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Holoprosencephaly
- 1. HOLOPROSENCEPHALIES, RELATED DISORDERS &MIMICS Dr. Vishnu Dakshin Dr. Rudresh Hiremath
- 2. HOLOPROSENCEPHALY • Rare congenitalbrain malformation resulting from incomplete separation of the two hemispheres. • “Holo” – Single ventricle • “pros” – Prosencephalon • “encephaly” - Brain
- 3.
- 4. TYPES - DEMYER •CLASSIC - Alobar - Semilobar - Lobar • VARIANTS - Syntelencephaly. - Septopreoptic HPE. • Minimal HPE. • Microform HPE.
- 5. CLASSIC • Alobar HPE. •Semilobar HPE. • Lobar HPE. • The distinction between these 3 forms is based primarily on the presence or absence of a midline fissure separating the hemispheres.
- 6. ALOBAR HPE • Mostsevere. • No midline fissure, no identifiable lobes. • Fused basal ganglia. • Agyric /disordered gyri /shallow sulci. • Single crescent monoventricle - opening dorsally into a large CSF filled dorsal cyst.
- 7. ALOBAR HPE Small rimof cortex surrounds "horseshoe" central monoventricle. Thalami are fused. More cephalad scan in the same patient shows a large dorsal cyst and central monoventricle with thin rim of surrounding brain.
- 8. SEMILOBAR HPE • Intermediateform. • Primitive ventricular horns, third ventricle. • Fused basal ganglia&hypothalami, thalami often separated. • Rudimentary falx, posterior IHF. • Posterior CC forms while anterior aspects are absent.
- 9. SEMILOBAR HPE H-shaped centralventricle with primitive- appearing temporal horns, fused basal ganglia, and rudimentary interhemispheric fissure. Axial T2WI - Rudimentary posterior interhemispheric fissure, primitive ventricular horns, and anterior midline fusion.
- 10. SEMILOBAR HPE Sagittal T1WIshows sHPE with partial differentiation of third ventricle, occipital horns. Axial T2WI in the same patient- Rudimentary temporal and occipital horns. The third ventricle is partially formed. The thalami are separated, but the hypothalamus remains fused.
- 11. SEMILOBAR HPE More cephaladT2WI in the same patient shows fused basal ganglia, rudimentary posterior interhemispheric fissure, and absence of anterior interhemispheric fissure with the brain fused across the midline. More cephalad scan shows the upper aspect of a poorly differentiated central monoventricle
- 12. LOBAR HPE • Best-differentiated. •IHF & Falx are clearly developed, with shallow and dysplastic-appearing anterior aspects. • Third & lateral ventricles – well formed. • Cavum septum pellucidum is always absent. • Rudimentary frontal horns are typical , and only the most inferior portions of the frontal lobes are fused.
- 13. LOBAR HPE Sagittal T2WIof lobar HPE shows well-differentiated brain, nearly normal-appearing third ventricle & azygous ACA Axial T2WI shows well- developed occipital horns, third ventricle, and minimal anterior midline fusion. Coronal T2WI shows that the anteroinferior frontal cortex is fused across the midline.
- 14. VARIANTS • Syntelencephaly akamiddle interhemispheric variant of HPE. • Septopreoptic HPE - Solitary median maxillary central incisor syndrome. - Congenital nasal pyriform aperture stenosis.
- 15. SYNTELENCEPHALY • CC genu,splenium present, middle absent. (Only brain malformation with that morphology) • Mid-sections of falx, interhemispheric fissure absent. • Posterior frontal gray/white matter fused across midline.
- 16. SYNTELENCEPHALY Axial graphic-Absent midsectionof the IHF, upward extension of an anomalous sylvian fissure across the midline and foci of both gray & white matter that bridge the hemispheres. Axial NECT- Midportions of the hemispheres appear fused across the midline with bridges of both white and gray matter.
- 17. SYNTELENCEPHALY Corpus callosum genuand splenium are present without an intervening body. Note dysplastic gray matter deforming the lateral ventricle. Coronal T2- fused,"notched" lateral ventricles with a nodule of gray matter perched on top of the fused lateral ventricle.
- 18. SOLITARY MEDIAN MAXILLARY CENTRALINCISOR SYNDROME. • Single midline incisor. • Often coexists with nasal anomalies. • Brain anomalies of fornix, septi pellucidi, CC. common.
