Neurology

New Epilepsy Monitoring Technology Tailors Patient Care

by Lauren Woods

Research At The Birkbeck Babylab Into Brain And Cognitive Development LONDON, ENGLAND - MARCH 03: Research assistant Katarina Begus, prepares a 'Geodesic Sensor Net' for an electroencephalogram (EEG) experiment at the 'Birkbeck Babylab' Centre for Brain and Cognitive Development, on March 3, 2014 in London, England. Researchers at the Babylab, which is part of Birkbeck, University of London, study brain and cognitive development in infants from birth through childhood. The scientists use various experiments, often based on simple games, and test the babies' physical or cognitive responses with sensors including: eye-tracking, brain activation and motion capture. (Photo by Oli Scarff/Getty Images)

The new epilepsy unit will feature a high-density geodesic EEG with more than 250 sensors in a cap like the one pictured. Oli Scarff/Getty Images


UConn Health is now home to a high-tech Epilepsy Monitoring Unit.

Located on the first floor of the new tower at UConn John Dempsey Hospital, the unit has two large patient rooms with state-of-the-art technology; 24-hour video observation capabilities; the latest in advanced electroencephalography (EEG) monitoring; and a dedicated team of neurology and neurosurgery doctors, nurses, and staff.

If needed, patients can be monitored for up to several days so doctors can determine whether the seizures are caused by epilepsy, what kind of seizures they are, and where they originate, says Dr. L. John Greenfield, chair of the Department of Neurology at UConn Health and a nationally-recognized epilepsy specialist. The monitoring information is critical to figuring out the best way to halt the seizures.

For patients with epileptic seizures, the information gathered helps doctors create a personalized clinical care plan and choose the most appropriate medications or adjustments for the patient’s seizure type.

For patients who may need surgical intervention to control their seizures, the new unit will allow doctors to precisely localize where the seizures start in the brain to see if neurosurgery might be a beneficial treatment option. According to Greenfield, if the seizure starts in the temporal lobe, there is a 70 to 80 percent chance the seizures can be cured with brain surgery.

Greenfield hopes the data and insights gained from the new unit’s video and EEG monitoring will advance future brain research and clinical care for epilepsy patients. The new unit will soon offer high-density geodesic EEG recordings that can sample patient brain wave data using more than 250 electrode sensors contained in a wearable, stretchy web that fits over the head like a swim cap. This device can pinpoint epileptic activity with much higher precision than traditional EEGs, which record signals using only 19 electrodes.

“With the combination of our state-of-the-art monitoring unit, clinical care, research, and our new chief of neurosurgery, Dr. Ketan Bulsara, UConn Health can now provide comprehensive care for patients with epilepsy and with seizures due to brain tumors or vascular malformations,” saya Greenfield. Bulsara specializes in skull base, endovascular, and tumor neurosurgery.

Dr. Alessi and the Concussion (R)evolution

by Peter Nelson

an artsy illustration of a brain overlooking a landscape brain


“You wanna fight? You damn stupid fool,” says Jackie Gleason’s character, trainer Maish Rennick, to Louis “Mountain” Rivera (played by Anthony Quinn) in the 1962 film “Requiem for a Heavyweight.”

“Don’t you understand? The odds are, all you’ll wind up is a mumbling idiot — a stuttering jerk. Why don’t you go home?”

Dr. Anthony Alessi, UConn Health associate clinical professor of neurology and orthopedics and director of the UConn NeuroSport Program, has been giving fighters similar messages, albeit more tactfully phrased, for the last 21 years as the consulting neurologist during boxing matches at Mohegan Sun. He has gone on to study head trauma in other sports, how to measure recovery, how to gauge when an athlete is ready to return to play, and how to prevent head injuries. But he got his start as a “fight doctor.”

After working as an athletic trainer at Mount St. Michael Academy in the Bronx, Alessi eventually opened a neurology practice in Norwich, Connecticut. He started working with the Yankees’ Double-A team, and noticed during his hospital shifts that he was looking at many baseline, prefight brainwave EEGs for boxers on the cards at Mohegan Sun casino.

“The Connecticut boxing commissioner invited me to come down to watch a fight,” Alessi says. “After the fight, he said, ‘How would you like to work with us?’ I said, ‘Do I get to end the fight?’”
“He said, ‘We want you to.’ I’ve been ending fights since 1996.”

