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WATERSHED INJURY - keywords
watershed injury < Frontoparietal watershed injuryAfter disappearance of brain swelling MRI is superior to US to describe subcortical lesions. Hyperechoic parasagittal change may appear most prominent in perirolandic areas. We rarely observe cystic change in lesions that fit the diagnosis of pure watershed injury. If this happens the cortical ribbon is lost on T2 MRI in the acute stage (Coskun et al. 2001). On the other hand many infants with lost cortical ribbon in watershed areas, do not develop infarction with cavitation.  An important differential diagnostic entity is superior sagittal sinus thrombosis, which can also cause parasagittal subcortical (often haemorrhagic) damage. Temporal watershed injuryOn rare occasion symmetrical hyperechoic change in the posterior temporal lobe is detected, showing as bright elliptoid areas in the second part of the first week. We hypothesize these infarcts may also represent genuine border zone necrosis between posterior and middle cerebral artery at the surface and anterior choroidal artery in deeper tissue.  Other very focal kinds of necrosis may also be found in gyri around the upper hemispheric border, not necessarily in a border zone. n a v i g a t o r r e f e r e n c e s > Parasagittal cerebral (sub)cortical brain necrosis is diagnosed with ultrasound facing focal cystic lesions or atrophic scars at the junction (border zone) between major cerebral arteries, preceded by (sub)cortical hyperechoic change in the frontoparietal lobes at some distance from the falx. Those hyperechoic areas are triangular on coronal section with basis towards the surface. On CUS this entity often ‘drowns’ in more extensive injury, but some infants do have isolated watershed damage. The clinical presentation is of partial asphyxia with seizures but with retained consciousness and primitive reflexes, no signs of brainstem dysfunction (Sato et al. 2003). Watershed damage culminates in the posterior parietal areas, apparently because of a border zone there between three major cerebral arteries, as suggested by Meyer in 1953. Myers in 1971 and Brann and Myers in 1975 confirmed the entity in monkey experiments of partial (no asystoly) perinatal asphyxia, illustrating specific haemorrhagic change in postcentral gyrus and parieto-occipital cortex.  The acute MRI findings were first detailed by Kuenzle and Baenziger in 1994 as parasagittal hyperintensity on T2, mainly of the centrum semiovale but extending into the subcortex in boundary zones between major arteries (mild: F/O, no blurred cortex-subcortex border; moderate: F/O with blurred border; severe: F/P/O and blurred border).  The lesion is recognised on diffusion weighted sequences recorded in the latter part of the week after the insult (Roelants-van Rijn et al. 2001).  Recent MR studies link anterior watershed injury to cognitive dysfunction (Sato et al. 2003) and some infants develop cerebral palsy (Bax et al. 2006). Ulegyria can lead to childhood epilepsy and drug refractoriness is not uncommon (Villani et al. 2003). Of 731 children with term asphyxia and cortical injury, 484 (66%) had ulegyria (Stern et al. 2023). Ulegyria was most common in those cases with a combined watershed/basal ganglia-thalamic pattern (56%) and isolated watershed pattern (40%). Watershed injury in patients with ulegyria was most common at the posterior watershed (80.6%) and perisylvian watershed (76.7%). Predominant white matter/watershed injury is the most common pattern of injury (59%) in term infants that escaped cooling (Parmentier et al. 2022). asphyxia: parasagittal cerebral injury (watershed injury) typical images Adamsons K, Mueller-Heubach E, Myers RE: Production of fetal asphyxia in the rhesus monkey by administration of catecholamines to the mother. Am J Obstet Gynecol 109:248-262, 1971  Azzarelli B, Caldemeyer KS, Phillips JP, DeMyer WE (1996) Hypoxic-ischemic encephalopathy in areas of primary myelination: a neuroimaging and PET study. Pediatr Neurol 14:108-116. 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J Pediatrics 91:472-476. watershed injury references asphyxia: signal intensity changes on MRI following term birth asphyxia Normal neonatal cortex intensity on MR (up to ≈ 3 mo): - short T1 (brighter) and short T2 (darker), with longer white matter T1 and T2 → obvious cortex/white matter differentiation - gradual prolongation of cortical values causes loss of differentiation near 3 months post term - cortical highlighting by HIE and changes in white matter signal intensity were well documented in early research on this topic coronal scan with 4 columns of deep grey matter damage and extensive cortical necrosis: TBG 6, CWM 6 The Rotterdam score (n=80, Swarte et al. 2009), listed below, is a derived expansion of the Barkovich et al. 1995 score. Either MR (any sequence) or ultrasound with unequivocal findings can acknowledge damage to a brain part, day 3 after birth or later, only in term infants: - in light blue: extensive deep grey matter injury - in green: watershed subcortical injury - in dark blue: leukomalacia at term - in red: isolated cortical necrosis. Other scores were compared with each other in Langeslag et al. 2022. It is logical that the extent of damage on imaging correlates with outcome, and that MR quality is paramount. How to use these scores in redirection of care, is for several reasons, not generalisable, but scoring damage on images is essential in such decisions.  