Author: yec14002

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.

Pinpointing Risk Factors to Prevent Postoperative Delirium

by Lauren Woods


With rising surgery demands among the growing population of older adults, the UConn Center on Aging and UConn John Dempsey Hospital are teaming up to identify older patients at the greatest risk of developing postoperative delirium in order to prevent it.

Patients with delirium have an altered level of alertness and are sometimes excessively drowsy, hyper-alert, or agitated. Although postoperative delirium is usually short-term, lasting hours or days, the brain may not recover for weeks or months in older adults. If the condition is not identified and addressed, delirium can lead to a decline in an older patient’s surgical recovery and cognitive and physical health, a need for caregiver or nursing home care, or potentially an increased risk of death.

“Our goal is to do everything in our power to screen older patients before surgery for delirium’s risk factors and to prevent it after surgery — or at least minimize its duration and effect,” says UConn Center on Aging’s Dr. Patrick Coll, who has been working closely with surgeons and anesthesiologists to modify preoperative delirium screening protocols at UConn Health. “All doctors really should be adding delirium-risk-factor screening to their preoperative evaluations for patients age 75 and above.”

Risk factors for postoperative delirium in older patients include prior delirium after a surgery, underlying or existing cognitive impairment such as dementia or Alzheimer’s disease, heavy alcohol consumption that increases withdrawal risk, depression, frailty, malnutrition, immobility, infection, or taking certain medications.

Historically, surgery risk-prevention primarily focused on such areas as cardiac or pulmonary health. Last year, the American College of Surgeons and the American Geriatric Society issued new guidelines for optimal geriatric surgery patient management, which for the first time included screening for delirium risk before and after surgery.

“If a patient is deemed high-risk, the patient should have a geriatric assessment prior to surgery to help mitigate their risk and, after surgery, the hospital care team should plan to very closely monitor the patient,” said Coll.

The hospital care team can take simple, proactive steps to quickly reorient an older patient after surgery, Coll says. Even having a patient’s reading glasses and hearing aids readily available can make a big difference, as well as avoiding or limiting medications that can contribute to delirium, such as opioids.

With the help of aging expert Dr. Lavern Wright, UConn Health’s NICHE (Nurses Improving Care for Healthsystem Elders) program is expanding its scope to the surgical floors of the hospital to reduce older patients’ risk of delirium and other health complications. Further, all nurses now have access to the Confusion Assessment Method (CAM) tool and an electronic medical record order set to guide them in decreasing delirium’s impact.

In addition, Dr. Richard Fortinsky and his team are studying the effect of visiting clinical care teams at the homes of older adults with a history of delirium and other cognitive vulnerabilities to improve patient outcomes. This study, funded by the Patient-Centered Outcomes Research Institute, involves an in-home care program featuring a nurse practitioner who assesses older adults for delirium using a brief version of the CAM. The nurse practitioner also assesses for depression and dementia and teaches the patient and family members how to manage these conditions at home.

Blood Vessels in Your Brain Don’t All Act the Same

by Kim Krieger


Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published in the journal eLife.

Neuroscientists studying the brainstem have historically focused on neurons, which are brain cells that send signals to one another and all over the body. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules, which regulate neuron function. But until now, no one even considered the possibility that blood vessels may be similarly specialized.

For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes.

Neuroscientists have come to understand that astrocytes release signaling molecules that regulate neuron function. Until now, no one even considered the possibility that blood vessels may be similarly specialized.

UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn’t possibly be true in the part of the brainstem he studies. The retrotrapezoid nucleus (RTN), a small region in the brainstem, controls breathing. Mulkey has shown in the past that RTN neurons respond to rising levels of carbon dioxide in brain tissue by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job of driving us to breathe.

Mulkey’s team, primarily comprising UConn undergraduates, studied thin slices of brainstem and found that RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body.

Mulkey guessed that astrocytes had something to do with the change in blood vessel behavior, and his hypothesis was proved right in the lab. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released adenosine triphosphate signaling to the neurons and blood vessels that they should constrict.

“This is a big change in how we think about breathing,” Mulkey says.

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.”

