UCSF study indicates effective treatment should be far more common.

Edward Chang, UC San Francisco

Ten years ago, a landmark clinical trial in Canada demonstrated the unequivocal effectiveness of brain surgeries for treating uncontrolled epilepsy, but since then the procedure has not been widely adopted — in fact, it is dramatically underutilized according to a new study from the University of California, San Francisco.

The study, published this month in the journal Neurology, showed that the number of Americans having the surgery has not changed in the decade since release of the effectiveness study, though surgical treatment is now uniformly encouraged by neurology and neurosurgery professional societies.

The U.S. Centers for Disease Control and Prevention estimates that 2 million Americans have epilepsy. Hundreds of thousands of these men, women and children suffer from uncontrolled seizures, but nationally only a few hundred are treated surgically each year with UCSF performing about 50 of the operations.

Among people who do have the operation, the study found, there are significant disparities by race and insurance status. White patients were more likely to have surgery than racial minorities, and privately insured patients were more likely to undergo surgery than those with Medicaid or Medicare.

“As a medical community, we are not practicing evidence-based medicine with regard to the treatment of patients who have epilepsy,” said Edward Chang, M.D., chief of adult epilepsy surgery in the UCSF Department of Neurological Surgery and the UCSF Epilepsy Center. “There are a lot of people who are taking medications and continuing to have seizures even though they can potentially be seizure-free.”

Epilepsy has been recognized as an important neurological condition since ancient times and its name means “seizures” in Greek. It can be inherited or it can be caused by anything that injures or irritates the brain. Hippocrates, the father of western medicine, described it in detail in his writings some 2,500 years ago, and it is believed to have afflicted many famous people throughout history, including Julius Caesar.

UCSF is one of the world’s leading institutions involved in epilepsy research, with one of the few medical centers that has top-ranking departments in relevant areas: neurology, biomedical imaging and neurosurgery.

Paul Garcia, M.D., director of the clinical epilepsy program and a study co-author, said that most patients referred to UCSF for surgical evaluation have had uncontrolled seizures for many years despite trying several medications. Research has shown that after the first two medicines fail, it is uncommon for patients to gain complete seizure control with medical treatment alone. Without control over their seizures, patients are at risk for physical injuries or even dying. Furthermore, the seizures often interfere with normal life activities such as driving, studying and working.

To see how widely this type of surgery has been used, Chang and neurosurgery resident Dario Englot, M.D., Ph.D., accessed a national database of all of the surgeries across the United States for the last 20 years — a timeline centered on the Canadian study. They found that there has been no increase in the 10 years, even as diagnoses of epilepsy have increased along with the number of hospitalizations for seizures.

Part of the problem is awareness, both among patients and care providers, Chang said. New anticonvulsant drugs appear on the market often enough to provide physicians with new drug combinations for their patients to try. Brain surgery can be more daunting than having to swallow fistfuls of pills, even though surgery is much more effective for many people. The problem though is that new medications are not very effective if previous ones already failed, according to Chang. Epilepsy surgery in the modern era has been repeatedly shown to be safe and effective.

Also, many people with epilepsy are not getting the specialty care needed to properly identify the source of the seizures. The study found a significant trend that patients are being evaluated less at epilepsy centers and more at community hospitals often without dedicated epilepsy expertise. The result is that some patients may not receive an adequate workup, and in many cases, the source of the seizures can be very difficult to find without special expertise. “The success of epilepsy surgery totally depends upon the accurate localization of seizure onset region,” Chang said.

The decade-old Canadian study showed that more than nearly two-thirds of all people who underwent surgery as part of the study in the 1990s were seizure-free.  Fewer than 10 percent of patients in the study who relied on drugs alone achieved the same degree of freedom from seizures.

“Even though this important evidence was published 10 years ago now, we have not seen increases in the number of patients,” Chang said. “We need to do better.”

The article, “Epilepsy surgery trends in the United States, 1990-2008” is authored by Dario J. Englot, David Ouyang, Paul A. Garcia, Nicholas M. Barbaro, and Edward F. Chang and appears in the journal Neurology. See www.neurology.org/content/78/16/1200.abstract.

This work was supported in part by the Clinical and Translational Science Institute (CTSI) at UCSF.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

UCSF research explains “cocktail party effect” — ability to tune in a single voice in a crowded room.

Edward Chang, UC San Francisco

The longstanding mystery of how selective hearing works — how people can tune in to a single speaker while tuning out their crowded, noisy environs — is solved this week in the journal Nature by two scientists from the University of California, San Francisco.

