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.

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.

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.

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.

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 DisordersRead 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.

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.

Duke Neurology Research Round Up, March 2021

Research from members of the Duke Neurology Department advanced the fields of clinical, translational, and basic neurology in February. Over the past 28 days, our faculty, staff, and trainees contributed to journal articles answering questions about the use of mobile phones for stroke care, modifiable risk factors associated with cognitive decline in Parkinson’s, the genetics of Alzheimer’s disease, and more. The paragraphs below contain short summaries of each of the 13 articles published in February featuring members of our Department, along with links to the original articles themselves.

Stroke

  • A new analysis of data from more than 20,000 stroke patients treated for depression answers important questions about complications and outcomes associated for patients with both these conditions. The study found that stroke patients treated for depression had higher rates of mortality, readmission to the hospital, major cardiac events and other poorer outcomes, showing the need for further research and interventions for this vulnerable population. Shreyansh Shah, MD, Ying Xian, MD, PhD, contributed to this study, which was published in Stroke and Vascular Neurology.
  • Mobile phones offer enormous potential to improve the speed of thromboyltic therapy for ischemic stroke, but effective, reliable platforms that that work throughout the first aid process still need to be built and tested. Wuwei “Wayne” Feng, MD, MS, helped test one potential platform in a new observational study. Feng and colleagues examined the utility and use of a new platform in the management of ischemic stroke and in reporting door-to-needle time over a two-year period. They found sustained improvement in door-to-needle time overall observed months and across all facilities observed. Read the full study in JMIR Mhealth UHealth.
  • Direct factor Xa inhibitors have been developed as alternatives to warfarin for stroke prevention in atrial fibrillation. Some patients may experience intracerebral hemorrhage while taking these drugs. Because these adverse events are rare, there are limited data of these complications. Ying Xian, MD, PhD, was the first author of a new study that examined more than 200,000 patients with intracerebral hemorrhage. The analysis suggest that factor Xa inhibitors are a better choice than warfarin. Read that study in JAMA Open Network.
  • A new analysis by Brian Mac Grory, MB BCh, MRCP, and colleagues found that baseline hyperglycemia was associated with brain infarction growth in ischemic stroke patients. Finding ways to establish glycemic control before and after reperfusion in patients could be a way to improve outcomes and reduce complications for patients at risk of stroke. Read the full study in the Journal of Stroke and Cerebrovascular Disease.

Neurodegeneration and Neurotherapeutics

Translational Brain Sciences

  • The APOE gene is one of the strongest, most reproducible genetic risk factors for Alzheimer’s disease. It may also hold the key to developing the first effective therapies for the condition. Senior author Ornit Chiba-Falek, PhD, first author Anna Yang, and Duke Neurobiology’s Boris Kantor, PhD wrote an article discussing how precision medicine may allow APOE to be a new frontier in developing therapies for Alzheimer’s disease. Read that article in the International Journal of Molecular Sciences.
  • A new review article from the lab of Yong Chen, PhD, sheds important light on the molecular underpinnings of orofacial pain. The review article examines the experimental evidence involving TRP ion channels and the possible cellular and molecular mechanisms behind them, in orofacial pain. Senior author Yong Chen, first author Yuhi Luo, PhD, Qiaojuan Zhang, PhD, Peng Wang, MS, and Abbie Suttle, MSc, contributed to the article in Molecular Neurobiology. Read it here. 
  • Michael Lutz, PhD, contributed to a new Alzheimer’s and Dementia investigating genes associated with cognitive decline in Black Americans without Alzheimer’s disease. The team investigated the effects of the ‘523-short variant within the apolipoprotein E (APOE) genotype, finding the variants had different effects among non-demented Blacks depending on the APOE allele. This finding helps to explain previous mixed findings and cognitive decline observed in this population. Read the study in Alzheimer’s & Dementia.
  • Alzheimer’s disease is a growing national crisis, with more than 5 million Americans living with the condition, a number that will more than double by 2050. Michael Vitek, PhD, recently met with other Alzheimer’s experts as part of the Alzheimer’s Association Business Consortium Think Tank to address the massive unmet need to improve the discovery and successful development of Alzheimer’s therapies. Read what that group proposed in Alzheimer’s & Dementia: Translational Research and Clinical Interventions.

