ANTENATAL CYSTIC GERMINOLYSIS - keywords
antenatal cystic germinolysis
references to germinolysis
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Alarcón A, Carreras N, Muehlbacher T, Casas-Alba D, Arena R, Roca-Llabrés P, Navarro-Morón J, de Vries LS, Govaert P; EurUS.Brain group. Foetal disruptive brain injuries: Diagnosing the underlying pathogenetic mechanisms with cranial ultrasonography. Dev Med Child Neurol. 2025 Nov;67(11):1383-1408.Altman J, Bayer SA (2015) Development of the human neocortex: a review and interpretation of the histological record. A Free eBook from the Laboratory of Developmental Neurobiology, Inc. www.neurondevelopment.org © 2015, The Laboratory of Developmental Neurobiology, Inc. Ocala, FL 34481, USA
Averill LW, Kandula VV, Akyol Y, Epelman M (2015) Fetal Brain Magnetic Resonance Imaging Findings In Congenital Cytomegalovirus Infection With Postnatal Imaging Correlation. Semin Ultrasound CT MR, 36(6):476-486.
Bandaralage SP, Farnaghi S, Dulhunty JM, Kothari A (2016) Antenatal and postnatal radiologic diagnosis of holocarboxylase synthetase deficiency: a systematic review. Pediatr Radiol, 46(3):357-364.
Beltinger C, Saule H (1988) Sonography of subependymal cysts in congenital rubella syndrome. Eur J Pediatr 148:206–207.
Brossard-Racine M, du Plessis AJ, Vezina G, Robertson R, Bulas D, Evangelou IE, Donofrio M, Freeman D, Limperopoulos C (2014) Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease. AJNR Am J Neuroradiol, 35(8):1593-1599.
Clouchoux C, du Plessis AJ, Bouyssi-Kobar M, Tworetzky W, McElhinney DB, Brown DW, Gholipour A, Kudelski D, Warfield SK, McCarter RJ, Robertson RL Jr, Evans AC, Newburger JW, Limperopoulos C (2013) Delayed cortical development in fetuses with complex congenital heart disease. Cereb Cortex, 23(12):2932-2943. .
de Vries LS (2019) Viral Infections and the Neonatal Brain. Semin Pediatr Neurol, 32:100769.
Denbow ML, Battin MR, Cowan F, Azzopardi D, Edwards AD, Fisk NM (1998) Neonatal cranial ultrasonographic findings in preterm twins complicated by severe fetofetal transfusion syndrome. Am J Obstet Gynecol, 178(3):479-483.
Epstein AA, Janos SN, Menozzi L, Pegram K, Jain V, Bisset LC, et al. Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment. Cell Stem Cell. 2024;31(4):467-483.e6. Esteban H, Blondiaux E, Audureau E, Sileo C, Moutard ML, Gelot A, Jouannic JM, Ducou le Pointe H, Garel C (2015) Prenatal features of isolated subependymal pseudocysts associated with adverse pregnancy outcome. Ultrasound Obstet Gynecol, 46(6):678-687.
Heibel M, Heber R, Bechinger D, Kornhuber HH (1993) Early diagnosis of perinatal cerebral lesions in apparently normal full-term newborns by ultrasound of the brain. Neuroradiology 35:85–91.
Horsch S, Kutz P, Roll C. (2010) Late germinal matrix hemorrhage-like lesions in very preterm infants. J Child Neurol, 25(7):809-814.
Jain-Ghai S, Mishra N, Hahn C, Blaser S, Mercimek-Mahmutoglu S (2014) Fetal onset ventriculomegaly and subependymal cysts in a pyridoxine dependent epilepsy patient. Pediatrics, 133(4):e1092-1096.
Jelin AC, Norton ME, Bartha AI, Fick AL, Glenn OA (2008) Intracranial magnetic resonance imaging findings in the surviving fetus after spontaneous monochorionic cotwin demise. Am J Obstet Gynecol, 199(4):398.e1-5.
Kelly CJ, Arulkumaran S, Tristão Pereira C, Cordero-Grande L, Hughes EJ, Teixeira RPAG, Steinweg JK, Victor S, Pushparajah K, Hajnal JV, Simpson J, Edwards AD, Rutherford MA, Counsell SJ (2019) Neuroimaging findings in newborns with congenital heart disease prior to surgery: an observational study. Arch Dis Child, 104(11):1042-1048.
Larcos G, Gruenewald SM, Lui K (1994) Neonatal subependymal cysts detected by sonography: prevalence, sonographic findings, and clinical significance. AJR Am J Roentgenol, 162(4):953-956.
Leijser LM, de Vries LS, Rutherford MA, Manzur AY, Groenendaal F, de Koning TJ, van der Heide-Jalving M, Cowan FM (2007) Cranial ultrasound in metabolic disorders presenting in the neonatal period: characteristic features and comparison with MR imaging. AJNR Am J Neuroradiol, 28(7):1223-1231.
