Spring 2023 UTHealth Houston Neurosciences Journal

That Extra Something is Passion Stephen Hawking has said that science is not only a disciple of reason, but also one of romance and passion. What separates the best clinicians from the pack? Passion, perseverance, talent, skill, and support to pursue a vision. In this issue of the UTHealth Houston Neurosciences Journal, you will learn about a handful of physicians driven by a passion to help their patients live meaningful lives. In our cover story, “No Patient Left Behind,” Dr. Anjail Sharrief shares the roots of her passion for ensuring that patients who have suffered a stroke continue to receive outstanding care after discharge from the hospital.

Her passion, along with support from the Department of Neurology at McGovern Medical School at UTHealth Houston, allowed her to start the Stroke Transitions Education Prevention (STEP) Clinic at the medical school. Few stroke programs follow patients so closely after discharge from the hospital. Dr. Sharrief and her team work with patients intimately to identify their personal risk factors, solve any problems they have with community re-entry, and help them move toward a healthy lifestyle.

Dr. Shivika Chandra, chief of neurology at Lyndon B. Johnson Hospital and UTHealth Houston neurology clinics in the Harris Health System, works together with the other 31 UTHealth Houston specialty clinics operating at the hospital to develop innovative strategies for care as they build an ideal safety-net model for caring for outpatients.

Dr. Erin Furr Stimming, whose research is focused on Huntington’s disease, developed a passion for patients with the genetic, progressive, and ultimately fatal disease during her movement disorders fellowship. As principal investigator of the KINECT-HD Huntington Study Group, she presented positive findings from the Phase III study of valbenazine for the treatment of chorea at the 2022 American Academy of Neurology Annual Meeting in Seattle.

A special thanks to Mr. Xavier Alejandro Pech for sharing his story of illness and recovery. Known to have an adrenal adenoma, he was seen by an astute endocrinologist, Dr. Lavanya Sendos, who noticed that his symptoms pointed to the pituitary gland rather than the adrenals. She referred him to Dr. Spiros Blackburn, director of our Pituitary Tumor Clinic, who ordered an MRI and then used inferior petrosal sinus sampling to confirm the presence of a pituitary adenoma. After collaborative surgery by Dr. Blackburn and rhinologist Dr. William Yao, and continued management of his cortisol levels, Mr. Pech has found relief.

Congratulations to Dr. Eddie Patton, who has been named president of the Texas Neurological Society, and a special welcome to our 19 new faculty members. In this issue, we also highlight our upcoming events, including the 10th Annual Neuro ICU Symposium, to be held from May 10-12, 2023.

We continue our work together as neurologists, neurosurgeons, pain management specialists, neuro oncologists, neuroophthalmologists, neurocritical care specialists, neuropsychologists, pediatric neurosurgeons, and radiation oncologists to provide the best in clinical care and to advance research. If you would like to learn more about us, please feel free to contact us directly.

With best wishes,

No Patient Left Behind: STEP’s Patient-Centric Approach to Stroke Prevention and Recovery

The Stroke Transitions Education Prevention (STEP) Clinic at McGovern Medical School at UTHealth Houston offers a post-hospital lifeline to stroke patients regardless of their income, education, or social standing.

Begun in 2014 as the dream of Anjail Z. Sharrief, MD, MPH, associate professor in the Department of Neurology, the STEP Clinic serves patients who have had or are at high risk for having a transient ischemic attack, an ischemic stroke, or a hemorrhagic stroke.

“Stroke is a preventable disease with devastating consequences,” says Sharrief, the founding director of STEP, director of stroke prevention at the UTHealth Houston Institute of Stroke and Cerebrovascular Disease. “We work closely with our patients to identify their personal risk factors and help them move toward a healthy lifestyle by eating right, staying active, managing stress, connecting socially, and maintaining a healthy weight.

Changes like these take time, and our goal is to provide our patients in the community with the resources they need over the long haul.”

Sharrief’s passion for ensuring that patients with neurological disease receive outstanding post hospital stroke care has roots in her high school desire to become a neurosurgeon. “I read ‘Gifted Hands: The Ben Carson Story’ and was inspired. Dr. Carson was from Detroit, where I was born, and was one of the first Black neurosurgeons in the U.S. I wanted to be among that group.”

After graduating from Smith College with a bachelor’s degree in neuroscience, Sharrief worked at the National Institute of Mental Health as a post-baccalaureate research trainee and went on to earn her medical degree at Columbia University in New York City.

“I entered Columbia because it has an outstanding reputation in the neurosciences, and I still intended to be a neurosurgeon. I also had a strong interest in public health, so I started a public health group at the medical school. My strong interest in public health and experiences managing patients with neurological diseases in West Africa eventually led me to neurology,” she says.

Sharrief completed neurology residency training at the Johns Hopkins Hospital in Baltimore, where she served as chief resident from 2010 to 2011.

