Soliz initially shrugged it off as a pulled muscle. But the pain grew progressively worse. Soon, he was experiencing sharp pain throughout the day, using walls for support as he walked and struggling to find a comfortable position to sleep.

Soliz underwent an MRI, revealing a large tumor in his spine. Recognizing the critical diagnosis of this bone tumor, an orthopedic surgeon in Ventura County near Soliz’s home referred him to Cedars-Sinai.

An image-guided biopsy performed by interventional neuroradiologist Marcel Maya, MD, co-chair of the Department of Imaging at Cedars-Sinai, made the diagnosis of an aneurysmal bone cyst, a rare, blood-filled tumor that can grow rapidly and, as in Soliz’s case, destabilize the spinal column and compress the spinal cord.

Although the tumor was benign, its location made it dangerous, said his surgeon, Tiffany Perry, MD, associate professor of Neurosurgery and co-director of Spine Oncology.

“Spinal fluid normally surrounds the cord, providing space for the cord and the nerve roots as they exit the spinal column,” Perry said. “But in Ryan’s case, the tumor was taking up about 80% of the spinal canal and was blocking the flow of fluid and compressing the cord, causing weakness in his legs.”

For Soliz, the diagnosis quickly became about more than treating a rare tumor—it was about saving his ability to walk. Three days after his outpatient appointment in the neurosurgery clinic, Soliz began losing feeling in his legs, prompting doctors to act emergently. By the time he was admitted to the ICU, he had lost the ability to walk.

“It was a roller coaster of emotions. I was terrified thinking I might never be able to walk again,” Soliz said.

A Rare Tumor and Emergency Surgery

Aneurysmal bone cysts are uncommon, and involvement of the spine with significant spinal cord compression is particularly unusual, Maya said.  

“Although these tumors are benign, they can be locally very aggressive—destroying bone, bleeding significantly and, when they occur in the spine, compressing the spinal cord,” Maya said.

After Soliz was seen in the outpatient clinic, his case was reviewed by a spine tumor board, a group of specialists at Cedars-Sinai from different disciplines that discusses complex spinal tumors. The board ensures patients like Soliz receive coordinated care, formulating a comprehensive, individualized treatment plan for each patient. Maya said the multidisciplinary tumor board allows specialists in neurosurgery, imaging, interventional neuroradiology, pathology and other disciplines to develop a coordinated treatment strategy from the outset. Given the rapid decline of Soliz’s condition, his care team implemented the developed plan in an expedited manner.

Before removal of the tumor, Michael Alexander, MD, vice chair of Neurosurgery, performed a preoperative embolization of the tumor. This minimally invasive procedure blocked blood flow to the tumor, reducing the risk of major blood loss during surgery.

Following the embolization, Perry resected the tumor during a five-hour surgery, ultimately relieving the pressure on Soliz’s spinal cord and preserving his ability to walk.

In addition to Perry, Maya and Alexander, many Cedars-Sinai specialists contributed to Soliz’s care, including the pathologists who confirmed his diagnosis. The specialists and staff in the Neuroscience Critical Care Unit were also instrumental in his recovery, providing attentive care before and after surgery that helped him begin walking again.

“Ryan’s case reflects the importance of every team bringing its expertise together toward one shared goal—taking care of every patient and ensuring the best outcomes possible within our abilities,” Perry said.

A Recurrence, and Off to College

After surgery, Soliz spent time in rehabilitation recovering his strength. But in April, the tumor returned.

Alexander performed another embolization, blocking the blood vessels supplying the tumor. The approach allowed Soliz to avoid another operation to remove it and instead take medication to suppress the tumor’s growth.

Today, Soliz is in good health, golfing and hiking, and preparing to start his freshman year at the University of Hawaii, where he will be followed by a specialist throughout the school year. During breaks, he will continue his medical care at Cedars-Sinai.

Despite everything he has been through, Soliz is looking ahead to college and to a possible career in healthcare.

“I’ve always had huge respect for healthcare workers, but being a patient made me realize I want to work in healthcare and help others as a nurse,” he said.

For Perry, Soliz’s story feels personal.

“I have a daughter one year older than Ryan who just went through the college application process and moved away,” Perry said. “I could only imagine what Mrs. Soliz was feeling. I knew we had to work together for Ryan. He has amazing things he will do—and I cannot wait to see how he changes the world.”

Read more from Cedars-Sinai Stories and Insights: Seeking a Second Opinion for a Spine Condition

, a national recognition awarded to programs that bring together specialists across disciplines to advance care for patients with complex skull base tumors through clinical expertise, research, education and innovation. These programs offer advanced surgical approaches to treating skull base tumors, including some cases considered inoperable elsewhere.

The designation recognizes Cedars-Sinai’s collaborative approach to treating tumors that develop at the base of the skull—an anatomically complex area where tumors grow near nerves and blood vessels that control vision, hearing, facial movement and swallowing.

“There is very precious real estate, and treatment often requires expertise from multiple specialties,” said Vladimir Ljubimov, MD, assistant professor of Neurosurgery at Cedars-Sinai, where he and other neurosurgeons at Cedars-Sinai Medical Center and Torrance Memorial Medical Center collaborate with a range of specialists to remove some of the most complex tumors.

The Cedars-Sinai Newsroom spoke with Ljubimov about what skull base surgery involves, why a multidisciplinary team is essential, and how advances in surgical techniques are expanding treatment options for patients.

What is skull base surgery?

Skull base surgery involves treating tumors that develop in one of the body's most anatomically complex regions. But the goal isn't simply to remove the tumor—it's to do so while preserving the nerves and blood vessels that control critical functions. Even a small injury to one of these structures can have life-altering consequences, including stroke, vision loss or facial paralysis. That's why skull base surgery requires advanced techniques, meticulous planning and close collaboration among specialists.

Treatment is tailored to each patient. Depending on the tumor's location, we may perform a traditional craniotomy, in which surgeons temporarily remove a small section of the skull to reach the tumor. We also use minimally invasive endoscopic techniques through the nose, orbit, or mouth, or combine multiple surgical approaches. These techniques allow us to safely treat tumors that were once considered extremely difficult or even impossible to reach.

What does a multidisciplinary skull base team involve?

Skull base surgery is truly a team effort. Neurosurgeons and otolaryngologists often work together during surgery, especially for minimally invasive endoscopic procedures performed through the nose or ear. Depending on where the tumor is located, other specialists may join the team. For example, ophthalmologists and oculoplastic surgeons help us safely treat tumors near the eye while preserving vision and appearance. Plastic surgeons may assist with reconstruction when needed. We also collaborate with endocrinologists, neuro-oncologists, neurologists and radiation oncologists, depending on the patient's diagnosis.

Every case is reviewed by our multidisciplinary team before surgery. Together, we evaluate imaging, discuss treatment options and determine the safest, most effective approach. Just as important as removing the tumor is reconstructing the skull base afterward. Our specialists work together to rebuild these structures, helping prevent complications such as cerebrospinal fluid leaks or infection while allowing patients to recover safely. After surgery, we continue coordinating care, which may include hormone management, radiation therapy, chemotherapy or rehabilitation.

What are the symptoms of a skull base tumor?

Not all skull base tumors are cancerous. Many are benign, but because of where they're located, they can still cause serious problems by pressing on the brain, nerves or blood vessels.

Skull base tumors include tumors such as pituitary tumors, tumors that arise from the lining of the brain (meningiomas), rare tumors that develop near the pituitary gland (craniopharyngiomas), tumors of the bone and cartilage (chordoma, chondrosarcoma), as well as cancers that have spread to the skull base from other parts of the body.

Symptoms vary depending on where the tumor is located and may include vision changes or vision loss, double vision, dizziness, balance problems, headaches, nausea or hormonal changes.

What are the latest advances in skull base surgery?

One of the biggest advances is the development of sophisticated endoscopic techniques that allow us to reach tumors through the natural openings of the nose, avoiding large incisions in many cases. These approaches give us access to areas that were once considered too risky to operate on, including tumors deep within the skull base and around the cavernous sinus.

As technology continues to advance, we're able to treat increasingly complex tumors with greater precision while reducing complications and improving quality of life for our patients.

How should patients look for the right skull base surgeon for them?

Patients should look for a program that offers multidisciplinary care. Complex skull base conditions often require expertise from multiple specialists, and having those experts work together from the beginning leads to more comprehensive treatment planning.

At Cedars-Sinai, we evaluate each case as a team and offer the full spectrum of surgical and nonsurgical treatment options. If a patient has been told their tumor is too difficult to remove or has limited treatment options, seeking a second opinion at a high-volume skull base center can help determine whether additional approaches may be available.

Read more from Cedars-Sinai Stories and Insights: From Vacation Vertigo to an Acoustic Neuroma Diagnosis

“Spinal CSF leaks can be incredibly debilitating, and in many cases we haven’t understood why they happen,” said Wouter Schievink, MD, co-senior author of the study and professor of Neurosurgery at Cedars-Sinai.

The brain and spinal cord are bathed in protective cerebrospinal fluid. A tear or hole in the membrane that surrounds the spinal cord can allow this fluid to leak out, leading to nausea, neck stiffness and severe headaches that worsen when standing. Current treatments for spinal CSF leaks focus on sealing the leak after it occurs. Patients are often treated with epidural blood patches, which can provide temporary relief, or may require specialized surgery to repair the tear when symptoms persist.

Spinal CSF leaks are associated with genetic connective tissue diseases that affect tissues supporting the body’s structure, but for many patients without a diagnosis of connective tissue disorder, the cause of the ruptured membrane is unknown.

“Because some patients with unexplained spinal CSF leak show subtle signs of connective tissue disease, even though they do not have a defined diagnosis, we sought to find a genetic cause,” Schievink said.

Investigators, including lead author of the study Cassie Parks, MD, PhD, and co-senior author Hal Dietz, MD, analyzed whole-exome sequencing from 42 patients with unexplained spinal CSF leak and compared the results with more than 3,800 individuals without the condition. They tested how the genetic variants they detected behave in human cells and laboratory mice.

The study found that about 1 in 5 patients with this type of spinal CSF leak had changes in the FBN2 gene, and that these changes appeared significantly more often in patients with CSF leak than in those without the condition.

Additional experiments showed that these genetic changes disrupt the way cells attach to the supportive tissue surrounding the spinal cord, potentially weakening this protective layer. In laboratory mice carrying the same mutations, the spinal lining was more prone to tearing and leaking.

Together, these findings suggest that defects in connective tissue caused by FBN2 variants may increase a person’s risk of developing spinal cerebrospinal fluid leaks.

“By identifying a genetic contributor, we now have the first understanding of cellular events that may be targetable for prevention or treatment of spontaneous CSF leaks,” said Dietz, professor of Genetic Medicine at the Johns Hopkins University School of Medicine.

“Potential future treatments can include medications that strengthen connective tissue or target the biological pathways affected by the FBN2 gene,” Schievink added.

Additional authors include Mukti Singh, Elizabeth Wohler, Renan Martin, Silke Peeters, Emily Juzwiak, Xinyi Sun, Bart Loeys, Nara Sobreira and Claire Baldock.

Funding: This work was supported by the Howard Hughes Medical Institute, the Marfan Foundation, the Pease/Scheeler Fund and the Biotechnology and Biological Sciences Research Council.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Every minute counts when someone has a stroke, which occurs when blood flow to the brain is blocked. Without rapid treatment, brain cells begin dying within minutes, often leaving patients with permanent speech, movement or memory disabilities.

“Stroke is one of the most time-sensitive emergencies in medicine,” said Nestor Gonzalez, MD, director of the Neurovascular Laboratory in the Department of Neurosurgery at Cedars-Sinai. “The faster we restore blood flow to the brain, the more brain function we can preserve.”

Gonzalez’s advice is echoed in the American Heart Association and American Stroke Association’s new 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke. In the first update since 2019, the guidelines recommend more reliance on imaging, catheter-based procedures and emergency first responders. The guidelines also introduce the first national guidance for treating stroke in children.

Gonzalez, co-vice chair of the American Stroke Association group that developed the guideline, sat down with the Cedars-Sinai Newsroom to discuss the updates and leading-edge stroke research.

What are the most important changes in the updated guideline for acute ischemic stroke, in which a clot blocks blood flow to part of the brain?

Stroke treatment has advanced significantly over the past few decades, particularly with the development of clot-dissolving drugs and catheter-based procedures that can remove blockages in the brain. Since the previous stroke guidelines were published in 2019, new clinical trials have expanded our understanding of which patients can benefit from these treatments.

Previous guidelines recommended endovascular [minimally invasive] clot-removal procedures within six hours of stroke onset, with only a small group of selected patients eligible for treatment up to 24 hours after onset. The updated guideline broadens those criteria, allowing more patients to be considered for treatment in the 24-hour time frame.

The guidelines also expand treatment options for patients with large-core strokes—cases in which a significant area of the brain is affected. In the past, physicians were often hesitant to treat these patients because the potential benefit was uncertain. However, several recent studies have shown that intervention can still reduce disability in some cases.

The guidelines also expand eligibility for endovascular clot-removal procedures to include patients with preexisting disabilities, reflecting evidence that treatment may help them return to their baseline level of function.

You are a faculty member at Cedars-Sinai Guerin Children’s, and the updated recommendations include the first dedicated guidance for treating stroke in children. Why is that important?

Stroke can occur at any age, including in children. However, because it is rare, clinicians may not immediately consider stroke when a child presents with sudden neurological symptoms.

The updated guidelines provide clinicians with practical guidance for recognizing and managing stroke in children. Until now, there were no dedicated recommendations specifically addressing treatment in this population. The guidelines address early recognition of stroke symptoms, imaging strategies and circumstances in which treatments such as intravenous thrombolysis [clot-dissolving medication given through an IV] or endovascular thrombectomy [procedure removing clots from the brain] may be considered.

Over the past several years, specialized centers have begun applying some of the endovascular stroke treatments developed for adults to pediatric patients, and outcomes suggest that children can benefit from these interventions.

How will the updated guidelines change the treatment stroke patients receive in hospitals?

The guidelines emphasize improving the entire system of stroke care so patients can be evaluated and treated rapidly. That process begins with recognizing symptoms in emergency medical services, prompt evaluation and use of specialized treatment. They also synthesize a large body of research into recommendations that clinicians can apply in real-world practice.

The updated recommendations also highlight the importance of coordinated stroke systems that include rapid imaging, telemedicine support for smaller hospitals, and efficient patient transport to specialized stroke centers capable of performing advanced procedures, like Cedars-Sinai Medical Center.

For adult stroke patients, many of these systems are already in place. But for pediatric stroke, the impact may be even greater, as many hospitals are still developing formal systems for diagnosing and treating stroke in children.

What areas of stroke research are you most excited about right now?

Much of the recent progress in stroke care has focused on treating patients in the acute phase, when a clot suddenly blocks blood flow to the brain. But another challenge is helping patients whose brains receive chronically reduced blood flow, putting them at risk for repeated strokes. Two conditions that can cause this are Moyamoya disease, which often affects children and young adults, and intracranial atherosclerosis, which is more common in older adults.

In Moyamoya disease, the arteries at the base of the brain narrow or become blocked. To treat it, surgeons can perform bypass procedures that create new pathways to restore blood flow to the brain. My research has focused on improving these techniques and understanding how they benefit patients.

In adults with intracranial atherosclerosis, plaque buildup narrows, thickens or hardens the arteries in the brain. Medications help many patients, but in some cases, it is not enough. Working with the National Institutes of Health, we have been studying a surgical technique called indirect revascularization, or EDAS. Originally developed for children with Moyamoya disease, this approach is now being adapted for adults with severe vascular disease. Early clinical trials have shown encouraging results, and we are working to expand those studies to multiple centers to determine whether the technique can improve outcomes for patients who currently have limited treatment options.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

This condition not only can accelerate cognitive decline but is often mistaken for an underlying neurological condition—delaying proper diagnosis and treatment.

In a recent review published in the journal Alzheimer’s & Dementia, Cedars-Sinai researchers explored how UTI-induced delirium affects brain function, why individuals with dementia are especially vulnerable, and the critical need for early recognition and intervention.

“It’s a vicious cycle where dementia increases the risk of infection, and infection-related delirium accelerates cognitive decline,” said Shouri Lahiri, MD, principal investigator of the Critical Care Neurodegenerative Medicine Lab, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai, and senior author of the review.

Previous laboratory studies by Lahiri and his colleagues revealed that the immune system’s response to UTI-induced delirium—specifically the inflammatory protein interleukin-6—can cause changes in the brain. Blocking this pathway reversed delirium-like symptoms in mice.

Lahiri sat down with the Cedars-Sinai Newsroom to discuss UTIs as a potentially preventable and treatable contributor to cognitive decline and the importance of early recognition and swift treatment.

What is delirium, and how is it different from memory loss?

Delirium is a sudden change in thinking and awareness. It affects attention, judgment and short-term memory, and develops over hours or days.

