Apr 20

Gregory Honored for Breast Cancer Gene Discovery

By Alissa KocerS Gregory

In December 1995, the work of over 40 researchers culminated with a landmark publication in Nature. The team had discovered a second breast cancer susceptibility gene: BRCA2. Their discovery revolutionized cancer research and screening in breast, ovarian, and prostate cancers and has impacted millions of people’s lives in the years since.

One member of that team was Simon Gregory, PhD, professor in neurosurgery, neurology, and molecular genetics and microbiology at Duke. “I was constructing physical maps as part of the Human Genome Project at the Wellcome Trust Sanger Institute,” Gregory said. “The large insert cloned map of the BRCA2 region formed part of my PhD thesis.”

Earlier this year, just after the 25th anniversary of the discovery of the BRCA2 gene, that team of researchers was honored during an unveiling of two commemorative plaques in London. One of the plaques was placed at the laboratories of The Institute of Cancer Research, London, where part of the research was funded.

“The impact of discovering the BRCA2 gene cannot be understated,” Gregory said. “It is incredibly important for the diagnosis of inherited familial breast cancer and centrally important to healthcare decisions made by individuals and their families.”

Being part of that research team left a lasting impression. “It isn’t something that I speak of often,” Gregory said, “but it is probably one of my most proud achievements. It was the first time that I appreciated the broader impact of my own research on people’s lives.”

Apr 14

Calakos Receives 2023 ASCI Korsmeyer Award

N CalakosThe American Society for Clinical Investigation (ASCI) has awarded Nicole Calakos, MD, PhD, its 2023 Stanley J. Korsmeyer Award. The Korsmeyer Award recognizes outstanding achievements of ASCI members in advancing knowledge and mentoring future generations of life science researchers. Calakos received this award for her contributions to understanding basal ganglia physiology and its involvement in diseases such as compulsive behavior and movement disorders.

Calakos is the Duke Lincoln Financial Group Distinguished Professor of Neurology, Neurobiology, and Cell Biology, as well as Chief of the Duke Division of Parkinson’s and Movement Disorders. Her research focuses on mechanisms of adaptive plasticity involving the striatal circuitry of the basal ganglia.

The brain’s basal ganglia circuitry influences a wide range of behaviors that involve the selection and execution of action plans. A host of neuropsychiatric disorders ranging from obsessive-compulsive disorder (OCD) to Parkinson’s disease and dystonia are associated with basal ganglia dysfunction. Calakos’ research has helped reveal the ways the basal ganglia normally adapts to experience, such as in habit learning, and how brain diseases like compulsive behavior and movement disorders arise.

“Dr. Calakos is the epitome of a successful physician scientist and well deserving of the Korsmeyer Award,” said Richard O’Brien, MD, PhD, Disque D. Deane University Distinguished Professor of Neurology and Chair of the Department of Neurology. “Her research has advanced our understanding of plasticity within the brain while also identifying new therapeutic options for a variety of conditions. While conducting this research she has also helped mentor a generation of physician scientists and build a collaborative research network that reaches across Duke.”

Calakos’ research has revealed a crucial role for a biochemical pathway, known as the “integrated stress response” (ISR), that regulates protein synthesis in multiple inherited and sporadic forms of the movement disorder, dystonia. These insights have led to the development of new drug candidates for dystonia and uncovered non-canonical roles for the ISR in the healthy brain, where it was found to be constitutively active in neuromodulatory neurons to maintain the integrity of dopamine and acetylcholine signaling. The significance of recognizing new ISR roles in the brain’s acetylcholine system also reaches beyond dystonia because ISR-inhibiting small molecules are being advanced to treat traumatic brain injury and dementia.

Her laboratory continues work to study the basic-science ramifications of this unusual cell-type specific engagement of the ISR in neuromodulatory cells as well as advance ISR-targeting therapeutic approaches for dystonia toward the clinic. Based on the discovery that the HIV protease inhibitor ritonavir may be efficacious for dystonia in preclinical models through a mechanism involving the ISR, a multi-center collaborative project supported by the Department of Defense (DOD) is ongoing to advance to human subject studies.

Calakos received a bachelor’s degree in molecular biology from University of California-Berkeley followed by graduate research in Neuroscience under the mentorship of Richard Scheller, PhD, at Stanford University. She received her MD and doctoral degrees from Stanford, completed a residency in neurology at the University of California, San Francisco, and a postdoctoral fellowship with Robert Malenka, MD, PhD at Stanford.

Throughout her career, Calakos has advocated for physician-scientist development and built bridges between the scientific and medical communities to enhance translational research. She co-directs the Duke Scholars in Molecular Medicine Neurosciences track and has served on the executive committees for Duke’s Medical Scientist Training program, Strong Start program for physician-scientists, third-year research program for medical students and the NIH/NINDS K12 career development program for pediatric neurology physician-scientists.

Calakos’ laboratory has been continuously supported by the NIH (National Institute of Neurological Disorders and Stroke, National Institute of Mental Health). Her work has also been supported by the DOD and private foundations, including the Dystonia Medical Research Foundation, Tyler’s Hope for a Dystonia Cure Foundation, Bachmann-Strauss Dystonia Parkinson’s Foundation, Klingenstein Fund, McKnight Foundation for the Neurosciences, Harrington Discovery Institute, Tourette Syndrome Association, The Kahn family foundation, The Holland-Trice family foundation, the Ruth K. Broad Biomedical Research Foundation, the Chan-Zuckerberg Institute, and the Aligning Science Across Parkinson’s Foundation.

In addition to the Korsmeyer Award, Calakos has also received the Brain and Behavior Research Foundation Award (formerly NARSAD) (2007), Klingenstein Fellowship in the Neurosciences Robert H. Ebert Clinical Scholar distinction (2007), Tourette Syndrome Association Early Career Award (2009), Harrington Discovery Institute Scholar-Innovator Award (2015), and Duke Health Scholar (2016). She was elected to the American Neurological Association in 2012 (and served on its Board of Directors from 2012 to 2015), the ASCI in 2017, the American Association for the Advancement of Sciences in 2020, and the National Academy of Medicine in 2022.

