The Importance of Pathogen Surveillance Networks

High school students working in the lab of Florian Krammer, PhD, as part of the New York City Virus Hunters program. Image credit: Christine Marizzi, PhD, BioBus.

The H5N1 bird flu virus was detected for the first time in cows in March, and in May, a third person tested positive for bird flu, presumably from exposure to infected dairy cattle. With viral fragments detected in dairy, the Food and Drug Administration tested and announced that pasteurized milk was safe to drink, and the Centers for Disease Control and Prevention (CDC) has been working with city and state health authorities and institutions nationwide to monitor any new spread of the pathogen.

What goes into ensuring that we remain safe from pathogenic outbreaks? Are we adequately equipped to monitor, prevent, and treat another pandemic?

The co-directors of the Center for Vaccine Research and Pandemic Preparedness at the Icahn School of Medicine at Mount Sinai—Florian Krammer, PhD, Mount Sinai Professor in Vaccinology, and Viviana Simon, MD, PhD, Professor of Microbiology; Pathology, Molecular and Cell-Based Medicine; and Medicine (Infectious Diseases)—tell us how the research community worked to shed light on bird flu in cows, pathogenic surveillance, and what Mount Sinai is doing in this field.

Left: Florian Krammer, PhD. Right: Viviana Simon, MD, PhD.

Were the bovine cases of bird flu expected and detected quickly?

Dr. Krammer: It took a while before H5N1 avian influenza was detected in cows for several reasons. Typically, cows do not get infected with influenza A virus. So nobody’s looking at cows, because why would you look if it has historically not been there? Compared to the poultry industry, where there is a good system in place for rapid detection of any outbreaks. Also, in cows, the H5N1 avian influenza is a slow disease. In avian species, when they get infected, they tend to die quickly. Other mammals, like bears, raccoons, or foxes that get infected with H5N1 via ingestion of infected birds, they often get neurological symptoms and die quickly too. It is different with the cows.

Are there adequate systems to prevent and protect against unexpected pathogenic outbreaks?

Dr. Krammer: From a scientific perspective, we have very good capabilities for detecting pathogens quickly. But preventing outbreaks is a complex task that takes more than just good science. Take the cases of avian influenza in dairy cattle, for example: When the outbreak occurred, there were no legal grounds for initial testing, or even for restricting movement of cows across state borders—there was not much the government could do. Academic networks like the Centers of Excellence for Influenza Research and Response, funded by the National Institute of Allergy and Infectious Diseases, produced the first reports of the recent cases, and are much more flexible and can respond quicker. These networks work very closely with government agencies to provide needed recommendations to handle unexpected outbreaks. One of these centers is located at Mount Sinai and we have also been very active with H5N1 surveillance and research.

Dr. Simon: Besides global and national surveillance networks, local efforts are important, too, especially for a large metropolitan city such as New York City. We have known for a long time that because New York is a very popular place for tourists to visit, that makes it a very likely entry point for any virus or pathogen. The city and state have various surveillance programs, and Mount Sinai also has a pathogen surveillance program that is more than 10 years old. This program is co-directed by Harm van Bakel, PhD; Emilia Sordillo, MD, PhD; and myself. We have been tracking nosocomial infections—picked up while in a hospital—and gaining information about circulating pathogens, including influenza virus strains, bacteria, and fungi. Our Pathogen Surveillance Program has resulted in Mount Sinai being the only site in the United States that is part of the Global Hospital Influenza Surveillance Network, which works to provide a unified protocol on covering hospitalized cases of severe influenza at a global level.

Are there any particular pathogens these networks are keeping an eye out for?

Dr. Simon: Some pathogens that the Mount Sinai Pathogen Surveillance Program is watching include bacteria like Staphylococcus aureus, Enterococci and Clostridioides difficile; viruses like influenza, RSV, SARS-CoV-2, and hantavirus; as well as fungi such as Candida auris.

What are some research questions these surveillance networks are trying to answer?

Dr. Simon: Some major questions include how influenza strains change in humans—their escape from the human immune system or their change of glycosylation (the process where sugar molecules attach to lipids, proteins, or other organic molecules); how to improve vaccines; and ensuring our diagnostics are able to pick up all the strains that can cause disease in humans.

