Brain Regions Tied to Autism in Rare Disorder

WEDNESDAY, Oct. 10, 2001 (HealthDayNews) -- Growths and abnormal biochemical activity in several areas of the brain may be responsible for autistic behaviors in children with a rare genetic disorder, suggests a new study.

By uncovering clues to autism in children with tuberous sclerosis complex (TSC), the researchers say they hope to shed light on what's behind autism in general. The findings appear in the latest issue of Neurology.

TSC is caused by mutations in one of two genes, known as TSC1 and TSC2, that prompt the growth of benign tumors, also called tubers, mainly in the brain, eyes, heart, kidney, skin and lungs.

Co-investigator Diane Chugani, professor of pediatrics and radiology at the Children's Hospital of Michigan, in Detroit, says the numbers of growths in the brain can vary from one or two to 30 or 40. "They also vary in size. They can be very small, like maybe a quarter of an inch around, or they can be several inches big."

TSC affects an estimated 50,000 people in the United States and more than 1 million people worldwide. It affects both sexes and all races and ethnic groups equally and has no cure.

Most people develop symptoms only in some organs. The severity of the disease can range from mild skin abnormalities to mental retardation or renal failure. Mental retardation and epileptic seizures often are the first signs of the disease in children. People with this disorder also can develop some or all of the symptoms of autism.

Autism is characterized by three main types of behaviors: difficulties with communication, problems with social interactions and behaviors with rigid adherence to routines.

Previous research has shown that children with tubers in the temporal lobes on either side of the brain were more likely to have autism. Chugani and her colleagues looked into the potential link with the help of new technology.

The researchers enrolled 26 boys and girls, ages 7 months to 16 years, who had been diagnosed with TSC and intractable epilepsy.

The team used magnetic resonance imaging (MRI) to study brain structure in each child and positron emission tomography (PET), a non-invasive imaging technique that uses injected radioactive tracers, to look at biochemical activity in the body.

The researchers compared the scans of the autistic children with the non-autistic, mentally retarded children and with children with relatively normal intelligence. "Most of the children that we studied actually had tubers in both temporal lobes, and that wasn't predictive of autism," says Chugani.

"There are basically two kinds of lesions that we think about with tuberous sclerosis," Chugani says. "Some of them are in the cortex, the outer layer of the brain, and some of them are buried deep within the brain" in fluid-filled regions called the ventricles.

Chugani says the scans in both the mentally retarded group and the autistic group showed that "if the child had decreased glucose metabolism in the temporal lobes surrounding the tubers, that was associated with a decrease in their ability to communicate."

"In the area of the deep cerebellar nuclei, there was actually an increase in glucose metabolism. That was actually associated with all three features of autism," says Chugani.

"A combination of lesions and biochemistry in those particular regions, in a certain combination, would lead to children with autism," says Chugani. "There have been abnormalities found in cases of autism without tuberous sclerosis in some of these same regions."

Dr. Steven Sparagana, co-director of the Tuberous Sclerosis Clinic at the Texas Scottish Rite Hospital for Children, says some literature has suggested that the cerebellum is involved in certain types of autism.

"If you had a reliable means of finding specific PET or MRI [evidence] that clued you in to autistic behaviors, that would be very important, first in diagnosis and also in helping strategize," says Sparagana. "You might be able to find a lesion earlier on and potentially enact interventions earlier."

Chugani says scientists know that autism is associated with genetic disorders like tuberous sclerosis, Rett syndrome and fragile X syndrome. "By understanding how brain chemistry might be different in these different disorders, it might help us understand autism in other groups of children."

"Understanding some of these pathways … might be something that should be looked at for treatment of autism in children with tuberous sclerosis," says Chugani. However, she says more information about these pathways is needed before doctors can treat autism in general.

What To Do

For more information about this rare disorder, visit the Tuberous Sclerosis Alliance, the British Tuberous Sclerosis Association, the National Institute of Neurological Disorders and Stroke or the Pediatric Database.

You can also check out the Autism Society of America or the Epilepsy Foundation.