There’s no such thing as a minor concussion. And as I tell students, if you’ve seen one concussion, you’ve seen one concussion. They’re all different.

Alessi admits it’s odd for a neurologist to work in a sport where the entire goal is to induce maximum cognitive impairment in your opponent — but that’s exactly what makes his presence imperative.

“In mixed martial arts, you have the ability to tap out,” Alessi says. “In boxing, they can’t quit. But you’d be surprised how many times you go into the corner and the fighter doesn’t want to come back out. That’s the first question I ask them, and if they say no, I end the fight. He’ll still get paid, and I’ve saved his life.”

The American Academy of Neurology has backed off from its edict in the 1980s that boxing should be banned, instead calling for measures including more regulations and formal neurologic examinations for fighters. Alessi says more and more neurologists have gotten involved in the sport, screening individuals to determine whether they should fight.

Besides protecting individual athletes, Alessi has used boxing as a lens through which to view the larger picture surrounding head trauma.

“As the public awareness about long-term brain damage from concussions developed, I realized it was like I had my own lab,” he says.

More to Learn

The world has known for a long time about the dangers of head trauma, the syndrome codified in 1928 when New Jersey forensic pathologist Dr. Harrison Stanford Martland published a paper in The Journal of the American Medical Association on fighters and coined the term “punch drunk.”

Today, it seems that new findings on head injury are in the news daily. Since 2001, more than 60,000 scientific papers on chronic traumatic encephalopathy (CTE) and brain trauma have been published, raising awareness at both the public and professional levels, leading to protocols where athletes are pulled from games at the first sign of concussion. Trainers are taught to perform a SCAT5 (Sport Concussion Assessment Tool, 5th edition), elaborating on the questions the old cigar-chomping cornermen used to ask fighters between rounds: “What’s your name? What day is it? Do you know where you are?”

The SCAT5 is used because the greatest and most immediate danger to concussion sufferers is second-impact syndrome, a fatal edema caused by a second head trauma sustained before the brain has had time to repair torn tissues, ruptured blood vessels, or damage at the cellular level from an earlier injury. Other organs have room to expand if they swell. The brain, encased in a hard shell, does not.

“There’s no such thing as a minor concussion,” says Alessi, who teaches at the UConn School of Medicine. “And as I tell students, if you’ve seen one concussion, you’ve seen one concussion. They’re all different. In most cases, a single concussion should not cause permanent damage, but a second concussion, soon after the first, does not have to be very strong for its effects to be permanently disabling or deadly.”


Throughout his career, neurologist Dr. Anthony Alessi has served as a consultant for professional boxers and football and baseball players, as well as UConn student-athletes.

Throughout his career, neurologist Dr. Anthony Alessi has served as a consultant for professional boxers and football and baseball players, as well as UConn student-athletes. Over the decades, he has witnessed a sea change in the way people talk about, prevent, and treat head injuries in contact sports. Peter Morenus


The problem with studying concussions is that you can’t line up a variety of test subjects of various ages and sizes, take baseline measurements, and then hit them in the head with a 13-pound bowling ball moving 20 mph — the equivalent, experts estimate, to taking a punch from a pro boxer. You can’t then compare those results to the results from hitting them with 6-pound bowling balls moving 40 mph, or to what the results would be if you hit them once an hour, or once a day for a month, or in the side of the head instead of the front.

“Ninety percent of the time, after a concussion, you wait 10 days and the athlete is going to be okay. But we still don’t know what the long-term effects might be. We know how the cells repair themselves, but we don’t know what kind of debris might be left behind once the cells heal,” Alessi says.

Playing Smarter

In July, Boston University released the results of a study of the brains of 202 deceased football players, 111 of whom had played in the NFL. All but one of the NFL players’ brains were found to have CTE.

Alessi is, of course, aware of the current discussion of CTE in relation to professional sports, but he attends from a scientist’s detached distance.

“There’s an association with football, but it doesn’t mean there’s causation. It’s an important difference. There’s a lot of selection bias.”

Those who donate their brains, Alessi says, may be looking for a biological explanation for their depression, for example.

Alessi is more concerned that attention is being paid in the wrong places.

