It is before dawn on a clear Friday morning in September when Susanna and Santiago, a young couple from New York, push a stroller with their 10-month-old son through the glass doors of Ronald Reagan UCLA Medical Center, moving from the darkness outside into the light of the gleaming facility. For seven months, they had tried everything from anticonvulsant drugs to a high-fat, low-carbohydrate diet to control their child’s epileptic seizures.
“The hardest part was trying all the drugs and the diet, and every one of them failed,” Susanna says. “Once you get to the end of that list, that’s a pretty dark moment.”
Now they are about to try something radically different. At 7:30 a.m., they hug their baby, Thomas, and cry as anesthesiologist Oren Bernstein, M.D., wheels him toward Operating Room 7 for surgery to remove portions of the left temporal, occipital and parietal lobes of his brain. Stopping at a red line on the floor, Dr. Bernstein turns to the parents and tells them, “Here’s where you guys can get one last good-bye.”
They kiss Thomas, who looks back at them with large brown eyes. “Bye, Thomas,” Susanna says sweetly, holding his plush monkey, Mr. Jimenez. As Thomas moves down the corridor, the brown-haired bruiser looks very small in the middle of the hospital crib.
Thomas seemed fine when he was born, on October 26, 2009. But three months later, the seizures, termed infantile spasms, began. When the spasms worsened, a pediatric neurologist, who noticed white “ash-leaf”- looking spots on the child’s tummy, diagnosed Thomas with tuberous sclerosis complex (TSC), a rare condition caused by genetic mutations that can lead to abnormal growths in the brain, kidneys, heart, eyes and skin. Tuberous sclerosis, named for its potato-like tubers in the brain, occurs in about one-in-5,000 live births. TSC varies from person to person, and some people don’t even know they have the condition. But Thomas suffered two-to-three focal seizures and infantile spasms each day, and imaging tests identified some 30 tubers throughout his brain.
Of the hundreds of children with intractable epilepsy that neurosurgeon Gary W. Mathern, M.D., has operated on, 80 percent remain seizure free, but TSC is different. “Unlike other epilepsy surgeries, where you’re hunting for a target, these kids present with multiple targets,” says Dr. Mathern, neurosurgical director of UCLA’s Pediatric Epilepsy Program. “You have to figure out which targets to go after.”
Before deciding what they might do for their son, Susanna and Santiago (their last name is being withheld at the family’s request) read hundreds of articles about TSC, often while riding the subway from Brooklyn to their jobs in Manhattan. One surgeon’s name kept popping up in the literature: Gary Mathern in Los Angeles. Under Dr. Mathern, UCLA has emerged as a major center for treating patients with TSC. Using specialized, non-invasive tests to first identify the areas producing the seizures, and then surgically removing them, his multidisciplinary team has achieved a 68- percent seizure-control rate. And the younger the child, the better is the chance of taking advantage of the brain’s ability to reorganize itself.
At UCLA, neuroradiologist Noriko Salamon, M.D., Ph.D., has refined the use of MRIs and PET scans for TSC. “Many times, we don’t see structural abnormalities in the MRI, or the abnormalities are subtle,” she says. “In Thomas’s case, there were so many abnormalities. Which one do you go after? That’s the problem.”
The team, which includes pediatric neurologists Joyce Wu, M.D., director of UCLA’s TSC Clinic, and Raman Sankar, M.D., also evaluated electromagnetic activity, or dipoles, from deep within Thomas’s brain with magnetoencephalography (MEG) done at UC San Francisco. The test pointed to tubers on the left side of his brain as the main seizure driver. But the MEG also recorded right-sided seizures.
“We don’t know how those will behave after surgery,” Dr. Sankar says before the operation. “You’re always hedging some bets and making some judgment calls. In the end, not everything is easily explainable. It comes down to your intuition that’s honed by both science and experience.”
Three days before Thomas’ surgery, Susanna and Santiago meet with Dr. Mathern. They are braced for his “doom-and-gloom” informed-consent meeting. Parents have compared Dr. Mathern to a chewy chocolate bar: tough at first but ultimately warm and comforting.