(A version of this story appeared on the ACSI’s website. Read that story in its original context here).N CalakosN Calakos

Dec 05

DCNN Research Round Up, December 2022

Members of the Duke Neurology Department and Duke Center for Neurodegeneration and Neurotherapeutics advanced the fields of clinical and translational neuroscience this November, contributing to 16 new peer-reviewed studies. Highlights include an article providing insights into how mild traumatic brain injury can contribute to Parkinson’s disease co-authored by Andrew West, PhD

NIH

Neuron image courtesy NIH

, the 68th entry in the ALSUntangled examination of alternative therapies for amyotrophic lateral sclerosis, and an examination of sex-specific differences in gene expression underlying the risk of depression symptoms in late-onset Alzheimer’s written by senior author Ornit Chiba-Falek, PhD. Read the paragraphs below for short summaries of these and other studies, and find links to the original articles themselves.

Headache and Facial Pain

  • Roshni Dhoot, MD, and Sweta Sengupta, MD, wrote a case report of an 18-year-old male experiencing painful ophthalmoplegic neuropathy with headache and oculomotor palsy who had experienced a remarkably similar set of symptoms as a 13-month old. Read that report in the latest issue of Headache. 

Memory Disorders

  • Tau aggregates are present in Alzheimer’s disease (AD) and other  neurodegenerative diseases known as “tauopathies,” making them potential sources for tauopathy biomarker discovery. John Ervin and Shih-Hsiu “Jerry” Wang, MD, MS, contributed to an article that found that site-specific p-tau antibodies can not only differentiate AD from non-AD brains, but also discriminate AD from rare tauopathies. Read that article from ACS Chemical Neuroscience here.
  • Brenda Plassman, PhD, contributed to a new study that examines the associations of amyloid PET scan results  and diagnosis of either mild cognitive impairment or dementia with the likelihood of having an advance directive. Read what that study found in BMC Palliative Care.

Multiple Sclerosis and Neuroimmunology

  • Hypothermia is a rare presentation of multiple sclerosis (MS) that has the potential to cause dangerous or even fatal clinical outcomes. Senior author Suma Shah, MD, and Duke medical student Nidhila Masha wrote a recent case report of a patient with acute hypothermia without an active MS flare. The article discusses the case and its implications for hypothermia in MS. Read it in the latest issue of Neuroimmunology Reports.
  • The rare autoimmune condition neuromyelitis optica spectrum disorder (NMOSD), has been thought to follow a progressive disease course but the influence of factors such as seropositivity and serum titer levels of antibodies to aquaporin-4 (AQP4) has not been fully explored. Senior authors Suma Shah, MD, and Duke medical student Nidhila Masha, as well as Dorlan Kimbrough, MD, Christopher Eckstein, MD, Nicholas Hudak, PA-C, MMS, Mark Skeen, MD, and Michael Lutz, PhD, performed a retrospective chart review of 53 people with this condition. Their analysis provides an updated contemporary view  of the clinical course of NMOSD and shows a more favorable view of its disease course than earlier studies. Read that article in Multiple Sclerosis and Related Disorders
  • The autoimmune brain disorder anti-NMDA receptor encephalitis (NMDARe) is characterized by antibodies specific for the NMDA receptor in CSF. Senior author Christopher Eckstein, MD, as well as recent Duke School of Medicine graduates James Giarraputo, MD, Megha Gupta, MD, and M. Elizabeth Deerhake, MD, PhD wrote a Neurology journal article discussing a recent study on the use of serum neurofilament light chain (NfL) in differentiating NMDARe from first-episode psychosis caused by a psychiatric disease. Read that discussion here.

Neurocritical Care

  • Neurocritical Care Fellow Kristi Tempro, MD, and Cherylee Chang, MD wrote a review article discussing the history of neurocritical care as a subspecialty. The article reviews the multidisciplinary origins of this specialty as well as its critical role in providing patient care. Read it in the latest issue of Critical Care Clinics.

Neuromuscular Disease

  • The ALSUntangled series reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Richard Bedlack, MD, PhD, was the senior author of the 68th entry in the series, which examines the existing evidence and potential for ozone therapy, supporting investigation in cell or animal models, but not recommending it for people living with the condition. Read their full analysis in Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration.

Parkinson’s Disease and Movement Disorders

Stroke and Vascular Neurology

  • Low-intensity transcranial focused ultrasound (LI-tFUS) has gained considerable attention as a promising non-invasive neuromodulatory technique for examining human brains. A new article investigates the wave propagation of LI-tFUS on human skulls to improve our understanding of how ultrasound frequencies and skull morphology variations affect wave propagation through the skull. Wuwei “Wayne” Feng, MD, MS, Pratik Chhbatbar, MD, PhD, and Taewon Kim, MD, PhD, contributed to this article, which appears in Medical Physics. Read it here.
  • Near-infrared laser therapy, a special form of transcranial light therapy, has been tested as an acute stroke therapy in three large clinical trials. A new review article discusses the putative mechanism of light stimulation in the setting of stroke, highlights barriers and challenges during the translational process, evaluates light stimulation parameters, and proposes future opportunities for this therapy for future stroke treatment. Wuewei “Wayne” Feng, MD, MS, Pratik Chhatbar, MD, Swaroop Pawar, MD, Cherylee Chang, MD, Shreyansh Shah, MD, Estate Sokhadze, PhD, Alexis Domeracki, and Christine Park contributed to this study. Read it in Translational Stroke Research.