Memory loss from conditions such as Alzheimer’s disease progresses slowly over time. Delirium, by contrast, is acute and usually triggered by a medical illness, such as a urinary tract infection, dehydration or infection elsewhere in the body.

Why can urinary tract infections cause confusion, especially in older adults?

Our research shows UTIs can cause acute brain dysfunction through inflammation. An infection in the bladder releases inflammatory signals into the bloodstream, which can affect the brain and disrupt normal function, leading to delirium.

Older adults are more vulnerable because their brains are often less resilient to physiological stress.

UTIs aren’t the only infections that can trigger this response. Any systemic infection, including pneumonia, gastrointestinal infections or skin infections, can provoke widespread inflammation that affects the brain and causes acute confusion.

Why are people with Alzheimer’s disease at higher risk for UTIs?

People with Alzheimer’s may have challenges upkeeping with hygiene and age-related hormonal changes that increase UTI risk. Alzheimer’s can also impair sensation and communication, making it harder for patients to recognize or report well-known UTI symptoms such as burning or urgency to urinate. As a result, infections may go untreated until they trigger delirium.

For people without dementia, delirium increases the risk of developing dementia by about threefold. Repeated episodes further raise that risk.

Why can a UTI make Alzheimer’s symptoms suddenly worse?

A UTI can cause a rapid cognitive decline that looks like a sudden worsening of Alzheimer’s disease. The key difference is timing. Alzheimer’s progresses gradually, while delirium causes an abrupt change from a person’s baseline.

We believe inflammation related to infection places added stress on an already vulnerable brain, which can worsen dementia symptoms and, in some cases, cause lasting damage.

Is delirium from a UTI reversible?

Early treatment offers the best chance for recovery. When UTIs are identified and quickly treated, delirium symptoms can improve or resolve. However, in some cases, cognitive effects can persist or become permanent. That’s why early recognition is critical.

Because UTIs don’t always cause obvious urinary symptoms, especially in older adults, we need to change the way we diagnose UTIs, using a mix of clinical observations and urinary and blood tests that show infection, to recognize when a UTI is behind sudden confusion.

How can caregivers tell the difference between Alzheimer’s progression and a UTI?

Sudden change is the biggest warning sign. Dementia generally does not cause abrupt declines. If someone with Alzheimer’s suddenly becomes much more confused, less alert or behaves very differently, that may signal delirium.

Other changes to look out for include changes in urination patterns, incontinence, pain, or changes in urine color or odor.

What can caregivers do to help prevent UTIs and delirium?

Caregivers should make sure the person they’re taking care of maintains good hygiene and adequate hydration. Caregivers should also notify a physician if UTIs are recurrent, because treatments are available to reduce repeated episodes.

Also, being aware of sudden changes in mental status and seeking prompt medical care can make a significant difference.

Are UTIs linked to delirium in other neurological conditions?

Yes. Parkinson’s disease is a key example. Many people with Parkinson’s have difficulty fully emptying their bladder, which increases infection risk. UTIs can worsen Parkinson’s movement symptoms, just as they worsen cognition in Alzheimer’s disease.

What is your lab studying next?

We are studying new drugs that target inflammatory pathways involved in UTI-related brain dysfunction, with the goal of advancing them to clinical trials. We are also developing diagnostic approaches to better identify UTIs in patients who  don’t have the well-known urinary symptoms.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The 39-year-old father, who plays softball and ice hockey and spends weekends off-roading, was no stranger to minor injuries. But the anti-inflammatory drugs prescribed by his primary care physician only gave Starsiak temporary relief. Over the next few months, his hips stiffened, and he began to lose sensation and muscle mass in his leg.

Then, during a business trip, the pain caused Starsiak to reach a breaking point.

“I could not walk from one gate to the next at the airport and ended up having a breakdown, crying because I was in so much pain,” Starsiak said.

After multiple doctor visits, including a trip to the emergency room, an MRI revealed the cause: a 2-centimeter cyst lodged on the front side of a nerve, tucked beneath a joint in his spine. Its location made it particularly difficult to treat.

A physician near his home in Orange County referred Starsiak to Corey Walker, MD, an assistant professor of Neurosurgery and Orthopaedics at Cedars-Sinai, who specializes in minimally invasive and complex spine cases.

Starsiak, a medical device salesman with a focus on orthopedic products, was familiar with surgical options and trusted his instincts in choosing Walker to oversee his care.

“When I met Dr. Walker, I immediately knew he was the right surgeon—someone of integrity who listened carefully and was deeply passionate about his craft,” Starsiak said.

Cyst Removal Without Spinal Fusion

Walker performs endoscopic spine surgery, a minimally invasive technique that uses a small endoscope—about the width of a pen—to navigate hard-to-reach places inside the body. Compared with traditional surgery, the minimally invasive approach typically results in smaller incisions, less tissue damage and faster recovery.

In Starsiak’s case, the cyst was compressing nerves against his spinal canal, interfering with their ability to send signals between his brain and leg. That pressure can lead to loss of strength, sensation and coordination.

Removing the cyst would be challenging. In order to access the nerve and underlying cyst, a surgeon typically would need to remove a spinal joint and fuse the vertebrae with rods and screws to stabilize them.

“That would have been a life-altering operation for someone his age,” Walker said. “Fusion puts added stress on surrounding joints and can lead to future surgeries.”

Instead, Walker took a different approach.

Using an ultra-minimally invasive endoscopic procedure, Walker accessed the cyst through an endoscope with a small camera attached. After locating the affected nerve, he and his team were able to use the endoscope to guide them in removing the cyst—without cutting muscle, removing the joint or injuring the nerve.

“We had what felt like an impossible task,” Walker said. “I’m proud that Cedars-Sinai is able to treat patients who have complex cases.”

For Starsiak, avoiding fusion was critical.

“I was worried a fusion would significantly hamper—if not end—my ability to play sports and lift weights,” he said.

Life-Changing Relief

When Starsiak woke up from the procedure, he immediately felt relieved of the pain and pressure, as if a rock had been removed from his back.

His recovery took about eight weeks, and he focused on restoring mobility and strength in his hips, legs and back. Today, Starsiak is back to his normal routine—playing sports, off-roading and lifting weights at the squat rack.

The experience also changed his mindset.

Before the injury, Starsiak said, he measured success largely by career advancement. As a father of two, losing his mobility forced him to reconsider his priorities.

“The second you lose your health, you realize none of the other things really matter,” he said. “You can’t enjoy success if you’re not healthy.”

For Walker, that impact is what makes the work meaningful.

“As a neurosurgeon, it’s incredible to hone your craft—to work with your hands and see a problem fixed by the end of surgery,” he said. “But what’s even more rewarding is hearing later how it’s changed someone’s life—that’s the best part.”

Read more from the Cedars-Sinai Newsroom: Defying the Odds – Father's Love Leads to Life-Changing Surgery

The study shows for the first time that Chlamydia pneumoniae can reach the retina—the tissue lining the back of the eye—where it triggers immune responses linked to inflammation, nerve cell death and cognitive decline.

“Seeing Chlamydia pneumoniae consistently across human tissues, cell cultures and animal models allowed us to identify a previously unrecognized link between bacterial infection, inflammation and neurodegeneration,” said Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology, and Biomedical Sciences at Cedars-Sinai Health Sciences University and the leading, senior author of the study. “The eye is a surrogate for the brain, and this study shows that retinal bacterial infection and chronic inflammation can reflect brain pathology and predict disease status, supporting retinal imaging as a noninvasive way to identify people at risk for Alzheimer’s.”

To conduct the study, researchers used advanced imaging, genetic testing and protein analysis to examine retinal tissue from 104 individuals, some with normal cognition, some with mild cognitive impairment and some with Alzheimer’s disease.

They found significantly higher levels of Chlamydia pneumoniae in the retinas and brains of people with Alzheimer’s disease than they found in people with normal cognition. The higher the bacterial levels detected, the more severe the brain changes and cognitive decline investigators found.

Higher levels of the bacterium were more common in people who carried the APOE4 gene variant, a known risk factor for Alzheimer’s disease.

Investigators also studied human neurons in the lab and in laboratory mice with Alzheimer’s disease. In both, infection with Chlamydia pneumoniae increased inflammation, nerve cell death and cognitive decline, showing the bacterium can accelerate disease processes. The infection also triggered production of amyloid-beta, the protein that accumulates in the brains of people with Alzheimer’s.

The findings were driven by co-first authors Bhakta Gaire, PhD, and Yosef Koronyo, MSc.

“This discovery raises the possibility of targeting the infection-inflammation axis to treat Alzheimer’s,” said Timothy Crother, PhD, co-corresponding author of the study and research professor at Cedars-Sinai Guerin Children's and the Department of Biomedical Sciences at Cedars‑Sinai.

The findings suggest that targeting chronic bacterial infection—and the inflammation it triggers—could represent a new treatment strategy. The research also supports potential use of the retina as a noninvasive way to help diagnose and monitor the disease.

Additional Cedars-Sinai authors include Bhakta Gaire, Yosef Koronyo, Jean-Philippe Vit, Alexandre Hutton, Lalita Subedi, Dieu-Trang Fuchs, Natalie Swerdlow, Altan Rentsendorj, Saba Shahin, Daisy Martinon, Edward Robinson, Alexander V. Ljubimov, Keith L. Black, Jesse Meyer, and Moshe Arditi.

Other authors include Julie A. Schneider, Lon S. Schneider, Debra Hawes, Stuart L. Graham, Vivek K. Gupta, and Mehdi Mirzaei.

Funding: This work has been supported by the NIH/NIA grants R01AG056478, R01AG055865, and AG056478-04S1 (M.K.H.), R01AG075998 (M.K.H. and T.R.C.), and Alzheimer’s Association grant AARG-NTF-21-846586 (T.R.C.). MKH is also supported by The Goldrich and Snyder Foundations. ER has been supported by The Ray Charles Foundation.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

It was in 2023, when Sarah underwent brain surgery with Keith Black, MD, that her mother, Dana, began to uncover the depth of her family’s ties to Cedars-Sinai. What Dana thought were fragments of family history—memories of her grandmother Reba Dubin’s volunteer work and her aunt Maxine Dunitz’s philanthropy—turned out to be a remarkable story of multigenerational dedication to advancing healthcare, championing women’s leadership and transforming a city.

The Pioneering Spirit of Reba Dubin and Maxine Dunitz

Dana’s childhood revolved around Cedars-Sinai, largely because of Helping Hand, which her grandmother Reba founded. The medical center was a constant presence in the family’s conversations, and visits to her grandmother’s house were filled with stories of philanthropy and service. Reba’s impact had started in 1929 when she’d created Helping Hand at Cedars of Lebanon—decades before the hospital merged with Mount Sinai—as a volunteer-run gift shop that was the first woman-run non-profit in Los Angeles. But her contributions went far beyond selling gifts. She was a trailblazer dedicated to supporting women and children in need. Inspired by her own mother’s activism and leadership, Reba, who was a college-educated pharmacist at a time when the roles of women were constrained, was determined to make a difference.

Through Helping Hand, she led initiatives to assist immigrants and refugees, provide medical support to the underserved and offer aid to low-income and expectant mothers. In an interview nearly 60 years after she established Helping Hand, Reba recalled visiting a woman’s apartment where a newborn slept in a dresser drawer for lack of a crib. She saw to it that the woman received a crib. Helping Hand also provided essentials for people in need, such as eyeglasses, artificial limbs and baby supplies—small gestures with big impacts. Over the coming decades, Reba’s work not only supported those who needed it most but also helped cement Cedars-Sinai as a major force for good in Los Angeles. One prominent example: In 1984, Helping Hand funded the first full-time endowed chair at Cedars-Sinai, the Miriam Jacobs Chair of Maternal Fetal Medicine.

Reba’s example inspired her niece, Maxine Dunitz, who first volunteered at Cedars-Sinai in 1948 as a teenager. Years later, Maxine took Reba’s dedication even further. Her generosity helped establish Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute and endow the position held by Black, who serves as the institute’s director. Maxine donated the funds the same year her great-niece Sarah was born. She could not have known that one day, Sarah would walk through the doors of that institute and that Black would free the young woman of a brain tumor. 

Dana and Sarah: A Legacy Comes Full Circle

Dana and her siblings were born at Cedars-Sinai in the 1960s, but her relationship to the medical center became far more personal in 1996. That year, her newborn son Daniel was rushed to Cedars-Sinai for emergency cardiac surgery with Alfredo Trento, MD. Born with an exceedingly rare condition that entailed seven heart anomalies, Daniel underwent a life-saving operation at just 24 hours of age. Dana had never wavered on where to turn for his care.

Then, some 25 years later, her daughter Sarah faced a medical crisis of her own. Athletic, independent and full of life, Sarah had always taken care of her health and rarely needed to see a doctor. She had grown up with a sense of perseverance, shaped by the knowledge that her brother Daniel had defied the odds—and that her mom had borne two other girls, both of whom succumbed to medical conditions in the early months of their lives. When Sarah began having seizures—the same symptom that had presaged the tragic deaths of the sisters she never knew—her family reached out to Cedars-Sinai again. “Through gasps and tears, I asked if we could meet Dr. Black,” Dana recalls.

Uncomfortable in medical settings, Sarah was anxious until she met Black. Unlike in previous medical encounters, where she often felt dismissed, here was a doctor who treated her with respect and compassion. “Dr. Black made me feel seen as a person, not just a case,” said Sarah, recalling that the Patient Relations Department also supported her parents as they dealt with the terrifying prospect of another severely ill child. Sarah was diagnosed with a ganglioglioma, a type of growth that accounts for only 0.4% of all brain tumors.

In July 2023, she successfully underwent surgery with Black. While Sarah lay recovering in her room, Dana, a historian by training, wandered into Helping Hand. What happened next was one of the most powerful experiences of her life. She unexpectedly met a 91-year-old volunteer who remembered her grandmother, Reba, and who brought out scrapbooks dating back to 1929. As Dana turned the pages, she discovered a treasure trove of stories, images, programs and more, and learned the full scope of both Reba and Maxine’s roles in the medical center’s growth. “It was both surreal and deeply nourishing,” said Dana. “My aunt was the reason that the institute existed and that my daughter could see the famous Dr. Black right here in L.A.”

A Sense of Connection

Since receiving her diagnosis, Sarah had been asking herself existential questions: Who am I? Where do I fit in? As her mother shared her discoveries about the family’s history with Cedars-Sinai, Sarah felt an overwhelming sense of belonging—she was part of something bigger than herself. And she had survived a serious health threat thanks to the skill of a surgeon whose position was endowed by her great-aunt. Her own progress was inextricably linked to Cedars-Sinai’s century-long story of progress and growth, highlighting the ties between each patient’s journey and the journey of the institution itself.

Knowing what her ancestors had achieved—and what she owed them—made her even more determined to keep fighting. It deepened her commitment to giving back and embracing life fully. Four months after her surgery, Sarah went bike riding in India. Her remarkable recovery is yet another testimonial to the resilience that runs through her family—and to Cedars-Sinai’s commitment to providing the very best care, and to making progress toward that goal by making sure each patient makes progress in their own health journey.

Read more on the Cedars-Sinai Blog: Faces of Cedars-Sinai--Neurosurgeon Keith Black

Cedars-Sinai has been named a Center of Excellence in Rare Neuroimmune Disorders, one of only 21 worldwide and two in California recognized for advancing research in immune-driven disorders of the central nervous system and providing the highest-quality comprehensive patient care.

The designation is awarded by the Siegel Rare Neuroimmune Association (SRNA), the patient advocacy group formerly known as the Transverse Myelitis Association.

“We’re proud to be known as an exceptional center offering streamlined access to specialists highly trained in addressing the varied and specific needs of patients with rare neuroimmune disorders,” said Paula Barreras, MD, assistant professor of Neurology and director of the new Center of Excellence at Cedars-Sinai. “This meaningful recognition by an organization that works with patients and the medical community helps us offer more people navigating these difficult conditions the services they need, without delay.”

The Center of Excellence in Rare Neuroimmune Disorders at Cedars-Sinai provides multidisciplinary, patient-centered care for people with:

• Acute disseminated encephalomyelitis
• Acute flaccid myelitis
• Idiopathic transverse myelitis
• Infectious myelitis
• MOG antibody-associated disease
• Neuromyelitis optica spectrum disorder
• Optic neuritis
• Neurosarcoidosis
• Paraneoplastic myelitis
  • Non-immune mimics of myelitis; vascular myelopathies; spinal cord stroke and spinal arteriovenous fistulas
  • Myelopathies of unclear cause

These often-complex disorders can affect the brain, spinal cord or optic nerve. Depending on the affected area, symptoms can range from muscle weakness, loss of balance and impaired vision to bladder or bowel incontinence and cognitive and communication changes.

“Because symptoms may span multiple physician specialties, patients who are not seen at a medical center with a multidisciplinary team are likely to experience delays on the road to an accurate diagnosis and treatment plan,” Barreras said.