- 19. SMMCI Axial bone CTin a 3d infant with breathing difficulty shows a single midline maxillary incisor. Coronal bone CT in the same patient shows the central incisor and narrowed pyriform aperture stenosis.
- 20. SMMCI Axial T2WI inthe same patient at age 7 months shows lobar HPE with mild hypotelorism and fusion across the ventral frontal lobes. More cephalad scan shows absent septi pellucidi and thickened dysplastic-appearing fused fornices.
- 21. CONGENITAL NASAL PYRIFORM APERTURESTENOSIS • Choanal atresia, mid-nasal stenosis, pyriform aperture stenosis. • Often coexists with SMMCI. • HPA axis dysfunction common.
- 22.
- 23. RELATED MIDLINE DISORDERS •Septooptic dysplasia. - SOD plus – associated with other anomalies ( Schizencephaly / callosal agenesis) • Arrhinencephaly.
- 24. SEPTOOPTIC DYSPLASIA • AkaDe Morsier syndrome. • Absence of septi pellucidi. - Squared-off frontal horns, pointed inferiorly on coronal T2WI • Hypoplastic optic nerves, chiasm. • Look for ○ Malformations of cortical development ○ Thin stalk, small gland, ectopic posterior pituitary
- 25. SEPTOOPTIC DYSPLASIA Absent cavumsepti pellucidi with flat-roofed anterior horns and small optic chiasm. Cavum septi pellucidi are absent ; boxlike lateral ventricles with inferiorly pointed frontal horns. Coronal T2WI in newborn- absent cavum septi pellucidi, schizencephaly,extensive polymicrogyria, fused fornices.
- 26. SEPTOOPTIC DYSPLASIA Empty-appearing lateralventricle with low-lying fornix. The optic chiasm appears small. Hypoplastic optic chiasm, absent septi pellucidi & the peculiar box-like or squared- off" appearance of the frontal horns.
- 27. SEPTOOPTIC DYSPLASIA Extreme hypoplasiaof the optic chiasm, small pituitary gland with inapparent stalk, and low-lying fornices that give a striking "empty“ appearance to the lateral ventricle. Coronal IR in the same case- unilateral schizencephaly with dysplastic gray matter lining the cleft. Note contralateral polymicrogyria.
- 28. ARRHINENCEPHALY • Absent olfactorybulb and tracts. • Often seen in association with other midline facial abnormalities (cleft lip/palate,…) • Kallman syndrome. • CHARGE syndrome – in 25% with olfactory agenesis.
- 29.
- 30. MIMICS • HYDRANENCEPHALY - Consequenceof severe brain destruction in utero. - “Water bag" brain. - Small nubbins of remnant brain with a normal falx cerebri and posterior fossa. - Hemihydranencephaly.
- 31. HYDRANENCEPHALY Large head withstriking transillumination indicating that most of the cranium is water-filled. The hemispheres are absent ("water-bag brain"), and only the basal ganglia are present. Note separation.
- 32. HYDRANENCEPHALY A falx cerebriand tentorium are present, as are the separated basal ganglia. The hemispheres are absent. Both hemispheres are replaced by CSF. BG/thalami are separated, falx is present. No brain is visible over CSF-filled cavities.
- 33. HYDRANENCEPHALY Sagittal T1WI -hydranencephaly with macrocephaly; CSF fills virtually all of the supratentorial spaces. Coronal T1WI in the same case- expanded, CSF-filled cranial vault, only tiny remnants of brain. A falx is present.
- 34. D/D • Severe obstructivehydrocephalus (OH) Sagittal T1–massively enlarged lateral ventricles & tectal dysplasia causing aqueductal stenosis. Thin rim of compressed but normally formed cortex and subcortical WM lying under the calvarium.
- 35. D/D • Alobar holoprosencephaly Almostthe entire calvarium is occupied by the CSF-filled monoventricle covered by a very thin rim of featureless brain. The basal ganglia are fused. Note absent falx, thin rim of smooth dysplastic appearing brain.
- 36. D/D • Severe bilateral"open lip" schizencephaly Axial T2WI- Severe "open lip" schizencephaly, another cause of "water-bag brain" appearance. Coronal T2WI- falx and tentorium are normal. The massive "open lip" schizencephalic clefts are lined by dysplastic-appearing gray matter.
- 37. PRENATAL DIAGNOSIS • Asearly as 6 weeks from the LMP. • 10 - 14 weeks -- abnormal facial morphology and absence of the “butterfly” sign. • Early closure of the metopic suture. • Absence of the cavum septum pellucidum – Hallmark.
