02 -Disorders of Neural Tube Closure

In 1896 he described a second type of hindbrain anomaly, known as Chiari type II, in which the vermis, pons, medulla, and an elongated fourth ventricle were displaced in feriorly into th

Disorders of Neural Tube Closure

Occipital and Parietal

Sincipital and Sphenopharyngeal

Nasal Cephaloceles, Dermoids, and Gliornas

Atretic Cephaloceles

Corpus Callosum Anomalies

Corpus Callosurn Agenesis

Corpus Callosurn Liporna

The formation of the brain and spinal cord is

referred to as dorsal induction (see Table 1-1) The two

general stages of dorsal induction are primary and

secondary neurulation Primary neurulation involves the

formation of the brain and upper spine; secondary

neurulation refers to formation of the distal spine.1

Disorders of primary neurulation are mostly neural

tube closure defects and early central nervous system

(CNS) anomalies, typically occurring at around 3 or 4

gestational weeks These include Chiari malformations,

cephaloceles, and myelomeningoceles During

secondary neurulation, interactions between the

notochord and mesoderm form the skull, dura, pia, and

vertebrae These occur at 4 to 5 gestational

weeks Abnormalities of secondary neurulation result

in spinal dysraphic disorders that range from simple, isolated anomalies such as spina bifida occulta to more complex malformations such as meningocele and lipomeningocele, neurenteric cysts, dermal sinus, and the caudal regression syndromes Only the skull and brain anomalies will be discussed here; congenital anomalies of the spine and spinal cord are delineated

in Chapter 19

German pathologist Hans Chiari described congenital hindbrain anomalies in which cerebellar tissue descends into the cervical canal In 1891 he described

an anomaly, now designated as Chiari type I, consisting of elongated peglike cerebellar tonsils displaced into the upper cervical canal In 1896 he described a second type of hindbrain anomaly, known

as Chiari type II, in which the vermis, pons, medulla, and an elongated fourth ventricle were displaced in feriorly into the cervical canal.2 He also reported a single case of cervical spina bifida combined with multiple cerebellar and brainstem anomalies that has since been called a Chiari type III malformation.3 Some authors have added a fourth type of hindbrain abnormality to the group of Chiari malformations, but the so-called Chiari IV malformation is actually a form

of severe cerebellar hypoplasia and occurs during a later stage of development4 (see Chapter 4)

C H A P T E R

CHIARI MALFORMATIONS

16 PART ONE Brain Development and Congenital Malformations

Chiari I Malformation

Pathology Chiari I malformation (sometimes

termed congenital tonsillar ectopia) is a relatively

simple anomaly that is unassociated with other

congenital brain malformations In contrast to the

Chiari II malformation (see subsequent discussion), in

this disorder the vermis, fourth ventricle, and medulla

are normal or only minimally deformed Elongated,

pointed, "peglike" cerebellar tonsils are displaced in-

feriorly through the foramen magnum into the up per cervical spinal canal (Fig 2-1)

-Tonsillar position and clinical presentation

Statistically significant differences in tonsillar position with age normally occur In general, the cerebella tonsils ascend with increasing age In the first decad of life, 6 mm should be used as the criterion for tonsillar ectopia This decreases to 5

mm in the second

Fig 2-1 A, Gross pathologic specimen of Chiari I malformation, lateral view Note the

peglike low-lying tonsils (arrows) Only minimal deformities of the fourth ventricle and

vermis are present B, Anatomic diagram of the Chiari I malformation Pointed,

low-lying tonsils are seen (large black arrow) Syringohydromyelia is indicated by the small

black arrows C, Sagittal T2-weighted MR scans in a patient with an incidental finding

of Chiari I malformation The foramen magnum is indicated by the large black arrows

The cerebellar tonsils (small black arrows) lie 10 mm below the foramen magnum (A,

Courtesy E C Alvord, Jr.)

