His seizure sparked terrifying fall that uncovered long-sought answer
For years Carter Caldwell had adamantly rejected doctors' recommendations that he consider surgery to treat the frequent, uncontrolled seizures that were ravaging his brain.
Caldwell, who had developed epilepsy when he was 28, regarded the operation that involved removing a portion of his brain as too big a risk - particularly because doctors weren't sure what was causing the seizures and couldn't pinpoint their location.
Instead the Philadelphia business executive had organized his life to minimize certain foreseeable hazards: He lived downtown and didn't drive. He didn't push his toddler's stroller. When taking the train he stood at the back of the platform - nowhere near the tracks in case he suddenly collapsed. His colleagues at work knew about his condition.
But that calculus changed abruptly in November 2014. Caldwell, accompanied by his wife, Connie, and their 3-year-old son, was atop a hill at Pennsylvania's Valley Forge National Historical Park posing for photos for a holiday card. Without warning he began an awkward shuffling walk that signified the onset of a seizure. Then he lost consciousness and fell head first down a rocky 15-foot embankment before landing at the edge of a stream.
"Thankfully," he said, "I didn't roll into the stream." He spent the next 2 1/2 weeks in a nearby hospital where a plastic surgeon performed multiple operations on his broken jawbone, lacerated cheek and shattered eye socket.
"I remember him saying, 'I can't believe this happened in front of my family,' " recalled his longtime neurologist John R. Pollard, formerly associate director of the epilepsy center at the University of Pennsylvania. Pollard had warned Caldwell that his intractable seizures, which had proved resistant to numerous medications, placed him at risk for sudden death or serious injury.
"It was a pivotal event," Caldwell, now 46, said of the accident that convinced him he had no choice other than brain surgery. "I had never had a seizure where I had become so injured."
In September 2015 a successful operation unmasked the very unusual cause of Caldwell's seizures, a culprit experts had long suspected but had been unable to definitively identify.
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Caldwell's first seizure occurred in December 2004 while he was living in Chicago. He said he walked into his condo, "froze briefly and stared into space, then kept walking." His former wife, a resident in emergency medicine, witnessed the episode and told him he needed to see a doctor.
A week later Caldwell was asleep when he suffered a grand mal or tonic-clonic seizure; his body stiffened and his arms and legs shook uncontrollably. He was hospitalized, diagnosed with epilepsy and began taking the first of what would be more than a dozen drugs to treat the neurological condition that affects more than 3 million Americans.
Epilepsy is characterized by unprovoked surges of electrical activity resulting in seizures that disrupt the normal connections between brain cells. Its causes include head injury, stroke, metabolic disturbances and tumors; often no underlying cause is found. Diagnosing epilepsy involves tests to rule out infection or other causes and to pinpoint the location where seizures originate, which guides treatment. Frequent or prolonged seizures can damage the brain by destroying or altering brain cells.
Doctors at a Chicago hospital determined that the seizures seemed to start in Caldwell's left temporal lobe, then spread to the right lobe. The temporal lobes play a vital role in processing language, emotions and visual perception; temporal lobe epilepsy is the most common form. Over the next two years Caldwell experienced several tonic-clonic seizures in addition to other types: focal seizures, which involve staring into space, and rare gelastic seizures, which result in bursts of uncontrolled laughter or gibberish.
In 2006 Caldwell traveled to another hospital in the Midwest for a second opinion, which involved extensive testing. Doctors detected seizures in his left and right temporal lobes along with an undetermined lesion on the right lobe, which they said could be a tumor or an indication of inflammation or infection that might not require surgery.
"There was just no clear narrative of where [the seizures] originated or what could be causing them," recalled Caldwell, who moved back to his native Philadelphia in 2006. "Generally speaking the tenor was, 'We'll keep trying medications.' "
As the years passed it was clear that Caldwell's seizures were increasing in frequency and that drugs - which work for about 80 percent of people with epilepsy - failed to control them.
"What was strange was that I would try a new [drug] and my seizures would change," remembered Caldwell, program director of the Co-Investment Program at Penn Medicine, which funds faculty-led biotech companies.
Unlike some people with epilepsy who report that they experience an aura shortly before a seizure, Caldwell's typically occurred without warning. He fell several times at work and once at a Philadelphia park, each time suffering only minor injuries.
Because so many medicines had failed, Pollard and other doctors recommended Caldwell consider surgery. The goal is to remove the part of the brain where seizures originate or to stop their spread, without causing a loss of brain function. In about 70 percent of cases, surgery on the temporal lobe can greatly reduce or eliminate seizures.
