Agenesis of the Corpus Callosum

Unraveling the mystery

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This article, submitted by Susan L. Koubek, won first place in the Student category of the 2004 RT Image Writing Competition.

The corpus callosum is the largest connection pathway in the human brain. It is made of more than 200 million nerve fibers that connect the left and right hemispheres of the brain. The corpus callosum allows the sides of the brain to "communicate" with each other and coordinate their efforts. Each hemisphere of the brain is specialized to control movement and feeling of the opposite half of the body, and each hemisphere specializes in processing certain types of information, such as language or spatial patterns. In order for the corpus to coordinate movement or think about complex information, the hemispheres must communicate with each other, and the corpus callosum is the main connector that allows that communication.

In a typical infant brain, the corpus callosum develops between 12 and 16 weeks after conception, near the end of the first trimester. The entire structure develops prior to birth. The fibers of the corpus callosum continue to become more effective and efficient into adolescence. By the time a child is approximately 12, the corpus callosum functions essentially as it will in adulthood, allowing rapid interaction between the two sides of the brain.

Agenesis of the Corpus Callosum

Agenesis of the callosum is the congenital absence of the brain's corpus callosum. Once thought to be a rare condition, it seems experts now cannot agree; some suggest as many as seven in 1,000 children may have agenesis of the callosum, while others believe it may be as rare as five in 1 million.

According to the National Organization for Disorders of the Corpus Callosum (NODCC), most patients are diagnosed within the first two years of life. The disruption to the development of the corpus callosum occurs during the fifth to 16th week of pregnancy. There is no single cause. Many different factors can interfere with the development such as:

• Prenatal infections or viruses such as rubella
• Chromosomal (genetic) abnormalities
• Toxic metabolic conditions such as fetal alcohol syndrome
• Blockage of the growth of the corpus callosum with cysts
  

Prenatal diagnosis is now routinely made with an ultrasound in the 20th week and an MRI completed in the 30th week. Physically, complete agenesis of the callosum is a condition that does not change and it will not get worse. Since the callosum is already absent, it cannot regenerate or degenerate, so disorders of the corpus callosum are conditions one must "live with" rather than "hope to recover from."

MRI is the modality of choice to check for abnormalities of the brain because it is non-invasive and provides detailed pictures of the brain and nerve tissues from multiple planes without obstruction by overlying bone. About 90 percent of all MRI scans are for brain and spine disorders.

MRI is useful in brain and neurological disorders because it can clearly show various types of nerve tissue. It provides clear pictures of the brain stem and posterior brain, which are difficult to view on a CT scan. MRI can help distinguish tumors or other lesions from normal tissues.

Symptoms and Associations

Disorders of the corpus callosum are not illnesses or diseases, but abnormalities of the brain. Many people with these conditions are healthy. Clinical findings vary widely with these patients, ranging from asymptomatic normal intellectual capacities to severe mental retardation. Some researchers have argued that this is a "natural" split brain with each side of the brain working independently, but there have been some children with agenesis of the corpus callosum who have shown that both sides of the brain do communicate.

The brain is a very redundant organ and can compensate for areas that are affected. No two children with agenesis of the corpus callosum show the same symptoms, which makes research on this condition difficult and almost impossible to predict the outcome of cognitive abilities.

Some findings in agenesis of the callosum as seen on an MRI are missing portions of the corpus callosum; high riding third ventricles; widely spaced, parallel, crescent-shaped lateral ventricles; medial impingement of the Probst bundle on ventricles, cyst or lipom; pointed frontal horns; and incomplete development of hippocampal formation.

In nearly half of all cases, agenesis of the callosum is associated with different congenital abnormalities, including Dandy-Walker syndrome, septo-optic dysplasia, Chiari one and two malformations, Aicardi's syndrome and holoprosencephaly. Arachnoid cysts and hydrocephalus may also develop in conjunction with these abnormalities.

