Even laid out on the operating table, his skull pierced by the screws of a metal halo and prepped for the drill that would bore a dime-size hole through to his brain, Alex Anisimov managed an engaging smile.
"How are you doing, Alex?" the anesthesiologist asked.
The smart and buoyant 15-year-old, increasingly imprisoned by a brain disease called dystonia, could barely talk anymore. His muscles often defied his will, jerking spastically. But he raised his thumb and smiled again.
For the next several hours, surgeons at Beth Israel Deaconess Medical Center used a hair-thin probe to explore Alex's brain, micron by micron, playing aloud the hissing rhythms of his firing neurons. At critical relay points deep inside, they implanted tiny electrodes meant to correct faulty brain signals.
When he was operated on last fall, Alex was among the youngest dystonia patients to receive "deep brain stimulation" implants.
Over the following year, he and his family would experience the excitement of cutting-edge medicine, but also confront its maddening uncertainties. They would venture ever deeper into an experimental realm where some patients recover dramatically but progress more often comes in small steps, through laborious trial and error.
The Anisimovs entered that world in faith, and in desperation.
Before his surgery, Alex's condition had been deteriorating so rapidly that he had started to lose not only his mobility, but his serenity, sinking into sorrow. At 10, he could still run and talk. At 15, he was silenced and unable to take a single step by himself.
"When I first knew that I could have the operation, my spirits were lifted," he said later, typing on the computer keyboard that substituted for his voice. "I knew that there was still some hope."
The surgery had helped hundreds of dystonia patients across the country, apparently by correcting the chaotic electrical messages that misdirected muscles. In some cases, people even went from jerky limbs and twisted torsos to just about normal. Some were able to leave their wheelchairs behind.
For Alex's mother and father, sitting in suspense hour after hour in a hospital waiting room, the operation Alex was undergoing felt like an answer to years of prayer. At the same time, they were terrified. Major brain surgery is tricky and can be fatal in exceedingly rare cases. They looked up intently each time someone entered. Lilia's eyes, light blue, filled with tears and dried again, filled and dried. Vitaliy, normally of unsinkable cheer, felt himself aging years in the course of a day.
"God gives the doctors wisdom to do what needs to be done," said Vitaliy.
Devout Russian Baptists, the Anisimovs had moved to Massachusetts from Kazakhstan in late 1997, when Alex was 6, seeking religious freedom and hoping American medicine would help him.
In the weeks before Alex's operation, their broad network of friends and family assured them that American doctors were the best in the world and that Alex would be fine. But their doctors at Beth Israel Deaconess took care to emphasize that the surgery's results were not guaranteed. The operation helped most patients, some a lot, some only a little. For a few, it made their condition worse.
Alex wanted most to get the use of his hands back. Despite doctors' warnings that it was unlikely, his parents wanted most to hear his voice again, to hear him expounding on philosophy, sharing jokes.
A childhood stolen
One evening in his old hometown of Chemkent, Kazakhstan, when Alex was just 2, he toddled to greet his father at the door. "Papa! Papa!" he shouted, happy as always to see him home from work.
But this time, Alex's right foot dragged a bit behind him. That was the beginning.
His mind remained sharp and his spirit light, but his body went mysteriously haywire, his limbs shooting out or bending of their own volition. By age 5, he could not hold a pen, could barely feed himself.
When Alex was 6, the Anisimovs settled in Westfield, near Springfield.
Alex started taking Artane, an antispasm medication that helped him move better. He could eat by himself and get around without a walker or braces on his legs.
In early elementary school, his vocabulary was studded with adult words, and he loved to talk so much that Lilia had to beg him not to recount every single detail of his home life in the classroom. He played happily with his older sister, Larisa, and his beloved cocker spaniel, Philip. Family videos show him loping, just a touch wobbly-kneed, through a field at age 7 and easily climbing steps at 10. When he fell, which was often, he gamely got up and went on. He sped merrily through life, heedless of his parents' frequent pleas to slow down.
