Growing a Miracle
Dr. Hulya Bukulmez's joy in learning she was carrying fraternal twins was tempered with the concern of hearing her obstetrician define the pregnancy as high-risk. The MetroHealth Medical Center pediatric rheumatologist and first-time mother-to-be was 43 years old, a fact that made a twin pregnancy a challenge, regardless of how healthy she remained. She and her electrical-engineer husband, Derya Ferendeci, soon discovered the reasons why.
Bukulmez began spotting blood around her eighth week of pregnancy. Her obstetrician told her it was caused by the uterus stretching to accommodate the rapidly growing twins. During her 12th week, she went to see a high-risk pregnancy specialist, MetroHealth interim director of maternal fetal medicine Dr. Bradley Stetzer, who ordered a week of complete bed rest.
A week after she returned to work, her water broke.
"At that point, I was in a panic," Bukulmez says.
She had suffered what is known as preterm premature rupture of the membrane, a common event in women who deliver their babies early. But the frequency with which PPROM occurs before 23 weeks of pregnancy — the point at which a baby can survive outside the womb — is unknown because it usually triggers a miscarriage. The amniotic fluid helps protect both mother and child from infection and is vital to lung development, particularly in the 16th through 20th weeks after conception. More importantly, the bag of water stretches the muscular uterine walls and allows the fetus to grow properly.
"The compression effect of this uterine muscle around a baby with no fluid is really a death sentence, no matter how long the mother is able to stay pregnant," Stetzer says.
But Stetzer had seen a couple of twin pregnancies in which both babies survived. The presence of a second fetus in a separate, unbroken amniotic sac was key.
"If you have another pregnancy inside the uterus, it allows the uterus to remain distended," he says. "The baby is not compressed to the same degree because of the protection of the other pregnancy."
Stetzer gently warned Bukulmez that she had a 10 to 15 percent chance that her pregnancy, then in its 14th week, would continue to the all-important 23rd week. But he also told her that the endangered baby's heart was beating and the placenta was still intact.
He once again ordered complete bed rest.
Stetzer's wait-and-see attitude was preferable to the second opinion Bukulmez got the next morning: The obstetrician told her the baby in the compromised sac would most certainly die.
"Dr. Stetzer said he would be supporting me until the end and monitoring me weekly," Bukulmez says. "It was still heartbreaking. But at least we had somebody who supported us."
Bukulmez returned to her bed, leaving only to go to the bathroom and take a quick shower every second or third day, and began researching her condition. When she read that amniotic fluid could be replenished daily — a process influenced by the mother's intake of fluids — she began drinking at least 4 liters of water a day. "At some point, I was able to hit 6 liters," she says.
Stetzer believes the break in the sac wasn't directly over the uterine opening because the leaking slowed or stopped depending on Bukulmez's position. Bukulmez discovered which positions stopped the leaking and remained in them.
"She would just go to all of these extremes, above and beyond what most patients would do — she was going to conquer this," Stetzer marvels. "It was very impressive."
Amazingly, Bukulmez reached her 23rd week of pregnancy. Stetzer admitted her to MetroHealth Medical Center and began administering antibiotics to protect against infection, steroids to help speed fetal development, and oral medication to control the gestational diabetes she had developed. Tests showed that the baby in the broken amniotic sac, now named Berk, was only slightly behind his twin Mert in lung development.
Bukulmez went into labor seven weeks later, on June 8. Berk was delivered first, via cesarean section. He weighed 3 pounds, 7 ounces, only 2 ounces less than Mert — a good weight for a preemie at that point in gestation.
"Dr. Stetzer took him out and said, •Here's your baby,' " Bukulmez remembers. "As soon as he said that, Berk started crying. I was so happy. I said, •My God, he has lungs!'"
Berk remained in the hospital for 11 weeks, Mert for six. The boys spent their first night at home together with their parents on Aug. 23. Neither child faces any long-term health issues. Stetzer calls Bukulmez's pregnancy "a 1-in-20,000 experience."
"Both of the babies are very precious to me," Bukulmez says. "But when I look at Berk, it's like looking at a miracle."
On the Cutting Edge
The health issues that plagued Matthew Hiznay during the summer of 2011 seemed unrelated and innocuous. The 24-year-old University of Toledo medical student attributed the ache in his neck and left shoulder, then the pain in his chest, to a recently adopted regimen of weight lifting. As for the persistent, dry cough he subsequently developed — well, that was merely a symptom of seasonal allergies made worse by the abnormally hot, dry weather.
"These are all symptoms I've had in my life before," the Youngstown native explains. "They gave me reason to think there was absolutely nothing wrong."