Neuro-Oncology

  • Among other challenges, reaching a culture of equity, inclusion and diversity in academic medicine will require a thorough evaluation of bias and evidence-based strategies to mitigate that bias. Katy Peters, MD, PhD, was a co-author of a new article providing a broad perspective on evaluating bias in the neuro-oncology workplace. Read that article here.

Movement Disorders

  • Cognitive impairment is one of the most feared, debilitating complications of Parkinson’s disease, and no therapies can slow or prevent this condition. Sneha Mantri, MD, MS, was part of a team that was able to identify modifiable behaviors or comorbidities including higher body mass index, anxiety, depression, and poor sleep associated with faster decline. These associations offer opportunities for early intervention to delay or reduce cognitive impairment. Read the full study in Movement Disorders Clinical Practice.
  • Mantri contributed to another study examining possible triggers and alleviating factors of fatigue in Parkinson’s disease. A sample of more than 1,000 individuals with Parkinson’s disease conducted by Mantri and colleagues identified several behavioral and environmental triggers and alleviating strategies for fatigue. Their study may inform future developments of treatments of coping strategies for this complication. Read it in PLoS One.

Other Topics

  • A team including Wolfgang Liedtke, MD, PhD, has developed a mechanically responsive bioartificial tissue that responds to mechanical loading to produce a preprogrammed therapeutic biologic drug. This engineered, living tissue constructed for coordinated drug delivery obviates many of the traditional limitations of “smart” materials, such as long-term integration, rapid dynamic responses, and extended drug delivery without the need for replacement or reimplantation of the drug delivery system. Read the full study in Science Advances.

Duke, UNC to collaborate in fight against Alzheimer’s disease

The Duke University and the University of North Carolina Alzheimer’s Disease Research Collaborative (Duke/UNC ADRC) brings together leading researchers in Alzheimer’s disease and related dementias across two major research institutions.

Together, the Duke/UNC ADRC aims to catalyze and support research, innovations in clinical care and academic work force development (with North Carolina Central University, East Carolina University and UNC Pembroke as partner institutions) in this field. Its ultimate purpose is to reduce the burden of Alzheimer’s disease and related dementias regionally and nationally. The outstanding scientific environment at both institutions enables novel research to identify effective methods of prevention and/or early intervention, and to reduce racial and urban/rural disparities associated with dementia. Read more about it here.

DCNN faculty involved in core areas of the Duke/UNC ADRC include Carol Colton, PhD, Shih-Hsiu “Jerry” Wang, MD, PhD, Michael Lutz, PhD, and Neurology Department Chair Richard O’Brien, MD, PhD.

Duke Neurology Research Round Up, January 2021

NIH EEGThe final month of 2020 saw fifteen new publications written or co-written by members of the Duke Department of Neurology. Sneha Mantri, MD, MS, was a lead author of a new study examining factors contributing to burnout and moral injury among health-care workers at Duke. Our Neuromuscular Disease faculty wrote multiple studies advancing our understanding of myasthenia gravis, including how the COVID-19 pandemic is affecting people with this condition. Other articles answered questions about stroke, Parkinson’s, and other diseases. Read short summaries of each of these publications, and find links to the original articles below.

