Neonatal Stroke Research Articles

Circonstances de révélation de l’accident vasculaire cérébral ischémique artériel chez le nouveau-né à terme ou proche du terme et orientation des patients

The neonatal arterial ischemic stroke is an emergency. Recurrent focal seizures, generally occurring in the first 24-72 hours after birth, are the commonest first clinical signs. When neonatal arterial ischemic stroke is suspected, optimal initial management involves careful supportive care including treatment of clinical and frequent or prolonged subclinical seizures, correction of the possible metabolic disorders and their prevention. Contrary to hypoxic ischemic encephalopathy, therapeutic hypothermia is not indicated. This newborn requires emergent transfer to a neonatal intensive care unit for the confirmation of the diagnosis by means of a specialized neonatal transport team.

Plasticité cérébrale et prise en charge rééducative précoce des enfants après infarctus cérébral artériel néonatal

Currently, in the literature of the evidence based medicine, little data are available to confirm the benefit and the specific procedures of an early intervention for a neonatal arterial ischemic stroke. However, data about the effect of an early physical rehabilitation program on the cerebral plasticity, and preliminary results of clinical studies in children with cerebral palsy strongly suggest the benefit of an early rehabilitation with a multidisciplinary approach. The type of the rehabilitation and its frequency must be determined because a wide variability in the practices exists. A comprehensive care, of the children and his family is necessary to limit the orthopaedics but also the social consequences of a neonatal stroke.

Place de l’électroencéphalogramme dans la prise en charge de l’accident vasculaire ischémique artériel du nouveau-né

The EEG has a key role in the management of neonatal seizures, which are the typical mode of revelation of neonatal ischemic stroke. The EEG should be started as soon as possible in case of suspected seizure. Some EEG features are evocative of neonatal stroke, typically asymmetry of background activity with the presence of focal spikes and focal seizures. The EEG should be prolonged and always associated with a video as pauci-symptomatic or subclinical seizures are frequent, including some status epilepticus. Video-EEG monitoring is therefore essential to judge the efficacy of anticonvulsant therapy. There is insufficient evidence so far to state if some EEG aspects are predictive of long-term cognitive and epileptic outcomes.

Surveillance biologique et autres explorations à la phase aiguë d’un accident vasculaire cérébral ischémique du nouveau-né (hors hémostase)

Neonatal monitoring and other explorations required just after neonatal arterial ischemic stroke (NAIS) diagnosis remain elusive. This review attempts to propose guidelines on this topic. During neonatal period, three major contexts related to NAIS emerge: 1) Metabolic disorders including hypoglycemia; 2) Early post-natal infections; 3) Cardio-vascular anomalies. Different patient profiles have been defined (typical, atypical and at risk profiles). According to these profiles, a final decisional tree including biological monitoring and complementary explorations has been suggested to caregivers.

Accident vasculaire cérébral ischémique artériel chez le nouveau-né à terme ou proche du terme : prévalence et facteurs de risque

The general designation ischemic perinatal stroke includes several disease states that differ in pathophysiology, timing of occurrence and presentation. While it seems logical to assume that their prevalence and their risk factors depend primarily on the considered type of stroke, most studies used inconsistent definitions or included heterogeneous populations, which limits their accuracy. Given these biases, the French Society of Neonatology and the French Centre for Paediatric Stroke wished to update the knowledge in this domain, focusing on a specific form of perinatal stroke, i.e neonatal arterial ischemic stroke (NAIS) in term or near term newborns. A comprehensive analysis of published epidemiological data was dedicated to the following issues:•Is the prevalence of NAIS well defined from epidemiological studies?•What are the best recognized risk factors and is it possible to delineate a maternal and fetal population at risk for this condition?On July 31, 2015 a total of four hospitalized-based and five population-based studies, and six case-control studies were found. The conclusions are the following:•The prevalence of NAIS in term or near term newborns varies from 6 to 17/100,000 live births (level of evidence 2). NAIS represents a half of total ischemic perinatal strokes (i.e. including those with delayed presentation as well) and one fourth of perinatal strokes (i.e. including cerebral haemorrhage stroke as well).•Four sets of risk factors are consistent across different studies (level of evidence 3): (1) male sex, (2) obstetrical determinants (first pregnancy, caesarean section), and two peripartum complications: (3) intrapartum hypoxia and (4) materno-fetal/neonatal infection. Bacterial meningitis, cardiac disorders/procedures and invasive care such as extra-corporeal circulation carry a risk of NAIS as well.A registry could help refining epidemiological descriptive data. It could also be used to develop etiological studies focusing on pathophysiological hypotheses derived from the identified aforementioned risk factors.

