Since February, the thunderstorms in 4-year-old Maranda Francisco's brain had come more frequently. As often as 120 times a day, sometimes only three minutes apart, seizures threw the right side of her body into herky-jerky uselessness.
First the right corner of her mouth would begin to tremble, then the right side of her face. Her right arm would start shaking, and her right leg, until the whole right side of her body would jerk out of control -- and then go slack.
Oddly, the seizures affected only her right side, but she was losing the ability to walk, talk, eat and learn. She was on constant medication and lived her life in brief intervals between convulsions.
Her right arm withered from disuse and continual paralysis. She spoke words, but couldn't carry on a conversation. Her attention span grew shorter. She couldn't finish a meal without interruption from at least one seizure that would leave her choking on her food. She was free of seizures only during sleep.
Maranda's epilepsy was caused by an extremely rare disease called Rasmussen's encephalitis -- a slow, progressive inflammation of the brain whose first symptom was a seizure nearly three years ago. Last spring, once her doctors began to suspect a diagnosis of Rasmussen's, Maranda began a medical odyssey that took her from her home in Denver to medical centers on both coasts -- and eventually to Johns Hopkins Children's Center in Baltimore, where last month she underwent extraordinary surgery.
In a 10-hour operation Aug. 7, doctors removed the left hemisphere of her brain.
Since the surgery, Maranda has not suffered a single seizure. She talks normally. Her memory is intact. She walks with a slight limp, a small brace holding her right foot in the walking position. She has regained partial use of her right arm, although she cannot grasp objects with her right hand.
"She's a pistol, I'll tell you," says her mother, Terry Francisco. "She's walking up and down the halls and getting into trouble."
"Over the long haul, I'd anticipate she'll be able to live quite a normal life, with a mild weakness on the right side," says Dr. Benjamin Carson, head of pediatric neurosurgery at Johns Hopkins, who performed her surgery.
"For all practical purposes, she'll have normal speech," says Dr. Theodore Rasmussen, emeritus director of the Montreal Neurological Institute, who identified the disease in 1955 and pioneered its treatment by radical brain surgery. "As for her other development, it all depends on how good the other hemisphere is."
No one knows for sure, of course, how well Maranda will adjust to the loss of half her brain. Risks remain. She may be more vulnerable to head injuries or an infection of the cavity where her left brain used to be. And no one can be absolutely certain that whatever causes Rasmussen's won't somehow spread to the rest of her brain. But for now, her doctors are euphoric.
"I would expect her intellect will be normal or above normal," says Dr. John Freeman, head of pediatric neurology and director of the epilepsy center at Johns Hopkins. "I would put her into kindergarten and let her go with the other kids. From a neurologic standpoint, she really doesn't need much follow-up."
Maranda left Johns Hopkins last Tuesday and flew back to Denver, where she stayed at Children's Hospital. She was expected go home yesterday for the first time in nearly six months.
She is off all medication except an antibiotic for a low-grade meningitis infection she contracted after surgery, and a daily dose of phenobarbital as a temporary "insurance policy" against recurrence of seizures. Both drugs will be stopped soon, her doctors say. She'll receive physical, occupational and speech therapy at home.
"She's got a lot of catching up to do," says her neurologist in Denver, Dr. Thomas T. Reiley, codirector of the epilepsy center at Denver's Children's Hospital. "She has a withered, spastic right side, which she tends not to use."
But already, he says, she has regained much of the ground she had lost in the past year.
When Reiley walked into Maranda's room last Tuesday night and she reached out to give him a hug and a kiss, he couldn't believe it was the same little girl who had left Denver under heavy sedation on a plane to Baltimore six weeks before.
Last week, at Maranda's request, her mother enrolled her in ballet and tap-dancing classes, beginning in October.
The human brain consists of two similar but distinct hemispheres. In an adult, the two halves of the brain become quite specialized, one side (usually the left in a right-handed person) handling most of the language and analytical functions, and the other handling artistic abilities and recognition of faces, for example. But there is considerable overlap, particularly in children.
The reason Maranda can manage so well without the left hemisphere of her brain is that the right hemisphere had already taken over many of the functions of its deteriorating left-side counterpart.
"The young brain is clearly relatively plastic," says neurologist Freeman, who oversaw Maranda's care at Johns Hopkins. "A newborn who's had a stroke in one side of the brain will transfer some of its functions to the other side. The older you are, the longer the delay in transferring speech to the other hemisphere."
Maranda is the sixth patient with Rasmussen's encephalitis treated with radical brain surgery at Johns Hopkins since 1970 -- and the youngest. Her doctors know of no similar case in a child so young anywhere in the world.
"Our only regret in all of these patients is that we didn't do it earlier," Freeman says.
