GMH AND IVH PLUS VENOUS INFARCTION - keywords
GMH and IVH plus venous infarction
references to germinolysis
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Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte-endothelial interactions at the blood–brain barrier. Nature reviews Neuroscience, vol 7, 41-53.
Adams-Chapman I, Hansen NI, Stoll BJ, et al. Neurodevelopmental outcome of extremely low birth weight infants with posthemorrhagic hydrocephalus requiring shunt insertion. Pediatrics 2008;121:e1167–77.
Adcock K, Hedberg C, Loggins J, et al. The TNF-alpha -308, MCP-1 -2518 and TGF-beta1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants. Genes Immun. 2003; 4(6):420–426.
Ancel PY, Goffinet F, and the EPIPAGE-2 Writing Group. Epipage Survival and Morbidity of Preterm Children Born at 22 Through 34 Weeks’ Gestation in France in 2011 Results of the EPIPAGE-2 Cohort Study. JAMA Pediatr. 2015;169(3):230-238.
Anstrom JA, Brown WR, Moody DM, Thore CR, Challa VR, Block SM. Subependymal veins in premature neonates: implications for hemorrhage. Pediatr Neurol. 2004;30(1):46-53.
Anstrom JA, Thore CR, Moody DM, Challa VR, Block SM, Brown WR. Morphometric assessment of collagen accumulation in germinal matrix vessels of premature human neonates. Neuropathol Appl Neurobiol. 2005 Apr;31(2):181-90.
Anström JA, Thore CR, Moody DM, Challa VR Block SM, Brown WR (2005) Histologial analysis of vascular patterns and connections in the ganglionic eminence of prematur neonates. Neuroembryology 3; 4-12.
Anstrom JA, Thore CR, Moody DM, Challa VR, Block SM, Brown WR (2005) Germinal matrix cells associate with veins and a glial scaffold in the human fetal brain. Developmental Brain Research 160; 96-100.
Anstrom JA, Thore CR, Moody DM, Brown WR (2007) Immunolocalzation of tight junction proteins in blood vessels in human germinal matrix and cortex. Histochem. Cell Biol 127; 205-213.
Armstrong DL, Sauls CD, Goddard-Finegold J. Neuropathologic findings in short-term survivors of intraventricular hemorrhage. Am J Dis Child. 1987;141(6):617-21.
Ballabh P, Braun A, Nedergaard M. Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res. 2004 Jul;56(1):117-24.
Ballabh P, Hu F, Kumarasiri M, Braun A, Nedergaard M. Development of tight junction molecules in blood vessels of germinal matrix, cerebral cortex, and white matter. Pediatr Res. 2005 Oct;58(4):791-8.
Ballabh P, Xu H, Hu F, et al. Angiogenic inhibition reduces germinal matrix hemorrhage. Nat Med. 2007; 13(4):477–485.
Ballabh P. Pathogenesis and Prevention of Intraventricular hemorrhage. Clin Perinatol. 2014; 41(1): 47–67.
Ballabh P, de Vries LS. White matter injury in infants with intraventricular haemorrhage: mechanisms and therapies. Nat Rev Neurol. 2021 Apr;17(4):199-214.
Bassan H, Benson CB, Limperopoulos C, Feldman HA, Ringer SA, Veracruz E, Stewart JE, Soul JS, Disalvo DN, Volpe JJ, du Plessis AJ (2006) Ultrasonographic features and severity scoring of periventricular hemorrhagic infarction in relation to risk factors and outcome. Pediatrics 117:2111-2118.
Bassan H, Limperopoulos C, Visconti K, Mayer DL, Feldman HA, Avery L, Benson CB, Stewart J, Ringer SA, Soul JS, Volpe JJ, du Plessis AJ. Neurodevelopmental outcome in survivors of periventricular hemorrhagic infarction. Pediatrics. 2007;120(4):785-92.
Battin MR, Maalouf EF, Counsell SJ, Herlihy AH, Rutherford MA, Azzopardi D, et al. Magnetic resonance imaging of the brain in very preterm infants: visualization of the germinal matrix, early myelination, and cortical folding. Pediatrics. 1998 Jun;101(6):957-62.
Bell AH, Miller SL, Castillo-Melendez M, Malhotra A (2020) The neurovascular unit: effects of brain insults during the perinatal period. Frontiers in Neuroscience 13; 1452.
Bejar R, Coen RW, Ekpoudia I, James HE, Gluck L (1985) Real time ultrasound diagnosis of hemorrhagic pathological conditions in the posterior fossa of preterm infants. Neurosurgery 16:281–289.
Bowerman RA, Donn SM, Silver TM, Jaffe MH. Natural history of neonatal periventricular/intraventricular hemorrhage and its complications: sonographic observations. AJR Am J Roentgenol.1984;143(5):1041-52.
Brann BS 4th, Qualls C, Wells L, Papile L. Asymmetric growth of the lateral cerebral ventricle in infants with posthemorrhagic ventricular dilation. J Pediatr. 1991;118(1):108-12.
Braun A, Xu H, Hu F, Kocherlakota P, Siegel D, Chander P, et al. Paucity of pericytes in germinal matrix vasculature of premature infants. J Neurosci. 2007 Oct 31;27(44):12012-24.
Bravo MC, Lubian S, Horsch S, Cabañas F, de Vries LS; EurUS.Brain group. Neonatal ventriculomegaly: Pathophysiology and management guided with cranial ultrasonography. Dev Med Child Neurol. 2024 Nov;66(11):1419-1431. doi: 10.1111/dmcn.15955. Epub 2024 May 15. PMID: 38747316.Brouwer A, Groenendaal F, van Haastert IL, Rademaker K, Hanlo P, de Vries L. Neurodevelopmental outcome of preterm infants with severe intraventricular hemorrhage and therapy for post-hemorrhagic ventricular dilatation. J Pediatr. 2008;152(5):648-54.
Brouwer MJ, de Vries LS, Groenendaal F, Koopman C, Pistorius LR, Mulder EJ, Benders MJ. New reference values for the neonatal cerebral ventricles. Radiology. 2012;262(1):224-33.
Brouwer AJ, van Stam C, Uniken Venema M, Koopman C, Groenendaal F, de Vries LS. Cognitive and neurological outcome at the age of 5-8 years of preterm infants with post-hemorrhagic ventricular dilatation requiring neurosurgical intervention. Neonatology. 2012;101(3):210-6.
Brouwer AJ, Brouwer MJ, Groenendaal F, Benders MJ, Whitelaw A, de Vries LS. European perspective on the diagnosis and treatment of posthaemorrhagic ventricular dilatation. Arch Dis Child Fetal Neonatal Ed. 2012;97(1):F50-5.
Brouwer AJ, Groenendaal F, Benders MJ, de Vries LS. Early and late complications of germinal matrix-intraventricular haemorrhage in the preterm infant: what is new? Neonatology. 2014;106(4):296-303.
Brouwer AJ, Groenendaal F, Han KS, de Vries LS. Treatment of neonatal progressive ventricular dilatation: a single-centre experience. J Matern Fetal Neonatal Med. 2015;28 Suppl 1:2273-9.
Brown LS, Foster CG, Courtney JM, King NE, Howells DW, Sutherland BA (2019) Pericytes and Neurovascular Function in the Healthy and Diseased Brain. Front. Cell. Neurosci., 28 June 2019 | https://doi.org/10.3389/fncel.2019.00282
Brown WD, Gerfen GW, Vachon LA, Nelson MD (1994) Real-time ultrasonography of arterial IVH in preterm infants. Pediatric Neurology 11:325–327.