“It’s a pyramid,” he says. “There are only 1,800 professional football players. In college football, there are 54,000. In high school football, about a million. In youth football, you have over 3 million children. Another 3 million children play youth soccer, and a half million play youth hockey. So you have 6.5 million young athletes playing high-velocity collision sports, all with brains that are still developing.”

Children lack both the myelin sheathing that protects older brains and the developed neck musculature that helps older athletes avoid injury. In addition to working with UConn student-athletes and teams, Alessi advises youth sports programs and is concerned for the younger athletes.

“They’re smaller and they don’t move as fast, so the force of impact is less, but they’re more vulnerable,” Alessi says. “We used to think if you let kids play full-contact sports, it will toughen them up — not true. The more contact you have, the greater the risk.

“There’s also inadequate medical attention at those levels,” he says. “We’re not paying attention to where our resources should be placed the most.”

The Korey Stringer Institute (KSI), a national sports safety research and advocacy organization based at UConn, recently urged state high school athletic associations to implement life-saving measures after KSI conducted the first comprehensive state-by-state assessment of high school sports safety polices. Each state received a score based on the extent to which it met best- practice guidelines addressing the four leading causes of sudden death among secondary school athletes, which include head injuries.

Requiring the presence of certified athletic trainers at every secondary school athletic event and training coaches on concussion symptoms are among the bare-minimum guidelines, which are endorsed by leading sports medicine organizations in the United States.

Still, progress has been made.

Banning checking and headers in youth hockey and soccer and reducing full-contact practices to once a week for professional and college football have been linked to reduced injuries, Alessi says. But many youth football teams still have full-contact practice five days a week.

No one wants collision sports to go away, Alessi says, but instead of striving to play harder, he believes we can strive to play smarter.

“You have to ask, what’s to be gained from high-velocity impact at a young age? The fastest-growing youth sport in America today is flag football. Archie Manning [former pro-football quarterback and father of Peyton and Eli Manning] didn’t let his sons play youth football. Tom Brady never played youth football. A lot of really good professional athletes in the NFL knew that they could build skill without getting hit,” Alessi says.

“I think there’s a lot to be gained by us changing the rules. We’ve made a lot of headway with all neurologic injuries in sports. Legislation isn’t required to deploy common sense.”

Thanks to the work of Alessi and people like him, athletes know the risks before they step on the field or in the ring. While there’s always more research to be done, at the very least, we’ve replaced the comical cartoon image of the cross-eyed concussion victim — with the lump rising from his noggin and stars and birds circling his head — with reliable information. The kind of information an athlete in a collision sport needs to make informed decisions and to play safely, avoiding injuries when possible and returning to play only when it’s safe to do so.

“If you gotta say anything to him,” Maish Rennick says of “Mountain” Rivera at the end of the movie, “tell him you pity him. Tell him you feel so sorry for him you could cry. But don’t con him.”

Matching Medicine to the MS Patient

UConn Health researchers have discovered why drugs for an aggressive form of multiple sclerosis work in the lab but fail in real patients: Each primary progressive multiple sclerosis patient has uniquely defective stem cells, perhaps making the debilitating illness a prime candidate for precision medicine.

By Kim Krieger

Illustration by Katie Carey

illustration of stylized silhouettes holding their perfectly matched medication


At first, Christine Derwitsch thought she was just really out of shape. She and her husband had gone out for a hike. They went hiking often, but this time, by the summit of the first hill she had to sit down. Her legs were so heavy.

She laughed it off, saying she’d been spending too much time sitting at a desk. But over the next few months, walking became harder and harder. And gradually, Derwitsch realized something was wrong.

“I went on Facebook, and I looked at what I’d been able to do before — hiking, my sister’s wedding — and I couldn’t do that anymore. I thought, ‘This isn’t right.’”

It took her almost a year, but 29-year-old Derwitsch was finally referred to a neurologist at UConn Health, who diagnosed her with primary progressive multiple sclerosis (PPMS). It was a relief to finally understand what was happening to her legs, but the news wasn’t good; there were very few treatment options available.

Most cases of multiple sclerosis have a pattern of illness and then remission: symptoms flare up, then go away, then flare up again. There are effective drugs that help patients extend the periods of remission, and someone diagnosed with MS in his or her 20s may live comfortably for decades.

