Colpocephaly

Gary M. Joffe, MD, Gerardo O. Del Valle, MD, Luis A.

Izquierdo, MD, Luis B. Curet, MD

Address Correspondence to Gary M. Joffe, MD, Department of Maternal-Fetal Medicine,

University of New Mexico Medical Center, 4th Floor, ACC 2211 Lomas, N.E., Albuquerque,
NM 87131- Ph: 502-272-6386 Fax: 505-272-6385

Synonyms: Vesiculocephaly1.

Definition: Disproportionate enlargement of the occipital horns of the lateral ventricles in

association with partial or complete agenesis of the corpus callosum.

Etimology: Greek: κ ο ι λ ο ς ,κο λ π ο ς : hollow and κ ε φ α λ η : head

Prevalence: Approximately 36 cases have been described in children, but the antenatal
diagnosis is infrequent2.

Etiology: Two theories are debated in the literature. The generally accepted theory is that of
interrupted migration of white matter precursor cells during the first two to five months of
fetal life1,3,4. Fibers radiating from and associated with the corpus callosum, such as the
anterior forceps, tapetum, and optic radiation are atrophic or absent. Absence of these
structures in the parieto-occipital regions leads to large outpouchings of the posterior
ventricular system4. The second theory, perhaps less accepted, is that of local destruction of
previously formed elements that give rise to the walls of the occipital horns of the lateral
ventricles2. Associated findings have included trisomy 8 mosaic5, trisomy 9 mosaic2, Toxo-
plasma gondii2, maternal ingestion of alcohol, oral contraceptive medication, diethylpropion
hydrochloride (Tenuate®), and doxylamine succinate (Bendectin®)2.

Associated anomalies: Optic nerve hypoplasia, chorioretinal coloboma, microcephaly,

micrognathia, cleft palate, hypoplastic nails, simian creases, cerebellar atrophy6, enlargement
of the cisterna magna, microgyria, macrogyria, pachygyria, lissencephaly7,
meningomyelocele, Pierre-Robin syndrome6, neurofibromatosis6, schizencephaly3.

Differential diagnosis: Porencephaly, stenosis of interventricular foramen, supratentorial ara-

chnoid cyst.

Prognosis: Mild to severe mental retardation, poor vision, mild to severe seizures,
developmental delay. Occasional report of normal physical and neurodevelopmental
assessment.

Recurrence risk: No reported figures given in the literature.

Management: Prenatal diagnosis should prompt search for associated anomalies, karyotypic
abnormality, gestational viral exposure, and maternal toxin ingestion.

MESH Cerebral-ventricles-abnormalities BDE 2012 CDC 742.280 ICD9 742.2

Introduction
The term colpocephaly, meaning disproportionate enlargement of the posterior horns of the
lateral ventricles, is found throughout the neurology literature. However, the term is rarely
found in the radiology literature. Perhaps, this is due to lack of consensus regarding the
pathogenesis of the process, numerous reported etiologic associations, and lack of strict
definition. The following is a case report of antenatal diagnosis of colpocephaly, and a review
of the literature.

Case report
The patient is a 26-year-old G1 white woman referred to our institution at 34 weeks of
gestation for evaluation of fetal ventriculomegaly. Her prenatal course had been remarkable
for an elevated maternal serum alpha-fetoprotein at 16 weeks. Amniocentesis revealed a 46
XX karyotype and a normal amniotic fluid alpha-fetoprotein. At 28 weeks of gestation, she
was noted to have a lag in fundal height. Repeat ultrasound revealed the fetus to have
measurements consistent with 26 weeks of gestation. The cisterna magna measured 10mm. A
repeat ultrasound was obtained at 34 weeks of gestation. Biometric measurements were
reportedly consistent with 31 weeks, and ventriculomegaly (fig. 1) was noted for the first
time.

Figure 1: Dilatation of the occipital horns without concomitant distention of the rest of the
ventricular system.

Upon referral to our institution at 35 weeks, an abdominal ultrasound revealed a

symmetrically growth retarded fetus with an estimated fetal weight of 1574g—well below the
5th percentile for gestational age. The intracranial anatomy was significant for marked
enlargement of the occipital horn of the lateral ventricles: the largest diameter measuring 22
mm (fig. 1-3).
Figure 2: A drooping choroid plexus is seen in the distended occipital horn.

Figure 3: The third ventricle is not distended.

In addition, the atria measured 14mm. The atrophic cerebellum measured 28mm in diameter,
with the vermis noted to be present (fig. 4). The cisterna magna was enlarged. The remaining
intracranial anatomy appeared normal. The remainder of the anatomy appeared normal, as did
the amniotic fluid index and Doppler assessment of umbilical arterial systolic to diastolic flow
ratio.

Figure 4: The cisterna magna is large.

The patient was offered amniocentesis for viral culture and lung maturity assessment. Cytomegalovirus
immunofluorescence assay was negative, and the fetal lung profile revealed maturity.
At 37 weeks of gestation, non-stress testing revealed a late appearing fetal heart rate
deceleration with an isolated contraction. A contraction stress test was performed and was
positive. A cesarean section was performed with delivery of a 2170g female infant with
Apgar"s of 4 and 7 at one and five minutes, respectively. The infant"s peripartum course was
complicated by a transient episode of bradycardia, but was otherwise unremarkable. Serum
TORCH titers were negative.