Hiznay would soon learn those symptoms were all a part of something far worse than he could have imagined. On Aug. 26, 2011, Dr. Nathan Pennell, director of the Cleveland Clinic's lung cancer and medical oncology program, diagnosed Hiznay with Stage 4 non-small-cell lung cancer, the most common form of the disease. Although the single tumor in his left lung was quite small, the cancer had spread to the lymph nodes in the center of his chest and lower neck, the fluid in the protective sacs around the lungs and heart, and the breastbone.
When he arrived at the hospital a week later to begin chemotherapy, he had a collapsed left lung and pneumonia.
Hiznay's condition continued to worsen in the hours after he was hospitalized. His blood-oxygen level dropped dangerously, and his heart stopped beating. Doctors resuscitated Hiznay, put him on a ventilator, and drained the fluid around his heart that was restricting the organ's function.
"If I had not wanted to get the chemo, I would have been at my parents' house," Hiznay says. "My heart would have stopped, and I would have died."
Hiznay's condition puzzled Pennell. The average age of patients diagnosed with non-small-cell lung cancer is 70 years old. And Hisnay had never smoked or been exposed to cancer-causing chemicals. Pennell ordered more tests, convinced that the cancer was rooted in some sort of genetic defect.
On Sept. 9, Pennell's persistence was rewarded. Lab results showed Hiznay had anaplastic lymphoma kinase-positive non-small-cell lung cancer, a rare form of the disease caused by a gene mutation in cells lining the lung airways. Pennell explains that the gene manufacturers a protein that triggers cells to grow and divide unchecked.
Just days after Hiznay was diagnosed with lung cancer, the U.S. Food and Drug Administration had approved a new drug for treating patients with ALK-positive lung cancer. Crizotinib "turns off" the protein made by the mutant gene.
"The minute that you turn it off, the cell dies," Pennell says. Side effects of the pill are mild — nausea, benign visual effects such as "trails," swollen ankles, electrolyte abnormalities — and easily managed with other medications. The biggest problem, in fact, was obtaining the medication, which had not been mass-manufactured and distributed to specialty pharmacies.
"Cancer, especially lung cancer, has never been like this before, where there is a treatment so effective that it's really an emergency to get it," Pennell says. "Historically, if someone was in the intensive care unit like Matt was, they just would have eventually died. We didn't have treatments that could work fast enough to save someone who was that sick."
On Sept. 21, Hiznay was discharged from the Cleveland Clinic. When he went in for a CT scan seven weeks later, Pennell saw no trace of the cancer.
"When people say to me, •Oh, that's amazing,' I say, •No, that's God,' " Hiznay says.
Unfortunately, Hiznay's cancer returned in May — a result, Pennell says, of the mutant gene developing a resistance to the medication. Pennell immediately arranged for Hiznay to enroll in a clinical trial at the University of Colorado for an experimental drug that eliminates ALK-positive cells in much the same way crizotinib did. The results have been equally impressive, although no one knows how long Hiznay and other clinical-trial participants will enjoy them. Hiznay, now working on a doctorate in molecular medicine at the clinic's Lerner Research Institute, calmly anticipates taking a succession of such cutting-edge drugs until researchers discover a cure. "There's always good old-fashioned chemotherapy," he adds. "Having cancer, you always have to be optimistic."
A Breath of Fresh Air
For months, Tracey Coleman attributed her breathing difficulties and barking cough to asthma. The 43-year-old North Royalton resident knew the symptoms well — she'd lived with them from childhood until she outgrew the condition in early adulthood. She never suspected the problem was more serious until the usual prescription drugs failed to provide relief. By then, she had noticed swelling in her feet and ankles and was having trouble completing the most basic of physical tasks. The insurance specialist couldn't even walk the short distance from the parking lot to her desk in a Broadview Heights optometrist's office without getting tired and winded.
"I had to stop six times to catch my breath," she remembers.
Coleman finally saw her family doctor in March. She expected to learn she had bronchitis; instead, the physician ordered a chest X-ray that showed she had an enlarged heart. An electrocardiogram and subsequent tests yielded a diagnosis of pulmonary arterial hypertension.
Dr. Touraj Taghizadeh, medical director of Southwest General Health Center's Pulmonary Hypertension Center in Middleburg Heights, explains that the pulmonary artery — the artery that carries blood from the right side of the heart to the lungs — becomes thickened, fibrous and constricted, making the right side of the heart work harder to pump blood through it.
"Over years, the right side of the heart eventually gives out," he says.