Devenir neurodéveloppemental après un infarctus cérébral artériel néonatal

Neonatal Arterial Ischemic Stroke (NAIS) affects 6-17 newborns on 100 000-birth term neonates, most of these children keeping long-term motor and cognitive impairments. Based on a literature review, the objectives of this paper are to describe motor and cognitive outcomes after a NAIS and to propose a consensual monitoring of these children to improve their management. About 30 % of children after a NAIS will develop a unilateral cerebral palsy requiring a management by a team with expertise in physical medicine and rehabilitation. Unlike adults, especially after a left NAIS, children will not present aphasia but between 50 and 90 % will present disorders of speech and language in expression and/or reception. After NAIS, the global intellectual efficiency is usually preserved except when the size of the lesion is very important or when severe epilepsy occurs. Several studies are also in favor of vulnerability in visuospatial functions. To quantify impairments, activity limitations and participation restrictions resulting from this NAIS, early and at least yearly evaluations with reliable tools must be carried out systematically until puberty. A multidisciplinary team with a longitudinal follow-up, in all the different developmental dimensions, must conduct these evaluations in term of motor skills, cognitive impairment, behavior, autonomy, quality of life, and participation. Consequences on family functioning need to be evaluate in order to help children and family coping with this event.

Recommandations concernant l’imagerie de l’accident vasculaire cérébral ischémique du nouveau-né

Neuroimaging is critical for the diagnosis of neonatal arterial ischemic stroke (NAIS) and for prognosis estimation. The purpose of this work is to define guidelines of clinical neuroimaging for the diagnosis of NAIS, for the optimization of the imaging timing and for the assessment of the prognostic value of each imaging technique.A systematic search of electronic databases (Medline via Pubmed) for studies whose title and abstract were focused on NAIS has been conducted. One hundred and ten articles were selected and their results were analyzed by three Senior Practitioners of pediatric radiology using common methodology for guidelines elaboration within the group of experts gathered by Scientific Societies in the field.MRI with a diffu si on-weighted sequence (DWI) and T1, T2, and T2*-weighted sequences must be performed in the case of suspected NAIS (no sedation is required). In the first hours after the injury, an acute ischemic lesion is characterized by a hypersignal on the diffusion-weighted sequence, with a decrease of the apparent coefficient of diffusion (ADC). The best time to evaluate the extent of the ischemic lesion is between day 2 and day 4 after injury, when the ADC decrease reaches its nadir. In the acute phase, US may be useful as first imaging at the bedside to exclude other pathologies like large space-occupying hemorrhages, but its specific added value on NAIS diagnosis or prognosis assessment is very low. CT scan has no added value in NAIS, compared to MRI.Motor outcome is correlated with the extent of the lesion and with the presence of a definite injury of the corticospinal tract, which is well seen on the diffusion sequence at the acute stage. A secondary atrophy within the mesencephalon (cerebral peduncles) is tied in with a high risk of hemiplegia. Visual outcome is more often compromised in the case of lesions of the posterior cerebral artery territory.

Prise en charge thérapeutique des convulsions associées à l’accident vasculaire cérébral du nouveau-né et perspectives de neuroprotection à la phase aiguë

Neonatal seizure related to stroke is a common diagnostic feature. Their treatment, although widely debated even today must be initiated in case of status epilepticus, clinical seizures of more than 5 minutes duration or short (> 30 secondes) and repeated clinical seizures (2 or more per hour). The treatment of neonatal seizures is a challenge that remains only partially solved. It should take into account the etiology of seizures, type of brain lesions and clinical/electrical response to treatment after the first line treatment. It is based on using a single anti-epileptic at its maximum dosage, and if needed, on the association with another anti-epileptic drug with a different mechanism of action. Phenobarbital remains the most commonly used drug for initial treatment of neonatal seizures and for which the most clinical experience has been accumulated. The lack of randomized controlled trials makes difficult recommendations about the optimal duration of treatment, but most experts agree that once arrested seizures, the duration of treatment should be as short as possible because of its potential risk on the developing brain. Novel neuroprotective strategies for reducing impact of neonatal stroke or promoting brain repair remain for the moment the concept stage, pre-clinical or parcel clinical data.

Association of transcallosal motor fibres with function of both hands after unilateral neonatal arterial ischemic stroke.