and the third decades, to 4 mm between the fourth to

the eighth decades, and to 3 mm by the ninth decade.5

Symptomatic patients with Chiari I malformation

often present with long-tract signs and other

symptoms that mimic demyelinating disease As a

group, patients with brainstem or cerebellar signs

have the largest mean inferior tonsillar displacement

In a recent series, herniations greater than 12 mm

were invariably symptomatic However, nearly 30%

of patients with tonsillar displacements ranging from

5 to 10 mm below the foramen magnum were

asymptomatic.6

Associated abnormalities Chiari I malformation

is usually not associated with other brain anomalies

However, spinal cord, skull base, and spine lesions are

common in this disorder

Spinal cord Accumulation of cerebrospinal fluid

(CSF) within the spinal cord is a frequent finding in

patients with Chiari I (Figs 2-1, B, and 2-2) Simple

Chapter 2 Disorders of Neural Tube Closure 17

distention of the ependymal-lined central canal is

classically termed hydromyelia, Dissection of CSF

through the ependyma to form paracentral cavitations

within the cord is termed syringomyelia The distinction

between these two conditions is not possible on imaging studies and is sometimes difficult to establish even after detailed histologic examination.7 Therefore the term

syrinx, or syringohydromyelia, is used subsequently to

describe any pathologic CSF containing cord cavity, whether or not it is continuous with the central canal

A syrinx is present in 20% to 40% of all patients with

Chiari I If only symptomatic patients are considered, the occurrence of associated syringohydromyelia is even higher, ranging from 60% to 90%.6, 8The cervical spinal cord is the common site, although occasionally patients with Chiari I have a lesion that involves the entire cord

An isolated thoracic cord syrinx is uncommon

The etiology of the hydrosyringomyelia associated

with Chiari malformations is unknown but is likely

Fig 2-2 Sagittal T1-weighted (A) and T2-weighted (B) MR scans in a patient

with Chiari I malformation The peglike, low-lying tonsils are indicated by the large black arrows A collapsed syrinx of the cervical spinal cord is present

(small black arrows) This 40-yearold female had a 3-year history of long tract

signs Cranial MR scan had been requested to evaluate for demyelinating disease No evidence for multiple sclerosis was seen on T2WI of the brain

18 PART ONE Brain Development and Congenital Malformations

secondary to pathologic cerebrospinal fluid dynamics

Postulated causes include posterior compression at the foramen

magnum and anterior indentation of the medulla and cord

secondary to basilar invagination.9 Some studies show that

syrinx is more frequent in patients with moderate degrees of

cerebellar tissue hemiation.8, 10 Others report little correlation

between increasing tonsillar descent and more extensive or

distended synnxes.11

Skull base and spine Osseous anomalies are seen in about

one quarter of all patients with Chiari I malformation and

include atlantooccipital assimilation, platybasia, basilar

invagination, and fused cervical vertebrae (Klippel-Feil)6 (see

box, below)

Imaging Tonsillar configuration and position, as well as the

presence of associated hydrosyringomyelia, are easily detected

on sagittal T1- and T2 weighted MR scans (Figs 2-1, C, and

2-2) CT is less satisfactory for assessing tonsillar position and

configuration unless intrathecal contrast is used

Chiari II Malformation

Etiology Chiari II malformation is a complex anomaly with

skull, dura, brain, spine, and cord manifestations Although its

exact etiology is unknown, recent evidence suggests that the

fetal neural folds fail to neurulate completely, leaving a dorsal

opening Consequently, the developing spinal cord walls do not

appose properly and abnormal drainage of CSF through the

dehiscent neural tube into the amniotic cavity results The

primitive ventricular system then decompresses and collapses

Chiari I Malformation Peglike, pointed tonsils displaced into upper

Subsequent development of the cerebellum and brain stem within the abnormally small posterior fossa leads to upward herniation, resulting in an enlarged tentorial indsura and dysplastic tentorium, and to downward herniation of the cerebellar vermis and brain stem through an enlarged foramen magnum into the upper cervical canal.12, 13 Other relate cerebral and skull anomalies observed in the Chia II malformation (such as

a large massa intermedia, corpus callosum dysgenesis, and the so-called luckenschadel, or lacunar skull) have also been accounted for by this unified theory

Pathology and imaging manifestations The spec-

trurn of abnormalities in Chiari II malformation is very

broad, with many different findings reported (see box, p

19) The Chiari II malformation has abnormalities of the following:

1 Skull and dura

2 Hindbrain, cerebellum, and midbrain

3 Cerebrospinal fluid spaces

4 Cerebral hemispheres

5 Spine and spinal cord

It is helpful to consider these abnormalities seprately

Skull and dura The pathologic changes of Chiari II

malformation are shown schematically in Figure 2-3 Normal membranous bone formation of the calvarial vault requires distention of the underlying brain and ventricular system that is lacking in the Chiari II malformation Radial growth of the developing calvarium is profoundly altered.12 The result is the

so-called lacunar skull (luckenschadel)