Dr. Krammer: The tracking of the changes is not a problem. The World Health Organization does that on a regular basis, and we can do that too at Mount Sinai. A bigger challenge might be: can we catch up with seasonal viruses with our vaccines, or are we always a step behind? One way to tackle that is trying to design a vaccine that gives us broad protection, no matter if the viruses change, or if the strain is an H5N1 or an H1N1. Mount Sinai is very active in working on a vaccine that would work against any type of influenza—a universal influenza virus vaccine. As for diagnostics, there are so many subtypes of influenza viruses, but you never know which one presents a risk. We’re trying to find out what are the pathogenicity markers that make a strain dangerous for humans and make it transmit well. Or, what determines the risk of avian influenza jumping to humans? That’s why we have a program that looks at not only human influenza, but also avian influenza in animals in an urban space in New York City.

What does it take for such surveillance networks to succeed?

Dr. Krammer: You have to consider the fact that influenza viruses were not human viruses originally—they were bird viruses—and to tackle the vast topic of “One Health,” an approach that seeks to address the health of people, animals, plants, and the environment interconnectedly, you might need a wide range of expertise. This includes epidemiologists, immunologists, molecular virologists, structural biologists, doctors of veterinary medicine, and medical doctors. And that’s the nice thing about health systems like Mount Sinai, where we have a lot of those experts and they are able to come together to tackle this issue.

Beyond the science, collaboration is key. We have initiated the New York City Virus Hunters program, which is our science outreach surveillance program for H5N1. In this program, we work with local high school students to collect samples from birds in urban parks and greenspaces in the city, which are then screened for the presence of the virus. This is done in collaboration with Christine Marizzi, PhD, from the science education nonprofit BioBus and the wild bird rehabilitation center Wild Bird Fund. What’s important about getting high school students involved, especially those from backgrounds traditionally underrepresented in science, is getting them interested in science and steering them towards careers in science, technology, engineering, and math (STEM), specifically in molecular biology, virology, and so on. It’s about building the next generation of biologists and about involving the community in pandemic preparedness.

Mount Sinai does not exist in a vacuum—we help by sharing our information with the New York City Department of Health and Mental Hygiene, as well as with the government agencies. On the COVID-19 side of things, we are actively participating in the National Institutes of Health’s SARS-CoV-2 Assessment of Viral Evolution (SAVE), which tracks emerging variants. Our information feeds into the scientific community, but it also feeds into government agencies, who use that information to make their health policy decisions.

Dr. Simon: To be able to do what Dr. Krammer outlined, we need to keep our infrastructures intact. And that is really hard because we need all the funding and support we can get from the school, hospital, and government. But we are excited for what we can learn to continue keeping everyone safe from outbreaks.

The New York City Virus Hunters program works with local high school students not only to track the presence and spread of H5N1 virus in animals, but also to foster an interest in science and a career in STEM fields among students.

Image credit: Christine Marizzi, PhD, BioBus.

Team at Mount Sinai Fuster Heart Hospital Performs First U.S. Procedure With New Implant to Improve Circulation Below the Knee

Top, from left: Rheoneil Lascano, MSN, FNP, Vishal Kapur, MD, David Song, MD, Prakash Krishnan, MD, FACC, FSCAI, Raman Sharma, MD, and Moinuddin Syed, MBBS. Bottom, from left: Dr. Song, Samin K. Sharma, MD, Annapoorna S. Kini, MD, Dr. Kapur, Dr. Krishnan, and Raman Sharma, MD.

A team at the Mount Sinai Fuster Heart Hospital has successfully performed the first procedure in the United States using an innovative drug-eluting, below-the-knee resorbable scaffold.

The team was led by Prakash Krishnan, MD, FACC, FSCAI, Assistant Professor, Medicine (Cardiology and Radiology), and Director of Endovascular Interventions at The Mount Sinai Hospital’s Cardiac Catheterization Laboratory. The Food and Drug Administration approved the device in April.

“FDA approval of this long-awaited new technology of a dissolving bioabsorbable scaffold is a remarkable addition in the treatment of lower limb arterial blockages where balloon and regular stents results are suboptimal, and these scaffolds are poised to restore blood flow for a long time,” says Samin K. Sharma, MD, Director of Interventional Cardiology for the Mount Sinai Health System. “We are proud of Dr. Krishnan, who played a major role in getting this innovative device approved.”