- 38. BUTTERFLY SIGN • Normalappearance of the choroid plexuses on axial imaging of the normal first-trimester brain.
- 39. SUMMARY • Incomplete separationof the two hemispheres. • Types - Classic – Alobar, Semilobar, Lobar. D/D – Hydranencephaly. D/D – Alobar/ Lobar HPE, depending on severity of sHPE. D/D - SOD,Arrhinencephaly , Syntelencephaly
- 40. SUMMARY • Variants- mivHPE,Septopreoptic HPE.
- 41. SUMMARY • Related midlinedisorders – SOD, Arrhinencephaly. D/D – Well-differentiated Lobar HPE.
- 42. SUMMARY • Mimics –Hydranencephaly.
- 43. CONCLUSION • HPE isnot uniformly lethal, as is commonly thought. • Survival depends on the severity of the brain and facial malformations, the presence of chromosomal abnormalities, the involvement of other organs, and the presence of a multiple anomaly syndrome.
- 44. REFERENCES • Osborn’s BrainImaging, Pathology, and anatomy – Second edition. • Holoprosencephaly: A Survey of the Entity, with Embryology and Fetal Imaging - Thomas C. Winter , Anne M. Kennedy, Paula J. Woodward. • Holoprosencephaly: A Guide to Diagnosis and Clinical Management - Manu S Raam, Benjamin D Solomon and Maximilian Muenke.
- 45. THANK YOU! Visit www.jssmcradiology.comfor more Radiology Education
Editor's Notes
- #4 In the earliest stages, bilateral outpouchings from the neural tube initially form a single central fluidfilled cavity (“monoventricle”) that will eventually develop into the lateral and third ventricles (see Chapter 34). The separation into two hemispheres is normally completed by the fifth gestational week. The embryonic ventricular system is a series of interconnected fluid-filled chambers that arise as expansions from the central cavity of the embryonic neural tube. As the developing brain bends and expands, it forms fore-brain, midbrain, and hindbrain vesicles. The forebrain cavity divides into two lateral ventricles, which develop as outpouchings from the rostral third ventricle and are connected to it by the interventricular foramen (foramen of Monro) (34-1). The cerebral aqueduct develops from the midbrain vesicle. The fourth ventricle develops from the hindbrain cavity and merges proximally with the aqueduct and caudally with the central canal of the spinal cord The holoprosencephalies are characterized by failure of normal dorsal-ventral induction and lack of rostral forebrain cleavage. In the most severe forms, diencephalic-derived structures such as the basal ganglia also remain fused in the midline. As ventral induction is closely related to facial development, HPE is also associated with a number of characteristic facial anomalies. The eye field begins as a single midline structure. Under the signaling influence of the prechordal plate, the eye field in vertebrates splits into separate left and right eyes. If this developmental process is not completed correctly, the result is cyclopia
- #5 Probst- presence or absence of a dorsal sac and cleavage of basal structures are used to categorize the process in children “minimal” HPE, which is associated with subtle craniofacial malformations and mild developmental delay; and microform HPE, which by definition excludes brain involvement. (a) synophthalmia and a proboscis in a patient with alobar holoprosencephaly; (b) severe hypotelorism, flat nasal bridge, bilateral colobomas, and midline cleft lip and palate in a patient with alobar holoprosencephaly; (c) hypotelorism, flat nasal bridge, and closely spaced nostrils in a patient with lobar holoprosencephaly; (d) hypotelorism, sharp nasal bridge, and single maxillary central incisor in an individual with a microform of holoprosencephaly
- #7 The most severe facial malformations are seen in association with alobar HPE. The presence of a dorsal cyst strongly correlates with thalamic fusion, hence the high frequency with alobar HPE. It is thought that the flow of cerebrospinal fluid out of the third ventricle is obstructed by fusion of the thalami, and, as a result, the third ventricle balloons out posteriorly at the point of least resistance in the suprapineal recess.
- #8 The single primitive ventricle and fused thalami are perhaps the two most valuable US clues for alobar HPE. Important differential diagnostic considerations for alobar HPE, such as hydranencephaly and severe hydrocephalus (42), exhibit normal thalamic cleavage and usually at least a partially visualized falx cerebri. Hydranencephaly – Face normal, Falx +, Most of cerebral tissue has been destroyed, usually by intrauterine vascular accident or infection.