Browning W (1884) The Veins of the Brain and Its Envelopes: Their Anatomy and Bearing on the Intracranial Circulation. FB O’Connor, Brooklyn.
Camfferman FA, Govaert P, Groenendaal F, Vanderhasselt T, Cools F, Dudink J. Internal Cerebral Vein Doppler Velocities Reflect Maturational Changes and Hemorrhage Risk in Preterm Infants. AJNR Am J Neuroradiol. 2026 May 7.
Camfferman FA, Govaert P, Lequin MH, Groenendaal F, Tataranno ML, KizilatesU, Benders MJNL, Dudink J. Toward a Broader Classification of Deep Venous Cerebral Anatomy in Extremely Preterm Infants: A Literature-Based Approach andIts Relevance to Intraventricular Hemorrhage. AJNR Am J Neuroradiol. 2026 Feb 3;47(2):496-502. Carteaux P, Cohen H, Check J, George J, McKinley P, Lewis W, Hegwood P, Whitfield JM, McLendon D, Okuno-Jones S, Klein S, Moehring J, McConnell C (2003) Evaluation and development of potentially better practices for the prevention of brain hemorrhage and ischemic brain injury in very low birth weight infants. Pediatrics 111:e489-96.
Chang CL, Chiu NC (2010) Developmental venous anomaly found by cranial US in a neonate. Pediatr Radiol 40: 374.
Chen B, Herten A, Saban D, Rauscher S, Radbruch A, Schmidt B, Zhu Y, Jabbarli R, Wrede KH, Kleinschnitz C, Sure U, Dammann P (2020) Hemorrhage from cerebral cavernous malformations: The role of associated developmental venous anomalies. Neurology 95(1):e89-e96.
Chen Z, Gao C, Hua Y, Keep RF, Muraszko K, Xi G. Role of iron in brain injury after intraventricular hemorrhage. Stroke. 2011;42:465-70.
Cizmeci MN, de Vries LS, Ly LG, van Haastert IC, Groenendaal F, Kelly EN, Traubici J, Whyte HE, Leijser LM. Periventricular Hemorrhagic Infarction in Very Preterm Infants: Characteristic Sonographic Findings and Association with Neurodevelopmental Outcome at Age 2 Years. J Pediatr. 2020 Feb;217:79-85.e1.
Corbin JG, Gaiano N, Juliano SL, Poluch S, Stancik E, Haydar TF. Regulation of neural progenitor cell development in the nervous system. J Neurochem. 2008 Sep;106(6):2272-87.
Counsell SJ, Maalouf EF, Rutherford MA, Edwards AD (1999) Periventricular haemorrhagic infarct in a preterm neonate. Eur J Paediatr Neurol 3:25-7.
Darrow VC, Alvord EC jr, Mack LA, Hodson WA (1988) Histologic evolution of the reactions to hemorrhage in the premature human infant’s brain. A combined ultrasound and autopsy study and a comparison with the reaction in adults. Am J Pathol 130:44-58.
Davies MW, Swaminathan M, Chuang SL, Betheras FR. Reference ranges for the linear dimensions of the intracranial ventricles in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 2000;82(3):F218-23.
Davis AS, Hintz SR, Goldstein RF, Ambalavanan N, Bann CM, Stoll BJ, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Outcomes of extremely preterm infants following severe intracranial hemorrhage. J Perinatol. 2014;34(3):203-8.
Dawes WJ, Zhang X, Fancy SPJ, Rowitch D, Marino S (2016) Moderate-grade germinal matrix haemorrhage activates cell division in the neonatal mouse subventricular zone. Dev Neurosci 38; 430-444.
Debus O, Koch HG, Kurlemann G, et al. Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly. Arch Dis Child Fetal Neonatal Ed. 1998; 78(2):F121–124.
Del Bigio MR. Cell proliferation in human ganglionic eminence and suppression after prematurity-associated haemorrhage. Brain 2011;134:1344–61.
Dempsey EM, Barrington KJ. Treating hypotension in the preterm infant: when and with what: a critical and systematic review. J Perinatol 2007;27:469–78.
De Vries LS, Groenendaal F, van Haastert IC, Eken P, Rademaker KJ, Meiners LC (1999) Asymmetrical myelination of the posterior limb of the internal capsule in infants with periventricular haemorrhagic infarction: an early predictor of hemiplegia. Neuropediatrics 30(6):314-9.
De Vries LS, Groenendaal F, Gooskens R, Hanlo P. Unilateral posthaemorrhagic hydrocephalus in the neonatal period or later in infancy. Acta Paediatr. 2000;89(1):77-81.
de Vries LS, Roelants-van Rijn AM, Rademaker KJ, Van Haastert IC, Beek FJ, Groenendaal F (2001) Unilateral parenchymal haemorrhagic infarction in the preterm infant. Eur J Paediatr Neurol 5:139-49.
Dewbury KC, Bates RI. Neonatal intracranial haemorrhage: the cause of the ultrasound appearances. Br J Radiol. 1983;56(671):783-9.
Dolfin T, Skidmore MB, Fong KW, Hoskins EM, Shennan AT (1983) Incidence, severity, and timing of subependymal and intraventricular hemorrhages in preterm infants born in a perinatal unit as detected by serial real-time ultrasound. Pediatrics 71(4):541-6.
Donn SM, Bowerman RA. Neonatal posthemorrhagic porencephaly. Ultrasonographic features. Am J Dis Child 1982; 36:707-709.
Dudink J, Lequin M, Weisglas-Kuperus N, Conneman N, van Goudoever JB, Govaert P. Venous subtypes of preterm periventricular haemorrhagic infarction. Arch Dis Child Fetal Neonatal Ed. 2008;93(3):F201-6.
El-Khoury N, Braun A, Hu F, Pandey M, Nedergaard M, Lagamma EF, et al. Astrocyte end-feet in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res. 2006 May;59(5):673-9.
EXPRESS Group, Fellman V, Hellström-Westas L, Norman M, Westgren M, Källén K, Lagercrantz H, Marsál K, Serenius F, Wennergren M. One-year survival of extremely preterm infants after active perinatal care in Sweden. JAMA. 2009 Jun 3;301(21):2225-33
Fleischer AC, Hutchison AA, Allen JH, Stahlman M, Meacham WF, James AE (1981) The role of sonography and the radiologist–ultrasonologist in the detection and follow-up of intracranial hemorrhage in the preterm neonate. Radiology 139:733–736.
Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev. 2010; (7):CD000174.
Funato M, Tamai H, Takeda Z (1994) Moment of intraventricular hemorrhage—clinical pathogenic events. In: Lou, H.C., Greisen, G., Larsen, J.F. (Eds.) Brain Lesions in the Newborn. Hypoxic and Haemodynamic Pathogenesis. Alfred Benzon Symposium No. 37. Munksgaard, pp. 456–469.
Geraldo AF, Messina SS, Tortora D, Parodi A, Malova M, Morana G, Gandolfo C, D'Amico A, Herkert E, Govaert P, Ramenghi LA, Rossi A, Severino M (2020) Neonatal Developmental Venous Anomalies: Clinicoradiologic Characterization and Follow-Up. AJNR Am J Neuroradiol 41(12):2370-2376.
Ghazi-Birry H, Brown W, Moody D, Challa V, Block S, and Reboussin D (1977) Human Germinal Matrix: Venous Origin of Hemorrhage and Vascular Characteristics. Am J Neuroradiol 18:219-229.
