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POLYMICROGYRIA - keywords
polymicrogyria references to arterial porencephaly r e f e r e n c e s n a v i g a t o r Barkovich AJ, Rowley H, Bollen A. (1995) Correlation of prenatal events with the development of polymicrogyria. Am J Neurorad 16(4 Suppl):822-7. Breunig JJ, Haydar TF, Rakic P (2011). Neural Stem Cells: Historical Perspective and Future Prospects. Neuron 70: 614-625. Byrd SE, Osborn RE, Bohan TP, Naidich TP. (1989) The CT and MR evaluation of migrational disorders of the brain. Part II. Schizencephaly, heterotopia and polymicrogyria. Ped Radiol 19(4):219-22. Bystron I, Blakemore C, Rakic P (2008) Development of the human cerebral cortex: Boulder Committee revisited. Nat Rev Neurosci 9:110–22. Chi JG, Dooling EC, Gilles FH (1977) Gyral Development of the human brain. Ann Neurol 1:86-93. Choi BH, Ruess WR, Kim RC (1986) Disturbances in neuronal migration and laminar cortical organization associated with multicystic encephalopathy in the Pena-Shokeir syndrome. Acta Neuropath (Berl) 69(3-4):177-83. Crome L (1952) Micorgyria. J Pathol Bact 64; 479-494. du Plessis AJ, Kaufmann WE, Kupsky WJ (1993) Intrauterine-onset myoclonic encephalopathy associated with cerebral cortical dysgenesis. J Child Neurol 8(2):164-70. Ferrer I, Catala I (1991) Unlayered polymicrogyria: structural and developmental aspects. Anat Embryol (Berl) 184(5):517-28. Friede RL, Mikolasek J (1978) Postencephalitic porencephaly, hydranencephaly or polymicrogyria. A review. Acta Neuropath (Berl) 43(1-2):161-8. Friede RL (1989) Dysplasias of cerebral cortex, ch 27 in Developmental Neuropathology, Springer Verlag Berlin. García-Moreno F, Molnár Z (2015) Subset of early radial glial progenitors that contribute to the development of callosal neurons is absent from avian brain. Proc Natl Acad Sci U S A 112(36):E5058-67. Golden JA (2001) Cell migration and cerebral cortical development. Neuropath Appl Neurobiol 27(1):22-8. Govaert P, Swarte R, De Vos A, Lequin M (2004) Sonographic appearance of the normal and abnormal insula of Reil. Dev Med Child Neurol 46:610-6. Govaert P, Lequin M, Korsten A, Swarte R, Kroon A, Barkovich AJ (2006) Postnatal onset cortical dysplasia associated with infarction of white matter. Brain Res 1121(1):250-5.  Harding BN, Copp AJ (2002) Malformations, chapter 7, pp 396-416 in Graham DI, Lantos PL (eds) Greenfield’s Neuropathology, Seventh Edition, Edward Arnold London. Hevner RF, Horoupian DS (1996) Pena-Shokeir phenotype associated with bilateral opercular polymicrogyria. Ped Neurol 15(4):348-51. Kappers A, Huber GC, Crosby EC (1967) The development of the cortex in mammals, chapter X in The comparative anatomy of the nervous system of vertebrates including man. Kappers A, Huber GC, Crosby EC (eds) Harper Publishing Company, New York. Kho N, Czarnecki L, Kerrigan JF, Coons S (2002) Pena-Shokeir phenotype: case presentation and review. J Child Neurol 17(5):397-9. Kuzniecky RI (1994) Magnetic resonance imaging in developmental disorders of the cerebral cortex. Epilepsia 35 Suppl 6:S44-56.  Lai A, Neil JE, Akula SK, Amrom D, Andermann E, Bergin A, Caraballo R, Chen AY, Gaitanis J, Mochida GH, Gotoff JM, Kuchukhidze G, Marom D, ElAchkar CM, Regev M, Rodan LH, Olson H, Zhang B, Poduri A, Shao DD, Walsh CA, Yang E. Diverse Genetic Etiologies of Unilateral Polymicrogyria. Ann Neurol. 2026 Feb 11.  Larroche JC, Girard N, Narcy F, Fallet C (1994) Abnormal cortical plate (polymicrogyria), heterotopias and brain damage in monozygous twins. Biol Neonate 65(6):343-52. Lawson G, Sheeka A, Gaur P, Alifieraki S, Basheer N, Jan W, Kachramanoglou C, Lyall H. Polymicrogyria in infants with symptomatic congenital cytomegalovirus at birth is associated with epilepsy: A retrospective, descriptive cohort study. Dev Med Child Neurol. 2025 Aug;67(8):1026-1033.  