No one knows exactly when the brain loses its ability to shift functions from one side to the other, but it seems to be more difficult after age 6 or 7.
"People think all intelligence resides in the brain," Freeman says, "and therefore, if you take out half the brain, the patient ought to be half as intelligent. Clearly, that's not true.
"Sometimes, having a damaged part of the brain that's 'seizing' is worse than having no brain at all. It's like having static on the radio. It's better to turn the radio off for a while."
Maranda's brain surgery, he says, helped eliminate the interference, so that the healthy signals from the right side of her brain could get through.
"For reasons we don't understand," Freeman says, "it seems to work."
There's no longer any doubt that Maranda's power of speech shifted to the right side of her brain.
"We know it's got to be in the right hemisphere," Freeman says, "because there ain't no left hemisphere."
In a crowded operating room at Johns Hopkins Children's Center, neurosurgeon Benjamin Carson drilled six holes the size of shirt buttons in Maranda Francisco's skull. The holes formed a semi-circle, beginning in front of her left ear, curving up across her temple, above the ear and down behind the ear.
With an air-powered saw, Carson connected the holes into an incision, and folded back the left side of Maranda's skull "like you would a book" to expose the outer covering of her brain.
The brain was swollen and abnormally hard, which would make the surgery even more difficult. He injected a drug to reduce the swelling, inserted a catheter to drain off some of the excess fluid and removed the hard outer covering of the brain.
"That leaves the brain surface staring at you," he says. "It was tense, swollen and angry-looking."
Carson's challenge, over the next eight hours, was to cut away the inflamed left hemisphere of Maranda's brain without severing vital blood vessels or damaging the exquisitely fragile cerebellum, brain stem and endocrine glands -- the thalamus, hypothalamus, pituitary and pineal.
"There are no borders between the part that must be removed and the parts of the brain stem that need to stay intact," he says. "It's a big struggle in a swollen brain. You're securing blood vessels as you go."
Large veins along the base of the brain bled "like crazy" when the brain tissue was pulled away. The tissue itself was extremely fragile and bled profusely wherever it was touched. Maranda lost nearly nine pints of blood during the operation.
Carson worked gradually from front to back, cutting away first the frontal lobe, then the temporal, parietal and occipital lobes of the cortex -- including all the "gray matter" on the left side. He clamped off the three major brain arteries with permanent steel clips to keep them from bleeding into the cavity where the left side of her brain had been.
By the end of the operation, Carson and his surgical team knew they had successfully removed the left hemisphere of Maranda's brain. What they didn't know was whether the seizures would stop and whether she would ever talk or walk again.
"There's nothing to describe the anxiety of the neurosurgeon at the time the operation ends and the patient is being awakened," Carson says. "It's almost like waiting for a baby."
Maranda didn't take long to offer some encouraging answers. After 10 hours in the operating room -- after losing the left half of her brain -- she woke up talking.
Her parents were in the waiting room. They had barely budged for 10 hours, hadn't eaten. They assembled an entire 1,000-piece jigsaw puzzle of chocolate chip cookies, with time to spare.
The Franciscos stayed fairly calm until early afternoon, when the operation went past the scheduled five hours. After that, they worried in silence.
When they finally saw Maranda, she was being wheeled from the operating room to the pediatric intensive care unit.
Her eyes were swollen shut from 10 hours of anesthesia, her mouth and lips puffed up grotesquely from the effect of the respirator tube down her throat.
Terry Francisco bent down and kissed her daughter, not knowing if she would respond or not.
"I love you, Mommy and Daddy," Maranda said.
Terry Francisco lost it. "I was totally . . . well, talk about tears of joy."
For Maranda, the risk of operating was compounded, because it was the left -- and dominant -- half of her brain that was removed. In most right-handed people, the left hemisphere of the brain dominates speech and language in addition to movement on the right side of the body.
"The major long-term risk," Carson says, "was that she'd be unable to talk and paralyzed on the right side. That was a very substantial risk."
"Obviously, we're always more comfortable taking out the right brain in a right-handed patient , but in her case, she would have become an invalid anyway because of her recurring seizures," Carson says. "So we took the chance."
Maranda is the Franciscos' only child. Terry Francisco's first child died of sudden infant death syndrome at the age of 4 months. Another pregnancy ended in miscarriage. Her husband, Luis, has a son from a previous marriage.
The Franciscos were fully informed of the risk of operating. They knew the danger. But they also could see the toll that more than 100 seizures a day were taking on their child.
"One always has to weigh the risk of operating against the risk of not operating," says Rasmussen.
So Maranda's parents would sit and talk about their harrowing choice, the competing risks. "Okay," one would say, "let's say she doesn't speak." The other would try to imagine the unimaginable, and rationalize it: "Well, there are other ways to communicate."
