Children with epilepsy view disorder one way; their parents view it another way

The fact that kids' perceptions differ from parents' perhaps isn't surprising. But when each is asked about the child's illness, the implications of that disconnect can be thought-provoking.

Researchers from UCLA's department of neurology asked 143 children with epilepsy, each of whom had a healthy sibling, what they thought of their quality of life as compared to that of their siblings. They asked the parents to weigh in as well.

The kids, with an average age of 12, thought: Eh, about the same. The parents thought: Oh, much worse.

The researchers suggest that, for starters, kids are simply worried about different things than their parents. That math test still needs to be passed, that ballgame still beckons. Second, parents are more likely to be anxious about how the condition will affect their kids both in the short term and in the long term. They understand that the potential for seizures is just the beginning -- they worry about the possible long-term ramifications for jobs, income, education and marital status.

But the researchers also write: "Having a chronic disease, or disability, does not necessarily mean that a person is unsatisfied with their life, despite what others may think — a term denoted the disability paradox."

Here's the news release from UCLA; the abstract of the epilepsy study, published online in Value in Health; and epilepsy information from the Epilepsy Foundation.

Similar results have been found, the researchers note, among kids with cancer, asthma, diabetes and other disorders.

It would seem this paradox should be kept in mind when considering the needs of children -- and adults -- with other conditions as well.

-- Tami Dennis

Photo: Kids are kids, with kids' concerns.

Credit: Los Angeles Times

Deep brain stimulation reduces epileptic seizures, study finds

Electrodes implanted deep in the brain where they provide a minute electrical charge can sharply reduce the incidence of seizures in epileptics who cannot bring their seizures under control with drugs, Stanford researchers reported Wednesday. The approach, called deep brain stimulation, is already being used in more than 70,000 Americans with Parkinson's disease and other disorders, and its use is being studied for a variety of other applications.

Epilepsy, which strikes one in 100 people, is characterized by recurrent disabling seizures or electrical storms in the brain that occur when electrical circuits there start firing spontaneously, rhythmically and uncontrollably. This can cause disturbances in vision, hearing and behavior, as well as a loss of consciousness and involuntary muscle movements that can produce injury. About two-thirds of patients can control symptoms with drugs, but that still "leaves a large number of people in great need of something better," said Dr. Robert Fisher of the Stanford University School of Medicine, who led the study.

The researchers used a battery-operated, pacemaker-like device that delivers precisely measured and timed electrical impulses to the brain. It is manufactured by Medtronic Inc. of Minneapolis, which sponsored the trial. The small battery and electronic circuitry are implanted under the skin of the chest  and fine wires are threaded under the skin up to the neck, behind the ear and into the brain. For the study, the electrodes were implanted in the anterior nucleus of the thalamus, where epileptic seizures often are triggered.

Fisher and his colleagues enrolled 110 patients whose seizures could not be controlled with drugs and who were suffering an average of nearly 20 seizures per month. They implanted the device in all. During the first three months, half of the devices were turned on and half--the control group--were not, but neither patients nor doctors knew which was which. Then all devices were turned on.

At the end of three months, the team reported in the journal Epilepsia, patients whose stimulators were turned on had 40% fewer seizures than before the implantation, while those in the control group had 14.5% fewer--indicating a placebo effect. Only 7% of the patients receiving treatment experienced seizure-related injuries during the three months, compared with 26% in the control group.

By the end of the first year--nine months after the devices had been turned on in the control group--all patients reported an average of 41% fewer seizures. At two years, they reported 56% fewer seizures. Those patients who have now been followed for three years, Fisher added, have a 68% reduction in seizures. Fourteen patients reported having no seizures for periods as long as six months.

The primary side effects were limited to infections at the implant site, misplaced electrical leads that had to be repositioned, and tingling sensations.

A Food and Drug Administration advisory panel on Friday recommended that the agency approve the device for treating epilepsy. Although the agency does not have to follow recommendations from its advisory panels, it generally does.

-- Thomas H. Maugh II

Reflections on H.M., a man who couldn't remember

Memories can haunt, torment, energize, sustain, amuse, irritate ... and most people take their abilities to form them for granted. A man who couldn't do this managed to teach the rest of us.

"Henry Molaison lived in relative obscurity, but he possessed one of the world's most famous brains. Known to generations of scientists and psychology students as H.M., Molaison lost the ability to form new memories after surgery removed part of his brain and, by agreeing to be studied over several decades, transformed the way we understand memory. H.M. died last December, but science isn't done with his brain..."

So begins today's story in the L.A. Times. Read more.

For more on memory and how it works, McGill University in Montreal offers this primer: The Brain From Top to Bottom.

From NPR, we have audio recordings of Molaison and Brenda Milner, who studied Molaison for years. Hear his voice, and read the transcript here.

Here's a reprint from the original article about Molaison by Milner and surgeon William Beecher Scoville. It was published in 1957 in the Journal of Neurology, Neurosurgery and Psychiatry.

And, finally, there's this reflection, published earlier this year in the McGill Science Undergrad Research Journal, shortly after Molaison's death a year ago.

— Tami Dennis

Photo: Henry G. Molaison, long known only as H.M., is shown in the 1970s, years after the surgery that devastated his memory.

Reconsidering antiepileptic medications as a treatment for bipolar disorder

A study coming out in tomorrow’s edition of Archives of General Psychiatry may prompt doctors and patients to reconsider the merits of using antiepileptic drugs to treat people with bipolar disorder.

Just last year, the U.S. Food and Drug Administration issued an alert that antiepileptic drugs -- such as Neurontin (generic name gabapentin), Lyrica (pregabalin), Topamax (topiramate) and Tegretol (carbamazepine) -- increased the risk of suicidal thoughts and behaviors. That’s particularly important for patients with bipolar disorder, because they already have a higher risk of suicide compared to healthy people.