Translational Brain Sciences

  • Tatiana Segura, PhD, was the senior author of a new review article examining the role macrophages play in the body’s inflammatory and self-repairing processes, as well as how to engineer biomaterials that steer macrophages for tissue regeneration. Read that article in Frontiers in Bioengineering and Biotechnology.
  • While the APOE4 gene appears to increase Alzheimer’s disease risk by increasing neuroinflammation, the specific neuroinflammatory pathways involved are unclear. A team including Michael Lutz, PhD, analyzed targeted proteomic data from samples of cerebrospinal fluid using a linear regression model adjusting for age, sex, and APOE4 copy number, and additional linear models also adjusting for AD clinical status or for CSF Aβ, tau, or p-tau levels. Read what they found in the Journal of Alzheimer’s Disease.

Parkinson’s Disease and Movement Disorders

  • Burt Scott, MD, PhD, contributed to a new study that examined changes in the retina and choroid of eyes in individuals with Parkinson’s disease. The cross-sectional study found that individuals with Parkinson’s had significant differences in vessel and perfusion density, showing potential for a non-invasive biomarker for this condition. Read the full study in JAMA Ophthalmology.

General and Community Neurology

  • Sneha Mantri, MD, MS, was the first author of a Journal of Nervous and Mental Disease study that examined moral injury symptoms among health-care professionals at Duke. Nearly 1 in 4 (23.9%) of professionals had symptoms causing moderate or greater impairment. Burnout, recent medical errors, and lower religiosity were associated with greater moral injury. Read the full article here.

Multiple Sclerosis and Neuroimmunology

  • The COVID-19 pandemic has added new complexity to care for many chronic diseases, including multiple sclerosis. One model to quickly and effectively share information for this condition is Project ECHO, a videoconference-based education and case consultation program offered to providers caring for patients with MS. Mark Skeen, MD, was part of a team reporting on this project. Read that article in Multiple Sclerosis and Related Disorders.

Neuromuscular Disease

  • A new study offers important evidence about the use of non-invasive ventilation for ALS patients in hospice care. Senior author Rick Bedlack, MD, PhD, and colleagues performed a retrospective cross-sectional study of patients, finding those who continued on non-invasive ventilation had a similar length of stay without incurring overwhelming financial or administrative costs. Read that article in the American Journal of Hospice and Palliative Care.
  • A new study answers important questions about the immune profiles associated with autoimmune seronegative myasthenia gravis (SN MG). Senior authors Jeffrey Guptill, MD, MHS, John Yi, PhD (Department of Surgery), and colleagues performed high‐dimensional flow cytometry on blood samples from SN MG patients, healthy controls, and acetylcholine receptor antibody MG patients. The team found reduced plasmablast frequencies were strongly associated with a SN MG diagnosis, making them a potential diagnostic biomarker in the future. Shruti Raja, MD, Lisa Hobson-Webb, MD, Karissa Gable, MD, Vern Juel, MD, and Natalia Gonzalez, MD, contributed to the Muscle and Nerve article, which is available here.
  • Patients with myasthenia gravis may be particularly vulnerable during the COVID-19 pandemic from risks of worsening disease, potential adverse effects of COVID-19, and a limited ability to fight off infection related to immunosuppressive treatments. Lead authors Yingkai Li, MD, PhD, and Jeffrey Guptill, MD, MPH, and colleagues in our Neuromuscular Division (Douglas Emmett, the DCRI’s Marjan Cobbaert, MPH, Donald Sanders, MD, Vern Juel, MD, Lisa Hobson-Webb, MD, Janice Massey, MD, Karissa Gable, MD, Shruti Raja, MD, and Natalia Gonzalez, MD) conducted a survey of nearly 2,000 patients at Duke to better understand how patients are experiencing the COVID‐19 pandemic, including where they receive relevant information, how it has affected medical care, and what measures they use to protect themselves. Read what they found in Muscle and Nerve.