For Caldwell the prospect was too frightening. He worried surgery might irreparably damage his memory, language abilities or hand-eye coordination. The latter was especially important to him. Since college he had been an avid squash player. Epilepsy hadn't affected his ability to play, but surgery could end it.
And doctors could not tell whether the seizures were emanating from his left or right temporal lobe or even if the spot that had been seen on an early scan was clinically significant. A radiology report in 2014 described it as "no definite abnormality."
"I had to just do my best to live my life," Caldwell said.
That had become more difficult. In 2010 Caldwell was attending a lecture in business school when he suffered one of his most upsetting seizures: he lost consciousness, slumped onto his desk and began moaning. The next day he stood up in class and explained what had happened; his classmates applauded him. A year later while in Munich he landed in a hospital for two weeks after a seizure left him temporarily paralyzed from the waist down. The Valley Forge fall occurred three years later.
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To Pollard, Caldwell's resistance to surgery was neither surprising nor atypical. "I think it was not a totally irrational decision," said Pollard, now director of the epilepsy center at ChristianaCare in Delaware. "The data was sort of all over the place. Carter knew I wasn't going to force him to do anything or abandon him if he didn't" have surgery.
Many patients, the neurologist added, are "worried that brain surgery is going to change who they are" - one reason the average delay from onset of symptoms to surgery is about 20 years. "Any neurosurgery is terrifying. We think of ourselves as being our brain."
But Pollard didn't sugarcoat the possible consequences of the status quo, chiefly a serious injury or that Caldwell "might not wake up in the morning," a reference to sudden unexpected death in epilepsy (SUDEP), which can occur during or after a seizure and kills an estimated 3,000 Americans annually.
In early 2015 while Caldwell was recovering from his facial injuries, Pollard referred him to Penn neurosurgeon Timothy Lucas, now a professor of neurosurgery at Ohio State University.
Caldwell said his meetings with Lucas and the support from Pollard were reassuring. "Dr. Lucas was so calm," Caldwell said. "He would sketch things out for us." Lucas told Caldwell and his wife that the brain compensates after surgery by rewiring itself.
Caldwell enrolled in a research study that used a more powerful MRI to zero in on the abnormal spot which, reassuringly, had not changed. Years earlier doctors had speculated that it might be a DNET, a dysembryoplastic neuroepithelial tumor. The rare, benign brain tumor grows slowly and typically causes medication-resistant seizures that appear before age 20.
The MRI scan appeared to confirm the DNET hypothesis, but as Lucas noted, "There's no way to be sure until you take it out."
The next step was intracranial monitoring, which involves implanting electrodes inside the skull to record electrical activity and track the location of seizures. Monitoring also allows surgeons to map areas critical to brain functioning in an effort to protect them during surgery.
Although Caldwell by then had been having seizures several times a week, they inexplicably ceased after he was hooked up to monitoring equipment. Doctors attempted to provoke them using flashing lights, taking him off all his medications and sleep deprivation. When none of these worked doctors added a less commonly used trigger: alcohol. Carter was given tiny bottles of Sutter Home Chardonnay in preparation for a night of enforced sleeplessness.
It was too late to call anyone he knew on the East Coast, so Carter telephoned a friend in California. The pair spent five hours in the middle of the night drinking and talking. The plan worked. Caldwell had three seizures, all of which originated in that abnormal spot on his right lobe.
A few weeks later Lucas removed part of Caldwell's right temporal lobe, along with the hippocampus, which is vital to the storing of memories, and a portion of the amygdala, which processes fear. Pathologists confirmed the tumor was a DNET.
After a total of six weeks in the hospital, Caldwell went home. A few weeks later, eager to test his facial recognition skills, he attended an annual conference where he knew the participants. He was greatly relieved when he had no trouble recognizing anyone. Several weeks later he played squash with a friend; his game was unaffected.
Since his surgery Caldwell, who has resumed driving, has been seizure-free. Although people who are seizure-free a year after surgery can usually stop taking anti-seizure drugs, Caldwell has been reluctant to do so. "You don't mess with success," he said, but adds that with Pollard's encouragement he is considering weaning off the medications, which may be superfluous.
The biggest change has been the absence of fear, which had come to dominate his life.
"I'm not constantly worried" about having a seizure, he said, adding that he wishes he had considered surgery sooner. "It took that episode at Valley Forge Park to really wake me up."
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