Download Cerebellar cysts in children

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Cerebellar cysts in children:
a pattern-recognition approach
Andrea Poretti 1,2, Thierry A.G.M. Huisman1,
Eugen Boltshauser 2
1Section
of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H Morgan
Department of Radiology and Radiological Science, The Johns Hopkins University School
of Medicine, Baltimore, MD
2Department of Pediatric Neurology, University Children’s Hospital of Zurich, Switzerland
ASNR 53rd Annual Meeting, Chicago, April 25-30, 2015
©AP
Disclosure
• We have nothing to disclose
• No relevant financial relations interfering with
our presentation
©AP
Learning objective
• To provide an
1. Evaluation approach and
2. Differential diagnosis
of pediatric brain diseases associated with
cerebellar cysts
©AP
Cerebellar cysts
• Cerebellar cysts = uncommon
• Different etiologies includes
malformation and disruption
• General imaging properties:
– Variable size and shape
– Diverse location within the
cerebellum
– T1/FLAIR hypointense, T2
hyperintense
– No contrast enhancement
1-year-old child with cerebellar cysts,
cerebellar dysplasia, and LAMA1 mutation
Boltshauser E et al, Cerebellum, 2015
©AP
Cerebellar cysts: Diagnostic work-up
• Neuroimaging = key role in the diagnostic work-up
• Neuroimaging based pattern-recognition approach
taking into account clinical information 
facilitates correct diagnosis
• Correct diagnosis  essential for optimal therapy,
accurate prognosis, and correct genetic counseling
©AP
Purpose
• Provision of checklists (based on pathogenesis)
and pattern-recognition approach for pediatric
cerebellar cysts
• The checklists and pattern-recognition approach
should facilitate correct diagnosis, narrow
differential diagnosis, or, if required, help
planning of targeted diagnostic work-up
• Cerebellar tumors with a cystic component,
parasitic cysts, and postsurgical or posttraumatic
cysts were excluded
©AP
Cerebellar cysts: Pathogenesis
• Pathogenesis of cerebellar cysts  heterogeneous:
1. Normal cystic structures: cystic perivascular spaces in
mucopolysaccharidoses
2. Isolated cysts: e.g. neuroglial cysts
3. Destructive cysts: pontocerebellar hypoplasia
4. Malformative cysts: congenital muscular dystrophies,
Aicardi syndrome, GPR56 mutation, LAMA1 mutation
5. Cysts associated with cerebellar dysplasia: Cohen
syndrome, disruptive
6. Various: leukoencephalopathy with calcifications and
cysts, early-onset multiple carboxylase deficiency
Boltshauser E et al, Cerebellum, 2015
©AP
Pattern-recognition approach for
cerebellar cysts: What to look for
1. Cyst location: cortical/subcortical, within the white
matter, focal, or widespread
2. Cerebellar morphology: areas of cortical dysplasia,
hypoplasia
3. Brainstem morphology: hypoplastic pons, clefts, tectal
dysplasia, and kinking
4. Supratentorial abnormalities: migration anomalies, white
matter changes, cysts within the white matter,
hydrocephalus
5. Clinics: muscle involvement, ataxia, ocular motor
apraxia, intellectual disability, and ophthalmological
abnormalities
©AP
1. Cysts involving normal structures
• Cystic dilatation of cerebellar perivascular spaces
(PVS) in mucopolysaccharidoses:
– Particularly types 1 and 2, also seen in type 3 Sanfilippo
– Location: hilus of the dentate nucleus and the
surrounding cerebellar white matter
– Typical constellation: cystic PVS dilatations in the region
of the dentate nucleus/cerebellar white matter in an
otherwise normal cerebellum
– Diagnosis not problematic considering the overall
clinical and neuroimaging aspects (PVS dilatation, white
matter changes, ventriculomegaly, cortical atrophy)
Alqahtani E et al, Eur J Paediatr Neurol, 2014
©AP
1. Cysts involving normal structures
Axial (a), coronal (b) and sagittal (c) T2-weighted MR images of a 13-year-old child
with MPS type 1. Enlargement of the PVS is present within the dentate nuclei and
surrounding white matter (white arrows). In addition, the PVS are enlarged in the
periventricular and subcortical white matter, corpus callosum, basal ganglia, and
thalami. Ventriculomegaly, mild cerebral atrophy with enlargement of the cortical
sulci, and widening of the diploic space are also seen.
