The CT scan, left, shows the 85 cc intracerebral hemorrhage. The CT scan, right, was performed on postoperative day 1 and shows complete evacuation of the hematoma.
Spontaneous bleeding in the brain, known as intracerebral hemorrhage (ICH), remains the least treatable and most devastating form of stroke. While it accounts for only 15 percent of all strokes, it is a leading cause of mortality, morbidity, and disability worldwide, and few effective treatment options exist. Over recent months, however, Mount Sinai physicians have taken a leading national role in creating and implementing a new minimally invasive technique that is showing promise.
ICH occurs when a small artery in the brain leaks blood directly into surrounding tissue and forms a localized hematoma (clot), which continues to destroy neurons and causes life-threatening pressure on the brain. Loss of balance, blurry vision, and difficulty speaking are among the common symptoms, as well as headache and vomiting, which increase gradually over minutes to hours.
This sequence demonstrates the steps of the endoscopic evacuation procedure including placement of the sheath into the hematoma (A), aspiration of the hematoma (B), irrigation ofthe cavity (C), and removal of the sheath (D).
The effort is being led by J Mocco, MD, MS, Director of the Cerebrovascular Center at the Mount Sinai Health System, and Professor and Vice Chair for Education in the Department of Neurosurgery at the Icahn School of Medicine at Mount Sinai, and Christopher Kellner, MD, Director of the Intracerebral Hemorrhage Program at Mount Sinai and Assistant Professor of Neurosurgery.
Over the course of 15 months, they have treated nearly 50 patients with a novel strategy to evacuate blood clots using ultrasound imaging, paired with intraoperative CT
scanning and MRI-guided navigation, to precisely locate the blood clot within the brain. Through a tiny hole in the skull, a sheath containing a camera and an experimental suction device, known as the Apollo™ System, is navigated to the clot. The physicians then aspirate the clot with the Apollo device, normalizing the brain pressure.
J Mocco, MD, MS, left, and Christopher Kellner, MD
In 2016, Dr. Mocco was named co-principal investigator of a Phase I clinical trial that will enroll approximately 50 patients at 10 sites across the United States to test the feasibility, safety, and efficacy of this procedure when compared to previously published standards. The trial, called the INVEST trial, is funded by Penumbra, Inc., the company that developed the Apollo System, and is scheduled to commence in May.
“We have just completed a six-month follow-up for the first 28 patients treated with this device, and although the data are preliminary, it appears that patients overall are doing very well with this procedure,” says Dr. Mocco.
One recent patient—an extremely active 86-year-old classical pianist—presented to Mount Sinai Beth Israel in February. “He came in with left arm and leg paralysis, slurred speech, and lethargy,” says Dr. Kellner. A CT scan revealed a very large 85 cc hemorrhage, and he was transferred to the Intracerebral Hemorrhage center at Mount Sinai West. Given his age, and the size and the location of the hemorrhage, he scored a ‘4’ on the ICH Score, which predicts a 97 percent chance of mortality within 30 days.The physicians removed the clot within 24 hours of the hemorrhage.
“He has made a remarkable recovery,” says Dr. Kellner. “He was discharged to the rehabilitation unit at The Mount Sinai Hospital after only 10 days. Currently, he is cognitively almost back to normal, can walk with a walker, and is back to playing the piano.”
Dr. Mocco has received research grants from Penumbra, Stryker, Microvention, Medtronic, and Codman.
Members of the Long Island Transplant office include, far right, Priya Grewal, MD, Associate Professor, Medicine (Liver Diseases), with, from left, Taneil Wilson, Maureen O’Reilly, RN, and Geena Mapoy, RN.
Comprehensive pre- and post-surgical follow-up care for adult patients undergoing liver, kidney, and pancreas transplants at the Recanati/ Miller Transplantation Institute at Mount Sinai in Manhattan is now available at a new Mount Sinai Doctors facility in Hewlett, New York.
The Long Island Five Towns practice provides patients with the convenient expert care that is critical to their successful outcomes both in the weeks before surgery, when patients make regular office visits to check on their health and perform tests, and in post-surgical visits, when their immunosuppressant medications are carefully monitored.
“Patients are much happier, and they say they actually feel better knowing they don’t have to travel into the city for every visit,” says Priya Grewal, MD, Associate Professor, Medicine (Liver Diseases), who leads Mount Sinai’s liver transplant efforts on Long Island. The patients also understand that having the transplant procedure performed at The Mount Sinai Hospital is a critical component in ensuring a successful outcome.
