ADHD symptoms and executive function.

Prevalence & Risk Factors for Perinatal Stroke: A Population-Based Study.

Objectives: The study objective was to calculate the birth prevalence of perinatal stroke and examine risk factors in term infants. Some risk factors are present in healthy infants, making it difficult to determine at-risk infants. Study Design: Prospective population-based perinatal stroke data were compared to the Australian general population data using chi-squared and Fisher's exact tests and multivariable logistic regression analysis. Results: Sixty perinatal stroke cases were reported between 2017 and 2019. Estimated stroke prevalence was 9.6/100,000 live births/year including 5.8 for neonatal arterial ischemic stroke and 2.9 for neonatal hemorrhagic stroke. Eighty seven percent had multiple risk factors. Significant risk factors were cesarean section (p = 0.04), 5-min Apgar score <7 (p < 0.01), neonatal resuscitation (p < 0.01) and nulliparity (p < 0.01). Conclusions: Statistically significant independent risk factors do not fully explain the cause of perinatal stroke, because they are not a direct causal pathway to stroke. These data now require validation in a case-control study.

Long-term developmental condition following neonatal arterial ischemic stroke: A systematic review.

BACKGROUND: Neonatal arterial ischemic stroke (NAIS) is the most frequent subtype of perinatal stroke. Its elusive pathophysiology, its abrupt and unexpected occurrence, and the uncertainty of the post-NAIS developmental condition may lead to parental emotional distress and psychological difficulties. The aim of this study was to summarize the current data on long-term developmental conditions following NAIS to support parental information given within the neonatal unit. METHODS: This systematic review included clinical studies of term infants with NAIS, who had a developmental assessment at ≥5 years of age. Studies were identified from the Medline and Embase databases on June 1, 2022. The Joanna Briggs Institute (JBI) appraisal tool was used to assess the risk of bias. Results were synthesized using a narrative approach. The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed to report this work. RESULTS: Three cohort studies enrolling 205 children assessed from 5 to 7 years after NAIS were included. Most of the children presented long-term developmental conditions allowing them to be integrated into a regular school program, to participate in physical activities, and to have a good quality of life. Global intellectual deficiency and moderate-to-severe cerebral palsy occurred in less than 10% of the children. CONCLUSION: Physicians should not overestimate the incidence of moderate-to-severe developmental outcome following NAIS when discussing the prognosis with parents. A parental information sheet about NAIS and its long-term developmental conditions is provided.

The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke.

Background: Epilepsy 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. Methods: The 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. Results: During 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. Conclusion: In 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.

Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas / A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae

Introduction. Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. Aim. The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. Patients and methods. We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. Results. Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. Conclusions. If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible. (AU)

Introducción: El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes.ObjetivoDescribir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas.Pacientes y métodosEstudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital.ResultadosSe incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio.ConclusionesAnte un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible. (AU)

Perinatal Stroke in a Chinese Neonatal Center: Clinical Characteristics, Long-Term Outcomes, and Prognostic Factors.

BACKGROUND: Neonatal stroke manifests atypically and can potentially result in significant neurological sequelae in affected infants. Studies on long-term neurodevelopmental outcomes and prognostic factors are limited. We aimed to assess the clinical characteristics, long-term outcomes, and prognostic factors of perinatal stroke. METHODS: Patients diagnosed with perinatal stroke were enrolled from 2009 to 2018. Clinical data including general information, clinical manifestations, and risk factors were collected and compared. Follow-up was performed for at least two years. Statistical analysis was performed using the chi-square test, t tests, and logistic regression analysis. RESULTS: Sixty-nine cases were identified with an incidence of one of 2049 live births (51 boys and 18 girls). Twenty-seven patients (39%) experienced perinatal ischemic stroke (PIS) and 42 (61%) perinatal hemorrhagic stroke (PHS). In 48 cases (69%) onset involved acute symptomatic stroke (21 ischemic strokes and 27 hemorrhagic strokes). Seizures within 12 to 72 hours (20 cases, 29%) were the most common presentations. Most (57%) perinatal arterial ischemic strokes focused on the left middle cerebral artery. About 43% of PHS was diagnosed with temporal lobe hemorrhage, and 40% of patients exhibited multiple lesions of cerebral parenchymal hemorrhage. There was no association between adverse prognosis after perinatal stroke and different risk factors. During follow-up, six patients (10%) were dead and 22 patients (35%) experienced adverse neurodevelopmental outcomes. CONCLUSIONS: More infants exhibited hemorrhagic stroke than ischemic stroke. Among infants with asymptomatic perinatal stroke, PHS was more common. The first symptom of perinatal stroke within 12 to 72 hours after birth is convulsions, with the left middle cerebral artery and the temporal lobe being the most common lesion sites for ischemic and hemorrhagic strokes, respectively. PIS was more likely to achieve adverse outcomes.

