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Rhombencephalosynapsis:
Review of Cerebellar Embryology, Key Imaging
Findings and Associated Anomalies
eEdE-175
Abhijit Y. Patil, M.D.*
Vinay Kandula, M.D. +
Michael Benstock, M.D.#
Hemant A. Parmar, M.D.*
*Department of Neuroradiology, University of Michigan Health System, Ann Arbor, MI
+
Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE
#
Bryn Mawr Hospital, Bryn Mawr, PA
Disclosure
Authors have no relevant financial disclosures
Purpose
Rhombencephalosynapsis is a rare congenital malformation
characterized by fusion of the cerebellar hemispheres and absence
of the cerebellar vermis
The exhibit will allow radiologists to:
 Identify classic features of rhombencephalosynapsis
 Recognize associated abnormalities such as aqueductal stenosis
and other supratentorial anomalies
 Be familiar with associated syndromes like Gómez-LópezHernández syndrome and VACTERL
 Improve communication with pediatric neurologist
Approach
 After discussing normal cerebellar development and anatomy, five
cases of rhombencephalosynapsis ranging from a newborn to an
adult patient are presented to illustrate key imaging findings and
associated anomalies
 The cases include isolated rhombencephalosynapsis as well as
cases with associated supratentorial anomalies such as aqueductal
stenosis and septo-optic dysplasia
 Diffusion tensor imaging illustrating cerebellar fusion is shown for
one patient
Cerebellar Anatomy: Landmarks
1.
2.
3.
4.
5.
6.
7.
8.
Quadrigeminal plate
Cerebral aqueduct
Fourth ventricle
Vermis
Cerebellar tonsil
Pons
Tentorium cerebelli
Superior medullary
velum
Cerebellar Anatomy: Landmarks
1. Vermis
2. White matter of cerebellar
hemisphere
Cerebellar Anatomy: Fissures
Primary Fissure (yellow arrow)
Horizontal Fissure (blue arrow)
Suboccipital Fissure (green arrow)
Cerebellar Anatomy: Lobes
Anterior Lobe: Anterior to
the primary fissure
Posterior Lobe: Posterior
to the primary fissure
Flocculonodular Lobe:
Anterior to the
posterolateral fissure
* Posterolateral fissure
Cerebellar Anatomy: Nuclei
Dentate Nucleus: Responsible for
the planning, initiation and control of
voluntary movements. Efferent
fibers from this travel through red
nucleus to contralateral ventrolateral
thalamus
Interposed Nucleus*: Consists of
globose and emboliform nuclei.
Send efferent fibers to contralateral
red nucleus. Origin for the
rubrospinal tract that mainly
influences limb flexor muscles
Fastigial Nucleus *: Afferents from
vermis. Efferents via inferior
cerebellar peduncle to vestibular
nuclei
Cerebellar Anatomy: Peduncles
Superior Cerebellar Peduncle *:
Primary output of the cerebellum with
mostly fibers carrying information to the
midbrain. Most efferent fibers travel in
this and arise from dentate nucleus
(Tonsil *)
Middle Cerebellar Peduncle *: Carry
input fibers from the contralateral
cerebral cortex. Cortico-pontocerebellar form major fibers
(Flocculus*)
Inferior Cerebellar Peduncle:
Connects the spinal cord and medulla
oblongata with the cerebellum. Contain
dorsal spinocerebellar tract,
olivocerebellar and vestibulocerebellar
tracts
Afferent fibers are far more numerous that efferent fibers by a ratio of 40:1
Cerebellar Embryology
 The cerebellum represents a specific development of the alar plate from the
rhombic lips of the metencephalon
 At 50 days, the pontine flexure folds the metencephalon back against the
myelencephalon. The rhombic lips of the pontine flexure will give rise to the
cerebellum
 The caudal region of the cerebellar primordia forms the more primitive
flocculonodular lobe, whereas the cranial region produces the much larger (and
less primitive) vermis and cerebellar hemispheres
Rhombencephalosynapsis: Discussion
 Rhombencephalosynapsis (RES) is a rare midline brain
malformation defined by fusion of the cerebellar hemispheres with
partial or complete absence of the intervening vermis
 RES is a rare condition. Approximately 150 cases have been
reported in the literature to date
 RES was first described by Obersteiner in 1914 from a routine
autopsy of a 24-year-old male suicide victim
 RES is probably due to an exaggerated fusion of the two lateral
cerebellar primordia. The cause of this exaggerated fusion,
associated with a failure of vermian differentiation, is unknown
 The anomaly is mostly sporadic. Although genetic basis has been
suggested based on clinical observations, no single genetic cause
has been ascertained
Clinical Presentation of RES
 Clinical presentation is variable due to associated supratentorial
anomalies. This may account for the variable age difference at
presentation in our cases
 Wide spectrum of clinical presentation from symptoms such as
generalized hypotonia, nystagmus, ataxia, mild to severe mental and