“We have removed barriers and improved access to care,” says Vinita Sehgal, MD, Assistant Clinical Professor, Medicine (Nephrology), who leads Mount Sinai’s kidney and pancreas transplant efforts on Long Island.
Removing the stress associated with traffic, parking, and longer commuting time makes the entire process easier on patients and their families. While the actual transplant surgeries will continue to take place at The Mount Sinai Hospital in Manhattan, patients will be able to see the entire transplant team—doctors, nurses, social workers, nutritionists, and support staff—in the Long Island office. The location features a large, comfortable waiting room and plenty of parking.
Sander S. Florman, MD, Director of the Recanati/Miller Transplantation Institute, and the Charles Miller, MD Professor of Surgery, says the response to the opening of the Long Island office has been overwhelmingly positive and many patients are booking appointments there, a reflection of the reputation and track record of the transplant program at Mount Sinai.
“When considering a highly delicate and technical operation like a liver or kidney transplant, experience matters,” Dr. Florman says. The Institute, one of the largest and most comprehensive adult and pediatric abdominal transplantation centers in the world, has performed nearly 9,000 transplants and marked the 50th anniversary of its first kidney transplant this year. Having performed more than 4,000 liver transplants—many more than other Manhattan programs— Mount Sinai’s team is among the most experienced.
The new Long Island office is located within a large Mount Sinai Doctors practice, which also houses primary care physicians and specialists, and features expanded hours.
Children who have older siblings or frequent interaction with grandparents are diagnosed with autism spectrum disorders (ASD) earlier than those who do not, according to new research conducted at the Seaver Autism Center for Research and Treatment at Mount Sinai, and published in the journal Autism.
The study, titled “Grandma Knows Best: Family Structure and Age of Diagnosis of Autism Spectrum Disorder,” found that about 50 percent of friends and family members reported they had suspected a child to have a serious condition before they were aware that either parent was concerned. Maternal grandmothers and teachers were the two most common relationship categories to first raise concerns. “Our work shows the important role that family members and friends can play in the timing of a child’s initial diagnosis of autism,” says Joseph D. Buxbaum, PhD, the G. Harold and Leila Y. Mathers Research Professor, and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience, Icahn School of Medicine at Mount Sinai, and Director of the Seaver Autism Center. He is senior author of the paper, which was published online February 8, 2017. The study included colleagues at Columbia Business School and Carnegie Mellon University.
The team conducted an online survey of 477 parents of children with autism. In addition, they carried out novel, follow-up surveys with 196 “friends and family,” who were referred by parents. Eighty percent of the children with ASD were boys, and the median age of diagnosis was 33 months. Frequent interaction with a grandmother reduced the age of diagnosis by 5.18 months, and frequent interaction with a grandfather reduced the age of diagnosis by 3.78 months. “Since early detection of ASD is critical to effective treatment interventions, we hope the study will serve as a call to action to encourage family and friends to share concerns early on,” Dr. Buxbaum says.
In other news, the Autism Sequencing Consortium, a multi-institute research group founded by Dr. Buxbaum, has received a $7 million extension of a grant from the National Institutes of Health to collect, analyze, and share samples and genetic data from people diagnosed with autism.
The Consortium now includes more than 40 international groups and 150 researchers who have generated gene sequencing data from 29,000 individuals, making it the largest such study to date in autism. All shared data and analyses are hosted on a supercomputer called Minerva, designed by Mount Sinai faculty, which enables joint analysis of largescale data. The new grant will extend the project through 2022 and expand the sample to include more than 50,000 individuals.
Kenneth Teasley, HIV-positive with end-stage renal disease, had been on a waiting list for a kidney transplant for five years. He learned from The Mount Sinai Hospital in the spring of 2016 about his eligibility for an organ from another HIV-positive patient. Mount Sinai was the first hospital in New York State and only the second in the country approved to perform kidney and liver transplants from a deceased HIV-positive donor to an HIV-positive recipient.
Here is his story:
“I was originally diagnosed with HIV in 1993. Then a couple months later, I was diagnosed with CKD at 23 percent,” Kenneth says. “I basically thought I had two years to live.”
CKD or Chronic Kidney Disease is a condition characterized by gradual loss of kidney function over time. Kenneth’s kidneys were functioning at only 23 percent of capacity. After years of suffering, Kenneth began three times a week dialysis treatment sessions.