Thomas arrives for the meeting in his brown-and-white cow pajamas and matching socks. Dr. Mathern coos as Thomas babbles and scoots on the floor. But he is blunt as he explains the risks of surgery, including death. But doing nothing also has risks: Seizures could cause death or stall brain development, leaving Thomas with an IQ below 50. Dr. Mathern explains everything, from the parts of the brain he would remove to whether or not the surgery might alter Thomas’s princely good looks. “This is Hollywood!” he says. “Looks count.”
Dr. Mathern flashes MRIs, PET scans and EEGs on a monitor. The PET images show large dark-blue areas, indicating poor metabolic activity. “It’s essentially almost stone cold,” he says, pointing to the left temporal region. Moreover, an EEG recorded numerous subclinical seizures from the same area while Thomas slept.
Dr. Mathern recommends targeting the temporal, occipital and a little of the parietal lobe on the left side in the hope that this will quiet the seizures coming from the right side. But because of the tuber load in both hemispheres, he worries about language acquisition. “My guess is you’re going to struggle with language with him,” Dr. Mathern says, urging the concerned parents to consider language therapy or teaching Thomas sign language.
Susanna and Santiago agree to proceed, though not without tears. “This is one of the toughest decisions that a parent is ever going to make,” the surgeon says, handing Susanna a tissue.
After the meeting, Susanna, 31, a witty, analytical woman, is upbeat and defiant. “We’re here because we haven’t given up,” she says. “Very rationally, I think he could be okay. I know Dr. Mathern says he might not talk. I’ll be damned if this kid doesn’t talk!”
“Friday is going to be tough,” adds the soft-spoken Santiago, 30. “Yes, there are risks. He could die on the operating table. But for the life that we envision for him, it’s better to have this surgery.”
Friday is a beautiful late-summer day. Susanna and Santiago wait on the patio outside the hospital for any news from the O.R. Meanwhile, the windowless operating room buzzes with noises: beeps of the equipment monitoring Thomas’s vital signs, muffled voices, whirs of machinery. A white board lists the schedule for Thomas’s “left craniotomy” and notes that a unit of Santiago’s blood is in the fridge. On one wall are posted paper printouts of Thomas’s MRIs and PET scans, which Dr. Mathern studies throughout the long hours.
Dr. Mathern says he was drawn to neurosurgery because “you have to figure out the puzzle. Epilepsy surgery is one of the few procedures where you purposely go in to remove portions of someone’s cortex,” he says. “It is, in essence, the purest form of brain surgery. And if you do it on these individuals with intractable epilepsy, you can often turn around their lives.”
Just after 9 a.m., Dr. Mathern performs a “time-out” to ensure that the members of the O.R. team – neurosurgery resident Justin Dye, M.D.; medical student Joshua Lucas; nurses Nancy Fukumoto, Maria Okuda Loravell and Julie Byrd; anesthesiologists Ihab Ayad, M.D., and Dr. Bernstein; and neurodiagnostic technician Andrea Duran – are ready to begin the operation.
“Identify the patient,” Dr. Mathern says.
“Thomas,” a nurse responds.
“The left side of the head is the proper side of the head,” Dr. Mathern confirms.
Turning to Dr. Bernstein, Dr. Mathern emphasizes the importance of monitoring blood loss.
“We’re on it,” Dr. Bernstein assures.
“We’re going to start,” Dr. Mathern says at 9:30 a.m. “Let the family know.”
It takes 40 minutes to cut through the scalp and skull. As Drs. Mathern and Dye drill through the bone, blood dribbles out, and Dr. Bernstein reminds nurse Fukumoto: “The blood is in the fridge if we need it.”
By 10:10 a.m., Drs. Mathern and Dye pry the skull flap to the side, exposing the pink, smooth dura surrounding Thomas’s brain. The surgeons cut through the thin yet tough membrane as Lucas, the medical student, rinses the site with saline from a rubber bulb. By 10:50 a.m., Dr. Dye rolls back the dura, revealing the pale white cortex laced with red arteries.
As if on cue, neurodiagnostic tech Duran positions monitors 10 feet from the operating table: a motor/ sensory monitor to map the area and electocorticography (ECoG) equipment to record abnormal brain activity. For Dr. Mathern, surgery is about process, not miracles. “If you’re sitting there in awe, you’re not paying attention to the details,” he says. “In neurosurgery, the details count. A perfectly good operation can be screwed up by inattention to one little detail.”