motor developmental delays and early death, to a few reported cases
diagnosed at a late age without significant associated clinical findings
Complete vs. Partial RES
 Rhombencephalosynapsis can be considered an anomaly with variable degrees
of severity as partial RES has been reported in the literature
 Complete RES: total absence of the vermis with complete fusion of cerebellar
hemispheres
 Partial RES: retained parts of the anterior and posterior vermis including the
nodulus, with partly unfused cerebellar hemispheres
 One of the cases discussed in this review (Case #3) also demonstrated imaging
findings suggestive of partial RES, similar to previously reported cases with
fused posterior cerebellar hemispheres, unfused hemispheres anteriorly with
intervening anterior vermis, presence of primary fissure as well as normal 4th
ventricle fastigial recess
 Partial RES can be explained by an alternative model of cerebellar development
that considers RES as a failure of vermian differentiation with undivided
development of the cerebellar hemispheres. This model considers cerebellar
primordium as an unpaired structure where the posterolateral fissure is formed
initially with subsequent development of the posterior vermis before the anterior
vermis
Imaging Findings of RES: Sagittal
 Partial or complete absence of
vermis
 Abnormal shape of 4th ventricle *
 Absent flow void of aqueduct
(yellow arrow)
 Absence of fissures
 Absent primary fissure
(green arrow)
 Absent suboccipital fissure
(red arrow)
 Hydrocephalus due to
aqueductal stenosis *
Imaging Findings of RES: Axial
 Continuity of transverse folia
across midline without
intervening vermis (red arrow)
 Continuity or apposition of
middle cerebellar peduncles
 Fusion or apposition of dentate
nuclei (blue arrow)
 Keyhole or teardrop shape of 4th
ventricle due to absence of
vermis
Imaging Findings of RES: Coronal
 Fusion of inferior colliculli
 Fusion or approximation of
superior cerebellar peduncles
 Continuity of normal appearing
transverse folia across midline
without intervening vermis
(yellow arrow)
Neuropathological studies
 Total or partial absence of the cerebellar vermis, including its
lobules
 Absent fastigial nuclei
 Fusion of cerebellar hemispheres across midline without cleft
 Reduced transverse diameter of the cerebellum
 Fusion or close approximation of dentate nuclei
 Nodulus preserved in subtotal rhombencephalosynapsis
 Present globose and emboliform nuclei
 Presence of flocculi
Neuropathological studies: contd.
 Absent incisura cerebelli posterior
 Absent anterior medullary velum
 Normal appearing major sulci
 Normally oriented folia that are fused across midline
 Absence or abnormality of olivary complexes
 Midline facial anomalies
Associated Abnormalities
Prognosis and severity of clinical presentation depends on
associated supratentorial anomalies
 Hydrocephalus : most common
associated anomaly
 In majority of cases due to aqueductal
stenosis (green arrow)
 In a study by Ishak et. al., aqueductal
stenosis was present in 22 of 42
subjects and was strongly associated
with the degree of cerebellar fusion
 Other less common reported causes of
hydrocephalus include: thalamic fusion
and obstruction of 4th ventricle by
cerebellar tissue
Imaging pearl: In patients with aqueductal stenosis, look for presence of RES
Associated Abnormalities
 Absence of septum pellucidum (arrow)
 2nd most common associated abnormality
 Septo-optic dysplasia has been reported
 Other associated midlines defects such as fusion of fornices have been
reported
Associated Abnormalities
 Dysgenesis of corpus callosum (yellow arrow)
 Can be associated with septal aplasia
Other Associated Abnormalities
 Holoprosencephaly
 Absent olfactory bulbs
 Fusion of thalami
 Neural tube defects
 Neurocortical dysplasia
Associated Syndromes
Gómez-López-Hernández syndrome (GLHS)
(aka Cerebello-trigeminal-dermal-dysplasia)
 Craniosynostosis causing tower-like skull
 Trigeminal anesthesia
 Rhombencephalosynapsis
 Bilateral parietal or temporal alopecia
 Mental retardation, delayed speech
 Imaging Pearls:
 Look for rhombencephalosynapsis in cases highly suggestive of GLHS
 If rhombencephalosynapsis is diagnosed, the clinical signs of GLHS
should be sought
Associated Syndromes
VACTERL association
 Frequent occurrence of Vertebral anomalies, Anal atresia,
Cardiovascular anomalies, Trachea-oesophagEal fistula, Renal
anomalies, Limb defects (VACTERL) as associated findings with RES
has been reported
Case 1: MRI brain at day 1 and CT at 8 months
Axial T2WI MR (a) shows transverse folia (red arrow) and fusion of dentate nuclei
(blue arrow). Sagittal T2W MR (b) in the same child shows moderate to severe
enlargement of the lateral ventricles (*), and to a lesser degree the third ventricle (*).