They decided to take the risk.
Until the age of 18 months, Maranda Francisco was a normal child developing normally. Then, for unknown reasons, she suffered her first seizure, a grand mal convulsion characteristic of epilepsy and often compared to an electrical storm in the brain. A couple of weeks later, she had a second grand mal seizure, and was put on anticonvulsive medication.
Over the next two years, her seizures became more frequent -- and they changed. Only the right side of her body was affected, and she didn't lose consciousness. Instead of grand mal seizures, she was having focal seizures -- which one doctor describes as "half a grand mal" -- that apparently originated in the left side of her brain and disrupted only the right side of her body. They left Maranda weak on her right side and sometimes unable to talk normally for as long as two hours.
As the seizures worsened, Maranda ricocheted from specialist to specialist, diagnosis to diagnosis, treatment to treatment, hope to disappointment.
"We tried everything -- medicines, diets, totally bizarre things," says her mother. One doctor prescribed strong coffee twice a day. Another put Maranda on aloe vera, a plant-derived laxative. Nothing worked. More than once, the Franciscos were told that Maranda was a mentally retarded epileptic for whom nothing could be done.
"I didn't believe it, and I just kept reading and reading and reading," says Terry Francisco. "I've asked all the questions."
Finally, last winter, the Franciscos were referred to Dr. Reiley at the children's epilepsy center at Children's Hospital in Denver. He switched her medication, which helped briefly, but in April Maranda's epilepsy got dramatically worse.
Her seizures became nearly continual -- so frequent that she could not complete a conversation, take a short walk or chew food without being interrupted by a sudden loss of control of the right side of her body.
Reiley tried an armamentarium of drugs -- singly and in every possible combination -- in hopes of bringing Maranda's seizures under control. But the seizures persisted.
Even worse, a brain scan taken in April showed a surprising and disturbing result: The left side of Maranda's brain seemed to be changing shape. Not only was her brain misfiring, but the brain cells themselves -- on the left side only -- were deteriorating.
"I was, quite frankly, not sure what was happening," Reiley says.
He consulted another pediatric neurologist, who suggested a possible explanation: Rasmussen's encephalitis.
Reiley knew that time was short, because Rasmussen's is a progressive disease that can lead to permanent paralysis on one side of the body and mental retardation. He knew also that a few medical centers in the country had treated a few young Rasmussen's patients with radical brain surgery that might be Maranda's only hope. He arranged to have Maranda diagnosed at UCLA Medical Center, the nearest hospital with any experience in treatment of Rasmussen's encephalitis.
But before Maranda flew to Los Angeles, her doctors in Denver made one last-ditch effort to quell the firestorm in her brain.
On May 22, her fourth birthday, Maranda was given a heavy dose of barbiturates that put her into a deep coma. She was kept alive by a respirator and other artificial life support.
For 17 hours, Maranda's brain wave went completely flat.
"We kind of skipped her birthday this year," says Terry Francisco.
The doctors hoped to break the seizures' chain reaction by inducing a coma and putting Maranda's brain completely at rest.
Maranda had no seizures during the coma, but as soon as she regained consciousness, they re- sumed. That suggested that her epilepsy was due not just to electrical misfiring in her brain, but to a progressive deterioration such as might be caused by Rasmussen's.
In early June, Maranda flew to UCLA for yet more tests, yet more drugs in yet more combinations and an operation called a craniotomy. Surgeons cut out a tiny piece of brain tissue for testing and attached electrodes to the surface of her brain to measure its electrical activity in an effort to pinpoint the source of her seizures.
But the inflammation could not be pinpointed. It had spread throughout the left hemisphere of Maranda's brain -- further confirmation of the diagnosis of Rasmussen's encephalitis.
Now that they finally had a diagnosis, Maranda's parents and doctors began the search for possible treatment. She was still suffering nearly constant seizures that stopped only when she managed to fall asleep.
Since the inflammation seemed confined to the left side of her brain, and since she was only 4, Maranda was a candidate for surgery to remove one hemisphere of her brain. Scheduling difficulties precluded such an operation at UCLA, so Maranda moved back to Denver. Neurologist Reiley consulted with specialists at three other medical centers -- Johns Hopkins, Yale and the Montreal Neurological Institute -- before he and Maranda's parents decided to send her to Hopkins.
Before the operation, the Franciscos talked it over with Maranda herself. They explained that the doctor would make a cut on her head. They took a doll from the playroom and drew lines on its head to show Maranda where the incision would be. They told her she'd have a really short haircut for a while (that part delighted her).
When her mother asked her if she wanted anything special after the operation, Maranda came up with only one request: "No more seizures."
So far, she has gotten her wish.