Agenesis of the Corpus Callosum

Bs. Võ Tá Sơn

Bệnh viện Phụ sản – Nhi Đà Nẵng

HCM, 14.01.2017

• Mỏ: rostrum

• Gối: genu

• Thân: body

• Lồi: splenium

Anatomy

Prevalence

• From 0.3%–0.7% in the general population to 2%–3% in the developmentally disabled population.

Pathophysiology

• The formation of the CC starts with the development of the genu; the body and spleniumdevelop at a later stage.

• If the normal developmental process is disturbed, the CC may be completely or partially absent (hypogenetic). Because the developmental process starts from the anterior part and progresses front to rear, when the CC is hypogenetic, usually the posterior portion is affected (the posterior body and the splenium).

Pathophysiology: Rostrum?

• More recent studies based on diffusion tensor MRI showed that the rostrum, the genu, and the anterior part of the body were already present at around 15 weeks’ gestation.

• Diagnosis of ACC is usually impossible before 18 to 20 weeks’ gestation because the formation of the corpus callosum is incomplete.

Pathophysiology• 2 mechanisms:

• (1) a developmental injury (hypogenesis) from an acquired one (destruction).

• (2) association with hypoxic-ischemic injury and infectious causes.

• � 2 types of ACC

• (1) the axons are present but are unable to cross the midline; they form large aberrant fiber bundles (Probst bundles) along the medial hemispheric walls.

• (2) apparently less frequent, the axons fail to form; no Probst bundles are found.

Etiology

• Chromosomal, monogenic, and teratogenic.

• Chromosomal abnormalities are present in 20% of cases, especially trisomies 18 and 13.

• More than 100 syndromes involving ACC have been reported.

• Some environmental and metabolic factors also have been implicated in ACC, such as in utero cytomegalovirus and rubella infection and fetal alcohol exposure.

Characteristics of ACC• Lateral separation of the frontal horns and bodies

of the lateral ventricles

• Angled lateral peaks of the frontal horns and bodies of the lateral ventricles

• Elevation and variable dilatation of the third ventricle

• Dilatation of the occipital horns

• Concave medial wall of the lateral ventricles related to the bundles of Probst

• Abnormal radial orientation of medial cerebral gyriextending from the roof of the third ventricle

Ultrasound diagnosis

• In fetuses in cephalic presentation, the transvaginal approach is preferred; in fetuses in breech presentation, a transfundalapproach is suggested.

Ultrasound diagnosis

Axial planes (Indirect signs)• (1) On the axial transventricular view at 2nd trim:

hypoplastic or absent CSP � complete ACCbecause of common anatomic and embryogenetic formation.

• (2) Colpocephaly (= tear drop sign) (dilatation of the atria and occipital horns, “which is determined by the absence of the splenium and by a defect of the intrinsic association bundles of the occipital lobe);

• (3) Increased separation of the hemispheres with the bodies of the lateral ventricles parallel to each other and shifted laterally.

• Dorsal elevation of the third ventricle can be also present.

Axial planes

Axial planes

Axial planes

ACC: Lateral ventricle in the case of agenesis of corpus callosum, with the “teardrop sign.” The distance between the medial border of the lateral ventricle and the falx cerebri is larger in the part of the sharply pointed anterior horn than that fromthe posterior horn. The third ventricle is seen centrally; the septum pellucidum cannot be seen.

Coronal plane

• The frontal horns separated more than usual with inner walls that are concave medially because of the longitudinal bundle of Probstthat fail to cross the hemispheres and instead are rerouted parasagittally, parallel to the midline.

• Absence of the CC.

Coronal plane

• ACC. Frontal view of the anterior part of the brain in agenesis of corpus callosum: “three lines sign.” The longitudinal fissure separating the cerebral hemispheres is widened.

The midsagittal plane

• Direct signs: absence of the CC (still see in the coronal plane)

• And, in advanced gestation or postnatally, an atypical radiating appearance of the median sulci, which converge toward the third ventricle. In this view, usually no cingulate gyrus can be recognized, or it appears incomplete.

The midsagittal plane

Partial ACC

• Usually the posterior portion is affected (the posterior body and the splenium);

• The CSP can be present, and often the only indirect US sign is a mild colpocephaly.

• Sometimes the indirect signs of partial ACC may also be completely absent.

• A sagittal view is the only way to make the diagnosis, visualizing a small CC that is lacking the posterior partand only partially surrounds the 3rd ventricle.

• Less frequently, the remaining structure is the genu; it can appear thin and barely discernible with gray-scale imaging and can be identified only when highlighted by the course of the pericallosal artery.

Partial ACC

Color Doppler

• The semicircular loop, normally formed by the pericallosal artery along the superior surface of the CC, is lost.