Cedars-Sinai evaluates patients through comprehensive testing and imaging to pinpoint an accurate diagnosis. Patients are then connected with the appropriate on-site specialists and additional resources they may need, including social and neuropsychological services, help navigating insurance and medications, and physical therapy and rehabilitation.

Nancy L. Sicotte, MD, chair of the Department of Neurology and director of the Multiple Sclerosis and Neuroimmunology Program at Cedars-Sinai, as well as an expert in multiple sclerosis—a more common neuroimmune disease—said the designation also helps expand research and education efforts in rare neuroimmune disorders.

“Patients benefit because they have more opportunities to participate in research that can give them access to the most innovative treatments,” said Sicotte, the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “Our institution benefits from increased opportunities for research funding, and our research fellows benefit as they gain a greater understanding of the mechanisms of rare neuroimmune disorders and ways to improve outcomes for patients.”

In addition to Barreras and Sicotte, Cedars-Sinai’s specialist team for patients with rare neuroimmune disorders includes:

• Marwa Kaisey, MD, assistant professor of Neurology; multiple sclerosis specialist
• Omar Al-Louzi, MD, director of the Visual Outcomes Laboratory in the Department of Neurology; multiple sclerosis specialist with expertise in optic neuritis
• Swaraj Bose, MD, neuro-ophthalmologist and orbital surgeon
• Alexandra Dubinskaya, MD, urology specialist
• Mitzi Gonzales, PhD, neuropsychologist and director of Translational Research in the Jona Goldrich Center for Alzheimer’s and Memory Disorders
• Marcel Maya, MD, interventional neuroradiologist and co-chair of the Department of Imaging
• Christopher Boudakian, DO, medical director of the California Rehabilitation Institute
• Sadie Loera, social worker, Outpatient Neuroscience Department
• Laura Locke, NP, Department of Neurology
• Neurological rehabilitation team, including physical therapy, occupational therapy and speech therapy

“I’m thankful for our enthusiastic and knowledgeable team of clinicians, and I’m proud we can provide world-class care to patients,” Barreras said. “I’m also grateful for increased awareness for rare neuroimmune disorders, which will lead to advances in research and improved treatments. Our goal is to ensure patients are not jumping through hoops to access good care and experience a better quality of life.”

Read more from Discoveries Magazine: No Time for MS

“Our model, called the Unified Structural and Functional Connectivity model, provides a step toward mapping how different parts of the brain functionally communicate,” said Wei Gao, PhD, director of Neuroimaging Research and professor of Biomedical Sciences at Cedars-Sinai and senior author of the study. “The model shows that certain structural pathways, especially in networks related to emotions, self-awareness, and sensory processing, are heavily used for brain communications. The model also enhances our understanding of how these interactions relate to cognitive function.”

The investigative team—led by Gao, study co-author Pascal Sati, PhD, director of the Neuroimaging Program and associate professor of Neurology, and first author Arzu Silemek, PhD, a postdoctoral fellow supervised by Gao and Sati—found that certain areas serve as crucial hubs, with a significant corridor facilitating overall brain connectivity. They believe this mapping of brain communication could inform future research on cognitive processes and neurodevelopmental disorders. Clinically, they suggested it could improve physicians’ diagnostic tools by providing insights into how structural changes affect brain function, potentially leading to better-targeted interventions for conditions such as Alzheimer’s disease and other cognitive disorders.

Additional author: Haitao Chen

Funding: This work was supported by the National Institutes of Health (R01DA042988 and R01DA043678) and by Cedars-Sinai Precision Medicine Initiative Award and institutional support (to W.G.).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Delirium causes confusion and behavior changes, affects millions of patients each year and can increase a patient’s risk of long-term neurological problems. It is common in hospitalized patients who are placed on ventilators to assist their breathing.

“Microglia, the resident immune cells in the brain, can be destructive to brain cells in some neurological diseases, but also can be protective,” said Shouri Lahiri, MD, director of the Neuroscience Critical Care Unit and director of Neurocritical Care Research in the Department of Neurology at Cedars-Sinai and senior author of the study. “While previous research has suggested that the action of microglia may cause or worsen delirium, we found that the opposite is true. When we depleted levels of microglia in laboratory animal experiments, delirium-associated brain changes and behaviors increased. And when we restored microglia levels to normal, the changes were almost completely reversed.”

Medications that activate neuron-protecting microglia could be one option for managing delirium. Investigators previously determined that a protein called interleukin-6 damages neurons, and future studies could clarify whether it or other proteins activate neuron-protecting microglia. Future research is also planned to help determine the conditions under which microglia can cause damage to neurons, said Lahiri, an associate professor in the departments of Neurology, Neurosurgery, and Biomedical Sciences.

First authors: Landon Scott, Kevin D. Winzey

Additional authors: Debbie Moreira, Catherine Bresee, Jean‐Philippe Vit, Warren G. Tourtellotte, S. Ananth Karumanchi, and Shouri Lahiri

Funding: F. Widjaja Foundation

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These cells are located in the hippocampus, the brain area affected in the earliest stages of Alzheimer’s disease, the earliest symptoms of which are working memory deficits.

“Working and long-term memory are different types of memory that were previously thought to be supported by different parts of the brain,” said Ueli Rutishauser, PhD, director of Neural Science and Medicine and professor of Neurology, Neurosurgery and Biomedical Sciences at Cedars-Sinai and senior author of the study. “Based on this study and our previous work, we have concluded that the hippocampus, long known to support long-term memory, is often essential for working memory as well. In fact, neurons in the hippocampus that we have named ‘persistently active cells’ are critical for both types of memory. Protecting or restoring these cells could help in treating the devastating effects of memory disorders.”

Additional authors: Jonathan Daume, Jan Kamiński, Yousef Salimpour, Andrea Gómez Palacio Schjetnan, William S. Anderson, Taufik A. Valiante, Adam N. Mamelak

Funding: This work was supported by the National Institutes of Health (U01NS117839 to U.R.), a Postdoctoral Fellowship by the German Academy of Sciences Leopoldina (to J.D.) and a Postdoctoral Award by the Center for Neural Science and Medicine at Cedars-Sinai (to J.D.).

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The CurePSP designation means a medical center offers multidisciplinary clinics and movement disorder expertise for patients with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA).

“These disorders are similar to Parkinson’s disease, but are more rare,” said Yvette Bordelon, MD, PhD, who is part of the Movement Disorders Division in the Department of Neurology at Cedars-Sinai, and is director of the new Cedars-Sinai CurePSP Center of Care. “This designation will help consolidate our resources and outreach for patients with these disorders, generate additional interest in research and fuel community education.”

Movement disorders affect parts of the brain that control the body’s ability to walk and coordinate movements. Among other symptoms, these disorders can also cause tremors, slowness, rigidity, difficulty with speaking, swallowing, balance and, in some patients, problems with cognition.

“People with PSP, CBD or MSA often confront diagnostic delays, barriers to participating in clinical trials, and lack of familiarity with their disease among healthcare professionals,” said Jessica Shurer, director of clinical affairs and advocacy at CurePSP. “With its long history of comprehensive care and the strong collaboration between the movement and cognitive teams, Cedars-Sinai is well positioned to serve the large and diverse Los Angeles community with these diseases and will help to advance the thought leadership of the CurePSP network.”

Bordelon said each of these neurodegenerative disorders is defined by specific prominent symptoms:  

• Progressive supranuclear palsy often manifests in eye movement difficulties caused by abnormal clumps of tau protein, which have also been implicated in Alzheimer’s disease. It also often involves unexplained falls and difficulty with impulsivity and decision-making.
• Corticobasal degeneration also is associated with abnormal tau protein accumulation and causes challenges with word-finding and the loss of the ability to perform complex movements, such as using eating utensils or buttoning clothes.
• Multiple system atrophy is caused by abnormal clumps of the alpha-synuclein protein, similar to Parkinson’s disease. MSA disrupts involuntary bodily processes, such as heart rate and blood pressure, and leads to clumsy walking and slurred speech.

“There is perfect synergy between being a CurePSP Center of Care and our existing Neurobehavior and Movement Disorders programs,” said Sarah Kremen, MD, director of the Neurobehavior Program at Cedars-Sinai, and co-director of the Center of Care. “We have a full complement of specialists to help patients manage cognitive and behavioral symptoms of these rare conditions, as well as access to leading-edge translational research for those with neurodegenerative illnesses.”

The new center will take advantage of the robust pipeline of clinical trials at Cedars-Sinai, as well as a monthly multidisciplinary movement disorders clinic that brings together patients and neurologists, neuropsychologists, social workers, and specialists in physical therapy, occupational therapy and speech therapy.  

“Cedars-Sinai Neurology embraces a holistic approach to patient-centered, multidisciplinary care coupled with access to novel, cutting-edge research opportunities,” said Nancy L. Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “Our department has grown tremendously in recent years with this focus in mind, and with our current team of providers, it is well positioned to serve patients as a CurePSP Center of Care.”

Cedars-Sinai is one of just four Centers of Care in California; the other three are in Palo Alto, San Francisco and San Diego.

“Incredible advances in our understanding of these disorders in recent years have put us on the cusp of identifying meaningful and effective therapies to integrate into our care of patients,” Bordelon said. “This designation will fuel additional research opportunities and brings a level of distinction we're very proud of.”

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“In older adults, higher levels of amyloid beta and tau have been associated with poorer memory and cognition," said Mitzi Gonzales, PhD, director of Translational Research in the Jona Goldrich Center for Alzheimer’s and Memory Disorders at Cedars-Sinai and lead author of the study. “Our study found that this was also true in adults age 55 and younger—a period thought to be important for prevention. We also found higher levels in individuals with a higher genetic risk for Alzheimer's disease. Future studies should examine memory and cognitive changes over time and look at why some individuals remain mentally sharp despite having high levels of these proteins, to provide important clues about maintaining cognitive health over the lifespan.”

The findings highlight the importance of understanding the effects of amyloid beta and tau proteins on memory and thinking abilities at earlier ages. The work could also help focus dementia-prevention efforts in younger at-risk populations.

Additional authors: Adrienne O’Donnell, Saptaparni Ghosh, Emma Thibault, Georges El Fakhri, Sudha Seshadri, Jeremy Tanner, Claudia L. Satizabal, Charles S. Decarli, Keith A. Johnson, Alexa S. Beiser, Matthew Pase.

Funding: National Institutes of Health, Grant/Award Numbers: N01-HC-25195, HHSN268201500001I, 75N92019D00031; National Institute on Aging, Grant/Award Numbers: RF1AG059421, R01AG054076, R01AG049607, R01AG033090, R01AG066524, R01NS017950, R01AG077472, P30AG066546; National Health and Medical Research Council of Australia Investigator, Grant/Award Number: GTN2009264. 

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“The retina, a layer of tissue at the back of the eye, is part of the central nervous system and is directly connected with the brain,” said Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai and senior author all three studies. “It has similar cell types and vascular structures to the brain, but is not shielded by bone, so it is more accessible to noninvasive imaging. Our latest research unearths new details about the eye-brain connection.”

Tau

Tau is a protein that helps stabilize the structure of nerve cells in the brain and the retina and is one of the key markers of Alzheimer’s disease. When tau disengages from nerve cells it can form tangles that interfere with cellular function and contribute to cognitive decline.

In a study published in the peer-reviewed journal Acta Neuropathologica, Koronyo-Hamaoui and fellow investigators compared retinal tissue from 45 patients diagnosed with Alzheimer’s-related cognitive impairment or dementia with tissue from 34 individuals with normal cognition or non-Alzheimer’s forms of dementia.

Investigators found that higher levels of abnormal tau in the retina corresponded to levels of tau in the brain, other brain changes related to Alzheimer’s disease, and cognitive decline.

Vessels and amyloid plaques

Clumps of a protein called beta-amyloid, also known as amyloid plaques, are another hallmark of Alzheimer’s disease.

In a study published in the peer-reviewed journal Acta Neuropathologica Communications, Koronyo-Hamaoui and co-investigators used leading-edge imaging and image-processing technology to compare amyloid plaques in the retinas of living patients who had early-stage cognitive impairment with those in individuals who had normal cognition.

Thirty-four patients underwent retinal and brain imaging, and cognitive testing. Analysis in 28 patients revealed two to three times as many plaques clustered near blood vessels in the retinas of patients with mild cognitive impairment or Alzheimer’s disease when compared with individuals with normal cognition. The numbers and position of the plaques correlated with cognitive decline and physical changes in the brain.

Diagnosis in development

Koronyo-Hamaoui’s team also published a review article in the peer-reviewed journal Progress in Retinal and Eye Research that detailed additional Alzheimer’s disease biomarkers that have been identified in the retina.

These include reduced blood flow, deposits of amyloid-beta proteins inside blood vessel walls, damage to the barrier that prevents harmful substances from entering retinal tissue, inflammation, and damage to nerve cells.

“Imaging technology now being developed will allow us to see these changes in patients in clinical settings,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai and co-author of these studies. “This technology, which is noninvasive and affordable, allows us to see changes in the cells and blood vessels in tremendous detail.”

Black and Koronyo-Hamaoui envision this technology as a tool to screen patients in primary care settings, with those who show features suggestive of Alzheimer’s disease referred for additional testing, such as a PET brain scan or cerebrospinal fluid or blood test. The technology could also assess disease progression and the effectiveness and safety of new treatments.

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“Abstraction allows us to ignore irrelevant details and focus on the information we need in order to act, and inference is the use of knowledge to make educated guesses about the world around us,” said Ueli Rutishauser, PhD, professor and Board of Governors Chair in Neurosciences at Cedars-Sinai and co-corresponding author of the study. “Both are important parts of cognition and learning.”

Humans often use these two cognitive processes together to rapidly learn about and act appropriately in new environments. One example of this is an American driver who rents a car in London for the first time.

“The English drive on the right-hand side of the car and on the left-hand side of the road, the opposite of the way we do in the U.S.,” Rutishauser said. “For someone from the U.S., driving in London means reversing many of the rules they have learned, and making that mental shift requires abstraction to focus on driving-sidedness, and making inferences to avoid pulling directly into oncoming traffic.”

In the study, investigators worked with 17 hospitalized patients who had electrodes surgically implanted in their brains as part of a procedure to diagnose epilepsy. In total, the researchers recorded the firing of thousands of brain cells as participants performed an inference task on a computer.

Looking at the activity of so many brain cells required the use of artificial intelligence to extract the responses that were relevant, allowing investigators to see the coordination between the neurons during successful inference.

“These are high-dimensional geometrical shapes that we cannot imagine or visualize on a computer monitor,” said Stefano Fusi, PhD, a principal investigator at Columbia University’s Zuckerman Mind Brain Behavior Institute and co-corresponding author of the study. “But we can use mathematical techniques to visualize simplified renditions of them in 3D.”

During the recordings, participants were repeatedly shown four pictures—a person, a monkey, a car and a watermelon. In response to each picture, they were asked to press a left-hand or right-hand button. Individuals then received a “correct” or “incorrect” message.

Through repetition, participants eventually learned the correct response for each of the four pictures. At that point, the rules of the game were reversed without the participants being informed, and the opposite response for each picture was counted as correct.

After the switch, some participants were able to quickly figure out the rule change and infer the correct responses without relearning them, meaning they performed inference.

Investigators saw striking geometric patterns in the brains of those participants. Groups of neurons were firing together, much like birds flying in formation or a crowd of people spontaneously taking up a chant at a sporting event. The way the neurons coordinated their activity and encoded the relevant information indicated that the subjects had gained the conceptual knowledge needed to perform the task. Investigators saw no such patterns in the brains of participants who were not successful in using inference.

“Building conceptual knowledge is an important aspect of learning,” said Hristos Courellis, PhD, a researcher at Cedars-Sinai and first author of the study. “In our study, we identified a neural basis for this process, which in cognitive psychology is referred to as abstraction.”

Some subjects were initially not able to perform inference from experience with the task alone. For these subjects, investigators provided verbal instructions that allowed the subjects to then infer the correct answers.

“A remarkable discovery was that the same neural geometries emerged in participants who received verbal instructions as in those whose ability to infer was based on experiential learning,” said Adam Mamelak, MD, director of the Functional Neurosurgery Program and professor of Neurosurgery at Cedars-Sinai and co-author of the study. “This crucial discovery shows that verbal input can result in neural representations that otherwise might take a long time to learn through experience.”

The study, which relied on data from Cedars-Sinai and the University of Toronto, was led by Cedars-Sinai and conducted as part of a multi-institutional consortium funded by the National Institutes of Health’s The Brain Research Through Advancing Innovative Neurotechnologies Initiative, or The BRAIN Initiative.

“This study provides new insights into how our brains allow us to learn and carry out tasks flexibly and in response to changing conditions and experiences,” said Merav Sabri, PhD, program director for The BRAIN Initiative. “These insights build on the body of knowledge that could one day lead us toward interventions for neurologic and psychiatric conditions that involve deficits in memory and decision-making.”

A surprise to investigators was the discovery that these particular patterns of brain activity emerged only in the hippocampus, a region deep in the center of the brain that is known to be crucial for the formation of new long-term memories.

