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Duke Neurology Research Round-Up, May 2018

Thursday, May 31, 2018

Members of the Duke Department of Neurology contributed to 13 new studies in peer-reviewed journals in the past month, with stories spanning from genetic analysis to the population level. At the genetic level, a study from the Chiba-Falek lab answered questions about specific proteins that turn genes associated with Alzheimer’s on and off. Meanwhile Ying Xian, MD, PhD, Shreyansh Shah, MD and colleagues analyzed outcomes from hundreds of thousands of patients visiting thousands of stroke centers nationwide. Other new recent research by our faculty and trainees includes an analysis of the optimal treatment for critically ill patients with seizures to the case study of a 65-year-old man experiencing a tumor normally associated with children under three years old.

Here’s a summary of these studies organized by topic:

Memory Disorders

  • The transcription factor PPARy governs pathways implicated in the development of late-onset Alzheimer’s disease (LOAD). Senior author Ornit Chiba-Falek, PhD, Julio Barrera and Shobana Subramanian found that PPARγ may act as a master regulator of the transcription of several genes involved in LOAD. Read their article in PLOS One here.
  • Chiba-Falek, as well as Lidia Tagliafierro, PhD, also co-wrote a recent Neurogenetics article examining how specific short sequence repeats affect the transcription regulation of the SNCA gene. Read that article here.
  • A variety of modifiable and non-modifiable risks exist for Alzheimer’s disease; however, the relative importance of those risks remains unclear. A team including Michael Lutz, PhD and Brenda Plassman, PhD used machine learning to analyze these risks, finding that non-genetic factors contribute more than genetic factors. Read the full extent of their findings here.

General and Community Neurology

  • Lead author Jennifer Kang, MD, senior author Matthew Luedke, MD, and colleagues wrote a case report about a 45-year-old man with hemoglobin sickle cell disease and whose MRI findings showed a “star field pattern of multifocal small cerebral emboli.” Read their findings in Neurology: Clinical Practice here.

Epilepsy and Sleep Disorders

  • Generalized periodic discharges (GPDs) are a type of generalized discharges of electrical activity within the brain. Aatif Husain, MD, and Clinical Neurophysiology fellow Krystal Sully, MD review advances in our understanding of these conditions in the most recent issue of the Journal of Clinical Neurophysiology. Read that article here.
  • For critically ill patients, the best treatment of nonconvulsive seizures is still uncertain. A consortium including lead author Aatif Husain, MD, Brad Kolls, MD, PhD, Christa Swisher, MD, and Keith Dombrowski, MD, helped to answer this question by evaluating two antiseizure drugs in a group of 74 subjects in this population. Read what they found here.

Stroke

  • Despite significant reductions in mortality over the past 20 years, spontaneous intracerebral hemorrhage remains a devastating form of stroke. In the latest issue of Neurology, an editorial co-written by Michael “Luke” James, MD, examples trends and opportunities in treating this condition. Read that article here.
  • Sex-based differences in mortality and outcomes have been noticed in intracerebral hemorrhage, but the reasons for these differences have remained poorly understood. Senior author Michael “Luke” James, MD, Daniel Laskowitz, MD, MHS, Ellen Bennett, PhD, and colleagues examined these differences at the level of genetics and protein expression. The team examined gene and protein expression, as well as a variety of health outcomes, in a sample of mice undergoing a model of ICH. Read their article in Translational Stroke Research here.
  • Laskowitz and Bennett also contributed to a phase-1 clinical trial of a potential therapy for ischemic stroke: allogeneic umbilical cord blood. Laskowitz, Bennett, and colleagues conducted an open-label trial of this therapy in a group of 10 participants, finding that a single IV infusion therapy of this blood appears to be safe and that a phase-2 study is in order. Read more about their study here.
  • The establishment of comprehensive and primary stroke centers holds promise to reduce death and injury from stroke, yet many population-level questions about how effective hospitals with these certifications are remains unanswered. Ying Xian, MD, PhD, Shreyansh Shah, MD, and colleagues helped to answer this question for acute ischemic stroke in the most recent issue of Circulation: Cardiovascular Quality and Outcomes. Read their article here.

Neurodegeneration and Neurotherapeautics

  • New research from the lab of Al La Spada, MD, PhD, and colleagues offers insights into the development of a rare subtype of amyotrophic lateral sclerosis (ALS). ALS4  is a rare, early-onset and inherited form of the disease. The team, which included La Spada, Craig Bennett, PhD, Somasish Dastidar, PhD, Mandheer Wadhwa, and colleagues, developed a mouse model for ALS4 and how mutations in the senataxin lead to the development of the condition. Read what they found here.

Neuro-Oncology

  • Atypical teratoid rhabdoid tumors are, rare, aggressive tumors of the central nervous system that usually appear in children under three years old. Senior author Yasmin O’Keefe, MD, Olinda Pineda, MD, Matthew Luedke, MD, and colleagues present a case report of a 65-year-old man with this condition. In addition to reporting on the oldest known case of this condition, the authors discuss more about the tumors here.