asphyxia: Rotterdam scoring system  On MRI affected deep nuclei develop a higher than normal signal intensity on T1 from day 4 to the end of the first month (or permanently), accompanied by low signal intensity on T2. Perirolandic and peri-insular cortical highlighting (high signal on T1 and low signal on T2, especially in the depths of the sulci) is variably associated with TBG scores 3 to 6.ADC values are low even within the first day, but exceptions exist where affected nuclei have normal ADC values. ADC values normalise around the end of the first week.  In asphyxia network effects in tracts cause diffusion changes in addition to local damage of axons and collateral effects of nearby cells in thalamus and putamen. Signal inversion refers to altered signal intensity on T1 MR. CWM cortex and white matter PLIC posterior limb of the internal capsule TBG thalamus and basal ganglia Thompson et al. 1997 moderate HIE 0.1 % - handicap in 25 % severe HIE 0.1 % - handicap in 90 % Clinical phenotypes are arbitrarily separated into subacute partial and acute near-total type, following insights from animal studies. Sonographic changes other than brain swelling will, as a rule, not be found after asphyxia with mild encephalopathy (Sarnat grade 1). The group for which imaging is most relevant consists of babies with moderate encephalopathy, usually presenting with hypotonia and clinical seizures. Criteria have been suggested to withhold the diagnosis of intrapartum asphyxia (Hankins and Speer 2003): 4 major criteria are obligatory: - severe metabolic acidosis - HIE = hypoxic-ischaemic encephalopathy - later development of CP - exclusion of other causes than intrapartum asphyxia.  At least 3 of 5 minor criteria to retain the diagnosis “intrapartum”: - a sentinel event before or during labour - an abnormal CTG preceded by a normal recording - Apgar score ≤ 3 at five minutes - multi-organ failure/ 72 h of birth - acute brain injury on imaging. asphyxia: criteria and clinical scores Sarnat and Sarnat 1976 Insight into injury paradigms with asphyxia derives from the match of in vivo and postmortem findings in humans with large animal models (Painter 1995, Northington et al. 2007, Koehler et al. 2018). In general mixed patterns are common, because asphyxia in the human newborn starts as prolonged hypoxia, often climaxing by cardiovascular collapse with extreme bradycardia or asystoly, in some followed by hypoglycaemia and in many by seizures.  Interarterial injury is also called watershed or border zone injury. It is presumed that distal fields are at risk when there is a restricted episode of cerebral hypoperfusion, not severe enough to cause frank arterial infarction or widespread neuronal necrosis. Typical waterhsed injury is also seen with fetomaternal transfusion, septic shock, acute blood loss and in infants with neonatal cardiosurgery. The neuropathological changes by term intrapartum asphyxia may be divided into two groups. On the one hand biochemical changes lead to immediate cytotoxic edema, whilst triggering a chain of reactions provoking microvascular lesions and delayed primary neuronal death in specific areas, spread over hours to a few days. Correspondingly macrovascular phenomena follow a quadriphasic pattern: (1) initial hyperaemia (minutes), (2) no reflow (lasting hours) with lowered brain activity and low voltage EEG, (3) luxury perfusion (for a few days) and (4) late hypoperfusion.  As a first paradigm, in many human intrapartum asphyxia, deep grey matter injury to ventro- and ventroposterior relay nuclei in thalamus plus variable portions of striatum is associated with direct perirolandic/insular/calcarine (sub)cortical injury. Selective cell death prefers highly metabolically active and functionally linked areas in this paradigm (somehow related with the time frame of myelination, Azzarelli et al. 1996). Apoptosis in afferently or efferently connected neurons follows in thalamus, cortex or striatum. A cycle of injury is triggered in the thalamo-cortico-striatal loop, often relatively sparing pallidum (Johnston and Hoon 2000). Prolonged ischaemia leads to brainstem damage, especially when deep bradycardia or cardiac arrest supervene.  A second paradigm consists of (multi)focal damage to cortex and white matter in inter-arterial border zones, often ascribed to hypoperfusion (Volpe and Herscovitch 1985). Subcortical white matter injury in this model is typical. Loss of autoregulation and simultaneous hypotension are the probable causes of border zone infarction (arterial watershed zone destruction) presenting as parasagittal cerebral injury.  