Living with seizures

SHE is well known in Britain as an author, both of fiction and nonfiction, a broadcaster and a journalist, but Polly Toynbee has recently extended her range by writing two plays with campaigning medical themes.Two years ago she wrote one about the impact of breast cancer; now she has written Brain Storm, which illustrates the difficulties people experience in coming to terms with a diagnosis of epilepsy, and with discussing their worries with the medical professions. Apparently they find it hard to get across the effects that some drugs can have on everyday life. Although sufferers understand that the primary aim must be to control, or even to stop, the seizures, this goal is sometimes attainable only at a cost of blunted memory, reduced attention span and slower thought processes.

Even comparatively minor changes in quality of life may have dramatic consequences on professional and domestic life. Patients are the first to agree that having to tolerate uncontrolled seizures would be even more disruptive to their office and household; however, they would be grateful for some time to discuss with their consultant the possibility of changing treatment, or dosage, so as to discover the best regimen suited to physique, psyche and lifestyle.

As in much of medicine, a plethora of treatments is available and changing to a different drug of the same group without changing the type of drug can make a difference to side effects and to the patient's quality of life. Personal tailoring of drugs is increasingly common, and in time it may be possible to select the ideal fit of a drug by studying a patient's genotype.

Brain Storm, which had its premiere in Sydney earlier this month to coincide with the opening of the 18th World Congress of Neurology, examines sufferers' hopes of being given a clearly defined diagnosis and an effective treatment that frees them of seizures without giving rise to detrimental side effects. The quandaries, problems and messages of the play are explored through the thoughts of a professor of neurology, who does not come face to face with the patients but nevertheless hears them recount their case histories on stage.

Too often, it seems, patients' expectations are not entirely met by the reality of the treatment; in many cases, the drugs should have changed years earlier and new, more beneficial treatments could perhaps have been offered but were never considered. These stories prompt the professor to analyse his own cases, assessing the treatment that he hands out _ in some cases he had to admit to himself that the regimens had been determined by his own inertia rather than the patients' needs. He was also made more aware of the difficulties that many patients have in communicating with healthcare professionals. On occasions, there are also problems in establishing good lines of communication between people working with different medical disciplines.

Epilepsy is the most common brain disorder in every country; 40 million people worldwide suffer from the condition at any one time, and more than 100 million have displayed epileptic symptoms at some time in their lives. In Britain there are 400,000 sufferers, while 1 million have had it at some point in their lives and 1.5 million will have experienced a seizure on at least one occasion _ epilepsy is not diagnosed on the basis of one incident.

In Australia there are about 90,900 people who had conditions associated with epilepsy in 1998, or about 0.5 per cent of the population. As those watching the television series Rome will have noticed, Julius Caesar had seizures; he took them in his stride and did not let them spoil his parties. Most people are not so laid-back, or so powerful that they can ignore not only the convulsions but the effect that it has on those around them.

Brutus et al denied historians the opportunity of finding out what effect the disease might have had on Caesar _ and the Empire _ in the long term; in 21st century Britain, however, the condition increases the unemployment rate by a factor of three when comparing people with similar qualifications and education. The objective of those treating epilepsy is not only to rid their patients of convulsions, but also to rid society of the stigma attached to the condition. Perhaps the latter would be easier if more people realised that a seizure occurs when the brain spontaneously undergoes aberrant changes in electrochemical activity. Seventy to 80 per cent of attacks can now be controlled with drugs.

The play in Sydney was funded and organised by the International Bureau of Epilepsy and by UCB, one of the new international biopharmaceutical manufacturers that produced, among other products, Keppra (levetiracetam). It was not mentioned throughout the evening, but it is perhaps no coincidence that its use so far has shown it to be a very clean drug, with a good side effect profile that can now be used to treat partial seizures.

Epilepsy treatment for kids

Epilepsy is a condition caused by periods of abnormal electrical activity in the brain. The disruption of brain signals leads to a seizure. According to the Epilepsy Foundation, more than 2.7 million people in the U.S. have epilepsy. Roughly 200,000 new cases are diagnosed each year. Epilepsy is slightly more common in males, African-Americans and socially disadvantaged populations.

Epilepsy is typically classified into two categories of seizures: generalized seizures and partial seizures. Generalized seizures affect both sides of the brain and lead to a loss of consciousness. They are further classified into one of four types: absence seizures, atonic seizures, myoclonic seizures and tonic clonic seizures. Absence seizures (petit mal seizures) are brief lapses of awareness that usually only last a few seconds.

Since they are very brief, the seizures are often unnoticed. A patient may have a blank stare and be temporarily unresponsive. Absence seizures are more common in children. Atonic seizures (drop attacks) cause a sudden loss of muscle tone and collapse. Since the symptoms occur without warning, patients are at risk for serious injuries from a fall. Myoclonic seizures are brief, rapid contractions of muscles, causing sudden jerks.

The condition usually affects both sides of the body at the same time. Generalized tonic clonic seizures (grand mal seizures) initially cause stiffening (tonic phase) and breathing disruptions (including breathing cessation). The symptoms are followed by limb and facial jerking and a return of breathing. Generalized tonic clonic seizures are the most common type of generalized seizure. Some patients may only experience the tonic phase and others only the clonic phase of the seizure.

Partial seizures are those that affect one side of the brain. They are the common type of seizure and are subdivided into simple partial seizures and complex partial seizures. Simple partial seizures don’t cause a loss of consciousness, but a patient may not be able to respond during seizure activity. It can affect movement (shaking of a hand or foot or tongue or eye movement), emotions (sudden sense of fear, rage or joy) or sensation (unusual taste sounds, sights, smells or skin touch).

Complex partial seizures affect a larger area of the brain and cause an altered state of consciousness. Although a patient may be appear to be awake, he/she is unable to respond and is completely unaware of what’s happening. A patient may pick at clothing (or try to remove clothes), mumble, wander or cry out. Treating Epilepsy in Children About 326,000 patients with epilepsy are 14 and under.

The primary treatment for epilepsy is medication to prevent onset of seizures. About 90 percent of patients can be successfully treated with drugs. However, every patient responds to medication differently. Not all drugs work and some cause undesired side effects (like dizziness, stomach upset, sleepiness, inability to concentrate and weight gain. It can take several trials of different medication (and trying various doses) to find one that works without too many side effects.

The FDA has recently approved the use of three medications for children four and older: Topamax® (topiramate), Trileptal® (oxcarbazepine) and Keppra® (levetiracetam). The addition of these medications provide doctors with more choices in prescribing safer, effective drugs to children with epilepsy with less risk of side effects.

The Epilepsy Foundation estimates 70 percent of patients with epilepsy eventually go into remission (i.e., stop having seizures). Once patients have been seizure-free for two or more years, doctors may try to discontinue medication. If the patient no longer has seizures, medications may be permanently stopped.

