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(36-34) Elevated torcular , steeply angled TS, superiorly rotated hypoplastic cerebellar vermis , and hydrocephalus reveal DWM.

(36-35A) Autopsy of DWC shows mildly hypoplastic, superiorly rotated vermis , 4th ventricle open dorsally to a large CSF cyst .

Hindbrain Malformations

Cystic Posterior Fossa Anomalies and the

Dandy-Walker Continuum

Terminology

The Dandy-Walker continuum (DWC) is a spectrum of anomalies that includes Dandy-Walker malformation (DWM), vermian hypoplasia (VH), Blake pouch cyst (BPC), and mega cisterna magna (MCM). Two measurements are important in distinguishing these entities: (1) the tegmento-vermian angle (the angle formed by lines along the anterior surface of the vermis and the dorsal surface of the brainstem, normally < 18°) and (2) the fastigium-declive line (a line drawn from the fastigium—the dorsal "point" of the 4th ventricle on sagittal images—and the dorsal most point of the vermis) (36-2).

Dandy-Walker malformation (DWM) is a generalized disorder of mesenchymal development that affects both the cerebellum and overlying meninges. It consists of a large PF with a high-inserting venous sinus confluence, large PF pia-ependyma-lined cyst extending dorsally from the fourth ventricle, and varying degrees of vermian and cerebellar hemispheric hypoplasia (36-34). The fourth ventricle choroid plexus is absent.

Vermian hypoplasia (VH) is part of the DWC spectrum. There is superior rotation of the vermis, increased tegmento-vermian angle (18-45°), and variable cerebellar hypoplasia (diminished vermian volume below the fastigium-declive line). The overall posterior fossa volume is normal in VH.

Blake pouch cyst (BPC) is an ependyma-lined protrusion of the fourth ventricle through the foramen of Magendie into the retrovermian cistern. The fourth ventricle choroid plexus is present but displaced into the superior cyst wall. The tegmento-vermian angle is increased, but the vermis is normal in size and configuration. The fourth ventricle has a "key hole" appearance.

Mega cisterna magna (MCM) is an enlarged retrocerebellar CSF collection (> 10 mm). There is no mass effect on the cerebellar hemispheres or vermis. The vermis is normal as is the tegmento-vermian angle (< 18°). Cerebellar veins and elements of the falx cerebelli can be seen crossing through the MCS.

(36-35B) DWC shows normal 4th ventricle flooropening through widened vallecula into a dorsal cyst . (Courtesy R. Hewlett, MD.)

Etiology

Embryology. If (1) the anterior membranous area of the embryonic fourth ventricle fails to incorporate properly into the choroid plexus or (2) there is delayed opening of the foramen of Magendie, CSF pulsations cause the nonintegrated anterior membranous area to balloon posteriorly within the PF. This large CSF-filled cyst does not communicate with the subarachnoid space.

Etiology and Genetics. Three main DWM causative genes have been identified: FOXC1 on chromosome 3q24 and the linked ZIC1 and ZIC4 genes on chromosome 6q25.3. Each member of the ZIC gene family encodes a highly related zinc-finger transcription factor that is broadly expressed throughout cerebellar development. Both ZIC1 and ZIC4 have key roles in the regulation of both cerebellar size and normal cerebellar foliation. Zic proteins compete or interact with Gli proteins to regulate Shh signaling, which is crucial for normal cerebellar development.

DWM is accompanied by more than 18 types of chromosomal abnormality and co-occurs with more than 40 genetic syndromes. In addition, DWM can

arise as a result of maternal diabetes, use of warfarin, or fetal infection by cytomegalovirus, rubella, or Zika virus.

Known clinical associations with DWM include PHACES, neurocutaneous melanosis (Figure 39-67), midline anomalies, and trisomy 18.

Pathology

Gross Pathology. The most striking gross findings in DWM are (1) an enlarged PF with (2) upward displacement of the tentorium and accompanying venous sinuses and (3) cystic dilatation of the fourth ventricle. Vermian abnormalities range from complete absence to varying degrees of hypoplasia. In DWM, the 4th ventricle choroid plexus is absent.

DWM is frequently associated with other CNS anomalies. Almost two-thirds of patients have gyral abnormalities (e.g., pachyor polymicrogyria and heterotopic GM). Callosal dysgenesis is common. Craniofacial, cardiac, and urinary tract anomalies are frequent.

