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Jim Eliassen, PhD, Associate Director of the Neuroscience Graduate Program
and Professor of Psychiatry, asks a question during the annual Nasrallah Lecture
on Schizophrenia. Photos by Cindy Starr / Mayfield Clinic.

The University of Cincinnati Neuroscience Institute’s mission has three components: patient care, research and education. The third part of that mission was on proud display this week as multiple neuroscience disciplines and centers of excellence staged premier lectures and presentations. From brain metastasis to multiple sclerosis to schizophrenia to rare movement disorders, the topics of the educational sessions were designed to intrigue and inspire clinicians, researchers and supporters to continue pressing forward in new directions at the UC Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health.

What do dandelions and brain metastases have in common?

Ronald Warnick, MD, Medical Director of the UC Brain Tumor Center, spelled out the problem of brain metastasis in stark terms at the fourth annual Wine Tasting Celebration at the Myers Alumni Center Tuesday night on the UC campus. This year, 170,000 people will be diagnosed with a brain metastasis in the United States alone, and the problem is increasing because people increasingly survive cancer. Whereas only 50 percent of cancer patients lived five years in 1975, 70 percent do so today. Lung cancer, breast cancer and melanoma are the most likely cancers to metastasize, or spread, to the brain.

Dr. Warnick explained brain metastasis with an analogy to seed and soil. Just as a dandelion’s seeds break away, blow in the wind and land in the soil, a lung or breast cancer’s cells break off and spread through the bloodstream and settle in another part of the body. And just as dandelions sprout anew in fertile, nutrient-rich soil, cancer cells take root as new tumors when they settle in the brain.

James Driscoll, MD, PhD, of the UC Brain Tumor Center

The source of nutrients, Dr. Warnick said, is healthy brain cells. With the help of funding generated by the 2012 Wine Tasting event, James Driscoll, MD, PhD, and his research team looked at how normal brain cells are providing nutrients to the invading cancer cells and causing uncontrolled growth, Dr. Warnick said. “A signal called micro RNA is stimulating the tumor cells to grow uncontrollably, while activating a force field that protects the cancer cells from chemotherapy. The result is a brain metastasis that is growing rapidly and is resistant to our common therapies.”

Dr. Driscoll’s next step was to introduce a suppressor that blocked that micro RNA signal, thereby preventing the cancer cell from receiving nutrients from healthy brain cells. This, in turn, caused the cancer cells to wither and die, like dandelion seeds that land on dry, barren soil. Dr. Driscoll is now testing the therapy in an animal model. If successful, it could lead to a phase I clinical trial for brain metastasis in early 2014.

Dr. Warnick closed his remarks by thanking the Brain Tumor Center’s supporters. “Your generosity and support last year allowed us to do this cutting-edge research, and your support tonight will allow us to take on the next promising avenue of research.”

What is plaguing our patients with rare movement disorders?

The Unusual Movement Disorders Marathon Symposium drew more than 150 neurologists, residents-in-training and experts from six countries Wednesday evening at the Cincinnati Club in downtown Cincinnati. The event was directed by Alberto Espay, MD, Research Director at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders and a neurologist at UC Health.

Symposium Director Alberto Espay, MD, of the UC Gardner Center

During the symposium 12 professors each presented one of the most challenging cases of their careers, and a group of three internationally known specialists (pictured above) with no prior knowledge of the cases then discussed them and worked to arrive at the correct diagnoses and optimal treatment plans.

The heart-rending cases, illustrated by video, depicted once-healthy people struggling with ruinous symptoms that included cognitive decline, shaking, rigidity and freezing of gait. The cases were also staggeringly difficult, in some cases stumping the panel. They demanded knowledge of genetics, pathology, neurology and physiology, and they illuminated the profound difficulties that can confront a neurologist who is working independently.

Among these, there was a rare case of galactosemia and a singular case of “slowly progressive” rapid-onset dystonia parkinsonism (RODP). (Only 50 cases of RODP have been recorded since 1993.) There was a syndrome precipitated by legionella, the pathogen that causes Legionnaires disease. Another case presentation, which had bedeviled doctors at a leading center for four years, was just recently solved with an observation from a neurologist from another center.

The event, endorsed by the Movement Disorder Society and likely to be repeated in the future, was supported by educational grants from Merz, Ipsen, Allergan, USWorldMeds, Athena diagnostics, Medtronic and UCB.