Stroke in the Developing Brain: Neurophysiologic Implications of Stroke Timing, Location, and Comorbid Factors.

BACKGROUND: Pediatric stroke, which is unique in that it represents a static insult to a developing brain, often leads to long-term neurological disability. Neuroplasticity in infants and children influences neurophysiologic recovery patterns after stroke; therefore outcomes depend on several factors including the timing and location of stroke and the presence of comorbid conditions. METHODS: In this review, we discuss the unique implications of stroke occurring in the fetal, perinatal, and childhood/adolescent time periods. First, we highlight the impact of the developmental stage of the brain at the time of insult on the motor, sensory, cognitive, speech, and behavioral domains. Next, we consider the influence of location of stroke on the presence and severity of motor and nonmotor outcomes. Finally, we discuss the impact of associated conditions on long-term outcomes and risk for stroke recurrence. RESULTS: Hemiparesis is common after stroke at any age, although the severity of impairment differs by age group. Risk of epilepsy is elevated in all age groups compared with those without stroke. Outcomes in other domains vary by age, although several studies suggest worse cognitive outcomes when stroke occurs in early childhood compared with fetal and later childhood epochs. Conditions such as congenital heart disease, sickle cell disease, and moyamoya increase the risk of stroke and leave patients differentially vulnerable to neurodevelopmental delay, stroke recurrence, silent infarcts, and cognitive impairment. CONCLUSIONS: A comprehensive understanding of the interplay of various factors is essential in guiding the clinical care of patients with pediatric stroke.

EEG functional connectivity after perinatal stroke.

Impaired cognitive functioning after perinatal stroke has been associated with long-term functional brain network changes. We explored brain functional connectivity using a 64-channel resting-state electroencephalogram in 12 participants, aged 5-14 years with a history of unilateral perinatal arterial ischemic or haemorrhagic stroke. A control group of 16 neurologically healthy subjects was also included-each test subject was compared with multiple control subjects, matched by sex and age. Functional connectomes from the alpha frequency band were calculated for each subject and the differences in network graph metrics between the 2 groups were analyzed. Our results suggest that the functional brain networks of children with perinatal stroke show evidence of disruption even years after the insult and that the scale of changes appears to be influenced by the lesion volume. The networks remain more segregated and show a higher synchronization at both whole-brain and intrahemispheric level. Total interhemispheric strength was higher in children with perinatal stroke compared with healthy controls.

Term-born infants with a perinatal stroke frequently had seizures and were prescribed anti-seizure medication at discharge.

AIM: We investigated the prevalence of seizures in term-born infants with a perinatal stroke in Swedish neonatal wards, assessed the anti-seizure medication prescribed and determined the accuracy of diagnostic codes. METHODS: This cross-sectional study used data from the Swedish Neonatal Quality Register. The cases were infants born at ≥37 weeks in 2009-2018 and admitted to a neonatal ward in Stockholm County with a stroke diagnosis, confirmed by their medical chart. The controls were all Swedish infants born during those years. RESULTS: There were 76 infants with a confirmed perinatal stroke: 51 ischaemic and 25 haemorrhagic. Seizures were documented in 66/76 (87%) of infants with a stroke and 0.2% of the controls. Anti-seizure medication was administered to 64/66 (97%) infants with a stroke and seizures. In 60 cases, the drugs administered were specified, with phenobarbital used in 59/60 cases (98%). More than one drug was administered to 25/60 (42%) infants and 31/60 (52%) were discharged with anti-seizure medication. The positive predictive value for the stroke diagnostic codes was 80.5% (95% CI 76.5-84.5). CONCLUSION: Seizures were common in infants with a perinatal stroke. More than one anti-seizure drug was often required and many infants were on anti-seizure medication at discharge, against Swedish recommendations.

A National, Electronic Health Record-Based Study of Perinatal Hemorrhagic and Ischemic Stroke.