With Thomas’s brain exposed, Dr. Mathern gently prods a spongy white area. “That swollen area almost screams tuber,” he says. Meanwhile, pediatric neurologist Jason T. Lerner, M.D., and fellow Shaun Hussain, M.D., enter the O.R. and join Duran near the monitors. At 11:15 a.m., Dr. Mathern places a suture in the dura to mark the central focus between the motor and sensory cortex.
Now they turn their attention to the ECoG. The nurses turn down the lights. As Dr. Mathern places electrodes on Thomas’s cortex, the monitors glow and crackle with spikes and waves, revealing slow activity. Dr. Mathern calls out numbers as waves flow across the screens. “Sixteen is bad. Seventeen is bad. Eighteen is on the border, 19 and 20,” Dr. Mathern says. “It’s slow, a bad tuber. One through 10 are tuber-ish, 11 through 20 the uber-tuber.”
Dr. Lerner translates: “Eleven through 20 are the meaty part of the tuber, the other numbers are kind of on the edge.” “
Hello!” Dr. Mathern says suddenly, looking at the monitors. “I think this thing is driving it. Look at that! It’s substantial. Those are your spasms. Based on prior experience, that’s about all I would go for. I would vote primarily for a tuber resection.”
Dr. Lerner concurs. “Right now, we’re going to do surgery on the tuber itself and the immediate area around it,” he says. “After he’s done, we’ll come back and look at the area superior to the tuber [with the ECoG] and see if that’s still as active as it looks, or if the tuber was causing it to go bad.”
The nurses turn up the O.R. lights. Dr. Mathern marks the area for resection and snaps a “before” picture with his Nikon Coolpix.
At 11:45 a.m., Dr. Mathern carefully removes two pieces of tuber tissue, the first mid-temporal, the second occipital. My Huynh, a senior research assistant, catches the tissue in a vial and whisks it across the street, where neurophysiologist Carlos Cepeda, Ph.D., is waiting to peer at 400-micron-thick slices of tissue using infrared electron microscopy.
Dr. Mathern is a surgical-scientist at heart, and he believes his work is about discovery as much as high-level clinical care. “We’re trying to learn what is wrong with the tissue, what causes the seizures, so we can hypothesize potential mechanisms for treating it,” he says.
Since 1999, the National Institutes of Health has funded Dr. Mathern and Dr. Cepeda’s efforts to understand epilepsy at the cellular level, examining abnormal electrical activity and the effects of drugs such as rapomycin on neurons.
Back in the O.R., Drs. Mathern and Dye begin removing a large rectangular piece of cortex. They use a bipolar scalpel, which allows them to coagulate the blood vessels with electricity while they cut through the brain tissue. The tool emits a “Bzzzzt!” of electricity. Air bubbles trapped in the tissue burst, sending out a “Pop!” Throughout, steady “beeps” represent Thomas’s heart rate, 103 beats per minute.
“This is how you find where your borders are,” Dr. Mathern says, instructing Drs. Dye and Lucas. He relies on experience and touch to decide how deep to cut. “It’s like Braille,” he says. “The tuber is harder, the edge is firm.”
Dr. Mathern guides Dr. Dye as together they slowly resect the temporal and occipital lobes. “Don’t rip,” Dr. Mathern says to the younger surgeon, pushing the tissue with a curved black tool. “I want you to have control.”
Dr. Lerner has updated the waiting family after the ECoG. But just before 1 p.m., nurse Laurie Ann Colton, hoping to give Susanna and Santiago more information, asks Dr. Mathern for an update.
“Everything is fine,” he says.
Just after 1 p.m., Drs. Mathern and Dye remove the tuber-laden chunk, which is sent to Harry Vinters, M.D., chief of neuropathology. “The tubers showed a profound degree of malformation of the cortex,” Dr. Vinters says later. “Our challenge is to find out why the genetic abnormality that causes TSC leads to the brain malformation that produces seizures.”
Drs. Mathern and Dye clean up the area, cutting small pieces of tissue. Some samples will be stored in Dr. Mathern’s lab, which houses one of the world’s largest collections of epileptic tissue. One piece will be used by Massoud Akhtari, Ph.D., a researcher in the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, who, with Dr. Mathern, is investigating the electrical conductivity of the abnormal tissue compared to normal parts of the brain.
Following the second ECoG, which shows improvement but still records parietal spikes, Dr. Mathern decides against further resections. “We got the main target. Let’s see if it works. You don’t want to take out too much cortex,” he says.
