Review articleMorphological spectrum of prenatal cerebellar disruptions
Introduction
The high spatial resolution, the excellent tissue contrast, and the multiplanar imaging offered by magnetic resonance imaging (MRI) have facilitated a more accurate and precise identification and description of cerebral and cerebellar developmental abnormalities in children.1 These abnormalities include both malformations and disruptions.
Malformations are defined as morphological defects of an organ, part of an organ, or a larger region of the body resulting from an intrinsically abnormal developmental process.2 Cerebellar malformations such as Dandy–Walker malformation,3, 4 Joubert syndrome,5, 6 or rhombencephalosynapsis7, 8 have been extensively described. Furthermore, classification schemes of cerebellar malformations have been proposed combining imaging with molecular biology.9, 10
Disruptions are defined as morphological defects of an organ, part of an organ, or a larger region of the body resulting from an extrinsic breakdown of, or an interference with, an originally normal developmental process.2 It may well be that genetic factors contribute to the susceptibility to disruptions.
Good examples of disruptions are twin disruption sequence,11 amnion rupture sequence,12 and hydranencephaly.13 Intrauterine death of one foetus in a monochorionic twin pregnancy is associated with high morbidity and mortality in the surviving co-twin. Alternatively, acute blood loss into the dying twin through placental anastomoses may result in hypotension and hypoxic-ischaemic damage to cerebral and visceral tissue in the surviving twin. The ensuing clinical picture often results primarily from the cerebral lesions and is characterised by severe neurological symptoms.11 Amnion rupture sequence represents a disruption sequence characterised by major anomalies of the craniofacial region, body wall, and limbs. The mechanism involved in the pathogenesis may be vascular disruption,12 which includes ischaemic or haemorrhagic lesions. Hydranencephaly is characterised by a virtual absence of the cerebral hemispheres, leaving only glial membranous sacs filled with cerebrospinal fluid. The aetiology includes several disruptive factors such as vascular lesions or infection.13
To date, cerebellar disruptions have received less attention in the literature than cerebellar malformations. Therefore we have reviewed our patients and published cases of cerebellar disruptions in an attempt to facilitate their characterisation on the basis of the morphological pattern and the postulated aetiology.
Section snippets
Case selection
This study addresses only prenatal cerebellar disruptions with the exception of neonatal cerebellar disruption related to very preterm neonates. Therefore cerebellar disruptions occurring outside of this period, such as neonatal cerebellar haemorrhages or profound perinatal hypoxia, have not been included. The conditions listed in Section 3 have been compiled from the following sources: for many years we have been collecting patients with cerebellar disruptions in our clinical practice and from
Global cerebellar hypoplasia
The term “global cerebellar hypoplasia” describes a cerebellum of reduced volume. On midsagittal sections the vermis is small but retains a (near) normal shape. Owing to the reduction in size of the cerebellum, the subarachnoid spaces are passively enlarged.
Global cerebellar hypoplasia is a heterogeneous condition and can be due to a variety of causes, both malformation and disruptions.14 Typical malformations causing global cerebellar hypoplasia include chromosomal aberrations such as
Discussion
The spectrum illustrated demonstrates the importance of cerebellar imaging as a clue to a wide range not only of malformations, but also of disruptions. Disruptive mechanisms can affect the cerebrum and/or the cerebellum. However, cerebrum and cerebellum are variably vulnerable to the different disruptive factors in the prenatal period. On the basis of the disorders described, it appears that in the prenatal period the cerebellum is particularly vulnerable to infections and haemorrhages, as
Conclusion
Cerebellar disruptions appear to be common, potentially mimicking cerebellar malformations, although the pathogenesis is completely different. Cerebellar disruptions presenting different morphological patterns can be caused by the same disruptive agent, such as a cerebellar haemorrhage. This fact reveals that the different disruption patterns are not several independent disorders, but are likely to represent a morphological spectrum of the same pathogenetic mechanism. Therefore, a clear
Acknowledgements
Dr. Poretti was financially supported by a donation from the United Bank of Switzerland (UBS). This donation was made at the request of an anonymous client.
References (82)
- et al.
Human malformations of the midbrain and hindbrain: review and proposed classification scheme
Mol Genet Metab
(2003) Structural anomalies resulting from vascular disruption
Pediatr Clin North Am
(1992)- et al.
Merosin-positive congenital muscular dystrophy with transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation
Neuromuscul Disord
(1999) - et al.