More than 20 million people in the United States are living with peripheral artery disease (PAD) yet there have been limited treatment options. The new procedure is the first to treat people with chronic limb-threatening ischemia (CLTI) below-the-knee, a severe stage of PAD. The goal is to prevent amputation, heart attack, and stroke among these patients.

For individuals battling chronic limb-threatening ischemia, blocked vessels restrict blood flow to the lower extremities. While balloon angioplasty serves as the current standard of care, recurrent blockages often necessitate further intervention.

Unlike traditional metal stents, the drug-eluting below-the-knee resorbable scaffold is a temporary implant. Crafted from naturally dissolving material, this scaffold gradually disappears after opening a clogged artery, presenting a significant advancement in sustaining open arteries below the knee.

“A resounding applause to the team at Mount Sinai Fuster Heart Hospital for their relentless pursuit of excellence in advancing patient care,” said Dr. Krishnan. “Many times doctors tell patients amputation is the only option, so this new technology is a game changer.”

Annual Symposium of the BioMedical Engineering and Imaging Institute Focuses on Precision Medicine and the Future of Digital Medicine

The 12th annual symposium of the BioMedical Engineering and Imaging Institute (BMEII) at the Icahn School of Medicine at Mount Sinai focused on precision medicine and the future of digital health.

The event featured renowned academic and industry representatives from around the world who participated in panel discussions about the precision medicine imperative and the quest to extend the “health span”—defined as the number of years people live a heathy life free of disease—in a multidisciplinary manner with a focus on medical imaging and engineering.

The innovation station and poster session provided hands-on demonstrations of current research.

More than 325 people, including researchers, physicians, industry leaders, medical students, and high school students, attended the event at the New York Academy of Medicine. The event was held Wednesday and Thursday, March 20-21.

The symposium began with welcome remarks from BMEII’s Director Zahi A. Fayad, PhD, who emphasized the need to back up recent developments in screening, longevity, and pharmaceuticals with evidence and data. He shared this vision during the event, ensuring attendees walked away with a better and more holistic understanding of the current and future state of precision medicine.

A major highlight of the symposium was the panel discussion about the future of digital medicine. With five industry and academic leaders, this discussion addressed many of the challenges health care is facing as consumer health technologies grow rapidly and move into clinical areas. These challenges center on user compliance and data privacy.

“I think the biggest problem is also trying to get the stakeholders around the same table and developing some consensus as to how they can share, if not the proprietary information, but how can they kind of use all of that [data] towards the good of humankind,” said Jagmeet P. Singh, MD, ScM, DPhil, Professor of Medicine at Harvard Medical School. He works closely with patients within the cardiology department who have received implantable cardiac devices and has first-hand experience with the long-term challenges that come with working with multiple manufacturers.

“So, now you have third-party vendors—in fact, over the course of the last year, there are almost 120 different remote monitoring companies that have come up—that are trying to standardize the data from these implantable devices that can be used uniformly by all health care givers,” he added.

Brendan Carr, MD, MA, MS

The symposium also included sessions for high school, undergraduate, and graduate students to build their interest in scientific research. A professional development panel, hosted by PhD candidates at Icahn Mount Sinai, allowed leaders in the field to share their personal experiences, challenges, and successes with the students. The innovation station and poster session provided hands-on demonstrations of current research in the medical imaging space by BMEII members and scientists from other institutes.

Health care is bound to change in dramatic ways in the future, and the symposium addressed the research and innovation that is shaping these changes.

Brendan Carr, MD, MA, MS, Chief Executive Officer of the Mount Sinai Health System, summarized the importance of the research BMEII is doing: “The clinical delivery system doesn’t exist without the pioneering research portfolio, and the pioneering research portfolio exists because it’s so unbelievably compelling to save lives and improve people’s health outcomes. That synergy is special—it’s a big piece of what this conference is about.”

Annual Gala Celebrates Advances in Prostate Cancer Research and Treatment at Mount Sinai

Frorm left: James Tisch, Co-Chairman of the Boards of Trustees of the Mount Sinai Health System, Dennis Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai, and Ash Tewari, MBBS, MCh.