Translational Brain Sciences

  • Senior author Alexandra Badea, PhD, Kim Johnson, and Rich O’Brien, MD, PhD, contributed to a new article that revealed predictive brain networks associated with risk factors for Alzheimer’s disease, including age, sex, and genotype. Read that article in Cerebral Cortex. 
  • Senior author Ornit Chiba-Falek, PhD, Michael Lutz, PhD, Suraj Upadhya, and Daniel Gingerich authored a new study which discovered sex-specific differences in gene expression underlying the risk of depression symptoms in late-onset Alzheimer’s Disease. Read their article in the latest issue of Biomolecules.
  • Microgels are the building blocks of microporous annealed particle (MAP) scaffolds, which serve as a platform for both in vitro cell culture and in vivo tissue repair. Tatiana Segura, PhD, was the senior author of a new article covering the fabrication, lyophilization, and rehydration of microgels for controlling particle fraction in MAP scaffolds, as well as annealing the microgels through bio-orthogonal crosslinking for 3D cell culture in vitro. Read it in the Journal of Visualized Experiments.
  • Repeated mild traumatic brain injury is known to be associated with an increased risk for Parkinson’s diseases, but the specifics of this process have not been fully explored. Andrew West, PhD, contributed to a new study that sheds light on this area. West and colleagues devised an injury device to deliver a surgery-free repetitive mild TBI to rats and then induced human-like PD pathology by intracranially injecting recombinant αSyn preformed fibrils. Read what they found in Acta Neuropathologica Communications.

Aug 01

Duke Neurology Research Round Up, August 2022

NIH nerveMembers of the Duke Neurology Department contributed to eight articles and two correspondence letters published in peer-reviewed journals this July. The subjects of these publications include an analysis of the “gender gap” for treatment of acute stroke, a discussion on challenges and opportunities in academic research on structural racism and health care,and a review of the social amoeba Dictyostelium discoideum’s potential to better understand how neurodegenerative diseases in humans. Read the paragraphs below for more information on these and other recent publications from our Department, along with links to the original articles themselves.

Epilepsy, Sleep, and Clinical Neurophysiology

  • Advanced interventional pain management approaches need to lesion neural targets to achieve desirable analgesia while also preserving motor and sensory function for regional bystander nerves. Aatif Husain, MD, was the senior author of a new report that provides an interventional radiology directed framework of thermoprotective techniques available during thermal ablation. Read that article in Seminars of Interventional Radiology.

Equity, Diversity, and Inclusion

Memory Disorders

  • Brenda Plassman, PhD. contributed to an article estimating the relationship between traumatic events over the lifespan and cognitive trajectories and predicted dementia incidence. The team found that traumatic events experienced later in life were associated with cognitive decline, but no overall relationship between lifetime trauma and predicted dementia incidence. Read the article in the American Journal of Preventive Medicine.

Neurocritical Care

  • Daniel Laskowitz, MD, MHS, and David Van Wyck, DO, were the senior authors of a new study evaluating the potential of CN-105, a 5-amino acid apolipoprotein E (ApoE) mimetic peptide, to mitigate the effects of traumatic brain injury (TBI) if administered beforehand in a clinically relevant murine model. The team found that CN-105 improved functional outcomes and reduces hippocampal microglial activation, showing its potential as a pre-injury prophylaxis for soldiers at high risk for TBI. Brad Kolls, MD, PhD, MCii, Haichen Wang, MD, and Viviana Cantillana also contributed to the article, which appears in Experimental Brain Research.

Neurodegeneration and Neurotherapeutics

  • The genome of the  social amoeba Dictyostelium discoideum contains a huge number of microsatellites, or repetitive sequences associated with many neurodegenerative diseases. Matthew Scaglione, PhD, was the senior author of a review article discussing the microsatellites in this species as well as its potential utility for identifying novel mechanisms that utilize and regulate regions of repetitive DNA. Read that article in Frontiers in Neuroscience.

Neuromuscular Medicine

Translational Brain Sciences

  • Michael Lutz, PhD, was part of a study that examined single nucleotide polymorphisms (SNPs) associated with accelerated aging to see whether those SNPs were also associated with the progression from mild cognitive impairment to Alzheimer’s disease. Their analysis found multiple genetic variants with pleiotropic effects on both epigenetic accelerated aging and progression to Alzheimer’s suggested a shared genetic architecture between the two. Read the full result in the Journals of Gerontology: Series A.

Vascular Neurology and Stroke

  • A new JAMA Network Open study provides new insights into current practices of prescribing patterns in dual antiplatelet therapy for secondary prevention among patients with acute ischemic stroke changed after recent clinical trial findings and American Heart Association/American Stroke Association practice guideline updates. Wuwei “Wayne” Feng, MD, MS, Brian Mac Grory, MB BCh, MRCP, and Daniel Laskowitz, MD, MHS, contributed to the analysis of more than 132,000 patients from nearly 2000 hospitals participating in the AHA/ASA Get With The Guidelines–Stroke program. Read that story here.
  • William Powers, MD wrote a “Stroke Lore” article discussing common but unsubstantiated beliefs and customs about intracranial volumes and pressures following cerebral hemorrhage, as well as what the existing data and studies on the subject indicate. Read that discussion in the Journal of Stroke and Cerebrovascular Disease.
  • The “gender gap” for endovascular therapy (EVT) use for acute ischemic stroke has disappeared after 2015, along with increases in EVT for both genders, according to a new analysis of more than 300,000 patients between 2012 and 2019 by  Brian Mac Grory, MB BCH, MRCP, and colleagues at the Duke Clinical Research Institute. Read the full analysis in the latest issue of Stroke.NIH nerve

Apr 01

Postdoc Spotlight: Ziyong Liu, MD, PhD

ZLZhiyong Liu, PhD, learned about the devastating effects neurodegenerative diseases have on patients and their families firsthand during his senior year of college, when he worked in a clinical research lab. Now, as a postdoctoral associate within the lab of Andy West, PhD, he’s performing translational research to develop new treatments for one of those conditions, Alzheimer’s disease. In this week’s “Spotlight” interview, Liu talks about the focus of his work, his recent K99/R00 award, and enjoying running, fishing, and time with his family when he’s not at work.