Psychologists have known for decades about the so-called “cocktail party effect,” a name that evokes the “Mad Men” era in which it was coined. It is the remarkable human ability to focus on a single speaker in virtually any environment — a classroom, sporting event or coffee bar — even if that person’s voice is seemingly drowned out by a jabbering crowd.

To understand how selective hearing works in the brain, UCSF neurosurgeon Edward Chang, M.D., a faculty member in the UCSF Department of Neurological Surgery and the Keck Center for Integrative Neuroscience, and UCSF postdoctoral fellow Nima Mesgarani, Ph.D., worked with three patients who were undergoing brain surgery for severe epilepsy.

Part of this surgery involves pinpointing the parts of the brain responsible for disabling seizures. The UCSF epilepsy team finds those locales by mapping the brain’s activity over a week, with a thin sheet of up to 256 electrodes placed under the skull on the brain’s outer surface or cortex. These electrodes record activity in the temporal lobe, home to the auditory cortex.

UCSF is one of few leading academic epilepsy centers where these advanced intracranial recordings are done, and, Chang said, the ability to safely record from the brain itself provides unique opportunities to advance our fundamental knowledge of how the brain works.

“The combination of high-resolution brain recordings and powerful decoding algorithms opens a window into the subjective experience of the mind that we’ve never seen before,” Chang said.

In the experiments, patients listened to two speech samples played to them simultaneously in which different phrases were spoken by different speakers. They were asked to identify the words they heard spoken by one of the two speakers.

The authors then applied new decoding methods to “reconstruct” what the subjects heard from analyzing their brain activity patterns. Strikingly, the authors found that neural responses in the auditory cortex only reflected those of the targeted speaker. They found that their decoding algorithm could predict which speaker and even what specific words the subject was listening to based on those neural patterns.  In other words, they could tell when the listener’s attention strayed to another speaker.

“The algorithm worked so well that we could predict not only the correct responses, but also even when they paid attention to the wrong word,” Chang said.

The new findings show that the representation of speech in the cortex does not just reflect the entire external acoustic environment but instead just what we really want or need to hear.

They represent a major advance in understanding how the human brain processes language, with immediate implications for the study of impairment during aging, attention deficit disorder, autism and language learning disorders.

In addition, Chang, who is also co-director of the Center for Neural Engineering and Prostheses at UC Berkeley and UCSF, said that we may someday be able to use this technology for neuroprosthetic devices for decoding the intentions and thoughts from paralyzed patients that cannot communicate.

Revealing how our brains are wired to favor some auditory cues over others it may even inspire new approaches toward automating and improving how voice-activated electronic interfaces filter sounds in order to properly detect verbal commands.

How the brain can so effectively focus on a single voice is a problem of keen interest to the companies that make consumer technologies because of the tremendous future market for all kinds of electronic devices with voice-active interfaces. While the voice recognition technologies that enable such interfaces as Apple’s Siri have come a long way in the last few years, they are nowhere near as sophisticated as the human speech system.

An average person can walk into a noisy room and have a private conversation with relative ease — as if all the other voices in the room were muted. In fact, said Mesgarani, an engineer with a background in automatic speech recognition research, the engineering required to separate a single intelligible voice from a cacophony of speakers and background noise is a surprisingly difficult problem.

Speech recognition, he said, is “something that humans are remarkably good at, but it turns out that machine emulation of this human ability is extremely difficult.”

The article, “Selective cortical representation of attended speaker in multi-talker speech perception” by Mesgarani and Chang appears in the April 19 issue of the journal Nature.

This work was funded by the National Institutes of Health and the Ester A. and Joseph Klingenstein Foundation.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

He pioneered surgical approach to treat epilepsy.

Paul Crandall

Dr. Paul H. Crandall, who co-founded the UCLA Department of Neurosurgery and pioneered surgical approaches still used today to treat stubborn epileptic seizures, died March 15 from complications related to pneumonia at UCLA Medical Center–Santa Monica. He was 89.

“Paul was the father of UCLA’s epilepsy program,” said Dr. Neil Martin, chair of neurosurgery at the David Geffen School of Medicine at UCLA. “His clinical work laid the foundation for our current strategies to treat epileptic seizures, and his scientific research informs neurosurgeons’ treatment of epilepsy today.”

The youngest of seven children, Crandall was born to Arthur and Ellen Crandall on Feb. 15, 1923, in Essex Junction, Vt. He looked up to his siblings: One was a physician, two were attorneys, two owned businesses and one became food editor for the Boston Globe. According to Crandall’s wife, Barbara, his older brother who was a surgeon encouraged him to pursue a career in neurosurgery.