Microscopic Features. The PF cyst in DWM is typically lined by two layers: an outer layer of pia-arachnoid and an inner layer of ependyma. Occasionally, microscopic remnants of cerebellar tissue are present in the cyst wall.

Clinical Issues

Epidemiology and Demographics. DWM is the most common congenital cerebellar malformation with an estimated prevalence of 1:5,000 live births. There is a slight female predominance (F:M = 1.5-2:1).

Presentation. The most common presentation of DWM is increased intracranial pressure secondary to hydrocephalus. Despite the extensive cerebellar abnormalities, cerebellar signs are relatively uncommon.

Natural History. Early death is common in classic DWM. If DWM is relatively mild and uncomplicated by other CNS anomalies, intelligence can be normal and neurologic deficits minimal.

Treatment Options. CSF diversion, usually ventriculoperitoneal shunting with or without cyst shunting or marsupialization, is the standard treatment for DWM-related hydrocephalus.

Imaging

The spectrum of imaging abnormalities in DWM is broad, affecting—to varying degrees—the skull and dura, ventricles and CSF spaces, and brain.

Skull and Dura, Venous Sinuses. In contrast to CM2, in which the PF is abnormally small, the PF in DWM is strikingly enlarged. The straight sinus, sinus confluence, and tentorial apex are elevated above the lambdoid suture ("lambdoid-torcular inversion"). The transverse sinuses descend at a steep angle from the torcular herophili toward the sigmoid sinuses (36-36).

The occipital bone may appear scalloped, focally thinned, and remodeled with all posterior fossa cysts. Retrocerebellar CSF cysts (formerly termed "mega cisterna magna") often demonstrates partially infolded duraarachnoid (falx cerebelli) on axial T2 scans. The falx cerebelli is usually absent in DWM.

Ventricles and Cisterns. The floor of the fourth ventricle is present and appears normal in DWM. The anterior medullary velum and fastigium are absent. The choroid plexus is absent, and the fourth ventricle opens dorsally to a variably sized CSF-containing cyst that balloons posteriorly behind and between the cerebellar hemisphere remnants.

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(36-36A) DWM shows large PF cyst elevating torcular , superiorly rotated vermian remnant, small pons, dysgenetic corpus callosum .

(36-36B) Axial T2WI in DWM shows 4th ventricle open dorsally to the large PF cyst. Cerebellar hemispheres are small, "winged" anteriorly .

(36-36C) Axial T2WI in the same case shows callosal dysgenesis with polymicrogyria .

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Generalized obstructive hydrocephalus is present in over 80% of neonates with DWM at birth. If callosal dysgenesis is present, the lateral ventricles are widely separated and may have unusually prominent occipital horns (colpocephaly).

In DWC (previously called Dandy Walker "variant"), the fourth ventricle has a "keyhole" configuration on axial imaging caused by a widely patent vallecula that communicates with a prominent cisterna magna (36-37) (36-38).

BPC is an ependyma-lined protrusion from the fourth ventricle. The vermis is normal in size and morphology but is elevated and superiorly rotated with increased tegmentovermian angle (18-45°). The posterior fossa is normal in size.

The fourth ventricle is normal in retrocerebellar arachnoid cysts and shows a normal fastigium (dorsal point) on sagittal MR scans.

Brainstem, Cerebellum, and Vermis. The brainstem appears normal in mild forms of DWM but often appears somewhat small in moderate to more severe DWM.

The vermis is normal in BPC and retrocerebellar arachnoid cysts. Varying degrees of vermian hypoplasia are seen in DWM (36-39) (36-40). The inferior lobules are often hypoplastic in mild DWC. In classic DWM, the vermian remnant is rotated and elevated above the large PF cyst.

The cerebellar hemispheres appear normal in VH and BPCs but are hypoplastic in DWM. In severe cases of DWM, the cerebellar remnants appear "winged" outward and displaced anterolaterally.

Retrocerebellar arachnoid cysts exert mass effect on the cerebellar hemispheres, which otherwise appear normal in morphology.

Associated Abnormalities. Other CNS abnormalities are present in 70% of DWM. The most common finding is callosal agenesis or dysgenesis. A dorsal interhemispheric cyst may be present. Gray matter abnormalities (e.g., heterotopias, clefts, and pachyand polymicrogyria) are common associated abnormalities.