Dandy-Walker Syndrome

Dandy-Walker syndrome is a congenital brain malformation involving the cerebellum   the part of the brain that controls movement and the fluid filled spaces around it. The main conditions of the syndrome are an enlargement of the fourth ventricle (a small channel that allows fluid to flow freely between upper and lower areas of the brain and spinal cord), a partial or complete absence of the cerebellar vermis (the area between the two cerebellar hemispheres) and cyst formation near the internal base of the skull, called arachnoid cysts. These cysts may develop between the surface of the brain and the cranial base. Small cysts are usually asymptomatic while larger cysts may cause cranial deformations, headaches, seizures, hydrocephalus and increased intracranial pressure.

Treatment for these cysts is symptomatic. When pressure gets to be too much, a surgical placement of a shunt may be required. Untreated, these cysts may cause permanent neurological damage due to progressive expansion of the cyst or bleeding. But with treatment most pediatric patients do well.

An increase in the size of the fluid spaces surrounding the brain and an increase in pressure can also occur, called hydrocephalus  a condition that causes an enlargement of the ventricles of the brain because of buildup of cerebrospinal fluid, which can lead to increased intracranial pressure. This can be caused by the spinal fluid not being properly absorbed or by some kind of blockage to the flow of the fluid. Ultrasound and MRI are the modalities of choice to check for this abnormality. Treatment entails putting in a shunt to drain some of the excess fluid. This syndrome, much like agenesis of the callosum, can appear dramatically or develop unnoticed. Symptoms that often occur in early infancy include slow motor development and progressive enlargement of the skull.

In older children, symptoms of increased intracranial pressure, such as irritability, vomiting and convulsions, and signs of cerebellar dysfunction like unsteadiness, lack of muscle coordination or jerky movements of the eyes, may occur, as well as other symptoms like increased head circumference, bulging of the back of the skull and problems with nerves that control the eyes, face and neck. Dandy-Walker is commonly associated with agenesis of the corpus callosum. Treatment for this syndrome includes placing a tube to reduce intracranial pressure and control swelling.

Children with this syndrome may never have normal intellectual development, even when the hydrocephalus is treated early and correctly. A long life depends on the severity of the syndrome and associated malformations. The presence of multiple congenital defects may shorten the life span.

Aicardi Syndrome

Aicardi syndrome is characterized by absence of the corpus callosum, infantile spasms, mental retardation, lesions of the retina, enlarged ventricles and porencephalic cysts (gaps in the brain where there should be healthy brain tissue). Children are most commonly identified with this syndrome between the ages of three and five months and it seems to only affect females. A large number of these girls come from normal births and seem to develop normally until around the age of three months, when they begin to have infantile spasms (seizures or convulsions). The cause of infantile spasms at this age is due to closure of the final neural synapses in the brain  a stage of normal brain development. The known age range of affected children is from birth to early 20s.

There is no cure for Aicardi syndrome nor is there a standard course of treatment. Treatment of Aicardi syndrome involves management of seizures and early, continuing intervention programs to help parents and children cope with developmental delays.

Septo-Optic Dysplasia

Septo-optic dysplasia is a rare disorder characterized by abnormal development of the optic disc, pituitary deficiencies and often agenesis of the septum pellucidum (the part of the brain that separates the anterior horns or the lateral ventricles). Symptoms may include blindness in one or more eyes, inward and outward deviation of the eyes, hormonal problems and low muscle tone. Some children have normal intelligence while others have learning disabilities and mental retardation. Most are developmentally delayed due to vision impairment or neurological disorders.

Treatment of septo-optic dysplasia is symptomatic. Hormone deficiencies may be treated with hormone replacement therapy. The optical problems associated with septo-optic dysplasia are usually not treatable. Vision, physical and occupational therapies may be required.

Holoprosencephaly

Holoprosencephaly is another disorder associated with agenesis of the callosum, but its specific cause is unknown. It is estimated that this disorder affects one in 5,000 to one in 10,000 live births. This disorder is often caused by failure of the embryonic forebrain to sufficiently divide into two double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects.