What are your current responsibilities within the lab of Andy West, PhD? What does a typical day look like for you? 
I am currently a research associate in the lab of Dr. Andy West. My research has been focusing on the role of LRRK2 in endolysosomal dysfunction in neurodegenerative diseases. I usually start my day in the lab with a cup of coffee and about 20 mins reading the newly published research articles in the field, before I start to do my bench work.

How and when did you first get interested in the overlap between neuroscience and pharmacology?
I joined a clinical research lab when I was in my senior year at college. In shadowing neurologists, I learned how devastating neurodegenerative diseases are to the patients and their families, and how clinicians are largely focused on symptomatic treatment without any ability to positively affect the course of disease. That’s when I started to get interested in the molecular pathways underlying neurodegenerative diseases and novel therapeutic strategies targeting the disease relevant molecules.

You recently received a K99/R00 transition award to start your research laboratory focused on vesicle trafficking defects in Alzheimer’s disease. When will this work begin, and how will it help us better understand, treat, or prevent Alzheimer’s disease?
The title of my K99/R00 transition award is for my project, the role of Rab10 in Alzheimer’s disease. This work officially started on 3-15-2022, although I have been working on the function of Rab10 in endolysosomal dysfunction for more than 3 years.

Recent genetic analysis showed Rab10 variant carriers confers resiliency to AD susceptibility. In this project, we will test whether knockdown of Rab10 using antisense oligonucleotides (ASOs) attenuates AD relevant neuroinflammation and neuropathology in animal models. If this is tested to be true, the Rab10 ASOs can potentially move pretty fast into clinical trials and eventually help patients.

What do you enjoy most about your work?

I enjoy finding novel pathways that can potentially be targeted for therapeutic purposes, and eventually help patients. I also enjoy the process of making a hypothesis and testing it.

What’s the hardest part of your job? 
A lot of the neurodegenerative diseases are age-dependent. The molecules that we study might only have subtle phenotype at the early stage of disease. We will have to optimize our models and be extremely patient to be able to see significant effects. The hardest part of research in general is making hypotheses that can actually impact the field.

What other passions or hobbies do you have outside of the Department?
I run 5k 5 times a week, and I enjoy taking my kid to local parks and playgrounds. If I have extra free time, I wish I could go fishing more often.

Feb 24

Duke Neurology Research Round Up, January 2022

brainResearch authored by members of the Duke Neurology Department published during the final month of 2021 advanced our knowledge of stroke, epilepsy, dystonia, and other conditions. Highlights from the eight peer-reviewed journal articles our faculty contributed to this December include an analysis of the optimal approach to manage blood pressure among patients with stroke co-authored by Shreyansh Shah, MD, a device to isolate and purify biomarkers of Alzheimer’s disease developed by Laurie Sanders, PhD, and colleagues, and an examination of patterns of opioid use among patients who have had a stroke. Read the paragraphs below for short summaries of each of these and other articles, and find links to the original articles themselves.

Stroke

  • Michael “Luke” James, MD, contributed to a new article that proposes a single pipeline of a multi-task model for end-to-end hemorrhage segmentation and risk estimation for intracerebral hemorrhage. The new model involves a segmented hemorrhage volume clinical features such as CT angiography spot, Glasgow Coma Scale, age to predict the ICH stability, and state-of-the art machine learning techniques. Read the full article in Medical and Biological Engineering and Computing.
  • Shreyansh Shah, MD, contributed to a new study that sheds light on the optimal approach to blood pressure management in acute ischemic stroke. Examining data from patients with acute ischemic stroke and uncontrolled blood pressure,Shah and colleagues found that the initial use of an intermittent or continuous infusion antihypertensive did not significantly impact the time to alteplase administration. Read the full article in the American Journal of Emergency Medicine.
  • While people with intracerebral hemorrhage often experience severe headaches or other medications that necessitate opioid medications, prescribing patterns among this patient group have not been well described. In a retrospective cohort study, a team including Brian Mac Grory, MB BCh, MRCP, examined prevalence and risk factors for short and longer-term opioid use in patients with intracerebral hemorrhage. They found that inpatient opioid use was common, but that inpatient opioid use does not necessarily lead to a high rate of long-term opioid dependence in this patient group. Read that study in Neurocritical Care.

Memory Disorders

  • Laurie Sanders, PhD, was part of a team that designed and fabricated a surface acoustic wave-based acoustofluidic separation device to isolate and purify biomarkers of Alzheimer’s disease. Their device obtained label-free detections of surface-enhanced Raman scattering and electrochemical immunoassay of clinical plasma samples with high sensitivity and specificity, for both Alzheimer’s patients as well as health controls. Read the full article in Biosensors & Bioelectronics.

Epilepsy, Sleep, and Clinical Neurophysiology

  • Understanding the cellular and circuit mechanisms underlying development of temporal lobe epilepsy will provide a foundation for improved therapies. Senior authors James McNamara, MD, PhD, and Enhui Pan, PhD, and Ram Puranam, PhD, studied a model in which an episode of prolonged seizures is followed by recovery lasting two weeks before emergence of spontaneous recurrent seizures. Read what they found in the latest issue of eNeuro.

Parkinson’s and Movement Disorders

  • A new article in Data in Brief by senior author Nicole Calakos MD, PhD, Kunal Shroff, Zachary Caffall, MS, and colleagues presents quantitative subcellular compartment-specific proteomic data from wildtype and DYT-TOR1A heterozygous mouse embryonic fibroblasts basally and following thapsigargin treatment.  The data presented provide subcellular compartment-specific proteomic information within a dystonia model system both basally and under cellular stress. Read that article here. 
  • Current rating scales for Tourette’s syndrome rely on subjective self-estimates or brief assessments to estimate tics. A team including Kathryn Moore, MD, developed a more objective approach: wearable sensors that capture voluntary and tic movements.  The device captured tics with greater than 96% accuracy, sensitivity, and specificity, potentially allowing for improved, tailored care for people with Tourette’s. Read the full study in Clinical Neurophysiology.