The objective of this study was to investigate the involvement of the motor fibres of the corpus callosum after unilateral neonatal arterial ischemic stroke (NAIS) of the middle cerebral artery territory and the relationship to both ipsilesional and contralesional hand function. Using high-resolution structural magnetic resonance imaging (MRI), functional MRI, and magnetic resonance diffusion-tractography, we compared the midsagittal area of the motor part of the corpus callosum (defined by the fibres connecting the precentral gyri) between 33 7-year-old children after unilateral NAIS and 31 typically developing 7-year-old children. Hand motor performance was assessed by the box and blocks test. Children after NAIS showed on average significantly smaller motor corpus callosum area compared to typically developing children (p<0.001, without differences of the non-motor corpus callosum area). In addition, there was a significant positive association between the motor part of the corpus callosum and both contralesional (Pr(>|t|)=0.034) and ipsilesional hand motor performance (Pr(>|t|)=0.006) after controlling for lesion volume and sex. In a post-hoc analysis the additional contribution of corticospinal tract damage was evaluated. Compared to typically developing children, children after NAIS exhibited a smaller motor part of their corpus callosum associated with reduced contralesional but also ipsilesional manual dexterity. These results indicate that the affection of transcallosal motor fibres in unilateral NAIS might be of functional relevance and an important part of the involved structural network that should be elucidated in further studies.

Neuroinflammation in Ischemic Pediatric Stroke

Over the last decades, the importance of inflammatory processes in pediatric stroke have become increasingly evident. Ischemia launches a cascade of events: activation and inhibition of inflammation by a large network of cytokines, adhesion and small molecules, protease, and chemokines. There are major differences in the neonatal brain compared to adult brain, but developmental trajectories of the process during childhood are not yet well known. In neonatal stroke ischemia is the leading pathophysiology, but infectious and inflammatory processes have a significant input into the course and degree of tissue damage. In childhood, beside inflammation lanced by ischemia itself, the event of ischemia might be provoked by an underlying inflammatory pathophysiology: transient focal arteriopathy, dissection, sickle cell anemia, Moyamoya and more generalized in meningitides, generalized vasculitis or genetic arteriopathies (as in ADA2). Focal inflammatory reactions tend to be located in the distal part of the carotid artery or the proximal medial arteries, but generalized processes rather tend to affect the small arteries.

Sonographic and Doppler Sonographic Diagnosis ofNeonatal Ischemic Stroke.

Children are particularly at risk for stroke in the neonatal period. 1/3 of all strokes in children occur during the perinatal period. The incidence of perinatal stroke is 1:4000. A differentiation is made between ischemic stroke and hemorrhagic stroke. Ischemic strokes are caused by arterial occlusion due to thrombosis or embolism. As a result of the nonspecific clinical symptoms in this age group, diagnosis is usually made too late. The only relatively specific symptom is focal cerebral seizure during the first week of life. Therefore, stroke should be ruled out by diagnostic imaging in the case of any seizure in the first days of life. Although the diagnostic method of choice is MRI, it is not always available. Most neonatal ischemic strokes can be detected with high-resolution duplex ultrasound. On ultrasound, ischemic stroke appears as a wedge-shaped focal increase in echogenicity in the supply region of an artery, typically the middle cerebral artery. The corresponding arterial inflow can be visualized with duplex ultrasound and measured with spectral Doppler. Doppler ultrasound can be used to differentiate between complete occlusion and severe stenosis. The success of therapeutic measures can be determined in the further course with Doppler ultrasound on the basis of the recanalization of vessels and the morphological consequences of stroke (cyst formation due to liquefactive necrosis).

Workup for Perinatal Stroke Does Not Predict Recurrence.

Perinatal stroke, including neonatal and presumed perinatal presentation, represents the age in childhood in which stroke occurs most frequently. The roles of thrombophilia, arteriopathy, and cardiac anomalies in perinatal ischemic stroke are currently unclear. We took a uniform approach to perinatal ischemic stroke evaluation to study these risk factors and their association with recurrent stroke. We reviewed records of perinatal stroke patients evaluated from August 2008 to February 2016 at a single referral center. Demographics, echocardiography, arterial imaging, and thrombophilia testing were collected. Statistical analysis was performed using Fisher exact test. Across 215 cases, the median follow-up was 3.17 years (1.49, 6.46). Females comprised 42.8% of cases. Age of presentation was neonatal (110, 51.2%) or presumed perinatal (105, 48.8%). The median age at diagnosis was 2.9 days (interquartile range, 2.0-9.9) for neonatal stroke and 12.9 months (interquartile range, 8.7-32.8) for presumed perinatal stroke. Strokes were classified as arterial (149, 69.3%), venous (60, 27.9%), both (4, 1.9%), or uncertain (2, 0.9%) by consensus imaging review. Of the 215 cases, there were 6 (2.8%) recurrent ischemic cerebrovascular events. Abnormal thrombophilia testing was not associated with recurrent stroke, except for a single patient with combined antithrombin deficiency and protein C deficiency. After excluding venous events, 155 patients were evaluated for arteriopathy and cardioembolic risk factors; neither was associated with recurrent stroke. Positive family history of thrombosis was not predictive of abnormal thrombophilia testing. Thrombophilia, arteriopathy, or cardioembolic risk factors were not predictive of recurrent events after perinatal stroke. Thrombophilia evaluation in perinatal stroke should only rarely be considered.

