Researchers Detect “Silent” Seizures in Alzheimer’s Patients

First let’s define a key word:
Hippocampus: The brain structure responsible for memory development. The hippocampus is a key part of the brain affected by Alzheimer’s disease, and also a common source of seizures in people with epilepsy.

New research from Massachusetts General Hospital suggests a potential new connection between the devastating memory loss associated with Alzheimer’s disease (AD) and “silent” seizures in the memory center of the brain.

The small study enrolled two female patients in their 60s with early AD and no known history of seizures. Because electrodes placed on the scalp are often unable to detect seizure activity deep in the brain, researchers surgically implanted electrodes on both sides of the brain through the foramen ovale (FO), a narrow opening at the base of the skull, in addition to scalp EEG. Each patient’s brain activity was monitored for 24 to 72 hours.

The FO electrodes recorded evidence of seizures in the hippocampuses of both patients, while the scalp EEG readings did not detect any abnormal electrical activity. Most notably, these seizures primarily occurred when patients were asleep, a critical time for memory consolidation.

“While it is not surprising to find dysfunction in brain networks in Alzheimer’s disease, our novel finding that networks involved in memory function can become silently epileptic could lead to opportunities to target that dysfunction with new or existing drugs to reduce symptoms or potentially alter the course of the disease,” says Andrew Cole, MD, Director of the Mass General Epilepsy Service and senior author of the Nature Medicine paper.

One patient received anti-seizure medicine as a treatment following the scan, which seemed to cut down on AD-linked symptoms such as confusion and repeating the same question. The other patient started on the medication but it had to be discontinued due to adverse effects on her mood.

A recent study led by Alice Lam, MD, PhD, also of the MGH Epilepsy Service and lead author of the current study, demonstrated a novel tool for detecting hippocampal seizures not detectible by scalp EEGs in patients with epilepsy. Cole and his team are working to refine this tool and apply it to AD.

Due to the small size of the study, further research is also needed to validate the results with a broader population.

Celebrating the Important Role of Nurse Researchers at Mass General

Gaurdia-Sara-Jeanette
From left: Gaurdia Banister, director of the Munn Center for Nursing Research, Sara Looby, a nurse scientist at the Munn Center and the keynote speaker at Nursing Research Day, and Jeanette Ives Erickson, Chief Nurse and Senior Vice President for Nursing and Patient Care Services

Attendees of the 2017 Nursing Research Day celebration at Massachusetts General Hospital on May 9 certainly had a lot to be inspired by.

The event began with a poster session featuring 45 posters submitted by nurse researchers at Mass General, and concluded with a series of engaging presentations highlighting the important role that nursing research plays in improving patient care.

“As providers, we have patient experiences that influence our careers and are truly impactful,” said keynote speaker Sara Looby, PhD, ANP-BC, FAAN.

Looby, a Nurse Scientist at the Yvonne L. Munn Center for Nursing Research at Mass General, described several such formative experiences in her own nursing career, including an interaction with a young mother who was suffering from a terminal illness. Witnessing that mother’s experience firsthand gave Looby a better understanding of the human response to illness—and the despair, grief and suffering that comes with it.

Looby said her career as a nurse researcher has been guided by the desire to find ways to help patients cope with these feelings, by providing information, support and connections to clinical trials. Many of her research projects started by understanding the needs and concerns of her patients, she explained.

“Our patients are talking. We are asking them on a daily basis how they are feeling, and they are sharing their concerns, thoughts and opinions. In doing so, they are identifying gaps in knowledge that can be solved by asking research questions.”

Looby acknowledged that nurses already have a full plate of responsibilities taking care of patients, but she encouraged them to go the extra mile to pursue research questions as well. “What more can be done? What questions are not answered?”

“Each of you makes a difference every day, small or large, independently or as a team to help patients. So don’t be afraid to share your ideas with others, and don’t be intimidated by the research process.”