Crandall graduated cum laude and earned his medical degree from the University of Vermont in 1946, then completed his residency training in neurosurgery at the University of Illinois in Chicago in 1952. There, he met his wife, now a professor emeritus of pediatrics and genetics at UCLA, who was in residency training at the same time.

In 1944, Crandall enlisted in the U.S. Army and served for two years. After the service paid for his medical education, he enlisted again in the Army Medical Corps in 1952 and was stationed for two years in Frankfurt, Germany, where he served as chief of neurosurgery at the military hospital.

In 1954, Crandall joined the UCLA School of Medicine as one of three founding members of the neurosurgery division, which was upgraded to a department in 2008. He taught and conducted clinical research for 32 years, retiring in 1988 as a professor emeritus.

Moved by his epileptic patients’ suffering, Crandall launched in 1960 UCLA’s first research program in the surgical treatment of the brain disorder, which provokes sudden and repeated seizures that can damage the brain, causing cognitive impairment and memory loss. While anti-convulsant drugs controlled epileptic seizures in most people, the medications didn’t work in up to 40 percent of patients.

Funded by one of the longest running UCLA grants from the National Institutes of Health, Crandall performed or supervised surgeries on more than 300 epileptic patients, not including those he treated in the clinic. He developed experimental techniques for identifying the brain region causing epileptic seizures that didn’t respond to drugs — an approach now standard at all major medical centers.

He achieved this by using electroencephalography (EEG), a test that tracks brain waves to uncover abnormal electrical patterns. Crandall was the first to pinpoint the origins of epileptic seizures by implanting EEG wires directly into the brain over several days to record electrical activity during spontaneous seizures.

Crandall next worked with UCLA neurologist Dr. Richard Walter to develop the first EEG telemetry unit, which allowed prolonged recording of brain activity to capture spontaneous seizures in patients with epilepsy. Later coupled with continuous video recording, the technique enables physicians to correlate how a patient behaves during seizures with simultaneous brain activity. Hospitals worldwide now use EEG telemetry to test patients whose epileptic seizures don’t respond to drugs.

Crandall was the first to use ultra-fine wire electrodes to record activity from single brain cells during a patient’s evaluation before surgery and to combine this approach with a surgical technique that removed the epileptic tissue in one piece. Previously, the tissue was suctioned from the brain, making it impossible for researchers to study the causes of epilepsy at the cellular level. His efforts enabled scientists to correlate the function of single cells with the cellular abnormalities revealed by examinations of the excised brain tissue.

Crandall’s findings set the stage for human research on the fundamental physiological mechanisms that cause epilepsy. He also participated with the UCLA team that was the first to use positron emission tomography (PET) to scan epileptic patients and image their brains’ abnormal metabolic activity.

“Paul was the first to insert EEG electrodes in the brain over long periods of time to record irregular brain waves during spontaneous seizures, the first to perform EEG telemetry on patients with epilepsy, and the first to perform prolonged recordings of single human brain cells,” said Dr. Jerome Engel Jr., UCLA’s Jonathan Sinay Professor of Neurology, Neurobiology and Psychiatry and director of the UCLA Seizure Disorder Center. “Those of us who followed in his footsteps owe him a huge debt for his contributions.”

Crandall served on the U.S. Department of Health’s national commission for epilepsy from 1976–77. After his work demonstrated the value of longtime monitoring of seizures and procedures for managing difficult cases, the commission recommended the establishment of specialized centers for epilepsy in all major urban centers. His efforts also resulted in the field extending the benefits of surgery to children with epilepsy.

Last year, Thomas and Nadia Davies committed $2 million to the UCLA Department of Neurosurgery in memory of their daughter, Alfonsina (Nina), and in honor of Crandall, who ended her epileptic seizures in the late 1970s.

The Davies family had invested more than a decade in seeking ways to stop the uncontrollable seizures that had assailed their daughter since birth. When they arrived at UCLA in 1977, Crandall suggested an experimental surgery to control Nina’s intractable epilepsy. At the time, few surgical programs for epilepsy existed in the United States, and doctors were often reluctant to consider a surgical approach to treating the disease.

“Dr. Crandall’s scientific knowledge and surgical skills saved our daughter’s life,” said Nadia Davies. “We are eternally grateful for his lifelong study of surgical interventions to prevent epileptic seizures.”

