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Author: Manohar Aribandi, MD, Academic Chief, Section
of Neuroradiology, Department of Radiology, Geisinger
Medical Center
Introduction
Background
Agenesis of the corpus callosum (ACC) is an anomaly that may
occur in isolation or in association with other CNS or
systemic malformations. Because the corpus callosum may be
partially or completely absent, the term dysgenesis has also
been used to describe the spectrum of callosal anomalies
Corpus callosum, agenesis. Sagittal T1-weighted MRI of
the brain shows the normal appearance of the corpus callosum.
Corpus callosum agenesis: Sagittal T1-weighted MRI of the
brain shows the normal appearance of the corpus callosum.
Corpus callosum, agenesis: Sagittal T1-weighted MRI of
the brain shows complete absence of the corpus callosum. The
cingulate sulcus is absent, and the medial hemispheric sulci
reach the third ventricle in a radial fashion.
Corpus callosum, agenesis: Sagittal T1-weighted MRI of
the brain shows complete absence of the corpus callosum. The
cingulate sulcus is absent, and the medial hemispheric sulci
reach the third ventricle in a radial fashion.
Corpus callosum, agenesis: Sagittal T1-weighted MRI of
the brain shows partial agenesis of the corpus callosum. The
genu and anterior body of the corpus callosum are
visualized, whereas the posterior body, splenium, and the
rostrum are absent.
Corpus callosum, agenesis: Sagittal T1-weighted MRI of
the brain shows partial agenesis of the corpus callosum. The
genu and anterior body of the corpus callosum are
visualized, whereas the posterior body, splenium, and the
rostrum are absent.
Recent studies
Moes et al studied 720 individuals with
agenesis of the corpus callosum to develop a profile of
characteristics and diagnostic indications and identified
the following: delayed motor development, difficulty with
balance and bimanual movements, large head size, poor muscle
tone, poor depth perception, reduced pain perception,
sleeping difficulties, and an increased proportion of left-
and mixed-handedness.
Tang et al did a retrospective study of
29 fetuses with agenesis of the corpus callosum, including
fetal MR imaging, postnatal MR imaging, and autopsy
findings. A total of 23 fetuses had delayed sulcation and/or
too-numerous cortical infoldings; 15 fetuses had cerebellar
and/or brainstem abnormalities. Fetal MR imaging findings
suggested a genetic syndrome in 5 fetuses and an acquired
etiology or genetic/metabolic disorder in 2 fetuses.
Findings were confirmed in 8 cases with postnatal MR
imaging, except for delayed sulcation and small vermis, and
in 4 cases with autopsy, except for periventricular nodular
heterotopia and abnormalities in areas not examined by
autopsy. Neurodevelopmental outcome was good in 7 and poor
in 9 children. Abnormal sulcal morphology and/or
infratentorial abnormalities were present in those with poor
outcome and absent in those with good outcome.
Pathophysiology
Agenesis of the corpus callosum (ACC)
is usually a sporadic occurrence, although the incidence is
increased in patients with trisomy 18, trisomy 13, and
trisomy 8. Several familial cases have been reported. Organ
systems other than the CNS, particularly the musculoskeletal
and genitourinary systems, may be affected as well.
Fibers of the corpus callosum arise
from the superficial layers of the cerebral cortex; they
project to the homotypic region of the contralateral cortex
by passing through the corpus callosum in crossing the
midline. Disturbance of embryogenesis in the first trimester
of gestation by some unknown insult leads to failure of the
callosal axons to pass across the midline. These arrested
axons form the longitudinally oriented bundles of Probst
that are located medial to the lateral ventricles in
patients with agenesis.
Spectrum of abnormalities
ACC may be complete, partial, or atypical.
With complete agenesis, the corpus callosum is totally
absent.
With partial agenesis (hypoplasia), the anterior portion
(posterior genu and anterior body) is formed, but the
posterior portion (posterior body and splenium) is not
formed. The rostrum and the anterior/inferior genu are also
not formed.
An atypical appearance occurs when the anterior to posterior
formation is not respected.
In holoprosencephaly, callosal anomalies are atypical; for
example, the splenium may be present without a genu or body.