Rufinamide, an anti-epilepsy drug

Eisai Medical Research Inc. (Headquarters: Ridgefield Park, NJ, President: Mindell Seidlin), a U.S. pharmaceutical subsidiary of Eisai Co., Ltd. (Headquarters: Tokyo, President and CEO: Haruo Naito), announced today that they resubmitted the New Drug Application (NDA) for the anti-epilepsy agent rufinamide on Nov. 16, 2005. Eisai Medical Research had withdrawn the original NDA in early November and has supplemented its filing to include copies of some of the data from the original NDA in a more accessible electronic format.

Rufinamide has been evaluated as an adjunctive treatment for partial-onset seizures in adult and adolescent patients (12 years and older) and as adjunctive treatment for seizures associated with Lennox-Gastaut Syndrome (LGS) in children (4 years and older).

About Eisai Co., Ltd.

Eisai Co., Ltd. is a research-based human health care company that discovers, develops and markets products in more than 30 countries. Through a global network of research facilities, manufacturing sites and marketing subsidiaries, Eisai actively participates in all aspects of the worldwide health care system. Eisai employs 8,000 people worldwide.

About Eisai Medical Research Inc.

Eisai Medical Research Inc. is a U.S. pharmaceutical subsidiary of Eisai Co., Ltd. Eisai Medical Research Inc. was established to focus solely on clinical research and to expedite clinical drug development of new chemical entities and of new indications for marketed products.

Torture victim suffering from seizures had a rough time

An asylum seeker who suffered from severe epilepsy after being tortured in his home country was left to sleep rough after his local authority caseworker went on leave.

The Local Government Ombudsman has ordered Waltham Forest Council to pay compensation and legal costs as well as send a letter of apology, after reviewing the case.

The ombudsman heard that the man, who was in his twenties, had fled Eritrea after being held and tortured by soldiers. His treatment had left him suffering from daily epileptic seizures as well as clinical depression and post traumatic stress.

Initially he sayed at accommodation provided by the National Asylum Support Service, but after being granted leave to remain in the UK they could no longer pay for him to be housed.
When the man, who the report refers to as 'Mr Temtemie', was interviewed by a council caseworker she failed to use an interpreter and booked him into a local hostal.

However, after one day the hostel told the council they could not house Mr Temtemie due to his medical problems. When he returned to the council his caseworker was on leave and he was handed a list of churches that operated night shelters.

Despite him returning to the council three times in a week for help the council made no effort to find him accommodation. Instead he was left to sleep in bus stations or use winter shelters.

The ombudsan Mr Temtemie also heard that when the case was heard by the council's vulnerability panel his doctor was not invited. Despite strong written medical evidence they ruled he was not vulnerable.

An appeal was abandoned after he was offered a six-month lease at a young person's housing project. He has now been rehoused by the council.

The ombudsman ruled that the council breached its duty in failing to priovide temporary accommodation, had failed to explain why it disregarded medical evidence, failed to use interpreters in interviews and did not properly andle complaints made by Mr Temtemie's solicitor.
The council was ordered to pay £7,200 in compensation, plus legal costs, as well as sending a letter of apology and arranging for housing staff to receive a talk on the needs of torture victims.
A spokesperson for the council said: 'The council apologises unreservedly to Mr Temtemie for our failure to provide him with the quality of service that he deserved.

'Since 2003, the time this complaint referred to, the Council has made a number of improvements to the Homelessness Service.

'We are confident that any client, especially those as vulnerable as Mr Temtemie, would now receive a much better service.

'Not only have we improved our systems - from clear protocols with hostels to better record-keeping at reception areas - but staff have undergone a wide range of training to improve how they deal with customers with language and other issues.'

The council also insists that it did provide emergency accommodation to Mr Temtemie for two nights.

Visually impaired runner displayed great performance

Even prior to the race, the 32nd real,- BERLIN-MARATHON was somewhat special for me. For one, it was the interest demonstrated by the press, and on the other, the special starting group of blind and visually impaired runners. I thus gave interviews for both the Tagesspiegel and the BZ (Berliner Zeitung).

Shoelaces

Among the 39,000 runners on September 25th at the real,- BERLIN-MARATHON, there were also 10 blind and visually impaired runners. We are tethered to our guides with shoelaces. Our special starting group, made up of five women and five men, was able to start from the second starting block directly behind the elite runners. We would like to take the opportunity here to thank the organisers, SCC-RUNNING, for this opportunity.

Being able to start so far ahead in the field generated a general feeling of excitement for the blind and visually impaired runners. For me, this was the second time getting to start behind the elite runners, after doing so in Hamburg in April 2005.

Words of attention

Uneven areas, curves, our times, and the distance marks had to be announced to us. We also require more space than other runners, so that someone can run next to us. It is easier to pass us than it is for us to pass others. In addition, attempts to pass not only cost us more energy, they also require a great amount of concentration on the part of our sighted guides.

I had my first small surprise at the start. My trainer, Jürgen Köllner, was at the start giving me the last advice on the race. This was the first marathon where I had my own trainer with me. My goal was to surpass my own world best performance of 3:31:36h.

Three guides

I had three guides supporting me for the race. For me as a blind runner, it is important that each guide is a better runner than I am, in order to assist me safely along the course. If I were to have decided on only one single guide, he would have to have been able to run the marathon course approx. 20 minutes faster than my targeted time.

If one wishes to have one’s time accepted as a world best performance, international regulations must be adhered to. These regulate that a blind or visually impaired runner may have up to four guides. Of course, only one can accompany you at one time. The changes have to take place at the 10, 20 or 30 km marks.

Claus Rasmus

Claus Rasmus accompanied me along the first 10 kilometres, as he wanted to run the entire race for himself, as well. Before the race it was also agreed upon that another visually impaired runner would run behind me. His remaining vision just sufficed to be able to run the race on his own. He knew, of course, that my target time was 3.25h to 3.28h.

Stephan Möhnle

Already after five kilometres, he was no longer behind me, and I thought he must have fallen back. Afterwards upon looking at an internet report, I discovered to my astonishment that he had passed me after 5 kilometres and that he had a lead of two minutes at the 21-kilometre mark. He probably regretted his decision on the second half of the course, however. I reached the 10 km mark in a time of 48:10, and from there Stephan Möhnle was my guide.

Franz Feddema

Several other runners cheered me on along the first 20 km, shouting things like: “Fantastic, how you do it!” I reached the 30-km mark as I had planned in a time of 2:23:50h. For the last and most difficult kilometres, I had the well-known runner Franz Feddema on my side. It was naturally always nice to hear the enthusiasm of the spectators, “There goes the blind woman!”