Magnetic resonance imaging of the infant"s cranium revealed marked enlargement of both
occipital horns of the lateral ventricles, agenesis of the corpus callosum, cerebellar
hypoplasia, and enlargement of the cisterna magna (fig. 5). The infant was discharged home
on the fifth day of life.

Figure 5: Coronal and axial MRI of the newborn head reveals marked enlargement of both
occipital horns of the lateral ventricles, agenesis of the corpus callosum, cerebellar
hypoplasia, and enlargement of the cisterna magna.

Discussion
Prevalence

Approximately 36 reports of colpocephaly have appeared in the literature. This figure may be
misleading, however, as there is a lack of consensus as to the precise definition of the term
colpocephaly.

Most authors appear to agree that the findings of colpocephaly include disproportionate
enlargement of the occipital horns, with the remaining ventricular system maintaining normal
size and configuration. In addition, most, but not all, authors believe that the condition is
associated with partial or complete agenesis of the corpus callosum2.

Definition

The debate in the literature centers around the morphogenesis of the process, with some
authors viewing it strictly as developmental anomaly3. Others view the term colpocephaly as
only being descriptive. They find no inconsistency in using the term to describe isolated
occipital ventriculomegaly resulting from destruction of neural elements that had previously
been normally formed2.

From the standpoint of antenatal diagnosis, the term should probably be descriptive of
isolated occipital ventriculomegaly rather than as a unique clinical entity. This is because, in
most cases, the underlying etiology, be it failure of morphogenesis or a destructive process,
will not be known.

Embryology

The lateral ventricles arise as cavities within the telencephalon. The telencephalon gives rise
to two diverticula that expand over the diencephalon and mesencephalon to give rise to the
cerebral hemispheres. “During the third gestational month, there is formation of the temporal
pole and the ventricles are now in a `U" shape4”.

The appearance and growth of the occipital ventricular projection takes place between 23 and
34 weeks8.

The normal reduction in diameter of the occipital horns of the lateral ventricles is critically
dependent upon correct morphogenesis of the corpus callosum. “The fibers of the corpus
callosum, the forceps and the tapetum, the internal parietooccipital fissure, and the calcarine
fissure all take part in shaping and reducing the size of the occipital horn4”.

Pathogenesis

The term colpocephaly was originally coined by Yakovlev and Wadsworth, who stated that
“in the apparent dilatation of the occipital horns...it represented a failure of development of
the cerebral wall with persistence of the embryonal vesicular character of the brain3”.

If colpocephaly is the result of abnormal morphogenesis, then any process that inhibits the
normal neuronal migration from within the ventricle, and likewise the normal genesis of the
corpus callosum, may result in this entity.

Clearly, however, not all patients with agenesis of the corpus callosum manifest isolated
ventriculomegaly of the occipital horns. Therefore, the precise pathogenesis of this process
remains incompletely explained.

Etiology

Colpocephaly has been associated with chromosomal anomalies such as trisomy 8 mosaic5
and trisomy 9 mosaic2. Infectious associations have included gestational exposure to
Toxoplasma gondii2. Maternal gestational ingestion of ethanol, oral contraceptive
medications, dipropion hydrochloride (Tenuate®), and doxylamine succinate (Bendectin®)
have been reported in association with colpocephaly2. Colpocephaly has been described in
conjunction with Pierre-Robin syndrome6.

Associations such as those listed above must be viewed with caution, however, as timing,
duration, and quantity of exposure are rarely reported in the literature.

Associated anomalies

In cases not associated with chromosomal aberration, extra-cranial anomalies have included
cleft palate and chorioretinal coloboma4. Associated intracranial anomalies have included
microcephaly, agenesis of the corpus callosum, meningomyelocele6, optic nerve atrophy,
lissencephaly7, periventricular leukomalacia, enlargement of the cisterna magna and
cerebellar hypoplasia6.

Prenatal diagnosis

Antenatal diagnosis is made with the demonstration of enlargement of either or both occipital
horns of the lateral ventricles. The atria may be enlarged as well. The remainder of the
ventricular system should have normal dimensions and configuration. To meet the criteria
established by Yakovlev, partial or complete agenesis of the corpus callosum should be noted
as well.

Prognosis

A wide range of neuro-developmental outcomes has been reported in the presence of

colpocephaly2. Perhaps this is because of uncertainty as to the exact etiology of the process.

Of 36 cases reported in the modern literature, 13 patients had seizures. Twelve patients were
noted to have mental retardation. Thirteen of 36 cases were affected by mild to severe
movement disorders. Other reported outcomes include poor vision, speech and language
difficulties, deafness, and chorioretinitis.

Three of the 36 cases reviewed had completely normal neurologic and motor development2-6.

Management

Antenatal diagnosis of colpocephaly should prompt a search for underlying associations such
as karyotypic abnormalities. In addition, maternal exposure to viral or parasitic pathogens
should be considered. Finally, maternal ingestion of medication or toxic substances should be
evaluated.

In the absence of macrocephaly, there should be no contraindication to vaginal delivery.