But the new analysis finds that bipolar people who took one of 11 antiepileptic medications had the same rate of suicide attempts -- 13 per 1,000 patients per year -- as those who didn’t take any drugs for their condition. That rate was slightly lower than for bipolar people who took lithium (18 suicide attempts per 1,000 patients per year). It was also much lower than the rate of suicide attempts among bipolar people in the year before they began taking antiepileptic medications (72 per 1,000 patients per year).

The findings are based on records of 47,918 patients with bipolar disorder who were included in the PharMetrics medical claims database. The study was conducted by researchers from the Center for Health Statistics at the University of Illinois at Chicago and the Columbia University College of Physicians and Surgeons in New York. Two of the researchers have produced expert testimony for Pfizer Pharmaceuticals in litigation involving Neurontin. Pfizer purchased the dataset from PharMetrics for $15,000 but was not involved in the research and didn’t influence or review the results, according to the researchers.

The work was funded by grants from the National Institute of Mental Health and the Agency for Healthcare Research and Quality.

You can read the FDA’s 2008 statistical review of antiepileptic drugs and suicidal ideation and behavior here. The most up-to-date info from the agency is online here.

-- Karen Kaplan

Photo: Perhaps this drug is safer, and more useful, than thought. Credit: Pfizer Inc.

For pregnant women with MS or epilepsy, some good news

Researchers at Stanford University have found that women with multiple sclerosis or epilepsy have only a slightly higher risk of abnormal fetal growth and C-section delivery compared with women without the conditions. Let's repeat, only a slightly higher risk. Nor do they appear to suffer a higher rate of other complications compared with pregnant women in general.

Here's ...

The news release from Stanford University.

The abstract from the study, based on an analysis of a large national database and published Wednesday in the journal Neurology.

And more on pregnancy and MS (from the National Multiple Sclerosis Society) and on pregnancy and epilepsy (from the Epilepsy Foundation).

Both MS and epilepsy are relatively common in women of child-bearing years. And the findings should provide some reassurance to those with the conditions who are pregnant -- or contemplating becoming so.

-- Tami Dennis

FDA approves first drug for infantile spasms

The Food and Drug Administration on Friday approved the first drug for treating infantile spasms, a rare and devastating disease that wracks infants with hundreds of spasms every day, interferes with neurological development and kills as many as 20% of victims.

The approval of the drug, called Sabril, represents the end of a 15-year odyssey for Dr. W. Donald Shields, a pediatric neurologist at UCLA's Geffen School of Medicine, who pioneered studies of the drug in the U.S.

"I can't tell you how excited I was yesterday when I found out" the drug was approved, he said today. "This is a drug we really need to have."

The drug, known generically as vigabatrin, is not perfect. As many as 30% of those who use it suffer from a loss of peripheral vision, although it does not affect central vision and such tasks as reading. Patients who use the drug will have to be monitored very closely for loss of vision, but most parents Shields has encountered are not overly concerned about the problem. "If you lose peripheral vision but are developmentally normal, it is probably worth it," he said.

The FDA also approved the drug for use in epilepsy patients suffering a phenomenon called complex partial seizures, which can cause impaired consciousness. About a third of the 3 million American epileptics suffer from such seizures and about a third of those do not get relief with existing drugs. Sabril would be a treatment of last resort for them.

Infantile seizures, which affect about 2,500 American infants each year, usually strikes those ages 3 to 6 months. Victims have as many as 100 seizures per episode, and several episodes a day. Click here to see the frightening episodes. There is no approved treatment for the seizures in the United States, but parents who can afford it have been importing Sabril from Canada and Europe, where it is available.

Vigabatrin was developed by French scientists in the 1970s as a suicide inhibitor of the enzyme gamma-aminobutyric acid transaminase, which breaks down gamma-amino-butyric acid or GABA in the brain. Researchers postulated that infantile seizures were caused by a deficit of GABA in the brain and hoped the drug would raise levels by preventing its destruction. The drug was originally owned by Sanofi-Aventis.

In the early 1990s, Shields talked to the president of Aventis and persuaded him to give his team 65,000 tablets of the drug and to provide funding for a research study. But when the visual-field problem emerged in 1993, the company lost interest in the drug. All of the pills given to Shields expired in 2001, and he had to stop his research. "We thought that was the end of it, even though it works really well for a lot of patients," he said.

At the beginning of this decade, however, he talked to Mike Burke, head of sales and marketing for Ovation Pharmaceuticals Inc. -- now Lundbeck Inc. of Deerfield, Ill. When Burke asked if there were any drugs he needed, Shields pointed him to Sabril. By 2003, Lundbeck had acquired U.S. rights to the drug, and the company helped Shields assemble his data from the previous trial into a form that could be submitted to the FDA. The data were presented to an FDA advisory committee in January, and the committee unanimously recommended approval.

As a condition of approval, physicians who prescribe the drug must do a baseline test of visual acuity before the patient begins taking the drug, and then every three months afterward. It is usually clear within a month or two if the drug is going to work, Shields said. If it doesn't, the patient should stop taking it to avoid side effects that are not counterbalanced by benefits.

In infants, the drug is normally given for six to nine months, then tapered off to see if the symptoms reappear. If they do, then the cycle is repeated.

Because so few infants have the condition, Sabril is designated as an orphan drug, so that the government provides Lundbeck with financial incentives to promote its development.

Some research suggests that the drug is also useful in blocking cravings for heroin and other addictive substances, and Lundbeck has applied for approval for that application as well.

-- Thomas H. Maugh II

Photo: Dr. W. Donald Shields

Credit: UCLA