But as he entered adolescence, growing into a lanky teen with soft brown hair and a long, angular face, the Artane stopped helping and, with no other effective treatments, Alex's condition deteriorated.
His speech, once full of czarist history and biblical interpretations, faded. He had to struggle ever harder to make his mouth form words, and his voice emerged only a whisper, hard for a stranger to decipher. He could type on a slim laptop-like computer, but it was slow.
He and his family made medical pilgrimages to Pittsburgh and New York, wherever there was a hint of hope.
Through it all, Alex never complained out loud, never hinted that his unruly body oppressed him or that he missed singing at church. "I felt very sad I couldn't take one step," he said, typing. But he believed in destiny, he said, and accepted what life brought him.
"I also think that every person is different," he wrote. "Some people walk, others use wheelchairs."
He went to school, where his friends, Adam Giles and Patrick Michaud, would help him in the lunchroom. He studied the Bible for hours at a time. He could get around on a motorized scooter and play with his baby brother, Roma, whom the family nicknamed "Alex's toy." Roma prayed every night for Alex to get better. When Alex turned 15, 3-year-old Roma blew the birthday candles out for him.
But Vitaliy and Lilia grew increasingly concerned. If Alex's slide continued, where would he end up? Bedridden? Worse? Dystonia's progression is not predictable.
They rejoiced when Dr. Daniel Tarsy, of Beth Israel Deaconess's Movement Disorders Center, deemed Alex a good candidate for surgery. At long last, they could stop praying for an operation to help him.
Now, they needed to pray only for the operation to go well.
"We saw him getting worse and worse, and we had no choice," Lilia said. "A lot of people are afraid of the risk, but if you're in a no-exit situation, then you do it. If he were a little better, we probably wouldn't have."
Harrowing journey of hope
At 5 a.m. on Oct. 3, 2006, the day of the surgery, Alex's shiny eyes looked expectant, as if, despite all that destiny had done, he still foresaw only good.
"Why be scared?" Vitaliy said to Alex. "Isn't it better to be able to walk?"
Their hope was based on solid clinical research, but there was reason for fear, too. Lilia had read the complication rates, 2 percent to 6 percent, over and over. The area around the electrodes could become infected. The electrodes could trigger a small brain bleed. Rarely, a patient could find that the stimulation actually exacerbated the dystonia. Between 5 percent and 10 percent developed hardware problems that required repair.
How deep brain stimulation works is not fully understood, but it creates an electromagnetic field that changes the pattern of activity in the brain and thereby corrects the bad signals traveling through malfunctioning circuits.
Over two decades, the implants have helped tens of thousands of patients with the tremor and rigidity of Parkinson's disease. The Food and Drug Administration approved them for dystonia in 2003.
Recent peer-reviewed journal articles reported dozens of documented cases in which these brain implants proved generally safe and effective for dystonia, which affects an estimated 300,000 Americans. The operation costs about $60,000, and it is usually covered by insurance, as it was for Alex.
One French study from 2005 found that in 22 dystonia patients, the implants, on average, reduced their level of impairment by half, as measured on standard scales of disability. But that was the average. It was not clear what Alex's specific condition might mean for his outcome. Many patients in the studies carried genes linked to dystonia; Alex had tested negative for them.
Still, Alex had inherited Vitaliy's incorrigible optimism.
"I've never lost hope I'll see him healthy," Vitaliy said that early morning of the surgery. "Lilia has suffered a lot and cried a lot. Inside, I've always known he would be healthy."
Alex's thoughts veered from the operation to a video he had watched the night before. "Did you hear about the Kursk?" he whispered, referring to the Russian nuclear submarine that sank in the Barents Sea in 2000. Some of the crew apparently survived for days, a period when rescue seemed possible. All eventually perished.
Yes, a visitor said. What did you think?
"I thought they would be saved."