Meyer G, González-Gómez M (2018) The Subpial Granular Layer and Transient Versus Persisting Cajal-Retzius Neurons of the Fetal Human Cortex. Cereb Cortex 28(6):2043-2058.  Meyer G, González-Gómez M (2018) The heterogeneity of human Cajal-Retzius neurons. Semin Cell Dev Biol 76:101-111. Montiel JF, Wang WZ, Oeschger FM, Hoerder-Suabedissen A, Tung WL, García-Moreno F, Holm IE, Villalón A, Molnár Z (2011) Hypothesis on the dual origin of the Mammalian subplate. Front Neuroanat. 5:25.  Namata TT, Tumusiime MC, Nabaweesi J, Sebunya R. Congenital Bilateral Perisylvian Syndrome: A Rare Case. Pediatr Neurol. 2025 Feb;163:82-84.  Neeman B, Sudhakar S, Biswas A, Rosenblum J, Sidpra J, D'Arco F, Löbel U, Gómez-Chiari M, Serrano M, Bolasell M, Reddy K, Ben-Sira L, Zakzouk R, Al-Hashem A, Mirsky DM, Patel R, Radhakrishnan R, Shekdar K, Whitehead MT, Mankad K. Sotos Syndrome: Deep Neuroimaging Phenotyping Reveals a High Prevalence of Malformations of Cortical Development. AJNR Am J Neuroradiol. 2024 Oct 3;45(10):1570-1577. Norman MG, Mc Gillivray BC, Kalousek DK, Hill A, Poskittt KJ (1995) Congenital malformations of the brain. Oxford University Press.  Nosrati MSS, Doustmohammadi A, Severino M, Romano F, Zafari M, Nemati AH, Velmans C, Netzer C, Breuer J, Broekaert IJ, Joachim A, Almasri N, Kruer MC, Skidmore P, Bisarad P, Hoque J, Bakhtiari S, Torella A, Nigro V, Buffelli F, Fulcheri E, Müller A, Zara F, Capra V, Scala M. Novel KIF26A variants associated with pediatric intestinal pseudo-obstruction (PIPO) and brain developmental defects. Clin Genet. 2025 Jan;107(1):83-90.  Paladini D, Biancotto G, Della Sala F, Severino M, Rossi A. Neurosonographic and MRI diagnosis of fetal cerebral lesions heralding polymicrogyria. Ultrasound Obstet Gynecol. 2024 Mar;63(3):293-302. Pascual-Castroviejo I, Pascual-Pascual SI, Viano J, Martinez V, Palencia R (2001) Unilateral polymicrogyria: a common cause of hemiplegia of prenatal origin. Brain Develop 23(4):216-22.Pellicer A, Cabanas F, Perez-Higueras A, Garcia-Alix A, Quero J (1995) Neural migration disorders studied by cerebral ultrasound and colour Doppler flow imaging. Arch Dis Childh  73:F55-F61. Price D, Jarman A, Mason J, Kind P (2001) Building brains: an Introduction to neural development, first edition. John Wiley & sons.  Rakic P, Arellano JI, Breunig J (2009) Development of the primate cerebral cortex. In Gazzaniga (ed) The cognitive neurosciences, MIT press. Ramos JN, Soares P, Caetano A. Unilateral perirolandic polymicrogyria with ipsilateral brainstem hypoplasia and compensatory contralateral hyperplasia. Neurol Sci. 2023 Jul;44(7):2617-2619. Sakai T, Kikuchi F, Takashima S, Matsuda H, Watanabe N (1997) Neuropathological findings in the cerebro-oculo-facio-skeletal (Pena-Shokeir II) syndrome. Brain Develop  19(1):58-62. Sasaki M, Nakasato T, Goto H, Yanagisawa T, Suzuki T, Matsuda I, Fujiwara M, Hashimoto S, Saito K. (1989) Normal sonographic findings of the infant temporal lobe in coronal sections. Brain Develop 11:230-235. Shevell MI, Carmant L, Meagher-Villemure K (1992) Developmental bilateral perisylvian dysplasia. Ped Neurol 8:299-302. Trounce JQ, Fagan DG, Young ID, Levene MI (1986) Disorders of neuronal migration: sonographic features. Dev Med Child Neurol 28(4):467-71. < > typical images Recognition of cerebral polymicrogyria (PMG) in the neonatal period is important to predict epilepsy early on, to search for causes and to differentiate with other conditions leading to neonatal seizures. PMG covers a spectrum of clastic as well as genetic types.  In the neonatal period polymicrogyria may present with: hypotonia, micrognathia, multifocal clonic seizures, apnea; weak suck, drooling; polyhydramnios, clenched fists and limb contractures, multifocal seizures of clonic as well as tonic nature, weak facial movements, absent suck and gag reflex, stupor; Pena-Shokeir phenotype (Choi et al. 1986, Hevner and Horoupian 1996, Sakai et al. 1997, Kho et al. 2002); congenital hemiparesis. It is a strong predictor of later epilepsy (e.g. Lawson et al. 2025 for congenital cytomegalovirus infection). mantle layers migration cortical plate histological types PMG is due to abnormal organization of the cortical plate into an erratic pattern of miniature gyri with fused molecular layers.  