Dr. Carol Tamminga, the 2013 Nasrallah Lecturer, and Dr. Henry Nasrallah of the UC Mood Disorders Center

What is the role of the hippocampus in schizophrenia?

Carol Tamminga, MD, Professor and Chairman in the Department of Psychiatry at the University of Texas Southwestern Medical School and a longtime leader in the field of schizophrenia, presented the 2013 Nasrallah Lecture Wednesday at UC.

Schizophrenia is a brain disease whose “bizarre and almost unbelievable symptoms,” in Dr. Tamminga’s words, have driven her quest to answer the question: “How can a brain do that?”

For the last 15 years she has focused her attention on the hippocampus, a small area of the brain that is “the size of your little finger” and that plays a role in synthesizing experiences into coherent memories. The brain has two hippocampi, one on each side, and within the hippocampi are “little stations that perform unique tasks and have unique functions,” she said. “We rely on the hippocampus, which is highly plastic, to learn something new.”

People with schizophrenia have alterations in parts of their brains, including the hippocampus, which appear to contribute to psychosis (hallucinations, delusions or other break from reality).

Dr. Tamminga and her team are examining hippocampal plasticity in schizophrenic psychosis with brain imaging and post-mortem tissue. They have found many things, including increased blood flow in one part of the hippocampus, a decrease in glutamate levels in another area and an elevated concentration of GluN2A, a subunit of the NMDA receptor, which ideally works like a good traffic cop in keeping brain signals flowing smoothly and efficiently but can become involved in several brain pathologies. Elevated GluN2A makes an area of the hippocampus “more susceptible to plasticity,” Dr. Tamminga said. “We speculate that it gets going too fast, makes mistakes, produces memories with psychotic content.”

Dr. Tamminga also noted that dendrites, the long, branching tails of brain cells that transmit stimuli to the cells, have smooth borders and occasional bumps in healthy brains but, in schizophrenic brains, are burdened “with a great clutter of stuff, a huge increase in spines.” These rough-edged dendrites produce super-sensitivity in part of the hippocampus, increasing the excitability of neurons.

The ultimate goal of her research, she said, is to translate these discoveries into new treatments for people who develop schizophrenia.

The Nasrallah Schizophrenia Lecture is made possible
by the Henry A. Nasrallah, MD, Endowed Lectureship Fund.

What is the role of T cells in multiple sclerosis?

Dr. Michael Racke, Chair of Neurology at the Wexner Medical Center at Ohio State University, discussed the role of T cells in multiple sclerosis at the annual Aring Lecture Wednesday at UC. “T cells are thought to be an important determinant in why some patients get MS and others do not,” explains Joseph Broderick, MD, Research Director at UCNI and the Albert Barnes Voorheis Professor and Chairman of UC’s Department of Neurology and Rehabilitation Medicine.

“In particular, Dr. Racke’s laboratory is examining the effect of micro RNAs that regulate gene function and changes in the T cell response, in both animal models and humans. This work could potentially lead to new, specific treatments for MS. In the meantime, this works provides some insights on how some of the medications we use for MS actually work.”

The Aring Lecture is named in honor of Dr. Charles Aring,
founder of the Department of Neurology at the University of Cincinnati College of Medicine.

– Cindy Starr

Henry Nasrallah, MD, Course Co-Director of the 3rd Annual
Mood Disorders Symposium. Photo by Cindy Starr / Mayfield Clinic.

What did Abraham Lincoln, Winston Churchill, Leo Tolstoy, Virginia Woolf and Jimi Hendrix have in common? And what condition do Judy Collins, James Taylor, Kitty Dukakis, Kay Jamison and Catherine  Zeta-Jones also share? The answer is bipolar disorder, a mood disorder characterized by periods of high energy, euphoria or irritability, and sleeplessness followed by periods of depression.

The condition was the topic of Saturday’s third annual Mood Disorders Symposium, a continuing education event that was held at UC Health Drake Center. The event was sponsored by the Mood Disorders Center at the UC Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health; the Department of Psychiatry and Behavioral Neuroscience; and the Center for Clinical & Translational Science & Training.