• Its value is even greater in the case of partial ACC.

• In partial ACC, the pericallosal artery closely follows and depicts the small anterior part of the CC, often discernible with difficulty on gray-scale imaging. Its course is then lost, being usually absent in the posterior part of the CC.

Color Doppler

Color Doppler

Differential diagnosis

• Lobar holoprosencephaly

Associated with ACC• (1) Interhemispheric cysts: two main

categories:

– the cysts are herniations of the ventricular system, representing the dorsal expansion of the roof of the 3rd ventricle.

– clearly separated from the ventricles.

• (2) Intracranial lipoma: visible only in the 3rd

trimester as a hyperechogenic image under the inferior part of the interhemisphericscissure.

Associated with ACC

Fetal MRI

• Fetal MRI allows good visualization of the corpus callosum and its anomalies.

• The main advantage of MRI is the recognition of possible additional cerebral anomalies, such as late sulcation, migration anomalies, and heterotopias. In these cases, it is more sensitive than US.

• However, the presence of these anomalies usually can be recognized only from the late second trimester onward, when advanced development of the sulci and gyri has occurred.

Fetal MRI

Association with other malformations

• Cerebral and/or extracerebral malformations, including a number of syndromes and metabolic diseases.

• The risk of associated brain anomalies is extremely high (up to 80%) including Dandy–Walker complex, gyral anomalies, and neuronal heterotopia.

• The risk of associated extra-CNS abnormalities is high (up to 60%), including congenital heart disease and skeletal and genitourinary defects.

Risk of chromosomal anomalies

• .This is relatively high (20% of cases): trisomy 13 and 18, deletions [del(4)(p16), del(l6)(q23), del(X)(p22)], and duplications [dup(8)(p21–23), dup(11)(q23–qter)].

Risk of nonchromosomal syndromes

Obstetric management.

• Mandatory karyotyping

• Full family hystory

• Careful search for additional structural anomalies (hematologic diseases, asplenia, anophthalmia, cleft lip/palate, albinism, bone lesions, congenital megacolon, and camptodactyly).

• Fetal MRI: late sulcation, migration anomalies, and heterotopia, with late development of the sulci and gyri.

Prognosis

Prognosis of ACC is controversial.

The presence of additional anomalies � a worse prognosis.

Isolated ACC � a better prognosis.

BUT

Neurodevelopmental delay is present in about 25% of cases of isolated ACC at 3 years AND subtle neuropsychologic, perceptual, and motor defects can emerge later in life.

� Follow up to 6 years of age to update status of these patients.

Prognosis, survival, and quality of life

• Most of individuals with ACC suffered from developmental delay and often from seizures.

• Several postnatal case series suggest a direct relationship between the occurrence of associated brain abnormalities and poor neurodevelopmental outcome.

• With isolated ACC, caution must be adopted when assessing the fetal/neonatal prognosis.

• Significant neurodevelopmental delay develops in a consistent proportion of cases (20%–30%), even if ACC is confirmed postnatally to be isolated. The same also applies to isolated partial ACC.

Prognosis, survival, and quality of life• Even when the outcome is good, subtle

neuropsychologic, perceptual, and motor defects can emerge later in life, because all individuals with CACC/PACC have some neuropsychological symptoms.

• Considering the presence of neurosensorialinformation transfer defects, no differences seem to exist between PACC and CACC in terms of the performance accuracy of the somatosensory functions.

• The functions of the CC are not completely understood and it is difficult to assess correctly the neuropsychologic status of individuals with CACC/PACC and normal-range IQs, and the role of possible compensatory mechanisms

Prognosis, survival, and quality of life

• The recurrence risk is 5% when syndromes are excluded.

Postnatal care

• MRI is considered the best method of confirming the diagnosis and excluding other central nervous system anomalies.

• Treatment is symptomatic and includes physiotherapy, psychotherapy, speech therapy, and antiepileptic drugs for seizures.

Information for the patient

• Up to 1% of adults have congenital agenesis of the corpus callosum, without their knowledge and without symptoms.

• In the absence of associated anomalies, mental development is normal.

Summary• Incidence. From 0.3%–0.7% in the general population

to 2%–3% in the developmentally disabled population.

• Ultrasound diagnosis. Midsagittal view: Complete or partial absence of the corpus callosum. Axial views: Colpocephaly, absence of the CSP (in complete agenesis). Coronal views: lateral convexity of and increased distance between the frontal horns.

• Risk of chromosomal anomalies. High: 20%.

• Risk of nonchromosomal syndromes. High.

• Outcome. About 20%–30% rate of significant neurodevelopmental delay in isolated forms has been reported; in nonisolated form the prognosis is poor.

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