- #9 varying degrees of separation of the deep nuclei. When thalamic fusion is present, there may be a dorsal cyst in semilobar HPE The farther anterior the cc forms, the better the brain is developed. IH fissure- rudimentary in most severe forms, forms in better-differentiated shpe.
- #10 Coronal autopsy case of severe semilobar HPE shows Hshaped central ventricle with primitive-appearing temporal horns , fused basal ganglia ſt, and rudimentary interhemispheric fissure. Axial T2WI shows severe sHPE with rudimentary posterior interhemispheric fissure st, primitive ventricular horns ſt, and anterior midline fusion. Diffuse frontal migration arrest with subcortical heterotopic GM is also present.
- #11 Sagittal T1WI shows sHPE with partial differentiation of third ventricle , occipital horns . The midbrain, pons, and cerebellum are comparatively normal.(38-8B) Axial T2WI in the same patient shows mild hypotelorism with no other midface anomalies. Rudimentary temporal ſt and occipital st horns are present. The third ventricle is partially formed. The thalami are separated, but the hypothalamus remains fused.
- #12 More cephalad T2WI in the same patient shows fused basal ganglia ſt, rudimentary posterior interhemispheric fissure st, and absence of anterior interhemispheric fissure with the brain fused across the midline . (38-8D) More cephalad scan shows the upper aspect of a poorly differentiated central monoventricle. The corpus callosum and all normal midline structures are absent.
- #14 Sagittal T2WI of lobar HPE shows well-differentiated brain, nearly normal-appearing third ventricle , and azygous ACA ſt. Coronal T2WI shows that the anteroinferior frontal cortex is fused across the midline st. Axial T2WI shows well-developed occipital horns ſt, third ventricle , and minimal anterior midline fusion st.
- #15 Mih – inbetween semilobar and lobar in terms of severity.
- #17 Axial graphic depicts syntelencephaly with absent midsection of the interhemispheric fissure, upward extension of an anomalous sylvian fissure across the midline , and foci of both gray and white matter that bridge the hemispheres. (38-11A) Axial NECT scan in a patient with syntelencephaly shows that the midportions of the hemispheres appear fused across the midline with bridges of both white ſt and gray matter .
- #18 Sagittal T1WI shows classic findings of MIH. Corpus callosum genu ſt and splenium are present without an intervening body. Note dysplastic gray matter st deforming the lateral ventricle. (38-11C) Coronal T2 shows fused, "notched" lateral ventricles ſt with a nodule of gray matter perched on top of the fused lateral ventricle. The posterior frontal lobes are continuous across the midline st without an interhemispheric fissure.
- #20 Axial bone CT in a 3d infant with breathing difficulty shows a single midline maxillary incisor ſt. (38-12B) Coronal bone CT in the same patient shows the central incisor ſt and narrowed pyriform aperture stenosis . In the term newborn, the normal aperture width should be > 8 mm.
- #21 Axial T2WI in the same patient at age 7 months shows lobar HPE with mild hypotelorism and fusion across the ventral frontal lobes ſt. (38-12D) More cephalad scan shows absent septi pellucidi and thickened dysplastic-appearing fused fornices ſt.
- #23 (A) Patient with alobar HPE. (A1) Note cyclopia with doubling of eye structures, arrhinia, rudimentary proboscis and agnathia. (A2) microcephaly and malformed ears. (B) Patient with alobar HPE note premaxillary agenesis and hypertelorism. (C) Patient with semilobar HPE. (C1) Note hypotelorism, squint and cleft lip. (C2) Microcephaly, brachycephaly and large ears. (D) Patient with semilobar HPE showing hypotelorism. (E), (F) and (G) are patients with semilobar HPE showing hypertelorism. (H) Patient with semilobar HPE and Dandy Walker malformation showing normal facial features except for ear asymmetry (simple right ear). (I1) Patient with MIH having hypertelorism and (I2) occipital cephalocele
- #26 Coronal graphic shows SOD with absent cavum septi pellucidi with flat-roofed anterior horns and small optic chiasm ſt. Coronal T2WI in newborn shows absent cavum septi pellucidi , schizencephaly ſt, extensive polymicrogyria , fused fornices . Cavum septi pellucidi are absent ; boxlike lateral ventricles with inferiorly pointed frontal horns are seen.