Golden JA, Gilles FH, Rudelli R, Leviton A. Frequency of neuropathological abnormalities in very low birth weight infants. J Neuropathol Exp Neurol. 1997;56(5):472-8.
Gopel W, Hartel C, Ahrens P, et al. Interleukin-6-174-genotype, sepsis and cerebral injury in very low birth weight infants. Genes Immun. 2006; 7(1):65–68.
Gould SJ, Howard S, Hope PL, Reynolds EOR (1986) Periventricular intraparenchymal cerebral haemorrhage in preterm infants: the role of venous infarction. J Pathol 151:197–202.
Govaert P, Smets K, Matthys E, Oostra A (1999) Neonatal focal temporal lobe or atrial wall haemorrhagic infarction. Arch Dis Child Fetal Neonatal Ed 81(3):F211-6.
Govaert P, De Vries LS. An atlas of neonatal brain sonography, 2nd ed. London, England: Mac Keith Press, 2010:199-224.
Govaert P, Triulzi F, Dudink J (2020) The developing brain by trimester. Handb Clin Neurol 171:245-289.
Gram M, Sveinsdottir S, Ruscher K, Hansson SR, Cinthio M, Akerström B, Ley D. Hemoglobin induces inflammation after preterm intraventricular hemorrhage by methemoglobin formation. J Neuroinflammation. 2013 ;10:100.
Grant EG, Kerner M, Schellinger O, et al. Evolution of porencephalic cysts from intraparenchymal hemorrhage in neonates. Sonographic evidence. AJNR 1982;3:47-50, AiR 1982; 138:467-470.
Grant EG, White EM (1986) Pediatric neurosonography. J Child Neurol 1:319–337.
Greisen G. Autoregulation of cerebral blood flow in newborn babies. Early Hum Dev. 2005;81:423-28.
Gressens P, Richelme C, Kadhim HJ, Gadisseux JF, Evrard P. The germinative zone produces the most cortical astrocytes after neuronal migration in the developing mammalian brain. Biol Neonate 1992;62:4-24.
Guzzetta F, Shackelford GD, Volpe S, Perlman JM, Volpe JJ. Periventricular intraparenchymal echodensities in the premature newborn: critical determinant of neurologic outcome. Pediatrics. 1986;78(6):995-1006.
Habas PA, Kim K, Corbett-Detig JM, Rousseau F, Glenn OA, Barkovich AJ, et al. A spatiotemporal atlas of MR intensity, tissue probability and shape of the fetal brain with application to segmentation. Neuroimage. 2010 Nov 1;53(2):460-70.
Hambleton G, Wigglesworth JS. Origin of intraventricular haemorrhage in the preterm infant. Arch Dis Child. 1976;51(9):651-9.
Harteman JC, Groenendaal F, van Haastert IC, et al. Atypical timing and presentation of periventricular haemorrhagic infarction in preterm infants: the role of thrombophilia. Developmental Med Child Neurol. 2012; 54(2):140–147.
Harteman JC, Nikkels PG, Kwee A, Groenendaal F, de Vries LS. Patterns of placental pathology in preterm infants with a periventricular haemorrhagic infarction: association with time of onset and clinical presentation. Placenta. 2012 Oct;33(10):839-44.
Hope PL, Gould SJ, Howard S, Hamilton PA, Costello AM, Reynolds EO. Precision of ultrasound diagnosis of pathologically verified lesions in the brains of very preterm infants. Dev Med Child Neurol. 1988; 30(4):457-71.
Horbar JD, Carpenter JH, Badger GJ, Kenny MJ, Soll RF, Morrow KA, Buzas JS. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics. 2012;129(6):1019-26.
Horsch S, Kutz P, Roll C. Late germinal matrix hemorrhage-like lesions in very preterm infants. J Child Neurol. 2010;25(7):809-14.
Horsch S, Govaert P , Cowan FM, Benders M, Groenendaal F, Lequin MH, Saliou G, de Vries LS (2014) Developmental Venous Anomaly in the Newborn Brain. Neuroradiology 56(7):579-88.
Kent T, Sinha V, Ceyhan E, et al. Deep cerebral venous abnormalities in premature babies with GMH-IVH: a single-centre retrospective study. BMJ Paediatr Open 2023;7.
Kersbergen KJ, Groenendaal F, Benders MJ, van Straaten HL, Niwa T, Nievelstein RA, de Vries LS. The spectrum of associated brain lesions in cerebral sinovenous thrombosis: relation to gestational age and outcome. Arch Dis Child Fetal Neonatal Ed. 2011;96(6):F404-9.
Kinoshita Y, Okudera T, Tsuru E, Yokota A (2001) Volumetric Analysis of the Germinal Matrix and Lateral Ventricles Performed Using MR Images of Postmortem Fetuses. Am J Neuroradiol 22:382–388.
Kirks DR, Bowie JD (1986) Cranial ultrasonography of neonatal periventricular/intraventricular hemorrhage: who, how, why and when? Pediatric Radiol 16:114–119.
Klebermass-Schrehof K, Czaba C, Olischar M, Fuiko R, Waldhoer T, Rona Z, Pollak A, Weninger M. Impact of low-grade intraventricular hemorrhage on long-term neurodevelopmental outcome in preterm infants. Childs Nerv Syst. 2012;28(12):2085-92.
Kluckow M, Evans N, Osborn D. Low Systemic Blood Flow and Brain injury in the Preterm Infant. Neoreviews 2004; 5(3): e98–108.
Koumanidou C, Vakaki M, Anagnostara A, Pitsoulakis G, Kakavakis K, Mirilas P. Hemorrhage in the cavum septi pellucidi, and a brief review of the literature. Neuroradiology. 2002 ;44(9):770-4.
Kuban K, Teele RL (1984) Rationale for grading intracranial hemorrhage in premature infants. Pediatrics 74:358–363.
Larroche J-Cl (1977) Developmental pathology of the neonate.North-Holland: Elsevier.
Larroque B, Marret S, Ancel PY, Arnaud C, Marpeau L, Supernant K, Pierrat V, Rozé JC, Matis J, Cambonie G, Burguet A, Andre M, Kaminski M, Bréart G; EPIPAGE Study Group. White matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study. J Pediatr. 2003;143(4):477-83.
Lee C, Pennington MA, Kenney III CM (1996) MR evaluation of developmental venous anomalies: medullary venous anatomy of venous angiomas. Am J Neuroradiol 17: 61-70.
LeFlore JL, Broyles RS, Pritchard MA, Engle WD (2003) Value of neurosonography in predicting subsequent cognitive and motor development in extremely low birth weight neonates. J Perinatol 23:629-34.
Leijser LM, Miller SP, van Wezel-Meijler G, Brouwer AJ, Traubici J, van Haastert IC, Whyte HE, Groenendaal F, Kulkarni AV, Han KS, Woerdeman PA, Church PT, Kelly EN, van Straaten HLM, Ly LG, de Vries LS. Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene? Neurology. 2018 ;90(8):e698-e706.
Levene MI, Starte DR. A longitudinal study of post-haemorrhagic ventricular dilatation in the newborn. Arch Dis Child. 1981;56(12):905-10.
Levene MI. Measurement of the growth of the lateral ventricles in preterm infants with real-time ultrasound. Arch Dis Child. 1981;56(12):900-4.
Leviton A, Pagano M, Kuban KC, Krishnamoorthy KS, Sullivan KF, Allred EN. The epidemiology of germinal matrix hemorrhage during the first half-day of life. Dev Med Child Neurol. 1991;33(2):138-45.