Added to the above paradigms are focal arterial infarction and primary haemorrhage (for instance with haemostatic problems or due to congestion and mechanical vessel rupture on the venous side. Episodic hyperperfusion can transform ischaemic areas in haemorrhagic infarcts, a tableau of microvascular leaks through interrupted basal laminae.  There is evidence for the existence of other paradigms such as isolated cortical necrosis and primary leukomalacia following term birth asphyxia. Secondary neurodegeneration follows the above mentioned primary injuries, so that connected thalamic and brainstem nuclei wither due to loss of trophic support from their cortical targets and/or due to seizure-induced excitotoxic injury (Govaert et al. 2007). The interplay between cell injury in one region (e.g. cortex) and cell strain in a connected distant region (e.g. thalamus) is problematic for most thalamic nuclei. Knowledge of the physiological status of these networks is relevant for understanding injury patterns. For instance, connections to putamen are relatively restricted to perirolandic cortex, whereas caudate is connected to almost all neocortical areas except the cerebral poles. This type of transsynaptic cell death is apoptotic and develops over a period of days, peaking in intensity slightly later than necrosis in cortex or striatum (Northington et al. 2001). Unusual thalamic lesions, e.g. to anterior thalamus, can follow extensive cortical injury. cortical arteries neuropathology examples the complex imaging situation injury patterns in asphyxia conventional MR intensity changes asphyxia: causes decelerations imaging watershed pattern arterial collaterals monkey model partial asphyxia outcome watershed injury in a complex of lesions associated with asphyxia clinical scores cord knot uterine rupture tight cord abruptio/solutio placentae From the point of view of fetal well-being, the time spent in the second stage is to be limited (Defoort 1993). The deleterious effects of prolongation of the second stage can be due to interference with fetal oxygenation (acidosis) and to mechanical effects on the fetal head (pathological moulding). The mean pH of umbilical artery blood exceeds 7.31 when the second stage takes less than 15 minutes, but falls to 7.25 when 30 minutes are exceeded. A prolonged expulsion can make the moderate respiratory acidosis in the fetus, that normally resolves rapidly after birth, evolve into a potentially dangerous metabolic acidosis. The correlation between the increased risk for an untoward fetal outcome and the duration of the second, and also the first, stage cannot be considered as clearly defined. The period of risk is the perineal phase, being the interval between the presentation of the head at the pelvic floor and the completion of birth, or the duration of perineal 'bulging'. The duration of the phase of active bearing down has a three to seven times increased influence on fetal acid-base parameters compared to the whole duration of the second stage. When cord compression occurs this influence is much higher. Taking into account statistical exceptions to the general trend, a limit of 45 minutes is advisable. When monitoring, and in the presence of a normal heart frequency registration, an expectant attitude may be sustained longer.  Although pure presentation phenotypes of asphyxia are observed in term human neonates, the picture is often more complicated than in animal models. But the subacute type with subcortical injury and the acute total type with injury to deep grey matter, certainly exist. Thalamic neurons start to die after 10 minutes of severe bradycardia or asystoly. asphyxia: subacute type, fetal distress during the second stage of labour Most fetuses enter labor with a reserve of placental capacity. Contraction strength, frequency, and duration are the key factors that determine the rate at which fetal asphyxia develops during labor (Gunn and Thoresen 2019). Critically, the proportion of time the uterus spends at resting tone compared with contracting tone will determine the extent to which fetal gas exchange can be restored between contractions: any intervention that increases the frequency and/or duration of uterine contractions clearly places the fetus at increased risk of compromise. A progressive fall in cerebral oxygen saturation sets in (studied with NIRS) when contractions occur more frequently than every 2.3 min (Peebles et al. 1994). Repeated hypoxia is more critical with preexisting placental insufficiency or fetal inflammation that sensitize the brain to hypoxia–ischemia. Conversely, even a fetus with normal placental function may be unable to adapt to tonic contractions or uterine hyperstimulation related to oxytocin infusion used for induction or augmentation or prostaglandin preparations for induction of labor. The disposition of the vascular network varies between the top of a gyrus and the bottom of a sulcus according to variations of the cell layers: at the top of the gyrus, layers V and VI are highly developed, vascular layers are less distinct and the vascular network is uniform in structure; at the bottom of the sulcus, layers IV, V and VI are reduced in thickness and thus difficult to observe due to the vascular network; in contrast, layers III, II and especially I are highly developed. There are also variations among different areas: parietal granular cortex is characterized by the particularly dense third vascular layer while the frontal agranular cortex has a more homogeneous vascular network.  