Address correspondence to Patricia Karstaedt, MD, Dept. of Radiology, Vanderbilt University, 21st and Garland, Nashville, TN 37232-5316. Ph: 615-343-0595, Fax: 615-343-4890

Synonyms: None.

Definition: Cystic collection located in the interhemispheric fissure, with or without communication with the ventricular system.

Prevalence: Fifteen cases have been described between 1937 and 1992. Most are detected in young children, with very few reported cases in fetuses. In some cases, the cysts can be multiple. The prevalence of interhemispheric cyst in dysgenesis of the corpus callosum is not known.

Etiology: Dysgenesis of the corpus callosum, though unclear, may result from X-linked recessive syndrome, trisomy 13, 15 and 18, Aicardi syndrome, as well as vascular, traumatic, infectious and toxic insults.

Pathogenesis: Superior extension of the roof of the third ventricle in the interhemispheric fissure forming an interhemispheric cyst. The extension may lose its communication with the third ventricle, earning it the title of. The presence of choroid plexus tissue (originating from the third ventricle) is responsible for the cerebrospinal fluid content of the cyst.

Associated anomalies: Always associated with dysgenesis of the corpus callosum and therefore with the anomalies associated with dysgenesis of the corpus callosum such as Dandy-Walker malformation, interhemispheric arachnoid cyst, gray matter heterotopias, cephaloceles, lipomas, and midline facial anomalies.

Differential diagnosis: Arachnoid, intradural and several other cysts, and some forms of holoprosencephaly (see text).

Prognosis: Patients with classical isolated dysgenesis of the corpus callosum may have normal intelligence or only mild neurological impairment4. Those with an accompanying interhemispheric cyst have a poorer prognosis, usually with gross mental and motor deficits^2,15. Children with interhemispheric cysts shunted within the first three months of life have the best prognosis.

Recurrence risk: Unknown.

Management: When the cyst is large and associated with hydrocephalus and cranial enlargement, the option of pregnancy termination can be offered to patients. Prenatal shunting has not been attempted, but shunting of simpler conditions such as hydrocephalus has not proven very useful. Assessment by MRI and shunting after delivery appears to be the most reasonable course of action.

MESH Agenesis of the corpus callosum; cyst ICD9 742.4 CDC 742.420 (cerebral cysts) 742.210 (anomalies of the corpus callosum)

Introduction

Ultrasound is useful in diagnosing complex intracranial malformations of the fetal and neonatal brain⁴. Many cases of interhemispheric cyst and partial or total dysgenesis of the corpus callosum are found in young children affected with complex clinical symptoms³. We present a case of interhemispheric cyst associated with dysgenesis of the corpus callosum.

Case report

The mother of the patient was a 29-year-old G1P0. On a routine antenatal ultrasound at 26 weeks, an intracranial midline septated cystic mass was identified which displaced and distended the right ventricle (fig. 1).

 Figure 1: 26 weeks: Coronal (left) and para-axial (middle & right) views of the cystic structures in the head. The cysts are predominently midline, deflecting the right hemisphere most and producing obstruction on the left.

  The biparietal diameter at 28 weeks was 5-6 weeks larger than expected (fig. 2).

Figure 2: 28 weeks: The cysts have enlarged and the right hemisphere is further displaced, particularly in the occipital region.

The pregnancy was otherwise unremarkable. At 37 weeks (fig. 3), an elective cesarean section was performed for cephalopelvic disproportion under epidural anesthesia. A viable male infant was delivered weighing 3,430g with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively.

Figure 3: 36 weeks: The cysts have not progressed any further, and their growth has been proportional to that of the brain.

 Postnatal course

At examination, the infant was noted to have macrocephaly with widely split sutures. The head circumference measured 395 mm (>2.5 SD from the mean). The patient was admitted to the neonatal intensive care unit, and a head ultrasound again revealed the presence of a midline, septated, cystic mass with ventricular dilatation, especially on the right, and shift of the midline to the left. An MRI (fig. 4) demonstrated a large midline cyst adjacent to and communicating with the dilated third ventricle, dilatation of the lateral ventricles, especially on the right, dysmorphic brain parenchyma in both hemispheres and dysgenesis of the corpus callosum.