The Milton and Carroll Petrie Department of Urology at the Icahn School of Medicine at Mount Sinai hosted its annual Prostate Cancer Research Gala and exceeded its goal of raising more than $1 million for the Center of Excellence for Prostate Cancer within the Department of Urology. Its mission is to eliminate prostate cancer through programs that support innovative research, patient care, prevention, and education for students, trainees, professionals, and the public.

“We are fortunate that at Mount Sinai the best minds across specialties like immunology, pathology, medical oncology, radiology, and others collaborate with the common goal of making prostate cancer insignificant while improving the quality of life for our patients,” said Ash Tewari, MBBS, MCh, Chair of the Department of Urology at the Mount Sinai Health System and the Kyung Hyun Kim, MD Professor of Urology at Icahn Mount Sinai, who spearheaded the gala and directs the Center of Excellence.

Goutam Chakraborty, PhD, left, and Dr. Charney

More than 200 people attended the event, which was held Wednesday, April 10, at the Rainbow Room in Rockefeller Center. Actor and singer Peter Gallagher served as the emcee for the evening.

At the event, the second annual Steven Southwick, MD Memorial Award was presented to Goutam Chakraborty, PhD, Assistant Professor, Urology, and Oncological Sciences and a member of The Tisch Cancer Institute at Mount Sinai. Named after renowned researcher and scientist Steven M. Southwick—a leading expert in psychological trauma and human resilience, who passed away in 2022 after a lengthy battle with prostate cancer—this award recognizes outstanding achievements in prostate cancer research.

Dr. Chakraborty was honored for his focus on lethal metastatic prostate cancer, which has no available treatments. He and his team made the groundbreaking discovery that the BRCA2 gene—most commonly known for its link to breast cancer—also has a connection to prostate cancer. Dr. Chakraborty is now looking at how mutations of genes like BRCA2 change cells from benign to metastatic disease, potentially leading to important new therapies.

“Research is like climbing a mountain, like climbing Everest, but we have not reached the top of Everest yet,” said Dr. Chakraborty in a video shown at the event. “Every day is a different challenge.”

Dr. Tewari, left, and John A. Levin

The gala also honored John A. Levin, who was recognized for his extraordinary commitment to the Prostate Cancer Program and longtime leadership on the Mount Sinai Board of Trustees. Dr. Tewari praised Mr. Levin’s unwavering support of the Mount Sinai Health System’s efforts to redefine cancer care, including his involvement with the International Prostate Cancer and Urology Symposium held at Mount Sinai, which draws the world’s top experts together to explore the latest advancements and challenges in urological cancer.

“His philanthropy has made an immense impact, not just on our prostate cancer program, but on a global understanding of prostate cancer, and to Mount Sinai itself, guiding and supporting research in different subspecialties,” said Dr. Tewari in a video.

In accepting the award, Mr. Levin noted that he’s proud to be part of Mount Sinai’s extraordinary service to New York City and beyond.

“We treat an enormous number of people. It is also an education arm and a research institution which creates new drugs, creates new devices,” he said in a video. “It’s really being part of a community and I want to help that community in whatever limited capacity I can.”

Advancing Heath Equity With Data: Collaborating With Stakeholders at Mount Sinai Queens

Jill Goldstein, MA, MS, RN

At Mount Sinai, a key pillar in advancing health equity focuses on the collection and use of self-reported patient demographic data to identify gaps in care. The Health Equity Data Assessment (HEDA) team is engaging key stakeholders across the Health System and collaborating to address variances.

A highlight of these efforts is the Mount Sinai Queens Nurses Against Racism (NAR) system council, which endeavored to evaluate incidences of hospital-acquired pressure injuries (HAPI) using an equity lens.

A pressure injury is a localized injury to the skin and/or underlying tissue, resulting from compression between a bony prominence and an external surface for a prolonged time. Monitoring HAPI specifically focuses on the occurrence of these injuries during an inpatient hospital stay.

According to Jill Goldstein, MA, MS, RN, Deputy Chief Nursing Officer, Vice President of Nursing at Mount Sinai Queens, and NAR sponsor, their collaboration with HEDA began in January 2023, combining subject matter expertise and data modeling to evaluate differences in HAPI rates across patient populations. She  noted that the interdisciplinary team explored the impact of race, gender, age, language, payor, length of stay, clinical service, and other factors on the incidences of hospital-acquired pressure injuries.