But PPMS is a different story.

“It’s a harder diagnosis to make because there are no attacks,” says Dr. Matthew Tremblay, Derwitsch’s neurologist at UConn Health, who specializes in treating MS.

And the same thing that makes PPMS harder to diagnose makes it harder to treat.

Most drugs for MS are designed to prevent relapses by suppressing the immune system. But PPMS patients don’t have relapses. To help them, a drug would need to help them regrow myelin, the insulation around our nerves that people with multiple sclerosis can’t reliably repair. Doctors seeking this kind of drug for PPMS keep chasing a mirage.

It’s like you bring in the National Guard to stop a riot, and [instead] they all sit down and start having lunch.

For PPMS, many researchers look for possible treatments among medications that have already been approved for other illnesses. That way they can go right from lab to patient if they show promise. And so far many medications have shown promise — in the lab. But no matter how well a compound works in the lab, it never seems to help many people in the clinic. It’s a conundrum that frustrates both doctors and patients.

But researchers at UConn Health now think they know why the drugs coming out of labs are duds. And they have an idea of how to fix it.

In a new study, UConn Health neuroscientist Stephen Crocker and his colleagues collected blood cells from patients with PPMS, as well as the patients’ siblings or spouses. Then in the lab, they “reprogrammed” the cells and turned them into neuroprogenitor stem cells.

Stem cells can turn into any type of cell in the body; neuroprogenitor stem cells are found only in the brain and specialize in turning into new brain and nerve tissue, such as the oligodendrocyte cells that re-myelinate nerves. These neuroprogenitor stem cells are known to protect the brain from injury, but this recent study was the first to ask whether these stem cells from someone with PPMS had the same ability to protect the brain as those from someone without the disease.


Christine Derwitsch

While primary progressive multiple sclerosis is harder to treat than typical MS, UConn Health researchers have found why drugs that work in the lab fail on real patients with PPMS, like Christine Derwitsch (pictured). Photo: Tina Encarnacion


To explore this question, the researchers first tried adding the stem cells to brain tissues in animals with damage similar to PPMS. Stem cells from the healthy relatives and spouses started repairing the damaged areas. But the PPMS stem cells didn’t do anything.

“It’s like you bring in the National Guard to stop a riot, and [instead] they all sit down and start having lunch,” Crocker says.

Crocker and his colleagues then tested how these stem cells were different by growing them in dishes in the lab. They collected the soup that the cells grew in, called conditioning media, and tested how this affected other cells grown in it afterward. The stem cells had left behind chemicals and proteins in the conditioned media, little messages that tell other cells that come later what they need to do.

Oligodendrocyte cells grown to maturity in media conditioned by healthy stem cells matured into nice, big oligodendrocytes with no problems. But the cells added to dishes conditioned by PPMS stem cells didn’t mature at all. Something about the neural stem cells from PPMS patients was messing up the young oligodendrocytes, leading them astray.

So members of Crocker’s research team next tested some drug candidates for PPMS and added them to the young oligodendrocytes. The drugs absolutely helped the young oligodendrocytes mature when they were growing in media conditioned by stem cells from healthy people. But the same drugs didn’t help the young oligodendrocytes when they were grown in media conditioned by diseased stem cells. In those cases, the cells responded differently every time.

As Tolstoy might have said, healthy stem cells are all alike, but stem cells with PPMS are all unhealthy in their own way. It might appear to be the same disease from the symptoms, but each patient’s PPMS seems to be caused by a different problem with that specific patient’s cells.

But that means that doctors may be able to screen drugs for brain repair on a patient-by-patient basis, Crocker says. He and his colleagues published their findings in the Feb. 1 issue of Experimental Neurology.

Tremblay has begun collaborating with Crocker as they plan the next steps to this research, looking to recruit patients for future studies.

And in the lab they’ve already found that some drugs that have been dismissed as ineffective when tested using more typical techniques may have the potential to work very well for certain PPMS patients — patients like Derwitsch.

Derwitsch hasn’t participated in the study yet, but it’s exactly patients like her who could benefit from this personalized approach.

In the meantime, she is staying mobile and positive. She credits Tremblay for getting her insurance to cover her treatment — he actually got on the phone with her insurance company, she says.

