Research and Education at The

University of Chicago Neurology Department

Matt Burns, MD PhD

Neurology pgy3

matthewburns847@gmail.com

Matt Burns, MD PhD

Neurology pgy4

matthewburns847@gmail.com

Research and Education at The

University of Chicago Neurology Department

Neuro ICU• Drs. Goldenber, Kramer, Hornik, and Martinez

• STATUS Trial: The STATUS Trial is randomized, double-blind, placebo-controlled phase III study to evaluate the efficacy and safety of SAGE-547 injection in the treatment of patients with super-refractory status epilepticus (SRSE).

• MISTIE III: Minimally Invasive Surgery Plus rt-PA for intracerebralHemorrhage Evacuation is an international, Phase III, 500-patient clinical trial with the primary goal of defining a successful treatment for ICH, and the primary endpoint of modified Rankin Scale measured at 180 and 365 days after stroke.

Stroke• Dr. Brorson

• ACTIsSIMA: Double-Blind, controlled phase IIB study of Modified Stem Cells (SB623) in the treatment of motor deficits in ischemic stroke

• CREST-II: Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial.

• RESPECT-ESUS: A randomized, double-blind evaluation in secondary stroke prevention comparing the efficacy and safety of the thrombin inhibitor dabigatran etexilate vs acetylsalicylic acid in patients with embolic stroke of underdetermined source (ESUS).

Neuro-immunology

• Dr. Javed

• Advanced MRI measures of repair in relapsing/remitting MS patients and Alemtuzemab-treated patients.

• Dr. Reder

• Abnormal IFN-b-1b signaling, cellular and molecular mechanisms of IFN, and IFN resistance in MS.

• Dr. Roos

• Mechanisms of immune-mediated demyelination in an MS model using Theiler’s murine encephalomyelitis virus.

• Dr. Kraig

• Exosome RNA-Therapeutics to Promote CNS Myelination.

• Dr. Popko

• Targeting the integrated stress response to protect oligodendrocyte lineage cells, DTA oligodendrocyte ablation model in the study of inflammatory demyelination, and investigating the role that ZFP191 phosphorylation state plays in regulating oligodendrocyte maturation, and new PET imaging technology.

• Dr. Arnason

• Fc-IgG tetramer to modify immunity in experimental autoimmune enchephalitis and MS.

Neuro Oncology

• Dr. Lukas• A Randomized Phase III Open Label Study of Nivolumab vs Temozolomide Each in

Combination with Radiation Therapy in Newly Diagnosed Adult Subjects with Unmethylated MGMT (Tumor O6-Methylguanine DNA Methyltransferase) Glioblastoma.

• A Phase 3, Randomized, Controlled, Double-Arm, Open-Label, Multi-center Study of VB 111 Combined with Bevacizumab vs. Bevacizumab Monotherapy in Patients with Recurrent Glioblastoma

• A Randomized Phase 2 Single Blind Study of Temozolomide Plus Radiation Therapy Combined With Nivolumab or Placebo in Newly Diagnosed Adult Subjects With MGMT-Methylated (Tumor O6-methylguanine DNA Methyltransferase) Glioblastoma -CheckMate 548: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 548

• A Phase 1/2 Study of the Combination of Indoximod and Temozolomide for Adult Patients with Temozolomide-Refractory Primary Malignant Brain Tumors

• A071101: A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 Vaccine Given With Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM)

• A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Subjects with Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma

Neuro-physiology

• ALS• Dr. Rezania

• A Double-Blind, Randomized, Multicenter, Placebo Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Fingolimod 0.5 mg Administered Orally Once Daily Versus Placebo in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

• Assessment of intermuscular coherence as a biomarker for ALS, and commercialization of a diagnostic test for ALS

• Dr. Roos• SOD1 Designed ankyrin repeat protiens (DARPins), a genetically

engineered antibody mimetic protein, as a treatment for ALS

• Brain Machine Interface

• Dr. Towle• Development and implementation of visual prostheses

Movement and Dementia

• Dr. Xie• Deep brain stimulation in gait and swallowing function, and biomarkers in Parkinson disease (funded

by Michael J Fox Foundation)• Antibody infusion in the treatment of Progressive Supranuclear Palsy (BMS and Abbvie sponsored,

multi-sites). • Dystonia coalition: The purpose of this study is to create a “repository” or an organized collection of

medical data and samples to be used for future research on dystonia and other diseases. We will collect information, videos and blood samples from adults who have dystonia or related disorders and store this in the repository. (NIH), National Institute of Neurological Disorders and Stroke (NINDS) and the Office of Rare Diseases Research (ORDR).

• Dr. Gomez• A novel role for a bicistronic calcium channel gene in neurodevelopment and neurodegeneration,

overlapping cistrons in a family of ion channel genes in spinocerebellar ataxias (funded by NINDS)

• Dr. Mastrianni• Imaging Dementia – Evidence for Amyloid Scanning (IDEAS) Study. Assessing the impact of amyloid

positron emission tomography (PET) imaging on outcomes in patients with mild cognitive impairment or dementia of uncertain origin.