cerebrocortical arteries Whatever their morphology, arteries and veins generally have the same orientation in the cortex (Scharrer 1940, Duvernoy et al. 1981). Along a sulcus parallel arteries and veins are perpendicular to the surface resulting in a palisading effect. Vessels reaching white matter bend often at right angles (tangential to the surface), and continue their course in the gyrus axis. Arteries and veins thus bend twice at right angles: once, when penetrating the cortex and again when entering the white matter. At the bottom of the sulcus, the vessels cross the cortex and diverge. In the deep cortical layers they give off parallel arched branches which underline the curvature of the cortex. In contrast, vessels at the top of the gyrus continue their rectilinear course in white matter (Pfeifer’s Dolcharterien). A great number of vessels are found at the sulcus bottom, in particular large diameter medullary arteries (A6).  There is a polarity of the superficial cortical zone vascularization (I and II) whose arterial supply is largely of deep origin (arteries recurring from middle layers) whereas venous drainage is superficial. Long branches of principal veins found between cortex and white matter drain the deepest layers of the cortex (V and VI), whereas arteries primarily come from more superficial zones (layers IV and V).  A regular organisation of vessels in the human cortex results in a circular pattern with a particular position of the veins: there appear to be venous units centered by a principal vein or by smaller veins surrounded by an arterial ring. The largest venous units are centered by a principal vein (V5), may be surrounded by several concentric arterial rings. A large number of arteries compared to veins is a result of this special arrangement: an average of four times the number of arteries as veins reach the middle and deep layers of the cortex. The volume of venous units is variable: units centered by intermediate size veins generally range from 0.75 to I mm in diameter and those centered by principal veins range from I to 4 mm.  to superficial layers: A1 and A2 to layers 1 to 4: A3 to all layers: A4 and A5 to white matter: A6 ——> non-immune fetal hydrops by chronic fetomaternal transfusion transposition of the great arteries fetomaternal transfusion 1 proximal: optic tract, crus posterius and pallidum mediale 2 medial: pedunculus cerebri, nu. ruber, su. nigra, subthalamus, ant. lat. thalamus 3 lateral: uncus, gyrus parahippocampalis, dentate gyrus, amygdaloid nuclei, cauda nuclei caudati 4 distal: optic radiation and lateral geniculate 5 plexus of temporal horn OR: optic radiation term, fetal distress without sentinel event, seizures first seen at 5 hours, too late for cooling temporal lobe watershed fetal distress ? watershed ++ and thalamus network injury watershed injury: typical images septic shock at 34w PMA term, meconium aspiration syndrome, prior to cooling era; MRI day 5 term boy, second of twins, born by emergency caesarean after cord prolapse; Sarnat stage 2 encephalopathy, seizures within the first day of life; bilateral posterior temporal hyperechoic foci appeared on day 5 (arrows), no follow-up septic shock asymmetric perirolandic meconium aspiration between f1 and f3 term, transposition of the great arteries, hypotension prior to surgery In the more severely affected infants with watershed injury, extension can also be seen in the parasagittal cortex and the subcortical white matter. Neonatal encephalopathy in infants with this type of injury is often not severe and short, in contrast to infants with BGT pattern of injury who in general, have lower Apgar scores, need more intensive resuscitation at birth, and present with severe prolonged encephalopathy. Although some affected infants appear within normal or only mildly affected at 1-2 years of age, these children are likely to grow into their deficits and develop cognitive problems over the years, highlighting the importance of long-term follow-up to detect disabilities early in life and ensure an early start of interventions (Parmentier et al. 2022). One hundred one patients with mean age of onset of epilepsy at 28.9 ± 33.1 months were recruited based on video EEG findings and of parieto-occipital cortical gliosis on MRI (Ray et al. 2021) The commonest type of focal onset ictus was tonic seizures with impaired awareness (n = 26, 29.9%). Myoclonic jerks (n = 20, 23%) were the commonest type of generalised onset seizures. Ictal onset from the parieto-occipital region was observed in 28 patients. Ictal onset from frontal, temporal and fronto-temporal region was observed in 6 (6.8%), 7(7.9%) and 9 (8.9%) patients, respectively.  