Memory Disorders

  • A new case report case report highlights the importance of assessing clinical trajectory in patients with rapidly progressing dementia. Lead authors Andy Liu, MD, and Elijah Lackey, MD, as well as Jodi Hawes, MD, wrote the case report for Case Reports in Neurological Medicine. Read it here.
  • Sarah Cook, PhD, was a co-author of a recent article in Neuropsychology that used comprehensive neuropsychological criteria to identify patients with mild cognitive impairment (MCI) in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. The team found that NP criteria identified a proportion of MCI and reversion rate within ACTIVE that is consistent with prior studies involving community-dwelling samples. Read more about the study here.
  • Brenda Plassman, PhD, was the senior author of a new study examining cognitive decline in relation to hearing loss, vision loss, or the loss of both senses. Their analysis of nearly 300 older individuals found a significant association between hearing loss, dual sensory loss and faster cognitive decline. Read that study in the Journal of the American Geriatric Society.

Neurocritical Care

  • The shortage of available donor lungs remains an impediment to life-saving organ donation for those with end-stage pulmonary disease. Cherylee Chang, MD, wrote an editorial discussing the significance of this problem, factors limiting the availability of lungs for donation, and risks and benefits of deepening the pool of potential donors. Read that article in Critical Care Medicine. 

Stroke

  • Wayneho Kam, MD, and Nada El-Husseini, MD, wrote a new chapter in the ASPC Manual of Preventive Cardiology. The chapter, “Prevention of Ischemic Stroke,” provides the latest evidence-based practice guidelines on the primary prevention of ischemic stroke, focusing on nine vascular risk factors and their conferred stroke risk. Read that chapter here.
  • A new study by senior author Ying Xian, MD, PhD, Daniel Laskowitz, MD, MHS, and colleagues examined how changes in informed consent policies affected door-to-needle times in stroke patients receiving thrombolytic therapy with tissue plasminogen activator (tPA). Their analysis of nearly 1,000 patients found that changing policy to require verbal rather than written consent reduced door to needle times by 5.6 minutes on average. Read the full study in the Journal of Stroke and Cerebrovascular Disease.
  • Xian also contributed to a new study examining the American Heart Association’s Target: Stroke quality initiative, which disseminated feasible strategies to shorten door-to-needle times for thrombolytic therapy. Xian and colleagues at the DCRI analyzed date from nearly 1500 Get with the Guidelines-Stroke hospitals, finding that door-to-needle times decreased from 80 to 68 minutes on average. Read that study here.

Duke Neurology Research Round Up, November 2020

NIH

Neuron image courtesy NIH

Members of the Duke Neurology Department contributed to 14 new peer-reviewed studies this October, advancing our understanding of or ability to treat Parkinson’s disease, Alzheimer’s, stroke, and other conditions. Laurie Sanders, PhD, and Claudia Gonzalez Hunt, PhD, advanced our understanding of the links between mitochondrial DNA damage and Parkinson’s disease, providing a potential avenue for future therapies. Andy Liu, MD, contributed to a study that compared how changes in the structure of the eye differ between patients with Alzheimer’s, mild cognitive impairment, and healthy individuals. Tatiana Segura, PhD, was the senior author of a study discussing how the injection of hydrogel biomaterial scaffolds to the brain after stroke may improve brain plasticity and endogenous repair. And Andrew Spector, MD, discussed the founding, mission, and future plans of the Society of Black Neurologists in a short article in Lancet Neurology.

Read more about those articles, and find links to the original research, below.

General Neurology

  • The Society of Black Neurologists (SBN) was founded almost two years ago to foster discussion, mentorship, and camaraderie among Black neurologists.Since then it has grown to more than 200 members worldwide and has organized in-person events and webinars. First author Andrew Spector, MD, and colleagues discuss the SBN and its goals for the future in the latest issue of Lancet Neurology. Read that article here.

Memory Disorders

 

Epilepsy, Clinical Neurophysiology, and Sleep

  • A new article in the Journal of Clinical Neurophysiology answers questions about double train transcranial electrical stimulation (dt-TES) for motor-evoked potentials (MEP). Senior author Aatif Husain, MD, first author Emily Kale, and Michael Lutz determined that MEP amplitudes benefited the most from asymmetric dt-TES with 2 + 7 pulses. Read that article here.

