SCHIZENCEPHALY - keywords
schizencephaly
references to schizencephaly
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al-Alawi AM, al-Tawil KI, al-Hathal MM, Amir I. Sporadic neonatal schizencephaly associated with brain calcification. Ann Trop Paediatr 2001;21(1):34-7; discussion 7-8.
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.
Barkovich AJ, Kjos BO. Schizencephaly: correlation of clinical findings with MR characteristics. Am J Neuroradiol 1992;13(1):85-94.
Barkovich AJ, Kuzniecky RI, Bollen AW, Grant PE. Focal transmantle dysplasia: a specific malformation of cortical development. Neurology 1997;49(4):1148-52.
Bataglia G, Granata T. Schizencephaly. in International review of child neurology series: Disorders of neuronal migration, Barth PG (Ed). MacKeith Press 2003, pp 127-134.
Bordarier C, Robain O, Ponsot G. Bilateral porencephalic defect in a newborn after injection of benzol during pregnancy. Brain Dev 1991;13:126–129.
Bosnjak VM, Daković I, Duranović V, Lujić L, Krakar G, Marn B (2011) Malformations of cortical development in children with congenital cytomegalovirus infection - A study of nine children with proven congenital cytomegalovirus infection. Coll Antropol 35 Suppl 1:229-34.
Briellmann RS, Jackson GD, Torn-Broers Y, Berkovic SF. Twins with different temporal lobe malformations: schizencephaly and arachnoid cyst. Neuropediatrics 1998;29(6):284-8.
Curry CJ, Lammer EJ, Nelson V, Shaw GM (2005) Schizencephaly: heterogeneous etiologies in a population of 4 million California births. Am J Med Genet A, 137(2):181-189. doi: 10.1002/ajmg.a.30862.
Dale ST, Coleman LT. Neonatal alloimmune thrombocytopenia: antenatal and postnatal imaging findings in the pediatric brain. AJNR Am J Neuroradiol. 2002;23(9):1457-65.
Dominguez R, Aguirre Vila-Coro A, Slopis JM, Bohan TP. Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs. Am J Dis Child. 1991;145(6):688-95.
Govaert P. Prenatal stroke. Semin Fetal Neonatal Med. 2009 Oct;14(5):250-66.
Griffiths PD (2018) Schizencephaly revisited. Neuroradiology, 60(9):945-960. doi: 10.1007/s00234-018-2056-7.
Hahn JS, Lewis AJ. Unilateral schizencephaly and contralateral polymicrogyria associated with umbilical cord mass. J Child Neurol. 2003;18(3):232-4.
Hayashi N, Tsutsumi Y, Barkovich AJ. Morphological features and associated anomalies of schizencephaly in the clinical population: detailed analysis of MR images. Neuroradiology 2002 May;44(5):418-27.
Howe DT, Rankin J, Draper ES (2012) Schizencephaly prevalence, prenatal diagnosis and clues to etiology: a register-based study. Ultrasound Obstet Gynecol 39(1):75-82.
Hung PC, Wang HS, Yeh YS, Lui TN, Lee ST. Coexistence of schizencephaly and intracranial arteriovenous malformation in an infant. AJNR Am J Neuroradiol 1996;17(10):1921-2.
Iannetti P, Nigro G, Spalice A, Faiella A, Boncinelli E. Cytomegalovirus infection and schizencephaly: case reports. Ann Neurol 1998;43(1):123-7.
Kuban KC, Teele RL, Wallman J. Septo-optic-dysplasia-schizencephaly. Radiographic and clinical features. Pediatr Radiol 1989;19:145-50.
Kuijpers RW, van den Anker JN, Baerts W, von dem Borne AE. A case of severe neonatal thrombocytopenia with schizencephaly associated with anti-HPA-1b and anti-HPA-2a. Br J Haematol. 1994;87(3):576-9.
Landrieu P, Lacroix C. Schizencephaly, consequence of a developmental vasculopathy? A clinicopathological report. Clin Neuropathol 1994 ;13(4):192-6.
Mancini J, Lethel V, Hugonenq C, Chabrol B. Brain injuries in early foetal life: consequences for brain development. Dev Med Child Neurol. 2001;43(1):52-5.
Naidich TP, Griffiths PD, Rosenbloom L (2015) Central nervous system injury in utero: selected entities. Pediatr Radiol, 45 Suppl 3:S454-S462. doi: 10.1007/s00247-015-3344-6.