"An attempt to keep up the pace"

On the last 12 kilometres I was also able to experience the cheers from a different perspective. Many running friends cheered Frannz on, and that too was a great feeling for me. And of course I cannot forget all of the friends who lined up along the course on this beautiful day. At km 33 I met my trainer, Jürgen Koellner. When he asked, "How are you doing?" I only answered quickly that I was not sure if I could keep up the pace. With the tip: “Just try to keep your pace,” he said goodbye.

A good training is worth a lot - Jürgen Köllner

After the race I really realised how important it is to have a good trainer. What I did not know was that at that time the visually impaired runner, Michaela Kummer, still had three minutes on me (at 21 km she even had an 5-minute lead!). So I tried to keep the pace. Then about 250 m before the finish, Franz suddenly told me that there was another visually impaired runner still ahead of me. So I had to mobilise all of my energy. After a final sprint, we crossed the finish just ahead of Michaela. I was completely exhausted and elated with my time of 3:22:08h.

The visually impaired now have their own cooking show

Ken Lexer can cook pasta primavera like a pro.

Every Tuesday, he feeds 200 people at a local soup kitchen, and they know they're going to get something special on his shift - like the time he made mini-pizza, using donated bread. Not having the freshest ingredients doesn't stop Lexer.

Neither does the fact that he is legally blind.

Lexer, 54, of recently was a guest chef on the new show Cooking Without Looking.

The show teaches cooking skills and kitchen safety to blind people and those with impaired vision. Show producers put together an audio-heavy program with play-by-play descriptions. It also helps that the visually impaired hosts describe the action, producers said.

Each show features a visually impaired or blind audience, three hosts with different stages of vision loss and a guest host who shares a favorite recipe.

Lexer served up some Oriental stir-fry.

"It smells so good," said Allen Preston, 56, of West Palm Beach. Preston is a former high school shop teacher and show host who lost his vision during childhood. His service dog, John T, a black Labrador, sits close by.

"I'm putting in some fresh garlic," Lexer says, as he maneuvers a silver spatula in a wok. The aroma of garlic and tangy ginger lingers.

After suffering a stroke eight years ago and being diagnosed with diabetic retinopathy, Lexer became blind. He slowly regained only limited vision and needs a powerful magnifying glass to see.

"I thought, `What am I going to do?'" Lexer said. "I would just sit in a chair, try to watch TV or take a walk, that's it."

But he found some hope in cooking. Lexer eventually enrolled in a number of cooking classes over the years and learned how to cook.

"The only time I go in the kitchen now is to clean up," said his wife, Marciene. "When he lost his sight, he thought his life was over, but cooking has given him focus."

During his Cooking Without Looking episode, Lexer shared tips with the audience, including how to adjust stove temperature safely and using pre-cut vegetables and meats for recipes. Other guest hosts have showed how they use different container sizes and shapes to identify specific ingredients, such as paprika and basil. Everything starts with having an extremely organized kitchen, some said.

The show's producer Ren'ee Rentmeester, president of the Vision World Foundation, an organization that provides services to the visually impaired, came up with the concept for the program after scouring the Internet and discovering that cooking was a popular topic among the blind. A veteran TV producer, Rentmeester said the show combines two of her interests, TV and helping people.

Cooking Without Looking began airing in February and is taped at WXEL's Boynton Beach studio. The show includes segments that discuss common eye diseases and interviews with health professionals. The show has also explored topics such as AIDS and vision loss and children's blindness.

Another host, Annette Watkins, 46, of Sunrise, who lost her vision to macular degeneration, conducts the interviews.

Earlier this year, Rentmeester found a sponsor, John Palmer, owner of Magnifying America, a store for the visually impaired in Coral Springs. He underwrote the first season of Cooking Without Looking, which consists of 13 episodes. WXEL is offering the show nationally to 350 PBS stations, Rentmeester said.

"The show is a good tool to educate the public (about blind people), what we can do and who we are," said Celia Chacon, 54, of Plantation, a show host who lost her eyesight 13 years ago. A former caterer, Chacon had to teach herself to cook again, relying mostly on her sense of smell and touch. Now she makes a mean cheesecake and apple pie pizza, she said.

Producers said they hope Cooking Without Looking attracts not only people with vision loss, but also their families.

For the show's target audience, the benefits could be more than just a tasty meal.

"The best thing we can do is encourage people who have lost their eyesight to maintain their independence," show host Preston said. "Cooking is one of those things that keeps you independent."

Center for the visually impaired receives award

The Center for the Visually Impaired took the top honors in the Managing for Excellence Awards competition presented by The Community Foundation for Greater Atlanta. The award was presented to Subie Green, CVI executive director, and Anne B. Skae, CVI board chair, at the Foundation's annual meeting on November 4, 2005.

Sponsored by The Boston Consulting Group, the award was created by The Community Foundation to recognize nonprofit organizations that demonstrate outstanding managerial achievement and thoughtful planning. The award includes a $15,000 grant from the Foundation. The Center for the Visually Impaired is Georgia's largest comprehensive, fully accredited, private facility providing vision rehabilitation.

The mission of the Center for the Visually Impaired is to offer comprehensive services to promote independence with dignity and the preservation of self worth for individuals of all ages who are blind or visually impaired. "Perhaps it is because CVI's mission personally touches most of the Trustees," said Anne B. Skae, CVI board chair, "but CVI has an unusually committed board.

They want to be involved and they are committed to advancing CVI so that the many Georgians who need vision rehabilitation can be served." "It's most gratifying to receive this award in recognition of the vital contributions of CVI's board, staff and volunteers," said Subie Green, CVI executive director.

"This award would not have been possible if it had not been for the dedication of each person affiliated with the Center. We have a great mission and it is thrilling to receive recognition for the good work that takes place here every day. We appreciate the opportunity that The Community Foundation for Greater Atlanta has made possible."

Tradition in the name of the visually impaired

One would be hard-pressed to find anyone who does not recognize the iconic Lions Clubs International "White Cane" lapel pin. Once a year Lions Clubs worldwide go into their communities to collect donations for sight related programs. What many do not realize is that this tradition is but a small part of Lions service to the blind and the visually impaired.

Unexplained seizures may be symptoms of illness

Pittsburgh Public Works Director Guy Costa woke up 10 days ago in the back of an ambulance, speeding toward UPMC Presbyterian hospital with an IV in his arm and an oxygen mask on his face.

Disoriented and confused, Costa struggled with paramedics, telling them he was OK.
"It was a nightmare. I was petrified. I told them to stop, that there's nothing wrong with me," said Costa, 49, a lifelong city resident who graduated from Allderdice High School and Duquesne University.

Doctors will perform a biopsy Monday to determine the severity of what they're calling an abnormality on Costa's brain. An MRI test conducted Thursday revealed a small mass, and doctors told Costa it could be anything -- including a low-grade glioma, or cancerous tumor.
Depending on what it is, treatment options could include chemotherapy and radiation, or surgery, Costa said.

