Motor Outcomes After Neonatal Arterial Ischemic Stroke Related to Early MRI Data in a Prospective Study

OBJECTIVE: We aimed to correlate early imaging data with motor outcomes in a large, homogeneous, cohort of infants with neonatal (diagnosed before 29 days of life) arterial ischemic stroke (AIS).METHODS: From a prospective cohort of 100 children with neonatal AIS, we analyzed the MRI studies performed within the 28 first days of life for 80 infants evaluated at 2 years of age. The relationships between infarction location and corticospinal tract (CST) involvement and motor outcomes were studied RESULTS: Seventy-three infarctions involved the middle cerebral artery (MCA) territory. Of those, 50 were superficial infarctions, 5 deep infarctions, and 18 mixed infarctions. The CST was involved in 24 cases. Nineteen patients with MCA infarctions (26% [95% confidence interval: 16%–34%]) developed hemiplegia. Mixed infarctions (P < .0001) and CST involvement (P < .0001) were highly predictive of hemiplegia. In contrast, 88% of children with isolated superficial MCA infarctions did not exhibit impairment. CONCLUSIONS: Accurate prediction of motor outcomes can be obtained from early MRI scans after neonatal AIS. The absence of involvement of the CST resulted in normal motor development in 94% of cases. CST involvement resulted in congenital hemiplegia in 66% of cases

Molecular Implication of PP2A and Pin1 in the Alzheimer's Disease Specific Hyperphosphorylation of Tau

Tau phosphorylation and dephosphorylation regulate in a poorly understood manner its physiological role of microtubule stabilization, and equally its integration in Alzheimer disease (AD) related fibrils. A specific phospho-pattern will result from the balance between kinases and phosphatases. The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit PR55/Bα (PP2A(T55α)) is a major Tau phosphatase in vivo, which contributes to its final phosphorylation state. We use NMR spectroscopy to determine the dephosphorylation rates of phospho-Tau by this major brain phosphatase, and present site-specific and kinetic data for the individual sites including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes.We demonstrate the importance of the PR55/Bα regulatory subunit of PP2A within this enzymatic process, and show that, unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be released by the phosphorylation dependent prolyl cis/trans isomerase Pin1. Because the stimulatory effect is lost with the dimeric PP2A core enzyme (PP2A(D)) or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the interaction between the PR55/Bα subunit and the AT180 phospho-epitope on Tau.Our results show that phosphorylation of T231 (AT180) can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope, even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231 AT180 is required for efficient PP2A(T55α)-mediated dephosphorylation of pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported for certain Tau kinases and the one described here for Tau phosphatase PP2A(T55α) may contribute to the hyperphosphorylation of Tau observed in AD neurons

Obstetrical and neonatal characteristics vary with birthweight in a cohort of 100 term newborns with symptomatic arterial ischemic stroke

ObjectivesMany questions remain regarding the mechanism of perinatal stroke. Methods In a series of 100 prospectively enrolled term neonates with symptomatic arterial ischemic stroke, we explored family antecedents, pregnancy and delivery conditions and clinical presenting features and distinguished features of the 50 larger infants with the remainder. Cardiac and cervical arterial imaging were performed in 70 and 51 cases. Results Previous fetal loss, first pregnancy, primiparity, twin-gestation, cesarean and traumatic delivery, neonatal distress, male sex and premature rupture of membranes were statistically more common than in the general population. Normal pregnancy proportion and mean birthweight were in the normal range, arguing against a vasculo-placental origin in the majority. Furthermore, there was an excess of large babies. The larger infants were more subject to suffer from acute perinatal events, with a trend for an excess of neonatal distress (p = 0.065) and for more severe presenting features (p = 0.027), while the lighter were more likely to have experienced longstanding obstetrical risk factors such as complicated pregnancy (p = 0.047) and tobacco exposure (p = 0.028). Cervical MR angiography showed an internal carotid occlusion in two babies, whereas echo-Doppler was always normal; in one case the two methods were discordant. Echocardiography was non-informative. Interpretation The data from this prospective cohort of neonates with stroke confirm that many obstetrical and perinatal factors are risk determinants. They also suggest that birthweight and gender may be biomarkers of two populations of neonates with different pathological mechanisms. MR angiography appears more sensitive than echo-Doppler for the exploration of the neonatal cervical vasculature

A Golgi-study of the Brain Malformation in Zellwegers Cerebro-hepato-renal Disease

Characteristic neuronal heterotopias in two cases of Zellweger's cerebro-hepato-renal disease were studied with the Golgi method. In the corona radiata, heterotopias consist of large fields of small or medium-sized radial pyramids, and of dense clusters containing larger, randomly oriented pyramidal cells and multipolar neurons, some of which resemble granule cells. The latter type of heterotopia could result from a focal destructive process at a relatively early stage of neuronal migration. In the cerebellar white matter, heterotopic masses contain Purkinje cells and possibly Golgi neurons but no granule or basket cells. The mispositioned Purkinje cells resemble the subcortical and intragranular Purkinje cells of the reeler mutant mouse and those of the weaver mutant. The morphology of neurons in the abnormally convoluted olivary nucleus is normal

The association between developmental handicaps and traumatic brain injury during pregnancy: An issue that deserves more systematic evaluation

Aims: Trauma during pregnancy is commonly viewed as benign for the foetus when the delivery occurs normally. This study revisits that point of view. Method: We included eighteen patients having a neurological handicap with an anamnesis of an accident during pregnancy and a follow-up sufficient to determine a definite outcome. Results: Pregnancy outcome and observed management. Foetal abnormalities were detected in six cases between the first and the thirteenth day after the trauma. Emergency delivery or rapid birth after signs of foetal distress occurred in five cases. One baby died soon after birth. One-third of cases were not submitted to any investigation. Various neurological handicaps were recorded: Congenital microcephaly (three patients), congenital hydrocephalus (three), Infantile cerebral hemiplegy (six), quadriplegy with severe encephalopathy (four), diplegy (one), clumsiness with cerebellar atrophy (one), Moebius syndrome (one), mental retardation with autistic features (two), learning disability (one) auditory agnosia (one).Cerebral imaging showed macroscopic abnormalities in fourteen patients, evoking various pathogenetic hypotheses. Conclusion: The association between maternal trauma and foetal brain lesions lacks sufficient investigation in many cases. Prospective studies are needed to clarify both medical and legal issues. Guidelines are proposed for obstetrical and paediatric management after significant maternal trauma

Preface: the 2022 edition of the XXIVth ISPRS Congress

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