“Dr. Tremblay has so much knowledge about MS, but also a dedication and passion. Every time I have a question, he has an answer.”

Diagnosing Disruptions in the Autonomic Nervous System

UConn Health Hospital Building


Since the bodily functions it controls are automatic and involuntary, people don’t think much about their autonomic nervous system (ANS). But ANS dysfunction can indicate serious medical problems, and early detection is key to avoiding complications.

UConn Health is home to the only testing laboratory in the state dedicated to diagnosing disruptions in the body’s ANS.

ANS is the control center that regulates the body’s automatic functions, including stress response, heart rate, blood pressure, digestion, and urinary functions. Interruptions in the system can occur if there is a disruption in communication between the brain, spinal cord, and peripheral nerves.

Abnormal ANS reflexes can be a sign of medical conditions such as cardiovascular problems, diabetic neuropathy, and Parkinson’s or other neurodegenerative diseases.

“A series of simple ANS tests can help a patient finally find potential answers and treatment options for lingering, undiagnosed symptoms,” says UConn Health neurologist Dr. Matthew Imperioli. “The Neurology Department’s ANS Lab at UConn Health is proud to be filling a patient-care gap to meet the needs of patients
across Connecticut.”

Testing at UConn Health’s ANS lab can be performed in less than an hour by Imperioli, who has advanced fellowship training in this growing neurology subspecialty. Since it opened in May 2016, the lab has been busy assessing patients referred by neurology and primary care physicians searching for answers for their patient’s symptoms, such as recurrent fainting or dizziness.

The panel of four tests hunts for any abnormal ANS reflexes. Quantitative sudomotor axon reflex testing (QSART) uses specialized electrode technology on the arm and leg to measure sweat capabilities. Simultaneous heart rate and blood pressure technology captures any variability during deep breaths and forceful exhales.

Also, an automated tilt table with EKG and specialized heartbeat-to-heartbeat blood pressure monitoring repeatedly checks for any changes as a patient rotates from a lying-down position to nearly standing.

“Early detection of an ANS disorder is critical so we can prevent patient falls or injury, avoid health complications, prescribe the correct medications, and improve a patient’s quality of life sooner rather than later,” Imperioli says.

New Neurology Chair Sees UConn’s Possibilities

UConn Health Exterior, Farmington CT


Dr. L. John Greenfield looks forward to helping push UConn Health’s Department of Neurology to the next level as its new chair.

Greenfield, a nationally known epilepsy expert, came to UConn Health in early September from the University of Arkansas for Medical Sciences College of Medicine, where he also served as chair of neurology. He will also serve as the academic chair of neurology at Hartford Hospital.

“I see a lot of possibilities at UConn,” Greenfield says.

These include goals of establishing an epilepsy monitoring unit, developing a high-density electroencephalography (EEG) facility, and continuing to expand the stroke, neuromuscular, MS, and movement disorders programs.

Because we’re training the next generation of neurologists, we’re focused on … doing research and developing new treatments.

Greenfield’s arrival as UConn Health’s third epilepsy specialist puts the department at a “critical mass for moving things to the next level,” he says.

Previously, UConn Health has relied on Hartford Hospital for inpatient monitoring of epilepsy patients to determine if they are candidates for epilepsy surgery. Greenfield hopes UConn can establish its own unit for the initial phase of the process. He plans for continued and expanded collaboration with neurologists at Hartford Hospital in epilepsy and other areas. Neurologists at UConn and Hartford Hospital already work closely together in training neurology resident physicians and fellows.

UConn Health is also developing a high-density EEG facility, which would be a resource for the region, he says. Traditional EEGs monitor brainwaves using 15-20 electrodes. A high-density EEG involves a special cap with more than 250 contact points, providing more detailed information on where seizures are coming from, along with other potential uses.

The department also plans to hire more doctors to support its successful movement disorders, neuromuscular, MS, and stroke programs, according to Greenfield, while continuing to provide top-quality care in more “bread and butter” neurological disorders, such as chronic headaches.

“The fact that we’re accessible, very highly trained and patient focused, and an academic medical center gives us an edge against our competitors,” Greenfield says. “Because we’re training the next generation of neurologists, we’re focused on not only using the latest techniques and information so we can teach them, and also doing research and developing new treatments.”