"It's in God's hands at this point," he said. "It's given me a whole new appreciation of life. I'm confident, along with the doctors, that we're going to get through this thing."

Costa had been suffering unexplained seizures since January, which he described as "spells." He suffered a seizure about 6:10 p.m. on Nov. 2 while lying on his bed. His son Joey, 15, found him, and Costa's wife, Cathy, called 911. Although Costa can no longer drive a car because of the seizures, he continues to work and says he feels healthy.

"It's a real shocker. My family always thought we'd have problems with our hearts, not our brains," Costa said, referring to a family history of heart disease.

Costa, of Schenley Park, took the reins at public works in 1999 when Mayor Tom Murphy offered him the job. As director, Costa oversees a $30 million budget and 635 employees.

Costa has earned a reputation as a fair, hard-working manager who often rolls up his sleeves and works alongside employees repairing roads and working on other infrastructure projects.
He previously headed the Pittsburgh Parking Authority, serving as director for five years in the 1990s.

"He's a fine public servant -- a devout family man who loves his family, his mother, his brothers and sisters," said the Rev. Edward Bryce, pastor of St. Bede parish in Point Breeze, who has known the Costa family for years.

Most recently, Costa was a steadying presence for crews who cleaned up Downtown streets in August after an underground water pipe ruptured on Fort Duquesne Boulevard, closing the Gateway Center complex for several days.

"I love this job," Costa said during an interview in his office. "I'm really intrigued by it, because something different happens every day. It's been a rewarding career."

Costa's family includes a long line of public servants. His father, Jay, was Allegheny County treasurer from 1980 until his death in 1989. His brother, Jay Jr., is a state senator from Forest Hills, and brother Paul is a state representative from Wilkins.

Costa and his four brothers and sisters grew up in Larimer before the family moved to Squirrel Hill in 1968, following riots sparked by the assassination of civil rights leader Rev. Martin Luther King Jr.

Known for his easy-going demeanor, Costa said he tries to get along with just about everyone -- a trait he inherited from his father.

"He always said to be nice to everybody at work, because you never know -- your co-worker could someday become your boss," Costa said.

Bryce said the parish is praying for Costa.

"He's a vital young man, and we're praying he gets through this," Bryce said.

Ketogenic diet may help prevent seizures

Although the high-fat, calorie-restricted ketogenic diet (KD) has long been used to prevent childhood epileptic seizures that are unresponsive to drugs, physicians have not really understood exactly why the diet works. New studies by a research team at Emory University School of Medicine show that the diet alters genes involved in energy metabolism in the brain, which in turn helps stabilize the function of neurons exposed to the challenges of epileptic seizures. This knowledge could help scientists identify specific molecular or genetic targets and lead to more effective drug treatments for epilepsy and brain damage.

The research will be presented at the annual meeting of the Society for Neuroscience in Washington, D.C. by Kristopher Bough, PhD, a postdoctoral student in the laboratory of Emory pharmacology professor Raymond Dingledine, PhD.

"These findings support our hypothesis that a dietary regimen can dramatically affect the expression of genes and the function of neurons within the brain, which enhances the ability of these neurons to withstand the metabolic challenges of epileptic seizures," Dr. Dingledine said.
The ketogenic diet causes molecules called ketone bodies to be produced as fat is broken down. Scientists have understood that these molecules somehow cause a change in metabolism leading to a potent anticonvulsant effect. According to some animal studies they also may limit the progression of epilepsy.

The Emory research team studied the link between diet and epileptic seizures on the behavioral, cellular and genetic level. They found, as had others, that in rats fed the KD the resistance to seizures develops slowly, over one to two weeks, in contrast to rats treated with conventional anticonvulsant drugs. On the cellular level, they found that the anticonvulsant effect of the ketogenic diet did not correlate with a rise in plasma ketone levels or with a decrease in plasma glucose. Because longer treatment with the KD was necessary to increase the resistance to seizures, they concluded that changes in gene expression might hold the key to the diet's anticonvulsant effects.

To identify which genes might be involved, the researchers used microarray "gene chips" to examine changes in gene expression for more than 7,000 rat genes simultaneously. They focused on the hippocampus, a region of the brain known to play an important role in many kinds of epilepsies. More than 500 of the genes they examined were correlated with treatment with the KD. The most striking finding was the coordinated up-regulation of genes involved in energy metabolism.

To explain this genetic effect, the scientists first eliminated the possibility that the KD diet might cause enhanced production of GABA, a chemical messenger in the brain that helps limit seizure activity. They found that GABA levels in the hippocampus were unchanged with the KD.
To test whether energy reserves in hippocampal neurons were enhanced with the KD, they counted the number of energy "factories," or mitochondria, within cells using electron microscopy.

They found that KD treatment significantly increased the number of mitochondria per unit area in the hippocampus. This finding, along with the concerted increase in the expression of genes encoding energy metabolic enzymes, led them to conclude that KD treatment enhances energy production in the hippocampus and may lead to improved neuronal stability.

Finally, the researchers tested whether brain tissue affected by the KD would be more resistant to low levels of glucose (an effect of seizures) because of their enhanced energy reserves. They found that synaptic communication in KD-fed rats was more resistant to low glucose levels than in control animals fed a regular diet.

The researchers believe their new knowledge could lead to the development of more effective drug treatments for epilepsy and brain damage.

And because the diet enhances the brain's ability to withstand metabolic challenges, they also believe the ketogenic diet should be studied as a possible treatment for other neurodegenerative disorders such as Alzheimer's or Parkinson's diseases.

Man's memory loss may be caused by seizures

Adam Brown said he had a strange feeling when he dropped off his friend and former roommate, Ryan Brow, at the Littleton light- rail station last week.

"I knew something crazy was going to happen," Brown said Friday.

But he had no idea just how crazy until an Arapahoe County sheriff's deputy stopped by Tuesday night and told him that Brow, 20, had turned up at a church in West Vancouver, British Columbia, a couple of days earlier with $1,000 of Canadian currency, a hockey bag stuffed with wet goalie equipment and not a clue as to who he was.

"I was flabbergasted. I was really nervous for him," Brown, 21, said from his Centennial home, where Brow lived for a year before briefly moving to Omaha in August.

On Friday, Brow remained in Lions Gate Hospital in North Vancouver. Five days earlier, he had walked into the West Vancouver United Church and told the Rev. Don Collett: "This may sound funny, but I don't know my name. I don't know who I am."

Police at first thought Brow was a victim of amnesia but said medical tests ruled that out.
Brow was not carrying any identification, but authorities were able to learn his name Tuesday from a Canadian customs agent, who had processed the young man when he entered the country by bus from Washington State three days earlier.

Brown, who graduated from Aurora's Grandview High School in 2003 and attended Metropolitan State College with Brow, said Brow moved to Colorado from California in the ninth grade.
He said his friend had experienced seizures since being involved in a major car accident in California four years ago.