“Our finding expands our knowledge of the role of the hippocampus in learning,” Rutishauser said. “This is the first direct demonstration of the involvement of the human hippocampus in the learning of abstract knowledge and inference behavior. Many neurological conditions, including Alzheimer’s disease, obsessive-compulsive disorder and schizophrenia, affect this brain region, and our finding could help explain the impaired decision-making we see in these patients.”

Additional Cedars-Sinai authors include Juri Minxha, and Chrystal M. Reed.

Other study authors include Araceli R. Cardenas, Daniel Kimmel, Taufik A. Valiante, and C. Daniel Salzman.

Funding: This work was supported by The BRAIN Initiative through the NIH Office of the Director (U01NS117839 to U.R.) and the Simons Foundation Collaboration on the Global Brain (to S.F., and U.R.).

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“I am excited to have Dr. Tuchman as a partner in elevating and building the Cedars-Sinai Spine Center,” Skaggs said. “I have enjoyed partnering with Dr. Tuchman in research, educating the next generation of spine surgeons, and in the operating room. It takes a comprehensive team including both neurosurgical and orthopedic spine expertise to build on our foundation of leading-edge research while at the same time providing the highest-quality clinical care.” 

Tuchman, an assistant professor of Neurosurgery at Cedars-Sinai, attended medical school at the University of Miami Miller School of Medicine and completed his neurosurgery fellowship at the University of Southern California. Before joining Cedars-Sinai in 2018, Tuchman also completed a spine deformity fellowship at Columbia University Medical Center in New York.

It was during his residency that Tuchman discovered the complexity, challenges and rewards of providing adult spinal care, and he did extra training in treatment of spinal malalignments and deformities such as scoliosis, sagittal plane deformities and flat back syndrome.

“These surgeries have impressive impacts on people’s quality of life,” Tuchman said. “The spine is the center connection point for your extremities and brain, and anytime there's a structural issue, it can cause devastating consequences. With reconstructive spine surgery, we can often restore function and relieve pain, taking someone who is basically homebound, or even bedridden, and getting them back out into the world.”

Tuchman also conducts research focused on outcomes for spine surgery patients, and treats adult patients with rare spinal conditions such as achondroplasia, a genetic condition that truncates the growth of the arms and legs and is the most common form of short-limbed dwarfism.

He said proper selection of spine patients—and treatments—is paramount. An open dialog between the patient and the surgeon is essential so that the patient feels comfortable expressing their wants and needs and the surgeon can adapt a treatment plan to address those things.

“One of the biggest challenges for a spine surgeon is determining whether we can genuinely help,” Tuchman said. “If a patient’s spine problem is not going to respond well to spine surgery, then that person shouldn't have spine surgery, and if a spinal malalignment isn’t affecting the patient’s quality of life, perhaps it does not need to be treated.”

Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai, said that the robust resources of Cedars-Sinai and Cedars-Sinai Spine Center also are key factors in quality care.

“Spine surgery is a team sport and we have internists, cardiologists, physical and occupational therapists, anesthesiologists, surgical technicians, pain specialists, hospitalists, and top-notch nurses working with our surgeons to care for hundreds of spine surgery patients each month,” Black said. “Dr. Tuchman taking the reins as co-leader means continued excellence for the team and the best possible outcomes for our spine patients.”

Read more on the Cedars-Sinai Blog: Seeking a Second Opinion for a Spine Condition

“After several decades of research, we understand that Alzheimer’s disease is not going to be easy to conquer,” said Zaldy Tan, MD, MPH, director of The Maxine and Bernard Platzer Lynn Family Memory and Healthy Aging Program. “There is no magic infusion, injection or pill that will cure it, but there are tactics to prevent or reduce one’s risk for it. While we continue to search for a viable path for stopping this disease in its entirety, prevention is of the utmost importance.”

An estimated 6.7 million Americans are living with Alzheimer’s disease, according to the National Institutes of Health. As advances in medicine and disease prevention are helping more people live longer and reach the age—65 and older—at risk for developing Alzheimer’s disease and dementia, Cedars-Sinai’s healthy aging program focuses on personalized risk profiling using clinically validated tools.

Risk factors for developing Alzheimer’s disease or dementia include family history of the disease, a gene called APOE4, diabetes, high blood pressure, sleep apnea, unhealthy weight, history of traumatic brain injury or head trauma, and social isolation.

The Cedars-Sinai program is open to anyone 40 to 60 years old with at least two of these risk factors, and anyone 60 or older who doesn’t have signs of Alzheimer’s disease or dementia but wants to protect their brain health.

Prior to their first clinic visit, patients complete a questionnaire that delves into their physical activity, diet, social networking, history of physical and emotional trauma, and level of education, among other things.

During the clinic visit, Tan and colleagues perform a detailed physical and neurological exam and cognitive tests. They also assess each patient’s grip strength, how many times they can sit in a chair and stand up again unsupported in 30 seconds, their level of frailty and risk of falling. Some patients are sent home with digital devices to continuously measure blood pressure, sleep patterns and oxygenation during sleep.

“These are things that are not necessarily asked about in primary care, or even in general neurology clinics,” said Tan, who is also medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders and the Carmen and Louis Warschaw Endowed Chair in Neurology at Cedars-Sinai. “We use clinically validated tools to evaluate each individual’s risk and resilience factors. And based on that information, we teach them strategies to reduce their risk and maintain brain health.”

The team includes a dietitian to help participants improve their eating habits, a health psychologist who assists with behavior change issues such as smoking cessation, sleep specialists, and an occupational therapist who helps participants understand how their brains work and offers cognitive training to improve memory habits. Patients also can be referred to other specialists, including those from the Smidt Heart Institute at Cedars-Sinai, as brain and heart health are closely linked, Tan said.

“Studies show that as many as 40% of cases of Alzheimer’s disease and related dementias can be prevented or delayed with the right clinical guidance,” said Nancy L. Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “We launched this program to help our patients optimize their brain health throughout life, and also to push the science forward through continued translational research.”  

Tan noted that recommendations and referrals are personalized and specific to each patient. He said that everyone is different, and while some people have more areas to improve on and others have fewer, everyone has something.

“We want to help people take preventive action as early as possible,” Tan said. “Delaying the onset of Alzheimer’s disease for even five to eight years is tantamount to a cure for many people, because the greatest risk is in those ages 80 and up. Those who delay onset until their late 80s might avoid it altogether.”

Read more on the Cedars-Sinai Blog: When Should I Be Concerned About Memory Loss?

This could lead to new applications for the therapy, allowing it to influence higher-level functions such as learning and memory.

“Deep brain stimulation has typically been used to overexcite or shut down all neurons in a target area,” said Costas Anastassiou, PhD, associate professor of Neurology, Neurosurgery and Biomedical Sciences at Cedars-Sinai and senior author of the study. “We found that by varying the shape of the electrical pulse waves we apply, we can selectively influence specific neuron types while leaving others unaffected.”

In the study, investigators applied electrical fields to individual cells in tissue samples from the visual cortex and the hippocampal regions of the brains of patients and laboratory mice. The investigators recorded the activity of excitatory and inhibitory neurons, which act as the gas pedal and brakes, respectively, in brain circuits.

Results showed that different electrical wave frequencies influenced the timing of spikes, which are changes in electrical voltage that travel down neuron fibers and are transmitted to other neurons. Anastassiou called spikes “the coin of communication between neurons.”

“We found that electrical frequencies that influenced one cell type did not necessarily influence another, and vice versa,” Anastassiou said. “Surprisingly, the effects on each cell type were the same in both brain areas we examined, and in both species—though more pronounced in humans than in mice.”

Given that previous research has found that higher-level functions in the brain require coordination and communication between different cell types, the ability to manipulate this communication could be of great importance, Anastassiou said.

“This study offers new understanding of how to stimulate the human brain to promote or suppress specific activity patterns, and could pave the way for new directions in basic research and clinical applications,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai. “These results offer the possibility for electrical protocols that are more selective, more controlled, and allow for different parts of the brain neural network to be manipulated in different ways.”

Investigators are now working to determine the exact mechanisms required to produce various results in the brain, and to replicate their brain tissue experiments in living patients.

“This data supports the idea that electrical brain stimulation could be used in new ways that target specific groups of brain cells,” said Adam Mamelak, MD, director of the Functional Neurosurgery Program at Cedars-Sinai. “This gives us an exciting opportunity to imagine new uses for this therapy and the chance to address disorders involving learning and memory.” 

Other Cedars-Sinai authors involved in the study include Konstantinos Kozalakis, PhD.

Funding: This work was supported by National Institutes of Health grants R01 NS120300 and RO1 NS130126.

Conflict of interest: Anastassiou is listed as an inventor on a patent application related to this work.

Learn more on the Cedars-Sinai Blog: A Patient’s Journey With Deep Brain Stimulation

How do you know you’re having a stroke?

Know the symptoms, says Shlee S. Song, MD, director of the Comprehensive Stroke Center and the Telestroke Program at Cedars-Sinai.

Unfortunately, while many people are on the lookout for well-known symptoms such as paralysis on one side of the body or face, some 20% of strokes don’t cause those symptoms, Song said. Called posterior circulation strokes, they occur in the arteries that supply blood to the back of the brain and are often mistaken for other ailments.

Song sat down with the Cedars-Sinai Newsroom to discuss the signs and symptoms of this under-recognized type of stroke.

How are symptoms of posterior circulation stroke different from the symptoms that people recognize for other stroke types?

Patients with posterior circulation stroke can appear as if intoxicated or on a rocking boat, with dizziness, loss of balance and coordination, and nausea. Posterior circulation stroke can also cause larger blind spots, double vision, hearing loss, and trouble with swallowing.

To help people recognize signs of all types of stroke, we use the acronym BE FAST. This stands for “balance” and “eyes,” which are signs of posterior circulation stroke, plus “face,” “arms,” and “speech,” which are more commonly recognized stroke signs. The T is for “time,” because if you suspect someone is having a stroke, it is time to call 911.

What makes posterior circulation strokes particularly dangerous?

Because of the more subtle symptoms to witnesses or bystanders, these strokes are more likely than other stroke types to be misdiagnosed or delayed in diagnosis. It's very common for these patients to miss the time window for treatment—which can mean permanent disability or even death. Some people assume the tipsiness and loss of balance are due to a sedative or sleeping pill they took, or maybe an inner ear issue. Because of the gastrointestinal symptoms, some patients may assume that it is something they ate, or a GI infection. People experiencing vision changes might go first to the ophthalmologist or optometrist. Sometimes even patients who come to the emergency department have their diagnosis delayed because they are in a bed or on a stretcher, and it takes some time to determine that they have loss of balance or coordination because walking assessments are not often part of stroke screening.

How can people tell the difference between posterior circulation stroke and these other conditions?

While a gastrointestinal infection, inner ear problem or vision problem usually comes on gradually and builds over time, strokes happen suddenly. Stroke symptoms hit patients like a lightning bolt, out of the blue.

What treatments are available for posterior circulation stroke?

If a patient has a clot, we have drugs that can dissolve it and get the blocked vessel open. If the patient’s clot is too large to be dissolved with medication, our interventional colleagues can go in with a catheter and remove the clot. If a patient has a burst blood vessel, we can make sure their blood pressure is controlled and reverse the action of any blood thinners they might be taking. This prevents blood from accumulating in that smaller area in the back side of the head, where space is limited. Swelling that can occur after a posterior circulation stroke can compress critical brain structures.

What are the risk factors for posterior circulation stroke?

Some are similar to risk factors for other stroke types. Uncontrolled high blood pressure, high cholesterol, and diabetes all increase risk for stroke. For posterior circulation stroke, sudden trauma to the neck can also increase risk for artery dissection. Common causes of this include car accidents, whiplash injuries and sports neck trauma. These types of injuries can cause a tear in the inner wall of an artery. Clots can form around the vessel tear and block blood flow.

So be gentle with the neck. Avoid chiropractic neck manipulations and deep tissue massage at the neck, because such critical blood vessels are there. Take care with inversions in yoga and Pilates, and in martial arts classes where there might be twisting or hyperextending of the neck. If it feels uncomfortable, that's your body signaling to say this neck turn is probably a little too much.

And if you are injured, especially if you experience any loss of function, no matter how temporary, you need an appropriate evaluation. This should include blood vessel studies to look at the flow inside the blood vessels, so that we can see if there is a vessel tear or blockage.

Learn more on the Cedars-Sinai Blog: Strokes That Are Treatable—and Beatable

as director of Electromyography.

Jabari comes to Cedars-Sinai from the University of Kansas Medical Center, where he was associate director of the Neuromuscular Medicine Fellowship.

“We are delighted to add Dr. Jabari’s expertise in neuromuscular medicine and as a mentor to the next generation of neuromuscular clinicians to our department,” said Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “His planned collaboration with our Department of Pathology is certain to help further our understanding of these disorders and improve outcomes for patients.”

The breadth and depth of neuromuscular medicine—dedicated to treating a broad variety of genetic, neurodegenerative and autoimmune disorders affecting the nerves and muscles—helped attract Jabari to the specialty.

“We have a good understanding of some of these disorders, but are still learning about others,” Jabari said. “Neuromuscular medicine offers an opportunity to conduct research and translate our results to better care for our patients. This research can include electrodiagnostic studies and studies of nerve, muscle and skin biopsies, making good use of my training and interest in pathology.”

Electromyography is a diagnostic tool used to detect neuromuscular abnormalities and help diagnose neuromuscular disorders.

Some neuromuscular conditions are acquired, while others are inherited. Jabari’s specific interest is in autoimmune neuromuscular disorders. He was principal investigator of a recent study of a new therapy for inclusion body myositis, a disease with inflammatory and degenerative features. The condition causes progressive muscle weakness and currently has no approved treatment. He has also been involved in clinical trials of other inflammatory myopathies and clinical care for Sjogren’s syndrome, a rheumatological condition where the immune system attacks glands that make moisture in the eyes and mouth, and is also known to cause multiple neurological complications.

Jabari attended medical school at Tishreen University in Syria, then completed his neurology residency at the University of Texas Health Science Center at Houston and his fellowship in neuromuscular medicine at the University of Kansas Medical Center.

Read more on the Cedars-Sinai Blog: Specialized Care for Neuromuscular Disorders

The study detailing their discovery was published in the peer-reviewed journal Nature.

“We have identified for the first time a group of neurons, influenced by two types of brain waves, that coordinate cognitive control and the storage of sensory information in working memory,” said Jonathan Daume, PhD, a postdoctoral scholar in the Rutishauser Lab at Cedars-Sinai and first author of the study. “These neurons don’t contain or store information, but are crucial to the storage of short-term memories.”

Working memory, which requires the brain to store information for only seconds, is fragile and requires continued focus to be maintained, said Ueli Rutishauser, PhD, director of the Center for Neural Science and Medicine at Cedars-Sinai and senior author of the study. It can be affected by different diseases and conditions.

“In disorders such as Alzheimer's disease or attention-deficit hyperactivity disorder, it is often not memory storage, but rather the ability to focus on and retain a memory once it is formed that is the problem,” said Rutishauser, who is a professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai. “We believe that understanding the control aspect of working memory will be fundamental for developing new treatments for these and other neurological conditions.”

To explore how working memory functions, investigators recorded the brain activity of 36 hospitalized patients who had electrodes surgically implanted in their brains as part of a procedure to diagnose epilepsy. The team recorded the activity of individual brain cells and brain waves while the patients performed a task that required use of working memory.

On a computer screen, patients were shown either a single photo or a series of three photos of various people, animals, objects or landscapes. Next, the screen went blank for just under three seconds, requiring patients to remember the photos they just saw. They were then shown another photo and asked to decide whether it was the one (or one of the three) they had seen before.

When patients performing the working memory task were able to respond quickly and accurately, investigators noted the firing of two groups of neurons: “category” neurons that fire in response to one of the categories shown in the photos, such as animals, and “phase-amplitude coupling,” or PAC, neurons.

PAC neurons, newly identified in this study, don’t hold any content, but use a process called phase-amplitude coupling to ensure the category neurons focus and store the content they have acquired. PAC neurons fire in time with the brain’s theta waves, which are associated with focus and control, as well as to gamma waves, which are linked to information processing. This allows them to coordinate their activity with category neurons, which also fire in time to the brain’s gamma waves, enhancing patients’ ability to recall information stored in working memory.

“Imagine when the patient sees a photo of a dog, their category neurons start firing ‘dog, dog, dog’ while the PAC neurons are firing ‘focus/remember,’” Rutishauser said. “Through phase-amplitude coupling, the two groups of neurons create a harmony superimposing their messages, resulting in ‘remember dog.’ It is a situation where the whole is greater than the sum of its parts, like hearing the musicians in an orchestra play together. The conductor, much like the PAC neurons, coordinates the various players to act in harmony.”

PAC neurons do this work in the hippocampus, a part of the brain that has long been known to be important for long-term memory. This study offers the first confirmation that the hippocampus also plays a role in controlling working memory, Rutishauser said.