The neuropathological entity comprises (Friede and Mikolasek 1978, Larroche et al. 1994, Ferrer and Catala 1991, Harding and Copp 2002):  (1) coarse gyral pattern, reminiscent of a cauliflower; (2) thickened cerebral cortical plate (5 to 9 mm) and (3) irregular interdigitation ‘en guirlande’  of some or all cortical layers into subcortical white matter, not parallel to the surface (festooned aspect).  Neuronal masses project into white matter like a finger, a narrow-based glove with several fingers or a pseudogland. Miniature gyri fuse and are piled on top of each other. The disorder is unilateral in slightly less than half the cases.The genetic causes of bilateral and unilateral PMG can overlap, but some are unique to certain distributions of the malformation. Germline testing for the unilateral presentation is warranted (Lai et al. 2026). polymicrogyria typical polymicrogyria with very irregular inner cortical plate organisation; fetus at 24w postmenstrual age with porencephaly Friede 1989 major disorders of neuronal migration cortical dysplasia imaging causes of PMG flat insula normal contralateral insula <---- megalencephaly and extensive bilateral PMG, flat insulae ——> unilateral PMG with linear nevus sebaceus congenital cytomegalovirus infection fetal ventrciulomegaly: dysmorphic lateral ventricles, flat insulae polymicrogyria: typical imaging OSVZ venous infarction end of neuronal migration: glioneuronal heterotopia, polymicrogyria, cortical dysplasia MZ ISVZ GMH mantle layers, migration and effects of GMH/IVH onset of neuronal migration: subependymal heterotopia One may suspect PMG with ultrasound and confirm with MRI (Trounce et al. 1986, Sasaki et al. 1989, Byrd et al. 1989, Kuzniecky 1994, Pellicer et al. 1995, Govaert et al. 2004 and 2006). Most but not all instances of PMG lead to alteration of insular gyri. On parasagittal CUS of PMG the posterior margin of the insular lobe is inseparable from the Sylvian fissure, the insular triangle is “compressed in the vertical plane". In opercular view no branches are seen from the lateral fissure, an image akin to that seen at 28 weeks. An insular triangle is not recognized in any of these sections, unlike the normal state at 28 weeks where the insular triangle is already present. The mature aspect in PMG at term thus differs from the immature normal aspect at 28 weeks. In coronal section short penetrating branches do not leave the medial aspect of the recumbent Y representing the insular space. Polymicrogyria in the posterior opercular area may be associated with indentation of the mantle resembling schizencephaly. The cleft in such instance does not reach the ventricular lumen. Ventricular dilatation is common in PMG. MRI of PMG has the following characteristics: thickened cortical gray matter, irregular (bumpy) cortex-white matter junction, increased number of small grey matter extensions into white matter, abnormal gyral pattern with steep lateral fissure, incomplete opercularization. The neonatal recognition of PMG with MR is not always straightforeward.  Deep lesions may on the other hand also alter the cortical plate above it. Perinatal human clastic deep brain lesions, below subplate and cortex, like a medullary venous infarct in a preterm infant at 23-25 weeks can cause macroscopically recognizable cortical dysplasia in the form of polymicrogyria (Govaert et al. 2006). At postmortem, changes in the cerebral cortex have been reported above bilateral deep white matter lesions referred to with the term leukomalacia (Marin-Padilla 1996 and 1997), now lumped under the umbrella “punctate white matter lesions”.  