He remembered Brow falling "right on his face" from a seizure on prom night a couple of years ago. So when he heard about Brow's amnesialike state in Canada, Brown said he began to suspect the seizures.

Worse yet, Brow's mother in Omaha told him that her son can't remember anything from the past four months.

"It blows my mind because I hung out with him for the last three weeks," Brown said.
West Vancouver police said this week that doctors say Brow does not have amnesia but haven't said what may have caused his memory lapse.

Police also haven't been able to confirm the details of an account Brow gave them of being dropped off at a Vancouver bridge by a crying woman claiming to be his mother.
Brown said he is skeptical it ever happened.

"I can guarantee you that it's not his mother or any girl he knows," he said.
Brown said his friend may have been at a point in his life where he was attempting to try new things and gain fresh experiences and it simply overwhelmed him.

Brown said his friend recently decided to join an overseas philanthropic group that was going to Indonesia.

"He said he was tired of living for himself and that he wanted to help other people," Brown said.
Brow left Omaha and returned to Centennial about a month ago to say goodbye to his friends in Colorado, Brown said.

But Brown said when the Indonesia trip was canceled last week over concerns about avian bird flu, Brow sold off his belongings and asked Brown for a ride to the light-rail station.

He told Brown he was headed to Alaska to do forest revitalization.

"He's not a crazy person," Brown said of Brow. "He's a very positive person, and he's in a part of his life where he wants to help out other people."

"I want to make sure everything works out for him. When your friend goes through something like this, it's a scary situation," he said.

Some dogs can sense seizures in advance

Four o'clock in the morning a little more than two weeks ago, Cheryl Huey of Monroe, La., felt herself being roused from sleep.

Chelsea, the new 2-year-old female golden retriever that Huey and her teenage son Taylor had just brought home the day before had run from his bedroom to hers and was now agitatedly pawing at her arm.

"I got up and went to Taylor's bedroom and said, 'Hey, looks like we got to take her outside, she needs to go to the bathroom,'" Huey recalled.

However, "About 10 minutes later we were out in the parking lot, and Taylor starts having a seizure," Huey said. Taylor, 16, has epilepsy and experiences a temporarily debilitating attack about once a month.

Because the onset of a seizure is unpredictable and injury is possible if her son falls or is otherwise hurt during an attack, Cheryl Huey decided to adopt Chelsea — a dog specifically trained to alert epileptics to seizures before they occur — to help protect Taylor and give him an independence he hadn't had before.

Witnessing Chelsea's ability to sense the onset of an attack even as Taylor lay sleeping was extraordinary, Huey said. "At the time, I just couldn't believe it," she said.

"Then, out in the parking lot after he had stopped the seizure, I told her 'Stay, Chelsea,' and she crawled across his body and lay on top of him as I ran inside to get help. When I came out again, she was still across his body — part of her training is to just protect and stay with him."

Jennifer Arnold, founder and operator of nonprofit Canine Assistants, where Chelsea was born and trained, said seizure-alert dogs can also be taught to push a button to dial 911, tug open doors to run and get help, and even use their mouths to bring their human a cordless phone or any medication they might need.

"Seeing Chelsea's reaction that first time, the response she had, I now have confidence that in the event of a seizure she's going to be in charge," Huey said.

Taylor Huey's new companion is giving him new freedom and peace of mind, too. "She's going to make me more confident and independent, help me do more stuff by myself," he said.

That's not always easy for people with epilepsy, which is still a very poorly understood disorder.
"It's a chronic condition and [an attack] is literally an electric storm in the brain that can change behaviors," explained Dr. Blanca Vasquez, director of clinical research at New York University's Comprehensive Epilepsy Center. While seizures can vary greatly in their intensity and outward manifestations, many are preceded by sensations known as an aura, she said.

Even from far across a room, seizure-alert dogs seem to be able to pick up on extremely subtle physiological changes — minute alterations in odor or movement — that may begin anywhere from 45 to five or 10 minutes before an actual attack. "More research needs to be done," Arnold said. "We don't exactly know right now what the dogs are responding to."

But their ability to sense these changes for their owners can be invaluable, since early warning of a seizure's onset helps people with epilepsy find a safe environment or take precautionary measures.

The Labradors and retrievers trained by the experts at Alpharetta, Ga.-based Canine Assistants begin their 18 months of instruction at just 2 days of age, learning over 90 standard commands. More mysteriously, some protective measures seem to come to the dogs by instinct, Arnold said. For example, when sensing an oncoming seizure, "they tend to want their person to lie on the ground," she said.

As any person with epilepsy will tell you, that's about the most sensible action an individual can take before a seizure, since falling is the leading cause of serious injury during an attack.
"It's fascinating — dogs who have never seen anyone have a seizure will tug at their person's sleeve, they want you on the ground," Arnold said. "How do they have that instinct that lying on the ground is safer? We have no idea."

Arnold's investment in Canine Assistants is a very personal one. Stricken with multiple sclerosis at 16, she was confined for a time to a wheelchair. Seeking to help his daughter, Arnold's father, now deceased, discovered that people were training dogs to help partially immobilized patients navigate the tasks of daily living.

Fortunately for Arnold, her MS has improved so she can walk again. But her experience, combined with a love of dogs, compelled her and her mother to start Canine Assistants in 1991. The company matches dogs with owners in need, charging no fees.

Right now, the seizure-alert arm of Canine Assistants is funded by pharmaceutical company UCB Pharma, Inc. Arnold's team also trains dogs to help individuals with other disorders such as Parkinson's disease, multiple sclerosis, muscular dystrophy and amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease).

And the ability of these canines to sense other, hidden health dangers is emerging, too.
"There are already dogs that have been anecdotally reported to be able to pick up on dangerously low blood sugar, including one of our own seizure-alert dogs," Arnold said. "And a service dog a few years ago alerted his owner in the middle of the night that he was having a heart attack in his sleep — and then did it again for a stranger in a mall."

For people with epilepsy, having a four-legged, early warning system that can be taken everywhere gives them a sense of security and independence many haven't had before.

Taylor Huey said he hasn't yet decided whether he'll start taking Chelsea to school, but he certainly feels comfortable bringing her to daily outings such as church or shopping.

And Chelsea's arrival means Cheryl Huey can finally let her teenager go off on his own without worry.

"Sunday we went to the mall, and he went with me," she said. "I went to get my nails done and, as usual, I said 'Come on, Taylor.' He looked at me and said, 'No, it's OK, I've got Chelsea.' And I thought, 'Yeah, you do.' "

Lawsuit for not medicating victim of seizures disorder properly

The family of former Duval County inmate John Laughon has filed a lawsuit against the J.S.O., accusing its officers of beating a man so severely that it left him in a permanent vegetative state.
The lawsuit claims Laughon was not given the proper amount of medication to prevent his seizures.