DANDY-WALKER CONTINUUM (DWC): DIFFERENTIAL DIAGNOSIS

Dandy-Walker Malformation (DWM)

•Large posterior fossa (PF)

•Cyst extending posteriorly from fourth ventricle

•Vermian agenesis or hypogenesis

○Seriously increased tegmento-vermian angle ( > 45°)

•Torcular-lambdoid inversion

Vermian Hypoplasia (VH)

•Old term = Dandy-Walker variant

•Reduced vermian tissue below fastigium-declive line

•Superior rotation of vermis

○Increased tegmento-vermian angle (18-45°)

•PF normal size

Blake Pouch Cyst (BPC)

•Ependyma-lined protrusion from fourth ventricle

•Normal size and morphology of vermis

•Elevated vermis

○Increased tegmentovermian angle (18-45°)

Mega Cisterna Magna (MCM)

•Enlarged retrocerebellar CSF (> 10 mm)

•No mass effect on vermis or cerebellum

•Normal vermis

○Tegmento-vermian angle < 18°

•Fluid crossed by veins, falx cerebelli

•May scallop, remodel occiput**

○** All categories in DWC may "scallop" inner occipital bone

Arachnoid Cyst

•Not truly in the Dandy-Walker Continuum

○Cerebellopontine angle > retrovermian

•No communication with 4th ventricle

•No crossing veins or falx cerebelli

•Causes mass effect

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(36-40A) Sagittal T1WI shows mild DWC (MCM). Note thinned , scalloped occipital bone. Pons, vermis, 4th ventricle are normal.

(36-40B) Axial T2WI in the same patient shows bone "scalloping" and partially infolded duraarachnoid of falx cerebelli .

(36-44) Coronal graphic of rhombencephalosynapsis shows that no vermis is present in the midline of the cerebellum. Instead, the folia, interfoliate sulci, and cerebellar white matter are continuous across the cerebellar midline.

A retrocerebellar arachnoid cyst is not part of DWC. It is a midline arachnoid-lined cyst located behind the vermis and fourth ventricle that does not communicate with the latter.

Although there may be mass effect on the cerebellum, there is no associated hydrocephalus and no communication with the 4th ventricle. The cerebellum otherwise appears normal. Veins and a falx cerebelli do not traverse the CSF collection.

In the absence of other findings, a prominent retrocerebellar CSF collection > 10 mm with crossing vessels and a traversing falx cerebelli is most often a mega cisterna magna (MCM), a normal variant that is of no clinical significance.

Miscellaneous Malformations

A number of less common PF malformations occur. We now discuss several of those in which the abnormalities are largely defined by imaging features: rhombencephalosynapsis, Joubert syndrome, cerebellar hypoplasias, and unclassified dysplasias.

Rhombencephalosynapsis

Terminology. Rhombencephalosynapsis is a midline brain malformation characterized by (1) a "missing" cerebellar vermis and (2) apparent fusion of the cerebellar hemispheres

(36-44).

Pathology. Severity ranges from mild (partial absence of the nodulus and anterior and posterior vermis) to complete (the entire vermis, including the nodulus, is absent). Dorsal midline continuity of the cerebellar hemispheres is characteristic. The tonsils, dentate nuclei, and superior cerebellar peduncles are usually fused.

(36-45) Coronal T2WI shows classic rhombencephalosynapsis. Note absent vermis, transversely oriented folia, continuity of cerebellar white matter across the midline .

Clinical Issues. Rhombencephalosynapsis can be seen in patients with VACTERL (vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistulas, renal anomalies, and limb defects).

Imaging. Sagittal MR scans show an upwardly rounded fastigial recess of the fourth ventricle and lack of the normal midline foliar pattern of the vermis. Coronal and axial images show transverse folia and continuity of the cerebellar white matter across the midline (36-45). Images through the rostral fourth ventricle may demonstrate a diamond or pointed shape.

Aqueductal stenosis and hydrocephalus are common. Absent cavum septi pellucidi is seen in half of all cases. The thalami, fornices, and tectum may be partially or completely fused. Other forebrain anomalies include absent olfactory bulbs and corpus callosum dysgenesis.

Joubert Syndrome and Related Disorders

Terminology and Classification. Joubert syndrome (JS) and related disorders (JSRD) are a group of syndromes in which the obligatory hallmark is the "molar tooth" sign, a complex midand hindbrain malformation that resembles a molar tooth on axial MR scans.