Ley D, Romantsik O, Vallius S, Sveinsdóttir K, Sveinsdóttir S, Agyemang AA, Baumgarten M, Mörgelin M, Lutay N, Bruschettini M, Holmqvist B, Gram M. High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage. Front Physiol. 2016;7:330.
Maitre NL, Marshall DD, Price WA, Slaughter JC, O'Shea TM, Maxfield C, Goldstein RF. Neurodevelopmental outcome of infants with unilateral or bilateral periventricular hemorrhagic infarction. Pediatrics. 2009;124(6):e1153-60.
Marin-Padilla M (1996) Developmental neuropathology and impact of perinatal brain damage. I : Hemorrhagic lesions of neocortex. J Neuropath Exp Neurol 55:758-773.
Miletin J, Dempsey EM. Low superior vena cava flow on day 1 and adverse outcome in the very low birthweight infant. Arch Dis Child Fetal Neonatal Ed 2008;93:F368–F371
Meek JH, Tyszczuk L, Elwell CE, Wyatt JS (1999) Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage. Arch Dis Child Fetal Neonat Ed 81, F15-F18
Ment LR, Stewart WB, Ardito TA, Huang E, Madri JA. Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup. Stroke. 1992 Aug;23(8):1132-7.
Ment LR, Vohr BR, Makuch RW, et al. Prevention of intraventricular hemorrhage by indomethacin in male preterm infants. J Pediatr. 2004; 145(6):832–834.
Moody DM, Brown WR, Challa VR, Block SM (1994) Alkaline phosphatase histochemical staining in the study of germinal matrix hemorrhage and brain vascular morphology in a very-low-birth-weight neonate. Pediatr Res 35:424-430.
Murphy BP, Inder TE, Rooks V, Taylor GA, Anderson NJ, Mogridge N, Horwood LJ, Volpe JJ. Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome. Arch Dis Child Fetal Neonatal Ed. 2002;87(1):F37-41.
Nadeem T, Bommareddy A, Bolarinwa L, Cuervo H (2022) Pericyte dynamics in the mouse germinal matrix angiogenesis. Faseb Journal 2022;36:e22339.
Nakamura Y, Okudera T, Fukuda S, Hashimoto T (1990) Germinal matrix hemorrhage of venous origin in preterm neonates. Human Pathol 21:1059-1062.
Nakamura Y, Okudera T, Hashimoto T (1991) Microvasculature in germinal matrix layer : its relationship to germinal matrix hemorrhage. Modern Pathol 4:475-480.
Okudera T, Huang YP, Fukusumi A, Nakamura Y, Hatazawa J, Uemura K (1999) Micro-angiographical studies of the medullary venous system of the cerebral hemisphere. Neuropathology 19:93-111.
Osborn DA, Evans N, Kluckow M (2003) Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants. Pediatrics 112:33-9.
Ozduman K, Pober BR, Barnes P, Copel JA, Ogle EA, Duncan CC, Ment LR. Fetal stroke. Pediatr Neurol. 2004;30(3):151-62.
Padget DH (1956) The cranial venous system in man in reference to development, adult configuration, and relation to the arteries. Am J Anat 98:307-356
Paneth N, Rudelli R, Kazam E, Monte W (1994) Brain Damage in the Preterm Infant. Clinics in Developmental Medicine No. 131. London: Mac Keith Press.
Pape KE, Wigglesworth JS (1979) Haemorrhage, Ischaemia and the Perinatal Brain. Clinics in Developmental Medicine No. 69/70. London: Spastics International Medical Publications.
Papile LA, Burstein J, Burstein R, Koffler H (1978) Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 92(4):529-34.
Parodi A, Morana G, Severino MS, Malova M, Natalizia AR, Sannia A, Rossi A, Ramenghi LA (2013) Low-grade intraventricular hemorrhage: is ultrasound good enough ? J Maternal Fetal Neonatal Medicine
Patra K, Wilson-Costello D, Taylor HG, Mercuri-Minich N, Hack M. Grades I-II intraventricular hemorrhage in extremely low birth weight infants: effects on neurodevelopment. J Pediatr. 2006;149(2):169-73.
Perlman JM, Volpe JJ. Intraventricular hemorrhage in extremely small premature infants. Am J Dis Child. 1986;140(11):1122-4.
Perlman JM, Rollins N, Burns D, Risser R (1993) Relationship between periventricular intraparenchymal echodensities and germinal matrix–intraventricular hemorrhage in the very low birth weight neonate. Pediatrics 91:474–480.
Pierrat V, Duquennoy C, van Haastert IC, Ernst M, Guilley N, de Vries LS. Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leukomalacia. Arch Dis Child Fetal Neonatal Ed 2001;84:F151–F156.
Pryds O, Greisen G, Lou H, Friis-Hansen B. Heterogeneity of cerebral vasoreactivity in preterm infants supported by mechanical ventilation. J Pediatr. 1989;115(4): 638–45.
Rabe H, Diaz-Rossello JL, Duley L, Dowswell T. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev. 2012;8:CD003248.
Rademaker KJ, Groenendaal F, Jansen GH, Eken P, de Vries LS (1994) Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Paediatr 83:602–608.
Raets MM, Dudink J, Govaert P. Neonatal disorders of germinal matrix. J Matern Fetal Neonatal Med. 2015;28 Suppl 1:2286-90.
Ramenghi LA, Gill BJ, Tanner SF, Martinez D, Arthur R, Levene MI (2002) Cerebral venous thrombosis, intraventricular haemorrhage and white matter lesions in a preterm newborn with factor V (Leiden) mutation. Neuropediatrics 33:97-9.
Ramenghi LA, Mosca F, Counsell S, Rutherford MA. Magnetic Resonance Imaging of the Brain in Preterm Infants. In: Tortori-Donati P. Pediatric Neuroradiology. Volume 1 (Brain). 1st ed. Berlin, Germany: Springer-Verlag, 2005:199-234.
Ramenghi LA, Fumagalli M, Righini A, Triulzi F, Kustermann A, Mosca F. Thrombophilia and fetal germinal matrix-intraventricular hemorrhage: does it matter? Ultrasound Obstet Gynecol. 2005;26(5):574-6.
Ramenghi LA, Fumagalli M, Groppo M, Consonni D, Gatti L, Bertazzi PA, Mannucci PM, Mosca F. Germinal matrix hemorrhage: intraventricular hemorrhage in very-low-birth-weight infants: the independent role of inherited thrombophilia. Stroke. 2011;42(7):1889-93.
Reeder JD, Kaude JV, Setzer ES (1982) Choroid plexus hemorrhage in premature neonates: recognition by sonography. Am J Neuroradiol 3:619–622.
Rhine W, Blankenberg FG. Cranial Ultrasonography. NeoReviews 2001 2(1): 3–11.
Roelants-van Rijn AM, Groenendaal F, Beek FJ, Eken P, van Haastert IC, de Vries LS. Parenchymal brain injury in the preterm infant: comparison of cranial ultrasound, MRI and neurodevelopmental outcome. Neuropediatrics. 2001 Apr;32(2):80-9.
Roze E, Benders MJ, Kersbergen KJ, van der Aa NE, Groenendaal F, van Haastert IC, Leemans A, de Vries LS. Neonatal DTI early after birth predicts motor outcome in preterm infants with periventricular hemorrhagic infarction. Pediatr Res. 2015 Sep;78(3):298-303.
Rypens F, Avni EF, Dussaussois L, David P, Vermeylen D, Van Bogaert P, Matos C (1994) Hyperechoic thickened ependyma: sonographic demonstration and significance in neonates. Pediatr Radiol 24:550–553.