Lu JH, Emons D, Kowalewski S (1992) Connatal periventricular pseudocysts in the neonate. Pediatr Radiol 22:55–58.
Lucca J, Baldisserotto M (2013) Cerebral ultrasound findings in infants exposed to crack cocaine during gestation. Pediatr Radiol, 43(2):212-218.
Larroche J-C (1972) Sub-ependymal pseudo-cysts in the newborn. Biol Neon 21:170–183.
Limperopoulos C, Tworetzky W, McElhinney DB, Newburger JW, Brown DW, Robertson RL Jr, Guizard N, McGrath E, Geva J, Annese D, Dunbar-Masterson C, Trainor B, Laussen PC, du Plessis AJ (2010) Brain volume and metabolism in fetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy. Circulation, 121(1):26-33.
Makhoul IR, Zmora O, Tamir A, Shahar E, Sujov P (2001) Congenital subependymal pseudocysts: own data and meta-analysis of the literature. Isr Med Assoc J, 3(3):178-183.
McQuillen PS, Barkovich AJ, Hamrick SE, Perez M, Ward P, Glidden DV, Azakie A, Karl T, Miller SP (2007) Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke 38(2 Suppl):736-741.
Mellerio C, Marignier S, Roth P, Gaucherand P, des Portes V, Pracros JP, Guibaud L (2008) Prenatal cerebral ultrasound and MRI findings in glutaric aciduria Type 1: a de novo case. Ultrasound Obstet Gynecol, 31(6):712-714.
Mito T, Ando Y, Takeshita K, Takada K, Takashima S (1989) Ultrasonographical and morphological examination of subependymal cystic lesions in maturely born infants. Neuropediatrics 20:211–214.
Pal BR, Preston PR, Morgan MEI, Rushton DI, Durbin GM (2001) Frontal horn thin walled cysts in preterm neonates are benign. Arch Dis Child Fetal Neonatal Ed 85; F187-F193.
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.Rademaker KJ, De Vries LS, Barth PG (1993) Subependymal pseudocysts: ultrasound diagnosis and findings at follow-up. Acta Paediatr Scand 82:394–399.
Ramenghi LA, Domizzio S, Quartulli L, Sabatino G (1997) Prenatal pseudocysts of the germinal matrix in preterm infants. J Clin Ultrasound 25:169-173.
Righini A, Cesaretti C, Conte G, Parazzini C, Frassoni C, Bulfamante G, Avagliano L, Inverardi F, Izzo G, Rustico M (2016) Expanding the spectrum of human ganglionic eminence region anomalies on fetal magnetic resonance imaging. Neuroradiology 58(3):293-300.
Righini A, Frassoni C, Inverardi F, Parazzini C, Mei D, Doneda C, Re TJ, Zucca I, Guerrini R, Spreafico R, Triulzi F (2013) Bilateral cavitations of ganglionic eminence: a fetal MR imaging sign of halted brain development. AJNR Am J Neuroradiol 34(9):1841-5. Russel IMB, van Sonderen L, van Straaten HLM, Barth PG (1994) Subependymal germinolytic cysts in Zellweger syndrome. Pediatr Radiol 25:254–255.
Russell LJ, Weaver DD, Bull MJ, Weinbaum M (1984) In utero brain destruction resulting in collapse of the fetal skull, microcephaly, scalp rugae, and neurologic impairment: the fetal brain disruption sequence. Am J Med Genet, 17(2):509-21.
Schlesinger AE, Shackelford GD, Adcock LM (1998) Hyperechoic caudate nuclei: a potential mimic of germinal matrix hemorrhage. Pediatr Radiol, 28(5):297-302.
Shackelford GD, Fulling KH, Glasier CM (1983) Cysts of the subependymal germinal matrix: sonographic demonstration with pathologic correlation. Radiology 149:117–121.
Shen E-Y, Huang F-Y (1985) Subependymal cysts in normal neonates. Arch Dis Child 60:1072–1074.
Smets K, De Kezel C, Govaert P (1997) Subependymal caudothalamic groove hyperechogenicity and neonatal chronic lung disease. Acta Paediatr 86(12):1370-3.
Thun-Hohenstein L, Forster I, Kunzle C, Martin E, Boltshauser E (1994) Transient bifrontal solitary periventricular cysts in term neonates. Neuroradiology 36:241–244.
van Straaten HL, van Tintelen JP, Trijbels JM, van den Heuvel LP, Troost D, Rozemuller JM, Duran M, de Vries LS, Schuelke M, Barth PG (2005) Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption. Neuropediatrics, 36(3):193-199.