“At Hopkins, I became even more interested in community outreach. I was working with a stroke group focused on public health and signed on for a neuro-infectious disease rotation in Dakar, Senegal. There were so many stroke patients in Dakar that patients with infectious diseases affecting the nervous system
had to be managed by internal medicine,” she says. “It was eye-opening to see a similar prevalence of high blood pressure and other uncontrolled risk factors in both Baltimore and Dakar. This led me to the idea that to have an impact on neurological care globally, I should start by acting locally.”

In 2012, she further pursued her interest in public health with a master’s degree from the Johns Hopkins Bloomberg School of Public Health. When it came time to consider her next step, she reached out to several academic institutions about her dream of extending stroke care from the hospital to the community, including UTHealth Houston, where James C. Grotta, MD, was then chair of the Department
of Neurology.

“Dr. Grotta suggested we schedule a phone call, and I shared my idea for a stroke prevention clinic,” Sharrief says. “He spoke to leaders at the medical school and secured funding to bring me on board. I named the clinic STEP – stroke, transitions, education, and prevention – and joined the faculty at McGovern Medical School as an assistant professor in 2013.”

The STEP Clinic started within a year and expanded more quickly than Sharrief expected. “At first, I thought it would be focused only on risk assessment and risk factor control, and then we realized that stroke patients are suffering with many additional problems,” she says. “Cognitive impairment, depression, fatigue, and return to work are very important to patients after stroke.” Houston, with its enormous diversity, turne out to be an excellent location for the program.

“There are very well-described disparities in stroke incidence, mortality, and stroke recurrence in Black adults in the United States,” she says. “The risk for stroke in young Black men between the ages of 45 and 55 is four times greater than their white counterparts. Black Americans are at highest risk for high blood
pressure, but it is clear that their overall risk for stroke is explained by more than medical factors. Socioeconomic status, education, health literacy, access to health insurance, social networks, social support systems, and structural racism also play roles.”

The staff is trained to recognize the consequences of stroke, including depression, fatigue, changes in thought patterns and memory, and other factors that affect recovery. Staff members include Sharrief and stroke physicians Chigozirim Izeogu, MD, assistant professor of neurology, and Munachi Okpala, DNP, MBA, MSN, APRN, assistant professor and stroke-trained nurse practitioner. Through Sharrief’s research program, she also works with three pharmacists and two social workers to improve the transition of care from hospital to home. The team provides education about stroke and TIA; screening for stroke risk
factors; management of hypertension, high cholesterol, and tobacco use; screening and treatment of fatigue, depression, memory/cognitive disorders; post-stroke pain; referrals for management of diabetes, nutrition programs and intensive tobacco cessation programs; referrals for driving assessments; and programs to assist with return to work.

Together, the team sees more than 1,000 patients each year at the Texas Medical Center alone.

In December 2021, Sharrief and her team started a STEP Clinic at UTHealth Houston Neurosciences-Memorial City, where Okpala meets with patients every Monday. In November 2022, they opened a third STEP clinic, led by Shalene Amin, MD, at UTHealth Houston Neurosciences-Southwest. Amin is a graduate of the fellowship program Sharrief started to train physicians in stroke risk assessment and prevention in the community.

“We also try to engage the family if the patient has that support,” Sharrief says. “We provide extensive education in person and through printed materials, including a brochure describing how to check blood pressure.”

Sharrief has a passion for mentoring and is ensuring the expansion of the STEP Clinic program through the one-year Stroke Prevention Fellowship she directs at McGovern Medical School. The fellowship program focuses on giving physicians who have completed neurology, internal medicine, or family medicine residencies specialized and multidisciplinary training in aspects of primary, secondary, and tertiary stroke prevention.

Fellows are trained to provide patient care and comprehensive preventive care focused on the management of risk factors that include hypertension, diabetes, dyslipidemia, and obstructive sleep apnea, as well as evaluation of depression, cognitive impairment, and other stroke complications. The program accepts one to two fellows per year.

“Many of our fellows have gone on to other medical centers and started stroke prevention programs,” Sharrief says. “We meet once a month as a consortium that includes physicians, nurses, pharmacists, and students who work on projects collaboratively to share new ideas and information about access to community resources.”

She is also conducting several clinical trials at UTHealth Houston funded by the National Institutes of Health and is principal investigator of VIRTUAL, Video-Based Intervention to Address Disparities in Blood Pressure Control After Stroke, a single-center study at UTHealth Houston and Memorial Hermann-TMC. The purpose of the study is to examine the impact of a multidisciplinary telehealth-based model of outpatient stroke care on blood pressure control following stroke, and further, to evaluate its impact on racial disparities in post-stroke blood pressure control.

The study was funded in September 2021 by the National Institute on Minority Health and Health Disparities and began enrolling participants in March 2022. Currently, 185 patients are enrolled out of 534 who will join the study over the next three years.