Rademaker KJ, Groenendaal F, Jansen GH, Eken P, de Vries LS (1994) Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Paediatr 83(6):602-8.
Rademaker KJ, Govaert P, Vandertop WP, Gooskens R, Meiners LC, de Vries LS. Rapidly progressive enlargement of the fourth ventricle in the preterm infant with post-haemorrhagic ventricular dilatation. Acta Paediatr. 1995;84(10):1193-6.
Robinson S. Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts. J Neurosurg Pediatr. 2012;9(3):242-58.
Roelants-van Rijn AM, Groenendaal F, Beek FJ, Eken P, van Haastert IC, de Vries, LS (2001) Parenchymal brain injury in the preterm infant: comparison of cranial ultrasound, MRI and neurodevelopmental outcome. Neuropediatrics 32:80-9.
Roze E, Benders MJ, Kersbergen KJ, van der Aa NE, Groenendaal F, van Haastert IC, Leemans A, de Vries LS. Neonatal DTI early after birth predicts motor outcome in preterm infants with periventricular hemorrhagic infarction. Pediatr Res. 2015;78(3):298-303.
Rushton DI, Preston PR, Durbin GM (1985) Structure and evolution of echo dense lesions in the neonatal brain. A combined ultrasound and necropsy study. Arch Dis Child 60:798–808.
Rypens E, Avni EF, Dussaussois L, David P, Vermeylen D, van Bogaert P, Matos C. Hyperechoic thickened ependyma: sonographic demonstration and significance in neonates. Pediatr Radiol. 1994;24(8):550-3.
Sannia A, Natalizia AR, Parodi A, Malova M, Fumagalli M, Rossi A, Ramenghi LA. Different gestational ages and changing vulnerability of the premature brain. J Matern Fetal Neonatal Med. 2015; 28 Suppl 1:2268-72.
Saunders NR, Dziegielewska KM, Mollgard K, Habgood MD (2018). Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain. J. Physiol. 596, 5723–5756. Schmidt H (1965) Untersuchungen zur Pathogenese und Ätiologie der geburtstraumatischen Hirnschädigungen Früh- und Reifgeborener. Jena: Gustav Fisher Verlag.
Schwartz P (1961) Birth Injuries of the Newborn. Basel/New York: Karger.
Scott JA, Habas PA, Kim K, et al. Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI. Int J Dev Neurosci 2011;29:529–36.
Shackelford GD, Volpe JJ. Cranial ultrasonography in the evaluation of neonatal intracranial hemorrhage and its complications. J Perinat Med. 1985;13(6):293-304.
Shaver DC, Bada HS, Korones SB, Anderson GD, Wong SP, Arheart KL. Early and late intraventricular hemorrhage: the role of obstetric factors. Obstet Gynecol. 1992;80(5):831-7.
Sheehan JW, Pritchard M, Heyne RJ, Brown LS, Jaleel MA, Engle WD, Burchfield PJ, Brion LP. Severe intraventricular hemorrhage and withdrawal of support in preterm infants. J Perinatol. 2017;37(4):441-447.
Slovis TL, Shankaran S (1984) Ultrasound in the evaluation of hypoxic–ischemic injury and intracranial hemorrhage in neonates: the state of the art. Pediatr Radiol 14:67–75.
Soltirovska Salamon A, Groenendaal F, van Haastert IC, Rademaker KJ, Benders MJ, Koopman C, de Vries LS. Neuroimaging and neurodevelopmental outcome of preterm infants with a periventricular haemorrhagic infarction located in thetemporal or frontal lobe. Dev Med Child Neurol. 2014 Jun;56(6):547-55. Stein RL, Rosenbaum AE. Deep supratentorial veins. Section I. Normal deep cerebral venous system. In: Newton TH, Potts DG, eds. Radiology of the Skull and Brain. St. Louis: Mosby; 1974:1903–1998.
Steinsmo Ødegård S, Jarmund AH, Pedersen SA, Govaert P, Dudink J, Nyrnes SA. A scoping review of variations in cerebral Doppler venous waveforms in infants. Neuroimage. 2026 Mar;328:121766.
Stoll BJ, Hansen NI,Bell EF,et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126(3):443-456.
Supramaniam V, Vontell R, Srinivasan L, Wyatt-Ashmead J, Hagberg H, Rutherford M. Microglia activation in the extremely preterm human brain. Pediatr Res. 2013 ;73(3):301-9.
Tajdar M, Orlando C, Casini A, Herpol M, De Bisschop B, Govaert P, Neerman-Arbez M, Jochmans K. Heterozygous FGA p.Asp473Ter (fibrinogen Nieuwegein) presenting as antepartum cerebral thrombosis.Thromb Res. 2017 Oct 28. pii: S0049-3848(17)30536-4.
Takashima S, Tanaka K (1978) Microangiography and vascular permeability of the subependymal matrix in the premature infant. Can J Neurol Sci 5(1):45-50.
Takashima S, Mito T, Ando Y (1986) Pathogenesis of periventricular white matter hemorrhages in preterm infants. Brain Develop 8:25–30.
Taoka T, Fukusumi A, Miyasaka T, et al. Structure of the Medullary Veins of the Cerebral Hemisphere and Related Disorders. Radiographics : a review publication of the Radiological Society of North America, Inc 2017;37:281–297.
Tarnow-Mordi W, Morris J, Kirby A et al. Delayed versus Immediate Cord Clamping in Preterm Infants. N Engl J Med. 2017;377(25):2445-2455.
Taylor GA. Effect of germinal matrix hemorrhage on terminal vein position and patency. Pediatr Radiol 1995; 25:Suppl 1 S37-40.
Testut L, Latarjet A (1948). Traité d’anatomie Humaine, Vol. 2. Paris: Doin.
Toft PB, Leth H, Peitersen B, Lou HC. Metabolic changes in the striatum after germinal matrix hemorrhage in the preterm infant. Pediatr Res. 1997;41(3):309-16.
Tortora D, Severino M, Malova M, Parodi A, Morana G, Sedlacik J, Govaert P, Volpe JJ, Rossi A, Ramenghi LA. Differences in subependymal vein anatomy may predispose preterm infants to GMH-IVH. Arch Dis Child Fetal Neonatal Ed. 2018;103(1):F59-F65.
Tortora D, Martinetti C, Severino M, Uccella S, Malova M, Parodi A, Brera F, Morana G, Ramenghi LA, Rossi A. The effects of mild germinal matrix-intraventricular haemorrhage on the developmental white matter microstructure of preterm neonates: a DTI study. Eur Radiol. 2017 Sep 27.
Tortora D, Severino M, Malova M, Parodi A, Morana G, Ramenghi LA, Rossi A. Variability of Cerebral Deep Venous System in Preterm and Term Neonates Evaluated on MR SWI Venography. AJNR Am J Neuroradiol. 2016 Jul 28.
Ulfig N. Ganglionic eminence of the human fetal brain--new vistas. Anat Rec. 2002 Jul 1;267(3):191-5.
Van Wezel-Meijler G. Neonatal cranial ultrasonography. 1st ed. Berlin, Germany: Springer-Verlag, 2007:53.
van Buuren LM, van der Aa NE, Dekker HC, Vermeulen RJ, van Nieuwenhuizen O, van Schooneveld MM, de Vries LS. Cognitive outcome in childhood after unilateral perinatal brain injury. Dev Med Child Neurol. 2013 Oct;55(10):934-40.