- #27 Sagittal T2WI in a 13m boy with septooptic dysplasia (SOD) shows an empty-appearing lateral ventricle with low-lying fornix . The optic chiasm appears small. Coronal T2WI shows the hypoplastic optic chiasm , absent septi pellucidi , and the peculiar box-like or "squared-off" appearance of the frontal horns. The inferior pointing ſt of both frontal horns is also characteristic of SOD.
- #28 Sagittal T1WI in a 26y woman with SOD shows extreme hypoplasia f the optic chiasm ſt, small pituitary gland with inapparent stalk st, and low-lying fornices that give a striking "empty" appearance to the lateral ventricle . Coronal IR in the same case shows unilateral schizencephaly with dysplastic gray matter lining the cleft st. Note contralateral polymicrogyria ſt.
- #30 Coronal T2WI in a normal newborn shows olfactory bulbs ſt and normal olfactory sulci Coronal T2WI in a newborn with multiple congenital anomalies demonstrates arrhinencephaly with absent olfactory bulbs ſt and no olfactory sulci .
- #31 A normal or large head with fluid-filled cranial vault. Compromise of the internal carotid artery circulation before 16 gestational weeks followed by diffuse liquefactive necrosis of the cerebral mantle is responsible. In hydranencephaly, most of the cerebral hemispheres have been destroyed and are totally or partially replaced by translucent thin-walled sacs of CSF that fill most of the supratentorial space.The outer layer consists of leptomeninges, and the inner layer is glial tissue without demonstrable ependymal elements.
- #32 Autopsy case of hydranencephaly demonstrates a large head with striking transillumination indicating that most of the cranium is water-filled. The thinned calvarium has been partially removed to show the fluid-filled cavity. The hemispheres are absent ("water-bag brain"), and only the basal ganglia are present. Note separation
- #33 This is the same case as Figure 38-22, seen from above. A falx cerebri and tentorium are present, as are the separated basal ganglia . The hemispheres are absent. NECT shows hydranencephaly. Both hemispheres are replaced by CSF. BG/thalami are separated , falx is present ſt. No brain is visible over CSF-filled cavities st.
- #34 Sagittal T1WI shows hydranencephaly with macrocephaly; CSF fills virtually all of the supratentorial spaces. Brainstem and cerebellum are normal. Coronal T1WI in the same case shows expanded, CSF-filled cranial vault, only tiny remnants of brain ſt. A falx is present.
- #35 - thin cortex can be seen compressed against the dura and inner table of the calvaria. Sagittal T1WI in a 4-week infant with macrocrania shows massively enlarged lateral ventricles and tectal dysplasia ſtcausing aqueductal stenosis . Coronal T2WI shows the massively enlarged lateral ventricles . There is a thin rim of compressed but normally formed cortex ſt and subcortical WM lying under the calvarium. This is maximal hydrocephalus.
- #36 This is alobar holoprosencephaly. Sagittal T2WI shows enlarged head with relatively normal appearing posterior fossa. Almost the entire calvarium is occupied by the CSF-filled monoventricle covered by a very thin rim of featureless brain . Coronal T2WI shows a horseshoe-shaped monoventricle. The basal ganglia are fused. Note absent falx, thin rim of smooth dysplastic appearing brain .
- #37 Axial T2WI shows severe "open lip“ schizencephaly, another cause of "water-bag brain" appearance. Coronal T2WI in the same case shows that the falx and tentorium are normal. The massive "open lip" schizencephalic clefts are lined by dysplastic-appearing gray matter.
- #38 3. height of the frontal bones at the suture was higher. 4. If the face is normal, inability to demonstrate a normal cavum septum pellucidum may be the only hint that there is severe brain malformation -- careful follow-up is essential with endovaginal US, three-dimensional volume acquisition, and fetal MR imaging.
- #39 Normal skull and brain at 13 weeks. Axial view of the head showing the normal calcification of the skull; the falx and the two choroid plexuses ("butterfly sign") are normal. (b) Alobar holoprosencephaly: transverse view of the head showing the fusion of the thalami and of the lateral ventricles. Inability to demonstrate this sign within a normal cranial vault is highly suggestive of HPE
- #40 D/D - SOD – frontal horns + - Arrhinencephaly – olfactory bulbs + - Syntelencephaly – CC, genu, splenium(+), body(-)
- #44 Among euploid patients with HPE, there is an inverse relationship between the severity of the facial phenotype and the duration of survival. In fetuses with HPE, look for additional anomalies, consider fetal MR imaging, offer karyotype with microarray analysis.