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

Authors have no relevant financial disclosures

Disclosure

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-López-Hernández syndrome and VACTERL

Improve communication with pediatric neurologist

Purpose

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

Approach

Cerebellar Anatomy: Landmarks

1. Quadrigeminal plate2. Cerebral aqueduct 3. Fourth ventricle4. Vermis5. Cerebellar tonsil6. Pons7. Tentorium cerebelli8. Superior medullary

velum

Cerebellar Anatomy: Landmarks

1. Vermis2. 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-ponto-cerebellar 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

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

Prognosis and severity of clinical presentation depends on associated supratentorial anomalies

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

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 1: MRI brain at day 1 and CT at 8 months

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 2: MRI brain at 2 years of age

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).

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

Conclusion

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References

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: abhijitp@med.umich.edu