The condition is often misdiagnosed as a far more common ailment such as left-heart failure, coronary artery disease, emphysema or asthma, Taghizadeh adds. Although pulmonary hypertension — a term that refers to increased pulmonary arterial pressure caused by a range of health problems — is common, pulmonary arterial hypertension is rare. Twice as many women are diagnosed with it as men. Like Coleman, many are already living with schleroderma, a connective-tissue disorder characterized by thickened, tight skin, particularly on the hands.
"One of the places schleroderma likes to attack is the pulmonary artery," Taghizadeh says. People with HIV, congenital heart defects or a history of using appetite suppressants, cocaine and amphetamines are also predisposed to developing PAH. "But some people just get it because they get it."
When Taghizadeh diagnosed Coleman with PAH, he staged her condition at between 3 and 4, the most serious phase. Coleman remembers someone telling her that she may need a heart-lung transplant at some point.
"Heart-and-lung transplant hit the bell in my head that made me go, •Oh! This is serious,' " she says.
The first step in treatment, however, was a drug protocol to dilate the pulmonary artery and increase blood flow to the lungs. After six months of trial and error, Taghizadeh prescribed two oral medications and a continuous infusion delivered under the skin by a pager-sized pump attached to a port in Coleman's abdomen.
"I actually wear my pump on the collar of my shirt," she says. "I realize this is my buddy for life."
Although Coleman is still battling water-weight gain, she feels pretty good. "Anybody who knows me will tell you I am vastly improved," she says. She can now climb a flight of stairs and talk on the telephone at the same time. Coleman even hopes to start exercising at some point. Taghizadeh is still adjusting her medication dosage, which gives Coleman hope that she can increase her physical activity.
"There are still things that we can do to improve how I feel and live every day, short of this heart-lung transplant. If they tell me I have to have that done, I'm actually not sure I could," she says. "But as long as we have options, I have a really positive outlook."
A New Outlook on Life
Nicole Born-Crow didn't think much about her son Finnegan's "staring spells" — at least, not at first. The seconds-long episodes, which began when he was 2 weeks old, were so brief and infrequent that the Shaker Lakes Nature Center office manager and her husband, Kevin, manager of the Key Center Starbucks, assumed it was normal infant behavior.
"We actually joked that he saw ghosts or dead people," Nicole recalls.
Tests ordered by a neurologist revealed nothing out of the ordinary, and the staring gradually subsided. The couple, convinced their now-5-month-old son was basically healthy, planned an August 2011 visit with friends in New York City. But during the road trip, the staring spells returned. Parental concern turned to terror on the family's last morning in the Big Apple: Finnegan went into a continuous series of the episodes while they were driving to brunch.
"He'd stare for five minutes, pop out real quick and start crying, and then go right back into staring," Nicole remembers. "There was just no reprieve."
The couple drove to New York-Presbyterian Morgan Stanley Children's Hospital, where emergency-room staffers immediately determined Finnegan was having epileptic seizures. The news stunned his parents. Like many others, Nicole and Kevin assumed all seizures were violent occurrences characterized by intense shaking and flailing.
"What he was doing was just so mild," Nicole says. "I had never heard of [an epileptic seizure] being something like unresponsive staring."
Three days later, the family drove home to Lakewood, armed with a prescription to control the baby's epilepsy and an emergency medication to bring him out of any prolonged "breakthrough" seizures. A series of tests at Rainbow Babies and Children's Hospital indicated that a portion of Finnegan's brain was not functioning properly, an area to the back and right called the right occipital lobe.
Dr. Jonathan Miller, director of functional and restorative neurosurgery and director of epilepsy surgery at University Hospitals Case Medical Center, goes so far as to call Finn's right occipital lobe "essentially nonfunctional." He attributes the problem to cortical dysplasia, a congenital condition in which cells do not form and migrate properly in a given area of the brain during pregnancy. In most cases, Miller says, doctors cannot determine exactly why.
"Epilepsy is abnormal activity in the brain that leads to a storm of synchronized neurofiring," he says. "That can happen for a lot of different reasons. Ultimately, it comes down to irritation of the brain's normal physiologic functions. The most common cause of epilepsy in little kids is a brain that doesn't quite form right."
For the next couple of months, medications provided control of Finnegan's epilepsy. But the frequency of 20- to 30-second "breakthrough" seizures increased dramatically over the holidays. "In the span of a few months, he went from having a couple of seizures a day to having eight to 15 a day," Nicole says. Giving Finn an emergency antiseizure suppository became part of her daily routine. But it was the sight of little Finnegan falling from a sitting position during a seizure that ultimately shocked Nicole and her husband into finally considering the brain surgery doctors had recommended.
