Schizencephaly

Definition

Schizencephaly, or "split brain," is a neurological disease caused by abnormal development of the brain, leading to the characteristic appearance of abnormal clefts in either one or both cerebral hemispheres. The exact etiology is unknown, although it is classified as a type of neuronal migration disorder and thought to be due to a defect in development that occurs during the period of one to seven months of fetal gestation.

Description

Schizencephaly may have different forms. The appearance of the abnormal schizencephalic brain varies depending on the size and extent of the clefts. Clefts may be unilateral or bilateral and usually extend from the surface of the brain to the fluid-filled ventricles. Clefts are usually located next to the Sylvian fissure, but may be located in any part of the hemispheres. Separation of the walls of the cleft is referred to as open-lip schizencephaly, whereas apposed walls are referred to as closed-lip schizencephaly.

Schizencephaly differs from porencephaly , another developmental disorder that is due to early injuries to the developing fetal brain. Porencephaly results from injured brain tissue that subsequently dissolves and leaves a fluid-filled area known as a porencephalic cyst. This cyst can resemble the cleft seen in schizencephaly. Whereas schizencephaly is thought to be a primary disorder of development or neuronal migration, porencephaly is thought to be due to secondary brain damage, although the distinction is not entirely clear. Some theories of schizencephaly also propose early brain injury as contributory, but at an earlier stage of development than in porencephaly. Differentiation between the two often requires brain imaging such as magnetic resonance imaging (MRI) to identify the nature of the brain tissue lining the cleft. In porencephaly, scar tissue and white matter is often present, whereas in schizencephaly, gray matter lines the cleft.

Demographics

Schizencephaly is a rare disorder and the incidence is unknown. It usually is noticed in infancy or childhood, although it may be diagnosed in adulthood with the onset of seizures .

Causes and symptoms

The cause of schizencephaly is unknown, although environmental and genetic factors have been proposed. Various theories exist as to the timing and nature of the defect in development. Early injury to the brain during the second trimester of pregnancy has been proposed to cause the characteristic clefts. These insults may be due to infection, poor blood flow causing stroke , or genetic abnormalities. The earlier onset of injury leading to absence of scar tissue around the defect presumably differentiates schizencephaly from porencephaly. A mutation in the EMX2 gene has been associated with schizencephaly in some familial cases, providing evidence for genetic causes. EMX2 is a transcription factor on human chromosome 10 that is important in early brain formation in mice and flies. The clefts in schizencephaly are often lined by normal brain tissue, but may often be surrounded by abnormal brain tissue that has an unusually high density of folding (polymicrogyria). Schizencephaly may also be associated with abnormal nerve clusters called heterotopias in different parts of the brain. Polymicrogyria and heterotopias are thought to be due to defective neuronal migration, and their association with schizencephaly suggests a common underlying mechanism.

Symptoms

Symptoms can vary widely depending on the extent and the size of the cleft. Patients may show developmental delay that can range from mild to severe. Bilateral and open-lip clefts are associated with more severe delay. Affected individuals may have small heads (microcephaly ) or increased pressure due to fluid accumulation inside the brain, known as hydrocephalus . Paralysis of the limbs may be present. The paralysis may be on one or both sides of the body depending on the location of the clefts. Abnormal muscle tone, including decreased tone (hypotonia ) and increased tone (spasticity ), can be seen. Some patients may have only seizures. Seizures usually present before three years of age, but patients may present with seizures in later life as their only symptom and then be diagnosed with schizencephaly by brain imaging.

Diagnosis

Diagnosis is made by imaging of the brain. A computed tomography scan (CT ) or MRI demonstrates the abnormal clefts, which may be bilateral or unilateral, open or closed lip. The clefts may appear symmetric or asymmetric. MRI may show evidence of polymicrogyria lining the clefts. There is no genetic testing available at this time for schizencephaly.