Lab Notes – Summer 2017

Melanoma’s Signature

illustration of a melanoma cell

Dangerous melanomas likely to metastasize have a distinctive molecular signature, UConn Health researchers reported in the February issue of Laboratory Investigation. Melanomas are traditionally rated on their thickness; very thin cancers can be surgically excised and require no further treatment, while thick ones are deemed invasive and require additional therapies. But melanomas of intermediate thickness are harder to judge. The researchers measured micro-RNAs produced by melanoma cells and compared them with the micro-RNAs in healthy skin. Micro-RNAs regulate protein expression in cells. The team found that melanomas with the worst outcomes produced lots of micro-RNA21 compared to melanomas of similar thickness with better outcomes. In the future this molecular signature could help dermatologists decide how aggressively to treat borderline melanomas.


Chili Pepper and Marijuana Calm the Gut

The medical benefits of marijuana are much debated, but what about those of chili peppers? It turns out that when eaten, both interact with the same receptor in our stomachs, according to UConn Health research published in the April 24 issue of Proceedings of the National Academy of Sciences. The scientists found feeding mice chili peppers meant less gut inflammation and cured those with Type 1 diabetes. Why? The chemical capsaicin in the peppers bonds to a receptor found in cells throughout the gastrointestinal tract, causing the cells to make anandamide — a compound chemically akin to the cannabinoids in marijuana. The research could lead to new therapies for diabetes and colitis and opens up intriguing questions about the relationship between the immune system, the gut, and the brain.

illustration of chili peppers and marijuana in the gut


Isolating Their Target

brain scan

Brain cells of individuals with Angelman syndrome fail to mature, disrupting the ability of the cells to form proper synaptic connections and causing a cascade of other developmental deficits that result in the rare neurogenetic disorder, according to UConn Health research. Neuroscientist Eric Levine’s team used stem cells derived from Angelman patients to identify the disorder’s underlying neuronal defects, an important step in the ongoing search for potential treatments and a possible cure. Previously, scientists had relied primarily on mouse models that mimic the disorder. The findings were published in the April 24 issue of Nature Communications. While Levine’s team investigates the physiology behind the disorder, UConn developmental geneticist Stormy Chamberlain’s team researches the genetic mechanisms that cause Angelman.


The Cornea’s Blindness Defense

eye

The formation of tumors in the eye can cause blindness. But for some reason our corneas have a natural ability to prevent that from happening. Led by Royce Mohan, UConn Health neuroscientists believe they have found the reason, findings that will be detailed in September’s Journal of Neuroscience Research. They link the tumor resistance to a pair of catalytic enzymes called extracellular signal-regulated kinases 1 and 2. When ERK1/2 are overactivated in a specific type of cell, the “anti-cancer privilege of the cornea’s supportive tissue can be overcome,” says Mohan. That happens in the rare disease neurofibromatosis-1. “These findings may inform research toward developing better strategies for the prevention of corneal neurofibromas,” says Dr. George McKie, cornea program director at the National Eye Institute, which funded the study.

A Path With Less Pain

Genetic Clues Show Which Breast Cancer Patients Are Prone to Post-Treatment Agony

By Kim Krieger

woman chooses between two marked paths


Sickness and pain go together. We think of them as a matched pair, a married couple. Pain signals sickness, sickness causes pain. But this is not always the case. Especially in early stage cancer, often there is no pain — until the patient is treated.

UConn Health researchers have discovered genetic clues that could eventually reveal which people might be vulnerable to post-treatment pain, they reported in the June issue of Biological Research for Nursing.

“We’ll hear women say ‘If I knew the pain would be this bad, I’d have rather died of breast cancer,’” says Erin Young, a UConn Health pain geneticist. Young and her research partners wondered: Can we really call such treatment a “cure”? It would be better if we could know in advance which patients might suffer from which treatments.

Young worked with data collected as part of a broader study involving nurse-scientist and director of UConn’s Center for Advancement in Managing Pain Angela Starkweather, neuroscientist Kyle Baumbauer, and colleagues at the University of Florida and Kyung Hee University in Seoul, South Korea. Young’s analysis found that common variants in two genes contribute to certain symptoms during and after chemotherapy treatment for breast cancer. The results could one day help patients, and their nurses and doctors, make informed treatment decisions and prepare for — or avoid — damage to patients’ quality of life.

The researchers looked at the genetics of 51 women with early-stage breast cancer who had no previous chemotherapy and no history of depression. The women rated their well-being both before and after treatment for cancer, reporting on their pain, anxiety, depression, fatigue, and sleep quality. Young and her colleagues then looked for connections between genes and symptoms.

Can we really call treatment a “cure”? It would be better if we could know in advance with patients might suffer from which treatments.