In most cases, the malformations are so severe that they cause death before birth. In less severe cases, babies are born with normal or near-normal brain development and facial deformities that may affect the eyes, nose and upper lip. The least severe of the facial anomalies is the median cleft lip.

The most severe abnormality is characterized by a single eye located in the area normally occupied by the root of the nose, a missing nose or a tubular-shaped nose located above the eye. Another anomaly is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped, closely set eyes.

There is no standard treatment for holoprosencephaly. Treatment is symptomatic and supportive. The prognosis for people with this disorder depends on the severity of the brain and facial deformities. The most severely affected children may live several months or years and the least affected may live a normal life span.

Development and Behavioral Characteristics

Behaviorally, people with agenesis of the callosum may fall behind their peers in social and problem-solving skills in elementary school or as they approach adolescence. In typical development, the fibers of the corpus callosum become more efficient as children approach adolescence. Children with an intact corpus callosum show rapid gains in abstract reasoning, problem solving and social comprehension. Although a child with agenesis of the corpus callosum may be able to keep up with his or her peers early on, as the peer group begins to make use of an increasingly efficient corpus callosum, the child with agenesis of the corpus falls behind in mental and social functioning. Behavioral challenges for people with agenesis of the callosum may become more evident as they grow into adolescence and young adulthood.

According to the NODCC, some behavioral characteristics associated with agenesis of the callosum may be:

• Delays in attaining developmental milestones such as walking, talking and reading
• Clumsiness and poor motor coordination, generally on skills that require coordination of left and right hands and feet such as swimming, bike riding, tying shoes and driving
• Atypical sensitivity to particular sensory cues, such as food textures and certain types of touch, but often with a high tolerance to pain
• Difficulties on multidimensional tasks like using language in social situations, such as jokes and metaphors; appropriate motor responses to visual information, such as stepping on others' toes and handwriting that runs off the page; and the use of complex reasoning, creativity and problem solving, such as trying to understand math and science requirements in junior high school and high school
• Challenges with social interactions due to difficulty imagining potential consequences of behavior, being insensitive to the thoughts and feelings of others and misunderstanding social cues, such as vulnerable suggestion, gullibility and not recognizing emotions communicated by tone of voice
• Mental and social processing problems become more apparent with age, with problems particularly evident from junior high school into adulthood
• Limited insight into their own behavior, social problems and mental challenges
  

Prognosis for Agenesis of the Corpus Callosum

The outlook with agenesis of the corpus is variable. The condition does not cause death in the majority of patients. Although many children with the disorder lead normal lives and have an average intelligence, careful neuropsychological testing may reveal subtle differences in higher cortical function compared to individuals of the same age and education without agenesis of the callosum. Children with this disorder and with developmental delay and/or seizures should be screened for metabolic disorders. Mental retardation associated with this disorder is not progressive.

Treatment is symptomatic and consists of physiotherapy, speech therapy, antiepileptic drugs and psychotherapy. To further understand the natural history of the malformation and to determine its outcome, data should be collected using standardized evaluation tests and sufficient follow-up in prospective studies with children with agenesis of the corpus callosum. A pediatrician can manage the individual's overall health, but it is recommended to follow up with a neurologist at least yearly, as well as an endocrinologist and ophthalmologist.

There are many things that do not come easily for children with agenesis of the corpus callosum, such as learning to reach for toys, lifting their heads up while lying on their stomachs, rolling over from stomach to back, sitting up, eating table foods, walking, talking and jumping. The learning period is a struggle for these kids. But with each struggle comes a deep sense of appreciation for each and every small accomplishment they make.

— Susan L. Koubek is a second-year radiology student living in North Platte, Neb. She is completing her clinical rotations at Great Plains Regional Hospital in North Platte and is working part-time at Gothenburg Memorial Hospital in Gothenburg, Neb. Questions and comments can be directed to editorial@rt-image.com.