In middle interhemispheric fusion, which is a variety of
holoprosencephaly, the genu and splenium may be present
without the callosal body.
With pseudo–corpus callosum, which involves conditions of
complete or partial agenesis, the hippocampal commissure may
become enlarged and appear like the posterior part of the
corpus callosum.
Secondary destruction of corpus callosum occurs when the
genu and anterior body are destroyed, leaving the posterior
portion of the corpus callosum intact. This may occur
secondary to porencephaly or schizencephaly; as a surgical
complication in cases involving the transcallosal approach
to the lateral and third ventricle; and with hemisection of
the callosum for the treatment of seizures.
Other cerebral malformations may coexist with callosal
dysgenesis. Examples of these include interhemispheric
cysts; intracranial lipomas; and disorders of neuronal
migration, such as schizencephaly, neuronal heterotopias,
lissencephaly, and pachygyria.
Frequency of abnormalities
The frequency of occurrence of some of the more commonly
associated anomalies is as follows:
• CNS anomalies (85%)
• Dandy-Walker cyst (11%)
• Interhemispheric cysts
• Hydrocephalus (30%)
• Midline lipoma of corpus callosum (10%)
• Arnold-Chiari malformation (7%)
• Midline encephalocele
• Porencephaly
• Holoprosencephaly
• Hypertelorism median cleft syndrome
• Polymicrogyria
• Gray-matter heterotopia
• Cardiovascular, GI, and GU anomalies (62%)
Frequency
United States
The reported frequency of agenesis of the corpus callosum in
the US is 0.7-5.3%.
International
Internationally, the frequency of agenesis of the corpus
callosum is not known but could be similar to that in the
US.
Mortality/Morbidity
• Agenesis of the corpus callosum may occur as an isolated
defect, but it is frequently associated with other
malformations, chromosomal abnormalities, and genetic
syndromes.
• Although ACC has been found in asymptomatic individuals,
it is generally considered a potential marker for neurologic
impairment.
• In children, the prognosis is frequently related to other
associated abnormalities.
Sex
Agenesis of the corpus callosum is reported to be more
common in males than in females.
Age
Agenesis of the corpus callosum is a congenital or a
developmental anomaly and so is present at the time of
birth. In many cases, agenesis is diagnosed later in infancy
or in childhood because of its associated congenital
malformations.
Anatomy
Development and anatomy
The corpus callosum develops from the lamina reuniens in the
telencephalon; it begins to appear between the anterior and
hippocampal commissures at about 10.5 weeks. The adult form
of the corpus callosum is achieved by 17 weeks' gestational
age. Initial formation of the corpus callosum occurs in the
genu and the body, progressing posteriorly. The anterior
genu and rostrum develop last, folding back under the genu.
The callosum thickens with increasing myelination.
When the corpus callosum is absent, the third ventricle is
often high riding, extending superiorly between the lateral
ventricles. On coronal imaging, a candelabra appearance
occurs, with the third ventricle forming the central
vertical portion and the lateral ventricles the peripheral
arms of the candelabra. On axial imaging, the lateral
ventricles are parallel.
Medial to the lateral ventricles, longitudinal bundles of
white matter are present in patients with agenesis of the
corpus callosum (ACC). These are known as Probst bundles and
presumably would have formed a normal corpus callosum.
Probst bundles are best seen on coronal or axial T1-weighted
MRIs. The occipital horns of the lateral ventricles are
dilated in patients with ACC, probably because of a
deficiency of peritrigonal white-matter fibers. This
anatomic finding is known as colpocephaly. When the corpus
callosum is absent, the cingulate gyrus is inverted, the
normal cingulate sulcus is absent, and the medial cerebral
sulci radiate toward the midline in a radial configuration.
This finding is especially helpful in evaluating newborns in
whom the corpus callosum is normally thin.
The hippocampal formations are frequently hypoplastic in
patients with ACC, with resulting mild dilatation of the
temporal horns. In partial callosal agenesis, the posterior
body, splenium, and rostrum are usually absent. Absence of
the posterior body and splenium is especially common in
patients with a Chiari II malformation. Barkovich has
described the unusual absence of the genu or the midbody of
the corpus callosum in patients with atypical or mild forms
of holoprosencephaly.