They looked at three genes in particular: NTRK1, NTRK2, and COMT. These genes are already associated with pain from other research. NTRK1 is connected to rapid-eye-movement sleep (dream sleep), and a specific variant is linked to pain insensitivity. NTRK2 is associated with the nervous system’s role in pain, fatigue, anxiety, and depression. And some common versions of COMT are linked to risks of developing certain painful conditions. The researchers also chose these genes because the variants associated with pain, fatigue, and other symptoms are fairly common, making it possible to get meaningful results from a sample size of just 51 people.

After the analysis, a couple results jumped out at them. Two of the genes, COMT and NTRK2, had significant correlations with pain, anxiety, fatigue, and sleep disturbance. The other gene didn’t.

“I always like having a yes/no answer — if we get some nos, then we know the analysis wasn’t just confirming what we wanted to see,” says Young.

Such a quick look at a small sample of cancer patients can’t give all the answers as to who is going to develop postoperative and post-chemotherapy pain. But what they did find is very suggestive. Some of the gene variants were associated with symptoms before surgery. For example, women with two copies of the A variant of COMT reported more anxiety than other women did. COMT was also linked with pain, both during and after cancer treatment: women with one variant of COMT reported more pain, while women with a different variant reported less.

Fatigue also seems to have a genetic component. Women with one copy of the T variant of NTRK2 reported more posttreatment fatigue than others, and women with two copies reported much more.

Surprisingly, the genes linked to various symptoms worked independently, and didn’t work together to increase overall pain and discomfort. In other words, they weren’t synergistic; they didn’t make each other worse.

The gene variants predicted pain and fatigue above and beyond any differences explained by treatment effects.

The genes’ effects were also independent of the type of treatment the women received; the 51 women followed a number of different types of treatments: different surgeries, different chemotherapies. The gene variants predicted pain and fatigue above and beyond any differences explained by treatment effects. Other experiments by other researchers have shown the COMT variants are connected to the development of skeletal muscle pain.

“So it’s not just our study but the entire literature that suggests COMT could be playing a role in how sensitive you are to many different types of pain,” says Young.

“We are focusing on how we can identify women who are at risk of experiencing persistent pain and fatigue, as these symptoms have the highest impact on reducing quality of life after treatment,” says Starkweather. “It’s a great example of how we can make progress toward the goal of personalized health care. The next piece of the puzzle is to identify the most effective symptom-management interventions based on the patient’s preferences and genetic information.”

Young, Starkweather, and their colleagues say further research, ideally looking at a person’s whole genome, is needed to refine the connections between genetic profiles and the risk of pain. With that knowledge, patients could work together with their care team to develop individualized symptom-management plans. Properly prepared patients would feel more control and less suffering. And perhaps the cure would no longer hurt worse than the disease.

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.”

Honor Roll – Summer 2017

Radenka Maric, Ph.D., was named UConn’s vice president for research effective July 1, 2017. Maric was previously the CT Clean Energy Fund Professor of Sustainable Energy in the UConn School of Engineering.


Dr. Anthony G. Alessi received the 2017 President’s Award at the American Academy of Neurology’s 69th annual meeting, held this April in Boston.


UConn Health’s Board of Directors named Howard Tennen, Ph.D., the 2017 winner of its Faculty Recognition Award.


UConn Health had 34 physicians named to Connecticut Magazine’s 2017 “Top Docs” list.


Dr. Jane Grant-Kels was elected vice president-elect of the American Academy of Dermatology.


Dr. R. Lamont “Monty” MacNeil, dean of the UConn School of Dental Medicine, was appointed to a one-year term as chair-elect of the American Dental Education Association’s board of directors in March.


Dr. Augustus D. Mazzocca will receive the Arthritis Foundation’s Champion of Yes Prestigious Excellence in Medicine Award for 2017.


Kyle M. Baumbauer, Ph.D., has received the 2017 Award in Pain from the Rita Allen Foundation and the American Pain Society for his research on pain after spinal cord injury.


Dr. Linda K. Barry was named one of Savoy magazine’s Top Black Doctors for 2017.


UConn medical student Laura Hatchman and her faculty mentor Lisa Barry, Ph.D., received the Biomarkers and Frailty Best Paper Award at the American Geriatrics Society annual meeting held in May.


UConn John Dempsey Hospital was recognized with a Gold Plus rating, the highest for heart failure patient care by the American Heart Association. In addition, the hospital was added to the AHA’s Heart Failure Honor Roll for 2017.