• Ongoing work in molecular mechanisms of neurodegeneration in Alzheimer’s Disease and Prion diseases, the role of sleep in memory consolidation in early stage Alzheimer’s disease, and detecting tau protein from nasally expired air in Alzheimer’s and other diseases.

Epilepsy• Combining intracranial electrophysiological recording and imaging to

develop biomarkers for hippocampal epilepsy (Dr. Wu)

• Development and testing of a cortical visual prosthesis (a multi-institutional collaboration led by Dr. Towle)

• Understanding the deep brain circuits involved in attention and memory (collaboration with the Departments of Neurobiology and Psychology)

• Investigating genetic susceptibilities in primary generalized epilepsy (collaboration with the Department of Neurobiology)

• Using neurophysiological recordings and mathematical analysis to better understand how central motor systems coordinate limb movement (collaboration with the neuromuscular section).

• Understanding the role of seizures in the pathophysiology of neurocysticercosis (collaboration with the Atahualpa Project, Ecuador).

• Dr. Tao is leading research into understanding and preventing SUDEP.

Neuro-informatics

• Dr. Maraganore• The department of Neurology at NorthShore University HealthSystem

has built into its commercial EMR structured clinical documentation support and clinical decision support tools that standardize care, write progress notes, and capture up to 1000 discreet and cascading fields of neurology data per office visit.• Ongoing implementation of structured clinical data intake across 10

common neurological diseases and 7 national sites.

Medical Education research within Neurology

-Albert DV, Blood A, Park YS, Brorson JR, Lukas RV. Breadth vs. volume alone: the outpatient neurology clinic experience in the education of medical students. Journal of Clinical Neuroscience. 2016;28:20-23.-Sethi NK, Lukas RV, Brorson J, Albert DV. Structure of neuroscience clerkships in medical schools and matching in neuromedicine. Neurology. 2016;86(4):403.- Blood A, Park YS, Lukas RV, Brorson JR. Is case specificity a given? The reliability of a neurology clerkship objective structured clinical examination (OSCE) as examined through a generalizability study. Neurology. 2015;85(18):1623-9.- Albert DV, Yin H, Amidei C, Dixit KS, Brorson JR, Lukas RV. Structure of neuroscience clerkships in medical schools and matching in the neuromedicine. Neurology. 2015;85(2):172-6.

…Even more teachers

Naoum Issa, MD, PhD Assistant ProfessorDirector, Epilepsy Research

Shasha Wu, MD, PhD Assistant ProfessorDirector, Epilepsy Monitoring Unit

James Tao, MD, PhDAssociate ProfessorDirector, EEG laboratoryInterim Director, Clinical Neurophysiology Fellowship Program

Sandra Rose, MDAssistant ProfessorDirector, Intra-operative Monitoring

…Even more teachersBetty Soliven, MDProfessor of NeurologyDirector, Electrodiagnostic Laboratory for Neuromuscular Disease (EMG Lab)Co-Director, Neuropathy and Neuromuscular ClinicCo-Director, Amyotrophic Lateral Sclerosis (ALS) Clinic

Helene Rubeiz, MDAssociate Professor of NeurologyDirector, neurology residency program

Karoush Rezania, MDAssociate Professor of Neurology

Faculty Teaching awards

• 03-04: James Tao MD PhD

• 04-05: Kenneth Silver MD (Child Neurology Attending)

• 05-06: Fernando Goldenberg MD

• 06-07: Helene Rubeiz MD and Thomas Kelly MD

• 07-08: Raymond Roos MD

• 08-09: Jeffrey Frank MD

• 09-10: Jeffrey Frank MD

• 10-11: Agnieszka Ardelt MD PhD

• 11-12: Tao Xie MD PhD

• 12-13: Tao Xie MD PhD

• 13-14: Thomas Kelly MD

• 14-15: Thomas Kelly MD

• 15-16: Agnieszka Ardelt MD PhD

• 16-17: Thomas Kelly MD

Educational & Teaching Opportunities

• MERITS (Medical Education Research, Innovation, Teaching, and Scholarship)• Two year residency track focusing on a curriculum to develop

educational leaders and scholars through workshops, mentored projects, lecture series, and national conferences

• Symposia (Roos rounds, Barry G. Arnason Symposium, SchorrRounds, stroke conference, Neuro ICU conference, neuromuscular conference).

• Med student teaching and mentorship

Maclean Fellowship in Medical Ethics

• Maclean Center = nation’s first clinical ethics program

• Part-time fellowship during PGY4 year designed for physicians interested in gaining experience in medical ethics

• 5 weeks of full time coursework in July/Aug (Intro to clinical, research, pediatrics, transplant, and surgical ethics, religious tradition, social/policy issues)

• Longitudinal courses on moral philosophy and law throughout the year

• Themed seminar series (Reproductive ethics 2015, Neuro-ethics 2016, Trauma ethics 2017)

• Ethics consult service and case conference

• Mentored research project by Maclean Center faculty• Examples: ALS patient experiences w/ genetic testing, structuring goals of

care discussions in the ICU, capacity evaluations in patients with neurological injury

What I’m doing