Associated midline cysts are noted in some cases. The exact
origin and nature of these cysts are controversial. Whereas
some of these cysts represent a dilated superiorly migrated
third ventricle, others represent true midline cysts that
may be lined by ependymal cells or by arachnoid membranes.
Types of midline cyst formation
Raybaud and Girard suggest that there are 3 types of midline
cyst formation in association with agenesis or hypogenesis
of the corpus callosum.
Type 1 is a large midline cyst that communicates with the
third ventricle and the lateral ventricles.
Type 2 is similar to type 1; associated cortical anomalies
(e.g., polymicrogyria, gray-matter heterotopia,
schizencephaly) are present.
Type 3 involves complex, multilocular cysts that are
asymmetric and independent of the ventricles. Cortical
malformations are uncommon. With large cysts, the
ipsilateral lateral ventricle may be compressed, and the
contralateral ventricle may be obstructed and enlarged
(hydrocephalus). A CT cystogram may be helpful in
identifying the communications between the loculations of
the cysts and the ventricles and in guiding the placement of
a ventriculostomy shunt.
Associated anatomic abnormalities
Other anatomic abnormalities in patients with ACC include
hydrocephalus; cephaloceles; and neuronal migration
disorders such as lissencephaly, schizencephaly, gray-matter
heterotopias, pachygria, and polymicrogyria.
Presentation
The white-matter fibers forming the corpus callosum
predominantly connect symmetrical regions in the frontal,
parietal, temporal, and occipital lobes. Experimental
observations indicate that the corpus callosum allows the
sharing of learning and memory between the 2 cerebral
hemispheres.
The clinical manifestations of callosal agenesis may be
described under 2 headings: nonsyndromic and syndromic.
Nonsyndromic forms are the most common. An unknown, though
probably small, proportions of patients are completely
asymptomatic; commonly, their condition is incidentally
discovered during neuroimaging. Patients may present with
mental retardation or delayed development; seizures; and
cerebral palsy.7 Macrocephaly may occur as a result of
hydrocephalus; it is sometimes associated with
interhemispheric cysts.
A number of syndromes may be associated with ACC. Some of
the more common ones include Dandy-Walker syndrome, Aicardi
syndrome, fetal alcohol syndrome, and several of the
trisomies.
Preferred Examination
The diagnosis of callosal agenesis depends on neuroimaging.
In the newborn, before closure of the anterior fontanelle
occurs, screening ultrasonography (US) may clearly show the
absence of the corpus callosum; it may also show parallel
lateral ventricles, interhemispheric cysts, hydrocephalus,
and other related anomalies. USA was the first imaging
modality to allow direct sagittal imaging of callosal
dysgenesis.
Antenatal diagnosis of agenesis of the corpus callosum (ACC)
is possible from about 20 weeks' gestation. Characteristic
intrauterine US findings include colpocephaly and parallel
ventricular walls. CT findings are also diagnostic of ACC.
Parallel lateral ventricles, colpocephaly, and extension of
the third ventricle into the interhemispheric fissure is
particularly pertinent findings. In patients with ACC who
have an interhemispheric cyst, the preoperative injection of
nonionic water-soluble contrast material into the cystic
loculations for CT evaluation enables assessment of the
ventricular system or of the communication of the cystic
components with one another.
MRI is currently the imaging procedure of choice in infants
and children with ACC, even in patients who have previously
undergone CT and US examinations. The multiplanar capability
and high soft tissue contrast that are possible with MRI
permit confident diagnosis of ACC and its associated
anomalies, especially neuronal migration anomalies or
atypical forms of holoprosencephaly. These entities may be
extremely subtle or indiscernible on CT or US images.
Limitations of Techniques
Agenesis of the corpus callosum may be depicted on both CT
and US, but MRI is the preferred imaging modality because of
its greater sensitivity for depicting associated cerebral
anomalies.
Differential Diagnoses
Other Problems to Be Considered
Holoprosencephaly
Acrocallosal syndrome
Aicardi syndrome
Apert syndrome
Chromosomal anomalies (13, 18, 11q-, etc)
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