This study was conducted as part of a multi-institutional consortium funded by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies Initiative, or the BRAIN Initiative, and led by Cedars-Sinai. The data in this study is pooled across Cedars-Sinai, the University of Toronto, and the Johns Hopkins School of Medicine, resulting in a statistically powerful study that a single institution could not accumulate on its own given the difficulty of these experiments.

"One of the aims of the BRAIN Initiative is to uncover—through the use of innovative technologies—properties of the human brain that have so far been difficult, if not impossible, to study,” said Dr. John Ngai, PhD, director of the NIH BRAIN Initiative. “Here, by leveraging unusual opportunities supported by the initiative to illuminate complex processes in humans, the Rutishauser Lab is shedding light on the way certain neurons support how memories are stored in the brain—a process that is far from understood in devastating brain disorders such as Alzheimer’s disease and other dementias.”

Other Cedars-Sinai authors involved in this study include Jan Kaminski, Umais Khan, Michael Kyzar, Chrystal Reed, and Adam Mamelak. Also involved in the study were Andrea Schjetnan and Taufik Valiante of the University of Toronto, and Yousef Salimpour and William Anderson of Johns Hopkins School of Medicine.

Funding: This work was supported by a German National Academy of Sciences Leopoldina Postdoctoral fellowship, a Cedars-Sinai Center for Neural Science and Medicine Postdoctoral fellowship, National Institute of Neurological Disorders and Stroke BRAIN initiative grants number U01NS103792 and U01NS117839, and National Science Foundation grant number BCS-2219800.

Conflict of interest: Authors declare no competing interests.

Read more on the Cedars-Sinai Blog: When Should I Be Concerned About Memory Loss?

Neuroprosthetics, a technology that allows the brain to control external devices such as robotic limbs, is beginning to emerge as a viable option for patients disabled by amputation or neurological conditions such as stroke. Cedars-Sinai investigators, in a study published in the peer-reviewed journal

“Neuroprosthetics have largely tapped the brain’s outermost cerebral cortex. The cerebellum has a well-known role in movement but has been ignored in neuroprosthetic research,” said Tanuj Gulati, PhD, assistant professor of Biomedical Sciences and Neurology and researcher in the Center for Neural Science and Medicine at Cedars-Sinai, and senior author of the study. “We are the first to record what is happening in the cerebellum as the brain learns to manipulate these devices, and we found that its involvement is essential for device use.”

Patients who use neuroprosthetic devices have electrodes permanently implanted in the portion of the brain—usually the cerebral cortex—that controls movement for the function the device is replacing. This technique can be used to help patients control a robotic limb, a motorized wheelchair or a computer keyboard, among other devices.

To learn how the cerebellum helps in learning neuroprosthetic control, Gulati and his team trained laboratory rats to use only their motor cortex activity to move a neuroprosthetic tube that delivered them water. The rats had electrodes implanted in the motor cortex and the cerebellum, and investigators listened in on the activity of neurons in both brain regions during the experiments.

“We found that activity of the neurons in the cerebellum was coordinated with the motor cortex, and that activity in the cerebellum was critical for neuroprosthetic task performance,” said Aamir Abbasi, PhD, a postdoctoral scientist in the Gulati Lab and the first author of the study.

Investigators next used an advanced technology called optogenetics to selectively silence different neuron populations in the laboratory rats’ brains during experiments. Optogenetics delivers light-sensitive proteins into brain cells, allowing light exposure to control these cells’ activity.

When they silenced neurons in the outer layer of the cerebellum, where the cerebellum receives input from other brain regions, they found that the laboratory rats had a difficult time learning to control movement of the pipe. When they silenced neurons deep in the cerebellum, which are responsible for outward communication from the cerebellum to the motor cortex, the rats had difficulty maintaining accurate control of the pipe.

“These results could help make neuroprosthetics an option for patients with damage to the motor cortex due to brain injury, stroke or diseases such as Parkinson’s or multiple sclerosis,” said Nancy L. Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “It’s possible that, eventually, implants in the cerebellar region could be used to help these patients manipulate external devices.”

It’s an exciting era for neuroprosthetics, said David Underhill, PhD, chair of the Department of Biomedical Sciences at Cedars-Sinai.

“There is a lot of buzz about neuroprosthetic technology, but there are still many unsolved problems,” Underhill said. “This study suggests that some of those could be resolved by involving the cerebellum as well as the motor cortex to help patients gain use of neuroprosthetic devices more quickly and improve their ability to control them accurately.”

Other authors involved in the study include Rohit Rangwani, Daniel W. Bowen, Andrew W. Fealy, and Nathan P. Danielsen.

This work was supported by American Heart Association postdoctoral fellowship 897265, American Heart Association predoctoral fellowship 1018175, American Heart Association career development award 847486, National Institutes of Health grants R00NS097620 and R01NS128469, National Science Foundation grant 2048231, and a Cedars-Sinai Medical Center’s Center for Neural Science and Medicine postdoctoral fellowship.

No conflicts of interest to disclose.

Read more on the Cedars-Sinai Blog: Bolster Your Brain by Stimulating the Vagus Nerve

The Rutishauser Lab collaborates with several leading universities and medical centers, including the California Institute of Technology, Johns Hopkins University, the University of Toronto, Boston Children’s Hospital and the University of Colorado at Denver. A key aspect of this collaboration is open data-sharing. Cedars-Sinai is part of the National Institutes of Health BRAIN Initiative Research Opportunities in Humans Consortium, representatives of which recently penned an article for the peer-reviewed journal Neuron on the benefits of data-sharing.

“Dr. Rutishauser’s work advances our understanding of the workings of the human brain and also connects Cedars-Sinai with top medical institutions across the country and beyond,” said Jeffrey Golden, MD, vice dean of Research and Research Education at Cedars-Sinai. “Work of this caliber simply isn’t possible if institutions guard their discoveries and data, encumbering collaboration.”

Rutishauser, who holds the Board of Governors Chair in Neurosciences, sat down with the Cedars-Sinai Newsroom to discuss the role of data-sharing and scientific collaboration in his work and the broader scientific community.

What type of data does your lab’s research generate, and how has it advanced our understanding of the human brain?

Our data is acquired from patients with epilepsy who are undergoing depth-electrode monitoring, which means they have tiny electrodes surgically inserted into the brain to monitor seizure activity.

We use these recordings of the electrical pulses sent between individual neurons within the brain to study how the brain records and recalls memories, how we make decisions, and how these processes go wrong under certain conditions. For example, we have discovered how we monitor our own behavior for errors using this approach.

The same data, which is rare and difficult to acquire, can also be used to study many other aspects of the human brain, but this is only possible if the data is made accessible to other investigators inside and outside of Cedars-Sinai.

What is the current state of data-sharing in human neuroscience?

Funding agencies and journals require that research teams make their data available to others. However, they require sharing of only the exact data needed to reproduce a given study, often only on request.

This requirement is often viewed as a burden by investigators. But in our recent editorial, we point out the many benefits of investigators sharing all of their data freely and in a standardized format, so it is easily accessible. We found that when we, as the data producer, released data in this way, we discovered new collaborators who used our data to explore questions we had never thought about. Within our own lab, using a standardized data format also facilitated reuse of that data. And schools and universities have even used the data for teaching purposes.

Why is cross-institutional collaboration so important to the future of science?

Collaborating and sharing data is a way for us to broaden our impact. One of the inherent difficulties of the work I do is that the experiments are challenging to perform and the number of patients available is limited. To increase the amount of data available, we collaborate with research groups at other institutions. This allows us to perform large, well-powered studies and increases confidence in our findings by replicating findings at other institutions.

What challenges need to be overcome to increase data-sharing in neuroscience?

There are three challenges. First, the field has to agree on a standard data format. While there are formats that could fill this requirement, there’s no universal agreement on which should be the standard format. The use of a single standard data format in the field of neuroimaging, for example, shows the immense benefits of the practice. Second, we need data archives where very large files can be uploaded, stored and made available. Third, and perhaps most challenging, investigators must be willing to openly share their data.

What is your advice for investigators who want to share their data?

I strongly advise using a standardized data format. We chose to use the Neural Data Without Borders (NWB) format. Develop an expectation in your lab that when a project is finished, your team will export the data in that format, document it and publicly release it upon publication.

Strickler launched her own art studio shortly after graduating from the prestigious School of the Art Institute of Chicago in the late 1980s. She painted murals at more than 100 Chicago restaurants, hotels, nightclubs and bars, and relocated to Southern California shortly before her seizures began in 2007.

“Every month or so, I would have another seizure and wake up in the hospital about four days later,” Strickler said. “Little by little, the business I had built up came to a halt. After a seizure caused a major car crash where, thankfully, no one was killed, I had to give up driving. My life was absolutely leveled.”

Jeffrey M. Chung, MD, director of the Epilepsy Program at Cedars-Sinai, met Strickler in 2019 when she was referred by a former Cedars-Sinai resident.

“Syril had been prescribed many different medications and they were not controlling her seizures, which were frequent and severe,” Chung said. “If a patient’s seizures aren’t controlled by the first two medications they try, there is less than a 5% chance that additional medications will help. It was time to look into other treatment options.”

To locate the exact point in Strickler’s brain where her seizures were originating, the epilepsy team first monitored her seizure activity using EEG electrodes attached to her scalp. When that didn’t yield enough information, Adam N. Mamelak, MD, director of the Functional Neurosurgery Program at Cedars-Sinai, implanted electrodes at various locations in Strickler’s brain to make more precise recordings possible.

During a hospital stay of several days, Strickler also volunteered to assist Cedars-Sinai investigators by performing experimental tasks similar to computer games while they recorded the activity of cells in different regions of her brain—something possible only in patients who are undergoing invasive EEG monitoring.

“The data from these experiments is rare and precious, and allows us to discover how the brain works,” said Ueli Rutishauser, PhD, director of the Center for Neural Science and Medicine at Cedars-Sinai. “We have used this data to gain insights into how the brain records and recalls memories, how it makes decisions, and how these processes go wrong in certain conditions. And for the patients, we’ve found it is uplifting and empowering, because it gives them the chance to contribute to science and possibly help develop new treatments that help future patients.”

Strickler said that working with the research team helped brighten her time in the Epilepsy Monitoring Unit. “We had a great time, and I still keep in touch with them,” she said. “It was neat that I got to be involved in that.”

If a patient’s epileptic seizures originate from a single point in the brain, surgeons can remove a tiny portion of tissue at that point to stop them. Because Strickler’s seizures were coming from two points, Mamelak suggested an alternative treatment called neuromodulation.

“We found that most of Syril’s seizures were originating in the right hippocampus, but some were coming from the left,” Mamelak said. “We placed permanent electrodes in each of those locations. They are connected to a tiny device implanted in her skull that detects seizures just as they are starting and delivers electrical pulses to shut them down.”

Mamelak said that advanced imaging and robotic surgery have significantly reduced the risks from these procedures, and that patients have more treatment options than ever before. Chung noted that long-term neuromodulation with the device used to treat Strickler results in at least a 50% reduction in seizures for more than 70% of patients. Strickler has been seizure-free for more than a year.

“I’m busy painting again and am about to graduate from Ventura Adult and Continuing Education with a certificate in print and web design. I just started a new job doing video painting tutorials for an L.A.-based manufacturer of plasters and decorative paints,” Strickler said. “And after 6 ½ years without a driver’s license, I am able to drive. I feel like I’ve been given an absolute miracle.”

Chung, who has now begun weaning Strickler off her anti-seizure medications, urges patients who have tried more than two medications and are still having seizures to seek out an evaluation at an epilepsy center.

“With a proper evaluation, you can learn what your options for treatment are and make a conscious choice,” Chung said. “The saddest thing is when we have options that could stop a patient’s seizures, and they're not being evaluated for those options.”

Read more on the Cedars-Sinai Blog: Personalized Epilepsy Treatment for Each Child

in the Department of Neurology at Cedars-Sinai. She will treat patients with Alzheimer’s disease and related dementias as well as lead research programs aimed at preserving cognition across the lifespan.

“Dr. Gonzales will be instrumental in strengthening our research infrastructure that follows individuals through the cognitive continuum so that we can more fully understand the biology of Alzheimer’s disease,” said Zaldy Tan, MD, MPH, medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders. “She will also help us expand our research diversity so that our discoveries more closely represent the broad spectrum of communities we serve.”

Gonzales is also part of the Center for Translational Geroscience at Cedars-Sinai, a multidisciplinary effort that focuses on preventing age-related disease and improving health and wellness for older adults.

“Innovative research and integrated clinical care are key to our mission to enable a life free from significant disease or disability,” said Sara Espinoza, MD, director of the Center for Translational Geroscience. “Dr. Gonzales’ neuropsychology background and expertise in research and patient care will be an important contribution to these efforts.”

Neuropsychologists study how the biology of the brain and nervous system relate to behavior and cognition. 

“Biology is extremely important to our cognitive trajectory in life and whether we decline faster as we age,” Gonzales said. “But our environment is also crucial in shaping synaptic plasticity—the ability of our brain cells to form new connections—throughout the lifespan. My interest is in exploring the role of biology and environment in age-related brain changes.” 

Gonzales comes to Cedars-Sinai from The University of Texas Health Science Center at San Antonio, where she was an assistant professor in the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases and the Department of Neurology. She earned her PhD in clinical psychology from the University of Texas at Austin. She completed her pre-doctoral internship at the University of Illinois at Chicago and postdoctoral fellowship in clinical neuropsychology at the VA Northern California Health Care system.

“A multidisciplinary approach is critical for diagnosing and treating complex neurodegenerative disorders,” said Nancy Sicotte, MD, chair of the Department of Neurology at Cedars-Sinai. “As the Jona Goldrich Center for Alzheimer’s and Memory Disorders and the Center for Translational Geroscience continue to grow, the addition of clinician-scientists such as Dr. Gonzales puts us in the best possible position to offer innovative memory care to our patients.” 

Gonzales finds patient care an important element in her work.

“I love the fact that neuropsychology offers me the opportunity to work directly with individuals grappling with the changes associated with cognitive decline, and to conduct research that moves the science forward and brings better care to these patients,” Gonzales said. “That one-on-one patient contact keeps the urgency of the work that we're doing in focus.”

Gonzales helps patients and families understand the opportunity presented by clinical trials and the need for long-term planning to ensure that patients’ wishes are communicated and the necessary supports are in place to accommodate changes that might be on the horizon.

“I tell patients and families that this is going to be a journey together,” Gonzales said, “and I try to always give a message of hope.”

She predicts significant innovation and transformation in the landscape of Alzheimer’s disease diagnosis and treatment over the next decade.

“One of the most exciting developments that I think will come to full fruition within the next few years is the validation of an inexpensive blood-based screening test for Alzheimer's disease,” Gonzales said. “This will help us engage people in research at earlier stages, before disease symptoms show up, and to detect very early changes that might lead to new therapeutic targets.”

Read more on the Cedars-Sinai Blog: How to Help a Loved One With Alzheimer’s or Dementia

Multiple sclerosis is a disease of the brain and spinal cord in which the body’s immune system attacks the protective sheaths that surround nerves, disrupting communication between the brain and the rest of the body. Brain imaging, which allows physicians to see the lesions that form at the point of attack, is essential for diagnosing the condition and guiding patient treatment.

Sicotte and Sati are among co-authors of a consensus statement from the North American Imaging in MS Cooperative that seeks to standardize imaging techniques for identifying chronic active lesions, an important indicator of chronic brain inflammation in MS. The statement, published in the peer-reviewed journal Brain, is designed to set guidelines for imaging chronic active lesions and how imaging will be used for diagnosis, predicting patient outcomes, and clinical trials.

They recently spoke with the Cedars-Sinai Newsroom about the role of imaging in MS today and in the future.

How has imaging changed treatment for patients with MS?

Sicotte: When I started treating patients with MS more than two decades ago, there were essentially no treatments, and now we have more than 25. One of the reasons we have these medications is because of advancements in the use of MRI to track disease activity in the brain and spinal cord of people who have MS. Because MRI is more sensitive than clinical attacks, it became a powerful tool to test the effectiveness of new therapies, and that energized research and led to the development of a whole suite of new MS treatments that decrease the likelihood of new lesions appearing.

How do lesions appear on an MRI?

Sicotte: In patients with active MS, the blood-brain barrier, which keeps potentially harmful substances from reaching the brain, breaks down due to immune activation. This results in what we call a contrast-enhancing lesion, the classic acute inflammatory lesion. These lesions show up as bright spots that are easily detected using MRI after injection of contrast. Over time, the blood-brain barrier repairs itself and leaves behind a chronic lesion that is akin to a scar that can also be tracked over time using dedicated MRI techniques.

What are the newest lesions that have been identified?

Sati: We and others have recently identified a new type of lesion, called a paramagnetic rim lesion, that we think is an indicator of chronic brain inflammation that may be the primary driver of disease progression in treated patients who do not have acute inflammatory lesions.