Alert during brain surgery
At nearly 7 a.m., Alex left his parents behind with a reassuring smile and was wheeled off for the most painful part of the day: the procedure to attach a metal-alloy halo, called a stereotactic frame, to his skull.
The frame provided the hard-and-fast reference points that neurosurgeon Efstathios Papavassiliou would need to navigate his brain, where good landmarks are rare and missing a target by a few millimeters could render the surgery worthless. Even worse, hitting the wrong spot could cause headaches, speech problems, or hallucinations.
To ensure that the halo could not move a smidgen, it had to be screwed directly into the bone of Alex's temples. "Ow," he said softly.
Sedated and groggy, Alex then lay still in the dark tunnel of an MRI as Papavassiliou pored over images of his brain, looking to pinpoint a small structure deep inside called the globus pallidus, a relay point in a brain circuit involved in movement.
After a few minutes, Papavassiliou found what he was looking for on the screen: brain tissue shaped like parentheses.
By a little after 8 a.m., Alex was lying beneath the bright light shining off the peach walls of the operating room, and the surgical staff was attaching his halo to a head-holder on the table. A nurse shaved a swatch of fine brown hair from his head, and a blower filled his warming blanket with toasty air.
Papavassiliou numbed Alex's skull and then neatly drilled the dime-size hole. Whenever prompted, Alex gave a thumbs-up to attest that he was doing fine.
He needed to be conscious so that the operating team could be sure important brain functions such as speech and vision remained intact. The brain has no sensory nerves inside it, so no pain is felt when it is penetrated.
"We're going to start our recordings," Papavassiliou told Alex. "Is anything hurting?"
"No." A scratchy whisper.
"Are you just excited, maybe?"
The smile. "Yeah."
Neurophysiologist Rami Burstein slowly twirled a dial on a device that lowered a recording electrode into the left side of Alex's brain, while watching and listening to the activity of neurons on a specialized monitor.
At times, the images of neuron activity on Burstein's screen went from ^^^^^^^ to /\/\/\/\/\/\/\/\/, and the neurons hissed as furiously as water dancing on a hot frying pan. Those areas of high and low activity helped Burstein navigate his way to and around the globus pallidus.
As Tarsy explained, "the brain imaging gets you into the ballpark, and the microelectrodes get you to home plate."
Alex's brain presented unusual challenges. The firings in his globus pallidus area were exceptionally sparse, an abnormality possibly connected to his dystonia. In some such cases, surgeons have decided to abort the operation, but the team persevered.
By noon, they had settled on a spot for the electrode on the left side of Alex's brain, which controls the right side of the body.
Previously, surgeons would have burned or cut out a key part of the globus pallidus, risking permanent problems with speech, vision, or movement. One great advantage of deep brain stimulation is that it can be turned off and on and painstakingly fine-tuned. "This doesn't destroy anything," Tarsy said.
Soon after the first electrode was placed, Papavassiliou asked Alex to count to 10.
"1. . . 2 . . . 3 . . ."
He did it, slowly and with effort, but audibly, a clear improvement over his voice before surgery - a good sign.
Just before 1 p.m., Papavassiliou drilled a second hole into Alex's skull, this time on the right side. Once again, the electrode wended its slow, careful way in.
When it was nearly 4 p.m., and Alex had been awake on the table for six hours, he started to squirm, clearly nearing the end of his tolerance.
"We're almost done, OK?" Papavassiliou told him. "Just stay with us five minutes, and then we can sedate you."
Once again, the metal halo hurt Alex - this time, as it was being unscrewed. "Ay!" he exclaimed. "Don't!"
Then it was out. "You're a good man!" said a surgical technician. "You did it!"
The surgery had gone without mishap, but Alex was not done. A week later Papavassiliou would operate on him again, this time to insert batteries under the skin on each side of his chest and to hook them up to the electrodes in his brain.
Alex would have to wait about six weeks to be "turned on." Then the batteries would begin to send constant electrical pulses into his brain. Only then would the effects of the operation begin to come clear.