cortical dysplasia in imaging Neuronal migration can be disturbed across a wide range of stages of maturation and at many different molecular steps of a complex process (Barkovich et al. 1995). Often disruptions by external factors like ischaemia, infection or metabolic disorder, also lead to clinical presentation in the perinatal period with prematurity, growth retardation, microcephaly, seizures. In some they are a chance finding during ultrasound. Polymicrygria (one form of cortical dysplasia) is the result of abnormal late stages of neuronal migration and cortical settling. Severe changes are associated with abnormalities of the corticospinal tract (Ramos et al. 2023)    Focal cortical brain injury can directly alter final gyral morphology during either primary or post-primary gyration. Any significant lesion of the cortex itself, be it an arterial or venous infarct, watershed injury, inflammation or other, changes gross cortical morphology. In postmortem descriptions this is referred to as ulegyria, i.e atrophy and alteration in shape of gyri (Friede 1989, Paneth et al. 1994). When lesions to the cortex occur before the end of the brunt of neuroblast migration (around 25 w) they lead to focal interruption of cortical formation, histologically often referred to as polymicrogyria, the existence of far too many erratic small gyri in a specific region (Friede 1989).  steps in neuronal migration sources of neuronal production in the lateral, medial and caudal ganglionic eminences ganglionic eminences end of month 3, Retzius 1896 TRN (thalamic reticular nucleus) shares genetic expression with amygdala A and subplate S; TRN and subplate together orchestrate thalamic axonal pathfinding into the cortical plate CP stages of cortical plate formation Stage IV : Secondary condensation (from the 13th to the 15th fetal week).  During this period, the ventricular zone becomes progressively thinner, while the subventricular zone remains relatively wide. The cortical plate again condensates into a uniform appearance. At the end of this stage, an accumulation of large cells appears below the cortical plate, and the subplate zone enlarges further, with early regional differences (also in the prefrontal cortex). For the fontal lobe a specific transcription factor expressed here is bFGF. Thalamic input is present at this stage, in the subplate, but most axons entering the subplate and cortex are from the basal forebrain (cholinergic) and from the brainstem tegmentum (mono-aminergic). Endogenous activity oscillations emerge in subplate, independent of sensory input. Stage V : Prolonged stage of cortical maturation (from the 16th fetal week, well into the postnatal period).  By the fifth month, relatively few neuronal precursors seem to be proliferating in the reduced ventricular zone of the human cerebral hemispheres. However, the interneurons, which continue to be generated in the subventricular zone and ganglionic eminence, are still being added to the cortex between the 20th and 25th weeks of gestation. Most neurons of the human neocortex are generated before the beginning of the third trimester of gestation, no neurons are generated in the cortex itself. Toward term, the ventricular zone disappears, the subplate dissolves, and as the intermediate zone transforms into the white matter, only a vestige of the subplate cells remain as interstitial neurons.  