Attorneys believe Laughon had a seizure while in custody and officers mistook the episode for a confrontation.

But police tell a different story, saying Laughon attacked them, and sent three of guards to the hospital.

Epilepsy Awareness Month

This is Epilepsy Awareness Month, and since some 2.7 million people in the United States have epilepsy, it is a good opportunity to iron out what is fact and what is myth when it comes to this disorder.

For example, contrary to popular belief, if someone is having a seizure, do not depress the person’s tongue, or restrain him or stop his movements.

Marianne Sailus, chaplain and patient advocate at the Allied Services John Heinz Institute, formed a support group in 1996 for those with epilepsy. Starting the group was a project close to her heart. Sailus had active epilepsy for 26 years, since being diagnosed at age 9. In 1994, she had brain surgery to help relieve the symptoms, and with the help of medication she has remained fairly seizure-free.

But she hasn’t forgotten what she went through before her surgery and sympathizes with those who have active epilepsy.

“There are so many myths out there,” Sailus said. At a former job, a colleague asked if he should stick an object in her mouth if she went into a seizure. No, Sailus answered.

“Well, wouldn’t Sailus swallow her tongue?” the man asked.

“Can you swallow your own tongue?” she countered. “Try it, right now.”

No, the man could not swallow his tongue.

“Well, neither can I,” Sailus said.

She said her life has changed since the surgery.

“People treat you different. People with epilepsy are sometimes looked at as different, strange,” Sailus said. “Now, I am looked at as just a normal person.”

One out of every 100 people has epilepsy, and one out of 10 will experience at least a single seizure in their lifetime. It is the third most common neurological disorder in the U.S., after Alzheimer’s disease and stroke.

The Epilepsy Foundation characterizes the disorder as a physical condition caused by sudden, brief changes in how the brain works, resulting in seizures. In more than 70 percent of cases, there is no apparent cause. The other 30 percent of epilepsy cases have a variety of causes, including head injuries, strokes, brain tumors, genetic conditions, lead poisoning, in-utero development problems, meningitis, encephalitis or severe cases of measles.

Plymouth resident Michael Loughlin, 25, became epileptic via encephalitis. Five years ago, he was studying civil engineering at Penn State University. As a credit requirement, he was getting hands-on work as manager of a road crew for PennDOT. One moment, he was standing on the road at his job, and the next he had collapsed on the ground in a seizure.

He was taken to the hospital, and eventually flown by helicopter to a Philadelphia hospital, where he was diagnosed with viral encephalitis and meningitis.

About three years ago, he had a Vagus Nerve Stimulation device implanted to help control seizures. Similar to a pacemaker, the implanted device sends a shock to the vagus nerve near Loughlin’s spinal cord, and the shock travels to the lower part of the brain. Every time Loughlin feels a seizure coming on, he rubs a magnet over his chest to bring him out of it.

Loughlin said that, like many people with epilepsy, he can sense a seizure coming on. Those who suffer from migraines may find familiarity in Loughlin’s description: “It’s so hard to explain. You get an aura, you lose your hearing, or may have déjÀ vu, you blank out, or have a feeling in your head that you know you’re going to get one.”

Back at school now, Loughlin is studying elementary education. He had gone through a great deal of rehabilitation after his illness, and now has to take it fairly easy. Things like lack of sleep, a cold and overworking can bring on seizures – and he’s had a couple of bad falls.

In the heat of summer last year, he was playing basketball and hit the pavement hard during a seizure, injuring his shoulder. He has fallen down stairs and through a glass coffee table.
“Thank God, I don’t feel a thing when I have a seizure,” Loughlin chuckles. When he regains consciousness, however, he feels the results of his seizure, like his shoulder injury on the basketball court.

He cannot go swimming alone, for fear he might suffer a seizure in the water. And by law, he cannot drive until he is six months free of seizures. While this is cramping Loughlin’s style, he said his family and friends have been great about giving him rides. His green 1995 Jeep Wrangler sits in the driveway waiting for his attention.

“I’m hoping it won’t be too long before I can drive again,” Loughlin said. “The Jeep is all ready to go.”

Clear the area around the person of anything hard or sharp.

Loosen ties or anything around the person’s neck that could make breathing difficult.

Put something flat and soft, like a folded jacket, under the person’s head.

If possible, turn him gently on his side, to help keep the airway clear.

Stay with the person until the seizure ends naturally.

Be friendly and reassuring as consciousness returns. Keep calm.

Herbal pills responsible for serious health risks

In a yet-to-be published study, lead researcher and emergency medicine specialist Paul Gee tallied up 61 patients who sought treatment at Christchurch Hospital's emergency department for severe reactions to party pills on 80 occasions over five months this year.

Numbers had not decreased since a law change in June restricting sales to those over 18, Dr Gee said.

A number had suffered seizures after taking the "recommended" dose of just two, he said.
Of those seeking medical treatment, 15 patients suffered "toxic seizures", falling unconscious, shaking uncontrollably, and in some cases had lost control of their bladder or bowels.
Such seizures could last from a few seconds to more than an hour, Dr Gee said.
"I'd like this stuff outright banned."

Many took the pills thinking they were safe because they were legal and described as herbal, he said.

But Associate Health Minister Jim Anderton said the Government was working "darn hard" on looking at the effects of herbal pills on users, but stopped short of saying a ban of the drugs would be recommended.

Mr Anderton said he had received advice from the Expert Advisory Committee on Drugs (EACD) that the herbal pills were not dangerous enough to ban.

"As far as I know BZP (benzylpiperazine – a chemical found in party pills) has not yet killed anybody."

Mr Anderton said the pills could make some people very ill, and occasionally they might come close to dying, "but no one yet has died as far as I know in New Zealand".

"I have taken advice from the EACD on this matter, and the advice was `we think there are reasons why this should be looked at more closely. Around the world we can only find one example of anyone who's died from this drug, but even then there are questions around it'."

Mr Anderton said two government-funded research programmes looking at the effects of BZP were running at the moment.

Mr Anderton said he would put measures forward to ban BZP if research found it was an inherently dangerous substance.

"I need the evidence, I haven't got it yet."

National's health spokesman Tony Ryall said his party backed more research on the pills but he also would not be calling for a total ban just yet.

National was in favour of close monitoring on the selling of the pills and felt regulation of access was required. " But in terms of banning access of these party pills, we're not in a position to state what our position on that is."

The New Zealand Drug Foundation warned against banning BZP, saying such a move would be against the best evidence available.

"It is absolutely imperative that we make decisions on the legal status of drugs based on the evidence, and the evidence alone," foundation executive director Ross Bell said.

By law, the pills could not be sold to anybody under 18 and the pills needed to carry appropriate health warnings.