Wada N, Matsuishi T, Nonaka M, Naito E, Yoshino M (2004) Pyruvate dehydrogenase E1alpha subunit deficiency in a female patient: evidence of antenatal origin of brain damage and possible etiology of infantile spasms. Brain Dev, 26(1):57-60.
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Main conditions with antenatal subependymal pseudocysts- Idiopathic
- Fetal infection (de Vries et al. 2019): cytomegalovirus, rubella, zika virus, other
- Antenatal asphyxia
- Maternal substance abuse (cocaine) (Lucca and Baldissserotto 2013)
- Twin-to-twin transfusion syndrome (Denbow et al. 1998, Jelin et al. 2008)
- Congenital heart disease (McQuillen et al. 2007, Limperopoulos et al. 2010, Clouchoux et al. 2013, Brossard-Racine et al. 2014, Kelly et al. 2019)
- Metabolic disorders
Organic acidurias (glutaric aciduria) (Mellerio et al. 2008)
Mitochondrial disorders (complex I, IV, pyruvate dehydrogenase
deficiency) (Wada et al. 2004, van Straaten et al. 2005, Leijser
et al. 2007)
Peroxisomal disorders (Zellweger syndrome) (Russel et al. 1995,
Leijser et al. 2007)
Pyridoxine-dependent epilepsy (Jain-Ghai et al. 2014)
Holocarboxylase synthetase deficiency (Bandaralage et al. 2016)
- Chromosomal abnormalities and genetic disorders (Esteban et al. 2015)
matrix pockets
different locations
Subependymal pseudocysts (SEPCs) result from germinolysis (i.e. germinal matrix cystic regression) (Larroche 1972). The term pseudocyst refers to the lack of ependymal lining. They should not be referred to as ‘periventricular cysts’, as this may faultily suggest periventricular leukomalacia. The most common location for SEPCs is the caudothalamic notch, while parafrontal and temporal germinolysis are less frequent. The cysts have a glial wall containing residual matrix pockets. Macrophages and some neuroblasts (NSE positive staining) were found in early postmortem descriptions. The nearby ependymal lining is intact. As germinal matrix begins to recede at approximately 28 weeks of gestation, but caudothalamic pockets remain until 34-35 weeks, frontal and temporal germinolysis are likely to form earlier than caudothalamic germinolysis. Often SEPCs are bilateral, though not necessarily symmetrical.
Germinolysis can thus be located in the rostral part of the temporal horns (Ramenghi et al. 1997), and a similar image of a thin strand of tissue crossing the distal end of the ventricle can be seen in the occipital horns (Averill et al. 2015). Temporal cysts and occipital horn septations are typical though not specific of congenital cytomegalovirus (CMV) infection. These septations may cause cystic dilatation in utero, which normally becomes less prominent after birth.
antenatal cystic germinolysis
examples
Small and single caudothalamic SEPCs are usually not pathological. Parafrontal pseudocysts can also be an incidental finding. In fact, SEPCs are found in 0.5-5 % of healthy neonates on CUS in the first days of life (Shen and Huang 1985, Heibel et al. 1993, Makhoul et al. 2001).
On the other hand, large or multiloculated caudothalamic SEPCs, as well as temporal cysts and occipital horn septations, require investigation of an underlying disease. In particular, CMV testing and metabolic testing are indicated. Prognosis is good in the absence of associated conditions. Most SEPCs disappear in the first few months after birth.
postnatal onset germinolysis
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rubella
parafrontal, monoZ twin
post GMH
cystic and not
twins
inborn errors
unilateral
cystic and not, MRI
parafrontal and temporal
glutaric aciduria
examples of antenatal cystic germinolysis
CMV
Caudothalamic SEPCs can be single or multiple, in the form of a multilocular rounded prominence protruding from the caudothalamic groove into the lumen of the lateral ventricle. Caudothalamic germinolysis is well illustrated by CUS, whereas MRI does not identify small cysts of a few millimeters in diameter.
A special antenatal variant, parafrontal germinolysis, has been described originating around the mid-second to early third trimester. This atypical type of germinolysis is not rare. In parafrontal germinolysis, SEPCs are adjacent to the lateral walls of the frontal horns of the lateral ventricles. They are located more medially and lower than the cysts of periventricular leukomalacia, and more laterally and anteriorly than the typical caudothalamic germinolytic SEPCs, well anterior to the foramina of Monro. On the coronal plane they can create the impression of an enlarged frontal horn, which has erroneously been interpreted as “coarctation of the lateral ventricle”. On parasagittal section they appear elongated, sometimes with septa within ("string of beads germinolysis”, with several compartments). It therefore lies in front of these foramina and is separated from the lateral ventricle by a single membrane, readily seen with high frequency probes.