Pediatric epilepsy is significantly associated with neonatal seizures and neonatal hypoglycaemia. Patients with PO gliosis can have florid interictal epileptiform discharges anteriorly and can have seizures with ictal onset from frontal and temporal region. The range of severity of outcome types is as wide as the range of extension of the pattern on MRI. In general CP is less common than after lesions to deep grey matter. But spastic diplegia and especially paediatric epilepsy are not uncommon (Van Kooij et al. 2010)(image example). In perinatal cortical injury types all sorts of CP, except ataxia, may follow (Bax et al. 2006). In 1,020 consecutive patients studied at a tertiary care epilepsy centre, eight cases of ulegyria were identified, all with a history of perinatal asphyxia (Gil-Nagel et al. 2005). In four there was psychomotor delay. Mean age at onset of postneonatal epilepsy was 5.8 years (range first week to 21 years). Brain MRI demonstrated predominant involvement of occipito-parietal cortical and subcortical areas. This posterior distribution of lesions was also supported by the presence of auras with occipital and parietal semiology in six, and signs of visuospatial dysfunction in five. Four had medically refractory epilepsy, two of them with significant improvement after surgical treatment. Four MRI scoring systems for term infants with perinatal asphyxia were compared: Rutherford score, Trivedi score, Weeke score, and NICHD NRN score (Langeslag et al. 2022). All four demonstrated an AUC of > 0.66 for the prediction of adverse outcome and ≥ 0.80 for the prediction of death. The inter-rater reliability analyses demonstrated the highest reliability for the Weeke and Trivedi scores. When only assessing the high-quality scans, the AUC increased further. watershed injury on MRI and outcome Explanations for the specific damage to the depth of sulci: a combination of initial molecular injury leading to oedema and later hypotension (Friede 1989), preservation only of neurons close to the pial arteries (Norman 1981), changes in cortical layer thickness at the depth of sulci (Duvernoy et al. 1981), different course of cortical arteries in sulcal depths versus gyral crowns (Duvernoy et al. 1981). Volpe and Pasternak 1977: capture of technetium in parasagittal areas especially posterior. Ulegyria is not restricted to term birth asphyxia. Focal gyral atrophy has been reported near arterial strokes, under subdural haematomas, in parasagittal areas around superior sagittal sinus thrombosis (Friede 1989), following severe hypoglycaemia and in metabolic conditions (e.g. molybdenum cofactor deficiency, Stence et al. 2013).  neuropathology of watershed injury Five control brain and nine brains with bilateral and large ulegyria were studied by Morys et al. 1993. Severe neuronal loss in the anterior part of the claustrum was observed after lesions that involved the frontal cortex. Pathological changes localized in the parietal and occipital cortices caused neuronal loss in the central and posterior part of the human claustrum. This suggests that the human claustrum is dependent on the neocortex and that it possesses extensive connections with the cerebral cortex that are topographically organized: anterior claustrum to frontal cortex, and central and posterior claustrum to parietal and occipital cortices. Volpe and Pasternak in 1977 demonstrated the interarterial location with radioactive technetium scans in term birth asphyxia, and Myers reproduced the event in asphyxiated monkeys in 1969 and 1972. The condition of focal destruction of sulci in their depth was described by Bressler in 1899 (references in Friede 1989). He presented a case of what is later referred to as polymicrogyria, but the second case involved focal destruction of the cortex, most pronounced in the depth of sulci, affecting paracentral zones as far as the occipital lobe. The lesions develop dense erratic myelin deposition and gliosis in the chronic stage (“plaques fibromyeliniques”), when the atrophied gyri resembled a mushroom with a thin stalk and a gyral head remaining. Bressler coined this lesion ulegyria. Ulegyria was later referred to as primary cortical necrosis by Malamud in 1964, mantle sclerosis by Courville in 1964. Ulegyria can be uni- or bilateral, it preferentially affects parieto-occipital border zones. The end stage leaves the local surface atrophic and granular. Some lesions cavitate. Arteries in the field show mineralisation and intima proliferation. asphyxia: decelerations  on the CTG are often present in term infants with watershed injury human term newborn asphyxia: major injury patterns If instead of an acute total asphyxial event, the fetus is subjected to partial asphyxia by sustained impairment of placental gas exchange, patterns of cerebral cortical injury with edema are noted: by rendering the mother hypotensive with flurothane, administering carbon monoxide, inducing tetanic uterine contractions with oxytocics or prostaglandins, impairing maternal placental circulation, administering catecholamines to the mother or by inducing maternal psychological stress. (Ranck and Windle 1959, Saxon and Ponce 1961, Saxon 1961, Brierley et al; 1969, Faro and Windle 1969, Sechzer 1969, Adamsons et al. 1971, Brann and Myers 1975, Myers 1969-1972-1977, Myers and Brann 1976).   