Neuromuscular Disorders

  • Recruiting enough clinical trial patients for rare, fatal diseases such as amyotrophic lateral sclerosis (ALS) is difficult, just as it is difficult for patients with these diseases to find and enroll research studies for which they’re eligible. In a new article for the Journal of Medical Internet Research, Rick Bedlack, MD, PhD, and colleagues describe how the federal Agency for Toxic Substances and Disease Registry’s (ATSDR) National ALS Registry is linking people with ALS to scientists who are conducting research, clinical trials, and epidemiological studies. Read that study here.

Feb 24

Duke Neurology Research Round Up, February 2022

NIH EEGThe first month of 2022 saw the publication of 18 new peer-reviewed journal articles from members of the Duke Neurology Department. Highlights include new articles providing insight into the origins of Parkinson’s disease by Andrew West, PhD, a Lancet Neurology discussing the epidemiology, diagnostics, and  biomarkers of autoimmune neuromuscular junction disorders, case reports describing the progression and treatment options for rare neurological conditions, and a summary of how the first year of the COVID-19 pandemic affects neurology residency programs in the United States. Read the paragraphs below for short summaries of each of these and other articles, and find links to the original articles themselves.

 

Translational Brain Sciences

  • Transcranial Magnetic Stimulation (TMS) has become a powerful tool both for exploring cortical function as well as developing therapies for psychiatric and neurological disorders. Unfortunately, much of the inference of the direct effects of TMS has been assumed to be limited to the area a few centimeters beneath the scalp. Simon Davis, PhD, contributed to a new study that examines TMS coil placement to non-invasively achieve activation of specific deep brain targets of relevance to the treatment of psychiatric disorders. Their new paradigm indicates a way to overcome depth limitations and allow noninvasive brain stimulation to influence deep brain structures. Read that study in Neuroimage.
  • Andrew West, PhD, was the senior author of a new article in Molecular Neurodegeneration examining how α-synuclein and LRRK2 interact in monocytes and subsequent neuroinflammatory responses. Their experiments found that Pathologic α-synuclein activates LRRK2 expression and kinase activity in monocytes and induces their recruitment to the brain. Read their full study here.

Neuro-Oncology

  • Katherine Peters, MD, PhD, was the first author of a new placebo-controlled, double-blind study examining the effects of low-dose naltrexone on quality of life and fatigue on patients with high-grade glioma. Their study found that the therapy had no effect on quality of life or fatigue for patients with high-grade glioma undergoing concurrent chemotherapy and radiation therapy. Read that article in Supportive Care in Cancer.

Memory Disorders

  • Fatal familial insomnia is an uncommon but fatal genetic condition characterized by severe progressive insomnia, dysautonomia, neuropsychiatric changes, and gait instability. Deborah Rose, MD, and Andy Liu, MD, MS, discuss diagnostic and therapeutic approaches to consider when treating patients with this condition in the latest issue of Neurocase. Read that here.

General and Community Neurology

  • Primary ductal adenocarcinoma of the lacrimal gland is a rare, aggressive malignancy that clinically and histologically resembles salivary duct carcinoma. Joel Morgenlander, MD, contributed to an article discussing the presentation, diagnosis, and treatment of this condition. Read that article in Ophthalmic Plastic and Reconstructive Surgery.

Parkinson’s Disease and Movement Disorders

  • Sneha Mantri, MD, MS, was the first author of a study that advances our understanding of the relationship between fatigue and health-related quality of life in individuals with Parkinson’s disease. Their survey of more than 1,000 patients found that the association between fatigue and lower quality of life was strongest in younger and more depressed symptoms, suggesting that targeted therapies may have the best impact on this group. Read that article in Movement Disorders and Clinical Practice.

Residency and Training

  • The COVID-19 pandemic imposed rapid, significant on neurology residency education and services in the United States, requiring residents to add as frontline providers while protecting themselves and other providers from infection and finding new ways to receive their training. Neuromuscular fellow (and new Duke Neurology faculty member) Yohei Harada, MD, wrote an article summarizing these changes and the adaptations health systems and trainees adapted to compensate for the Japanese journal Brain and Nerve. Read it here.

Neuromuscular Disease

  • Jeffrey Guptill, MD, MHS, contributed to a new review article which discusses the epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders, which are being increasingly recognized in people older than 50 years.The article also discusses treatment options and directions for future research. Read that article in Lancet Neurology.
  • A new expert consensus statement offers clinical guidance on the use of electrodiagnostic tests and neuromuscular ultrasound in the investigation of suspected carpal tunnel syndrome. Lisa Hobson-Webb, MD, was part of a panel of international leaders in neuromuscular ultrasound who contributed to this statement in Clinical Neurophysiology. Read that here.

Multiple Sclerosis and Neuroimmunology

  • Senior authors Christopher Eckstein, MD, and Elijah Lackey, MD, and Ariel Lefland, MD, wrote a case report of a 51-year-old man with known Leber’s hereditary optic neuropathy who also presented with recurring myelopathy from a genetic mutation. Read about the interaction of those symptoms in Case Reports in Neurological Medicine.
  • A new plain-language summary of side effects people with multiple sclerosis experience during their first year of treatment with cladribine tablets appears in the latest issue of Neurodegenerative Disease Management. Bryan Walker, PA-C, MMS, contributed to this summary, which is available here.