Vasileiadis GT, Gelman N, Han VK, Williams LA, Mann R, Bureau Y, et al. Uncomplicated intraventricular hemorrhage is followed by reduced cortical volume at near term age. Pediatrics. 2004;114:e367-72.
Verbeek E, Meuwissen ME, Verheijen FW, Govaert PP, Licht DJ, Kuo DS, et al. COL4A2 mutation associated with familial porencephaly and small-vessel disease. Eur J Hum Genet. 2012 Aug;20(8):844-51.
Verhage CH, Groenendaal F, van der Net J, van Schooneveld MM, de Vries LS, van der Aa NE. Bimanual performance in children with unilateral perinatal arterial ischaemic stroke or periventricular haemorrhagic infarction. Eur J Paediatr Neurol. 2022 Mar;37:46-52.
Vinukonda G, Dummula K, Malik S, et al. Effect of prenatal glucocorticoids on cerebral vasculature of the developing brain. Stroke. 2010; 41(8):1766–1773.
Volpe JJ. Brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. Semin Pediatr Neurol. 1998;5(3):135-51.
Volpe JJ (1989) Intraventricular hemorrhage and brain injury in the premature infant. Neuropathology and pathogenesis. Clinics Perinatol 16:361–411.
Volpe JJ (1990) Brain injury in the premature infant: is it preventable? Pediatr Res 27:S28–S33.
Volpe JJ. Neurology of the Newborn. 5th ed. Philadelphia, PA: Saunders Elsevier, 2008:517-88.
Wang J, Wang J, Sun J, et al. Evaluation of the anatomy and variants of internal cerebral veins with phase-sensitive MR imaging. Surg Radiol Anat 2010;32:669–674.
Wapner RJ. Antenatal corticosteroids for periviable birth. Semin Perinatol. 2013;37(6):410-3.
Whitelaw A. Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions. Semin Neonatol. 2001;6(2):135-46.
Xu H, Hu F, Sado Y, et al. Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone. J Neurosci Res. 2008; 86(7):1482–1500.
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outcome
Genuine mantle rupture from IVHExceptionally mechanical rupture does occur in the parenchyma under pressure by extensive IVH. Neonates nursed supine while ventilated will then show a ventricular bleed nearly completely replaced by an extracerebral density in the occipital region after rupture. This very rare event was formerly believed to underly all white matter infarcts associated with IVH of the preterm, whereas it is now clear that the intermediary is not mechanical rupture of the telencephalic wall, but venous infarction.
parenchymal haemorrhagic infarction associated with GMH/IVH
haemorrhage grading
preterm infant with grade 3 IVH that suddenly disappeared because of transparenchymal penetration of the blood into the subarachnoid/subdural space (7.5 MHz image)
Outcome for temporal lobe venous infarction is worse than for frontal lobe infarction. Unfavourable outcome (cognitive and behavioural) is observed in the majority of children with a temporal PHI compared with 1/3 of children with a frontal PHI. CP is typically associated with parietal (terminal vein) involvement, especially the extensive variant of infarction.
veins
PHI (periventricular haemorrhagic infarction) complicates GMH-IVH in approximately 15% of cases (Golden et al. 1997, Larroque et al. 2003). GMH-IVH of all grades can be complicated by PHI, but the higher the grade the more likely PHI is to occur (Guzetta et al. 1986). PHI follows venous obstruction induced by GMH. Congestion leads to ischaemia and to secondary haemorrhagic infarction. High intraventricular pressure dilating the ventricles due to a large IVH may additionally affect flow through the subependymal veins, increasing infarct size (Volpe 1998). Cerebral palsy and cognitive impairment are common in infants with PHI (Brouwer et al. 2008, Adams-Chapman et al. 2008, Klebermass-Shrehof et al. 2012). The prognosis is dependent on location and extent of the lesion (Bassan et al. 2006 and 2007, Dudink et al. 2008, Maitre et al. 2009). Classifying PHI into venous subtypes helps to counsel parents in this difficult situation (Dudink et al. 2008). Mortality in infants with extensive PHI is high, especially when it is bilateral. In many countries, redirection of care and end of life decisions are considered in infants with bilateral PHI. Although robust data on this are lacking, it is likely that redirection of care contributes significantly to the reported mortality rates (Davis et al. 2014, Sheehan et al. 2017).
In preterms with PHI on CUS, neonatal MRI can show unsuspected cystic PVL or blood in the posterior fossa (Roelants-van Rijn et al. 2001). Late MRI can show asymmetry at the posterior limb of the internal capsule (PLIC), predictor of hemiplegia.
Chorioamnionitis and funisitis are significantly more common in infants with a typical PHI; starting at 6 to 96 hours after birth (Harteman et al. 2012). Fetal thrombosis and placental infarction are significantly more often associated with an atypical PHI (antenatal or later neonatal onset).
DVA in the differential diagnosis
Developmental venous anomalies, relatively common in the newborn brain, may present with initial scans similar to venous infarction (Chang et al. 2010, Chen et al. 2020, Geraldo et al. 2020, Horsch et al. 2014, Lee et al. 1996, Okudera et al. 1999. The serial stability on CUS and typical MR findings confirm DVA.
ultrasound description
germinal matrix and veins near the caudate head
CUS examples via navigator
U-turn
ICV variation
GMH and veins
typical doppler
The terminal vein (thalamostriate vein) drains into the internal cerebral vein together with the septal vein near the stria terminalis. GMH in a matrix pocket in this area can compress the terminal or septal vein or one of their adjacent branches. This leads to medullary vein congestion, haemorrhagic diapedesis and finally venous infarction. On occasion one can observe with doppler that there may be an arterial ischaemic component to this infarction.
medullary veins
infarct types
——>
venous variations
Prognosis of venous infarction associated with GMH/IVH
Infants that suffer from grade 3 GMH-IVH have a significantly increased risk for disability, especially when complicated by post-haemorrhagic ventricular dilatation that needs surgical intervention. Cerebral palsy rates in infants with IVH grade 3 range between 7-63% (Brouwer et al. 2008, Adams-Chapman et al. 2008, Klebermass-Shrehof et al. 2012). Infants that suffer from mild low-grade (i.e. grade 1 or 2) GMH-IVH are clearly at much lower risk of developmental disabilities compared to infants with grade 3 GMH-IVH or IPL. Recent data suggest that this may not be entirely true (Patra et al. 2006, Klebermass-Shrehof et al. 2012). It has been shown that low-grade GMH-IVH is followed by microstructural impairment in the periventricular and subcortical white matter (Tortora et al. 2017). Size, number and location of these minor bleedings might be of importance in infants of the lowest gestational ages.
Moderate-to-severe haemorrhage dilates the ventricle and damages the periventricular white matter even in the absence of PHI (Ballabh and de Vries 2021). This white matter injury results from oxidative stress, glutamate excitotoxicity, inflammation, perturbed signalling pathways and remodelling of the extracellular matrix.
In addition, germinal matrix injury even after an uncomplicated GMH-IVH results in a relevant loss of glial precursor cells, leading to impaired myelination and cortical development (Gressens et al. 1992, Vasileadis et al. 2004). GMH-IVH can also trigger inflammation in adjacent white matter through activated microglia, passage of red blood cells and red blood cell degradation: resulting tissue injury may be secondary to free radical release and the presence of free iron (Chen et al. 2011, Gram et al. 2013, Supramaniam et al. 2013, Ley et al. 2016).