Active in many organizations devoted to improving the lives of people with epilepsy, Crandall served as president of the American Epilepsy Society in 1979, which presented him with the William G. Lennox Award in 1991 for his groundbreaking body of work. He was elected a fellow of the Royal Society of Medicine in 1991 and later received the University of Vermont’s distinguished alumnus award.

In addition to his wife, Crandall is survived by his four children and three grandchildren. The family requests donations to the Dr. Alfonsina Q. Davies Endowed Chair in Honor of Paul Crandall, M.D. for Epilepsy Research. Please make checks payable to the UCLA Foundation Fund #818830, c/o UCLA Department of Neurosurgery, 757 Westwood Plaza, Suite 6236, Los Angeles, CA  90095.

Winners include David Barba, Rohit Loomba, William Mobley, Howard Taras.

David Barba

Brain stimulation surgery for patients with Parkinson’s disease; promoting liver health on a national level; leading one of the nation’s top ALS clinics; and designing a law that protects the rights of students with epilepsy: these are significant reasons why four UC San Diego School of Medicine doctors were honored during the 18th annual Combined Health Agencies Health Hero Awards breakfast on March 15 at The Prado in Balboa Park.

Each year, the Combined Health Agencies’ 24 health nonprofit members each choose a person or company that works daily to improve the lives of local residents affected by chronic illness. This year, four winners who were recognized are UC San Diego physicians David Barba, M.D.; Rohit Loomba, M.D.; William Mobley, M.D., Ph.D.; and Howard Taras, M.D.

Since 2005, Barba, clinical professor of surgery in the Division of Neurological Surgery at UC San Diego Health System, has been involved with the Parkinson’s Association of San Diego. He routinely performs brain stimulation surgery on many patients with Parkinson’s disease and has demonstrated hisleadership by organizing a sold-out patient symposium securing top quality speakers in the field. Barba is currently establishing a UC San Diego system for those working on Parkinson’s research to be in direct contact with each other.

The American Liver Foundation considers Loomba, assistant professor of clinical medicine in the Division of Gastroenterology and the Division of Epidemiology in the Department of Family and Preventive Medicine, a collaborative partner as he serves on the National Board of Directors, and the non-profit local Speakers Bureau promoting prevention and care.

As Chair of the Department of Neurosciences at UC San Diego School of Medicine, Mobley garners national support from physicians and clinicians to join the UC San Diego ALS and Motor Neuron Treatment and Research Center team to raise the level of care and treatment of patients with ALS in San Diego. Through Mobley’s reputation and expertise, the ALS Clinic is quickly becoming known as a place where patients can receive the best care possible in their fight against what is commonly known as Lou Gehrig’s disease.

Taras, professor of pediatrics in the Division of Child Development and Community Health, is being recognized by the Epilepsy Foundation for his instrumental work in the passing of SB 161, a bill signed into law in 2011 that protects the rights of students with epilepsy. He has testified numerous times at California State Legislative hearings and spent hundreds of hours educating legislators and the public about the issue of emergency seizure rescue medications. Through this legislation, life-saving medication can be administered to students at school to prevent further brain damage or death.

“We are humbled by the service of these physicians and grateful to have UC San Diego Health System in our community,” said Susan Day, president of Combined Health Agencies.

This year’s event is possible by the generous support of community sponsors UC San Diego Health System, PhRMA, GlaxoSmithKline, Johnson & Johnson, BIOCOM, Rady Children’s Hospital-San Diego, Sonnenberg & Company CPAs, and The San Diego Business Journal.

Combined Health Agencies has been United Way’s health partner in the United Way/CHAD Campaign since 1974. As a federation of 24 local health charities, Combined Health Agencies is focused on improving the quality of life for individuals and families who are faced with chronic health conditions.

Most patients wait until it’s too late to prevent serious disability.

A PET scan of a brain from a patient with epiepsy, between seizures. The red indicates healthy tissue.

While the thought of any type of surgery can be disconcerting, the thought of brain surgery can be downright frightening. But for people with a particular form of epilepsy, surgical intervention literally can be life-restoring.

Yet among people who suffer from what’s known as medically intractable epilepsy, in which seizures are resistant to drugs, only a small fraction will seek surgery, seeing it only as a last resort. As a result, they continue to suffer seizures year after year. They can’t drive, they can’t work and they lose cognitive function as the years pass. Premature death is not uncommon.

But a multicenter study led by researchers at UCLA shows that for people suffering from intractable temporal lobe epilepsy, the most common form of intractable epilepsy, early surgical intervention followed by antiepileptic drugs stopped their seizures, improved their quality of life and helped them avoid decades of disability.