Brain magnetic resonance imaging abnormalities in merosin-positive congenital muscular dystrophy
Eur J Paediatr Neurol
(2000) Pontocerebellar hypoplasia—how many types?
Eur J Paediatr Neurol
(2000)- et al.
Pontocerebellar hypoplasia type 2: variability in clinical and imaging findings
Eur J Paediatr Neurol
(2007) - et al.
Late intrauterine cytomegalovirus infection: clinical and neuroimaging findings
Pediatr Neurol
(1996) - et al.
Fatal outcome following foetal cerebellar haemorrhage associated with placental thrombosis
Eur J Paediatr Neurol
(2006) - et al.
Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy
Lancet
(1998) Cerebellar agenesis versus vanishing cerebellum in Chiari II malformation
Comput Med Imaging Graph
(1995)
Vanishing cerebellum in myelomeningocoele
Eur J Paediatr Neurol
Differential diagnosis of cerebellar atrophy in childhood
Eur J Paediatr Neurol
Pediatric neuroimaging
Dysmorphology demystified
Arch Dis Child Fetal neonatal Ed
Dandy–Walker malformation: prenatal diagnosis and prognosis
Childs Nerv Syst
A different approach to cysts of the posterior fossa
Pediat Radiol
Molar tooth sign of the midbrain-hindbrain junction: occurrence in multiple distinct syndromes
Am J Med Genet A
Brain stem and cerebellar findings in Joubert syndrome
J Comput Assist Tomogr
Rhombencephalosynapsis: clinical findings and neuroimaging in 9 children
Neuropediatrics
Cognitive outcome in children with rhombencephalosynapsis
Eur J Paediatr Neurol
Analysis and classification of cerebellar malformations
AJNR
Natural history of twin disruption sequence
Am J Med Genet A
Limb body wall complex: I
Pathogenesis. Am J Med Genet
Human cerebellar hypoplasia: a syndrome of diverse causes
Arch Neurol
Cerebellar involvement in metabolic disorders: a pattern-recognition approach
Neuroradiology
Neocerebellar hypoplasia in a neonate following intra-uterine exposure to anticonvulsants
Dev Med Child Neurol
Prenatal cocaine exposure and the expanding spectrum of brain malformations
Arch Intern Med
A cerebellar ataxia locus identified by DNA pooling to search for linkage disequilibrium in an isolated population from the Cayman Islands
Hum Mol Genet
Nonprogressive autosomal recessive ataxia maps to chromosome 9q34-9qter in a large consanguineous Lebanese family
Ann Neurol
Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia
Brain
Autosomal recessive cerebellar hypoplasia in the Hutterite population
Dev Med Child Neurol
Cerebellar hypoplasia and quadrupedal locomotion in humans as a recessive trait mapping to chromosome 17p
J Med Genet
Lissencephaly with cerebellar hypoplasia (LCH): a heterogeneous group of cortical malformations
Neuropediatrics
Lissencephaly with agenesis of corpus callosum and rudimentary dysplastic cerebellum: a subtype of lissencephaly with cerebellar hypoplasia
Acta Neuropathol
Neuroimaging manifestations and classification of congenital muscular dystrophies
AJNR
MR findings in pontocerebellar hypoplasia
Pediatr Radiol
Congenital cytomegalovirus infection of the brain: imaging analysis and embryologic considerations
AJNR
The spectrum of cranial ultrasound and magnetic resonance imaging abnormalities in congenital cytomegalovirus infection
Neuropediatrics
Pattern of white matter abnormalities at MR imaging: use of polymerase chain reaction testing of Guthrie cards to link pattern with congenital cytomegalovirus infection
Radiology
Arthrogryposis, hydranencephaly and cerebellar hypoplasia syndrome in neonatal calves resulting from intrauterine infection with Aino virus
Vet Res
Cerebellar hypoplasia in three sibling cats after intrauterine or early postnatal parvovirus infection
Dtsch Tierärztl Wochenschr
Cited by (67)
Causes and consequences of structural aberrations in cerebellar development
2021, Factors Affecting Neurodevelopment: Genetics, Neurology, Behavior, and DietThe developing brain by trimester
2020, Handbook of Clinical NeurologyThe cerebellar “tilted telephone receiver sign” enables prenatal diagnosis of PHACES syndrome
2018, European Journal of Paediatric NeurologyPrenatal imaging of posterior fossa disorders. A review
2018, European Journal of Paediatric NeurologyUltrasound and CT of the posterior fossa in neonates
2018, Handbook of Clinical NeurologyConventional MRI
2018, Handbook of Clinical Neurology