 

Figure 4: Postnatal MRI pshowing a large midline cyst adjacent to and communicating with the dilated third ventricle, dilatation of the lateral ventricles, especially on the right, dysmorphic brain parenchyma in both hemispheres and dysgenesis of the corpus callosum.

A right occipital craniotomy was performed for placement of a shunt and reservoir (fig. 5). The patient did well postoperatively. Genetic examination revealed a mild lumbar kyphosis and left thoracoscoliosis, left simian crease, bilateral clinodactyly and camptodactyly of the right second, third, and fifth fingers. No genetic syndrome was recognized. TORCH titers on the mother and infant were negative. The family history was non-contributory.

At 3 years of age, the patient was noted to be significantly delayed developmentally. The patient also developed seizures and right hip subluxation.

 

Figure 5: Postnatal CT (after shunting) that demonstrates the cyst and residual hydrocephalus.

Discussion

Interhemispheric cysts are rare, and all reported cases have been associated with complete or partial dysgenesis of the corpus callosum1. Apart from a recent case in a newborn, published by Utsunomiya¹⁷, none of the cases in the literature were diagnosed as early as ours. Dysgenesis of the corpus callosum, a large interhemispheric cyst, and dilatation of the lateral ventricles are radiologic hallmarks of midline cerebral malformation². In the absence of the corpus callosum, the third ventricle tends to be indented and extends superiorly into the interhemispheric fissures, forming an interhemispheric cyst containing cerebrospinal fluid. This cyst may or may not communicate with the third ventricle⁵ or with a lateral ventricle².

Embryology

The embryology of dysgenesis of the corpus callosum is not completely understood. Several mechanisms have been suggested to be responsible for the arrest of the posterior development of the corpus callosum. These include¹⁰:

• an unpaired anlage of the telencephalon resulting in a failure of lateral migration; in this form, the dysgenesis of the corpus callosum would represent a mild form of holoprosencephaly,

·         a localized defect of the diencephalic pouch resulting in a cyst that interferes with the growth of the corpus callosum, and

·         a vascular anomaly such as an infarction of the commisural plate capillary plexus.

Table 110 outlines the relationships between embryological defects and disorders.

 Table 1: Relationships between embryological defects and disorders with dysgenesis of the corpus callosum.

 

Embryological defect	Anatomical finding	Diagnoses
Failure of normal development of the midline telencephalon and vesicles.	Absence of forebrain commissures,, development of midline structure in abnormal positions.	Holoprosencephaly or arrhinencephaly.
Failure of normal development of the midline telencephalon without defects of the vesicles.	Absence of forebrain commissures,, dilatation of the roof of the third ventricle.	Total agenesis of the corpus callosum,, anterior commissure and psalterium.
Defect in the posterior part of the midline telencephalon with associated cyst of the diencephalic pouch.	Absence of the corpus callosum with dilatation of the roof of the third ventricle.	Total agenesis of the corpus callosum,, but normal anterior commissure and psalterium.
Focal defect of the midline, occurring late in the formation of the corpus callosum, may be associated with a cyst of the diencephalic pouch.	Absence of part of the posterior portion of the corpus callosum, enlargement of the third ventricle.	Partial dysgenesis of the corpus callosum.

 Etiology

Many etiologies have been suggested for dysgenesis of the corpus callosum, including vascular malformation or occlusion7, teratogenic drugs8, infection in utero and chromosomal abnormalities9. However, none has been proven.

Pathogenesis

In the absence of the corpus callosum, the roof of the third ventricle is not limited. The third ventricle thus widens and extends superiorly in the interhemispheric fissure, forming the interhemispheric cyst. The extension may lose its communication with the third ventricle, earning it the title of cyst. The cyst can be lined with arachnoid, glial, choroid plexus, ependymal or neuroepithelial epithelium. The presence of choroid plexus tissue (originating from the third ventricle) is responsible for the cerebrospinal fluid content of the cyst.