Utility of Neurovascular Imaging in Acute Neonatal Arterial Ischemic Stroke

To evaluate the prevalence of magnetic resonance angiography (MRA) findings and clinically characterize neonates with arterial ischemic stroke (AIS) who have abnormal or variable vasculature. This was a single-center, retrospective study of patients with neonatal stroke from 1991 to 2012. We reviewed charts and neuroimaging, including MRA, in neonates with AIS. Clinical data of patients with MRA findings were compared with the control group of neonates with AIS and a normal MRA. We identified 142 cases of neonatal AIS, of which 81 patients had magnetic resonance imaging and MRA. Among the neonates with arterial neuroimaging, 29 had arterial findings (for a prevalence rate of 20%-35%). The majority of the findings were stenotic or hypoplastic branches. Two patients had presumed carotid artery dissection. Low Apgar scores and the presence of sepsis were significantly (P <.05) more common in neonates with MRA findings. The prevalence of arterial abnormalities or variations in neonatal AIS has been underestimated because neurovascular imaging is often not performed. We recommend an MRA for neonates with AIS, particularly those who have low Apgar scores and/or sepsis, to rule out a vasculopathy that may warrant therapeutic intervention.

Infantile spasms in Newfoundland and Labrador, a population based survey over the last 13 years

Objective: We review our experience of Infantile Spasms in Newfoundland and Labrador, Canada. This is a population based retrospective review over the last 13 years. Methods: All children with IS were identified from our own database. All charts were reviewed and information collated. Results: 36 patients were identified (17 Male/19 Female) from 2003-2016. Our incidence is 0.6/1000 live births which is higher than reported in other centers in Canada. 25 children had developmental issues prior to the onset of spasms and 28 after spasms were treated. 4 children died. 4 infants were born prematurely. 10 children had epilepsy before onset of spasms. 21 children had ongoing seizures after treatment of their spasms. 32 children were initially treated with Vigabatrin for variable periods of time; one was initially treated with Prednisone. 13 had Prednisone or ACTH as second line treatment. 5 required a repeat treatment of steroids. An etiology was identified in 19 children with CNS abnormalities being the commonest in 7 cases, genetic causes in 6, Tuberous Sclerosis in 3, Hypoxic Ischemic Encephalopathy in 3, non-accidental injury in 1, congenital CMV in 1, Low Vit B12 in 1 and neonatal stroke in 2. The majority of children developed infantile spasms in the first year of life; 12 below 6 months, 20 six months to 1 year, 3 in the second year of life and 1 child in the 3rd year of life. Conclusion: In this population based study CNS malformations were the commonest cause identified. Most children were treated with Vigabatrin. Despite controlling the IS, outcome was not good; the majority remained handicapped to some degree. Treatment of the IS may improve outcome but the underlying etiology remains a significant factor influencing development.

Epilepsy and neonatal arterial ischemic stroke: A French national cohort

Objective: To describe epilepsy within the French national multicenter cohort of neonatal stroke at the age of 7 years and then study the factors associated with risk of developing post-neonatal epilepsy (PNE). PNE was defined by occurrence of at least two seizures or introduction of antiepileptic drugs. Methods: The files of children aged 7 years from the national cohort of neonatal stroke were collected. Data related to the epilepsy profile (age at onset; type of seizure; antiepileptic drugs; motor and cognitive profile; electroencephalographic findings) have been recorded. Associated risk factors of PNE have been evaluated. Results: 78 children were included. 20.5% of patients had experienced at least one seizure during their follow-up, 18% of patients had PNE and 12% had active epilepsy and among them two thirds were controlled by monotherapy. Among the patients with epilepsy, 64% had structural partial epilepsy and 3.8% had presented infantile epileptic spasms. 57% of patients with EPN were attending a special school. Concerning intelligence, most of them had a deficit (score <70) concerning the performance index (43%) and the verbal index (43%). All patients with EPN presented with cerebral palsy. There was a statistically significant association between PNE and multiple vascular territories injured, head circumference at birth <−2DS, posterior cerebral artery involvement and low level of maternal education. Neonatal encephalographic abnormalities were not associated with risk of PNE. Conclusion: Though its low incidence, PNE is a major comorbidity in children with neonatal arterial ischemic stroke and is associated with worse neurologic global outcome. Neonatal encephalogram findings were not a predictive factor of PNE at 7 years.

