neurology

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.”

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.”

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.

The Power of MRI

A UConn Health physician is seen reviewing an MRI brain scan.

A UConn Health physician is seen reviewing an MRI brain scan. At UConn Health, doctors are pioneering ways to use MRI technology to diagnose and monitor a range of conditions affecting many parts of the body Photo: Peter Morenus


Magnetic resonance imaging (MRI) has come a long way since the technique was first used in the U.S. in the late 1970s. UConn Health is now taking this powerful, non-invasive imaging tool to the next level.

UConn Health physicians in a variety of specialties are using the technology — which captures images of the inside of the body using a large magnet rather than radiation — in new ways to detect and monitor illnesses.

Prostate Cancer

Dr. Peter Albertsen, chief of UConn Health’s Division of Urology, currently follows 100 patients with localized prostate cancer, which is slow-growing, using advanced multiple-parametric MRI imaging. The technology has now replaced ultrasound as the imaging method of choice for prostate cancer. The technique yields multiple imaging sequences of the prostate, providing information about the anatomy, cellular density measurement, and vascular supply.

There is growing evidence to support the idea that the best treatment plan for low-grade prostate cancer is “watchful waiting” to monitor its progression, instead of immediate surgery or radiation. Albertsen’s practice of active surveillance, and not intervention, for localized prostate cancer was reinforced by a recent long-term study published in September in the New England Journal of Medicine, on which Albertsen served as a consultant.

The technology is extraordinarily helpful, allowing us to avoid invasive biopsy testing and associated risks of bleeding and infection.

Liver Disease

UConn Health is the first in Greater Hartford to use MRI to measure the stiffness of patients’ livers to reveal disease without the need for biopsy. Its MR elastography technique involves placing a paddle on a patient’s skin over the liver during MRI to create vibrations and measure the velocity of the radio waves penetrating the organ. This can indicate a stiffer liver and help diagnose fibrosis, cirrhosis, a fatty liver, or inflammation associated with hepatitis. The initiative is led by Dr. Marco Molina, radiologist in the Department of Diagnostic Imaging and Therapeutics.

“The technology is extraordinarily helpful, allowing us to avoid invasive biopsy testing and associated risks of bleeding and infection,” Molina says. “Plus, with the obesity epidemic, patients developing nonalcoholic steatohepatitis (NASH), or fatty liver, can receive earlier diagnosis and take action to reverse their disease’s progression with diet and exercise.”

Breast Cancer

The new Women’s Center at UConn Health has opened its state-of-the-art Beekley Imaging Center, featuring advanced breast cancer screening. Dr. Alex Merkulov, associate professor of radiology and section head of women’s imaging, and his team are conducting research to test the effectiveness of using an abbreviated, five-minute MRI scan to confirm or rule out a breast cancer diagnosis. Typically, an MRI test takes 20 minutes, but researchers are seeing that a briefer MRI scan of just a few minutes can help provide a definitive answer to whether an abnormal breast growth is cancer or not — and potentially help women avoid the biopsy process.

Arthritis

The UConn Musculoskeletal Institute is now researching the use of MRI to assess and map the strength, weakness, and underlying makeup of a patient’s cartilage, especially for those with arthritis. The tool can allow orthopedic experts to identify any thinning or loss of cartilage in the body, which signifies moderate to late-stage disease. In early stages of arthritis, MRI can help pinpoint early morphological and subtle biochemical changes in cartilage.

Neurological Disorders

In neuroradiology, UConn Health is using the power of MRI to differentiate brain tumors, to detect strokes, to assess dementia, to diagnose multiple sclerosis, to evaluate traumatic brain injury, to find the source of epilepsy, and to guide brain surgery. In March 2017, leading neuroradiologist Dr. Leo Wolansky joins UConn Health to advance its research and chair the Department of Diagnostic Imaging and Therapeutics. Wolansky’s neuroimaging research has focused on enhancing understanding of MRI and its contrast agents, especially for multiple sclerosis and brain tumors. He also specializes in the hybrid imaging modality PET-MRI.

“Thanks to the power and advancement of MRI, doctors can see early evidence of disease and seize the opportunity to intervene and improve their patients’ health,” Molina 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.”

The Doctors Are In – Spring 2016

UConn Health welcomes the following new physicians:


Seth Brown, MD

Specialties: Ear, Nose, and Throat/Otolaryngology, Otolaryngology Surgery
Location: Farmington


Saira Cherian, DO

Specialties: Internal Medicine, Primary Care
Locations: Farmington


Alexis Cordiano, MD

Specialty: Emergency Medicine
Location: Farmington


Montgomery Douglas, MD

UConn School of Medicine Chair
of Family Medicine

Specialty: Family Medicine
Location: Farmington


Jeffrey Indes, MD

Chief of the Division of Vascular and Endovascular Surgery

Specialty: Vascular Surgery
Location: Farmington


Leah Kaye, MD

Specialty: Obstetrics and Gynecology
Location: Farmington


Glenn Konopaske, MD

Specialty: Psychiatry
Location: Farmington


Guoyang Luo, MD

Specialties: Obstetrics and Gynecology, Maternal-Fetal Medicine
Location: Farmington


Jose Montes-Rivera, MD

Specialties: Neurology, Epilepsy
Location: Farmington


Rafael Pacheco, MD

Specialty: Radiology
Location: Farmington


Mario Perez, MD, MPH

Specialties: Critical Care, Internal Medicine, Pulmonary Medicine
Location: Farmington


Edward Perry, MD

Specialty: Hematology/Oncology
Location: Farmington


Surita Rao, MD

Specialties: Addiction Psychiatry, Psychiatry
Location: Farmington


Belachew Tessema, MD

Specialties: Ear, Nose, and Throat/Otolaryngology, Otolaryngology Surgery
Location: Farmington


Cristina Sánchez-Torres, MD

Specialties: Child and Adolescent Psychiatry, Psychiatry
Locations: Farmington, West Hartford


Brian Schweinsburg, Ph.D.

Specialties: Child and Adolescent Psychiatry, Psychology
Locations: Farmington, West Hartford


Mona Shahriari, MD

Specialties: Dermatology, Pediatric Dermatology
Locations: Canton, Farmington


Kipp Van Meter, DO

Specialties: Family Medicine, Internal Medicine, Primary Care
Location: Canton

The Doctors Are In – Winter 2015

UConn Health welcomes the following new physicians:


Ridhi Bansal, MD

Specialties: Internal Medicine, Primary Care
Location: Canton


Philip M. Blumenshine, MD, MAS., M.Sc.

Psychiatry Emergency Department Medical Director

Specialty: Psychiatry
Locations: Farmington


Ethan I. Bortniker, MD

Specialty: Colon Cancer Prevention, Gastroenterology
Location: Farmington


Tilahun Gemtessa, MD, M.Sc.

Specialty: Infectious Diseases
Location: Farmington


Matthew Imperioli, MD

Specialty: Neurology
Location: Farmington


Neha Jain, MD

Specialty: Psychiatry, Geriatric Psychiatry
Location: Farmington


David Karimeddini, MD

Specialty: Radiology
Location: Farmington


Hsung Lin, DMD

Specialty: Family Dentistry
Location: Storrs Center


Janice Oliveri, MD

Specialty: Internal Medicine
Location: Farmington


Houman Rezaizadeh, MD

Specialty: Gastroenterology
Location: Farmington


Bernardo Rodrigues, MD

Speciaty: Neurology
Location: Farmington


Lenora S. Williams, MD

Specialty: Obstetrics and Gynecology, Women’s Health
Location: Storrs Center


Visit UConn Health’s online physician directory for information about all our specialists.