Treatment team

Treatment for patients with schizencephaly differs among patients due to the wide variety of clinical manifestations and symptoms. The team responsible for medical care may include a pediatrician and pediatric neurologist . A pediatric neurosurgeon may be involved in performing a shunt procedure for hydrocephalus. An orthopedic surgeon may perform surgeries to improve the mobility of spastic limbs. Physical and occupational therapists can help with improving mobility. A case manager may help in coordinating care and treatments.

Treatment

There is no cure for schizencephaly at this time. The treatment of schizencephaly is directed towards the symptoms caused by the abnormally formed brain. Seizures may require anticonvulsant drug therapy. Seizures that cannot be controlled with medications may be treated by surgical removal of the abnormal tissue surrounding the cleft. With complications of hydrocephalus, a surgical shunt procedure may be necessary to relieve fluid accumulation and pressure.

Recovery and rehabilitation

Due to the congenital nature of schizencephaly, symptoms tend to be unchanging and there is little recovery. Physical therapy may be useful in relieving symptoms of spasticity or paralysis and in improving mobility and ambulation. Occupational therapists may help maintain hand function in those with impaired ability.

Clinical trials

A clinical trial funded by the National Institutes of Health is underway to identify the genes responsible for schizencephaly and other developmental brain disorders associated with epilepsy . Contact information for the Walsh laboratory is listed under Resources.

Prognosis

The prognosis for individuals with schizencephaly depends on the amount of neurologic deficiency associated with the malformation. Some patients with unilateral clefts may only have seizures and no other cognitive or motor abnormalities. Seizures may respond to medications or require surgery if unmanageable. Patients with severe mental retardation and paralysis will often require lifelong dependent care and may have a shortened lifespan as a result of infections such as pneumonias. Bilateral clefts are associated with earlier onset of seizures and seizures that are more difficult to treat.

Special concerns

Due to developmental disability, individuals with schizencephaly may benefit from special education programs. Various state and federal programs are available to help individuals and their families with meeting these needs.

Resources

BOOKS

Menkes, John H., MD, and Harvey Sarnat, MD, eds. Childhood Neurology, 6th edition. Philadelphia: Lippincott Williams & Wilkins, 2000.

"Congenital Anomalies of the Nervous System." Nelson Textbook of Pediatrics, 17th edition, edited by Richard E. Behrman, MD, Robert M. Kliegman, MD, and Hal B. Jenson, MD. Philadelphia, PA: Saunders 2004.

PERIODICALS

Guerrini, R., and R. Carrozzo. "Epilepsy and Genetic Malformations of the Cerebral Cortex." American Journal of Medical Genetics 106 (2001): 160–173.

Ross, M. E., and C. A. Walsh. "Human Brain Malformations and Their Lessons for Neuronal Migration." Annual Review of Neuroscience 24 (2001): 1041–1070.

WEBSITES

National Institutes of Neurological Disorders and Stroke (NINDS). Schizencephaly Information Page. (February 26, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/schizencephaly.htm>.

National Institutes of Neurological Disorders and Stroke (NINDS). Cephalic Disorders Information Page. (February 26, 2004). <http://www.ninds.nih.gov/health_and_medical/pubs/cephalic_disorders.htm>.

ORGANIZATIONS

March of Dimes Birth Defects Foundation. 1275 Mamaroneck Avenue, White Plains, NY 10605. (914) 428-7100 or (888) MODIMES; Fax: (914) 428-8203. [email protected]. <http://www.marchofdimes.com>.

National Information Center for Children and Youth with Disabilities. P.O. Box 1492, Washington, DC 20013-1492. (202) 884-8200 or (800) 695-0285; Fax: (202) 884-8441. [email protected]. <http://www.nichcy.org>.

National Institute of Child Health and Human Development (NICHD). Bldg. 31, Rm. 2A32, Bethesda, MD 20892-2425. (301) 496-5133 or (800) 370-2943. [email protected]. <http://www.nichd.nih.gov>.

Walsh Lab Web Site. 4 Blackfan Circle, Boston, MA 02115. (617) 667-0813; Fax: (617) 667-0815. [email protected]. <http://walshlab.bidmc.harvard.edu/>.

Peter T. Lin, MD