The report appears in Wednesday’s (March 7) edition of the Journal of the American Medical Association.

“In short, they got their lives back,” said Dr. Jerome Engel, the study’s principal investigator and director of the UCLA Seizure Disorder Center.

But the frustration of Engel and his colleagues is this: Few patients are referred to them for surgical evaluation, and those who are have had epilepsy for an average of 22 years.

“By then, it’s often too late,” he said. “These people will likely remain disabled for life.”

Epilepsy is a brain disorder that produces sudden and repeated seizures that last from a few seconds to several minutes. Seizures are brief attacks of altered consciousness, muscle control or sensory perception. During a seizure, some brain cells behave abnormally, firing repeatedly. This usually begins with a small group of cells and spreads to involve a larger area of the brain.

Epilepsy affects nearly 3 million Americans and 50 million people worldwide; the health burden caused by the disease is equivalent to that of lung cancer in men and breast cancer in women. In the U.S., the 30-40 percent of epilepsy patients who suffer from medically intractable epilepsy account for 80 percent of the cost of the disorder.

For the study, 16 epilepsy centers nationwide recruited 38 individuals suffering from mesial temporal lobe epilepsy that was determined to be intractable — that is, the patients were still having seizures after trying two different anti-epileptic drugs (the international definition of medical intractability). Those recruited had to be within two years of having their disease declared intractable. Of the study participants, 15 underwent surgery and 23 were assigned to a program of best medical care.

The researchers found that after two years, 85 percent of the participants who underwent surgery were seizure-free in the second year after the procedure; by comparison, none in the medical care group were seizure-free.

The surgical group also reported a significantly higher quality of life, a significant increase in independence, and an improved willingness and ability to socialize with friends and family. The number of individuals who reported being able to drive a car rose from 7 percent to 80 percent in the surgical group at the end of two years. Cognitive problems such as memory loss were similar between both groups.

“The results of this study are very encouraging,” said Engel, who holds the Jonathan Sinay Chair in Epilepsy at UCLA. “Surgical treatment for temporal lobe epilepsy soon after the failure of two trials of anti-epileptic drugs stops seizures and improves quality of life. Continuing anti-epileptic drug treatment alone does not.

“So the message is clear: Early surgery, before the adverse social and psychological consequences of seizures become irreversible, offers the best opportunity to avoid a lifetime of disability.”

“This study shows that early surgical intervention works, it stops seizures and it improves quality of life,” said Dr. Karl Kieburtz, director of the Center for Human Experimental Therapeutics at the University of Rochester Medical Center, which served as the coordinating center for the study. “Individuals with epilepsy that is not controlled with medicine should be evaluated for surgical intervention at a comprehensive epilepsy center — not after decades of poor response to medicine but within two years. And if they are a surgical candidate, they should give strong consideration to that approach.”

The results were statistically significant, even though the study was terminated early due to slow enrollment. The study originally was intended to follow 200 patients, but only 38 ultimately were recruited. While some patients who were referred did not meet the study’s criteria, the major problem was a lack of referrals, researchers said. Engel is not sure why.

“Partly, it has to do with the larger number of available anti-epileptic drugs, so neurologists in the community will try more combinations of medications,” he said. “Also, there are many misconceptions about surgical criteria that prevent the referral of good candidates. If patients have intractable seizures, they should be given the opportunity to be evaluated at an epilepsy center. But the biggest reason is fear — that’s often cited by patients and their physicians as a reason for continuing drug therapy. They see surgery as a last resort. And this study shows that that’s just wrong.”

Other authors of the study included John Stern, Itzhak Fried, Sandra Dewar and Harry Vinters, of UCLA; Michael P. McDermott, John Langfitt, Giuseppe Erba and Irenita Gardiner, of the University of Rochester Medical Center; Michael Sperling and Scott Mintzer, of Jefferson University; Samuel Wiebe, of the University of Calgary; and Margaret Jacobs, of the National Institute of Neurological Disorders and Stroke.

The study was funded by the National Institute of Neurological Disorders and Stroke. The authors report no conflict of interest.

The UCLA Seizure Disorder Center is part of the UCLA Department of Neurology. With over 100 faculty members, the department encompasses more than 20 disease-related research programs, along with large clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer’s disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks in the top two among its peers nationwide in National Institutes of Health funding.

Study to sequence DNA from 4,000 people with epilepsy.

Daniel Lowenstein, UC San Francisco

To probe the genetic secrets of one of the most common neurological diseases, more than 4,000 people with various forms of epilepsy will have their DNA decoded over the next five years in a study led by researchers at the University of California, San Francisco and several collaborating institutions.