In paramagnetic rim lesions, microglia, the primary immune cells that respond to tissue injury and clean up debris in the brain, form a rim around lesions where the blood-brain barrier has healed. This is a sign that the inflammation is persisting at low intensity behind a closed blood-brain barrier. The rims are like a smoldering fire that continues to burn and slowly propagate. MS patients with a lot of paramagnetic rim lesions are more likely to have increased disability, so we think the lesions might be a good biomarker for progressive disease. Because our current therapies can’t cross a closed blood-brain barrier, we don’t have a way to treat these lesions at present.

Can advanced imaging techniques help identify therapies to treat chronic inflammation in MS patients?

Sati: We think so! We have received funding from the National Multiple Sclerosis Society and the National Institutes of Health to evaluate paramagnetic rim lesions as a diagnostic biomarker using detection techniques we developed. We are now exploring novel techniques to measure the amount of chronic inflammation and tissue damage in these lesions to evaluate the effects of new brain-penetrant therapies. We hope that these new quantitative techniques combined with AI will enable us to measure paramagnetic rim lesions in a fast, efficient way that could be put into practice in most imaging facilities and be deployed in clinical trials.

We’re doing this work in collaboration with all the stakeholders: the MRI physicists at our institution, the MRI vendors that provide the scanners and imaging technology, the neuroradiologists who read these scans, and the pharmaceutical industry that develops the therapies. We hope to prove that our concepts can be applied on different MRI scanners, so that they can be used in international clinical trials testing new therapies that can target these lesions and change the course of the disease.

What are your hopes for the future of MS care?

Sicotte: We're really lucky here at Cedars-Sinai. We have a large group of patients who are eager to participate in research, and we have been collecting MRI data over many years. Added to that, we're employing these newer techniques. We're hoping that the data we are collecting will tell us more about the drivers of progressive disease, how to predict which patients might not require treatment, and which we should treat aggressively from the outset.

Read more on the Cedars-Sinai Blog: Cedars-Sinai Neurology Chair Honored by National MS Society for COVID-19 Work

is designed to help medical staff tailor care to best serve these patients.

“People with dementia or cognitive impairment can be especially vulnerable in the hospital if their care team is unaware,” said Zaldy Tan, MD, MPH, medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders at Cedars-Sinai and first author of the study. “Our study is the first to investigate the feasibility of utilizing the electronic health record to identify these patients and alert the hospital team to help guide clinical care.”

If a patient with dementia is hospitalized for an unrelated condition, such as a fall or infection, they might not be able to accurately describe their medical history or safely make decisions about their medical care, Tan said. Patients with dementia might also need help to understand discharge instructions or just to stay calm in the hospital environment.

“Diagnoses such as Alzheimer’s disease, dementia or cognitive impairment are often not documented in a patient’s medical records,” said Tan, who is also director of the Memory and Healthy Aging Program and the C.A.R.E.S. Program at Cedars-Sinai. “And if providers are not aware that their patient has dementia, they may not call a loved one who can provide critical information, help with decision-making, and provide support.”

To identify these patients, investigators created a secure algorithm to search patients’ electronic health records for a diagnosis of dementia and for prescriptions for medications approved by the Food and Drug Administration to treat dementia.

“The biggest challenge in creating the algorithm was the variety of clinical scenarios that led to a potential diagnosis of dementia,” said Cameron Escovedo, MD, MS, physician leader of Enterprise Information Services at Cedars-Sinai and co-author of the study. “We had to account for multiple scenarios to ensure the algorithm was complex enough to capture everyone.”

When the algorithm detects a patient with possible dementia, a yellow banner pops up on the patient’s chart to make hospital staff aware.

“Given the poor patient outcomes currently associated with dementia care in the hospital setting—including increased risks for falls, use of restraints, and prescription of antipsychotic medications—there was a need for a method to accurately identify these patients,” said Nancy Sicotte, MD, chair of the Department of Neurology at Cedars-Sinai and senior author of the study. “Our algorithm alerts the hospital team to the presence of cognitive impairment so that they can employ targeted interventions and ultimately improve outcomes for vulnerable hospitalized patients.”

To help ensure that medical staff understand how to respond to these patients once identified, a team of nurses and physicians at Cedars-Sinai created and tested a training program and published their results in the peer-reviewed journal Geriatric Nursing.

“About 25% of the nursing staff on the units where we tested this training felt they had not previously received comprehensive training in the care of persons with dementia,” said nurse practitioner Deana Rhinehart, DNP, first author of the study. “Our goal was to help bridge the gap in knowledge and confidence within our nursing teams.”

The training was conducted over multiple 45-minute virtual sessions led by Rhinehart and nurse practitioner Dyane Gatmaitan, NP, a co-author of the study. Sessions included interactive case studies and question-and-answer segments.

“Topics included effective communication, documentation of behaviors, delirium versus dementia, refusal of medications, general behavior management and patient advocacy,” said Gatmaitan. “We are finalizing a rollout plan to expand this training to additional units in March.”

Tan said that the identification system will be expanded to all medical and some surgical units, and that the system and the training—currently in use only at Cedars-Sinai—could easily be deployed at other institutions as well.

Learn more on the Cedars-Sinai Blog: When Should I Be Concerned About Memory Loss?

“I had an attack,” said Albert, 76, who runs a court filing service and lives in View Park. “My limbs went limp like a rag doll and my arms were just dangling, my feet were dangling, and the tears were running out of my eyes. And that lasted for about 30 seconds, maybe a minute.” 

It wasn’t his heart that caused the issue, but Albert happened to be in the right place at the right time. After a round of imaging tests, Albert was diagnosed with intracranial atherosclerotic disease (ICAD). A buildup of plaque in the arteries supplying blood to parts of his brain caused his “ministroke,” also known as a transient ischemic attack, or TIA.

By Monday, Albert was having a lifesaving procedure to open the artery and restore blood flow in his brain.

His surgeon, Michael Alexander, MD, vice chair of Neurosurgery and director of the Neurovascular Center and Endovascular Neurosurgery at Cedars-Sinai, said that for patients with ICAD, plaque buildup can narrow the arteries, causing TIAs and temporary symptoms like those Albert experienced. If the narrowing is severe or the artery is completely blocked, the patient can have a more serious stroke and suffer permanent disability or death. 

“As little as four or five years ago, standard treatment for patients with ICAD was to prescribe medications to lower cholesterol and prevent blood clots,” said Alexander. “Mr. Albert was already taking those medications, and they clearly weren’t helping. With a minimally invasive procedure to place a stent and keep his arteries open, we relieved his symptoms and likely saved his life.”

A lifelong runner, Albert made the cardiologist appointment after experiencing two months of symptoms that included dizziness, weakness, loss of balance and hot flashes. The tests ordered by the cardiologist ruled out heart problems, but an imaging test called a magnetic resonance angiogram (MRA) showed an 85% blockage in one of the arteries supplying blood to the parts of his brain responsible for functions such as balance, coordination, breathing and swallowing.

To clear the blockage, Alexander threaded a tiny catheter through an artery in Albert’s groin, up into the blocked artery in his brain. He inflated a balloon to compress the blockage against the arterial wall, and then put a small tube called a stent in place to hold the artery open.

Results of two multicenter studies led by Cedars-Sinai, published in 2019 and 2021, concluded that this procedure, called intracranial stenting, safely and successfully reduced the incidence of future strokes in patients like Albert.

“Those studies changed how we’re treating ICAD patients today compared with just three years ago,” Alexander said. “Because the results were so positive, the American Stroke Association updated its treatment guidelines to recommend stenting as the best alternative treatment for patients who are having recurrent symptoms, even when they're on medications to prevent blood clots and lower cholesterol.”

Albert, who had been forced to give up driving because of his symptoms, said that recovery from the procedure was a matter of days, and that he is back behind the wheel.

“It felt like a miracle,” Albert said. “Six months after I left the hospital, they did an angiogram and told me that everything is great. The artery is 85% to 90% open. Those attacks were a real scary part in my life and having this procedure was a real blessing.”

Alexander said early ICAD diagnosis is key to preventing a disabling stroke, and that symptoms such as dizziness, double vision or temporary weakness are warning signs that a person should get a medical evaluation.

MRA imaging, which is similar to magnetic resonance imaging (MRI), helps clinicians evaluate blood flow through the brain’s blood vessels. And a newer tool called high-resolution intracranial vessel wall imaging allows clinicians to look at the artery wall to identify cholesterol plaques blocking the artery, tears in the arterial wall, or inflammation of the blood vessel due to vasculitis. Cedars-Sinai was one of the first medical centers to employ this technology.

For patients with an arterial blockage, stenting can be a life-changing option.

“If Mr. Albert had received the standard treatment offered four or five years ago,” Alexander said, “he might have suffered a major stroke and permanent disability. But because we were able to offer him current state-of-the-art treatment, in just a couple of hours we restored blood flow to his brain, his symptoms resolved, and he is back to his very active life.”

Learn more on the Cedars-Sinai Blog: Strokes That Are Treatable—And Beatable

“This is the best data to date on the question of surgery versus medical management in patients with this rare but serious condition,” said Adam Mamelak, MD, co-director of the Pituitary Center, director of the Functional Neurosurgery Program at Cedars-Sinai and lead author of the study. “It demonstrates in a prospective, controlled way what previous studies had begun to suggest, namely that pituitary apoplexy is very rarely a surgical emergency.”

The pituitary gland, located at the base of the brain, controls the function of several hormone-producing glands. Pituitary apoplexy occurs when a benign tumor in the pituitary gland area begins to bleed or dies, causing the tumor to grow and press on the surrounding brain tissues. This, in turn, causes symptoms such as severe headache, fatigue, confusion and vision problems that may include vision loss. Most commonly, these tumors are undetected prior to the apoplexy event.

To relieve the pressure on brain tissues and mitigate the symptoms of apoplexy, patients can either have the tumor surgically removed or be treated with medications to relieve pain and other symptoms while they wait for it to naturally shrink over time. In both cases, patients generally also need hormone-replacement therapy, Mamelak said.

Pituitary apoplexy has long been considered an emergency requiring rapid surgical treatment to achieve best results. Small retrospective studies, where investigators look back at previously collected data, have suggested that pituitary apoplexy patients have equally good outcomes with medical management, but these observations have failed to significantly change clinical practice.

“While we’ve seen a growing trend toward clinicians being a little more comfortable with medical management of pituitary apoplexy, in general, most patients still end up getting surgery,” Mamelak said. “Those small retrospective studies really didn’t move the needle that much.”

To provide a more solid basis for clinical decision-making, Mamelak and fellow investigators from the Department of Neurosurgery and the Pituitary Center at Cedars-Sinai—as well as colleagues from 11 other medical centers in North America, Japan, South Korea and Europe—developed the Pituitary Apoplexy Surgical Timing and Outcomes Registry (PASTOR).

The registry enrolled 97 patients with pituitary apoplexy at the time of diagnosis and compared outcomes for the 67 patients who had surgery with those for the 30 patients whose symptoms were medically managed. This type of prospective registry allows investigators to draw stronger conclusions because data collection is the same for all participants.

Investigators found that:

• Length of hospital stay was the same for patients who had surgery as for those who did not.
• Patients who had surgery experienced the same outcomes whether they had surgery right away or days after the onset of symptoms.
• There were no statistically significant differences in hormone function, vision or quality of life between the two groups of patients three and six months after treatment.

Mamelak noted that patients experiencing more severe vision symptoms were more likely to have surgery than those experiencing milder symptoms but that surgery didn’t necessarily lead to better outcomes.

“Cedars-Sinai and the other sites taking part in this study all have expert pituitary neurosurgery and endocrinology teams, which could help account for the positive outcomes experienced by surgical patients,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai. “A wealth of solid research tells us that outcomes from pituitary surgery are directly tied to surgical experience.”

Mamelak said that further research specifically looking at outcomes for people with visual field deficits would be needed to determine whether surgery is best in those cases. Meanwhile, the current findings could especially benefit medical centers that do not have the expertise to surgically treat pituitary tumors.

“These findings take some of the urgency out of managing these cases,” Mamelak said. “Clinicians at these centers now know that they can safely manage these patients medically and transfer them when it’s reasonable and available, or allow patients to forgo surgery entirely if they are comfortable with that.”

Read more on the Cedars-Sinai Blog: Neuroendoscopy Revolutionizes Skull Base Surgery

“Every day in clinic I see children who have had for years what many people call ‘funny spells,’” Holder said. “Sometimes I start talking to a parent and find out the parent has had ‘funny spells’ for years, but had no idea they were epileptic seizures.”

That’s because many people with epilepsy experience subtle symptoms, such as not being able to talk for a few seconds, Holder said. When the momentary symptoms disappear, people tend to forget to look for the source.

“Sometimes children experiencing seizures will see flashing lights or have temporary blurred vision, which leads them being misdiagnosed with migraine,” Holder said.

About 1 in 26 Americans are thought to have epilepsy, a neurologic condition in which a person experiences seizures, or episodes of abnormal electrical activity in the brain.

To mark National Epilepsy Awareness Month, Holder spoke with the Cedars-Sinai Newsroom about what seizures can look like—and why it is important that children get help as soon as possible.

What does a seizure look like?

A seizure can look like anything, depending on where in the brain the seizure comes from. A lot of people think a seizure is a convulsive seizure, where there's a loss of consciousness and the person falls down to the ground and the whole body experiences convulsive activity. That's actually the rarest type of seizure.

The most common seizures are barely noticeable. Sometimes a patient will just sit and stare and be unresponsive for three or four seconds. A child may have an uncontrollable motor activity, such as twitching of an arm or one leg or twitching of one side of the face that lasts for 30 seconds.

Patients may get a feeling of numbness or tingling in a part of the body, or get a funny smell or taste in the mouth that comes and goes. Sometimes they're not able to process language, and their speech is garbled.

If a child has the same feeling or sensation or behavior that happens over and over again, that is a sign the child might be having seizures.

How do you diagnose epilepsy in children?

We rely a lot on information we gather by talking to families. Often, we can make the diagnosis without any diagnostic test, although we still do an EEG, an electroencephalogram, to see if we can gather any further information. For this test, we place electrodes that look like little stickers on the head so that we can monitor brain waves.

How have smartphones changed how pediatric epilepsy is diagnosed?

I've been doing this for more than 20 years, and one of the things that has been most helpful to me is the advent of cell phones with video recording. I advise families, if you see a child having a funny spell, get it on a video camera. We are very good at being able to tell by looking at the recording if the event is a seizure or not.

What happens if a child is not diagnosed promptly?

Children are learning to read, write, think. Undiagnosed seizures can interfere with a child’s ability to learn and process information.

How do you treat epilepsy?

Most children are able to be seizure-free on medications alone. As the brain grows and develops, many children will outgrow seizures and not need to take medication long term.

More than a third of patients have seizures that are more difficult to control. For those children, we typically do advanced diagnostic testing to see exactly where the seizures are coming from. We then remove the part of the brain causing the seizures. Nowadays, this can be done by making a very small opening in the brain and treating the affected area with a laser. The opening is closed with just one suture and the patient usually goes home the next day.

Is epilepsy genetic?

Scientists have identified more than 500 genes that are associated with epilepsy. When we do genetic testing, we can tell not only what causes the epilepsy, but also which medications to use. We do genetic testing by swabbing the cheek. It takes five minutes.

We have a very strong genetics program at Guerin Children’s. The really exciting news is that we have, for the first time, a gene therapy in trials in patients with epilepsy. We may one day be able to treat children with this therapy.

Read more on the Cedars-Sinai Blog: Myths and Facts About Epilepsy

A recent study published in Frontiers in Immunology offers broader insight into the protein networks that allow immune cells to respond to harmful substances. This discovery could lead to treatments that leverage the body’s natural healing processes.

“This study demonstrates enormous potential for exploiting the natural immune process to better fight disease,” said Maya Koronyo-Hamaoui, PhD, a professor of Neurosurgery and Biomedical Sciences at Cedars-Sinai and senior author of the study. “White blood cells—which we studied here in the context of Alzheimer’s disease—are one of the first lines of defense against a variety of foreign and internal threats and are key for regulating tissue repair and maintenance.”

The study demonstrates the significance of osteopontin (OPN), a protein expressed by macrophages, a type of white blood cell that surrounds and destroys harmful organisms and clears cell debris and the buildup of abnormal proteins. Investigators, in collaboration with the Van Eyk Research Lab at Cedars-Sinai, concluded that OPN deficiency disrupts the balance of proteins in macrophages, eventually causing them to die.

“Macrophages clear toxic proteins, reduce inflammation, and help regenerate, rejuvenate, and encourage newly formed connections in the brain,” said Koronyo-Hamaoui.

The study builds on two previous studies from the Koronyo-Hamaoui Llab—published in Brain Behavior and Immunity and Brain—detailing the critical role played by bone-marrow derived macrophages and OPN expressed in macrophages in clearing Alzheimer’s disease-related amyloid-beta peptides and supporting central nervous system repair and regeneration.

