Duke Neurology Research Round Up, August 2023

By William Alexander

This July, members of the Duke Neurology Department contributed to 10 new peer-reviewed journal articles. Highlights of this research include a new study that found persistent associations between neighborhood income levels and poor outcomes for neurocritical care, a trio of studies that provide insights into the origins and development of Alzheimer’s disease, and a preliminary analysis of the merits of a potential off-label therapy for ALS.

Read the paragraphs below for brief summaries of each of these and other articles published over the past 31 days, and find links to the original research articles below.

Neurocritical Care

  • Resident Jay Lusk, MD, MBA, was the first author of a study that examined associations between neighborhood socioeconomic deprivation and  30-day mortality and readmission for patients with sepsis or critical illness. Their analysis found a strong association between neighborhood socioeconomic deprivation and 30-day mortality for critically ill patients even after controlling for factors such as individual poverty, demographics, or access to healthcare resources. Read the full article in Critical Care.

Neuromuscular Disease

  • A new article in Neurobiology of Disease furthers our understanding of the mechanisms of the progression of ALS at a cellular level. Rick Bedlack, MD, PhD, and colleagues found that aggregates of the TDP-43 and SO1 proteins correspond tightly with both ALS disease pathology and the spread of symptoms in patients. Read the full article here.
  • Xiaoyan Li, MD, PhD, and former neuromuscular fellow Yuyao Sun, MD, were the senior authors of the 71st entry in the ALS Untangled series, which reviews the potential off label use of the FDA-approved medication Nuedexta for ALS. Richard Bedlack, MD, PhD, also contributed to the study, which supports considering Nuedexta treatment for bulbar dysfunction in ALS patients. Read the full article in Amyotroph Lateral Scler Frontotemporal Degener.

Parkinson’s and Movement Disorders

  • A new analysis of close to 3,500 open-ended patient responses provides new insights into how people living with Parkinson’s report and are affected by their symptoms. Sneha Mantri, MD, MS, contributed to this new “human-in-the-loop”method, which found tremor, balance and gait problems, and pain/discomfort were the most frequently reported symptoms. Read the full analysis in the Journal of Parkinson’s Disease.

Stroke and Vascular Neurology

  • First author Katherine Peters, MD, PhD, and Sweta Sengupta, MD, contributed to a case report of a patient with optical complications of Behcet disease who manifested both papilledema due to cerebral venous sinus thrombosis as well as combined central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO). Read that article in the Journal of Neuro-Ophthalmology.
  • Over the past decade, randomized controlled trials have shown the enormous potential benefits of endovascular thrombectomy (EVT) for patients who have had acute ischaemic stroke, but determining which stroke patients are eligible for this treatment has been a challenge. William Powers, MD, wrote a new commentary discussing the use of CTA and the ASPECTS score to make this decision. Read that article in the Journal of Neurology, Neurosurgery, & Psychiatry.

Translational Brain Sciences

  • Michael Lutz, PhD, was the senior author of a new study that provides insights into the proteomics of Alzheimer’s disease.  Lutz, as well as co-authors Cathy Shi, Kirby Gottschalk, PhD, Carol Colton, PhD, and Duke Mathematics Sayan Mukherjee, PhD investigated the performance of two statistical methods for identification of proteins and biological pathways associated with Alzheimer’s disease for cross-species comparisons between humans and mouse models. This approach may help inform the development of improved mouse models to better study late-onset Alzheimer’s disease in humans. Read the full article in Frontiers in Systems Biology.
  • Michael Lutz, PhD, was also the senior author of a new pilot study that provides an exploratory assessment of proteomic network changes in cerebrospinal fluid of patients with mild cognitive impairment. Richard O’Brien, MD, PhD, contributed to the study, which appears in  Biomolecules. Read it here.
  • Michael “Luke” James, MD, PhD, and Haichen Wang, MD, contributed to an article in Neuron finding that programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway, with neuronal PD-1 signaling regulates learning/memory in health and disease.  Their findings suggest that conditions that reduce PD-L1 levels or PD-1 signaling could promote memory in both physiological and pathological conditions. Read the full article in Neuron.
  • Maintaining good cognitive function is crucial for well-being across the lifespan. Simon Davis, PhD, was part of a team that examined how the degree of cognitive maintenance within the brain is determined by the functional interactions within and between large-scale brain networks. Their multivariate analysis found that cognitive function is increasingly dependent on function-structure connectivity convergence as age increases. Read the full article in the Neurobiology of Aging.
  • The human chromosome 19q13.32 is a gene rich region and has been associated with multiple phenotypes, including late onset Alzheimer's disease (LOAD) and other age-related conditions. Senior authors William “Kirby” Gottschalk, PhD, and Ornit Chiba-Falek, PhD, as well as colleagues including Michael Lutz, PhD, and Dellila Hodgson, MS, developed the first humanized mouse model that contains the entire TOMM40 and APOE genes with all intronic and intergenic sequences including the upstream and downstream regions. This improved mouse model offers new opportunities for research studies on the APOE genomic region in relation to LOAD and other conditions in adulthood. Read more about it in the Journal of Alzheimer’s Disease.

Grants and Awards

  • Brian Mac Grory, MB BCh, MRCP, Carlene Moore, PhD, and resident Jay Lusk, MD, MBA were one of seven teams who recently received funding from the American Heart Association (AHA) to study the links between migraine, strokes, and cardiovascular disease.  will study the connection between migraine and ocular stroke. Read about that award here.
  • Brian Mac Grory, MB BCh, MRCP, and Jamila Minga, PhD, CCC-SLP, both received $30,000  from the Fund to Retain Clinical Scientists at Duke. These awards, supported by the American Heart Association, allow physician-scientists with significant care-giving responsibilities to continue their work. Minga will use her funding to investigate neuroanatomic correlates of language production after right hemisphere stroke, while Mac Grory will investigate atrial fibrillation as a novel risk factor for retinal stroke.