“We give participants a blood pressure monitor in the hospital, and their data comes to our team through a portal designed by collaborators at UTHealth Houston School of Public Health,” she says. “They see a stroke provider – either a neurologist or nurse practitioner – a social worker, and a pharmacist as part of the study.

The pharmacist reviews their blood pressure results weekly and adjusts their medication as needed.”

For more information about the VIRTUAL trial, please call (713) 600-6538 or email
[email protected]. For information or to refer patients to the STEP Clinic, call (832) 325-7080.

Diagnosis and Treatment of Cushing’s Disease Caused by a Pituitary Adenoma

In November 2021, Xavier Alejandro Pech, 49, began suffering severe bone and joint pain and dizziness. Prior to the onset of these symptoms, he endured others that came and went over a period of three years: difficulty swallowing, allergies, fatigue, muscle stiffness, flatulence, muscle weakness, and weight gain that fluctuated between 270 and 308 pounds.

“It was very frustrating and painful, and I felt hopeless,” Pech says. “If the weather was cold, it was unbearable, and I spent most of my days in bed. I had to be transported in a wheelchair and was unable to perform the most basic activities of daily life. I was taking so many medications for pain and my other symptoms that I was afraid my liver would be damaged.”

Pech had seen a rheumatologist and a cardiologist, without finding relief. Then his family physician referred him to Lavanya Sendos, MD, assistant professor in the Division of Endocrinology, Diabetes, and Metabolism at McGovern Medical School at UTHealth Houston. Sendos saw him in February 2022 at the UT Physicians Multispecialty Clinic in the Houston suburb of Bellaire.

“He was known to have an adrenal adenoma and came to me because imaging had shown an increase in the size of the nodule,” Sendos says. “His muscle weakness and weight gain pointed to high cortisol levels and are conditions concerning for Cushing’s disease. He also had an abnormal 2-milligram dexamethasone suppression test, a strong indicator for Cushing’s. I ordered an adrenocorticotropic (ACTH) blood test, and when I reviewed his lab studies, I found that the numbers pointed to the pituitary gland, rather than the adrenals.”

Sendos referred Pech to Spiros Blackburn, MD, associate professor and director of the Pituitary Tumor Center in the Vivian L. Smith Department of Neurosurgery at the medical school, for evaluation for a pituitary tumor that might be the cause of his Cushing’s disease. Blackburn ordered a pituitary protocol MRI that showed what appeared to be a small pituitary adenoma.

“The tumor was difficult to see on MRI, which concerned me that it would be hard to locate and remove during surgery,” he says. Sendos presented Pech’s case at the medical school’s pituitary conference, led monthly by Katie Guttenberg, MD, associate professor in the Division of Endocrinology, Diabetes, and Metabolism, with specialists attending from neurosurgery, endocrinology, neuroradiology, and neuropathology. Both Sendos and Guttenberg work closely with Blackburn on pituitary cases. “We review surgical cases from the previous month and discuss upcoming cases with clinical questions,” she says. “In Mr. Pech’s case, we recommended IPSS.”

Inferior petrosal sinus sampling is an infrequently used method of confirming the presence of a hormonally active pituitary adenoma when imaging alone has been insufficient. The technique can confirm that excess ACTH is being produced by the pituitary and can also help determine the exact location of the tumor.

Blackburn performed the IPSS endovascularly under anesthesia, inserting catheters through the femoral arteries into both petrosal sinuses. “Then we measure the levels of ACTH on both sides,” he says. “If the level is higher on the right, the tumor is probably on the right. We confirmed that the tumor was on the right side of the sella turcica, which was consistent with our MRI results. So in this case, the IPSS was a
good confirmatory test.”

Pech says he was hopeful that he would find relief. “Finally, someone had found the cause of my pain and the decline in my health,” he says. Blackburn took Pech to the OR in August 2022 and resected a 5-millimeter tumor through a small incision on the pituitary gland using an endoscopic transsphenoidal approach performed through the nose with William C. Yao, MD, associate professor of otorhinolaryngology. The two surgeons have worked together since 2015.

“The vast majority of patients leave the hospital two days after surgery and do quite well,” Guttenberg says. “For patients with Cushing’s disease, follow-up treatment is a little more complicated because they tend to have low cortisol after removal of the tumor.”

Sendos, who is seeing Pech in follow-up, prescribed hydrocortisone. “In patients with Cushing’s disease, the adrenal glands are suppressed and tend to recover slowly after tumor removal,” she says. “It generally takes about a year for patients to start producing enough cortisol to stop taking the hydrocortisone, but we’re slowly tapering it down. Recently, his wife noticed that he has been more active and that his sensitivity to cold has improved tremendously. He continues to improve daily.”

Although total recovery is a process, Pech says he’s finally found relief. “Dr. Sendos was wonderful. She was very thorough, and I thank her for taking over management of my medical care and for finding a solution,” he says. “I’m also thankful to Dr. Blackburn for his excellent care and how both of them continue to manage my health and address any concerns I have.”