The gross pathology and plain film radiographic appearance of lacunar skull are striking (Figs 2-4 and 2-5) Focal calvarial thinning and a "scooped-out" appearance are typical These skull changes are most striking at birth and tend to diminish with age Bcause the defects are not caused by hydrocephalus, their resolution is unrelated to surgical intervention and ventricular shunting Lacunar skull should distinguished from prominent convolutional markings that can occur normally or with hydrocephalus after sutural closure In the latter instance, other changes of increased intracranial pressure such as sellar erosion should be present

CT and MR scans of infants with a Chiari II mal- formation also demonstrate scalloping and thinning of the inner calvarial table Although the most obvious manifestations of lacunar skull resolve by about 6 months of age, subtle calvarial thinning and scalloping

Chiari II Malformation

Skull and dura

Calvarial defects (lacunar skull, or luckenschadel)

Small posterior fossa with low-lying transverse sinuses

Fenestrated falk,

Heart-shaped incisura with hypoplastic tentorium

Gaping foramen magnum

Concave clivus, petrous ridges

Brain

Inferiorly displaced vermis

Medullary spur and kink

Beaked tecturn

Interdigitated gyri

Cerebellum “creeps” around brainstern and "towers"

through wide tentorial incisura

Associated anomalies: callosal dysgenesis, heterotopias,

polymicrogyria, stenogyria

Ventricles

Whole system: hydrocephalus in 90%

Fourth: elongated, tubelike, inferiorly displaced

Third: large massa intermedia; may be high riding if

corpus callosurn absent

Lateral: colpocephaly; scalloped, pointed walls

Spine and cord

MyeIomeningocele in nearly 100%

Syringohydromyelia 50%-90%

Diastematomyelia

Segmentation anomalies in <10%; incomplete C1 arch

Chapter 2 Disorders of Neural Tube Closure 19

Fig 2-3. Anatomic drawing depicting the skull and dural abnormalities seen in the Chiari II

malformation 1, Hypoplastic, fenestrated falx cerebri 2, Wide, "heart-shaped" tentorial incisura 3, Gaping foramen magnum 4, Concave petrous ridges

5, Low-lying torcular Herophili 6, Low-lying

transverse sinuses, small posterior fossa 7,

luckenschadel (lacunar) skull

Fig 2-4 Gross specimen of the calvarium from a patient

with Chiari II malformation shows striking changes of

luckenschadel (lacunar) skull (From archives of Armed

Forces Institute of Pathology, Washington, D.C.)

Fig 2-5. Lateral plain film radiograph of a newborn with Chiari II shows the typical "scooped-out" changes of lacunar skull (small arrows) Note small posterior fossa with low-lying transverse sinuses

(curved arrow)

20 PART ONE Brain Development and Congenital Malformations

may persist into adulthood (Fig 2-6, B) Other skull

abnormalities seen in Chiari II include an abnormally

small and shallow posterior fossa with low-lying

transverse sinuses and torcular herophili The foramen

magnum is unusually large (gaping) (Fig 2-6, A), and

the posterior aspects of the petrous temporal bones are

often concave (Fig 2-6, C) The clivus also develops

abnormally and is often short, with a concave

configuration similar to the petrous ridges

The dural folds that form the faIx cerebri and

ten-torium cerebelli are frequently dysplastic in the Chiari II

malformation The tentorium arises laterally from the

low-lying transverse sinuses and is often deficient,

producing a widened or "heart-shaped" incisura (Figs 2-3 and 2-7) The faIx may be thinned, hypoplastic, or fenestrated The interhemispheric fissure often has an irregular, serrated appearance because apposing gyri cross the midline and even interdigitate (Figs 2-8 and 2-9)

Hindbrain, cerebellum, and midbrain The gross

parenchymal pathology of Chiari II is shown in

Fig-ure 2-10, A; an anatomic diagram summarizing the

features of this malformation is illustrated in Figure 2-10, B Hindbrain and cerebellar abnormalities in Chiari II are a constant (Fig 2-11, A) The medulla and cerebellum are displaced downward into the up-per cervical canal for a variable distance The inferiorly

Fig 2-6. Axial CT scans in a 27-year-old patient

with Chiari II malformation A, Gaping foramen magnum is indicated by the arrows B, Section

through the lateral ventricles shows the

hypoplastic, fenestrated faIx cerebri (large white arrow) with interdigitating gyri (small white arrows) that cross the midline, giving a “serrated”

appearance to the interhemispheric fissure Note that the inner table of the skull shows some persisting subtle areas of scalloped calvarial

thinning (black arrows) C, Black arrows indicate

the concave petrous ridges; the curved arrow indicates the tube-shaped fourth ventricle seen within the abnormally small posterior fossa