Park KB, Chapman T, Aldinger KA, Mirzaa GM, Zeiger J, Beck A, Glass IA, Hevner RF, Jansen AC, Marshall DA, Oegema R, Parrini E, Saneto RP, Curry CJ, Hall JG, Guerrini R, Leventer RJ, Dobyns WB (2021) The spectrum of brain malformations and disruptions in twins. Am J Med Genet A 185(9):2690-2718.
Pascual-Castroviejo I, Pascual-Pascual SI, Velazquez-Fragua R, Viaño J, Quiñones D (2012) Schizencephaly: a study of 16 patients. Neurologia 27(8):491-9.
Pati S, Helmbrecht GD. Congenital schizencephaly associated with in utero warfarin exposure. Reprod Toxicol. 1994;8(2):115-20.
Pellicer A, Cabanas F, Perez-Higueras A, Garcia-Alix A, Quero J. Neural migration disorders studied by cerebral ultrasound and colour Doppler flow imaging. Arch Dis Child Fetal Neonatal Ed 1995;73:F55-61.
Perez-Jimenez A, Colamaria V, Franco A, Grimau-Merino R, Darra F, Fontana E, et al. [Epilepsy and disorders of cortical development in children with congenital cytomegalovirus infection]. Rev Neurol. 1998;26(149):42-9.
Raybaud C, Girard N, Lévrier O, Peretti-Viton P, Manera L, Farnarier P. Schizencephaly: correlation between the lobar topography of the cleft(s) and absence of the septum pellucidum. Childs Nerv Syst. 2001 Apr;17(4-5):217-22.
Senol U, Karaali K, Aktekin B, Yilmaz S, Sindel T. Dizygotic twins with schizencephaly and focal cortical dysplasia. AJNR Am J Neuroradiol. 2000;21(8):1520-1.
Sener RN. Schizencephaly and congenital cytomegalovirus infection. J Neuroradiol 1998;25(2):151-2.
Sherer DM, Salafia CM. Midtrimester genetic amniocentesis of a twin gestation complicated by immediate severe fetal bradycardia with subsequent associated fetal anomalies. Am J Perinatol 1996;13(6):347-50.
Spalice A, Del Balzo F, Nicita F, Papetti L, Ursitti F, Iannetti P (2011) The role of cytomegalovirus in schizencephaly. Am J Med Genet 155A(7):1768; author reply 1769.
Steiner JL, Fink AM, Berkowitz RG (2013) Magnetic resonance imaging findings in pediatric bilateral vocal cord dysfunction. The Annals of Otology, Rhinology and Laryngology 122(7); 417-420.
Weissman A, Achiron R, Lipitz S, Blickstein I, Mashiach S. The first-trimester growth-discordant twin: an ominous prenatal finding. Obstet Gynecol 1994;84(1):110-4.
White AL, Hedlund GL, Bale JF Jr (2014) Congenital cytomegalovirus infection and brain clefting. Pediatr Neurol 50(3):218-23.
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typical images
This condition was also referred to as embryonic or early fetal porencephaly (< 24 w of gestation), to separate it from typical third trimester porencephaly following arterial or venous infarction. It is not classified with anomalies of migration because abnormal segmental growth of the prosencephalon is the presumed aberration and not a genetic migration disorder. If acquired, it is presumably the result of (vascular) damage to one stream of glioneuronal matrix products.
Schizencephaly has a very low prevalence of approximately 1.5 per 100,000 live-born infants (Curry et al. 2005, Howe et al. 2012). Less than half are detected antenatally.
Children with a unilateral closed cleft may present with epilepsy, whereas bilateral open clefts can cause microcephaly, spastic quadriplegia and mental retardation in addition. Seizures can be refractory.
insult at GA 22w
neuropathology
<—— absent septal wall
cleft
schizencephaly
Conditions leading to schizencephaly
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(i) genetic, isolated: EMX2 mutation
(ii) syndromal: tuberous sclerosis, Vici syndrome: callosal agenesis, schizencephaly, cardiopathy, albinism, Beckwith-Wiedemann syndrome, triple X syndrome, skeletal dysplasia, cephalocoele
(iii) toxic: fetal alcohol syndrome
(iv) non-infectious vascular disruptive: cocaine (Dominguez et al. 1991), umbilical cord hamartoma (Hahn and Lewis 2003), benzol injections in first trimester (Bordarier et al. 1991), trauma (Mancini et al. 2001), allo-immune thrombocytopenia (Kuijpers et al. 1994, Dale et al. 2002), warfarin (Pati and Helmbrecht 1994), arteriovenous malformation (Hung et al. 1996), vasculopathy (Landrieu and Lacroix 1994), with calcifications (al-Alawi et al. 2001)
(v) monozygous twinning (Weissman et al. 1994, Sherer and Salafia 1996, Briellman et al. 1998, Senol et al. 2000)
(vi) infectious: vasculitis plus direct invasion of neuroblasts/radial glial cells (CMV: Iannetti et al. 1998, Perez-Jimenez et al. 1998, Sener et al. 1998, Spalice et al. 2011, Bosnjak et al. 2011, Howe et al. 2012, Pascual-Castroviejo et al. 2012, White et al. 2014).