Blackburn and Guttenberg share a clinical space in Suite 2800 at 6400 Fannin St. in the Texas Medical Center, where they see patients in one visit. “We average about two pituitary surgeries per week,” Guttenberg says. “I see the majority of pituitary patients for preoperative evaluation, Dr. Blackburn performs the surgery, the inpatient endocrine service sees all patients while they’re hospitalized to screen for hormone problems after surgery, and then we follow up with them after discharge to check their
hormone levels.”

To refer a patient for evaluation, call (713) 486-7760.

The Harshest and Most Hidden Affliction: Shining the Light on Huntington’s Disease

Huntington’s disease (HD) is genetic, progressive, and fatal. The neurodegenerative disease typically strikes between the ages of 35 to 55 years, the most productive years of life. Its protracted deterioration of the brain causes involuntary motor movements, behavioral impairment, and cognitive decline that result in complete dependence and a slow, cruel death over about two decades.

Erin Furr Stimming, MD, professor of neurology and Memorial Hermann Chair at McGovern Medical School at UTHealth Houston and lead physician at the medical school’s designated top-level Huntington’s Disease Society of America (HDSA) Center of Excellence, first became interested in movement disorders during her third year of medical school. “I encountered patients with neurological disorders and fell in love with neurology,” she says. “At the same time, my dad’s oldest brother was diagnosed with Parkinson’s disease and I became involved with his care. He inspired me by showing that it’s possible have Parkinson’s and still live a life of dignity and grace.”

Furr Stimming treats patients with the full range of movement disorders, including Parkinson’s disease, Huntington’s disease, and atypical Parkinsonian syndromes, but her research is focused on HD. “I became fascinated with the genetics and pathophysiology of HD during residency, but it wasn’t until I started working with patients during my movement disorders fellowship that I decided I wanted to focus on Huntington’s disease,” she says.

As a new faculty member at McGovern Medical School, she managed the care of a woman with HD who was struggling to navigate life with the disease. “It was no longer safe for her to live at home, and her husband was heartbroken,” she says. “I sat with both of them as we had the difficult conversation about transitioning to a longterm care facility. At that moment, I decided I needed to build a team to help my patients through their HD journey.”

Furr Stimming received a donation from a Houston philanthropist that allowed her to hire a social worker. From there, she began assembling a team to care for her patients with HD. She applied for Center of Excellence (COE) designation from the HDSA and received it.

“We started as a Level 3 COE based on the number of patients we treated and the services we offered,” she says. “The following year we moved up to Level 2. In 2020, we were granted the Level 1 designation and are one of only five in the country. We are partnering with sites outside Houston – in Lubbock, Austin, and San Antonio – to expand HD awareness and care throughout Texas.”

When Furr Stimming makes presentations on Huntington’s disease, she shows photos of American singer-songwriter and folk musician Woody Guthrie, who has been the face of Huntington’s disease for more than 50 years. His wife Marjorie Mazia Guthrie was the force that led to the creation of the Huntington’s Disease Society of America. The two met in 1942 and married the following year. By the late 1940s, Guthrie’s health was in decline, and after various misdiagnoses, in 1952 he was found to have Huntington’s disease. In 1967, Marjorie Guthrie placed a small ad in a New York City newspaper, and gathered a handful of volunteers and HD families from across the United States. That same year, she and five other volunteers formed the Committee to Combat Huntington’s Disease (CCHD) to improve the lives of people affected by HD and their families. About two weeks later, her husband died from complications of HD at age 55.

Marjorie Guthrie dedicated the remainder of her life to raising awareness of HD and funds for research that might lead to a cure. She served on state and federal government panels and was a founder of the National Committee for Research in Communicative Disorders, a coalition of health agencies and scientists who worked to increase funding for the National Institute for Neurological Disorders and Stroke. She spoke at hundreds of medical conferences, seminars, and media interviews, and convinced President Jimmy Carter to form a Presidential Commission to study neurological diseases, including HD. Recommendations from the commission’s 1977 report serve as the cornerstone of CCHD’s commitment to the care of patients with HD and their search for a cure.

In November 1983, Marjorie Guthrie’s CCHD became the Huntington’s Disease Society of America, a living memorial to Woody and her tireless work to raise awareness. It also brought together hundreds of HD families in a shared determination to defeat HD. That same year, an HDSA Coalition for the Cure investigator found the first marker for the disease, and after a 10-year search that involved collaboration among the top HD researchers worldwide, the HD gene was located on the short arm of chromosome 4.

HDSA has supported laboratory research and translational research, as well as human clinical trials that test the most promising drug agents at HDSA Centers of Excellence, including Furr Stimming’s.