Glial cells are produced in the SVZ including oligodendrocytes, largely outnumber neurons. After cortical neurons have settled in their final positions, their differentiation, including the formation of synapses, proceeds for a long time and reaches a peak only during the second postnatal year. [Bystron et al. 2008, Meyer et al. 2018, Rakic et al. 2009] Neurons of the subpial granular layer (SGL) in the human marginal zone (MZ) migrate tangentially from the periolfactory subventricular zone all over the neocortex. At 14 to 18 gestational weeks, the SGL grows to attain maximum prominence around midgestation. At 20-25 GW, a transient cell type in the MZ expresses glutamate decarboxylase (GAD) and calretinin, and extends a varicose plexus surrounding somata of large transient Cajal-Retzius neurons (tCRN), potentially modulating their activity. Around 30 GW, after the disappearance of SGL a population of persisting subpial, perivascular Cajal-Retzius neurons (pCRN) appears and remains into adult life in the walls of sulci. Stage I : Initial formation of the cortical plate (approximately the 6th to the 10th fetal weeks).  During the 7th fetal week, postmitotic cells begin to migrate from the ventricular zone outward to form a new accumulation of cells at the junction of the intermediate and marginal zones. By the middle of this period, synapses are present (in a bilaminar setting) above and below the cortical plate in the marginal zone and in the pre-subplate which both contain early maturing neurons. Stage II : Primary condensation of the cortical plate (approximately the 10th and 11th fetal weeks).  The cortical plate increases in thickness, becomes more compact, and is clearly demarcated from the fiber-rich part of the intermediate zone, which seems to have fewer cells , indicating that the first major wave of migration is almost spent. This stage ends when layers 5 and 6 (the deep layers) are generated in most regions of the cortex.  Stage III : Bilaminate cortical plate (most pronounced during the 11th to the 13th fetal week).  The uniform and compact cortical plate of the second stage becomes subdivided into an inner zone occupied mainly by cells with relatively large, somewhat widely spaced oval nuclei and an outer zone of cells with densely packed, darker, bipolar nuclei. This heterogeneity results from the advanced maturation of the deep-lying neurons that had arrived at the cortical plate during earlier developmental stages, plus the addition of a new wave of somas of immature neurons that take up more superficial positions. This period is characterized by the appearance of the cell-sparse, fiber-rich subplate zone situated below the cortical plate, particularly wide in the regions subjacent to the association areas.  term, fetal ventriculomegaly Primary (genetic) isolated polymicrogyria  - CBPS (congenital bilateral perisylvian syndrome; facio-pharyngo-glosso-masticatory diplegia, Foix-Chavany-Mary, bilateral opercular syndrome: causes pseudobulbar paresis (Worster-Drought syndrome) with partial or general epilepsy in more than 50 %; familial cases reported     -> lobar and multilobar mixtures of bilateral symmetrical PMG     -> a unilateral variant (CUPS) may present with hemiparesis and epilepsy (some autosomal dominant); congenital unilateral perisylvian syndrome with septal agenesis overlaps with CBPS as well as septo-optic dysplasia - with Ohtahara syndrome - associated with other brain malformations  + schizencephaly-polymicrogyria complex with or without septal agenesis; overlap between PMG and true schizencephaly where a cleft bordered by PMG does not extend from surface to ependyma  + septo-optic dysplasia (SOD); opercular PMG with septal agenesis may exist without hypothalamic dysfunction  + anterior commissure agenesis and heterotopia  + semilobar holoprosencephaly and acalvaria  + meningomyelocoele  + neuroectodermal disorder: hemimegalencephaly, linear nevus sebaceus syndrome, incontinentia pigmenti achromians (unilateral discrete ventriculomegaly in the newborn)   - associated with a single gene disorder Aicardi syndrome  Galloway-Mowat syndrome  Klippel-Trenaunay-Weber syndrome with congenital hydrocephalus  Nezelof syndrome (short intestine)  non-ketotic hyperglycinemia  oro-facio-digital syndrome(s) short-rib polydactyly type IV (Beemer-Langer)  splenogonadal fusion and limb deficiency  