“This is the largest, most sophisticated project that has ever been attempted for identifying the genetic causes of epilepsy, and it has come about as the result of a great spirit of collaboration among scientists, clinicians, patients and their family members from throughout the world,” said Daniel Lowenstein, M.D., vice chair of the Department of Neurology and director of the UCSF Epilepsy Center.

Sorting the patients’ DNA sequences and comparing them to their histories, brain scans and other clinical data will help frame understanding of a disease that strikes tens of millions worldwide, including about 2 million people in the United States. The work may also reveal new ways to treat people with epilepsy.

UCSF has been one of the world’s leading institutions involved in epilepsy research for years and has one of the few medical centers in the world with top-ranking departments in the areas most relevant to this research: biomedical imaging, neurology and neurosurgery.

The new project, funded by a $25 million grant from the National Institute of Neurological Disorders and Stroke, follows on the heels of another study known as the Epilepsy Phenome/Genome Project and led by Lowenstein and colleagues worldwide, which is collecting detailed clinical data and DNA samples from 3,750 people with epilepsy and 1,500 of their relatives without the disease.

In addition to sequencing DNA from a larger number of people, the new project will apply cutting-edge methods for identifying disease-causing variations in the genome known as copy number variants (CNVs), and it will look for genetic clues that might explain why an apparently similar form of epilepsy can be responsive to treatment in one patient and not so in another.

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Baby Joey arrives healthy eight days after due date.

Luis Gutierrez, fiancee Eveth Martinez and their newborn son Joey, the first baby born at UC San Francisco in 2012

Joey Santino Gutierrez was supposed to be a Christmas baby, or so his parents thought. Due on December 24, his mother Eveth Martinez, 27, spent Christmas eve and Christmas day anxiously awaiting the arrival of her second son.

Instead, Joey kicked off 2012 for his parents and UC San Francisco, as the first baby born at UCSF Benioff Children’s Hospital in 2012. Born at 7:43 a.m. on Jan. 1, 2012, Joey weighed in at 7 pounds, 15 ounces, a healthy baby boy. Martinez was among seven women in labor on New Year’s Eve, but Joey was the first to make his debut at UCSF. The first baby born in San Francisco was delivered at California Pacific Medical Center at 12:02 a.m.

Martinez and fiancé Luis Gutierrez live in San Francisco’s Mission District with their seven-year-old son. And will they try for a girl? “Not for a long time!” said Martinez, just five hours after giving birth. “We’re going to space them out.”

Martinez was originally a patient at St. Luke’s Hospital, however because she suffers from epileptic seizures, she was transferred to UCSF to have access to world-renowned specialists in neurology.

Joey is the first of about 2,000 babies who will be born at UCSF Benioff Children’s Hospital this year. Starting in 2015, those babies will be born at UCSF’s new 289-bed children’s, women’s, and cancer hospital in Mission Bay – which will offer a 36-bed center for mothers and newborns, including nine deluxe labor and delivery rooms.

UCSF has not had the first San Francisco baby born in the new year since 2007, when it happened for the first time in nearly a quarter of a century.

Childhood disorder called PKD that causes epileptic seizures linked to genetic mutations.

Louis Ptacek, UC San Francisco

A large, international team of researchers led by scientists at the University of California, San Francisco, has identified the gene that causes a rare childhood neurological disorder called PKD/IC, or “paroxysmal kinesigenic dyskinesia with infantile convulsions,” a cause of epilepsy in babies and movement disorders in older children.

The study involved clinics in cities as far flung as Tokyo, New York, London and Istanbul and may improve the ability of doctors to diagnose PKD/IC, and it may shed light on other movement disorders, like Parkinson’s disease.

The culprit behind the disease turns out to be a mysterious gene found in the brain called PRRT2. Nobody knows what this gene does, and it bears little resemblance to anything else in the human genome.

“This is both exciting and a little bit scary,” said Louis Ptacek, M.D., who led the research. Ptacek is the John C. Coleman Distinguished Professor of Neurology at UCSF and a Howard Hughes Medical Institute Investigator.

Discovering the gene that causes PKD/IC will help researchers understand how the disease works. It gives doctors a potential new way of definitively diagnosing the disease by looking for genetic mutations in the gene. The work may also shed light on other conditions that are characterized by movement disorders, including possibly Parkinson’s disease.

“Understanding the underlying biology of this disease is absolutely going to help us understand movement disorders in general,” Ptacek said.