“Our work supports further study into gene editing or immunotherapies that could have multifaceted impact,” said Altan Rentsendorj, PhD, a senior research associate in the Koronyo-Hamaoui Lab and first author of the study.

Investigators studied macrophages in laboratory mice. They compared normal cells, diseased cells treated with an FDA-approved multiple sclerosis treatment that caused them to overexpress OPN, and cells without the ability to produce OPN.

They found that diseased macrophages treated with the multiple sclerosis medication more effectively cleared amyloid-beta proteins and increased their anti-inflammatory activity. However, in cells without the ability to produce OPN, treatment with the multiple sclerosis medication did not restore normal protein expression.

Investigators also discovered that the presence of OPN is necessary to produce two other crucial anti-inflammatory molecules. Dysfunction of the first, ubiquitin C-terminal hydrolase L1, has been implicated in neurodegenerative diseases such as Alzheimer’s. The second, heme oxygenase 1, plays a critical role in preventing vascular inflammation.

“We were surprised to find that other neuroprotective proteins are dependent on OPN,” Rentsendorj said. “This work shows that OPN is critical for the machinery of rejuvenation in these innate immune cells.”

The Koronyo-Hamaoui Lab also recently published a review paper in Frontiers in Physiology synthesizing knowledge about angiotensin converting enzyme (ACE) and its role in Alzheimer’s disease. ACE, expressed by immune cells, degrades amyloid-beta and improves immune response.

The review outlines findings from 1975 onward, including numerous studies from the Koronyo-Hamaoui Lab in collaboration with the Bernstein Lab at Cedars-Sinai.

Significant among these are a 2020 paper published in Brain, which demonstrated that overexpression of ACE enhances the ability of white blood cells called monocytes to rid the body of toxic forms of amyloid-beta oligomers and fibrils, and a 2014 paper published in The Journal of Clinical Investigation. The review also notes that an analysis of human genome sequencing found people with a genetic variant that leads to lower expression of ACE in their blood had higher risk for Alzheimer's disease.

“This review builds a strong case for targeting monocytes and ACE in Alzheimer's disease,” said neurology fellow Ron Danziger, MD, first author of the review paper. “In extensive studies by the Koronyo-Hamaoui and Bernstein labs, we have consistently found an amazing effect of ACE on the characteristics of macrophages in the context of Alzheimer’s disease.”

Taken together, the new papers support the need for further research into therapies that might leverage immune function in blood or bone marrow cells to fight neurodegenerative disease.

“We need a much more effective treatment to address many aspects of Alzheimer’s disease,” said Keith L. Black, MD, chair of the Department of Neurosurgery, the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai, and co-author of both studies. “Genetically manipulating monocytes to enhance ACE or OPN, which would target more than plaque clearance, could be a very promising technique.”

Funding: The study appearing in Frontiers in Immunology was funded by the National Institute on Aging of the National Institutes of Health (grant numbers R01AG056478, R01AG055865, AG056478-04S1 and R01AG075998) and the Tom Gordon, Haim Saban and Wilstein foundations.

The study appearing in Frontiers in Physiology was supported by the National Institute on Aging of the National Institutes of Health (grant numbers R01AG055865, R01AG056478, R01AG075998 and R01AG042195); a BrightFocus Foundation Award; The Coins for Alzheimer’s Research Trust (CART) Fund; the Cedars-Sinai Jona Goldrich Center for Alzheimer’s and Memory Disorders; the Saban, Gordon, Marciano and Wilstein private foundations; and the National Center for Advancing Translational Sciences (CTSI grant UL1TR000124).

Read more from the Cedars-Sinai Blog: How to Help a Loved One With Alzheimer’s or Dementia

The discovery, published in the peer-reviewed journal Nature Communications, has given investigators a potential target for treating stress-induced eating disorders in women.

“These results are very exciting because they help us understand an important aspect of how stress is regulated,” said Celine Riera, PhD, assistant professor of Biomedical Sciences and Neurology at Cedars-Sinai and senior author of the study. “We hope to leverage this knowledge to help develop treatments for anxiety-related eating disorders.”

The study is the first to examine specific neurons responsible for the body’s metabolic response to stress, Riera said, and the first to compare results in male and female laboratory mice to identify sex-based differences in the brain’s stress response.

Riera and fellow investigators induced stress by exposing both male and female laboratory mice to predator odor. Both male and female mice were more active and ate less when exposed to stress, but the effect was more pronounced and lasted longer in female mice than in male mice.

Investigators, including Predrag Jovanovic, PhD, then used two different methods to determine which brain cells were responsible for this reaction.

The investigators recorded which neurons were expressing high levels of a protein called c-Fos, which indicated they were activated by the scent. The investigators then traced the connections of the activated neurons, using a virus that makes a fluorescent probe, from the part of the brain receiving scent information from the nose to the neurons activated in another part of the brain by the scent.

Both experiments pointed to the dorsomedial hypothalamus, a brain region established as important for the regulation of feeding and energy expenditure. The region is known to contain neurons that signal when the body is full, and neurons that regulate body temperature, but this study pinpointed a third type of neuron in the region.  

“We're showing for the first time that there is another population of neurons,” Riera said. “They are called cholecystokinin-expressing, or CCK, neurons, and they play a role in metabolism by suppressing feeding and increasing energy expenditure in response to stress or fear.”

The team next plans to examine these same neurons in the context of obesity, Riera said.

“We want to investigate whether chronically activating these neurons will promote weight loss, and whether that effect is stronger in females compared with males,” she said. “We’re hoping we can confirm these neurons as a therapeutic target for treating metabolic disorders.”

Scientists and health experts are trying to learn more about why obesity rates worldwide continue to rise, and why the prevalence of obesity is higher in women than in men, Riera said.

“Male-female differences in response to stress and eating are poorly understood from a neurological perspective,” said Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “This line of inquiry and the focus of these investigators on including females in their work offers a potential key to better understanding these issues–and possibly improving the health of millions.”

Funding: The study was funded by American Diabetes Association Pathway to Stop Diabetes Grant number 1-15-INI-12, the Klingenstein-Simons foundation, the Larry L. Hillblom Foundation fellowship, and the Cedars-Sinai Center for Research in Women’s Health and Sex Differences.

Read more on the Cedars-Sinai Blog: Women’s Health and Sex Differences.

In July, the first direct-to-consumer blood test designed to assess a user’s risk for developing Alzheimer’s disease hit the market. The test, which has not undergone Food and Drug Administration (FDA) review, measures the level of a protein called beta amyloid, a key component of plaques that form in the brains of Alzheimer’s disease patients, disrupting brain function.

Zaldy Tan, MD, MPH, medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders and the Carmen and Louis Warschaw Endowed Chair in Neurology at Cedars-Sinai, sat down with the Cedars-Sinai Newsroom to answer questions about the test, as well as similar blood tests that are in development.

What do these new blood tests measure?

Blood tests for Alzheimer's disease provide a convenient way for patients to see whether they might be developing Alzheimer's-type changes or pathology in their brain years before memory issues even begin. The challenge here is that these brain changes do not necessarily mean that they have Alzheimer's disease, which is a clinical diagnosis. What blood tests do is to look at traces of certain proteins that are known to develop in patients with Alzheimer's disease.

Who should take this type of blood test?

First, it is important to remember that the test currently on the market has not been evaluated or approved by the FDA. Neither have any of the other, similar tests that are in development. And these blood tests should really be reserved for people who are at risk or are having early symptoms of memory issues. These types of blood tests do not have a place for people who do not have significant risk factors for developing memory problems, or are not having any functional or social issues related to cognitive change.

Does a blood test alone provide enough information to diagnose potential memory issues?

A blood test will not answer that question. Only a trained clinician can. So, for people who are interested in these kinds of blood tests, I would suggest that patients first speak with their healthcare professional to see if these tests are right for them.

Alternatives to these newer-on-the-market tests are things like cognitive testing, a neurologic examination, or consultation with memory specialists. These blood tests provide just one data point or piece of information among many that need to be collected to know if someone is having early signs of Alzheimer's disease.

Do these blood tests help patients qualify for some of the new Alzheimer’s disease treatments such as lecanemab?

Currently, we confirm the presence of amyloid beta in the brain and qualify patients for these treatments through a PET scan of the brain or a lumbar puncture to test cerebrospinal fluid. These blood tests will need to be tested further and will need to be cleared by the FDA to make sure that they are reliable before they can be used to qualify patients for these new treatments. 

What are the risk factors for Alzheimer’s disease?

Age is one of the main risk factors for developing dementia later in life. Others include family history, especially having dementia diagnosed in a first-degree relative. People who have had traumatic brain injury or have had a stroke or have Parkinson's disease or other neurologic conditions may also be at increased risk of developing dementia.

What can people do to reduce their risk of Alzheimer’s disease?

So, what we need to do is to make sure that our brains get the blood supply that they need, and that is best assured by a healthy lifestyle: good diet, good sleep, exercise, increased socialization to make sure those connections between brain cells are nice and healthy. And of course, protecting your brain from trauma by wearing a helmet when you cycle or skate, wearing a seatbelt when you're driving, is important. So, it's really a combination of things in order to reduce the overall risk. Just like we do for our hearts and our bodies, we need to have a multimodal approach to risk reduction of brain disease, including Alzheimer's disease.

Read more on the Cedars-Sinai Blog: Am I at Risk for Dementia? What You Need to Know

As part of the program, Ward and 30 other students tried out the latest robotic surgical tools in the medical education laboratory that Cedars-Sinai employees have nicknamed the Sim Center. In the Sim Center, all the rooms, including the operating rooms, are exact hospital replicas. Ward and his friends performed mock surgery on lifelike manikins, and learned CPR techniques and suturing.

And when Ward expressed an interest in neurology and neurosurgery, Cedars-Sinai arranged for the teenager and his grandmother to meet with Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai.

“At first, I couldn’t believe Dr. Black would really take the time to meet with a high school student, so I spent a lot of time writing my list of questions,” Ward said. “I was so impressed that he spent so much time with me and answered every single question.”

Lawson said the experience was a “pivotal moment” for her grandson.

“This is one of those things that can set the course for the rest of a young person’s life,” said Lawson. “Donnè described Dr. Black as very welcoming and said he was delighted to speak with a renowned doctor and learn about his path to success.”

Black has a passion for opening the field of medicine to minority communities through a variety of programs that he has championed, including Brainworks, where local students come to Cedars-Sinai for a day and learn about neurosurgery.

“My goal has long been to expose as many students as possible to the fascinating field of science, especially neuroscience,” said Black. “I’m grateful for the mentors and programs that encouraged my pursuit of medicine as a young man, and I want to encourage new generations of potential physician-scientists.”

The  simulation center, celebrating its 10^th anniversary this year, has opened its doors to hundreds of schoolchildren for hands-on educational programming and mentorship events.

“These programs really can make a difference in students’ lives,” said Russell Metcalfe-Smith, executive director of Interprofessional Education, Simulation, Medical Library. “We are exposing children to careers they may not have known existed and positively influencing their future career choices.”

Read more on the Cedars-Sinai Blog: Simulated Scenarios, Real Benefits

“This is the most promising therapy yet for Alzheimer’s disease, but delivering the treatment to patients is far from simple,” said Sarah Kremen, MD, who leads the Alzheimer’s Disease Clinical Trial Program in the Department of Neurology at Cedars-Sinai. “We want to be sure that potential patients understand the treatment process and risks, and are clear about what type of real-world gains it might deliver.”

Lecanemab, marketed under the brand name Leqembi, isn’t a perfect solution, but it is a positive step forward, said Zaldy Tan, MD, MPH, medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders in the Department of Neurology at Cedars-Sinai.

“More than 6 million people in the U.S. are diagnosed with Alzheimer’s disease, and this is the most effective treatment we have available,” Tan said. “We have to start somewhere.”

Kremen and Tan sat down with the Cedars-Sinai Newsroom to explain the screening and treatment process for patients interested in receiving lecanemab, and its risks and benefits.

How does lecanemab work—and how well?

Kremen: Clinical trial data showed that the treatment can pull amyloid—a protein that forms plaques and disrupts brain function—out of the brain in a significant way. Patients receiving lecanemab during clinical trials also showed moderately less decline on tests of memory and functional ability. Lecanemab also seems to decrease accumulation of tau protein, which forms tangles inside neurons of Alzheimer’s patients, particularly in the memory centers of the brain. That being said, treatment takes 18 months and only slows cognitive decline by about six months.

When will Cedars-Sinai start administering lecanemab to patients?

Tan: Cedars-Sinai hopes to begin offering this treatment in the next few months. Our multidisciplinary team—including experts in cognitive testing, brain imaging, pharmacy, infusion therapy and patient care coordination—has been working to create a robust process that will support patients from pre-treatment screening through follow-up care and account for every anticipated challenge that might present itself.

Who can be treated with lecanemab?

Kremen: This treatment is designed for people who have either mild cognitive impairment or mild dementia due to Alzheimer’s disease. This is not for people with moderate or severe dementia, where their memory and other cognitive functions are so impacted that they need to rely on other people for help with daily living. It is also not for people at risk for Alzheimer’s disease but who have normal memory and thinking. The medication isn’t recommended for anyone taking blood thinners or who has significant brain bleeds, brain swelling, aneurysms, vascular malformation, brain tumors, or an uncontrolled bleeding disorder.

What kind of real-world benefits might the drug have for patients?

Tan: We don’t yet know how many people will have observable benefits from this medication. We’re hopeful that it’s going to prolong our patients’ ability to function, but that might be a difference of as little as three months’ delay in disease progression. Still, three more months of better thinking and participating in activities of daily life may be meaningful to some of our patients and their families as they navigate this condition.

What are the risks associated with treatment?

Kremen: Risks include brain bleeding and brain swelling, which is also true of other, similar Alzheimer’s disease treatments that haven’t made it this far in clinical research tests. The side effect we’re most concerned about is large brain bleeds, which are fairly rare but can happen. So people need to go into this with eyes open, because we’re not going to be able to completely mitigate this risk.

What is the treatment process like?

Tan: The medication is given by IV infusion over one hour, every two weeks—so the time commitment is something to consider. And patients will need to have an MRI before the fifth, seventh and 14^th infusions, according to FDA guidelines, so that we can monitor for brain swelling and brain bleeds. We will also have to monitor for infusion reactions, such as low blood pressure or difficulty breathing, which could happen during any type of IV infusion. We will monitor for three hours after the patient’s first dose, two hours after the second and third doses, and 30 minutes after the remaining doses for patients who do not have infusion-related reactions.

What types of pre-treatment testing will patients need?

Kremen: Patients will need a diagnostic evaluation to confirm that their dementia or cognitive impairment is due to Alzheimer’s disease and not something else. This evaluation can be done by a primary care doctor, geriatrician, neurologist or psychiatrist. They will also need testing to confirm the presence of amyloid, which is what the medication is designed to treat. This can be done via specialized brain imaging—which is not widely available or covered by insurance—or through spinal fluid tests. Patients will also need genetic testing, because those with one or two copies of a gene called APOE4 are at increased risk of brain bleeds and swelling and will need to take this into account when deciding whether to be treated.

What costs are associated with treatment?

Tan: According to lecanemab’s manufacturer, Eisai, the drug itself will cost around $26,500 per year, and there are additional costs for required pre-treatment testing and monitoring during treatment. The Centers for Medicare & Medicaid Services has stated that if lecanemab receives full FDA approval, Medicare will cover the treatment in “appropriate settings.” It is still unclear whether Medicare or private insurers will cover testing and monitoring, and the out-of-pocket cost to patients is uncertain.

Read more on the Cedars-Sinai Blog: How to Help a Loved One With Alzheimer's or Dementia

Building on its visionary investment in Cedars-Sinai’s neurosurgery scholarship program, The Ray Charles Foundation has donated a second gift of $1 million to support critical training and research to advance the neurosciences.

The Ray Charles Foundation Scholars Fund in Neurosurgery is overseen by highly respected neurosurgeon Keith Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience.

Each year, a cohort of exceptional students from Historically Black Colleges and Universities is mentored by researchers personally selected by Black. The scholars also shadow him as he treats patients and develops groundbreaking therapies in Cedars-Sinai’s neuroscience laboratories.

“The students chosen for this program are destined for greatness in the world of medicine,” Black said. “What the scholars program aims to do, as a shared mission between Cedars-Sinai and The Ray Charles Foundation, is build the students’ scientific acuity as they establish their medical careers. This valuable funding is as much a catalyst for the program’s forward momentum as the students’ steadfast work ethic and the mentors’ expertise.”

Valerie Ervin, president of The Ray Charles Foundation, said Black’s leadership drives the foundation’s commitment to help future generations of neurosurgeons. “This program trains and mentors students from historically Black institutions, providing exposure and opportunities they may not otherwise have,” Ervin said. “That’s why it was so important for The Ray Charles Foundation to make a second $1 million gift.”