Gaurdia E. Banister, RN, PhD, NEA-BC, FAAN, Director of the Munn Institute and Executive Director of the Institute for Patient Care at Mass General, spoke about the center’s 25-year effort to establish a structure for nursing research at the hospital and credited Jeanette Ives Erickson, RN, DNP, NEA-BC, FAAN, the hospital’s Chief Nurse and Senior Vice President for Patient Care, for her unwavering support.

Banister noted that the nursing research posters on display during the event represented a broad cross section of interests, including non-pharmacological approaches to pain management, population-based care and strategies to manage care transitions from the hospital to the community.

She also encouraged nurses to continue their advocacy for science and medicine at a challenging time for both disciplines.

“Staying silent is no longer a luxury we can afford. We all must stand together and support science. At its core, science is a tool for seeking answers, and we must aggressively advocate for the right to do so.”

Research Awards and Honors: May 2017

Massachusetts General Hospital’s talented and dedicated researchers are working to push the boundaries of science and medicine every day. In this series we highlight a few individuals who have recently received awards or honors for their achievements:

weinMarc Wein, MD, PhD,of the Endocrine Unit, has received a Young Physician-Scientist Award from the American Society for Clinical Investigation. These recognize young physician-scientists who are supported by the National Institutes of Health or similar significant career-development awards, are early in their first faculty appointment and have made notable achievements in their research.

“As an endocrinologist, the problem of osteoporosis is extremely important to me. My laboratory studies how bone cells respond to external signals like hormones and mechanical cues. Ultimately, this knowledge will lead to new and improved drugs for our patients with osteoporosis. It was truly an honor to receive this award. Attending the ASCI meeting as a recipient of the Young Physician-Scientist Award was both exciting and inspiring. Four different Nobel laureates gave lectures about their career paths, and provided excellent advice about picking the right research questions that will ultimately help our patients.”

 

hawryluckElena B. Hawryluk, MD, PhD, of the Department of Dermatology, has received Weston Award from the Society for Pediatric Dermatology for her work “Melanoma and Dysplastic Nevi in Children”. This award is given to one pediatric dermatologist every two years and supports career development of future leaders, educators, clinical scholars and/or translational investigators in pediatric dermatology. Awardees must demonstrate a strong commitment to skin research that can advance the field of pediatric dermatology.

“My research investigates moles in children as well as pediatric melanoma, which is quite rare.  Patients with dysplastic (abnormal) moles have an increased risk of melanoma, however, studies of children and adolescents with these moles have not been performed.  I am collaborating with pediatric dermatologists across the country to identify features that might help us better understand which melanomas are most aggressive.  With an increased public awareness of sun protection and melanoma, it is important for pediatric dermatologists to be able to identify skin lesions of concern, and discuss risks that are relevant to children and adolescents.

This is an incredible honor coming from the Society for Pediatric Dermatology: just one pediatric dermatologist every two years is selected for the award.  It means so much to have the support of both the research I’m so passionate about and the investment in my development as a researcher.”

 

tingDavid T. Ting, MD, of the MGH Cancer Center, has received a Phillip A. Sharp Award through Stand Up To Cancer (SU2C), to advance “innovation in collaboration” among SU2C-affiliated scientists. The award program was established in 2014 by SU2C to honor Sharp’s keen interest in team research, and are intended to reward distinctive collaborations that propose to accelerate current research and development models, bringing therapeutic benefits for cancer patients. Ting’s research will focus on “Dissecting the Epigenetic Mechanisms of Repeat RNA Regulation in Cancer.”

“Our research focuses on identify novel methods to engage the immune system against cancer cells. We are working on a set of molecules called satellite RNAs, which we have found to be specifically expressed in cancers compared to normal tissues. These satellites are generated from areas of our genome thought to be silent and were considered “junk” DNA, but cancers have found a way to reactivate these regions through a mechanism called epigenetic regulation. Interestingly, these satellite RNAs appear to have behavior that is shared with viruses, and their presence in cancer cells are thought to alter the immune response to cancer. I am truly honored to receive this collaborative award with Dr. Shelley Berger who is an international leader in epigenetics. Together, we hope to understand how cancers turn on this primordial viral program and identify novel therapies that can enhance our ability to drive the immune system to attack cancer.”

