When Laughter Makes Little Children Die

Most mothers hope their child's life will be filled with laughter - but for Lucy Hoggan, the sound of her son's giggles fills her with dread.

Lucy's son three-year-old Cadell has a rare form of epilepsy that causes strange laughter fits, which could one day kill him.

'It's frightening,' his mother Lucy, 38, said.

'Cadell may sound like he's laughing but his eyes are filled with fear. He's laughing but his eyes are panic stricken.

'It happens about ten times a day, at the most inappropriate times. One minute he'll be serious or relaxed the next he'll be manically laughing. Afterwards he cries or wants a cuddle and some reassurance.'

Cadell's epilepsy is caused by a benign tumour in his brain. Doctors have warned his family he will one day need an operation to remove the tumour. If the fits are allowed to carry on too severely, Cadell may one day kill himself laughing.

'It seems that brain surgery is the best way to treat it in the future,' said Lucy.

'When he has a seizure most people would just think he is laughing, but I can always tell. I know his brain is malfunctioning.'

The devoted mother is a member of the international support group Hypothalamic Hamartoma Uncontrolled Gelastic Seizures, or HHUGS. She wants more research so other children can be diagnosed earlier.

A decade ago there was no effective treatment for the HH tumour.   But a pioneering team of neurosurgeons in Australia brought hope for sufferers.

The team at Melbourne Royal Children's Hospital, headed by Prof Jeffrey Rosenfeld, devised a delicate operation whereby the HH tumour is accessed though the top of the brain.

Now years later, the surgery has become available at Kings College Hospital in London.

Dr Chris Chandler, specialist neurosurgeon at King's, said: 'It's such a rare condition.

'The hypothalamus controls hormones, body temperature, hunger, thirst, fatigue and anger.

'After the operation some patients experience uncontrollable hunger which can lead to obesity.

'Parents literally have to bolt all their food cupboards because the child will feel ravenous all the time even if they've just eaten.

'However all my patents have seen an improvement in their quality of life. We have seen some amazing results.'

The tuber cinereum is a part of the hypothalamus located between the mamillary bodies and the optic chiasma.

A hamartoma is a focal malformation that resembles a neoplasm; it is not a malignant tumor and it is composed of tissue elements normally found at that site that grow in a disorganized mass.

Hypothalamic hamartoma in the brain typically occurs in the hypothalamus and presents as a discrete mass isointense to cortex on both T1 and T2, without contrast enhancement (notice that this picture
is a post-contrast T1). This lesion may cause gelastic seizures, visual problems or early onset of puberty. The symptoms often begin in early infancy and are progressive, often with general cognitive and/or functional disability.

Curiously:
tuber cinereum is named after its colour…in fact, being gray matter it is called “cinereum” - the colour of the ash.

The word “hamartoma” derives from the greek “hamartia”: in Greek tragedy, the concept of “hamartia” is an error in judgment or unwitting mistake, normally applied to the actions of the hero…in the same view, in medicine, hamartoma is considered an error of development.

“Gelastic” is a term often used in medical terminology to indicate an association of a symptom or syndrome with laughter. The word originates from the Greek “gelaein” that means “to laugh”.

Three-year-old Grace Webster perches on the operating table, tiny and cold, covered only by a diaper and her sandy-blond Raggedy Ann hair. Her blue eyes gaze warily at the monster-size machines sprouting tube tentacles that encircle her — machines that will guide surgeons four inches into her brain.

Grace had her first menstrual period at 14 months old. Her body is racked more than 10 times a day with seizures, some of them bizarrely mimicking laughter or rage.

The source of her suffering is a hypothalamic hamartoma, or H.H., a tumor on the hypothalamus that strikes only a few thousand people in the world. And while the tumor is not malignant, until five years ago it was considered incurable, even when baffled doctors could diagnose it. Surgery was risky and largely ineffective. Medication seldom helped. Many children were institutionalized.

Now, thanks to an innovative surgical procedure, scores of these children have been cured at two centers that specialize in the disease. One is in Melbourne, Australia; the other is the Barrow Neurological Institute here in Phoenix.

About six times a day for most of his two years, Nicholas Worthington would break out into a heartbreaking laugh.

In one of nature's cruel ironies, the laughter is a symptom of hypothalamic hamartoma, an extremely rare disorder that brings sorrow to the victims and their families.

"When one of the seizures would come on, Nicholas would come over to you and say, 'owee,' 'owee' 'owee,' " said Nicholas's mother, Tricia Worthington of Jacksonville. "You never get used to it."

The Worthingtons and two other families' lives were transformed this week under the skilled hands of a renowned Australian neurosurgeon who came to Gainesville to spread hope to patients and expertise to the neurosurgical staff at Shands at the University of Florida.

The hypothalamus
Hypothalamic hamartoma is characterized by benign but abnormally formed brain tissue that grows near or against the hypothalamus, the control center of the brain. The hypothalamus is a well-protected region near the center of the brain that performs many nervous-system functions.

It controls hormones, hence young HH patients often have an abnormally early puberty. The hypothalamus influences everything from body temperature and food intake to the body's fight-or-flight mechanisms.

In HH patients, tissue called hamartoma develops near or intertwines with the hypothalamus early in pregnancy. It typically causes "gelastic" seizures, which Rosenfeld described as short bursts of what could be called a hybrid of laughing and crying. In some cases tremors of the arms occur.

Patients also commonly develop severe aggression, he said, called "hypothalamic rage."

Rosenfeld said he once operated on a patient about 25 years old who had exhibited such severe rage that it was feared he would kill somebody.

But the surgical treatment, he said, is more successful on younger patients, and only about 10 of his 52 patients have been adults. Medication usually is prescribed to adults to control the epileptic seizures associated with HH.