Neurocritical Care

  • Neurocritical care fellow Vyas Viswanathan MD, contributed to a retrospective review of 152 patients with inflammation due to cerebral amyloid angiopathy. The team found evidence that corticosteroid-treatment leads to clinical and radiological short-term improvement for the condition. Read that study in the Journal of Neuroimmunology.
  • A new case study offers insights and understanding of the potential for spinal cord stimulation as a possible treatment for paraplegia. A team including Saurabh Sinha, MD, Dana Lott, DPT, and Emily Kale discuss the case of an individual with chronic complete L1 paraplegia and chronic pain who received spinal cord stimulation implantation, noting his progress over the next year and a half. Read the full study in Spinal Cord Series and Cases.

Translational Brain Sciences

  • New strategies are urgently needed to treat neurological deficits caused by stroke. Senior author Tatiana Segura, PhD, and colleagues discuss how the injection of hydrogel biomaterial scaffolds to the brain after stroke may improve brain plasticity and endogenous repair in a video article for the Journal of Visualized Experiments. View that article here.
  • The arrival of effective treatments for Alzheimer’s disease would have profound implications for the way we diagnose, study, triage, and allocate resources to patients with the condition. Ornit Chiba-Falek, PhD, was the senior author of a study that discusses what those treatments might mean for caregivers, clinicians, researchers, and the healthcare system at large. Read that discussion in Life Sciences, Society and Policy.
  • Mitochondrial DNA damage may be a sensitive measure of altered kinase activity in patients with Parkinson’s disease, according to a new article by lead authors Laurie Sanders, PhD, Claudia Gonzalez-Hunt, PhD, Catherine Toste, and colleagues. By providing an extended profile of LRRK2 kinase modulation, this finding may provide a biomarker-guided entry into clinical trials for Parkinson’s. Read that Scientific Reports article here.
  • A new article by lead author Alexandra Badea, PhD, and colleagues combined MRI and micro CT studies in an animal model of microcephaly. Their study shows that lack of the GIT1 protein results in skull shape abnormalities, that are associated with brain atrophy, white matter, and cortical layer deficiencies. The team used clustering of volume covariance adjacency matrices to identify vulnerable brain region networks that change in a concerted fashion. Read that article in Magnetic Resonance Imaging.

Stroke and Vascular Neurology

  • A new review article discusses carotid webs, a common mechanism for stroke, particularly for younger patients without vascular risk factors. First author Brian Mac Grory, MD, and colleagues discuss the origins, visualization strategies, and management of this condition, which appears in the Journal of Neurology, Neurosurgery, and Psychiatry.
  • Mac Grory also contributed to a new Neurology article examining impact of delirium on withdrawal of life-sustaining treatment after intracerebral hemorrhage. The single-center cohort study found that delirium was associated with withdrawal of treatment after intracerebral hemorrhage regardless of when it occurs. Read that article here.
  • A team including Ying Xian, MD, PhD, investigated whether the Centers for Medicare and Medicaid’s elimination of trial admissions and the initiation of documentation requirements limited inpatient rehabilitation facility access while increasing skilled nursing facility (SNF) utilization compared to home discharge (HD) in ischemic stroke (IS) patients. Read that article here.

Neuromuscular Disease

  • Lisa Hobson-Webb, MD, was part of a group that developed and tested a 12-week respiratory muscle training program to address progressive respiratory muscle weakness in late-onset Pompe disease (LOPD). Read the results of their sham-controlled clinical trial in Neuromuscular Disorders.
  • In the latest issue of Muscle and Nerve, a team including Don Sanders, MD, used Extrapolated‐Reference‐Values‐Procedure (E‐Ref) to compare data with the recently‐published reference‐value for concentric electrode jitter. The team found the E-Ref jitter cut-off value results were not significantly different from the reported reference values. Read that story here.