The scholars fund promotes diverse representation, specifically in neurosciences, and more broadly as part of Cedars-Sinai’s continuing commitment to diversity and inclusion across all medical specialties.

“Cedars-Sinai is resolute in its mission to create pathways of success for future medical professionals,” said Thomas M. Priselac, president and CEO of Cedars-Sinai and the Warschaw Law Chair in Health Care Leadership. “We’re honored and grateful that The Ray Charles Foundation has chosen our institution to collaborate with in this important effort.”

The iconic musician first showed his support for Cedars-Sinai some 20 years ago, naming the Ray Charles Cafeteria and Conference Center. He died in 2004.

Past and current scholars say participating in the program has changed their lives, introducing them to complex lab techniques and providing the focus and discipline required to take on a rigorous workload with precision.

When asked what guidance the legendary late entertainer would have imparted to scholars chosen for the coveted program, Ervin was quick with an answer: “If Ray Charles were with us today, he would tell the NeuroScholars, ‘Do your best practice, stay focused and keep on your journey.’”

Read more in Discoveries: Women in Neurosurgery

Cedars-Sinai has received a gift of more than $140 million—the largest gift in the hospital’s 121-year history—from the estate of longtime supporters Susanne and Ervin Bard. This gift will propel clinical and research innovation in the medical campus’ newest building.

The gift will name the Susanne and Ervin Bard Pavilion, home to internationally renowned institutes, centers and research facilities, including the Smidt Heart Institute and the Samuel Oschin Cancer Center.

The unprecedented gift will allow Cedars-Sinai to elevate and broaden its mission to provide unparalleled healthcare, advance biomedical discovery and educate future medical professionals for the benefit of Los Angeles and the world. The official ribbon cutting for the Susanne and Ervin Bard Pavilion takes place on March 27. 

“The generosity exhibited by the Bards was extraordinary throughout their lifetimes and now as part of their legacy,” said Thomas M. Priselac, president and CEO of Cedars-Sinai, and the Warschaw Law Chair in Healthcare Leadership. “This amazing gift has cleared new pathways to continue the pioneering research and thoughtful care that Cedars-Sinai is dedicated to delivering.”

Located in the heart of Cedars-Sinai’s main campus, the Susanne and Ervin Bard Pavilion is a 450,000 square foot state-of-the-art healthcare facility that opened in 2013. In addition to offering the highest quality of treatment through outpatient clinical care, Bard Pavilion laboratories and clinical areas generate groundbreaking translational research and medical expertise through the Neurosciences Program, along with Smidt Heart Institute and Samuel Oschin Cancer Center.

“Our outstanding employees in every division of the pavilion work tirelessly to save lives every single day,” said James Lippman, chair of the Cedars-Sinai Board of Directors. “With the generous support of Susanne and Ervin Bard, we will continue to build on this abiding commitment to healing.”

Natives of Hungary, the Bards were longtime supporters of Cedars-Sinai and believed deeply in the Hebrew concept of giving known as tzedakah. Mrs. Bard spent years volunteering in various Cedars-Sinai departments, even after her husband’s passing in 2006. She passed away in 2021.

“The Bards have and will continue to touch the lives of so many of our patients through their generosity,” said Arthur J. Ochoa, JD, senior vice president of Advancement and chief advancement officer at Cedars-Sinai. “Cedars-Sinai is humbled and eternally grateful for this historic gift that allows us to allocate funds where needed most in the advancement of medical science and care.”

Read more on the Cedars-Sinai Blog: Generations Ahead

are urging stroke patients not to stop taking daily low-dose aspirin without consulting their doctors. Confusion over a recent U.S. Preventive Services Task Force recommendation has caused some patients with a history of stroke to abruptly stop the medication, putting their health at risk.

Aspirin is typically prescribed for patients who have experienced or are at increased risk for ischemic stroke, where a blood clot blocks or narrows an artery supplying blood to the brain. Almost 800,000 people in the U.S. have a stroke each year, and ischemic stroke is the most common type.

The task force recommended that patients who have never had a heart attack or stroke not begin a low-dose aspirin regimen because the very slight risk of internal bleeding caused by the aspirin outweighs its potential benefit in preventing a first heart attack or stroke for these patients.

The Cedars-Sinai Newsroom asked Shlee S. Song, MD, director of the Comprehensive Stroke Center, vice chair for Neurology System Integration and professor of Neurology at Cedars-Sinai, and Konrad H. Schlick, MD, assistant professor of Neurology and director of the Vascular Neurology Fellowship Program, to clarify aspirin recommendations for stroke patients and others.

Why are some patients confused by this new recommendation?

Konrad Schlick, MD: The recommendation applies only to patients who have never had a heart attack or stroke. It does not apply to people who have already had a stroke or heart attack, or are at increased risk for one, but some of these patients mistakenly think that it applies to them as well.

Have any of your patients stopped taking their aspirin because of this recommendation?

Shlee S. Song, MD: Yes, many. And it was alarming. Even before this recommendation was so well publicized, we had stroke patients who stopped their aspirin and later arrived in the Emergency Department with a new stroke. Media reports about the recommendation made some of our stroke patients feel that there was not a clear benefit for them. This isn’t true. If a patient’s doctor has recommended low-dose aspirin—or any preventive medication—the patient shouldn’t discontinue taking it without discussing it with their physician.

Why is low-dose aspirin often recommended for patients who have experienced a stroke?

Konrad H. Schlick, MD: There are two distinct kinds of stroke: the bleeding type and the clotting type. Patients who have had a clotting type of stroke benefit from taking a daily aspirin because it reduces the tendency of the platelets in the blood to clump together and form clots, and so it reduces the patient’s risk of another stroke.
Shlee S. Song, MD: This also applies to patients who haven’t had a stroke but have had a stent placed somewhere. Stopping their recommended aspirin combination therapy could cause a stent blockage for those patients.

How do we know that aspirin use is safe for these patients?

Konrad H. Schlick, MD: Very large studies of many patients who take aspirin for secondary stroke prevention have made it clear that the benefits of reducing risk of recurrent stroke significantly outweigh the small risk of an adverse event with aspirin.
Shlee S. Song, MD: We also discuss bleeding risks with our patients and review their health screening evaluations like their colonoscopy results, history of stomach ulcer, and other details before recommending low-dose aspirin. We only recommend aspirin if the benefits outweigh the risk for that patient.

Once low-dose aspirin is recommended for a patient, how long do they need to stay on it?

Shlee S. Song, MD: Sometimes our patients whose stroke happened six months or a year ago think that taking aspirin is no longer necessary, but that stroke history actually stays with you. So, unless your doctor says you no longer need to take it, that regimen still needs to continue at year two, year three and beyond.

Read more on the Cedars-Sinai Blog: Code Brain: After Stroke Care

“Multiple sclerosis is a disease that can look very different in different people, and the path to diagnosis is equally varied,” said MS specialist Marwa Kaisey, MD, assistant professor of Neurology at Cedars-Sinai. “Diagnosis is complex because many other diseases mimic MS, and while we have a set of diagnostic criteria, there’s no single test that is definitive.”

Misdiagnosis Is Common

The immune system in patients with MS attacks the insulating layer that protects nerves. The disruption or loss of these layers results in lesions, which show up as white spots on MRI brain scans—the main tool for diagnosing the condition.

MS lesions disrupt communication within the brain and between the brain and other parts of the body, resulting in vision problems and eye pain, double vision, muscle weakness, trouble with coordination, fatigue, dizziness, and hearing and speech problems. But MS is not the only condition that can cause white spots to appear on an MRI.

“Almost 1 in 5 new patients coming into our clinic with an existing diagnosis of MS turned out not to actually have MS, according to a study that we published in 2019,” Kaisey said. “When we talk to other MS specialists about this, they're not surprised. They also see this trend of misdiagnosis.”

Kaisey said migraines are the most common cause of non-MS white spots on MRIs. “However, in our past study, among 43 people who were misdiagnosed with MS, we found as many as 27 different conditions actually causing the white spots on their imaging,” Kaisey said.

Patients who are misdiagnosed with MS are needlessly prescribed costly immune-modifying treatments that can increase risk for infection, cause organ damage and decrease the effectiveness of vaccines.

“If you have MS, the medications are worth the side effects because they are saving your life and protecting your brain,” Kaisey said. “But it’s a big deal to be on these medications if you don’t need to be.”

New Brain Signs

A newly identified biological sign called “central vein sign” could help physicians determine whether white spots on a patient’s MRI are caused by MS or by something else, ultimately reducing misdiagnosis.

MS lesions tend to form around tiny veins through which immune cells enter and attack brain tissue, so most lesions caused by MS have a vein in the middle. “We’ve known this for more than 100 years, but until recently we didn’t have a way to see it on an MRI,” Kaisey said.

New MRI techniques pioneered by Pascal Sati, PhD, director of the Neuroimaging Program in the Department of Neurology and associate professor of Neurology at Cedars-Sinai, make central vein sign visible.

“Current MRI images don’t give us the whole picture, which is why we developed MRI sequences that improve image quality so that we can see very small veins, called veinules, in the brain,” said Sati. “We superimpose that over a conventional MRI image of the lesions so that it is clear which brain lesions have a central vein and are likely caused by MS.”

Ongoing studies at Cedars-Sinai and 10 other MS centers in North America are using Sati’s technique to image 400 patients at risk of developing MS—the final step in scientifically validating central vein sign as a way to diagnose MS.

Importantly, the imaging technique Sati developed can be used with widely available MRI scanners and performed quickly enough to fit the workflow of the typical radiology center. He is also developing a machine learning algorithm to make evaluation of the imaging results easier for physicians.

“Once the image is taken, our deep learning algorithm can analyze it very quickly and tell the clinician how many lesions show the central vein sign,” Sati said. “The number of lesions with the central vein sign can indicate whether or not the patient has MS.”

The central vein sign could also help doctors determine how well a patient is responding to treatment by confirming that any new lesions that develop are caused by MS and not something else.

“With the central vein sign, we can clearly see which lesions are related to MS,” Sati said. “This information is empowering doctors to make decisions about whether to continue a patient’s current therapy, switch to a different MS therapy, or treat them for a completely new, or different, condition.”

Another Window Into MS

Imaging of the retina—the layer of tissue at the back of the eye—and the optic nerve can also help improve MS diagnosis. Neurologist Omar Al-Louzi, MD, director of the Visual Outcomes Laboratory at Cedars-Sinai, is at the forefront of this technology.

“Around 25% of MS patients experience vision loss or blurring as their first symptom, and as many as 80% experience vision problems at some point in the course of their disease,” said Nancy Sicotte, MD, chair of the Department of Neurology, director of the Multiple Sclerosis and Neuroimmunology Program and Women’s Guild Distinguished Chair in Neurology. “Dr. Al-Louzi’s research seeks to use the eye as a window to produce better outcomes for patients.”

Using a technology called optical coherence tomography (OCT), which functions like an MRI for the retina and optic nerve, Al-Louzi can detect MS lesions that an MRI can miss.

“The optic nerves are very small and difficult to image,” Al-Louzi said. “Detecting lesions there can help us clinch an MS diagnosis, especially in patients who are relatively early on in their disease course.”

Optical coherence tomography captures 3D images of patients’ retinal layers, including the ganglion cell layer, which sends visual information to the brain.

“Shrinking of the ganglion cell layer often mirrors overall brain degeneration, and occurs in 70% to 80% of MS patients,” Al-Louzi said. “This is why ganglion imaging could also help us improve diagnosis.”

Retinal imaging could also help indicate how well a patient is responding to treatment.

Al-Louzi is continuing to study the role of OCT, along with a related technique called optical coherence tomography angiography (OCTA), as a way to understand how MS affects the blood vessels in the retina.

“Our lab is collaborating with Dr. Kaisey to compare the vascular fingerprint of MS in the retina to that of other brain conditions involving blood vessels, such as migraine or small vessel disease, to see whether retinal vessels can help us distinguish between these different conditions,” Al-Louzi said.

While ocular nerve and retinal imaging is important to evaluate in MS patients, it is not yet widely available in practice. Al-Louzi hopes his research will help change the standard of diagnostic care.

“I think failing to use these imaging techniques is a missed opportunity,” said Al-Louzi. “Our hope is that these tests will become widespread and shorten the time between symptom onset and getting the right diagnosis.”

Seeing patients wrongly diagnosed with MS, and MS patients who have gone undiagnosed, drives these physicians to keep working toward better solutions.

“I didn’t really intend to go into this line of research, but being in clinic every day and seeing these problems firsthand, I just had to do something about them,” Kaisey said. “Almost 1 million people in the U.S. alone live with MS. Fortunately, these imaging techniques could offer an invaluable solution.”  

Read more on the Cedars-Sinai Blog: Faces of Cedars-Sinai – Neurologist Dr. Marwa Kaisey

Older women are among the most susceptible to developing UTIs, an infection of the bladder and urethra that causes urinary urgency and pain. UTIs also can cause delirium in older people, resulting in a sharp decline in mental abilities that triggers disoriented thinking.

“Up to one-third of elderly patients hospitalized with UTIs can experience some degree of confusion and reduced awareness of their surroundings,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study. “Delirium affects millions of patients a year in the U.S., contributing to longer hospital stays, long-term cognitive problems and increased mortality. Delirium can be a tipping point from which patients never fully recover. This is well established. What is less well established is why this is happening.”

To better understand the specific biological mechanisms behind UTI-associated delirium, Lahiri and colleagues observed laboratory mice with and without UTIs in specially designed mazes. In an arena where the animals could move about freely, uninfected mice spent more time in the center of the chamber. Those with UTIs huddled in the periphery, suggesting they had higher levels of anxiety, a common symptom of delirium.

In a Y-shaped maze with three arms to explore, uninfected mice tended to explore all three arms, while mice with UTIs kept returning to the same one, suggesting a lapse in short-term memory, another feature of delirium.

The investigators also observed structural changes in the brains of mice with UTIs.

In a previous study led by Lahiri, published in February in the American Journal of Respiratory Cell and Molecular Biology, investigators found a connection between ventilator-induced lung injury and delirium. Lahiri and colleagues theorized that in both cases this was because of the reaction of IL-6, which helps regulate immune response, to the lung injury or the UTI.

“Occasionally, when the response of IL-6 is excessive, our research indicates that there can be brain injury,” Lahiri said. “IL-6 induces changes within the neurons that our studies connected with delirium-like behavior. This is the first time this type of structural and functional change has been demonstrated. We’ve now shown two distinct models of this connection, one non-infectious and one infectious.”

In the current study, when investigators treated some of the infected mice with antibodies that blocked the effects of IL-6, the delirium-like behavior of those animals resolved. “Treatment with anti-IL-6 antibody in the UTI group normalized all the brain changes, both structural and functional,” Lahiri said. “A wealth of studies have shown a link between IL-6 and delirium, but only this study and our previous study have shown that IL-6 may play a direct pathological role in delirium.”

If symptoms are treated early, he added, full recovery is possible, and the next step is to design clinical trials with anti-IL-6 antibodies as a treatment for patients with UTI-induced delirium.

“Dr. Lahiri and his team have built a research framework with implications far beyond this study,” said Nancy Sicotte, MD, chair of the Department of Neurology who holds the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “Building on these efforts could improve outcomes for many of our patients.”

Lahiri believes the model he and co-investigators created could be used to study delirium in other conditions associated with increased incidence of UTI. These include those with pre-existing neurologic disorders like Alzheimer’s disease, Parkinson’s disease, stroke and multiple sclerosis where delirium can be hard to distinguish from the underlying disease but is important to treat.

“A huge population stands to benefit from these investigations,” he said. “We’re looking to apply this model to these other systemic disease conditions and states where the brain dysfunction caused is potentially reversible.”

Funding: This study was supported by National Institutes of Health/National Institute on Aging Grant R03AG064106, the American Academy of Neurology Institute and the F. Widjaja Foundation.

Read more on the Cedars-Sinai Blog: Alzheimer’s and Dementia FAQs

Black kicked off the day of learning by showing the young students photos of brain matter, blood vessels and tumors. Although some of the students from Dobson Middle School, Cochran Middle School and Rise Kohyang Middle School groaned and covered their eyes, Black was not discouraged. He noted that not everyone could be a brain surgeon and that it takes a team of people working in operating rooms, labs and rehabilitation centers to save lives in the high-tech world of brain surgery. 

“I see some of you guys cringing,” he told the crowd. “You guys can be the computer guys.”

Black seemed to expect the mixed reaction and encouraged the students to pursue their dreams, whether they were to follow in his footsteps or not.

“Whatever you guys decide to do, the key is to…find something you’re really passionate about,” he said.

After his presentation, Black said he knew that not all of the 115 or so kids who came to the 21st annual Brainworks would be fascinated by strokes and amyotrophic lateral sclerosis, otherwise known as ALS, or Lou Gehrig’s disease.

“Even if we only touch one out of 100, it’s a good day for us. We just need that little spark,” he said.

Click here to read the complete article in the Beverly Press.

Read more on the Cedars-Sinai Blog: What Do Vikings Have to Do With ALS?