Fig 2-7. Axial T1-weighted MR scan in a patient

with Chiari II malformation shows a gaping,

somewhat "heartshaped" tentorial incisura (single,

small arrows) that appears completely plugged with

the upwardly herniating cerebellum The cerebellar

hemispheres extend anteromedially (double arrows)

and almost completely engulf the brainstem The

petrous ridges are concave (curved arrows)

Fig 2-9. Axial T2-weighted MR scan in a 7-year-old

child with Chiari II malformation shows a

hypoplastic, fenestrated falx cerebri with striking

interdigitating gyri (arrows)

Chapter 2 Disorders of Neural Tube Closure 21

displaced cerebellar tissue is typically the vermian nodulus, uvula, and pyramis.13a The medulla is inferiorly kinked in 70% of all cases and may lie as low as the upper thoracic canal Formation of a medullary "spur" and "kink" with the cervical spinal cord are characteristic Occasionally, ectopic choroid plexus from the fourth ventricle is present Sagittal postcontrast T1WIs show an enhancing nodule at the tip of the caudally displaced cerebellar vermis that should not be mistaken for a pathologic mass.13b The displaced vermis and medulla form a "cascade"

of displaced tissue that protrudes through the gaping

foramen magnum to lie behind the spinal cord (Figs

2-10 and 2-11) The cerebellar hemispheres and vermis also herniate upward (towering cerebellum) (Fig 2-12) through the widened incisura that, in turn, appears completely plugged with the displaced cerebellar tissue (Fig 2-7) In addition to the cephaladcaudad displacement of posterior fossa contents, the cerebellar hemispheres often extend anteromedially around the brainstern (Fig 2-7) In particularly severe cases the pons and medulla are nearly engulfed by the cerebellum

Midbrain anomalies are various The tectal plate is often pointed or "beaked" (Fig 2-11) The tectal deformity is caused by pressure from the superiorly herniated cerebellum

Cerebrospinal fluid spaces Abnormalities of the ventricles are seen in over 90% of all patients with Chiari II malformation The fourth ventricle is displaced caudally and is typically small, elongated, and somewhat tubular, lacking a normal-appearing

dorsum or fastigium (Fig 2-10, B) The third ventricle

is frequently large with a very prominent massa inter-

22 PART ONE Brain Development and Congenital Malformations

Fig 2-10 Gross pathologic specimen (A) and anatomic diagram (B)demonstrate findings

of Chiari II malformation 1, Elongated, tubelike fourth ventricle 2, "Cascade" of inferiorly displaced vermis and choroid plexus (arrows) 3, Medullary "spur." 4, Medullary "kink." 5,

Cerebellar hemispheres "creep" anteriorly around brainstem 6, Low-lying torcular herophili, transverse sinuses 7, Concave clivus 8, "Beaked" tectum 9, Large massa

intermedia 10, Partial callosal agenesis (A, Modified from Naidich TP et al: The Chiari II

malformation: Part IV The hindbrain deformity, Neuroradiol 25:179-197, 1983)

Fig 2-11 A, Sagittal T1-weighted MR scan in Chiari II malformation 1, Elongated, tubelike fourth ventricle 2, "Cascade" of inferiorly displaced vermis behind medulla 3, Medullary spur 4, "Beaked" tectum 5, Large massa intermedia 6, Partial agenesis of corpus callosum 7, Low-lying torcular

herophili 8, Concave clivus 9, Narrow, constricted gyri (stenogyria) B, Axial

T1-weighted MR scan shows gross gyral interdigitation and stenogyria (arrows)

Fig 2-12. Coronal T1-weighted MR scan in a

patient with Chiari II malformation shows low-lying

transverse sinuses (white arrows) and a very small

posterior fossa A hypoplastic tentorium cerebelli

with gaping incisura (large black arrows) is present

with "towering cerebellum" (small black arrows)

The lateral ventricles have a serrated or scalloped

appearance (open arrows)

Chapter 2 Disorders of Neural tube Closure 23

media (Fig 2-11) The lateral ventricles vary in size from normal to markedly enlarged The atria and occipital horns are often disproportionately

enlarged (a condition termed colpocephaly) (Fig 2-13, A) The margins of the lateral ventricles have

a serrated or scalloped appearance that often persists after shunting (Fig 2-12), and the frontal horns are frequently pointed anteroinferiorly (Fig