This results in fetal metabolic acidosis with hypercarbia. When umbilical artery oxygen content is reduced from a normal value of 10-12 vol% to levels of 0.8-1.5 vol%, fetal bradycardia and hypotension develop. Even at these levels of hypoxia, periods of 30 to 40 minutes are required before the fetus shows evidence of brain injury. If oxygen content drops below 0.5 vol%, cardiovascular collapse and death follow. The degree of asphyxia required to produce brain injury is close to that resulting in death.  In Rhesus monkeys studied by Brann and Myers 1975, following such prolonged partial insult, 7/8 showed a prolonged time to first gasp until they began breathing spontaneously, 5 showed seizure activity consisting of generalized clonic, focal clonic, forced stare, eye fluttering, forced cries, and episodic opisthotonic posturing. The average time of appearance of the first seizure was 23 hours of age. Five fetuses showed significant cerebral edema. In about half the animals, asymmetry of cerebral injury was observed with the left hemisphere always the most affected. Pale or haemorrhagic necrosis involving the entire cortex of both hemispheres or restricted to a parasagittal posterior parietal distribution was noted, sparing thalamus, portions of adjacent white matter and medial aspects of the temporal lobe. More widespread cerebral necrosis was associated with myocardial injury and death from cardiovascular collapse. Animals subjected to partial asphyxia of shorter duration tended to survive and later showed focal cortical injury, predominant in the posterior parietal parasagittal regions.  the monkey model of partial asphyxia The pattern of injury with partial asphyxia resembles the typical pattern of injury seen in term human autopsy tissue (Larroche and Korn 1977, Friede 1989, Larroche and de Vries 1996) and in survivors (Martin and Barkovich 1995, Rutherford et al. 1996, Barkovich et al. 1995, Miller et al. 2005, de Vries and Groenendaal 2010, Ferrari et al. 2011). In the rhesus monkey model, partial asphyxia in association with total asphyxia leads to basal ganglia injury. The relative degrees of partial and total asphyxia are reflected in varying degrees of involvement of cortex. Animals subjected to severe partial asphyxia and relatively short episodes of total asphyxia showed lesions of both basal ganglia and cerebral cortex, whereas those subjected to more severe episodes of total asphyxia showed striking brainstem abnormalities.  Additional observations: (1) injury sufficiently severe to produce neocortical panlaminar necrosis is associated with seizures and augmented injury in hippocampus, (2) regional selective vulnerability tends to correlate with regional metabolic rate rather than with arterial watershed regions, (3) preterm fetal monkeys require longer durations of complete asphyxia to achieve similar brainstem and cerebellar injury as term fetuses.  Partial asphyxia (prolonged milder hypoxaemia) without acidosis results in white-matter injury (haemorrhagic or not). These fetuses do not show clinical signs of distress. The neuropathological findings are similar to those noted in juvenile monkeys exposed to cyanide or carbon monoxide (both impairing cerebral oxidative metabolism without altering CO2 or pH).  parasagittal posterior predominant haemorrhagic cortical necrosis in two different monkeys with partial asphyxia Interarterial collaterals at the pial surface may have an impact on the size of infarction following arterial occlusion. Linear anastomoses (collaterals) between major cerebral arteries in small preterm infants disappear gradually during the third trimester of pregnancy (Retzius 1896, van der Eecken 1959). This evolution renders watershed areas increasingly prominent and fragile, and at the same time reduces the collateral capacity in case of large artery occlusion. These and other maturational changes explain why arterial ischaemic stroke in preterm infants tends to spare cortex compared to underlying white matter, more often than in the term infant where this is rare (van der Aa et al. 2016). An MCA stroke may then be reduced to infarction of its central part only. cerebrocortical arterial collaterals, border zones Mac OS X  2:lATTRløtøcom.apple.TextEncodingHcom.apple.maclO com.apple.provenanceZcom.apple.quarantineutf-8;134217984@@ó$w'Gù�/J˜¡�…Â.Im0ÖWq/0081;00000000;;