thanatophoric dysplasia  X-linked hydrocephalus  Sotos syndrome (Neeman et al. 2024) intestinal pseudo-obstruction (Nosrati et al. 2025) Chudley–McCollough s. (hydrocephalus, partial ACC, arachnoid cyst) Joubert  s. (molar tooth, cerebellar hypoplasia, renal dysplasia, polydactyly) Knobloch s. (occipital cephalocele, heterotopia, ataract, hydronephrosis, duplex kidney) macrocephaly syndromes: MCAP, MPPH, Smith–Kingsmore s., Weaver s.Micrognathia    Zellweger spectrum with in utero haemorrhage due to collagen 4A mutations occludin mutations …. - associated with an anomaly of the karyotype: e.g. velocardiofacial syndrome (22q11 deletion) )(opercular PMG, may be unilateral); tetrasomy 12p (Pallister-Killian s.) Clastic PMG around cavities and cysts of hydranencephaly and porencephaly or with gliosis and calcification     with periventricular cavitation  fetal brain inflammation: CMV, rubella, syphilis, toxoplasmosis, pseudo-TORCH syndrome  asphyxia  in monozygous twinning (twin to twin transfusion)  CO intoxication  methylMg (Minamata disease) brain trauma in utero  drug abuse  threatened or attempted abortion  with a developmental vasculopathy  causes of polymicrogyria Heterogeneity of stem cells in the mammalian forebrain (Breunig et al. 2011). - initially, neuroepithelial cells constitute the major class of neural stem cells; these give rise to radial glia (RGC), which can self-renew (symmetrical division in the VZ) or generate neurons directly (asymmetrical division) - RGs can also generate classes of progenitor types such as intermediate neural progenitors (INPs), which divide in the SVZ, or short neural progenitors (SNPs), which contact and divide at the VZ surface, both of which can generate neurons; other RGCs further subdivide in the outer SVZ - RG transition into neurogenic SEZ astrocytes and SG radial astrocytes occurs during the gliogenic phase  - in addition, radial glia give rise to ependymal (EL) cells, oligodendrocytes (OC), and astrocytes (AC) pre- and perinatally and in the adjacent dentate gyrus (DG) during a prolonged postnatal stage RG radial glial cellsING intermediate neural progenitorSNP short neural progenitor stages of cortical plate formation: graphic congenital CMV: polymicrogyria and gliomeningeal heterotopia (Norman et al. 1995) porencephaly surrounded by polymicrogyria (preterm 33w GA, attempted abortion) (Crome 1952) polymicrogyria: histological types Polymcirogryia is the name for changes of the cerebral cortex characterised by an excess of small gyri, often of abnormal histology (Crome 1952, Norman et al. 1995). Outside the surface is a miniature cobblestone pavement. Due to irregular deepning of the small gyri, the cortex may appear macroscopically (also on MR) thicker than normal. The abnormal cortex is either laminated or not; If laminated there are often four layers (either in parallel or not). The four layers are molecular layer, irregular neuronal layer, cell sparse layer and deep neuronal layer.  Since time of onset (second or early third trimester) differs and there are many different mechanisms behind this process (acquired and genetic) the classification is complex: every case appears to be unique histologically (and on images in vivo). Even with one mechanism, e.g; congenital CMV, the changes may be due to destruction of neuronal precursors, aberrant migration, leptomeningitis and focal ischaemia due arteritis or phlebitis.  17 year old with unexplained left temporal polymicrogyria (hydrocephalus with shunting)(after Norman en al. 1995) glioneuronal heterotopion a spastic quadriplegic child with both cerebral and cerebellar polymicrogyria (Crome 1952) cresyl violet staining of an area of polymicrogyria in a watershed lesion (congenital heart defect and congenital CMV)(Norman et al. 1995)  polymicrogyria Mac OS X  2°âATTRâ¼&¼com.apple.TextEncodingËcom.apple.quarantineutf-8;134217984q/0082;69e772f7;Hype4;