A neuropsychological assessment was performed in 50 children with unilateral PHI (n=21) or perinatal arterial ischaemic stroke (n=29) at a median age of 11 years 9 months (van Buuren et al. 2013). In children with PHI, both the early Griffiths scores (mean 87; 95% CI 83-92) and the Full-scale IQ (FSIQ) scores at school age (mean 86; 95% CI 78-94) were below the test mean of 100. In the PAIS group, early Griffiths scores were within the normal range (mean 98; 95% CI 93-104), but at school age FSIQ scores were below average (mean 87; 95% CI 80-94).
In an assessment at 2 years of age of 160 infants with median gestational age of 26.6 weeks, PHI was scored to refine outcome prediction (Cizmeci et al. 2022). PHI was mostly unilateral (90%), associated with an ipsilateral extensive (grade 3) intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PHI died in the neonatal period. Of the survivors 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. Higher PHI severity score was associated with death. Trigone involvement (terminal vein area) was associated with cerebral palsy (41% vs 14%). Associated posthaemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes.
With a retrospective hospital-based preterm infants with frontal (n=21) or temporal PHI (n=13) were assessed for early imaging versus outcome (Soltirovska Salamon et al. 2014). Unfavourable outcome was observed in 12 out of 13 children with a temporal PHI compared with six out of 21 children with a frontal PHI. Only one of the included infants with a PHI in the temporal white matter developed cerebral palsy, which was due to a parietal PHI in the contralateral hemisphere. Cognitive impairment was noted in seven infants with a frontal PHI and five with a temporal PHI. There were more infants with a temporal PHI who developed visual impairment (n=5/13) or behavioural problems (n=7/13) compared with those with a frontal PVHI (visual impairment (n=2/21), behavioural problems (n=3/21).
Preterm infants with PHI were assessed with early (≤4 wk after birth) and term-equivalent age diffusion tensor MRI (Roze et al. 2015). Involvement of corticospinal tracts was assessed by visual assessment of the posterior limb of the internal capsule (PLIC) on DTI (classified asymmetrical, equivocal, or symmetrical) and by a fractional anisotropy asymmetry index. Motor outcome was assessed at ≥15 mo corrected age. Seven out of 23 infants with PHI developed unilateral spastic CP. Their PLIC was visually scored as asymmetrical in 6 and equivocal in 1 on the early DTI. Thirteen out of 16 infants with ymmetrical motor development had a symmetrical PLIC on early DTI, the remaining 3 were equivocal. All infants with unilateral CP had fractional anisotropy asymmetry on early DTI. 14/16 Infants with symmetrical motor development had symmetrical early anisotropy.
Bimanual dexterity is worse in children with unilateral spastic cerebral palsy (Verhage et al. 2022). In children without CP, those with unilateral perinatal arterial stroke show a better bimanual precision compared to children with PHI. This difference appears to be associated with a preserved full scale IQ.
GMH/IVH grading
grading
1. limited to subependymal matrix (GMH)
2. flooding of < 50% of the lateral ventricle and consequently without acute ventriculomegaly (limited IVH)
3. flooding of 50% or more of one or both lateral ventricles with acute distension by clot (extensive IVH)
PHI grades 1, 2 or 3 with periventricular haemorrhagic infarction in a more or less extensive area of the periventricular parenchyma
With CT, and later ultrasound, a classification was proposed in four grades (Papile et al. 1978, Pape and Wigglesworth 1979, Kuban and Teele 1984). Progression from GMH to IVH is still believed to follow mechanical rupture of bleeding under pressure, perhaps bursting through the weakest part of the ependymal lining at the stria terminalis, probably injured by some degree of hypoxia-ischaemia. Extension from limited to extensive IVH may relate to the cerebral perfusion pressure and deficient haemostasis. Progression to white matter or striatal infarction is due to compression of collector veins and is as such not a fourth grade but an association with any of the three genuine grades. Despite several ultrasound classifications subsequently published (Bowerman et al. 1984, Kuban and Teele 1984), the Papile classification, widely used for decades (Horbar et al. 2012) is now reduced to three grade: “grade 4” is now replaced by periventricular haemorrhagic infarction (PHI) (Volpe 1998, Paneth 1994). PHI can be associated to each grade of GMH-IVH.
To understand the images involved in venous infarction a schematic insight into deep vein anatomy is necessary. GMH sites are indicated in red.
1 sinus rectus (straight sinus)
2 great cerebral vein of Galen
3 internal cerebral vein
4 terminal (thalamo-striate) vein
5 longitudinal caudate vein
6 medullary veins to caudate collector veins
7 superior choroidal vein
8 direct lateral vein (surface thalamic vein)
9 superior thalamic vein
10 medial atrial vein
11 basal vein of Rosenthal
GMH and (large) veins
12 inferior striate vein
13 anterior cerebral vein
14 deep middle cerebral vein (insular vein)
15 inferior ventricle vein
16 inferior choroidal vein
17 lateral mesencephalic vein
18 lateral atrial vein
19 precentral cerebellar vein
20 superior vermis vein
21 inferior sagittal sinus
22 septal vein
III
IV. the presence of a direct lateral vein
I
I. the venous confluens at the stria terminalis near the foramen of Monro ——>
The (variable) shape and size of veins, still very developmental in third trimester, plays a role in the occurrence and evolution of GMH and IVH. Veins near matrix areas are at risk of compression by expanding GMHs. The fragile sites are mainly near the transition of internal cerebral to terminal vein, and near the inferior ventricle vein. Terminal vein infarction is most common.
venous variation that my influence onset of GMH and venous infarction
V. variable high draining lateral atrial vein to the basal vein of Rosenthal
II. the inferior ventricle vein in the roof of the temporal horn
V
III. the U-turn from internal cerebral to terminal vein ——>
II
IV
deep vein variation
There is an ongoing interest in variations in anatomy and in flow pattern that may predispose to GMH and its sequelae (Stein and Rosenbaum 1974, Takashima et al. 1986, Gould et al. 1987, Wang et al. 2010, Taoka et al. 2017, Tortora et al. 2018, Kent et al. 2023, Camfferman et al. 2026, Steinsmo Odegard et al. 2026). A comprehensive example of deep vein classification for further study is below. One example of such variation is the U-turn of the trasniation from terminal vein to internal cerebral vein (Larroche 1977), in recent papers studied for the position and degree of acuity of the angle.
Medullary veins from just below the subcortex drain into deep veins, gradually coalescing into larger trunks (Okudera et al. 1999). This high drainage with a peculiar organisation of confluence explains the feathered appearance of the outer (subcortical) contour of a medullary venous infarct. It also explains the triangular shape as veins fan out from the ependymal collectors near the GMH.
feathered outer margin of an extensive terminal vein infarction; interdigitation of spared and affected medullary veins
distended veins, diapedesis but no frank infarction ?
PHI, also referred to as parenchymal haemorrhagic infarction, or periventricular venous infarction, or intraparenchymal lesion, can complicate each grade of GMH-IVH. This seems to occur a few hours up to a few days after the initial GMH (Perlman et al. 1993). Post-mortem and doppler studies strongly suggest that this lesion is due to venous obstruction and congestion (Takashima et al. 1986, Gould et al. 1987, Nakamura et al. 1990 and 1991, Paneth et al. 1994, Taylor 1995, Ghazi-Birry et al. 1997, Volpe 1998). It has been suggested that parenchymal arterial ischaemia secondary to venous obstruction contributes to injury (Toft et al. 1997).