There is stenosis at the cerebral aqueduct (green arrow) , with absence of the normal
flow void. The fourth ventricle is normal in size. Absence of the primary fissure (yellow
arrow) in a child with Rhombencephalosynapsis (RES). RES is complete in this child.
Axial CT (c) also clearly depicts fusion of cerebellar hemispheres (white arrow).
Case 2: MRI brain at 2 years of age
Sagittal T2W MR (a) shows absence of the primary fissure (yellow arrow) in a child
with isolated Rhombencephalosynapsis (RES). Foliation is that of the cerebellar
hemisphere as no vermis is present. Note prominent corpus medullare (*).
Coronal T2W MR (b) shows transverse folia (red arrow) and interfoliate sulci (green
arrow) in the same child. RES is complete in this child. (c) DTI showing transverse
fibers across the cerebellar hemispheres (white arrow).
Case 3: MRI brain at 9 years of age
Coronal T2W MR (a) shows fusion of cerebellar hemispheres posteriorly with
continuous transversely oriented folia and fissures extending across the midline (yellow
arrow) in a child with partial Rhombencephalosynapsis (RES). Coronal T2W MR (b)
shows unfused cerebellar hemispheres anteriorly with intervening anterior vermis (blue
arrow). Sagittal T1W MR (c) shows presence of normal primary fissure (green arrow),
however, absence of prepyramidal fissure (red arrow). There is normal 4th ventricle
fastigial recess (*). Atrophy of corpus callosum (*) as a result of old stroke
superimposed on dysgenesis of corpus callosum with associated Wallerian
degeneration (white arrow) in brainstem.
Case 4: MRI brain at 10 years of age
Sagittal T2W MR (a) shows dysgenesis of corpus callosum (yellow arrow) in a child
with complete Rhombencephalosynapsis (RES). Primary fissure (green arrow) and
prepyramidal fissure (red arrow) are absent. Axial T2W image (b) showing absence
of septum pellucidum (white arrow). Coronal T1WI MR (c) shows associated mildly
hypoplastic optic chiasm (blue arrow).
Case 5: MRI brain at 28 years of age
Sagittal T1W MR (a) shows aqueductal stenosis (yellow arrow) causing hydrocephalus
with enlarged lateral ventricles (*) in an adult with complete Rhombencephalosynapsis
(RES). Absence of the primary fissure (green arrow) and prepyramidal fissure (red
arrow) is also seen. There is rounded 4th ventricle fastigial recess (*) secondary to
hypoplasia of nodulus. Coronal T2WI MR (b) shows fusion of cerebellar hemispheres
and continuous transversely oriented folia and fissures extending across the midline
without intervening vermis (blue arrow). Axial T2W image (c) showing fused dentate
nuclei without intervening vermis (white arrow).
Conclusion
 Rhombencephalosynapsis (RES) although a rare congenital
disorder, can be encountered in pediatric as well as occasionally in
adult patients
 RES is prone to be underreported due to radiologists’ relative lack
of awareness of this condition
 Familiarity with classic imaging findings, associated supratentorial
anomalies and related syndromes will allow correct identification
and reporting of this rare condition
References
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8. Ishak GE, Dempsey JC, Shaw DWW, Tully H, Adam MP, Sanchez-Lara PA, et al. Rhombencephalosynapsis: an
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Contact Information
Abhijit Y. Patil, M.D.
Fellow, Neuroradiology Division
Dept. of Radiology, University of Michigan
1500 E. Medical Center Drive, UH B2-A209,
Ann Arbor, MI 48109-5030
E-mail: [email protected]