Clinical Neurophysiology, Epilepsy, and Sleep

  • A new article in Epilepsy and Behavior discussing patient preferences for treatment options for drug-resistant focal epilepsy. Saurabh Sinha, MD, PhD, was the first author of the study, which administered a survey to 400 adult patients with drug resistant epilepsy. Their survey found that patients would be willing to accept lower treatment effectiveness in exchange for a minimally invasive procedure or lowered risk of mortality and neurological deficits. Read that study here.
  • The Journal of Clinical Neurophysiology’s first issue of 2022 marked the end of Aatif Husain’s, MD, eight years as the journal’s editor in chief. In his farewell message he shares how the journal has changed and grown during that time, and thanks the many people who have helped him expand its scope and vision. Read that essay here.

Stroke and Vascular Neurology

  • Hyperglycemia increases the risk for additional ischemic strokes for patients who have already experienced stroke, according to a new study in the Journal of the American Heart Association. Senior authors Wuwei “Wayne” Feng, MD, MS, Brian Mac Grory,  MB BCh, MRCP, and colleagues examined data from nearly 5,000 patients in the POINT trial. Their analysis found a 1.50 adjusted hazard ratio for subsequent stroke for patients with hyperglycemia compared to patients with normal blood glucose levels. Read the full study here.
  • In another analysis of the POINT trial, a new study has found that patients with an acute infarct on image imaging have an increased risk of recurring stroke and a pronounced benefit from clopidogrel-aspirin. Brian Mac Grory, MB BCh, MRCP, contributed to this analysis, which appears in JAMA Neurology. Read it here. 
  • People who experience a high-risk non-disabling ischemic cerebrovascular event continue to be at risk for a secondary stroke after this event. Wuwei “Wayne” Feng, MD, MS was the senior author of a four-center, single-arm study investigating whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months. The team’s investigation found that RIC is a safe add-on procedure with potential benefit for reducing recurring cerebrovascular events after high-risk events. Read the full study in Frontiers in Neurology.
  • Brian Mac Grory, MB BCh, MRCP, was the first author of a new study that examined data from patients with acute ischemic stroke presented within 24 hours but not treated with IV alteplase. Their analysis found this population had a high unmet need for care, with a high risk of readmission, mortality, and high total in-hospital and post-discharge costs. Read the full article in Stroke: Vascular and Interventional Neurology.
  • One in four patients with acute lacunar infarcts experience early neurologic deterioration, but the underlying pathophysiological features of this condition are poorly understood.  Mac Grory also contributed to an observational study that examined this phenomenon, which found that luminal stenosis may be associated with early neurologic deterioration after an acute lacunar infarct. Read the full study in Stroke: Vascular and Interventional Neurology. 

Neurocritical Care

  • A letter to the editors of Clinical and Translational Medicine discusses the authors’ work identifying the neuronal targets of a clinical‐stage stroke therapeutics CN‐105, and proposes a novel neuroprotective strategy involving the antagonism of nicotinic acetycholinergic receptors. Daniel Laskowitz, MD, MHS, and Brad Kolls, MD, PhD, co-authored this letter. Read it here.

Oct 27

Duke-led teams awarded $18 million to study Parkinson’s disease

Researchers at Duke University School of Medicine have been selected to lead two inter-institution team grants totaling $18 million to investigate Parkinson’s disease.

Calakos Liddle

The awards from the Aligning Science Across Parkinson’s (ASAP) initiative position Duke as a national leader in understanding the origins and development of this devastating movement disorder.

Duke’s coordinating lead investigators for the two research projects are Nicole Calakos, MD, PhD, (left) Lincoln Financial Group Distinguished Professor of Neurobiology and Neurology, and Rodger Liddle, MD, Professor of Medicine (right).

“This is an exciting moment for Duke, and an exciting moment for anyone with or affected by Parkinson’s disease,” Calakos said. “Duke has been invested in Parkinson’s for a long time, but this funding launches a new era because of the depth and diversity of new opportunities we will have to understand, fight, and prevent this insidious disease.”

Parkinson’s disease is a progressive neurodegenerative disease causing tremors, rigidity, slowed movement, and other symptoms. Close to one million people in the United States have Parkinson’s disease. While medications, lifestyle modifications, and surgical procedures can help with symptoms, no therapies can stop or reverse the course of the disease.

Calakos’ team project will examine how the vulnerability of dopamine neurons is influenced by the connections it makes with neighboring cells in the brain. Dopamine neurons die as Parkinson’s progresses and are a major cause of the slowed movements and other symptoms associated with the condition. While research has long focused on the dopamine neurons themselves, Calakos’ team proposes that cells that closely communicate with and support the dopamine neurons may also be important. Her team includes investigators new to the topic of Parkinson’s disease and innovative technologies that will allow the team to reveal the potential for disease modifiers among the dopamine neuron’s circuitry.

Liddle’s project will investigate the role that specialized cells in the gut known as enteroendocrine cells play in the origins of Parkinson’s disease. Parkinson’s is driven by the growth of toxic clumps of protein known as Lewy bodies in the brain. Lewy bodies are primarily made up of a misfolded protein known as alpha-synuclein. Liddle hypothesizes that enteroendocrine cells act as an entry point for corrupted alpha-synuclein from the gut to reach the brain. He believes these cells may be a target for future therapies.

“Enteroendocrine cells provide a potential pathway for corrupted alpha-synuclein all the way from the intestine through the vagus nerve directly into the brain,” Liddle said. “This knowledge gives us real insights into Parkinson’s disease — and may act as the foundation for designing therapies to treat Parkinson’s and other conditions caused by altered gut-brain signaling.”

ASAP is a coordinated research initiative to advance targeted basic research for Parkinson’s disease. Its mission is to accelerate the pace of discovery and inform the path to a cure through collaboration, research-enabling resources, and data sharing. The ASAP Collaborative Research Network, announced in 2019, comprises teams that bring together investigators across multiple disciplines, institutions, career stages, and geographies seeking to tackle key knowledge gaps in the basic mechanisms that contribute to Parkinson’s development and progression. The Michael J. Fox Foundation for Parkinson’s Research is ASAP’s implementation partner and issued the grant.