Henry Nasrallah, MD, Professor of Psychiatry and Behavioral Neuroscience and Vice Chair for Education and Training, said the topic was a fitting one for May, which is national Mental Health Awareness Month. April and May represent the peak suicide months of the year, and 15 to 18 percent of people with bipolar disorder will die of suicide if they go untreated. “Bipolar disorder can make a person more creative and productive, and there are many examples of high-achieving people with bipolar,” Dr. Nasrallah said. “Georg Friedrich Händel wrote the Messiah in two weeks during a manic episode. But the condition is also disabling. Bipolar disorder has one of highest associations with suicide in medicine.”

Stephen Strakowski, MD, explained the neurobiology of bipolar disorder.

Stephen Strakowski, MD, the Stanley and Mickey Kaplan Professor and Chair of the Department of Psychiatry and Behavioral Neuroscience and Vice President of Research for UC Health, said bipolar disorder is a brain disease. “It is not caused by bad parenting or the environment; it is caused by genetics,” he said.

Fortunately, many treatments for bipolar disorder exist, including longstanding medications (e.g., lithium), newer mood stabilizers and antipsychotics, various types of interpersonal and family-focused therapy, transcranial magnetic stimulation and electroconvulsive therapy.

Bipolar disorder exists on a spectrum, Dr. Nasrallah said, and a recent survey of 100,000 people suggests that it affects 3.7 percent of the population. People with bipolar I suffer severe depression and mania (disabling extreme moods) and may be hospitalized for both. People with bipolar II have less dramatic periods of “hypo-mania” and are hospitalized only for major depression. “Bipolar patients are the ones who are reading four or five books at the same time,” Dr. Nasrallah said. “They typically are not diagnosed until the mania interferes with their job or they are hospitalized.”

Treatment is vital because a brain bathed in cortisol – a stress hormone – can undergo serious changes. Although bipolar disorder cannot be diagnosed with brain imaging, brain imaging studies have revealed specific characteristics in the bipolar brain. Several imaging studies, but not all, have shown that the amygdala appears to develop abnormally in untreated patients with bipolar disorder.

“The amygdala, which processes our fight-or-flight reactions to fear, is smaller than normal in children and enlarged in adults with bipolar disorder,” Dr. Strakowski said. “The developmental process in the amygdala has gone awry.”

At the same time, the ventricles, reservoirs where fluids are exchanged, spread and grow larger, reflecting a loss of surrounding brain tissue. “These patients lose white-matter connections, the connecting neuronal pathways, in the brain,” Dr. Strakowski said. “We worry that the efficiency of these networks is degrading.”

Brain imaging of people with bipolar disorder reveals heightened activity in the amygdala and prefrontal cortex, where executive function resides. “Our hypothesis is that the prefrontal cortex is over-working to control an over-activated amygdala,” Dr. Strakowski said. “The brain is compensating at baseline, struggling to maintain a dysfunctional emotional regulatory system. During mania, the amygdala loses prefrontal control, which leads to wild emotional swings.” Glutamate, an  excitatory neurotransmitter, is elevated in people with bipolar disorder, as is lactate in the brain, reflecting abnormalities with energy management “at a very deep cellular level,” he said.

Other general points of interest from the symposium included:

Only 20 percent of people with bipolar disorder have been diagnosed, and the average person with the condition will suffer for eight years before receiving a correct diagnosis. The average age at onset is 18 to 24 years, although children have also been diagnosed with the condition. Sixty percent will initially be diagnosed with depression. Bipolar disorder is equally common in men and women, while unipolar depression is much more common in women.

In families with strong heredity, the onset of bipolar disorder may occur earlier with successive generations.

After April and May, October brings the second-highest wave of suicides. Researchers theorize that the light-dark change triggers mania, which leads to suicide. A lethal combination of “depressive thinking, combined with the energy to do something about it,” results in these tragedies, Dr. Strakowski said. “We need to keep a close eye on patients at those times.”

Medications for bipolar disorder can include a host of unpleasant side-effects and can be challenging for patients. A collaborative partnership among health care providers and caregivers and family can maximize the potential for recovery, said Cal Adler, MD, Associate Professor of Psychiatry and Behavioral Neuroscience and Co-Medical Director of the UC Mood Disorders Center.

Catherine, a social worker, shared her story of recovery.

Catherine, a survivor of bipolar disorder who is now a social worker, said that therapy, medication, family support and a consistent work and sleep schedule were all part of her recovery.

Melissa DelBello, MD, Professor of Psychiatry and Behavioral Neuroscience and Co-Medical Director of the UC Mood Disorders Center, said some data suggest that omega 3’s will help some depressive symptoms. Even if they fail to do so, they can help counteract risk factors like weight gain, a side-effect of some medications.

