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Neurology Department Fourth Annual Research Blitz
Fall 2019
Movement Disorders/Neurodegeneration divisionLeo Almeida - DBS
Melissa Armstrong – DLB/PDD, patient engagement, quality/guidelines
Wissam Deeb – Dystonia, Tourettes
Matthew Farrer – neurogenetics
Chris Hess – neurophysiology tremor, myoclonus, dystonia
Irene Malaty – PD outcomes, trials; Tics/Tourettes
Demetri Maraganore – Brain Health
Karen McFarland – transcriptomics, bioinformatics, ataxias, AD
Nick McFarland – neurodegeneration, biomarkers, PD/atypical parkinsonism, Huntington disease
Michael Okun – DBS
Addie Patterson – education and palliative care
Diego Rincon-Limas – Drosophila models of neurodegeneration
Adolfo Ramirez-Zamora – DBS, trials, collaborative projects
Aparna Shukla – Dystonia, tremor, rTMS
Yuquig Li – Dystonia, RLS models
Neil Weisbrod – palliative care in AD
Leo Almeida, MD
Current projects◦ DTI/tractography in DBS outcomes for movement disorders
◦ Augmented and Virtual reality for Freezing of Gait in Parkinson’s disease
◦ Novel stimulation patterns in DBS for movement disorders
◦ Use of exoskeleton as adjunctive therapy for movement disorders
Potential resident projects◦ Retrospective database review
◦ Side projects from the main projects above
◦ Case reports and series
Wissam Deeb, MD
Tic detector◦ Collaboration with Dr. Gunduz (biomed engineering)
◦ Surface EMG sensors (Delsys Trigno)
◦ Algorithm to detect tics
◦ Algorithm to characterize tics by frequency, severity, and location
VR-augmented CBIT◦ Collaboration with Dr. Santoso (digital worlds institute)
◦ Different VR settings to assess antecedent and consequent factors
1) Neurogenetics – from high-throughput genome sequencing to polygenic risk & precision medicine, in clinical service and discovery research
2) Translational neuroscience & drug development – modeling mutant gene dysfunction in mice via cre-loxP/AAV genome modification, focusing on behaviour, brain biochemistry and neurotransmitter physiology.
https://www.ncbi.nlm.nih.gov/pubmed/?term=farrer+m
Matt Farrer PhD.,Professor Of Neurology (Molecular Neuroscience)Norman Fixel Institute for Neurological Diseases,McKnight Brain Institute, L5-101D,Director, Clinical Genomics Program,UF Clinical and Translational Science Institute,University of Florida
E: [email protected]: 352.273.5611C: 352.538.8361Admin. support: E. [email protected]. 352 273 5550
Predict and Prevent – projects in PD, AD, brain aging & seizure disorders
Christopher Hess, MD
Current Projects◦ High Density EEG to study the cortical oscillations
associated with head turning in cervical dystonia and healthy controls
◦ NPF Apprise Clinical Trial (wearable sensors in PD)
◦ Tremor and myoclonus physiologic analyses
Possible Resident Projects◦ Movement disorders case reports
◦ CMDNR INFORM database retrospective studies
Center for Movement Disorders and Neurorestoration
Yuqing Li, PhD Current projects
◦ Animal models and pathophysiology of DYT1 dystonia (NIH R01 with Dr. Vaillancourt), using conditional knockin and knockout mice, brain imaging to map the pathological brain circuits.
◦ Animal models and pathophysiology of restless legs syndrome (NIH R01), using conditional knockout mice, brain imaging, and patch clamp recording.
◦ Chemogenetic or DREADD manipulation of striatal cholinergic interneurons in DYT1 dystonia as a potential treatment for DYT1 dystonia (DOD, CDMRP) , directed by Dr. Fumiaki Yokoi
◦ Opioid receptor knockout mouse models to study restless legs syndrome (Mundipharma, Inc)
◦ C9ORF72 and its interaction with other proteins, implications in dystonia, ALS, and FTD
Potential resident projects◦ Dystonia benchwork research, analyzing DNA/RNA/proteins samples, brain
anatomy or behavior◦ Restless legs syndrome bench work research, similar as above. ◦ C9ORF72 research, similar as above.
Irene Malaty, MD
Parkinson disease◦ Quality Improvement Initiative – international database with potential for
many different types of research on motor and non-motor outcomes in PD. Data is available for mining!