Recover then wait and wait
By mid-November, after a difficult recovery from the operations, Alex was back in high school. His electrodes were not turned on yet, but his life already offered a great new joy: As a reward for toughing it through the first operation, Vitaliy had impulsively bought him a gentle, 18-year-old, brown-and-white horse named Chance.
"I thought, 'I'll buy a horse and make Alex happy,' " Vitaliy said. "He was lying there, all hurt.'
As soon as he got home from school each day, Alex raced on his scooter into the backyard, bringing Chance treats of apples and carrots in the scooter's basket. Alex held out the food to Chance as best he could and snatched a caress of the horse's velvety face.
"Give me my hug," he mouthed softly to Chance, and Chance obliged.
Twice a week, when Vitaliy was home from his long work hours as a flooring installer, he helped Alex mount Chance, and carefully led the horse around the yard, on the theory that it could help Alex's balance.
Despite his disobedient muscles, Alex could sit on the horse securely, without fear.
If only Alex's arms and hands worked better, Lilia said, as she watched him, "he would love to be able to scatter corn for Chance." Alex was silent about his expectations, but Lilia said: "I think he's anxious. He hopes - and it will either be or not be."
She was tortured by the uncertainty for many sleepless nights. The closer the date of Alex's implant turn-on came, the more she feared that it would bring no change.
"To go through so much," she said, "and what if it gives nothing?"
Already, though - whether because of fresh hope or some early brain reaction to the surgery - Alex seemed slightly improved, as if the past few months of his deterioration had been erased. He seemed more confident with his eating, Vitaliy and Lilia thought. He held his fork more securely and brought a cup to his mouth better. His jaw chewed better. Alex thought his feet held his weight a little more stably, too.
But was he actually better? It was hard to say.
Turn-on day. Nov 17.
Alex, fresh-faced and wearing a bright-yellow fleece, beamed with anticipation as he officially began life as a cyborg - part human, part machine.
In a small examining room at Beth Israel Deaconess, nurse practitioner Linda Paul held a device resembling an oversized Blackberry to his chest, just over one of his implanted batteries. Using wireless signals, she was setting the voltage, frequency, and pulse-width of the electrical signals meant to fix flaws in Alex's brain.
So far, he felt nothing but fascination. "Cool," he said.
There was more reason to hope than ever. Earlier that month, a gold-standard clinical trial in the New England Journal of Medicine had confirmed that deep brain stimulation worked well for dystonia. During six months of stimulation, patients improved by an average of 46 percent, according to rating scales of movement and disability. Just under one-fifth of the patients failed to improve significantly.
Watching her ebullient son, her arm entwined with Vitaliy's as they sat nearby, Lilia said, "He expects a lot."
Paul told the family she would leave Alex with robust settings, high but not so high they could cause tissue damage.
"I don't want you being discouraged at all if you don't see anything today," she told Alex. "I had one gentleman I programmed and it took three months to take effect."
As Paul tapped and tapped her stylus on the device's screen, she asked Alex: "Feel anything? No? How about now?"
Alex did not, neither pain nor improvement.
Once Alex was programmed on both sides, Paul asked him to straighten his arms and move his legs; she thought she detected a slight improvement, she said.
Tarsy stopped in to check on Alex's progress and told the family that dystonia patients sometimes improved within a month, but it was typically a gradual process.
Paul was more of a cheerleader. The results so far were going in the right direction, she emphasized. "I really think in another month, certainly within three months, I'd like to see Alex walk, not need this thing," she said of his wheelchair. "I really think it's possible."
Alex left the neurology department still upbeat, but his parents were struggling with their high hopes.
"Everyone warned us," Lilia said. "But you always expect more."
In the next few days, Alex noticed that his legs seemed more able to hold his weight. One day he took a dozen steps in a row without holding onto anything, a feat he hadn't been able to accomplish for months.
But if there were other changes, they were subtle.
Lilia asked him again and again: Are you better?