There have been records of parafrontal germinolysis in infants with CMV fetopathy. Some cysts are almost 2 cm long. On coronal section they mimic a widened frontal horn, although a distinction can be made using ≥ 7.5 MHz US. At around 4 months after term nearly all cysts of this type have been integrated into the ventricle. As an isolated finding these germinolytic changes are most often not associated with developmental problems, but exceptions may exist. MRI in early childhood did not reveal gliosis around such benign parafrontal cysts and ventriculomegaly is not associated.
Friede 1989: parafrontal pseudocysts; multiloculated pseudocysts with budding germinal matrix remnants
antenatal cystic germinolysis: different locations
Postnatal cyst formation at the rear end of the head of the caudate nucleus is mainly found after a perinatal subependymal haemorrhage. In the absence of typical GMH, regularly one finds one or several rounded cysts in the caudothalmic grooves, sometimes with trabeculation from the walls. During the following few months those cysts are gradually integrated into surrounding tissue. Although such cysts are often rounded, they may sometimes appear flattened. They do not usually bulge into the ventricle lumen. This so called hyperechoic and later cystic germinolysis initially consists of bilateral, symmetrical, teardrop-shaped hyperechogenicity within the caudothalamic grooves (Schlesinger et al. 1998, Horsch et al. 2010).
We and others have noted a possible association between extreme prematurity, bronchopulmonary dysplasia treated by dexamethasone and slow postnatal matrix regression with multilocular character (Smets et al. 1997). After a period of slow triangular densification (hyperechogenicity) of the matrix, this tissue disappears, with or without an intermediate (micro)cystic stage. Such changes in matrix density have been observed in infants with proven postnatal CMV fetopathy. But much more frequent is the incidental finding on CUS of hyperechoic change in caudothalamic groove matrix tissue, present at birth or appearing later, with CMV excluded (Larcos et al. 1994). During the following few months those cysts are gradually integrated into surrounding tissue. Although such cysts are often rounded, they may appear flattened.
One explanation could be that this change is associated with enhanced apoptosis in this area of the brain that is under way for normal developmental regression, and where some cell reaction (macrophages) is present and causes the hyperechoic aspect. The significance of this type of matrix regression for development is uncertain. There is the recent suggestion that it may be associated with inflammation, as during necrotising enterocolitis, disrupting the glial progenitors in third trimester matrix and leading to motor impairment (Epstein et al. 2024).
GA 34w, day 3, CMV excluded
spontaneous labour, PPROM; spontaneous vaginal delivery of twin 1; GA 30w5d, 1400 g, AS 8/9/10, male, surfactant, NIV_NAVA 4 days; maternal and neonatal covid-19 infection, no clinical signs; CMV negative, normal ABR
GA 34w, day 14, CMV excluded
postnatal onset germinolysis
antenatal cystic germinolysis: pathology and differential diagnosis
There have been several descriptions of apparently enlarged (with cavitations or without) appearance of the matrix areas around the caudothalamic groove in fetal and neonatal MRI descriptions (Righini et al. 2013, 2016). Such findings have been associated with severe disorders of migration like microlissencephaly and ARX-related lissencephaly, but also in association with less pronounced changes like ventriculomegaly, small corpus callosum and small cerebellar vermis. In mitochondrial disorders (pyruvate carboxylase and pyruvate dehydrogenase deficiency) the combination of germinolytic cysts and ventriculomegaly is characteristic.
Haemorrhage and/or micro-infarction of this matrix, both in and ex utero, often lead to cyst formation in the affected area in the first weeks after the event. As we are dealing with cysts with glial walls encircled by germinal cells but not by ependyma, the term pseudocyst is appropriate (Larroche et al. 1972).
True ependyma-lined cysts are seen with unilateral hydrocephalus and other brain cavities.
The distinction with caudate to septum adhesions following bleeding or ventriculitis lies with the recognition of the typical location and with the elliptoid or rounded appearance of the pseudocysts.
Not surprisingly there have been many records of associated brain malformation, migration disorder or visceral anomaly (Mito et al. 1989), this may also be consequent to publication bias.
Germinal matrix is abundant within ganglionic eminences (present between 8 and 36 w PMA) in the floor of the lateral ventricle during the second trimester, but in the third it regresses, persisting mostly in the region around the foramina of Monro — the caudothalamic groove — and along the temporal horn lateral wall. These areas provide glutamatergic projection neurons, GABAergic interneurons and oligodendroglial precursors in the latter part of pregnancy. One can expect that subtle matrix lesions have an impact on telencephalic gliogenesis and on late stages of formation of the cortical plate.
GM volume reaches its maximum at 23-26 weeks PMA; reduction of this volume occurs site specific and is continues until the subventricular zone regresses at 36 weeks.
Part of the subventricular zone persists as a source of interneurons for the olfactory bulb as well as oligodendrocytes through adulthood.
Altman and bayer 2015: matrix pockets at GA 24w
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