 

demehriShawn Demehri, MD, PhD, has been awarded a grant from the Sidney Kimmel Foundation as part of its Kimmel Scholars Program for “Mechanism of CD4+ T-cell immunity against skin cancer precursors.” Begun in 1997, the program was designed to jumpstart the careers of the most promising and creative researchers and physician-scientists seeking solutions to the riddle of cancer. To qualify, grantees must demonstrate great promise and innovation in their work, and be in the early stages of their research careers.

“Skin cancer is the most common type of cancer and we often see patients in our clinics who are affected by multiple skin cancers. To prevent these cancers, our laboratory has recently developed a topical immune activating treatment, which showed high efficacy in activating T cells leading to the clearance of skin cancer precursors in a randomized clinical trial. We now aim to explore the exact mechanism underlying the potent anti-tumor immune response we observed with our immunotherapy. The Kimmel Scholar Award will enable us to expand this research effort and establish a fundamental role for immunoprevention in cancers of skin and other organs.”

Diet Known to Reduce Risk for Hypertension May Also Prevent Gout

Balanced diet

A recent study from Massachusetts General Hospital suggests that following the Dietary Approaches to Stop Hypertension (DASH) diet may reduce the risk of gout.

What is gout?

When excess uric acid in the bloodstream builds up too quickly or can’t be eliminated fast enough, it is deposited as needle-shaped crystals in the tissues of the body, including joints, causing intense pain. This pain, otherwise known as gout, is the most common type of inflammatory arthritis.

What are the current dietary recommendations for gout?

Doctors recommend a diet low in purines (chemical compounds that can be broken down into uric acid), which are found in certain meats and seafood. “But following such a diet has limited effectiveness and proves challenging for many patients,” says Hyon Choi, MD, DrPH, director of the Gout and Crystal Arthropathy Center in the MGH Division of Rheumatology, Allergy, and Immunology, senior author of the study.

What is the DASH diet?

The DASH diet (originally created to help patients with high blood pressure) emphasizes eating fruits, vegetables, low-fat dairy items, whole grains, poultry, fish and nuts while discouraging eating foods high in saturated fats, cholesterol, trans fats and sodium, as well as red meats and sweets. Several studies have confirmed its ability to reduce risks for hypertension and cardiovascular disease.

What did the study investigate?

The study enrolled over 44,000 men with no history of gout. The research team applied two scoring systems to the dietary patterns of participants:

  1. A DASH dietary pattern score (based on the criteria for the DASH diet)
  2. A Western dietary pattern score (based on high intake of red and processed meats, French fries, refined grains, sweets and desserts)

What did they find?

During the 26 years of follow up, 1,731 participants were newly diagnosed with gout. Researchers found that a higher DASH dietary pattern score was associated with a lower risk for gout, while a higher western dietary pattern score was associated with an increased risk for gout. “For individuals at high risk for gout, especially those who also have hypertension, the DASH diet is likely to be an ideal preventive approach,” says Sharan Rai, MSc, of the MGH Division of Rheumatology, Allergy and Immunology, and lead author of the paper.

What are the implications of the study?

While these findings need to be confirmed in future interventional trials, the researchers note that many individuals at risk for gout because of elevated uric acid levels might already be candidates for the DASH diets, since more than half of such individuals also have hypertension. The only group that probably should be careful with the DASH diet would be patients with severe kidney disease, since the diet can be high in potassium.

Distilling Your Message: A Workshop with Alan Alda

Earlier this month, the Mass General Research Institute organized a day-long workshop hosted by the Alan Alda Center for Communicating Science. Participating Mass General researchers learned how to succinctly and vividly speak about their work in terms lay persons can understand. Improvisation exercises also helped participants hone their ability to naturally connect with different audiences.