Dr. Mathern gets out his Coolpix for an “after” picture.
It is time to close. At 2:20 p.m., Dr. Dye sews up the dura. They reinforce the skull with a titanium plate, reconnect the scalp with 53 staples and drill a hole to drain fluid from Thomas’s ventricle. They dress the wound with a cranium cap.
Dr. Mathern walks onto the patio outside the ground-floor surgical waiting area at 2:30 p.m. to talk with Susanna and Santiago, who look both tired and excited. “It was another day at the office,” Dr. Mathern matter-of-factly says. The confluence of tubers that they removed from Thomas’s temporal and occipital lobes were clearly defined. They had used 225 MLs of the blood Santiago had donated, one third of Thomas’s blood volume.
“Don’t sweat the small stuff,” Dr. Mathern urges. “He’s going to come out looking like a pincushion, with catheters and hoses coming out of everything, His left eye will probably swell shut. All of that is normal.”
Seizures would not be unexpected during the first 48 hours, but more seizures after that would be of concern, he says.
Dr. Mathern pauses and looks at Susanna. “You can hug the surgeon now,” he says, smiling. Susanna embraces Dr. Mathern as Santiago grips his hand.
“It’s over,” Dr. Mathern says.
“You want to avoid chaos,” Dr. Mathern explains later. “If you work with your team, and do this enough, which we do, then everyone knows what will take place, from the nurses who know everything we need to the techs coming to do the ECoG. The process needs to be structured, ordered.”
But even if everything goes perfectly, Dr. Mathern cannot predict the outcome. “We target the area. Our data say we have a two-thirds chance this will work. You have to wait and see,” he says.
Nearly 12 hours after they arrived for the surgery, Susanna smiles as she receives a phone call telling her they can come up and see Thomas. Santiago holds Thomas the Train balloons from a friend as they hurry into the elevator to the pediatric ICU on the fifth floor. Thomas, swathed in his head dressing, opens his eyes as they enter. “You have a bigger hat than before,” Susanna says, holding out his monkey, Mr. Jimenez. “You’ve got all these ladies taking care of you.”
It is like the final scene from The Wizard of Oz, with Drs. Mathern, Dye, Lucas, Bernstein and Ayad and several nurses surrounding the crib. One nurse hands Santiago an envelope filled with Thomas’s hair.
“Hey cutie,” Dr. Mathern says to the baby. “You look like a million bucks.”
Thomas, oblivious, sucks his thumb and flashes his winning smile. Susanna and Santiago, grateful the ordeal is over, lean down and kiss their son.
The first 48 hours are indeed tough. “His heart rate was up,” Santiago says. “He was trying to figure out what was going on, he was upset and mad.”
During that first week, Thomas has a couple of seizures and fights off a fever. But eight days after surgery, he is discharged. Despite the ups and downs, Susanna and Santiago look very relaxed when they bring Thomas to Dr. Mathern’s office for a follow-up two days later. Thomas is sound asleep, but the scar on his head is clear evidence of what he’s been through.
As Dr. Mathern predicted, it would be a long road. A follow-up EEG shows no seizures, clinical or sub-clinical, although Thomas screamed the moment the EEG-tech touched his head. Two days later, however, Thomas suffers some clinical spasms. Another EEG suggests the new spasms are coming from the right side, but there are still no seizures coming from his left hemisphere, a good sign. Dr. Sankar prescribes zonisamide to try to control the spasms.
Before returning to New York, Susanna, Santiago and Thomas visit the set of the TV show 90210, where Thomas gets to pose for a picture with the cast. “This is Hollywood,” as Dr. Mathern says. Back home, Susanna and Santiago plan to take leaves from their work to care for Thomas.
It will take time before it’s clear if the surgery has put an end to Thomas’ seizures, and Dr. Mathern will see the family again next year for an evaluation. So far, a month after the operation, things appear to be going well, and Susanna reports that Thomas is doing wonderfully with his therapy in New York, babbling more and with greater focus. “His personality is different. He has more energy,” Susanna says. “He’s a completely different kid now.”
As usual, Dr. Mathern takes a wait-and-see approach. “The goal,” he says, “is seizure freedom. The only way to know is to be patient.”
LYNDON STAMBLER is a freelance writer and teaches journalism at Santa Monica College.