"By banning party pills, there is a real risk that these restrictions will disappear. The regulations provide useful controls that we would otherwise not have if the substances were illegal," he said.
"It would be interesting to know how many people are presenting to Dr Gee's emergency department with alcohol-related problems and whether he thinks alcohol should be banned accordingly."

Medical condition may be responsible for fatal car accident

A medical condition might be responsible for Monday's car accident that killed three people.
Veronica Brown was driving the car when she lost control and crashed at the Lackland AFB main gate.

Her family said she had a history of seizures, and they suspect she was having one right before the accident.

Brown was on her way to work at the base. Two of her co-workers, Georgia Mae Johnson and Socorro Moreno, were in the car with her.

"I hate that other people were involved, because she loved both of them," said Cheryl Papion, Brown's sister. "She had been working with them for awhile."
Brown leaves behind a 7-year-old son, and a 19-year-old daughter.

Increasing demand of seizures response dogs

UCB Pharma, Inc., and Canine Assistants today announced a multi-year partnership to sponsor seizure response dogs for epilepsy patients across the U.S. These dogs represent the fastest growing requests received by Canine Assistants. Under the sponsorship, UCB will provide support for the care, training and lifetime veterinary costs of all dogs given to epilepsy patients.
Priscilla McCabe knows first hand the devastating effects epilepsy has on patients and their families.

"When my son was diagnosed with epilepsy, I quickly learned that controlling seizures is only the first step; it's about improving his total quality of life," said Priscilla whose son Sean has received the first seizure response dog supported by the partnership between UCB and Canine Assistants. "When I heard about all the amazing things these animals can do, I had no doubt that a seizure response dog would change our lives. The dog will help keep Sean safe and allow him to once again enjoy all the things he loves to do like riding his bike and completing his college education. And the fact that there is no cost to us is tremendous-it's like an early Christmas present for the family."

Epilepsy, which affects 2.7 million Americans, is difficult to treat. Every patient reacts differently to treatment, and it can be challenging to find the appropriate treatment regimen to best manage an individual patient's seizures. In fact, nearly one-third of people with epilepsy are unable to manage their condition with medication and continue to have seizures. This lifelong battle can be emotionally taxing, affecting everyday activities, which can lead to depression, anxiety and loss of independence.

For epilepsy patients and their caregivers, getting a seizure response dog can mean the beginning of a new life for the entire family.

"The commitment UCB has made to Canine Assistants is critical to our ability to realize the full potential for this program," said Jennifer Arnold, founder and Executive Director of Canine Assistants. "The impact these dogs have is enormous-recipients want to go back to school, they get involved in extracurricular activities again and they come out of their shells to lead more independent lives with a renewed sense of confidence. Because of the support provided by UCB, we are able to provide these dogs-it is a whole new world for these recipients and a wonderful thing to see."

In addition to providing constant companionship, seizure response dogs are trained in over 90 general commands including picking up medicine, opening doors, turning on lights, and specialized commands such as helping recipients experiencing a seizure safely to the ground and going for help. The scientific community is currently engaged in research to determine why many of these dogs seem to be able to detect the onset of a seizure earlier than humans. One UK study shows trained dogs are able to provide overt signals alerting their owner of a pending seizure up to 45 minutes prior to the event.

"The partnership with Canine Assistants reflects our awareness at UCB that patients with epilepsy experience emotional, social and physical life challenges that cannot be addressed by medication," said Rich Denness, Vice President and General Manager, CNS Business Unit, UCB Pharma, Inc. "Our passion for a comprehensive and individualized approach to patient care goes beyond developing medications like Keppra(R) (levetiracetam) to help control seizures. UCB understands the value of treating the "whole" patient and we are thrilled to have a partner like Canine Assistants that allows us to attain a very personal commitment to the epilepsy community."

November is Epilepsy Awareness Month. As The Epilepsy Company, UCB has many programs for patients with epilepsy and their caregivers, including a dedicated Web site geared toward epilepsy education. By logging on to ucbepilepsy.com, patients can access a variety of resources including a downloadable seizure diary and application forms for the newly established UCB scholarship program. The scholarship program is unique as it provides financial assistance for epilepsy patients and their families and caregivers. UCB is also a proud sponsor of the Epilepsy Foundation's H.O.P.E Mentoring Program(TM) (Helping Other People with Epilepsy) that trains people with epilepsy to be "patient educators" throughout the epilepsy and neurology communities. H.O.P.E mentors also conduct educational sessions for local social and civic groups in the community.

About Keppra(R)

In the U.S., Keppra(R) (levetiracetam) is approved for adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy. Keppra(R) is available in 250, 500 and 750 mg tablets and a grape-flavored (100 mg/mL) oral solution for patients who prefer a solution or have difficulty swallowing tablets. Keppra(R) dosing must be individualized according to renal function status. Since its launch, Keppra(R) has had more than 600,000 unique patient starts in the United States.

In adults, Keppra(R) use is associated with the occurrence of central nervous system adverse events, including somnolence and fatigue, coordination difficulties, and behavioral abnormalities as well as hematological abnormalities. In pediatric patients 4 to 16 years of age, Keppra(R) is associated with somnolence, fatigue, and behavioral abnormalities, as well as hematological abnormalities. In adults, the most common adverse events associated with Keppra(R) in combination with other AEDs were somnolence, asthenia, infection, and dizziness. Of these, most appeared to occur predominantly during the first 4 weeks of treatment. In pediatric patients 4 to 16 years of age, the most common adverse events associated with Keppra(R) (levetiracetam) in combination with other AEDs were somnolence, accidental injury, hostility, nervousness, and asthenia.

Keppra(R) was approved in 1999 as adjunctive therapy for adults with partial onset seizures and is the most prescribed second-generation AED used in epilepsy. About Canine Assistants
Canine Assistants is a non-profit organization founded in 1991 that trains and provides service dogs for select children and adults with physical disabilities or other special needs. These dogs are adopted from various organizations and selectively screened for personality, temperament and general health.

Following general training of more than 90 commands, which include turning on lights and retrieving medication, seizure response dogs are trained to perform one of the following specialized behaviors, depending on the recipient's need: remain next to the person during the course of a seizure; summon help in a controlled environment; or retrieve a phone prior to the seizure when indicated by the recipient. In addition to physically assisting those with disabilities, Canine Assistants service dogs are instrumental in removing many of the barriers faced by the disabled in today's society.

Budget increase to develop people's awareness to seizures disorders

Pennsylvania is investing $750,000 in programs to increase public awareness of seizure disorders, according to state Health Secretary Dr. Calvin B. Johnson, who also announced November as Epilepsy Awareness Month in Pennsylvania.

"An estimated 120,000 Pennsylvanians have epilepsy or another type of seizure disorder making it important for us to reach out and educate the public -- especially our young people -- on how to better understand and accept the challenges of epilepsy," Dr. Johnson said. "While there is no cure, we can address this medical condition by increasing our ability to dispel the myths and negative stereotypes associated with epilepsy."