Anomalies of the kidneys, eyes, extremities, liver, and bile ducts are common in the JSRD spectrum. Six major JSRD phenotypic subgroups are recognized: pure JS, JS with ocular defect, JS with renal defect, JS with oculo-renal defects, JS with hepatic defect, and JS with oro-facio-digital defects.

Classic JS is the "pure" syndrome. The oculo-renal form is termed CORS (cerebello-oculo-renal syndrome). JS with preaxial or mesoaxial polydactyly and orofacial defects is

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known as type 6 oro-facial-digital syndrome (OFD-6). COACH syndrome consists of cerebellar vermis hypoplasia, oligophrenia, ataxia, ocular coloboma, and hepatic fibrosis.

Etiology. With the exception of rare X-linked recessive cases, JSRD follows autosomal-recessive inheritance. Mutations in at least 10 affected genes that help regulate normal axon growth and decussation have been identified in JS and JSRD.

JSRD is genetically heterogeneous. Molar tooth disorders are, at least in part, "ciliopathies" with mutations of ciliary/centrosomal proteins that affect cell migration.

Pathology. JSRD is characterized grossly by a dysmorphic vermis with sagittal clefting, nondecussating enlarged superior cerebellar peduncles, and an elongated rounded fastigium of the fourth ventricle (36-46) (36-47). The anteroposterior diameter of the midbrain is reduced. Microscopically, dysplasias and heterotopias of the cerebellar nuclei are common.

(36-46) Axial graphic shows Joubert malformation. Thickened superior cerebellar peduncles around an elongated 4th ventricle form the classic "molar tooth" sign. Note cleft cerebellar vermis . (3647) Autopsy specimen of JSRD shows foreshortened midbrain with narrowed isthmus, thick superior cerebellar peduncles , "bat wing" 4th ventricle, and clefted superior vermis . (Courtesy R. Hewlett, MD.)

(36-48A) Sagittal T2WI in a patient with classic Joubert shows small misshapen vermis , upwardly convex superior fourth ventricle , and rounded enlarged fastigial point . (36-48B) Axial scan in the same patient shows "molar tooth" sign, foreshortened midbrain with narrow isthmus , thick superior cerebellar peduncles surrounding an elongated fourth ventricle, and disorganized cleft vermis.

Clinical Issues. The estimated incidence of JSRD is 1:80,000100,000 live births. There is no sex predilection.

JSRD typically presents in infancy and childhood. Coloboma, encephalocele, and polydactyly are commonly associated with JSRD.

The classic clinical presentation is a child with developmental delay, ataxia, and oculomotor and respiratory abnormalities. Nystagmus, alternating hyperapnea and hyperpnea, and seizures are common.

Imaging. Axial NECT scans demonstrate vermian clefting and an oddly shaped fourth ventricle with a "bat wing" configuration.

MR is the cornerstone in establishing a diagnosis of JSRD. Midline sagittal scans show a small dysmorphic vermis. The fourth ventricle appears deformed with a thin upwardly

convex roof and loss of the normal pointed fastigium (3648A).

Axial scans demonstrate the classic "molar tooth" appearance with foreshortened midbrain, narrow isthmus, deep interpeduncular fossa, and thickened superior cerebellar peduncles surrounding an oblong or diamond-shaped fourth ventricle. The superior vermis is clefted, and the cisterna magna may appear enlarged (36-48B).

DTI shows that fibers of the superior cerebellar peduncles do not decussate in the mesencephalon and that the corticospinal tracts fail to cross in the caudal medulla.

Differential Diagnosis. The major imaging differential diagnosis of JSRD is vermian and pontocerebellar hypoplasia, in which the vermis is small but is not clefted. In rhombencephalosynapsis, the cerebellar hemispheres and dentate nuclei are fused across the midline, not split.

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Multiple syndromes exhibit "molar tooth" posterior fossa malformations. Genetic analysis may be required to distinguish among different JSRD subtypes.

Cerebellar Hypoplasia and Unclassified

Dysplasias

In severe cases of cerebellar hypoplasia, the cerebellar hemispheres and vermis are almost completely absent, and the pons is hypoplastic (36-49).

Unclassified cerebellar dysplasias are not associated with other known malformations or syndromes such as molar tooth malformation or Dandy-Walker continuum. A variety of findings including enlarged, vertically oriented fissures or clefts (36-50), disordered or primitive foliation, lack of normal white matter arborization, gray matter heterotopias, and small cyst-like cavities in the subcortical white matter are some of the many abnormalities seen in such cases (36-51).