Brain functional connectivity changes 7 years after Neonatal Arterial Ischemic Stroke (NAIS): A resting state fMRI study

Objective: Resting state fMRI (rs-fMRI) enables to study brain functional connectivity, i.e. the intrinsic functional architecture of brain networks at rest. NAIS is an exquisite model to study long-term plasticity after early focal lesions. We studied brain functional connectivity with rs-fMRI in school-age children after NAIS, focusing on language networks. Methods: From 100 newborns with NAIS followed until age 7 (n= 72, 2/3 boys, 85% MCA territory, 30% unilateral Cerebral Palsy, 49 % of atypical language profiles at N- EEL battery, without differences between left/right lesions, and with good global language performance), 38 patients and 29 age-matched controls underwent 3T rs- fMRI (exploitable in 32/26). After extended data preprocessing, we computed correlations (reflecting both direct and indirect connectivity) and partial correlations (direct connectivity only) within matrices of 64 bilateral homotopic regions grouped into 10 functional networks (the reference rs-fMRI functional atlas was derived from the controls data). Right lesions were flipped to the left side for group comparisons. Individual ROI volumes accounted for brain lesions, and statistics were corrected for multiple comparisons, FDR, p<0.05. Results: With both correlation and partial correlation, we found mostly reduced inter- hemispheric connectivity in the patient group as compared with controls (in motor, language and attentional networks). When restricting analysis to the language network, the reduction was strongest between homotopic inferior frontal and superior temporal regions (‘broca’ and ‘wernicke’). In the contralesional hemisphere, only intra- hemispheric correlations were increased mostly in the language network with stronger connections with the basal ganglia and motor network and within the visual occipital network. No connectivity difference could be evidenced between patients with either typical or atypical language. Conclusion: Rs-fMRI is useful to study the maturation of functional connectivity after NAIS, showing widespread reduction of inter-hemispheric connectivity and increased contralesional connectivity within the language network. The clinical correlates of this complex pattern remain to be fully understood.

Language plasticity after Neonatal Arterial Ischemic Stroke (NAIS): Clinical and fMRI evaluation at 7 years of age

Language plasticity after Neonatal Arterial Ischemic Stroke (NAIS): Clinical and fMRI evaluation at 7 years of age

Acute and retrospective diagnosed neonatal arterial ischemic stroke: Presentation, risk factors, evaluation and outcome

Acute and retrospective diagnosed neonatal arterial ischemic stroke: Presentation, risk factors, evaluation and outcome

Risk factors, clinical course and outcome of 69 cases of ischemic neonatal stroke

Risk factors, clinical course and outcome of 69 cases of ischemic neonatal stroke

Thrombophilia risk is not increased in children after perinatal stroke

AbstractPerinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders, but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias. Children with idiopathic magnetic resonance imaging–classified neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or fetal periventricular venous infarction (PVI) were recruited. Standardized thrombophilia evaluations were performed after 12 months of age on stroke cases and controls, including quantified proteins C and S, antithrombin, factors VIII/IX/XI, fibrinogen, lipoprotein(a), homocysteine, lupus anticoagulant, anticardiolipin antibodies and genotyping of factor V Leiden (FVL), factor II G20210A (FII), and methylenetetrahydrofolate reductase C677T. A total of 212 children were studied: 46 with NAIS, 34 with APPIS, 55 with PVI, and 77 controls (male, 53%; median age, 4.8 years). Of 14 parameters, no differences were observed in 12, including all common thrombophilias. Mean prothrombin time was shorter in arterial strokes (P < .001). Rates of antiphospholipid antibodies were low, comparable to those in controls, and resolved on repeat testing. FVL and FII rates were comparable to population norms. Total number of possible abnormalities did not differ between cases and controls. Our prospective, population-based, controlled, disease-specific study suggests minimal association between perinatal stroke and thrombophilia. This does not exclude the possibility of disordered coagulation at the time of stroke but suggests testing in childhood is not indicated.