The Department of Health has contracted with the Epilepsy Foundations of Western/Central and Eastern Pennsylvania to develop and implement programs to promote acceptance and understanding of people with epilepsy.

One of those programs is "Project School Alert" which is free school and classroom presentations about epilepsy for school students, staff, parents and community groups. The presentations focus on teaching children what to do when a friend or family member has a seizure.

Epilepsy is a neurological disorder that affects more than 2.5 million Americans with 181,000 new cases diagnosed each year. Trends show a decreasing incidence of epilepsy among children and increasing incidence in the elderly. Epilepsy is generally a chronic and/or lifelong condition, and seizures can often be controlled with anti-epileptic medications, special diets or surgery.
In 70 percent of new cases of epilepsy, no cause is apparent.

It is a physical condition caused by sudden, brief changes in the brain's electrical balance. Seizures commonly last between a few seconds and a few minutes with characteristics varying from person to person. Epilepsy may sometimes be confused with other health conditions like heart attack, stroke or lack of coordination.

Can brainpacemaker control seizures?

Medtronic, Inc. (NYSE:MDT) today announced that the U.S. clinical trial for its Intercept(TM) Epilepsy Control System has met an early milestone. Based on the intended interim review of blinded safety and efficacy data by an independent data safety and monitoring board, enrollment in the trial will continue, and the study of this innovative therapy will progress as planned.

This decision allows Medtronic to advance its focus on the unmet needs of individuals with epilepsy. Specifically, the Intercept trial will further explore the application of Medtronic's already proven neurostimulation technology to reduce seizure frequency and severity in people with difficult-to-treat epilepsy.

"We are encouraged by the board's decision, and are very pleased that the trial will move forward as this pioneering therapy provides hope for so many people who suffer through life with uncontrolled seizures," said Todd Langevin, vice president and general manager, global movement disorders, Medtronic Neurological.

Currently, 15 sites in the U.S. are participating in the pivotal trial, and more than half of all patients needed to complete the trial are enrolled. If the Intercept development plan continues to progress on target, the device could be available for patients as early as 2008.

About Epilepsy

According to the Epilepsy Foundation, epilepsy is a neurological condition that affects 2.7 million Americans and 50 million people worldwide. Despite trying a range of treatment options, about one-third of these people continue to experience debilitating, recurring seizures - or brief periods of abnormal electrical activity in the brain. These seizures can cause a change in sensation, awareness or behavior. The unpredictability of seizures affects daily activities and disrupts school days, work responsibilities and social activities.

About Medtronic

Medtronic, Inc., headquartered in Minneapolis, is the global leader in medical technology - alleviating pain, restoring health, and extending life for millions of people around the world.
Any forward-looking statements are subject to risks and uncertainties such as those described in Medtronic's Annual Report on Form 10-K for the year ended April 29, 2005. Actual results may differ materially from anticipated results.

Existing drug may prevent seizures in newborns

A diuretic drug called bumetanide may serendipitously help treat seizures in newborns, which are difficult to control with existing anticonvulsants, according to a study in the November Nature Medicine. The study findings could lead to clinical trials of bumetanide in newborns, whose immature, rapidly-developing brains are especially vulnerable to seizures.

Newborns' seizures can cause long-term neurologic impairments and a tendency toward seizures later in life.

Conventional anticonvulsants – phenobarbital and benzodiazepines – are ineffective in newborns because their brains are biochemically different from adult brains, says neurologist Frances Jensen, MD, of Children's Hospital Boston, a senior investigator on the study. Jensen's team, led by postdoctoral fellow Delia Talos, PhD, collaborated with Kevin Staley and colleagues at the University of Colorado Health Sciences Center to find a treatment for seizures that would work in newborns.

The researchers knew that conventional anticonvulsants work by mimicking the action of GABA, a natural inhibitory chemical in the brain, by activating GABA receptors on the surface of brain cells. In adult nerve cells, GABA activation opens up channels that allow chloride to move into the cell. The cell thereby acquires a negative charge and becomes less excitable, inhibiting seizure activity. But in newborns, chloride is already high, and therefore activating GABA receptors causes chloride to move out of nerve cells, creating a paradoxical excitatory reaction that may actually exacerbate seizures.

To better understand this paradox, the researchers focused on two molecules that regulate cellular chloride levels: KCC2, which transports chloride out of cells, and NKCC1, which brings chloride in. Previous studies in rats had shown that adult nerve cells mostly have KCC2, making their chloride concentrations lower inside than outside. Thus, when GABA receptors are activated, chloride tends to come in, with an inhibitory effect. In newborn rats, the situation is reversed: their nerve cells mostly have NKCC1, so chloride is actively transported inside, making initial chloride concentrations very high. As a result, GABA activation causes chloride to exit the cell, with an excitatory effect.

To see if the same pattern applies in humans, Talos and colleagues at Children's Hospital Boston examined NKCC1 and KCC2 levels in brain tissue from children who had died, ranging from second-trimester fetuses to preschool-age children. Just as in rats, NKCC1 levels were high during the fetal and newborn periods, peaking one week after birth, but fell during the first year of life, approaching the low levels found in adults. Also as in rats, KCC2 levels were initially low, but rose over the first year of life.

"We found that NKCC1 is expressed unopposed in the immature brain," says Jensen. "We thought that perhaps if we blocked its inward transfer of chloride, we could get immature neurons to act like older neurons and give GABA a chance to do what it's supposed to do."

The researchers knew that the diuretic bumetanide inhibits NKCC1 activity in the kidney, and reasoned that the drug might have a similar effect in the brain, lowering chloride levels and making nerve cells responsive to GABA activation. Staley and colleagues in Colorado conducted a trial in baby rats and found that bumetanide indeed inhibited seizure activity, while phenobarbital, as in humans, worked poorly.

The study's findings are in keeping with epidemiologic studies finding that adults taking diuretics for other reasons are less likely to have seizures. Jensen's group has begun discussions about launching a clinical trial of bumetanide in newborns. Although the drug is FDA-approved and has been used in newborns for other indications, a number of safety questions will first need to be addressed before a trial can proceed.

Last year, Jensen's lab found that another FDA-approved drug, topiramate, may prevent long-term seizure disorders in newborns who suffer seizures due to oxygen starvation. This drug acts by blocking another receptor, known as the AMPA glutamate receptor, which is much more abundant in newborns' brains than adult brains. Like bumetamide, topiramate targets proteins that are uniquely expressed in the neonatal brain.

"As we learn more about age-specific brain mechanisms, we can develop novel therapies for newborn seizures, but in the meantime, there may be things already on the shelf that we can use," Jensen says.

The current study was funded by the National Institute of Neurological Disorders and Stroke and the Hearst Foundation.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Children's research community.

Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 347-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School.