Associated anomalies

Interhemispheric cysts are always associated with dysgenesis of the corpus callosum. The associated anomalies are thus those of dysgenesis of the corpus callosum (Table 2), more than those of interhemispheric cyst, and include Dandy-Walker malformation, interhemispheric arachnoid cyst, gray matter heterotopias, cephaloceles, lipomas, and midline facial anomalies.

Ultrasound diagnosis

A key observation is the absence of the corpus callosum with its associated findings of separation of narrow frontal horns, colpocephaly, and enlarged third ventricle. In our case, however, the disorganization of the intracranial architecture by the cysts and the resulting hydrocephalus were such that these finding could not be identified.

Differential diagnosis

The most common midline cysts in the fetus are cysts of the cavum pellucidum, cavum vergae and cavum veli interpositi. In our experience, these have always been much smaller than the cysts observed in this patient. Other cysts associated with dysgenesis of the corpus callosum include (fig. 6):

·         an interhemispheric intradural cyst¹² (very rare),

·         an interhemispheric arachnoid cyst, on which the primary defect is in the arachnoid^13-14,16; these tend to be more common in adults than in young children¹⁶,

·         a porencephalic cyst, in which the brain is replaced, rather than displaced by the cyst², or

·         upward herniation of the third ventricle, which is very similar, and may be an intermediate embryological stage.

The interhemispheric cysts reported in association with dysgenesis of the corpus callosum may be confused with forms of lobar and semilobar holoprosencephaly, in which there is a single frontal horn. Other differential diagnoses include a paraphyseal diverticulum of the third ventricle and a diencephalic cyst (neither reported prenatally yet). When the anatomy of the brain is very disorganized, a cystic teratoma can be considered and areas of calcification searched for.

Table 2: Anomalies associated with dysgenesis of the corpus callosum (adapted from19).

 

g Central nervous system  1 Dandy-Walker malformation  1 Interhemispheric arachnoid cyst  1 Gray matter heterotopias  1 Cephaloceles  1 Lipomas  1 Gyral anomalies and heterotopias  1 Ageneses and hypoplasias  1 Meningeal abnormalities  1 Schisis malformations  1 Nuclear dysplasias  1 Foraminal obstructions and hydrocephalus  1 Encephaloclastic malformations  1 Vascular malformations	g Facial anomalies  1 Ocular abnormalities  1 Cleft palate, lip, uvula  1 Hypertelorism/ hypotelorism  1 Malformed ears  1 Hypoplastic mandible/maxilla  1 Failure of dentition  1 Low forehead  1 High palate  1 Malformed nose  1 Deformed tongue
g Cardiovascular  1 Patent foramen ovale  1 Patent ductus arteriosus  1 Ventricular septal defect  1 Atrial septal defect  1 Bicuspid pulmonary or aortic valve  1 Truncus arteriosus  1 Persistent left superior vena cava  1 Absent innominate vein  1 Tetralogy of Fallot	g Respiratory  1 Diaphragmatic hernia  1 Quadrilobed left lung  1 Hypoplasia of the lung  1 Cystic disease of lung  1 Fibrocystic disease
g Musculosketal anomalies  1 Malformed digits  1 Scoliosis or kyphosis  1 Short neck  1 Pectus excavatum  1 Redundant skin  1 Inguinal hernia  1 Short upper arms  1 Absent patella  1 Joint anomalies  1 Hypoplastic nails	g Gastrointestinal  1 Megacolon  1 Anal atresia  1 Thickened pylorus  1 Pancreatic cysts  1 Fibrocystic disease
g Genitourinary  1 Horseshoe kidney  1 Hamartoma  1 Dysplastic/hypoplastic kidney  1 Dilated ureter  1 Small penis  1 Undescended testicles  1 Ovarian cysts  1 Bicornuate uterus  1 Abnormal labia, clitoris  1 Septate vagina

 Figure 6: Differential diagnosis of the midline cysts that may be recognized in a fetus.