Further, the data showed that in terms of race, there were no meaningful differences observed between white, Black, or Hispanic patients in any model.

Notably, the most actionable finding was the elevated risk for patients who prefer to speak a language other than English or Spanish. In these patients, 40 percent were more likely to have documented HAPI when compared to English-speaking patients.

With the data the HEDA team helped to collect and interpret, the system-wide nursing team will seek interventions to eliminate this disparity. This interdisciplinary approach serves as a model to incorporate an equity lens into other quality work, according to Ms. Goldstein.

Purple Day: Raising Awareness, Ending Stigma of Epilepsy

Every year on March 26, people and organizations around the world band together in solidarity for Purple Day. They wear purple and host events to raise awareness about epilepsy, with the goal of ending its stigma. For Purple Day this year, we got together experts from the Mount Sinai Health System to explain what epilepsy is and answer other top questions people might have.

Is epilepsy contagious?
“You cannot spread epilepsy from one person to the other,” says pediatric neurologist Natasha Acosta Diaz, MD, Assistant Professor of Neurology at the Icahn School of Medicine at Mount Sinai.

Epilepsy is not an infection. It is a neurological condition characterized by seizures caused by abnormal brain electrical activity, says Dr. Acosta Diaz.

Is epilepsy electroencephalogram (EEG) testing painful?
In a standard EEG test, electrodes—small metal discs—are attached to the scalp with the help of a glue. The EEG test is not painful, says Anuradha Singh, MD, Director of the Epilepsy Monitoring Unit, and Professor of Neurology at Icahn Mount Sinai.

EEG tests study brain rhythms to look for any sign of irritability.  A standard EEG test records these brain rhythms for 20 minutes to an hour, says Dr. Singh. “Sometimes you get a little glue left on your scalp but it’s not painful at all,” she adds.

Is epilepsy surgery dangerous?
“The myths about the danger of epilepsy surgery come from the past, from about the last 100 years or so,” says neurosurgeon Fedor Panov, MD, Director of the Adult Epilepsy Surgery Program and Associate Professor of Neurosurgery at Icahn Mount Sinai. “What you currently find on the internet (about the dangers) unfortunately is not appropriate and it just perpetuates this myth that epilepsy surgery is dangerous,” he notes.

Epilepsy surgery has its risks and benefits. “Most certainly, the benefits outweigh the risks,” says Dr. Panov. As the epilepsy care team might phrase it to patients, the risk of going through a year with epileptic seizures far outweighs the risk of a surgical intervention to cure the epilepsy, he says.

Can epilepsy seizures be triggered by flashing lights?
There is a type of epilepsy that can be triggered by flashing lights, called photosensitive epilepsy. “However, this is very rare,” says Dr. Acosta Diaz.

When testing a patient for epilepsy, flashing lights are used to see if they provoke a seizure, and if so, appropriate recommendations for care can be given, she adds.

Can people with epilepsy drive a car?
“You can drive a car if you’re seizure-free,” says Dr. Singh. However, different states can have different rules and regulations. People with epilepsy will have to check with their state’s Department of Motor Vehicles, she notes.

What are some epilepsy surgical options?

Vagal nerve stimulator
Involves placing a small wire around a nerve in the neck to decrease seizure activity. The wire is attached to a small battery inserted under the skin of the chest.

Stereotactic laser ablation
Uses lasers to remove a part of the temporal lobe of the brain to help control seizures. The procedure is guided by magnetic resonance imaging (MRI), allowing for very precise cuts and removal.

Staged craniotomy
A two-stage surgery that involves removal of part of the skull to expose the brain, followed by removal of the brain tissue that is causing the seizures. Removing the damaged part of the brain does not cause deficits, as other parts of the brain adapt and pick up function. The procedure improves the overall brain network because it allows the healthy areas to work without constant electrical interference from the seizure “hot spot.”

Responsive neurostimulation
A device is implanted that automatically records and detects electrographic seizures, then rapidly delivers electrical stimulation to suppress seizure activity. It is the first device that the U.S. Food and Drug Administration has approved for use in the brain to listen, learn, and respond to seizures.