New Neurosurgery Chief Brings Elite Expertise to UConn Health

Dr.Ketan R. Bulsara speaks with patient inside patient room in UConn Health, Farmington CT USA


Dr. Ketan R. Bulsara, a world-renowned neurosurgeon, brings an unparalleled range of expertise in treating neurological disorders to UConn Health as the new chief of the Division of Neurosurgery.

Bulsara came to UConn Health from Yale, where he built successful programs in neurovascular and skull base surgery. He has trained with the pioneers in neurosurgery and is an author on many national and international guidelines
and standards.

Bulsara is among an elite few neurosurgeons in the world with dedicated dual fellowship training in skull base/cerebrovascular microsurgery and endovascular surgery. He is directing both of those disciplines in UConn Health’s Department of Surgery in addition to serving as chief of neurosurgery.

“Dr. Bulsara is a world-class neurosurgeon who brings a level of expertise that is almost unheard of in the field,” says Dr. David McFadden, chair of the UConn Health Department of Surgery. “Whether it’s complex tumors, aneurysms, or any sort of brain- or nerve-related problem, he is well-equipped to offer a full range of treatment options.”

That includes the full spectrum of treatment of both hemorrhagic stroke and ischemic stroke. Bulsara was an early adopter of mechanical thrombectomy, a procedure in which the surgeon removes a clot from a blocked blood vessel going to the brain. Bulsara’s collaboration with UConn Health’s stroke program puts UConn Health in a position to handle these more complex cranial cases.

Bulsara also will be involved in UConn Health’s efforts to expand its epilepsy program to include neurosurgical treatments, and will be recruiting additional neurosurgeons with other areas of expertise.

“It’s always been my dream to establish a world-class destination center for neurosurgical care,” Bulsara says. “Neurosurgery, the way I look at it, is a multidisciplinary specialty. The focus of my division is to optimize patient outcome. We’ll build a team that’s tailored and personalized for every single patient. Ultimately, as a team, we provide the best care for the patients.”

Working Together for Better Public Health

Q&A with Dr. Raul Pino, commissioner of the Connecticut Department of Public Health and a UConn Health board member

Q

What are some of the major public health issues facing Connecticut?

There are many public health issues facing both Connecticut and the nation as a whole. At the Department of Public Health, our emphasis is on the Centers for Disease Control and Prevention’s 6|18 initiative, which targets six major health conditions — asthma, high blood pressure, tobacco use, hospital-acquired infections, teen pregnancy, and diabetes — with 18 evidence-based public health interventions.

Each of these conditions is common, preventable, and costly, but importantly, all have proven interventions that can be effectively employed across the health care spectrum to improve both individual and community health, saving lives and dollars. Other areas where I believe we can see good results in Connecticut by employing evidence-based interventions include addressing HIV and the rising number of syphilis cases.


Q

How can physicians assist the DPH daily to address and reduce these issues?

Doctors, particularly primary care physicians, are the main point of contact with the public for health education. We need to engage practitioners in addressing the six major health conditions with their patients — screening for the conditions; educating in advance to enhance prevention of disease; and providing effective, evidence-based treatments when needed. Physicians play a critical role on the front lines of health care to shift our focus from treatment to prevention through lifestyle changes and other healthy choices. They are an indispensable part of the continuum of care between DPH, health care practitioners, and public health.


Q

As DPH commissioner, what drives your daily public health passion and mission?

I am convinced that we — as a nation, a state, and as public health professionals — can do more than we are currently doing to impact public and population health. Addressing the health disparities that continue to plague our population, costing millions of lives and countless health care dollars, is what drives me. We are so fortunate to live in one of the richest countries, and states, in the world, yet we spend so little on public health. My mission is to spread the message that modest investments of money, time, and effort in proven education and prevention methods can lessen these disparities, which will save millions of dollars in health care costs and, more importantly, save lives.


Q

Tell us about your connection to UConn Health and what you hope to accomplish as a member of the board of directors.

I am a 2009 graduate of the UConn Master of Public Health program and receive my own health care at UConn Health. Spending time there for my education and health care has really crystallized for me that UConn Health is the epicenter of clinical care and education in Connecticut. UConn Health is where advances in science and medicine happen, which allows patients to get the best in cutting-edge care. As a member of the board of directors, I am looking to learn and understand better the role that this large institution plays in public health work. I hope my passion for public health and the elimination of health disparities will allow me to give a voice to the importance of integrating education, prevention, public health, and clinical care in order to strengthen our health care system, curb rising health care costs, and foster healthy communities and individuals.