Alqahtani E et al, Eur J Paediatr Neurol, 2014
©AP
1. Cysts involving normal structures
Axial T1-weighted (A), axial FLAIR (B), and coronal T2-weighted (C) MR images
of a 10-year-old child with MPS 3A (Sanfilippo) show enlarged perivascular
spaces in the bilateral cerebellar white matter and adjacent dentate nuclei
(arrows). Marked supratentorial atrophy is also noted (C).
Courtesy of Asim F. Choudhri, MD, Le Bonheur Children’s Hospital, Memphis, TN
©AP
2. Isolated cysts
• Neuroepithelial cysts:
– Benign fluid-containing smooth, round, or ovoid
cavities that occur throughout the entire neuraxis
(most are supratentorial)
– No calcifications or hemorrhage
– Rarely space-occupying in the posterior fossa
– Typical constellation: mostly single cyst in the white
matter, usually an incidental finding in a normal
cerebellum
©AP
3. Destructive cerebellar cysts
• Pontocerebellar hypoplasia:
– Low prevalence, mostly type 2, but also reported in
type 1 and 6
– Location: lateral aspects of the hemispheres
– Size: large
– Pathology: reactive astrocytes and macrophages at
the border of the cysts  destructive process
– Typical constellation: few cysts in the lateral aspects
of the cerebellar hemispheres in a severely abnormal
cerebellum, dominated by atrophy (hemispheres >>
vermis), and pontine hypoplasia
Barth PG et al, Acta Neuropathol, 2007
©AP
3. Destructive cerebellar cysts
Sagittal T1-weighted inversion recovery MR images of a 12-month-old child with
pontocerebellar hypoplasia type 2 and TSEN54 mutation show large cysts in the
cerebellar vermis (B) and hemispheres (C).
Namavar Y et al, Brain, 2010
©AP
3. Destructive cerebellar cysts
Coronal T2-weighted MR-image
of a 1-month-old child with
pontocerebellar hypoplasia type
1 and EXOSC3 mutation show
large cysts in the lateral aspects
of the cerebellar hemispheres.
Coronal T1-weighted MR images of a child with
pontocerebellar hypoplasia type 6 and RARS2
mutation at the age of 5 days (D) and 5 weeks (E)
show large cysts in the lateral aspects of the
cerebellar hemispheres and a butterfly pattern. In
addition, a progressive volume loss of the
cerebellum and cerebrum is noted over time.
Glamuzina E et al, J Inherit Metab Dis, 2012; Eggens VR et al, OJRD, 2014
©AP
4. Malformative cysts
• Congenital muscular dystrophies (CMD):
– Mostly seen in α-dystroglycanopathies, but rare in
LAMA2 mutations (merosin-negative CMD)
– α-dystroglycanopathies:
• Clinically heterogeneous including Walker-Warburg syndrome,
(WWS), muscle-eye-brain disease (MEB), and Fukuyama CMD
• Genetically heterogenous: associated with 17 genes
• Characterized by:
– Muscle weakness, hypotonia, contractures
– Brain malformations such as cobblestone brain, cerebellar and
brainstem anomalies  impaired cognitive and motor development,
seizures
– Eye involvement such as retinal dysplasia and microophthalmia
©AP
4. Malformative cysts
• Cerebellar cysts in α-dystroglycanopathies:
– Location: cortical/subcortical in vermis
(anterior/superior part) and hemispheres
(posterior/superior part)
– Associated with cerebellar dysplasia
– Typically not seen on fetal and neonatal images, but
only on follow-up studies
– Pathology: formed from the subarachnoid spaces
engulfed by the dysplastic cerebellar folia
– Phenotype: mostly in MEB and Fukuyama CMD, rare
in WWS
©AP
4. Malformative cysts
• Cerebellar cysts in α-dystroglycanopathies:
– Genetics: mostly associated with mutations in FKTN,
FKRP, POMGnT1, LARGE, ISPD, TMEM5, GMPPB,
POMT1, POMT2
– Typical constellation: cerebellar cysts with a cortical/
subcortical predilection in a hypoplastic and dysplastic
cerebellum, often accompanied by brainstem
anomalies (pontine hypoplasia and clefts), in various
combinations with supratentorial abnormalities
(migration abnormalities, white matter signal changes,
ventriculomegaly)
©AP
4. Malformative cysts
A
B
C
D
Sagittal (A), axial (B,C), and coronal (D) T2-weighted MR images of a 5-month-old
child with MEB and POMGnT1 mutation show multiple cortical/subcortical cysts in
the cerebellar vermis and both cerebellar hemispheres, cerebellar dysplasia,
hypoplasia of the cerebellar vermis, flattened pons with a concave posterior border
and dorsal and ventral clefts, enlarged dysplastic tectum, polymicrogyria with frontooccipital gradient, thin corpus callosum, diffusely abnormal high signal intensity of
the white matter, and ventriculomegaly.