Initially, doctors suggested a traditional operation that removed the problem area of Finnegan's brain. Miller offered an alternative: simply severing the neural connections between the healthy and damaged areas by making a couple of deep, carefully mapped cuts. Although the procedure — called temporo-parieto-occipital disconnection — had been performed in Montreal, Switzerland and India, Finnegan would be one of the first patients in the United States to undergo it.
"The idea that you can just sever the neural tracks and leave the brain intact is an elegant one," Miller says. "But if you leave some tracks intact, then you haven't done any good. A lot of [surgeons] haven't learned how to do it or aren't comfortable with the possibility that [the patient] may end up with residual seizures."
The exact area to be "disconnected" controlled left peripheral vision and memory, among other things. But Miller knew from previous cases that rapid scanning eye movements and other areas of the brain could compensate for whatever function was lost. "That's the beautiful thing about operating on a kid this young," he says. Indeed, he believed that since that area was already "deceased," Finnegan's sight might already be compromised.
"If the parts of the brain that we're taking away are nonfunctional, then we end up not causing any problems," he says.
On March 1, Finnegan emerged from surgery "completely like he was before — minus seizures," says Nicole. "He just wanted to cuddle. He was babbling immediately. As soon as he was able to sit up, he was sitting up again."
Since then, he's continued achieving developmental milestones with the help of occupational and speech therapists.
"He certainly wouldn't be where he is now without the surgery," she says.
In the Nick of Time
Every time Dan Smith walked into the EMH Center for Health & Fitness in Avon Lake, he felt safe having an emergency room near the gym. He'd undergone double-bypass heart surgery in 2001. Doctors had inserted stents to open two blocked arteries in February. But five mornings out of seven, the 60-year-old Sheffield Lake resident arrived for a two- to three-hour workout, a schedule he'd maintained ever since he retired as chief operator of Avon Lake's municipal wastewater-treatment plant six years ago.
Smith's schedule was interrupted when his fear became a reality on a sunny Wednesday last April.
He was beginning a 30- to 40-minute session on the elliptical machine shortly after 8 a.m., when his vision suddenly seemed slightly out of focus. "I saw a friend of mine walking by, and I raised my hand to wave to him," he remembers. "I could barely raise my arm. I tried to say something, and nothing would come out." Smith stopped the machine and stepped off it for a few minutes. The puzzling episode seemed to pass, and he resumed his workout.
"That's when my legs gave out," he says. "I could see, I could hear, but I could not communicate. I could not make eye contact with anybody. It was the strangest thing — I wanted to talk, but I couldn't. I found out later the whole right side of my face had collapsed. The whole right side of my body was paralyzed."
Minutes later, Smith was in the emergency room next to the fitness facility. Dr. Allan Starr, the doctor on duty, quickly determined he'd suffered a major stroke in the left side of his brain.
Starr immediately ordered a CAT scan to make sure Smith hadn't developed a more serious variant of stroke caused by bleeding in the brain. Once testing indicated Smith had a large but common blood clot, he prepared to administer a clot-busting medication through Smith's IV.
Time was of the essence. The drug dissolves clots slowly, and Starr knew he only had a limited time to restore blood flow to the affected area of Smith's brain and minimize permanent damage. But first he had to check with Smith's wife to make sure he wasn't taking a major blood-thinner — a prescription that, combined with the clot-buster, could cause brain bleeding. Stroke experts at University Hospitals Case Medical Center subsequently told Starr that Smith had a 1-in-10 chance of suffering significant bleeding on the mild blood thinner his wife recalled he was taking.
"But you balance that against the chance of living like he was, and most people would choose to take that 1-in-10 chance," Starr says.
Smith's wife told Starr to give her husband the clot-buster as soon as she arrived at the emergency room — around 9 a.m., according to Starr's watch. By the time a transport team loaded Smith onto a helicopter at 9:50 a.m., Starr was already seeing improvement in Smith's condition.
"He had acquired the ability to move his right leg to command, and he could wiggle his right fingers a little more," Starr says.
As soon as Smith landed at University Hospitals Case Medical Center, he was rushed into an operating room. There, doctors threaded a catheter into his brain, via an artery accessed through his groin, and removed the clot.
When Smith awoke later that day, he could make eye contact, move his right arm and leg, and speak, although his words were unintelligible. By Thursday evening, his speech was slow but clear. "A lot of doctors were stopping in to say how lucky I was," he remembers. On Friday morning, he was walking. He went home that afternoon.
A month later, Smith was walking the track and riding a stationary bike at the EMH Center for Health & Fitness. In September, he resumed his full workouts. He still worries about suffering another stroke.
"It's always in the back of my mind, that anything can happen," he admits, then chuckles. "That's one of the really, really nice things about having an emergency room right next to the gym."