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke. METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. Odds ratios were calculated against a control group. RESULTS: A total of 535 (63%) neonates were identified with ischemic stroke and 312 (37%) with hemorrhagic stroke. The most common exposures for ischemic stroke were sepsis (n = 82, 15.33%), hypoxic injury (n = 61, 11.4%), and prematurity (n = 49, 9.16%). The most common comorbidities for hemorrhagic stroke were prematurity (n = 81, 26%) and sepsis (n = 63, 20%). No perinatal ischemic stroke patients had diagnosis codes for cytomegalovirus disease. Procedure and diagnosis codes related to critical illness, including intubation and resuscitation, were prominent in both hemorrhagic (n = 46, 15%) and ischemic stroke (n = 45, 8%). CONCLUSION: This electronic health record-based study of perinatal stroke, the largest of its kind, demonstrated a wide variety of comorbid conditions with ischemic and hemorrhagic stroke. Sepsis, prematurity, and hypoxic injury are associated with perinatal hemorrhagic and ischemic stroke, though prevalence varies between types. Much of our data were similar to prior studies, which lends validity to the electronic health record database in studying perinatal stroke.

BCI-activated electrical stimulation in children with perinatal stroke and hemiparesis: A pilot study.

Background: Perinatal stroke (PS) causes most hemiparetic cerebral palsy (CP) and results in lifelong disability. Children with severe hemiparesis have limited rehabilitation options. Brain computer interface- activated functional electrical stimulation (BCI-FES) of target muscles may enhance upper extremity function in hemiparetic adults. We conducted a pilot clinical trial to assess the safety and feasibility of BCI-FES in children with hemiparetic CP. Methods: Thirteen participants (mean age = 12.2 years, 31% female) were recruited from a population-based cohort. Inclusion criteria were: (1) MRI-confirmed PS, (2) disabling hemiparetic CP, (3) age 6-18 years, (4) informed consent/assent. Those with neurological comorbidities or unstable epilepsy were excluded. Participants attended two BCI sessions: training and rehabilitation. They wore an EEG-BCI headset and two forearm extensor stimulation electrodes. Participants' imagination of wrist extension was classified on EEG, after which muscle stimulation and visual feedback were provided when the correct visualization was detected. Results: No serious adverse events or dropouts occurred. The most common complaints were mild headache, headset discomfort and muscle fatigue. Children ranked the experience as comparable to a long car ride and none reported as unpleasant. Sessions lasted a mean of 87 min with 33 min of stimulation delivered. Mean classification accuracies were (M = 78.78%, SD = 9.97) for training and (M = 73.48, SD = 12.41) for rehabilitation. Mean Cohen's Kappa across rehabilitation trials was M = 0.43, SD = 0.29, range = 0.019-1.00, suggesting BCI competency. Conclusion: Brain computer interface-FES was well -tolerated and feasible in children with hemiparesis. This paves the way for clinical trials to optimize approaches and test efficacy.

Safety and feasibility of transcranial direct current stimulation stratified by corticospinal organization in children with hemiparesis.

Children with hemiparesis (CWH) due to stroke early in life face lifelong impairments in motor function. Transcranial direct current stimulation (tDCS) may be a safe and feasible adjuvant therapy to augment rehabilitation. Given the variability in outcomes following tDCS, tailored protocols of tDCS are required. We evaluated the safety, feasibility, and preliminary effects of a single session of targeted anodal tDCS based on individual corticospinal tract organization on corticospinal excitability. Fourteen CWH (age = 13.8 ± 3.63) were stratified into two corticospinal organization subgroups based on transcranial magnetic stimulation (TMS)-confirmed motor evoked potentials (MEP): ipsilesional MEP presence (MEPIL+) or absence (MEPIL-). Subgroups were randomized to real anodal or sham tDCS (1.5 mA, 20 min) applied to the ipsilesional (MEPIL + group) or contralesional (MEPIL- group) hemisphere combined with hand training. Safety was assessed with questionnaires and motor function evaluation, and corticospinal excitability was assessed at baseline and every 15 min for 1 h after tDCS. No serious adverse events occurred and anticipated minor side effects were reported and were self-limiting. Six of 14 participants had consistent ipsilesional MEPs (MEPIL + group). Paretic hand MEP amplitude increased in 5/8 participants who received real anodal tDCS to either the ipsilesional or contralesional hemisphere (+80% change). Application of tDCS based on individual corticospinal organization was safe and feasible with expected effects on excitability, indicating the potential for tailored tDCS protocols for CWH. Additional research involving expanded experimental designs is needed to confirm these effects and to determine if this approach can be translated into a clinically relevant intervention.