©AP
4. Malformative cysts
• Aicardi syndrome (OMIM 304050):
– “Classical” triad of infantile spasms, corpus callosum
dysgenesis, and chorioretinal lacunae
– Additional imaging findings: interhemispheric cysts,
polymicrogyria, subependymal and cortical heterotopias,
tectal dysplasia, inferior vermis hypoplasia, and
dysplastic or hypoplastic cerebellar hemispheres
– Cerebellar cysts in about 20% of patients
– Typical constellation: female infant with infantile spasms,
retinal abnormalities, and combination of supratentorial
(callosal dysgenesis) and infratentorial abnormalities
Hopkins B et al, Am J Med Genet A, 2008
©AP
4. Malformative cysts
Midsagittal (A), axial (B), and coronal (C) T2-weighted MR images of a 2-monthold female infant with Aicardi syndrome show agenesis of the corpus callosum,
supratentorial migration abnormalities, right intraventricular cysts, tectal
dysplasia, and cerebellar hypoplasia and dysplasia. A right microophthalmia and
coloboma are seen.
©AP
4. Malformative cysts
• Mutations in GPR56 (OMIM 615752):
– Clinic: motor and cognitive delay, seizures, ataxia, nystagmus
– Neuroimaging: generalized (antero-posterior gradient) or
fronto-parietal polymicrogyria, patchy or diffuse white
matter changes, cerebellar dysplasia
– Cerebellar cysts: common, subpial and cortical location in the
vermis and cerebellar hemispheres
– Typical constellation: multiple cysts associated with
cerebellar dysplasia, abnormalities of the supratentorial
white matter, and cortical architecture in a child with
seizures and intellectual disability
Bahi-Buisson N, Brain, 2010
©AP
4. Malformative cysts
A
B
C
Midsagittal (A) and axial (B,C) T2-weighted MR images of a 3.5-year-old boy
with GPR56 mutation show multiple small cysts in the cerebellar vermis and
posterior parts of the cerebellar hemispheres, diffuse cerebellar dysplasia,
extensive, bilateral polymicrogyria, hyperintense signal of the periventricular
white matter, and mild ventriculomegaly.
©AP
4. Malformative cysts
• Mutations in LAMA1 (OMIM 615960):
– Clinic: ataxia, intellectually disability, ocular motor apraxia,
severe myopia (inconsistent), retinal abnormalities (inconsistent)
– Neuroimaging: cerebellar dysplasia, vermis hypoplasia, abnormal
shape of the fourth ventricle
– Cerebellar cysts: common, cortical/subcortical in the vermis
(anterior/superior part) and cerebellar hemispheres
(posterior/superior part)
– Typical constellation: multiple cortical/subcortical cysts in the
vermis and hemispheres with cerebellar dysplasia, vermis
hypoplasia, and no supratentorial abnormalities
Aldinger KA, Am J Hum Genet, 2014; Poretti A et al, Cerebellum, 2014
©AP
4. Malformative cysts
A
B
C
Midsagittal (A), axial (B), and coronal (C) T2-weighted MR images of a 3.8-yearold boy with LAMA1 mutation show multiple cortical/subcortical cysts located
within the cerebellar vermis (anterior and superior part) and both cerebellar
hemispheres (posterior and superior parts), hypoplasia of the vermis, cerebellar
dysplasia, enlarged fourth ventricle with a peculiar elongated and squared
shape, mildly elongated midbrain, and a short pons.
©AP
5. Cerebellar cysts in cerebellar dysplasia
• Cerebellar dysplasia = deranged development of
the cerebellar tissue resulting in abnormal
cerebellar foliation, fissuration, and white matter
arborization
• Etiology = heterogeneous (genetic and acquired
causes), unknown in the majority of patients
• Typical constellation: cerebellar dysplasia is the
dominant feature; cysts: cortical/subcortical,
confined to dysplastic areas, most likely in the
upper vermis and hemispheres, diffuse or focal
©AP
5. Cerebellar cysts in cerebellar dysplasia
• Cohen syndrome (OMIM 216550):
– Clinic: non-progressive mental retardation,
microcephaly, hypotonia, and characteristic facial
features (high-arched eyelids, short philtrum, thick
hair, and low hairline)
– Neuroimaging: large corpus callosum, cerebellar
hypoplasia, cerebellar dysplasia (exceptional)
– Genetic: mutations in VPS13B
– Cerebellar cysts: exceptional, cortical/subcortical
within the vermis and cerebellar hemispheres
Kivitie-Kallio S et al, Neuropediatrics, 1998
©AP
5. Cerebellar cysts in cerebellar dysplasia
A
B
C
Midsagittal (A), axial (B), and coronal (C) T2-weighted MR images of a 6.8-yearold boy with Cohen syndrome and VPS13B mutation show global cerebellar
dysplasia and hypoplasia as well as multiple cortical/subcortical cysts located
within the cerebellar vermis (anterior and superior part) and both cerebellar
hemispheres (posterior and superior parts).