Yes, Alex said, but how he could not explain. "Something's better," he said vaguely.
Then began months of tweaking. Every month or so, Vitaliy took time off work, and Lilia got help to take care of little Roma, and they drove Alex the two hours to Boston to get his device reprogrammed.
In January, Alex's walking seemed, if anything, a little worse.
"He's afraid," Vitaliy told Paul. A recent fall had cut into Alex's eagerness to try to walk.
Paul looked intensely into Alex's eyes and said: "Alex, you are going to get better; we just need to work at it. Do you feel disappointed at all, Alex, that it hasn't been more successful?"
"No," he said.
"No, he's not," Lilia said.
"Just me," Vitaliy said.
Friends and relatives kept calling to ask whether Alex showed any new signs of improvement. Vitaliy and Lilia could answer only that they had no news.
By March, Alex had wisps of a first moustache, but no particular new progress to report. After she reprogrammed him, Paul said: "This time, I gave him a lot, a LOT [though still well within safety margins]. I'm becoming more and more aggressive here."
April, May, June - each with its monthly reprogramming - little changed. At one point, Alex's legs seemed to get a little more spastic, and Paul adjusted his programming and fixed the problem.
The lack of progress began to influence the family's choices.
Reluctantly, they boarded Chance at a friend's farm. He would have care and company there, and Alex could still ride him whenever Vitaliy could take him.
An uncertain future
In July, Dr. Ludy Shih, who had taken over Alex's case from Tarsy, raised a daunting new prospect: Was it time to start thinking about another operation?
The first operation had been difficult, Shih noted. Might the electrodes be in the wrong spots? Perhaps one or both needed to be repositioned.
Alex recoiled. "I don't want to go through that again," he mouthed to his parents.
On the two-hour ride home, Lilia and Vitaliy were at a loss, shocked by the sudden proposition of more major surgery. Would it help, or, Lilia wondered, "would we just torture the child again?"
Shih had said the second surgery might be more successful than the first, because doctors knew more about the anatomy of Alex's brain.
But if Alex did not want to do it, Lilia said, they must listen to him.
By the time they sat at the kitchen table that night for their customary evening chat, Alex had changed his mind: "Let's try it."
It wouldn't be as bad as the first time, he said. He wanted to get better.
Lilia reminded him of the pain he had suffered.
"Should we expect only good from God?" he answered. "We should accept everything."
In October, while the family was still grappling with the idea of another operation, Shih delivered shocking news again. X-rays showed that one of the wires snaking along under Alex's scalp appeared to have kinked. If it was only intermittently connected, it could have been limiting his progress.
When they met with Shih on Nov. 9, she told them she would discuss the X-rays with the manufacturer of the device. She encouraged them to seek a second opinion on Alex's treatment with New York experts.
And she suggested still more patience with the programming of Alex's electrodes; some dystonia patients, she said, get dramatically better only two or three years after the surgery.
"My point is not that we're guaranteeing you'll get better," Shih said, "but that you just have to keep trying and really pushing the limits on this, while in the back of our minds we keep thinking about whether you should get a second operation."
The doctors must sort through the confusing multitude of possible explanations for Alex's lack of progress, but for the family the way forward is clear.
They will keep trying, the Anisimovs say. They will go to New York. They will come for more programming appointments, even though it means more missed work and school. They will sign the papers for another operation.
The journey is a long one, with no sure success at the end. "When we'll come out of the other side of the tunnel, we don't know," Lilia said.
American medicine has taken them this far, and they feel compelled to go on.
"I no longer have great hope," Lilia said earlier this month. But "we've already been through so much, we can't stop now."
As for Alex, now 16, "I don't know what the Lord wants with me," he typed. "I will go anywhere the Lord wants."
"I'm just calm," he wrote. "For me, there is nothing to be scared about."
Carey Goldberg can be reached at goldberg@globe.com.
The Globe will continue to report periodically on Alex's status.