PKD/IC strikes infants with epileptic seizures that generally disappear within a year or two. However, the disease often reemerges later in childhood as a movement disorder in which children suffer sudden, startling, involuntary jerks when they start to move. Even thinking about moving is enough to cause some of these children to jerk involuntarily.

The disease is rare, and Ptacek estimates strikes about one out of every 100,000 people in the United States. At the same time, the disease is classified as “idiopathic” — which is just another way of saying we don’t really understand it, Ptacek said.

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Model lets researchers generate testable hypotheses, design highly targeted drug treatments.

Drawing on X-ray crystallography and experimental data, as well as a software suite for predicting and designing protein structures, a UC Davis School of Medicine researcher has developed an algorithm that predicts what has been impossible to generate in the laboratory: the conformational changes in voltage-gated sodium channels when they are at rest or actively transmitting a signal in muscle and nerve cells.

Structural modeling of the voltage-sensing mechanism is important because it allows researchers to generate testable hypotheses and design new, highly specific drugs to treat a wide range of disorders, from chronic pain to epilepsy. The study is published in today’s (Dec. 12) early edition of the Proceedings of the National Academy of Sciences.

Voltage-gated sodium channels are embedded in the plasma membranes of nerve and muscle cells. The channel consists of a large protein that allows sodium ions to pass when a change in voltage occurs across the cell membrane. While high-resolution structures of the voltage sensors that control ion-gate activation have been identified in an activated state, scientists need to know all of the conformational changes that occur throughout the cycle of activation and rest to develop better treatments for disease.

“Sodium channels transmit pain and are the sites of action of local anesthetics,” said Vladimir Yarov-Yarovoy, an assistant professor of physiology and membrane biology at the UC Davis School of Medicine who developed the models in collaboration with researchers from the University of Washington in Seattle. “They are critical targets for new drug development for the treatment of chronic pain, epilepsy and other conditions caused by gain or loss-of-function mutations in voltage-gated sodium channels, which hyperexcite sensory neurons or attenuate action-potential firing causing pain or seizures.”

Serious chronic pain affects at least 116 million Americans each year, and epilepsy affects nearly 3 million Americans and 50 million people worldwide. Yet, the treatment of chronic pain and epilepsy remains a major unmet medical need.

“Currently available drugs for these conditions have limited effectiveness and significant side effects,” said Yarov-Yarovoy. “While the research community has focused on identifying selective inhibitors of sodium-channel subtypes in nerve, heart and muscle cells, no new therapies have advanced to clinical trials. The algorithm is an innovative approach that fosters the design of novel subtype-selective sodium channel blocking drugs that have high efficacy and minimal side effects to treat these disorders.”

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UC Davis’ Michael Rogawski to receive American Epilepsy Society service award.

Michael Rogawski, UC Davis

Michael A. Rogawski, professor and chair of the Department of Neurology in the UC Davis School of Medicine, has been named the recipient of the American Epilepsy Society’s 2011 Service Award. The award honors Rogawski for his many contributions to the field of epilepsy and for his long record of service to the epilepsy society and its members. Among his leadership activities, Rogawski has for the past 10 years served as the co-editor of Epilepsy Currents, the society’s official journal.

Rogawski played a key role in the founding of the journal in 2001, and in the intervening years he has been instrumental in its establishment as a key educational resource for basic and clinical epilepsy researchers and clinicians. Among his other contributions to the work of the American Epilepsy Society (AES) during his more than 20 years of service, Rogawski has served on its board of directors, as chair of its technology committee and as a member of its long-range planning committee.

The AES Service Award will be presented Saturday (Dec. 3) during ceremonies at the society’s 65th Annual Meeting and Scientific Conference at the Baltimore Convention Center.

Rogawski is a leading international authority on the treatment of neurological disorders. During his career, he has investigated the mechanisms of drugs to treat epilepsy and other neurological conditions, and has advanced the development of new treatment approaches. His research encompasses cellular neurophysiological studies, animal models and clinical trials. Laboratory studies conducted in Rogawski’s laboratory on AMPA receptors and neurosteroids have been translated to new epilepsy treatment approaches.

Rogawski holds a medical degree and a doctoral degree in pharmacology from Yale University. Following a three-year residency in neurology at Johns Hopkins Hospital, he began research in the field of epilepsy as a medical staff fellow at the National Institutes of Health, where he rose to head of the Epilepsy Research Section, serving in that role from 1990 to 2006. In 2007 he joined the faculty of the UC Davis School of Medicine.