This workshop is one of several programs and initiatives we have launched since 2016 to help our researchers better communicate their science to the general public. In the fall of 2016, we presented “The Art of Talking Science,” a fun American Idol-style science event where eight researchers had the chance to deliver a four-minute summary of their research and receive feedback from a panel of “celebrity” judges, including nationally known science writer Carl Zimmer. This event was part of the programming for HUBweek, a citywide festival celebrating innovation.

You can learn more about our other science communication programs here.

30544914326_0608b39b21_z

Researchers Recommend New Eye Exam Screening for Patients with Type 1 Diabetes: Five Things to Know

12538332 - looking through the glasses at eye chartTreatment guidelines for patients with type 1 diabetes have long called for yearly eye exams. But is there an alternative to this one-size-fits-all approach that could reduce patient burden and costs while providing a quicker diagnosis? Findings from a recent study, published in the New England Journal of Medicine, lend insight into a possible new eye screening protocol. Here are five things to know:

  1. Diabetic retinopathy is the leading cause of blindness among adults. It occurs when chronically high blood sugar from diabetes damages the light-sensitive tissue in the back of the eye. Fortunately, screening can catch this disease before irreparable damage is done, and there are several therapies available to treat the condition. Guidelines currently recommend routine yearly eye exams within three to five years of a type 1 diabetes diagnosis, but these recommendations were based on now-outdated research.
  1. To reevaluate the current recommendations, David Nathan, MD, Director of the Diabetes Center and Clinical Research Center at Massachusetts General Hospital, and a team of researchers analyzed approximately 24,000 retinal exams obtained over 30 years from about 1,400 participants with type 1 diabetes.
  1. Based on their analysis, researchers developed new recommendations that suggest patients with type 1 diabetes should get eye exams to detect diabetic retinopathy based on the presence and severity of diabetic retinopathy, rather than on the automatic, annual schedule that is currently recommended. For patients with type 1 diabetes and a current average blood glucose level of 6 percent (within the American Diabetes Association’s recommended target range), researchers recommend the following eye exam schedule:
  • With no retinopathy, every four years.
  • With mild retinopathy, every three years.
  • With moderate retinopathy, every six months.
  • With severe retinopathy, every three months.
    Researchers suggest patients with higher current average blood glucose levels (for example, 8-10 percent as opposed to 6 percent) have eye exams more often, as they are at higher risk to develop the disease. The new recommendations also call for taking photographs of the back of the eye rather than physical examination with an ophthalmoscope, which is thought to be less accurate.
  1. Overall, researchers say the new, individualized schedule would result in earlier detection of the advanced retinopathy that requires treatment to save vision compared with annual exams, while at the same time reducing the frequency of eye exams by half. That would translate into an overall savings of $1 billion.
  1. Researchers are still questioning whether physicians would adhere to these new recommendations, if implemented. “The risk is that physicians may find it easier to schedule an annual eye examination compared with the new individualized schedule, which may be more difficult for physicians and patients to remember,” says Nathan. The next step is to discuss how to potentially incorporate the guidelines into patient care. They also plan to conduct further studies to investigate if this screening strategy could be applied to patients with type 2 diabetes.

Women’s Health Week 2017

In honor of National Women’s Health Week this week, we put together a few highlights of the many Massachusetts General Hospital researchers who are investigating important topics pertaining to women’s health:

Eve Valera, PhD, a researcher at the Martinos Center for Biomedical Imaging, is working to learn more about the traumatic brain injuries suffered by women in abusive relationships:
http://www.massgeneral.org/research/news/ResearcherProfiles/profile-valera-TBIs.aspx

A team from the Pediatric Surgical Research Laboratories in the Department of Surgery discovered a hormone that may protect and preserve ovaries during chemotherapy:
https://mghresearchinstitute.com/2017/02/22/hormone-may-protect-and-preserve-ovaries-during-chemotherapy/