“I am deeply moved by the resilience of our patients and families who continue to fight HD with strength
and courage,” she says. “HD is a devastating disease for many reasons. Each child of an affected parent has a 50% chance of inheriting the disease. We’re following some families in which most if not all of the children have inherited it. Every person with HD has the same type of mutation in one gene, while most other common neurodegenerative diseases have many different causes. In caring for individuals with HD, we strive to optimize quality of life with medication and other nonpharmacologic strategies. We aim to empower our patients with knowledge about the research underway searching for improved symptomatic medications and therapies that halt or slow disease progression.”

When Furr Stimming makes presentations about HD, she also shows Dr. Nancy Wexler’s photo. An American PhD geneticist whose mother was diagnosed with HD, Wexler is best known for her involvement in the discovery of the location of the gene that causes HD, working among a large community of families living in remote pueblos surrounding Lake Maracaibo, Venezuela, where the disease is prevalent. She traveled to the villages of Laguneta, San Luis, and Barranquitas to obtain DNA samples from a large family in which the majority had Huntington’s disease. The samples her team collected were instrumental in enabling a global collaborative research group to locate the gene. She also participated in the successful effort to create a chromosomal test to identify carriers of HD.

A National Institutes of Health-funded research consortium of interdisciplinary investigators isolated the gene using the hundreds of blood samples collected from the HDaffected families in Venezuela. Many scientific and medical findings that have improved the medical community’s understanding of HD were made possible through the participation of the Venezuelan HD patients, their families, and their communities.

“The causative mutation was identified by Dr. Wexler and her colleagues in 1993. Ongoing advances in technology have led to clinical trials evaluating various compounds that safely and effectively modify the gene or gene product,” Furr Stimming says. Furr Stimming is also involved with Factor-H, an organization created in 2012 that aims to improve the quality of life of people affected with Huntington’s disease living in extreme poverty and social neglect. Factor-H works with communities across Latin America to provide humanitarian and medical assistance.

“Factor-H also educates physicians as part of the effort to improve care,” she says. “It’s an honor to be part of the HD scientific community and to get to know clinicians around the world through this organization and others. As a result, HD is better known, also due in part to our ability to communicate across countries through videoconferencing, which was speeded up during the COVID-19 pandemic.”

Increased awareness and funding has allowed HDSA to fund more Centers of Excellence in the United States. “Our greatest need now, besides the approval of a disease-modifying therapy, is an increased number of care providers who specialize in HD,” Furr Stimming says. Charles Sabine, an Emmy Award winning television journalist who worked for NBC News for 26 years, tested positive for the HD gene in 2006. After retiring, he became a global spokesman for patients and families living with degenerative brain diseases. He is active through advocacy and charity across four continents and is the founder of the Hidden No More Foundation.

On his website, he describes Huntington’s disease as “not just the harshest affliction known to mankind but also the most hidden.” In May 2017, Sabine became the first person with Huntington’s disease to meet publicly with a world leader – Pope Francis. Speaking to a global TV audience and an in-person
audience of 1,800 in Vatican City, the largest number of people ever gathered publicly to discuss Huntington’s disease, the Pope said, “Today, we want to say to ourselves and all the world: HIDDEN NO MORE! ¡OCULTA NUNCA MAS! MAI PIU NASCOSTAI!. This is not simply a slogan, so much as a commitment we all must foster.”

When Queen Elizabeth II appointed Sabine to the Most Excellent Order of the British Empire (OBE) in January 2022, he pledged to use the honor to further his mission, “encouraging ever greater numbers to join the global collaboration with researchers and scientists so we can further enact a paradigm shift for all of us affected by Huntington’s disease and to empower ourselves with the resolve that we should be ‘Hidden No More.’”

“Charles Sabine speaks eloquently to the resilience that patients and families have and highlights the beauty amidst the pain,” Furr Stimming says. “HD is a heartbreaking disease but there is reason for hope. We are making progress with research. We hope that with continued efforts to raise awareness through advocacy and education about this disease, we will make a positive impact. It is truly an honor to work with and learn from HD families. These encounters give us all strength to keep moving forward toward an effective treatment and hopefully a therapy that slows or halts disease progression.”

Progress, Heart, and Passion in the Community at LBJ Hospital

Imagine a hospital where patients are diagnosed and treated in the context of their larger community. Lyndon B. Johnson Hospital, part of Harris Health System, is that and much more.

The 215-bed acute care hospital is the first accredited health care institution in Harris County to be designated by the National Committee for Quality Assurance as a Patient-Centered Medical Home (PCMH). A PCMH engages patients in a direct relationship with a chosen provider, who coordinates a team of health care professionals to take collective responsibility for providing integrated care and connecting patients with community resources.

“The population we serve is very different from the people we see at other Houston hospital campuses,” says Shivika Chandra, MD, assistant professor of neurology at McGovern Medical School at UTHealth Houston and chief of neurology at Lyndon B. Johnson Hospital and UTHealth Houston neurology clinics at Harris Health. “Our patients come from diverse backgrounds. About half have a primary language other than English. For the most part they are underserved, and many are uninsured, indigent, or undocumented.”