In addition to serving as editor of Epilepsy Currents, Rogawski is associate editor of Neurotherapeutics and is a member of the editorial boards of several other journals. He also has co-edited five books, including Jasper’s Basic Mechanisms of the Epilepsies, which will appear early next year.

“The friendships that I’ve made with AES colleagues have been important for me personally and professionally,” Rogawski said. “AES has provided invaluable opportunities to exchange scientific ideas and develop collaborations, which have benefited my research program. I have also made close lifelong friends. AES has been an enormously important community to be a part of all these years.”

The 3,000-member American Epilepsy Society, based in West Hartford, Conn., seeks to advance and improve the treatment of epilepsy through the promotion of research and education for healthcare professionals. Celebrating its 75th anniversary this year, it is today the nation’s leading medical society working to eliminate seizures, their fundamental causes and potential neurological effects.

The UC Davis School of Medicine is among the nation’s leading medical schools, recognized for its research and primary-care programs. The school offers fully accredited master’s degree programs in public health and in informatics, and its combined M.D.-Ph.D. program is training the next generation of physician-scientists to conduct high-impact research and translate discoveries into better clinical care. Along with being a recognized leader in medical research, the school is committed to serving underserved communities and advancing rural health. For more information, visit UC Davis School of Medicine at medschool.ucdavis.edu.

Computer models may help develop better therapuetics.

Maxim Bazhenov, UC Riverside

There are basically two main approaches to treating epilepsy — medication and surgery. About 70 percent of patients respond to current drug treatments and for those unresponsive to medication, surgery is another option. But researcher Maxim Bazhenov of the University of California, Riverside, explains that the surgery is a complicated procedure and may cause severe side effects.

“That’s why any new approach from pharmacology, which is a much easier way than surgery to deal with this, could benefit lots of patients especially considering how many people suffer from epilepsy,” Bazhenov said.

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Parents make endowment gift in memory of their late daughter, who was treated at UCLA.

Nadia and Thomas Davies (top) with Dr. Paul Crandall and Nina Davies

Thomas and Nadia Davies have committed $2 million to the UCLA Department of Neurosurgery in memory of their late daughter Alfonsina (Nina) Q. Davies and in honor of Dr. Paul Crandall, the UCLA neurosurgeon who ended her epileptic seizures.

The Davies family invested more than a decade in seeking ways to stop the uncontrollable seizures that had assailed their daughter since birth. The neurologists they met offered only temporary solutions.

When the Davieses arrived at UCLA in 1977, they consulted with Crandall. The founder of UCLA’s first epilepsy surgery research program, Crandall had been developing experimental treatments since the early 1960s. He is now retired and a professor emeritus of neurosurgery at the David Geffen School of Medicine at UCLA.

Crandall suggested an experimental surgery to control Nina’s intractable epilepsy. At the time, few surgical programs for epilepsy existed in the U.S., and doctors were often reluctant to consider a surgical approach to treating the disease.

“Dr. Crandall’s scientific knowledge and surgical skills saved our daughter’s life,” Nadia said. “We are eternally grateful for his lifelong study of surgical interventions to prevent epileptic seizures.”

After her surgery, Nina completed college and realized her dream of becoming a teacher. She went on to earn a doctoral degree in education, eventually becoming assistant superintendent for the Santa Ana Unified School District. She helped many students with disabilities, both social and physical, relating firsthand to the difficulties they faced.

Sadly, in 2011, Nina died at 52 from what is known as sudden unexplained death in epilepsy (SUDEP), a rare outcome for those who suffer from the disease.

The Davieses have established the Alfonsina Q. Davies Endowed Chair in Honor of Paul Crandall, M.D., for Epilepsy Research to recognize Crandall’s early research, which helped Nina and contributed to UCLA’s reputation as a world leader in the surgical treatment of epilepsy.

“We are extremely grateful to the Davieses for their generosity and support,” said Dr. Neil Martin, chairman of the UCLA Department of Neurosurgery. “This gift will pay tribute to Nina’s life by benefiting other patients for generations. Hundreds of children and adults with epilepsy worldwide have been cured by physicians using the techniques and technologies developed at UCLA.”

The UCLA Department of Neurosurgery is committed to providing the most comprehensive patient care through innovative clinical programs in minimally invasive brain and spinal surgery; neuroendoscopy; neuro-oncology for both adult and pediatric brain tumors; cerebrovascular surgery; stereotactic radiosurgery for brain and spinal disorders; surgery for movement disorders such as Parkinson’s disease; and epilepsy surgery. For 20 consecutive years, the department has been ranked among the top 10 neurosurgery programs in the nation by U.S. News & World Report.