When to switch doctors? A patient should switch if he or she does not like his or her physician and should not fear getting a second opinion. “Only a weak doctor would object to your getting a second opinion,” Dr. Strakowski said. “If your doctor objects to getting a second opinion, that alone suggests it’s time for a change.”

– Cindy Starr

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Bipolar disorder is a condition characterized by extremes. Dr. Melissa DelBello describes the disorder as one that includes periods of extremely elevated mood as well as periods of severe depression. During these cycles the risk of suicide is high and relationships often suffer with family members, coworkers and friends.  Dr. DelBello explains that understanding the symptoms of bipolar disorder is crucial to the future of its treatment.

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Alberto Espay, MD, MSc, a rising global star, is Symposium Director for an international educational event for clinicians on May 15. Photo by Cindy Starr / Mayfield Clinic.

In Dr. Alberto Espay’s hands, good ideas just keep getting better. A specialist at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health, Dr. Espay has elevated an educational concept called Movement Disorders Video Rounds from an institutional event to one that is regional, national and now international. On May 15, clinical experts from six countries will arrive in Cincinnati for the first Unusual Movement Disorders Marathon Symposium. For established neurologists and those in training, the symposium will distill into five hours lessons that normally might take a lifetime to learn.

During the symposium, which is targeted to clinicians, 12 professors will each present one of the most challenging cases of their careers. A group of three internationally known specialists with no prior knowledge of the cases will then discuss them and – theoretically – will arrive at the correct diagnoses and optimal treatment plans. Those in the audience will have a rare educational opportunity to experience dialogues about cases that they might see but not recognize as distinct diseases.

Clinicians can still register to attend
the Unusual Movement Disorders Marathon Symposium.
Register now >>

Dr. Espay, Symposium Director and a rising star internationally, describes his speakers as “a collective brain trust” that will present challenging cases “in a format that would be most instructive and deliver the highest yield of clinical pearls to trainees, physicians in our community, and neurologists interested in movement disorders.”

The cases themselves, Dr. Espay said, provided lasting lessons for the professors entrusted in presenting them. “The road to diagnosis and treatment was bumpy, but the bumps themselves represented educational opportunities for these professors that they feel are worth disseminating.”

“We will also learn how an expert addresses a complex situation that may take months or even years for someone else in the community. Our international experts are naive to these cases. The gift to the audience is seeing these experts digest in real time a set of complex information in a manner that leads to a focused work-up, a final diagnosis and, of course, appropriate treatment.”

At the end of each discussion, the original presenter will describe his or her own findings and share his own lessons learned.

Each case presentation will include video, because the visual component is vital in the diagnosis of movement disorders. A sampling of presentations include: “A Young Woman with a Long History of Shaking,” “Losing the Mind and then Gaining it Back,” and “The Man who Couldn’t Refrain from Coughing.”

Dr. Espay, Associate Professor of Neurology at UC and the Gardner Center’s Director of Clinical Research, began bi-monthly video rounds at UC seven years ago, building on an idea that had been used, and then discontinued, by the American Academy of Neurology.  The concept became popular among UC neurologists, fellows and residents and soon grew into a friendly TriState, then TetraState, Video Rounds competition. A national video rounds lecture, led by Dr. Espay and two colleagues, was sold out at the recent American Academy of Neurology Annual Meeting.

“We gave our own flavor to this concept, making it not just a challenge but an opportunity to say, ‘What lessons can I take away from this and apply in my practice?’“ Dr. Espay said. “We infused video rounds back into the Academy this year with an overhauled, educationally enhanced Unusual Movement Disorders Symposium.”

Speakers at the Cincinnati symposium, to be held at the Cincinnati Club downtown, will come from throughout the United States as well as Canada, Mexico, the United Kingdom, Italy and Brazil. The expert case discussants are Anthony Lang, MD, of the University of Toronto; Joseph Jankovic, MD, of Baylor College of Medicine in Houston; and Kapil Sethi, MD, of the Medical College of Georgia in Augusta.

The international Movement Disorders Society has endorsed the symposium and is so interested in the concept that it has asked Dr. Espay whether he would consider moving the event from Cincinnati and holding it twice a year, once on each coast. To this particular question, Dr. Espay does not yet have an answer.

– Cindy Starr

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