Courtesy of G. Christoph Korenke, MD, Children’s Hospital, Oldenburg, Germany
©AP
5. Cerebellar cysts in cerebellar dysplasia
• Bilateral cerebellar dysplasia with cysts:
– Clinic: variable, including developmental delay or
non-progressive ataxia
– Neuroimaging: bilateral cerebellar dysplasia and cysts
– Etiology: unknown, most likely malformative
– Cerebellar cysts: multiple, cortical/subcortical within
the vermis and cerebellar hemispheres
©AP
5. Cerebellar cysts in cerebellar dysplasia
A
B
C
Midsagittal (A), axial (B), and coronal (C) T2-weighted MR images of an 11-yearold girl with non-progressive cerebellar ataxia show multiple small cortical/
subcortical cysts in the upper and posterior parts of the cerebellar hemispheres
and a diffuse cerebellar dysplasia with disorganized cerebellar foliation and
fissuration as well as irregular white matter arborization.
©AP
5. Cerebellar cysts in cerebellar dysplasia
A
B
C
Midsagittal (A), axial (B), and coronal (C) T2-weighted MR images of a 4-monthold boy with hypotonia, bilateral ptosis, and unilateral congenital third nerve
palsy show multiple small cortical/subcortical cysts in the posterior and lateral
aspects of the cerebellar hemispheres and cerebellar dysplasia. In addition,
absence of the olfactory bulb and multiple periventricular heterotopias were seen
in this child (not shown).
©AP
5. Cerebellar cysts in cerebellar dysplasia
• Unilateral cerebellar dysplasia with cysts:
– Clinics: variable, including developmental delay or
non-progressive ataxia; imaging findings may be
“incidental”
– Neuroimaging: unilateral cerebellar dysplasia and
cysts in a cerebellar hemisphere of reduced volume
– Etiology: unknown, most likely disruptive in view of
the “focal” nature of the anomalies
– Cerebellar cysts: cortical/subcortical within a small
cerebellar hemisphere with focal dysplasia
©AP
5. Cerebellar cysts in cerebellar dysplasia
A
B
Axial (A) and coronal (B) T2-weighted MR images of a 6-year-old boy with history
of motor delay, moderate truncal ataxia, right predominant dysmetria, and
normal cognitive functions show a markedly smaller and dysplastic right
cerebellar hemisphere with multiple small cortical/subcortical cysts.
©AP
5. Cerebellar cysts in cerebellar dysplasia
A
B
C
Axial (A) and coronal (B,C) T2-weighted MR images of an 11-year-old girl with the
history of multiple hospital admissions for functional complaints including headache
show a mild reduction in volume and dysplasia (irregular cerebellar foliation and
white matter arborization) of the right cerebellar hemisphere and few small cysts in
the upper and medial part of the right cerebellar hemisphere. These findings are
considered “incidental” in view of the clinical presentation.
©AP
6. Others
• Leukoencephalopathy with
calcifications and cysts
(OMIM 614561):
– Clinic: spasticity, dystonia,
seizures, and cognitive decline
– Neuroimaging: white matter
changes, intracranial
calcifications, and enlarging
brain cysts
– Cerebellar cysts: uncommon,
postcontrast enhancement of
the cyst wall
Livingston JH et al, Neuropediatrics, 2014
• Early-onset multiple
carboxylase deficiency
(OMIM 253270):
– Disorder of biotin metabolism
– Clinic: lactic acidosis, alopecia,
keratoconjunctivitis, perioral
erosions, and seizures
– Neuroimaging: cerebral
atrophy, ventriculomegaly
– Cerebellar cysts: exceptional
Tsutsumi Y et al, Ultrasound Obstet Gynecol, 2010
©AP
Take-home messages
1. Cerebellar cysts  rare finding with different
pathomechanisms
2. Correct diagnosis  essential for optimal therapy,
accurate prognosis, and genetic counseling
3. Neuroimaging  key role in the diagnostic work-up
4. Imaging based pattern-recognition approach taking
into account clinical information  very helpful for
correct diagnosis
©AP