“Each team selected for the Collaborative Research Network brings unique expertise and perspective to ASAP’s mission of tackling key knowledge gaps in disease understanding through open science,” said Ekemini Riley, PhD, ASAP Managing Director. “We are proud to partner with Duke University on these innovative and impactful projects that will position the field closer to new treatments for the millions living with and at risk of Parkinson’s disease.”

Calakos’ co-investigators at Duke include Cagla Eroglu, PhD, Cell Biology; Scott Soderling, PhD, Cell Biology; Laurie Sanders, PhD, Neurology; and Michael Tadross, MD, PhD, Biomedical Engineering, and at Stanford University, Sergiu Pasca, MD.

Liddle’s co-investigators include Duke’s Andrew West, PhD, Pharmacology; Timothy Sampson, PhD, Emory University; Malú Gámez Tansey, PhD, University of Florida; and Haydeh Payami, PhD, University of Alabama at Birmingham.

Aug 24

Duke Neurology Research Round Up, August 2021

NIH EEGThis July, new research from the Duke Neurology Department answered questions about the subcellular origins of itching, how COVID-19 is affecting people with amyotrophic lateral sclerosis, what factors influence people eligible for epilepsy surgery to move forward with the procedure and topics. The paragraphs below summarize the 11 articles appearing in peer-reviewed publications from our faculty, staff, and trainees. Check them out and find links to the original publications below.

Neuromuscular Disease

  • People living with amyotrophic lateral sclerosis (ALS) have distinct pathophysiological risks and health determinants that may increase their vulnerability for infection, as well as their course of infection and recovery, from COVID-19. Rick Bedlack, MD, PhD, was the senior author of a letter to the editor in Muscle and Nerve that examines COVID-19 among the veteran population with ALS. Read their analysis here.
  • Don Sanders, MD, was the senior author of a new editorial in Muscle and Nerve that discusses the utility of acetylcholine receptor antibody titer as a pharmacodynamic biomarker for myasthenia gravis. Read that editorial here. 

Translational Brain Sciences

  • Early evidence indicates that occipito-temporal activation patterns for different visual stimuli are less distinct in older than younger adults, yet the extent of these deficits are unclear. Simon Davis, PhD, and colleagues at the Center for Cognitive Neuroscience investigated these issues by fMRI-scanning adults in both age groups who viewed and then remembered visual scenes. They found that sensory features in early visual cortex were less differentiated in older adults, suggesting that aging impairs visual and mnemonic representations in posterior brain regions but enhances them in anterior regions. Read the full article in Neurobiology of Aging.
  • Anhedonia, the loss of pleasure or motivation to engage in previously enjoyable activities, is implicated in several debilitating psychiatric disorders. Simon Davis, PHD, contributed to a narrative review discussing neural signatures of saliency-mapping in this condition. Read their discussion in Psychiatry Research.
  • A new case report in the Journal of Neuropathology & Experimental Neurology discusses the case of a young woman living with a papillary glioneuronal tumor with a novel GPR37L1-PRKCA fusion. John Ervin contributed to that article. Read it here.
  • Regular itching affects more than 20 million people in the United States, and its root causes are still not fully understood. Yong Chen, PhD, was the senior author of a new review article that sheds light on this problem. Chen, along with Qiaojuan Zhang, PhD, and Gwendolyn Henry discuss the role of the TRPV4 ion channel in both acute and chronic itching. Read that article in the International Journal of Molecular Science.

Epilepsy, Sleep, and Clinical Neurophysiology

  • A new consensus statement from  International League Against Epilepsy and the International Federation of Clinical Neurophysiology calls for the continued functioning of epilepsy monitoring units in hospitals during the continuing COVID-19 pandemic and other emergencies. Aatif Husain, MD, was part of this task force, which published its statement in the newest issue of Epileptic Disorders. Read it here.
  • A new study answers important questions about factors influencing whether or not patients with epilepsy proceed with resective epilepsy surgery. First author Vishal Mandge, MD, MPH, and colleagues found that employed patients were more than 4 times likelier than unemployed patients to proceed with surgery. Read more about this and other findings in the latest issue of Seizure.

Parkinson’s and Movement Disorders

  • The use of telemedicine to manage movement disorders and other chronic neurological conditions including movement disorders has expanded over time, especially over the past year. Jeffrey Cooney, MD, co-authored a new article that discusses current practices and recommendations for the use of telemedicine for deep brain stimulation. Read that article here.

Other Topics

  • A new study from the Archives of Physical Medicine and Rehabilitation provides insights into clinical variables associated with onabotulinumtoxinA adherence for spasticity. Wayne Feng, MD, MS, contributed to that article. Read it here. 
  • A recent article in the American Journal of Respiratory and Critical Care Medicine examined racial health disparities in the care of patients with obstructive sleep apnea. Andrew Spector, MD, co-wrote a letter to the editor in the same journal that discussed both the importance of examining racial health disparities in this area as well as a possible flaw in the design of the study that may mistakenly show lower adherence among Black and Hispanic patients. Read that discussion here.

May 07

Duke Neurology Research Round Up, May 2021

Members of the Duke Neurology Department advanced the fields of clinical, translational, and basic neuroscience this April with 14 new peer-reviewed studies. Nicole Calakos, MD, PhD, was the senior author of a new study in Science that  expands our understanding of the integrated stress response in the brain and how it influences learning and memory. Other studies include an analysis of demographic disparities in use of emergency medical services for stroke, the discovery that some skin cells can act as “pre-neurons,” and a national survey of clinical neurophysiology fellowships. Read about these studies and more, and find links to the original journal articles in the paragraphs below.