Can people with epilepsy have a job?
“Absolutely,” says Dr. Panov. “It’s a myth to say you cannot work if you have seizures.” Epilepsy care teams are available to help patients be a part of their community, including having and holding jobs. The Americans with Disabilities Act prohibits discrimination against people with disabilities in several areas, including employment.

While it is not mandatory that people with epilepsy disclose their condition to employers or coworkers, it is recommended that someone at the workplace is aware, says Dr. Acosta Diaz. “Just in case you have a seizure, somebody can be with you or help you,” she says.

Can people with epilepsy have children?
People with epilepsy can have happy, healthy children, says Dr. Singh. Women with epilepsy should work with their OB/GYN and epileptologist to ensure they’re on the safest drugs for the pregnancy, says Dr. Singh.

Can people with epilepsy stop taking medications when seizures stop?
The goal of any Comprehensive Epilepsy Center is to get patients seizure-free, and ultimately off the medications, says Dr. Panov: “The idea is that you will come off your meds once the seizures stop.”

It is important, however, that patients do not stop taking medications without discussing with their specialists, says Dr. Singh. A lot of factors go into the consideration of stopping medications, including EEG results and MRI scans, so that process should be done in consultation with an epileptologist.

Can people with epilepsy swallow their tongue?
“No way, there’s no way that you’re going to swallow your tongue,” says Dr. Acosta Diaz. During a seizure, the tongue can go to the side of the mouth and people can accidentally bite their tongue. To assist someone with a seizure, be calm and lay the person on the side, and definitely do not put anything in the mouth, such as a spoon, she says.

Does a ketogenic diet help people with epilepsy?
It does, in certain cases, says Dr. Singh. A ketogenic diet is a high-fat, adequate-protein, and low-carbohydrate diet. It is more often used in pediatric epilepsy, especially for children in whom medications do not work well, says Dr. Acosta Diaz.

Ketosis, a state where the body derives its sources of energy from fat rather than glucose, is known to have anticonvulsant properties. However, it’s not easy for a person to enter into ketosis. That is why an epilepsy care team involves overseeing a patient’s metabolism and nutrition as well, notes Dr. Acosta Diaz. “It’s not something you can try by yourself at home. It’s not just doing a keto diet to lose weight,” she says.

Caring for people with epilepsy is a team effort. At the Mount Sinai Epilepsy Center, staff members across all levels of care work together to provide exceptional care. Here’s the Center at a glance:

100+ team members

• Adult epileptologists  • Pediatric epileptologists  • Neurosurgeons  • Neuropsychiatrists  • Neuroradiologists  • Nurse practitioners  • Neurosurgery  • NPs and PAs  • Researchers  • Registered nurses  • Social workers  • Dietitians  • Recreational therapists  • EEG technicians  • Administrative staff

 

 

Designated as a Level 4 medical facility by the National Association of Epilepsy Centers (NAEC), which is the highest recognition of care and expertise for people with epilepsy

Three inpatient Level 4 epilepsy centers at The Mount Sinai Hospital, Mount Sinai Kravis Children’s Hospital, and Mount Sinai West, and six outpatient locations in New York City and Long Island.

ABRET-certified labs

Five Mount Sinai sites have received American Board of Registration of Electroencephalographic and Evoked Potential Technologists (ABRET) Lab accreditation for achieving highest levels of quality and competence performing neurodiagnostic tests.

In 2023

The Mount Sinai Health System performed more than 13,000 electroencephalograms and completed 100 surgeries to reduce or eliminate seizures for adult and pediatric patients.

In addition to treating patients with epilepsy, the Mount Sinai Health System and Icahn Mount Sinai conduct research to push the frontiers of understanding the neurological conditions and what is possible with treatment. Here are some examples of what Mount Sinai is doing to further science in epilepsy.

Clinical trial: Epilepsy associated with Lennox-Gastaut syndrome

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy, with seizures beginning in early childhood. To treat seizures that have not been well controlled through conventional medication, researchers are using novel responsive neurostimulation (RNS) strategies. This is the first clinical trial using RNS for LGS.

The trial is supported by a five-year grant from the National Institutes of Health, and conducted in collaboration with five other centers in the United States.

Click here for more info.