Of the patients seen at Harris Health in fiscal year 2020, 56% were uninsured, 57% were female, 57% were Hispanic/Latino, and 25% were undocumented. Fifty-one percent of these patients speak English, 45% speak Spanish, and 1.5% speak Vietnamese, according to the health system’s 2021-2025 strategic plan.

Since Chandra’s appointment as chief of neurology in 2020, she has continued to build a full-spectrum neurology service, from clinic to inpatient care and follow-up. “Neurology is one of 32 specialty clinics at LBJ Hospital, and we work together with other specialties to develop innovative strategies for care,” she says. “This gives us a broad sense of what we’re working toward as a group: building an ideal model for taking care of patients at a safety-net hospital. Many of our patients say they can see a doctor faster
in our clinics than they can get in to see their primary care physician. This is wonderful, because the most important theme of the day for us is always the patient.”

Under Chandra’s direction, UTHealth Houston Neurosciences also sees patients at Smith Clinic located southeast of the Texas Medical Center, El Franco Lee Health Center in southwest Houston, and Squatty Lyons Health Center in Humble, Texas. The neurology outpatient clinics include general neurology, neuromuscular disease, epilepsy movement disorders, and procedure clinics for EMG, nerve conduction studies, lumbar punctures, botulinum toxin injections, and occipital nerve blocks. Chandra works closely with Harris Health leadership on quality and patient safety initiatives.

“Our population is at higher-than-average risk for stroke,” she says. “We thought, what can we do to change this? We created a stroke committee that brings together multiple specialties to find ways to engage and educate the community.” In May 2022, they hosted a booth to raise awareness of stroke risk at the Northeast Community Farmers Market, held year-round on the first and third Saturday of each month at the LBJ Hospital’s Community Farm located at 5425 Troost St. in Houston. The farmers market gives access to a choice of healthy foods to the primarily Black surrounding neighborhoods of Trinity Gardens, Kashmere Gardens, and Settegast in northeast Houston.

“To provide outstanding neurological care to our patients, we focus beyond the diagnosis and understand the needs of the individual and their community. For example, the risk for stroke in Black men between the ages of 45 and 55 is four times greater than their white cohort,” Chandra says. “Black Americans have the highest risk for high blood pressure, but we know that the factors involved go beyond the medical to include socioeconomic status, health literacy, access to care, and social support systems.”

As a community-focused academic health care system dedicated to improving the health of those most in need in Harris County, LBJ Hospital and its diversity provide a rich learning experience for residents and medical students at McGovern Medical School, which helps them understand that there is more to medicine than disease.

“Many of us choose to work at LBJ for the shared experience. We are in a resource-limited setting, and to my mind, the patients are the best part of Harris Health,” Chandra says. “The gratitude and the way we’re embraced in their world is inspiring and rewarding. We all feel that we are part of a family living within
a community of heart and passion.”

Pushing the Boundaries of Innovation

UTHealth Houston Researchers Participate in a Study of Vagal Nerve Stimulation for Treatment-Resistant Depression

Designed in partnership with the nation’s top experts in treatment-resistant depression, the prospective multicenter, randomized, controlled RECOVER trial aims to provide additional information about the benefits of vagus nerve stimulation (VNS) therapy as an adjunctive treatment for patients with major depressive disorder or bipolar depression, who are not responding to the usual treatments.

The well-studied therapy was approved by the U.S. Food and Drug Administration in 2005 and has been used successfully to help patients who suffer from either disorder.

“The challenge for our patients is lack of insurance coverage for implantation, programming, and maintenance of vagal nerve stimulators for depression,” says João de Quevedo, MD, PhD, professor in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth Houston and director of the Treatment-Resistant Depression Program in the department’s Center of Excellence on Mood Disorders. “Through this study, which is funded in part by the Centers for Medicare and Medicaid Services, we aim to provide enough evidence of the therapy’s effectiveness to prompt insurers to pay for the treatment.”

The study, which began in September 2019 and will end in 2030, will enroll 1,000 participants with treatment-resistant depression at 100 sites across the United States. All participants will have VNS devices implanted; half will have the device turned on for 12 months. Following the initial yearlong period, the device will be activated for all participants.

“Our objective is to determine whether active VNS therapy treatment is superior to a nostimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization,” says Dr. de Quevedo, who, as the trial’s site principal investigator, screens patients and has enrolled more than 30 participants. Patients who qualify are referred to neurosurgeon Daniel Kim, MD, FACS, FAANS, for implantation of the device. Kim, professor and director of the Peripheral Nerve Surgery Program in the Vivian L. Smith Department of Neurosurgery at McGovern Medical School, is recognized for his work in neurorehabilitation through robotics and cortical stimulation, spinal biomechanics, and innovative neuromodulation treatments for chronic pain and other conditions.