Epilepsy, Sleep, and Clinical Neurophysiology

  • A new national survey of directors of accredited clinical neurophysiology fellowship programs found great variety in the number of CNP positions and CNP tracks offered. Saurabh Sinha, MD, PhD, was the senior author of the study, which appears in the Journal of Clinical Neurophysiology. Read that study here.
  • Senior authors Brad Kolls, MD, PhD, and Brian Mace outline a practical method for determining automated EEG interpretation software performance on continuous Video-EEG monitoring data in the latest issue of Informatics in Medicine Unlocked. Their approach offers a potentially better method for performance assessment than traditional metrics of sensitivity and specificity. Read more about it here.

Neurodegeneration and Neurotherapeutics

  • A new study found striking sex differences in monocyte gene expression in patients with early Parkinson’s disease. The results of this study have important implications for how inflammation may contribute to the development of this disease. Andrew West, PhD, contributed to the study, which appears in NPJ Parkinson’s disease. Read more.

Stroke and Vascular Neurology

  • A new study in the Journal of Thrombosis and Thrombolysis examined the emergency attendance rate for heart attacks and stroke in Beijing from 2018 through the first half of 2020, providing insight into how the pandemic shaped individuals’ use of these much-needed services. Analysis by Wuwei “Wayne” Feng, MD, MS, and colleagues found that emergency attendance for stroke and heart attacks fell by 50% in the beginning of the pandemic, and then gradually increased afterwards. Read that study here.
  • The New England Journal of Medicine’s THALES trial recently found that ticagrelor and aspirin were better at reducing recurrent stroke than aspirin alone. Senior author Ying Xian, MD, PhD, and colleagues put that trial in context with a new article that examines the past, present and future of antiplatelet therapy trials for ischemic stroke patients. Read that article in the Neuroscience Bulletin.
  • A new analysis identifies several disparities in use of emergency medical services (EMS) for stroke. Senior authors Matthew Ehrlich, MD, MPH, and Carmen Graffagnino, MD, found that EMS use was lower in stroke patients who were younger, had higher income, were married, more educated, and who identified as Hispanic, with EMS use also correlated with faster arrival to code, imaging, and thrombolytic treatment times. Michael Lutz, PhD, Shreyansh Shah, MD, and Brad Kolls, MD, PhD, also contributed to the study, which appears in the Neurohospitalist.
  • The carotid web is an important and under recognized etiology for recurrent cryptogenic strokes. A team including Brian Mac Grory, MB BCh, MRCP, describes the technical nuances involved in successfully performing a carotid endarterectomy for resection of a carotid web. Read that article in Acta Neurochirurgica.

Headache and Facial Pain

  • Wolfgang Liedtke, MD, PhD, wrote a commentary paper for Neuroscience Bulletin discussing a recent Nature paper, “STING controls nociception via type-I interferon signaling in sensory neurons” by Ru-Rong Ji, PhD, and colleagues at Duke. Read that analysis here.

Neurocritical Care

  • Extracranial organ dysfunction following traumatic brain injury remains an under-addressed public health problem. A team including Daniel Laskowitz, MD, MHS, Michael “Luke” James,” MD, and colleagues used a sensitive marker of myocardial injury—high sensitivity troponin (hsTn)—to examine the incidence of early myocardial injury following TBI and explored its association with neurological outcomes following moderate-severe TBI. Read what they found in the Journal of Neurosurgical Anesthesiology.

Parkinson’s Disease and Movement Disorders

  • Mindfulness-based stress reduction (MBSR) offers the potential to alleviate at least some of the harmful symptoms experienced by people with Parkinson’s disease and their care partners. Senior author Sneha Mantri, MD, MS, Allison Allen, MSW, Lacy Rardin, MSW, Jeffrey Cooney, MD, Margaret Ivancic, and former Duke Neurology resident Deepal Shah-Zamora, MD, examined the effects of a nine-week MSBR on both of these groups. The team found that the MBSR improved mindful awareness in care partners and improved health-related quality of life in people with Parkinson’s. Read the full study in Complementary Therapies in Clinical Practice.
  • A devastating itching of the skin driven by severe liver disease turns out to have a surprising cause. The study found that the keratinocyte cells of the skin surface are acting as “pre-neurons.” Senior authors Yong Chen, PhD, and Wolfgang Liedtke, MD, PhD,  as well as Carlene Moore, PhD, contributed to the study, which appears in Gastroenterology. Read it here.

Translational Brain Sciences

  • A new article in Science expands our understanding of the integrated stress response (ISR) in the brain and how it influences learning and memory. Lead authors Nicole Calakos, MD, PhD, and former Movement Disorders Fellow Ashley Helseth, MD, PhD, and colleagues found a class of neurons in the mouse brain, known as striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Genetic and pharmacological manipulations revealed that ISR signaling was necessary in CINs for normal type 2 dopamine receptor (D2R) modulation and that Inhibiting the ISR inverted the sign of D2R modulation of CIN firing and evoked dopamine release and altered skill learning. Calakos lab manager Miranda Shipman, lab analyst Zachary Caffall, postdoctoral associate Brandon Turner, research technician Connor King also contributed to the study, which is available here.
  • A devastating itching of the skin driven by severe liver disease turns out to have a surprising cause. The study found that the keratinocyte cells of the skin surface are acting as ‘pre-neurons.’ Senior authors Yong Chen, PhD, and Wolfgang Liedtke, MD, PhD,  as well as Carlene Moore, PhD, contributed to the study, which appears in Gastroenterology. Read it here.
  • Wolfgang Liedtke, MD, PhD, wrote a commentary paper for Neuroscience Bulletin discussing a recent Nature paper, “STING controls nociception via type-I interferon signaling in sensory neurons” by Ru-Rong Ji, PhD, and colleagues at Duke. Read that analysis here.

Other

  • Chromosomal instability and neuroendocrine CTC phenotypeare associated with worse survival in men with metastatic castration resistant prostate cancer who are being treated with abiraterone or enzalutamide, according to a new study in Clinical Cancer Research. Simon Gregory, PhD, contributed to that study. Read it here.

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