Clinical trial: Efficacy of subanesthetic doses of IV ketamine for treatment-resistant epilepsy

Ketamine is an anesthetic that provides pain relief, and came into clinical use in the 1960s. In a hospital setting, ketamine is used intravenously at anesthetic doses to treat unrelenting seizures known as status epilepticus in comatose patients. Mount Sinai researchers are exploring using ketamine at subanesthetic doses in an outpatient setting for patients who have treatment-resistant epilepsy. With subanesthestic dose-ketamine recently approved by the FDA for treatment-resistant depression, researchers are optimistic about its safety, and are hopeful that this will provide relief for patients with hard-to-treat epilepsy as well.

Click here for more info.

Clinical trial: Phase 3 trial for a once-daily, oral treatment for those living with focal seizures (XTOLE2)

Focal seizures are when brain cells on one side of the brain malfunction, causing symptoms, and are considered the most common type—making up more than half of all seizures. Symptoms could include one or more of the following: motor, sensory, autonomic, or cognitive. While treatment can stop or reduce the frequency of the seizures, for some patients, current treatment options may be insufficient. Mount Sinai is participating in a Phase 3 study with Xenon Pharmaceuticals to explore the use of XEN1101, a potassium channel opener, along with the patient’s existing medication, for focal seizures. Clinical data from previous trials have shown up to around 50 percent reduction in focal seizures among participants who have received the drug.

Click here for more info.

Clinical trial: Phase 3 trial for Staccato® Alprazolam in participants 12 years and older with stereotypical prolonged seizures

Benzodiazepines are more commonly known for treating anxiety or panic disorders, but they can also be used to terminate most seizures in an inpatient setting. Approved therapies include a rectally-administered gel and intranasal formulations. However, there are no approved treatments for rapidly terminating an ongoing seizure in an outpatient setting. Mount Sinai is participating in a Phase 3 trial with pharmaceutical company UCB to study the effectiveness and safety of Staccato® Alprazolam, a breath-triggered device that delivers the benzodiazepine deep into the lung for rapid absorption and systemic exposure, with the goal of achieving rapid epileptic seizure termination (REST). In a previous clinical trial, in an inpatient setting, nearly 66 percent of participants who received the drug responded to the treatment, compared to 43 percent of participants who received a placebo. For participants who responded to the intervention, the Staccato® Alprazolam group saw seizure cessation in a median time of 30 seconds, compared to 60 seconds for those who had received a placebo. The Phase 3 trial tests the treatment in an outpatient setting.

Click here for more info.

Clinical trial: Electrographic seizure pattern modulation biomarkers in responsive neurostimulation for epilepsy

Although the therapeutic benefit of RNS is well established, predicting how well and when a patient might respond to the device is difficult. It may take several months for a patient to report a reliable change in seizure status, during which time the programming clinician has no objective guidance regarding whether or not to adjust settings. RNS devices can provide EEG recordings, offering an insight to seizure patterns, but there is little knowledge about how to use these recordings in individual patients. Thus, a critical need exists to develop methods for using a patient’s own data to predict when seizure reduction should be expected or to confirm objectively the presence and maintenance of a clinical response.

Icahn Mount Sinai researchers are working with Massachusetts General Hospital to apply machine learning, neurostatistics, and data science to improve the effectiveness of RNS, especially for children and adults who are not considered suitable surgical candidates.

Click here for more info.

Laboratory for Human Neurophysiology

The Laboratory for Human Neurophysiology seeks to understand how human cognition arises from the interaction of multiple brain areas and neurotransmitter systems, particularly in decision-making behavior. These research efforts involve studying prefrontal cortical and subcortical areas directly in the human brain by conducting intracranial electrophysiology recordings in patients undergoing neurosurgical treatment.

Ongoing research projects in the laboratory include investigating the neural basis of human decision-making under uncertainty using distributed intracranial EEG recordings in epilepsy patients, decoding overt subject behavior from preceding, distributed brain activity in reward-related brain regions, and studying reward and mood processing across multiple brain areas in epilepsy patients with and without comorbid depression. The lab is led by Ignacio Saez, PhD, Associate Professor of Neuroscience, Neurosurgery, and Neurology at Icahn Mount Sinai.

Click here to read more about the lab.

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