postnatal at cingulum
insult at GA 26w
chance first day finding in a preterm of 25w GA
It is possible to identify even the finer slit on an ultrasound scan, alerted by ventriculomegaly with a colpocephalic character and with indented lateral ventricle margin (Pellicer et al. 1995). Arachnoid vessels are identified in the lips, this is impossible in clastic fetal porencephaly or transmantle dysplasia.
5 Weeks gestation preterm with wet lung, chance sonographic finding of schizencephaly. This boy developed epilepsy and a hemisyndrome in early infancy. The EEG was irritative on the right in the neonatal period. Observe closed cleft pointed at by an outdentation of the right ventricle (arrow) and observe the power Doppler signal within the cleft, diagnostic of a pio-ependymal seam with vessels in it.
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abnormal cleft along the “lateral fissure"
pio-ependymal seam with vessels in the wall
schizencephaly: characteristic findings
schizencephaly: well timed insult
Alarcon et al. 2025
schizencephaly: neuropathology
<—— open lip schizencephaly
https://neuropathology-web.org/chapter3/chapter3fPorencephaly.html
A (punched-out, soft-walled) defect exists in the brain parenchyma making contact between the ventricle and the arachnoid/pia (Barkovich et al. 1992, Hayashi et al. 2002). A stricter definition also includes a transmantle column of dysplastic grey matter extending from the ependyma to the pia without a complete cleft (Naidich et al. 2015).
The cleft replaces the entire cerebral mantle, with a porus visible on inspection of the surface, usually in the insular area. Location is predominantly frontal and parietal (rarely orbital and occipital), and bilateral schizencephaly is reported in 40–50% of cases (Raybaud 2001, Griffiths 2018). There may be more than one area of schizencephaly in the same hemisphere. Calcifications may present along the cleft.
Schizencephaly has been classified into (Griffiths 2018):
- type 1 (transmantle column of abnormal grey matter but no evidence of a CSF-containing cleft);
- type 2 (CSF-containing cleft lined with abutting lips of abnormal grey matter, traditionally known as ‘closed-lip’ schizencephaly);
- type 3 (CSF-containing cleft lined with non-abutting lips of abnormal grey matter, also known as ‘open-lip’ schizencephaly).
https://www.medlink.com/articles/schizencephaly
open lip schizencephaly seen from the surface around the “insular” area
Cortex bordering the cleft in schizencephaly is polymicrogyric. Schizencephaly may be associated with isolated contralateral polymicrogyria
(Griffiths 2018, Park et al. 2021). Some schizencephalies have heterotopia and not polymicrogyria lining the cleft, with radial arrangement of the gyri around the cleft.
Many other changes have been described in association with schizencephaly: septo-optic dysplasia, callosal agenesis, arachnoid cyst, syntelencephaly, lobar holoprosencephaly, mesial temporal lobe epilepsy (Kuban et al. 1989, Bataglia et al. 2003).
Schizencephaly is characteristically associated with absent or disrupted septum pellucidum in approximately 70% of cases (Griffiths 2018), where it is common for fornices to lie abnormally low. Absent septum pellucidum is more commonly associated with ‘open lip’ (type 3) schizencephaly.
Vascular disruption or a focal developmental disruption are different suggested mechanisms.
Focal transmantle dysplasia is recognized by finding an abnormal cell mass from ventricle to cortex, without cleft and with high signal intensity on T2-weighted MRI, unlike the behaviour of grey matter lining a schizencephalic cleft (Barkovich et al. 1997).
transmantle dysplasia ——>
Sarnat HB
Preterm born at GA 27w, first day sonographic finding of recent destruction (still hyperechoic) in the right frontal area, compatible with anterior MCA infarction in utero. The evolution opn the unit was toward porecnephaly imitating schizencephaly.Also small focal lesion left occipital.
courtesy dr Muhlbacher, Zürich
schizencephaly: well timed postnatal insult
complex porencephaly (mimicking schizencephaly) interrupting cingulum in a preterm infant (GA 25w) following first week subdural and parenchymal haemorrhage, consequent to problematic reintubation
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