Fetal obstructive hydrocephalus. Charles Raybaud Hospital for Sick Children, University of Toronto
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1 Fetal obstructive hydrocephalus Charles Raybaud Hospital for Sick Children, University of Toronto
2 Extensive definition No mention of aqueductal stenosis
3 Purpose Working definition of hydrocephalus vs ventriculomegalies Features of fetal obstructive hydrocephalus Causal, and causally associated lesions Brain plasticity in fetal hydrocephalus
4 Working definition: hydrocephalus vs ventriculomegaly 1. Disproportionate ventriculomegaly 2. Increased cephalic measurements 3. An identified obstruction Therefore, obstructive hydrocephalus only
5 Fetal obstructive hydrocephalus: ventricular size Measured at the atrium, on largest side normal 5-8mm throughout gestation Degree severe >20mm: 40 cases moderate 15-20mm: 11 cases mild 10-15mm : 5 cases 2 DW, 1 familial, 2 F/U confirmed Larger when late gestation, always larger on F/U studies Often asymmetric 14.1mm familial 23.4w (28mm), 1d postnatal (58mm)
6 Fetal obstructive hydrocephalus: cranial size Hydrocephalus BPD 2 weeks-above-average 48/56 borderline in 8/56 but 1 DW, 2 familial, 4 hemorrhages, 1 F/U Head circumference less increased than BPD HC = ½ (BPD+ FOD) x 3.14 head becomes rounded, turricephalic
7 Fetal obstructive hydrocephalus: case series Fetal MR diagnosis: 56 cases 44 early cases <32w (19.4w-29.5w) 12 late cases >32w (32.4w-38.4w) Special context (early gestation only) 1 family (2 siblings) 9 twin gestations (20%) (general population 3.2%) Initial diagnosis confirmed by fetopathology: 10 cases pre- or post-natal MR F/Us: 10 cases
8 Early fetal obstructive hydrocephalus: subtypes Mild subtype mantle thin but regular pericerebral spaces maintained septum pellucidum: rupture common Severe subtype mantle thin and focally dehiscent pericerebral spaces effaced septum pellucidum: rupture common
9 Early fetal obstructive hydrocephalus: cerebral mantle Mild subtype mantle thin but regular pericerebral spaces maintained septum pellucidum: rupture common Severe subtype mantle thin and focally dehiscent pericerebral spaces effaced septum pellucidum: rupture common
10 Late fetal obstructive hydrocephalus Not really different from post-natal ( congenital ) hydrocephalus 1/12 mild hydrocephalus: superior vermian mass 11/12 severe hydrocephalus (partial mantle loss)
11 Fetal obstructive hydrocephalus: etiologies Isolated aqueductal stenosis Early: N (%) 19 (43) Late: N (%) 1 Rhombencephalosynapsis 11 (25) 82% Ependymal nodules 6 (14) 1 Midline cysts Hemorrhages 3 (7) 4 (9) 4 (33) 5 (42) 75% Others 1 (avf) 1 (mass) 44 (100) 12 (100) Etiologies similar in mild and severe subtypes Etiologies of late hydrocephalus same as congenital hydrocephalus
12 Early fetal obstructive hydrocephalus: etiologies Aqueductal stenosis in 82% isolated 43% associated with other abnormalities rhombencephalosynapsis (& midbrain, oosterior thalamus) ependymal nodules Midline cyst, hemorrhage much less common
13 Early fetal obstructive hydrocephalus: etiologies Isolated aqueductal stenosis common = 43% classic explanations secondary to hydrocephalus undocumented TORCH, hemorrhage, dormant mass maldevelopment (D. Russel, DH Padget) recent literature data: animal, human fetus ependymal denudation +/- SCO changes ependymal nodules (6 cases) (Ferland 2011, Rodriguez 2102) factor of rupture of septum pellucidum? cause or effect of hydrocephalus?
14 Ependymal denudation, SCO and nodules Del Bigio. Neuropathological changes caused by hydrocephalus. Acta Neuropathol 1993, 85: Castañeyra-Perdomo et al. Alterations of the subcommissural organ in the hydrocephalic human fetal brain. Devel Brain Res 1994, 79: Jimenez et al. A programmed ependymal denudation precedes congenital hydrocephalus in the hyh mutant mouse. J Neuropathol Exp Neurol 2001, 60(11): Galarza: Evidence of the subcommissural organ in humans and its association with hydrocephalus. Neurosurg Rev 2002, 25: Dominguez-Pinos et al. Ependymal denudation and alterations of the subventricular zone occur in human fetuses with a moderate communicating hydrocephalus. J Neuropathol Exp Neurol 2005, 64(7): Del Bigio MR. Ependymal cells: biology and pathology. Acta Neuropathol 2010, 119: Rodriguez et al. A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus. Biol Res 2012, 45: McAllister. Pathophysiology of congenital and neonatal hydrocephalus. Semin Fet Neonat Med 2012, 17:285-94
15 Rhombencephalosynapsis Rhombencephalosynapsis (associated with aqueductal stenosis) fused cerebellar hemispheres & dentates, no vermis fused colliculi, posterior thalami Present in 11/44 early fetal hydrocephalus (25%) otherwise very rare: 100 cases published (Passi 2015)
16 Rhombencephalosynapsis Pasquier et al. Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases. Acta Neuropatol 2009, 117: mesencephalo- / diencephalosynapsis, aqueductal abnormalities Ishak et al. Rhombencephalosynapsis: a hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity. Brain 2012, 135: postnatal cases Whitehead et al, Rhombencephalosynapsis as a cause of aqueductal stenosis, Pediatr Radiol 2014, 44; postnatal cases
17 Early fetal hydrocephalus: evolution Ventriculomegaly increases (in weeks-above-average) Morphotype mild or severe does not change with advancing gestation Fetal hydrocephalus does not prevent gyration to develop except for the dehiscent mantle segment When treated early, fetal hydrocephalus seems to recover a reasonable mantle thickness except for the dehiscent mantle segment cellular lineages?
18 Early fetal aqueductal stenosis 25.4w 3d 8m/o Late fetal aqueductal stenosis Hypomyelination 38w 5y Plasticity: mantle restoration in early hydrocephalus Neonatal (early fetal) aqueductal stenosis Poor myelination 12d 4y
19 Early hydrocephalus and brain plasticity Persistent expression of signaling pathways for axonal growth andbranching Axonal progression and branching mostly subcortical Lack of myelination myelin: most potent inhibitor of axonal development myelin-associated inhibitors limit axon development Bonfanti Prog Neurobiol 2006; Fancy et al Ann Rev Neurosc 2011; Akbik et al Exp Neurol 2012
20 Fetal hydrocephalus: summary Fetal hydrocephalus triad ventriculomegaly, increased BPD, obstruction? communicating hydrocephalus Aqueductal stenosis, rhombencephalosynapsis & ependymal nodules surprisingly common Pathology: ependymal denudation common cause vs effect of hydrocephalus ependymal nodules & ruptured septum pellucidum Good morphologic recovery possible (role of lack of myelination?)
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