“The surgery, which takes about 40 minutes, is minimally invasive and involves an aesthetic incision into the skin crease line on the left side of the neck, leaving no visible scar,” Kim says. “We expose the left vagal nerve and thread a wire underneath the skin and connect it to a pulse generator implanted in the patient’s chest. Patients have very minimal postoperative discomfort and can resume all activities immediately after a very short recovery from anesthesia.”

Two weeks later, the device is activated – or not activated, depending on which arm of the study the patient is randomized to – by Dr. de Quevedo. The device is programmed to deliver an electric current in a continuous cycle or a set amount of time. After that period has passed, the process repeats itself. De Quevedo and Kim expect to implant one or two study participants per month.

“We’re just now scratching the surface of what neuromodulation can do to improve the quality of life for patients with a variety of conditions,” Kim says. “VNS originally was approved for treatment-resistant epilepsy and treatmentresistant depression, and recently was approved for select people to aid with rehabilitation after stroke. We expect neuromodulation to play an even greater role in improving quality of life for people who otherwise would be left with little hope.”

Participants in the study must have depression or bipolar depression that has lasted for more than two years or recurred several times, and have tried at least four types of antidepressant treatments without relief. For more details, visit www.recovervns.com.

Wireless Pain Management for Drug-Resistant Conditions Offers a Promising Alternative to Surgery

Using a 1-millimeter-sized wireless implant to stimulate peripheral nerves from within blood vessels has the potential to treat neuropathic pain resistant to medical therapy, according to a team of multi-institutional researchers, including co-principal investigator Sunil A. Sheth, MD, associate professor of neurology and director of the vascular neurology program at McGovern Medical School at UTHealth Houston. Other co-principal investigators of the study, published in Nature Biomedical
Engineering,¹ were Peter Tze Man Kan, MD, MPH, professor and chair of the Department of Neurosurgery at The University of Texas Medical Branch in Galveston, and Jacob Robinson, PhD, associate professor with dual appointments in electrical and computer engineering and in bioengineering at Rice University in Houston.

After receiving a grant from the National Institutes of Health in 2019, the three teamed up to create implantable, wirelessly powered nerve stimulators that can be used in place of opioids for pain management. The implants – roughly the size of a grain of rice – are small enough to be placed on stents and delivered within blood vessels adjacent to specific areas of the central and peripheral nervous system.

“We’re getting more and more data showing that neuromodulation, or technology that acts directly upon nerves, is effective for a huge range of disorders – depression, migraine, Parkinson’s disease, epilepsy, dementia, etc. – but there’s a barrier to using these techniques because of the risks associated with doing surgery to implant the device, such as the risk of infection,” Sheth says. “If you can lower that bar and dramatically reduce those risks by using a wireless, endovascular method, there are a lot of people who could benefit from neuromodulation.”

Neuropathic pain can be a disabling disorder and affects nearly 40% of chronic pain sufferers, often leading to anxiety, depression, and opioid addiction. Previous research revealed that electrical stimulation is an effective treatment for reducing pain when doctors target the spinal cord and dorsal root ganglia (DRG), a bundle of nerves that carry sensory information to the spinal cord. However, existing DRG stimulators require invasive surgery to implant a battery pack and pulse generator.

With this new type of technology, the researchers say they have found a way to perform minimally invasive bioelectronic therapy that helps with more precise placement of the implant and more predictable outcomes. Ultimately, Sheth hopes to seek regulatory approval of the device from the U.S. Food and Drug Administration. “We’re doing some longer-term studies to ensure that this approach is safe and that the device can stay in the body for a long period of time without causing problems,” says Sheth, who estimates the process will take a few years.

1 Chen JC, Kan P, Yu Z, Alrashdan F, Garcia R, Singer A, Lai CSE, Avants B, Crosby S, Li Z, Wang B, Felicella MM, Robledo A, Peterchev AV, Goetz SM, Hartgerink JD, Sheth SA, Yang K, Robinson JT. A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves. Nat Biomed Eng. 2002 Jun 6; (6): 706-716

KINECT-HD Trial for Huntington’s Disease Produces Positive Phase III Data

A new drug has proven beneficial in treating chorea, a movement disorder commonly associated with Huntington’s disease, according to a recent international study led by UTHealth Houston researcher Erin Furr Stimming, MD, who served as principal investigator on behalf of the KINECT-HD Huntington Study Group. Furr Stimming, professor of neurology and Memorial Hermann Chair at McGovern Medical School at UTHealth Houston, presented the findings from the Phase III, randomized, double-blind, placebo-controlled KINECT-HD study for the first time in April 2022 at the American Academy of Neurology Annual Meeting in Seattle, Washington.

She reported that valbenazine, a selective vesicular monamine transporter 2 (VMAT2) that is not yet approved by the U.S. Food and Drug Administration specifically for Huntington’s disease, was safe and effective when given as a once-daily treatment for chorea in patients with Huntington’s disease. Chorea is an involuntary, irregular movement and the cardinal motor feature in Huntington’s disease.