Researchers at the Cancer Center found that a specialized screening protocol may improve detection of ovarian cancer in high-risk women:
https://mghresearchinstitute.com/2017/03/06/specialized-screening-protocol-may-improve-detection-of-ovarian-cancer-in-high-risk-women/

A collaborative study between researchers at Mass General and Boston University School of Medicine found evidence implying that alcoholism may have different effects on the reward system in the brains of women than it does in men:
http://www.massgeneral.org/about/pressrelease.aspx?id=2092

Probe of Alzheimer’s Follows Paths of Infection

050117_Tanzi_060.jpg
Rudy Tanzi (left) and Robert Moir. (photo credit: Jon Chase/Harvard Staff Photographer)

Could the development of amyloid beta plaques in the brain — a hallmark of Alzheimer’s disease — be a response to infection? Mass General researchers Rudy Tanzi and Robert Moir are investigating amyloid beta’s role in the body. Their findings could possibly open new fronts for treating or preventing Alzheimer’s disease by attacking infection before plaques begin to form.

You can read more about their research here.

Research Staff Appreciation Day Celebrates Contributions to MGH Research

Research appreciation day

Every year, Massachusetts General Hospital celebrates Research Staff Appreciation Day to recognize and thank the research staff members who provide direct scientific support to faculty investigators across the Mass General research enterprise. Research staff members—a community of more than 3,700 people—include technicians, technologists and study coordinators.

Despite the dreary weather, hundreds of attendees came out on April 25th and 27th on the main campus and in Charlestown Navy Yard for the annual lunch and ice cream celebration. Prizes of mugs and movie tickets were raffled off courtesy of the Mass General Research Institute.

Harry Orf, PhD, Senior Vice President for Research, recognized the attendees for their many contributions. “Research staff comprise fully one third of our entire research community and, through their diligence and dedication, are the mainstay of our research enterprise,” said Orf.

Sue Slaugenhaupt, PhD, Scientific Director of the Mass General Research Institute, emphasized the crucial role research staff play. “The Mass General Research enterprise is so successful because of the thousands of people who support our work every day. We’re happy to honor them on Research Staff Appreciation Day.”

Maurizio Fava, MD, Director of the Division of Clinical Research, said the annual event is a way for the hospital to express its appreciation for this valuable part of the hospital’s scientific community. “Mass General is an institution that really values research, and values everyone who is involved in research.”

Mass General is home to the largest hospital-based research enterprise in the United States. Learn more about our research efforts.

A New Strategy for Assessing Sleep Apnea Risk in Individuals with Down Syndrome

Investigators at the MassGeneral Hospital for Children have developed a promising new method for assessing the risk of obstructive sleep apnea (OSA) in children with Down syndrome.

The new method, which employs information that can be gathered during a visit to a primary care physician, could help to reduce the need for overnight sleep studies, which can be expensive and difficult for children and their families.

OSA occurs when the airway becomes restricted or blocked during sleep, causing breathing to become shallow or temporarily stop. In addition to interrupting sleep, OSA lowers oxygen levels in the blood and can impair cardiac, metabolic and cognitive functioning.

It is estimated that close to half of individuals with Down syndrome have OSA due to alterations in their craniofacial features that result from the syndrome. The American Academy of Pediatrics recommends that all children with Down syndrome undergo an overnight sleep study to screen for OSA starting at age 4.

The sleep studies are effective in measuring OSA risk, but they can be expensive and difficult to access in certain areas of the U.S. The studies can also be a challenging experience for individuals with Down syndrome, particularly young children.

The new method, which was developed by a research team led by Brian Skotko, MD, MPP, co-director of the MGH Down Syndrome Program, uses a variety of factors – including the physical characteristics and vital signs of the participants plus information provided by parents on a questionnaire – to predict the risk of OSA.

In a study of 102 children with Down syndrome, the team’s new method was able to accurately predict the risk of moderate to severe OSA in 90 percent of those who were diagnosed with the condition following an overnight sleep study.

The team is now working to confirm those results in a follow-up study.