“It was very hard for me at the beginning. And all you want to do is go to sleep. I was also having issues with my blood pressure,” he says. “I actually fell once, really bad, and that’s actually how they found the stroke that I had earlier that year.”
Kenneth remained on dialysis for five years.
Sander S. Florman, MD: “He’s going to have a much better quality of life, and he’s going to live longer thanks to the gift of organ transplantation.”
“When you’re on dialysis your chances of having a heart attack or a stroke go up dramatically. In fact, most of the people who are on dialysis will die of a heart attack or a stroke,” says Sander S. Florman, MD, Director of The Recanati/Miller Transplantation Institute at Mount Sinai and Charles Miller, MD Professor of Surgery at the Icahn School of Medicine at Mount Sinai. “If you’re lucky enough to get a transplant that risk goes way down.”
Kenneth was placed on the transplant waiting list. But for HIV patients the wait was typically much longer than for those without disease.
“Mount Sinai was a big enroller in an NIH-sponsored trial offering transplants to very carefully selected people with HIV,” says Dr. Florman. “And it turns out, very counter-intuitively, that the medicines that we use for transplant to prevent rejection work synergistically, work right alongside with the medicines that are used to treat HIV. They did well, and this opened the door.”
Kenneth Teasley: “I think I can do anything now. I guess I could be Superman.”
After the surgery, “his kidney function was normal right away and he didn’t have any complications,” says Antonios Arvelakis, MD, MPH, Transplant Surgeon at the Recanati/Miller Transplantation Institute and Assistant Professor of Surgery at the School of Medicine. “Being able to offer an HIV patient the organ of an HIV donor, I’m pretty sure it’s going to help move forward the approach of the treatment for HIV patients.”
Adds Dr. Florman: “He’s going to have a much better quality of life, and he’s going to live longer thanks to the gift of organ transplantation. I couldn’t be more proud of Mount Sinai and of my team’s efforts to offer transplant to HIV because when it comes to transplanting people with HIV there’s a lot of stigma still and a lot of places talk ‘yes’ but very few places do ‘yes.’”
After a week in the hospital, Kenneth returned home.
“I finally realized that I actually can do anything, and it’s not what’s put on you, it’s what you do with it,” he says. “I think I can do anything now. I guess I could be Superman.”
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.
REVEL developers Weiva Sieh, MD, PhD, left, and Joseph Rothstein, MS
Sequencing-based genetic tests are making personalized medicine a reality for patients who carry certain mutations for serious diseases, including breast and prostate cancer. Armed with information about the pathogenicity of such variants in their genome, these patients can now make proactive decisions about their health care early enough to increase the odds of success in preventing or treating disease.
But for each step forward in this new frontier of personalized medicine, physicians and scientists are stymied by their lack of knowledge about thousands of other rare variants in a patient’s genome that could also portend disease. For this reason, two researchers at the Icahn School of Medicine at Mount Sinai developed REVEL, a novel tool designed to make sense of these variants of unknown importance in order to help guide patient care and risk management and to facilitate research.
Developed by Weiva Sieh, MD, PhD, Associate Professor of Population Health Science and Policy, and Genetics and Genomic Sciences; and Joseph Rothstein, MS, an Instructor of Genetics and Genomic Sciences, and Population Health Science and Policy, REVEL is an acronym for Rare Exome Variant Ensemble Learner. The tool predicts the likelihood of whether a particular coding variant in a person’s genome is disease-causing or benign.
“REVEL is timely and significant because the number of rare variants discovered by sequencing studies is vast and growing and little is known regarding their function,” says Dr. Sieh. “Yet few pathogenicity prediction tools have targeted rare missense variants, leaving researchers and clinicians to struggle with their interpretation.” The ability to distinguish among the approximately 10,000 missense variants in each person’s genome that result in protein changes that could potentially be harmful also helps researchers set priorities for the variants they may wish to study further as new disease-causing genes. Identifying more of these variants would enable personalized medicine to realize its potential in helping more patients benefit from prevention and treatment regimens tailored to their individual disease risks.
Other tools that use different predictive features do exist, but they often do not agree with each other on the likelihood of pathogenicity. Dr. Sieh and Mr. Rothstein created REVEL as an ensemble method that uses machine learning to combine information from many of these other tools in order to generate a consensus score. REVEL incorporates 18 pathogenicity prediction scores from 13 tools, and it specializes in prioritizing the most clinically or functionally relevant variants among the sea of rare variants that are being discovered through next-generation sequencing.
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.