The typical ultrasonographic appearance of PHI is a triangular, “fan-shaped” hyperechoic lesion in periventricular white matter, ipsilateral to the GMH-IVH (Guzzetta et al. 1986). In the earliest phase, the infarct is separated from the ventricular wall; it may subsequently grow, touch the ventricle and eventually merge into a single, large hyperechoic lesion together with the initial GMH-IVH. The parenchymal hyperechoic area tends to decrease after few days: this is believed to reflect the regression of venous congestion around it, leading to overestimation of the extent (Govaert and de Vries 2010). Multiple minute PHIs along the course of the medullary veins can also be observed. We speculate that these minor PHIs may result from a partial venous obstruction due to compression of a subependymal vein. The risk of developing PHI following GMH might also be related to the location of the GMH itself, especially in subjects with a peculiar venous anatomy prone to congestion.
parenchymal haemorrhagic infarction: ultrasound findings
typical terminal vein infarction and invisibility of the ependymal collector (two different infants)
PHI usually evolves into a cavity within periventricular white matter. As most PHIs develop adjacent to the ventricular wall, porencephaly - resulting from the cavity that merges with the ventricle - is a common observation after one or two months (Grant et al. 1982, Donn and Bowerman 1982, Fleischer et al. 1983). A cavitation resulting from PHI is usually single, asymmetric and persistent. It takes the shape of the infarcted area and will become round when submitted to increased pressure (‘porencéphalie soufflante’)(Laplace’s law). With smaller infarcts the end stage is ventricular bulging following gradual resportion of the cavities as in PVL.
Conversely, cysts of periventricular leukomalacia typically appear with symmetrical, mainly posterior distribution and tend to disappear within few weeks, insomuch that they are often undetectable at term-equivalent age (Pierrat et al. 2001).
Size and location of PHI depend on which vein is involved. In some cases, multiple veins are involved, leading to extensive unilateral PHI or to a much rarer bilateral PHI (Bassan et al. 2006, Dudink et al. 2008). The extensive IPL is extremely echoic, shows irregular, feathered borders with the cortex and allows no separation between density and ventricular clot (Perlman et al. 1993, Rademaker et al. 1994). Because PHI carries important prognostic implications (Maitre et al. 2009, Sheehan et al. 2017), classification should be routine. Dudink et al 2008 classified PHI based on venous anatomy and correlated this with outcome. Of course, advanced MRI techniques like DTI and SWI add useful information for prediction of outcome (Roze et al. 2015). Access to MRI is often limited by obvious logistic obstacles in the acute or early subacute phase of PHI. Recognizing the venous subtype of PHI with CUS, rather than labelling the lesion as unspecified PHI, can help the clinician to predict outcome, allowing the start of a targeted rehabilitation program at an early stage, and may enrich the quality of family counseling.
venous infarction types
1 sinus rectus (straight sinus)
2 great cerebral vein of Galen
3 internal cerebral vein
4 terminal (thalamo-striate) vein
5 longitudinal caudate vein
6 medullary veins to caudate collector veins
7 superior choroidal vein
8 direct lateral vein (surface thalamic vein)
9 superior thalamic vein
10 medial atrial vein
11 basal vein of Rosenthal
12 inferior striate vein
13 anterior cerebral vein
14 deep middle cerebral vein (insular vein)
15 inferior ventricle vein
16 inferior choroidal vein
17 lateral mesencephalic vein
18 lateral atrial vein
19 precentral cerebellar vein
20 superior vermis vein
21 inferior sagittal sinus
22 anterior thalamic vein
23 septal vein
24 posterior septal vein
25 superior striate vein
location vs su. centralis
porus location
network injury
multi-cavitating
effect on PLIC
effect on CST
catastrophic
+ late arteriopathy
venous infarction: terminal vein
typical small and large
home delivery
limited < direct lateral v.
antenatal onset
The terminal vein may be replaced by a thalamocaudate vein (= direct lateral vein, surface thalamic vein), which ends in mid part of the ICV (convex summit of ICV) posterior to foramen of Monro; this vein runs almost in a coronal plane and is present in about 4 % of all brains. This vein does not pass near the caudothalamic groove, and as such it might protect against complete terminal vein infarction when present. If the vein leads to infarction, suprainsular location would fit the mechanism.
venous infarction: direct lateral vein
A group of caudate veins drain deep medullary venous blood from the frontal area along a variable set of vessels; most consistent are the anterior caudate (also called anterior terminal) vein(s), the longitudinal caudate vein, and the transverse caudate vein(s). The anterior caudate veins run in parallel posteromedial arcs along the medial surface of the caudate head. They may be occluded directly or may be congested due to compression of stem collectors, transverse caudate veins, that drain the anterior caudate venous blood to the thalamostriate vein close to its entry into the internal cerebral vein together with the septal vein. The longitudinal caudate vein runs more superiorly and laterally on top of the caudate head.
unilateral
venous infarction: caudate collector vein
extensive
plexus
ICV
bilateral
caudate collector veins (Testut and Latarjet 1948
atrial versus temporal
hippocampal vein
venous infarction: inferior ventricle vein, atrial vein
inferior ventricle vein
basal vein
typical left temporal venous infarction in a preterm infant
porencephalisation
large atrial GMH with venous infarction
atrial infarction, MRI
inferior ventricle vein ->
postmortem atrial lesion
subtle callosal venous lesion
venous infarction: septal vein, callosal vein
extensive midline haemorrhage
The septal vein is a major medial subependymal vein; it collects deep medullary veins from the frontal pole, some blood from the septal leaflet and a few tributaries from the corpus callosum. It inflects at the septal anterior margin, changing direction from anterior and lateral to posterior and medial. This vein is also called the vein of the anterior horn. It usually curves laterally around the columna fornicis and above the foramen of Monro to end in the internal cerebral vein at a site where the thalamostriate and superior choroidal veins converge. Sometimes its point of entry lies more posteriorly on the internal cerebral vein. The septal vein may consist of two major branches, a superior and inferior one; near the fornix both septal veins may converge to end in the internal cerebral vein with one septal vein stem.
venous infarction: superior striate vein
Preterm infant surviving with extensive striatal haemorrhagic infarction underneath a large caudate GMH. Large parts of caudate and putamen are destroyed in such injury. If only the anterior limb of the internal capsule is affected these children do not develop spastic contralateral hemiplegia.
cavitation absent in striatum
large striatal infarction with GMH
axial CUS: haemorrhage extends to subinsular cortex
A typical venous infarct has a fan shape pointing to the affected collector vein. The infarct has irregular outer margins because of the interdigitation of venous drainage to the internal cerebral vein with veins draining to the pial veins. The affected area is perfusion poor. Pial veins above the infarct may appear dilated.
(three different infants)
typical separate GMH and venous infarction
SV
TV
AV atrial vein
IVV inferior ventricle vein
LCV longitudinal caudate vein
(anterior terminal vein)
SV striatal vein
TV terminal vein
AV
LCV
IVV
venous infarct locations
DLV
terminal vein to internal cerebral vein U-turn and tributaries
1 superior choroidal vein
2 internal cerebral vein
3 septal vein (in ICV at venous angle or more posterior)
4 thalamostriate vein (terminal vein)
5 anterior thalamic vein
6 superior striatal vein
7 transverse caudate vein
8 direct lateral vein (supra- or retrothalamic)(= thalamo-caudate vein)
9 medial atrial vein
10 superior thalamic vein
11 anterior inferior caudate vein
12 longitudinal caudate vein
13 basal vein
14 great cerebral vein
15 medullary veins
venous watershed area ——>
transmedullary vein
supra-insular DVA
Mac OS X 2Û
ATTR
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