“We are thrilled that this study yielded positive results. We saw a statistically significant decrease in Huntington’s disease-related chorea in patients taking valbenazine versus the placebo,” says Furr Stimming, who also is director of the Huntington’s Disease Society of America top-level Center of Excellence at UTHealth Houston Neurosciences. “While chorea is not the only symptom our Huntington’s disease patients experience, it can be quite problematic and can contribute to im pairment in daily activities such as eating and drinking, and can lead to frequent falls.” Interestingly, a majority of people with chorea do not receive a medication intended for the symptom, according to a separate abstract also presented by Furr Stimming, which retrospectively analyzed data from the Enroll-HD dataset, a dataset built from a worldwide observational study that includes more than 20,000 participants on four continents.

Chorea was documented in nearly 97% of participants; however, only 36% of these participants were prescribed medications for chorea, despite the availability of FDA-approved medications, such as VMAT2 inhibitors and off-label medications like antipsychotics and benzodiazepines. Furr Stimming says continued research is needed to better understand optimal treatment patterns for chorea in patients with Huntington’s disease.

“We do not yet have a disease-modifying therapy for Huntington’s disease, and therefore, we must continue to focus on optimizing symptomatic treatments for the motor and nonmotor symptoms of the disease,” she says. Huntington’s disease is a rare, inherited disease that typically begins in an individual’s 30s or 40s, causing nerve cells in the brain to break down over time. About 40,000 Americans have the fatal disease, while another 200,000 are at risk for inheriting it. No cure exists, but medications and physical, speech, and occupational therapy can help manage symptoms.

The KINECT-HD study was conducted by the Huntington Study Group, a global organization, together with its subsidiary, HSG Clinical Research, Inc., and in cooperation with the Clinical Trials Coordination Center at the University of Rochester Medical Center’s Center for Health + Technology, with funding from Neurocrine Biosciences, a biopharmaceutical company.

Identifying Brain Regions That Regulate Breathing as Eventual Targets for Direct SUDEP Intervention

With a grant from CURE Epilepsy, Nuria Lacuey Lecumberri, MD, PhD, and her team at McGovern Medical School at UTHealth Houston aim to identify specific parts of the brain essential for regulating breathing, a fundamental function whose failure following a seizure is primarily responsible for sudden unexpected death in epilepsy (SUDEP).

SUDEP is the most frequent cause of death among people with drug-resistant epilepsy. “Although a number of biological processes may contribute to SUDEP, the most common seems to be central apnea, a condition in which breathing repeatedly stops and starts, usually while sleeping during or immediately
after a severe seizure,” says Lacuey, an assistant professor in the Department of Neurology at the medical school. “There is compelling evidence that breathing irregularities are an underlying cause of SUDEP.”

To date, research has concentrated almost exclusively on the role of the brainstem, which connects higher cortical regions of the brain to the spinal cord. Although the brainstem plays a crucial role in maintaining respiratory activity, it may not be the only area contributing to SUDEP. Studies have shown that areas of the cortex are also implicated, but the roles they play are unclear.

“There are currently no strategies for improving respiratory function during the dangerous period between seizure-induced central apnea and death,” Lacuey says. “We need to assess the roles of specific areas of the brain and develop a detailed understanding of the relationship between brain electrical activity and breathing responses through the connectome – the regions that are structurally and functionally linked through their neuronal connections.”

For the study, the research team recruited 19 patients with drug-resistant epilepsy who were being evaluated for epilepsy surgery using electrodes implanted to electrically stimulate various brain regions for clinical mapping to pinpoint the seizure focus. They formally agreed to enroll in Lacuey’s study, which asked them to perform various breathing exercises while different areas of their brain were stimulated at varying intensities. The data were collected at Case Western Reserve University School of Medicine.

A neurosurgeon implanted electrodes in seven brain regions common to all 19 participants to determine whether electrical stimulation of each of these regions would affect breathing responses and, if so, whether the resulting respiratory activity would be enhanced or inhibited. They also needed to determine the stimulation intensity and the frequency necessary to affect breathing responses.

“In our analysis, the data showed that four specific areas of the cortex of the brain affected the patients’ breathing responses, depending on the strength and frequency of the electrical stimulation,” Lacuey says. “Stimulation of two of these areas – the temporal lobe and the cingulated gyrus – results in enhanced respiratory activity at a relatively low current but not at the higher electrical currents we tested. This was an exciting finding. It supports the idea that an implantable device capable of electrically stimulating pre-identified cortical regions of the brain could enhance breathing at critical times to prevent SUDEP. We need additional data from more patients, finer mapping of the brain regions we identified, and an exploration of more brain regions than the seven we studied, as well as a more thorough evaluation of electrical current and frequency.”

CURE Epilepsy’s mission is to find a cure for epilepsy by promoting and funding patient-focused research. Founded in 1998 by a group of parents of children with epilepsy, the organization has led a dramatic shift from treating seizures to expanding the understanding of their underlying mechanisms.