Prognosis

Patients with classical isolated dysgenesis of the corpus callosum may have normal intelligence or only mild neurological impairment⁴. Although in some patients the cyst can be asymptomatic18, the association of dysgenesis of the corpus callosum with an accompanying interhemispheric cyst may have a poorer prognosis, usually with gross mental and motor deficits^2,15. Byrd et al³ showed that children with interhemispheric cysts that were shunted early, within the first three months of life, had the best progress and development. Therefore, early recognition is important, as it facilitates patient management and parent counseling.

Management

When the cyst is large, associated with hydrocephalus and cranial enlargement and discovered before 24 weeks, the option of pregnancy termination can be offered to the patients. Prenatal shunting has not been attempted, but shunting of simpler conditions such as hydrocephalus has not proven very useful. Assessment by MRI and shunting after delivery appear to be the most reasonable course of action, and the management will be guided by the dysgenesis.

References

1. Solt LC, Deck JHN, Bain RS, et al: Interhemispheric cyst of neuroepithelial origin in association with partial agenesis of the corpus callosum. J Neurosurg 52:399-403, 1980.

2. Swett HA, Nixon AW: Agenesis of the corpus callosum with interhemispheric cyst. Radiology 114:641-645, 1975.

3. Byrd SE, Radkowski MA, Flannery A, McLone DA; The clinical and radiological evaluation of the abscence of the corpus callosum. Eur J Radiol 10:65-73, 1990.

4. McGahan JP, Ellis W, Lindfers KK, et al: Congenital cerebrospinal fluid containing intracranial abnormalities: A sonographic classification. JCU 16:531-544, 1988.

5. Barkovich AJ: Pediatric neuroimaging. Raven Press, New York, 80-82, 1990.

6. Barcock DS: The normal, absent and abnormal corpus callosum: sonographic findings. Radiology 151:449, 1984.

7. Dekaban A: Large defects in cerebral hemispheres associated with cortical dysgenesis. J Neuropathol Exp Neurol 24:512-530, 1965.

8. DeMyer W: Fifth International Congress of Neuropathology, Zurich, 1965.

9. Zingesser LG, Schechter MM, Medira A: Angiographic and neurocencephalographic features of holoprosencephaly. AJR 97:651-574, 1966.

10. Loeser JD, Alvord EC: Clinicopathological correlations in agenesis of the corpus callosum. Neurology 18:745-6, 1968.

11. Menkes JH, Philippart M, Clark DB: Hereditary partial agenesis of the corpus callosum: biochemical and pathological study. Arch Neurol 11:198-208, 1964.

12. Rao KC, Gunadi IK, Diaconis JN: Interhemispheric intradural cyst. J Comput Assist Tomogr 6:1167-1171, 1982.

13. Agamanolis DP, Traynor LA: Congenital dysautonomia, a case with posterior interhemispheric cyst and microcephaly. J Neuropathology Experim Neuro 42:469-78, 1983.

14. Zingesser L, Schechter M, Gonatas N, et al: Agenesis of the corpus callosum associated with an interhemispheric arachnoid cyst. Br J Radiol 37:905-9, 1964.

15. Lahat E, Strauss S, Tadmor R, et al: Infantile spasms in a patient with septo-optic dysplasia, partial agenesis of the corpus callosum and an interhemispheric cyst. Clin Neurol Neurosurg 94:165-7, 1992.

16. Hirohata M, Matsua H, Miyagi J, et al: Interhemispheric arachnoid cyst; report of three cases. No Shinkei Geka 20:701-5, 1992.

17. Utsunomiya H, Hayashi T, Honda E, et al: A case of interhemispheric glio-ependymal cyst in a newborn infant. No Shinkei Geka 15:771-6, 1987.

18. Munemoto S, Ishiguro S, Kimura A, et al: Interhemispheric cyst in an adult associated with partial agenesis of the corpus callosum. Rinsho Hoshasen 35:959-62, 1990.

19. Bertino RE, Nyberg DA, Cyr DR, et al: Prenatal diagnosis of agenesis of the corpus callosum. J Ultra Med 7:251-60, 1988.

20. Parrish ML, Roessman U, Levinsohn MW: Agenesis of the corpus callosum: a study of the frequency of the associated malformations. Ann Neurol 6:349-54, 1979.