2-13, B) Aqueductal stenosis may also occur with

Chiari II malformations

The subarachnoid spaces in patients with Chiari

II are also usually altered The cisterna magna is

small or inapparent (Figs 2-6, A, and 2-11, A), and

the interhemispheric fissure frequently appears irregular or serrated secondary to fenestration or hypoplasia of the faIx cerebri with secondary gyral interdigitation (Figs 2-8 and 2-9)

Cerebral hemispheres A spectrum of parenchymal abnormalities, commonly sulcation and gyration disorders such as polymicrogyria and gray matter heterotopias, contracted narrow gyri (stenogyria), and corpus callosum dysgenesis, are all seen in Chiari II malformations (Fig 2-11)

Spine and spinal cord Various spine and cord

anomalies are associated with the Chiari II malformation

Fig 2-13 Two gross pathology specimens showing abnormalities of the lateral ventricles

in Chiari II malformation A, The atria and lateral ventricles are disproportionately

enlarged (colpocephaly) Agenesis of the corpus callosum is also present B, Enlarged

lateral ventricles have a scalloped, pointed appearance (large arrows) The posterior interhemispheric fissure is abnormal, with constricted narrow gyri (stenogyria) (small arrows) Callosal agenesis is also present with gray matter heterotopias (outlined arrows)

(A, Courtesy Rubinstein Collection, University of Virginia Department of Pathology B

Courtesy E Tessa Hedley-Whyte.)

24 PART ONE Brain Development and Congenital Malformations

Fig 2-14.Whole gross neuraxis specimen of Chiari II

malformation Note tethered cord and

myelomeningocele (Courtesy Royal College of

Surgeons of England and Gower Medical Publishing.)

Myelomeningocele is present in virtually all cases14

(Fig 2-14) Syringohydromyelia and

diastematomyelia also often accompany Chiari II

Lipomyelomeningocele, however, is not typically

associated with the Chiari II malformation

Chiari III Malformation

Pathology The definition of Chiari III

malformation has been expanded recently to include

patients with hindbrain herniation into a low occipital

or high cervical encephalocele in combination with

features of the Chiari II malformation.15

Encephaloceles in Chiari III contain various amounts

of brain Cerebellum and occipital lobes are common

cephalocele contents; occasionally the medulla and

pons are also herniated The herniated tissue is

strikingly abnormal and often nonfunctioning because

of necrosis, gliosis, fibrosis, and the presence of

heterotopias

Imaging MR readily establishes the presence and

the contents, of cephaloceles (Fig 2-15).16 It is

particularly important to recognize position of the

brain stem, medulla, and potential anomalies of

venous drainage associated with the encephalocele

Herniation of the fourth and lateral ventricles is also

often present

Fig 2-15 Sagittal T1-weighted MR scan in a patient

with Chiari III malformation Note features of Chiari

II that include (1) a large massa intermedia, (2) cervical syrinx, and (3) cerebellar tissue herniated

inferiorly through the foramen magnum into the upper

cervical canal A low occipital encephalocele (open arrows) contains herniated, dysplastic-appearing

cerebellar tissue (Courtesy M Castillo Reprinted

with permission from AJNR 13: 107-113, 1992.)

Chiari IV Malformation

Chiari IV malformation is discussed under

cerebellar hypoplasias and dysplasias (see Chapter 4)

CEPHALOCELES

Pathology A skull defect in association with

herniated intracranial contents is termed a

cephalocele 17 If the herniation contains solely

leptomeninges and CSF it is termed a meningocele 18 Cephaloceles in which the protruding structures

consist of leptomeninges, CSF, and brain are termed

meningoencephaloceles Cephaloceles can be congenital or acquired (e.g., posttraumatic, surgical);

only congenital cephaloceles are considered here (see

box)

Incidence Cephaloceles occur approximately 1 to

3 times in 10,000 live births The different types of cephaloceles show significant geographic variations,

as well as substantial differences in race and gender.18 Occipital cephaloceles predominate in individuals of white European or North American origin, whereas sincipital (frontoethmoidal) lesions are more common

in Southeast Asians and aboriginal Australians.19 In North America, about 70% to 90% of all cephaloceles are occipital, with 5% to 10% each found in the parietal and frontal areas Basal encephaloceles are the rarest form of encephalocele