Tourette syndrome◦ Comorbid conditions in adults with persistent tics
◦ Relationship of comorbidity severity and tic severity in kids
Botulinum toxin injection◦ Outcomes in safety and efficacy across indications
Neurology in our state◦ Can look at trends in trainee versus population growth
Nick McFarland, MD, PhD• Rab GTPase proteins – mediate toxic protein buildup, “seeding”
• Synuclein/tau models in cells, brain slice culture
• Preclinical models with AAV
Parkinson/neurodegenerative disease models
• Gait/balance analysis – PD vs Atypical Parkinson disorders
• Mood disorders: free water diffusion, MRI brain
• MRI biomarkers (Dr. Vaillancourt – U01)
PSP/Atypical Parkinsonism Clinical-Research Initiative
• UTI/infection, Gut microbiome in PD
• PD cognitive subtypes, dementia (Dr. Price)
• Neuroimmune markers, LRRK2/GBA in PD (Dr. Malu Tansey - Emory)PD/APD Biomarkers
• Motor phenotype and neuropsychiatric symptoms (Enroll-HD)
• RAN proteins in HD (Dr. Ranum)Huntington disease
Karen McFarland, PhDCurrent Projects
Effects of Tau or alpha-Synuclein (separate projects, same approach) overexpression on translation and ribosome function
◦ AAV based expression in slice cultures from mouse brains
◦ Cell-type specific expression (can compare effects in neurons vs astrocytes vs glia)
Effects of Abeta seeding in vivo (mouse APP brains) and in vitro (cell culture)◦ Strain effects from diffuse vs core plaques?
◦ Transcriptomics read-out & bioinformatics
1Florida ADRC and Neuromedicine/CTRND brain bank◦ Coordinate sample procurement and distribution
◦ >130 brains: AD, PD, PSP, MSA and more…
◦ Remember! Great resource available to the neuro community
Michael Okun, MD
Closed Loop DBS
Novel Stim Patterns
Mobile Computing Platforms
Adolfo Ramirez-Zamora, MD
Potential collaborative Resident Projects
1. Participating in ongoing prospective studies; tremor and PD DBS
2. Parkinson outcomes projects (PF) database studies (Excellent opportunity!)◦ Projects using this large database with 12,000 patients
◦ Use of medications, gait, etc. Main outcome is PDQ-39, quality of life
3. Fixel, INFORM database retrospective studies◦ Literature Reviews, case reports, participating in ongoing projects with
fellows
Center for Movement Disorders and Neurorestoration
GOAL: To discover therapeutic targets that block Abeta42 and Tau pathology in a fly model of AD
Opportunities to learn: genetics, molecular and cellular biology, transcriptomics,
histology and optogenetic technologies.
Flies display:Aβ42 aggregatesPhospho TauNeuronal deathMemory decline
Aβ42TauAβ42Tau
Diego Rincon-Limas, PhD - Neurology Fly Lab: “Modeling Alzheimer’s disease in Drosophila”
Dystonia Tremor
Aparna Wagle Shukla, MDPhysiology of essential tremor in comparison to PD tremor
• Imaging networks for dystonic tremor• Physiological characterization • Effects of VIM DBS
Physiology and gait in orthostatic tremor
Physiology of Blepharospasm,Cervical dystonia lingual dystonia
Exercise and
dystonia
rTMS and dystonia
DBS for PD tremor
DBS for MS tremor, DBS for rubral tremorDBS and dystonia
Research Blitz!MS and General neurology
Tirisham Gyang M.DContact: [email protected]
Patient reported outcomes (PRO) database• Multiple PROs collected with potential to explore multiple projects
• Fatigue in patients treated with Ocrevus
• Effects of exercise on fatigue
DMT safety database• Safety monitoring in patients with MS on highly effective therapies
• Multiple potential research projects
Dance in MS• Impact of a structured dance routine on MS outcomes
• MRI, objective motor and patient reported outcomes
Tirisham Gyang M.D + Aaron Carlson, MDContact: [email protected]: [email protected]
Socio-economic status and disability in MS • Cross sectional study
• Correlation between SE at the time of diagnosis and disability
Clinical trials • TREAT-MS (Gyang)
• ASCLEPIOS (Carlson)
Case reports/series• Available for mentorship
Dr. Aaron Carlson, MD Contact: [email protected]
OneFlorida Projects:
• Prevalence of MS in a large population database
• Prevalence of NMO in the same database
• Goal: Understand who and where MS and NMO patients are in Florida, and how they are treated.
• May need assistance in chart review for NMO study
Multiple Sclerosis QI:
• Reviewing barriers to starting disease-modifying therapy
Review Articles / Case Reports:
• Available to mentor review articles /cases on neuroimmunologicalsubjects
Behavioral and Cognitive Division
“Modeling Alzheimer’s disease in Drosophila”Diego Rincon-Limas, PhD. - Neurology Fly Lab
Aβ42TauAβ42Tau
GOAL: To discover therapeutic targets that block Abeta42 and Tau pathology in a fly model of AD
Opportunities to learn: genetics, molecular and cellular biology, transcriptomics,
histology and optogenetic technologies.
Flies display:Aβ42 aggregatesPhospho TauNeuronal deathMemory decline
Neal Weisbrod
• “Responses to a Standardized Approach to Advance Care Planning in Cognitive Disorders Clinic”
• Enrolling new patients and performing ACP discussion at 3 month followup
• Pre and post 3 month follow up surveys to evaluate depression, anxiety, hopelessness
• Comparing to another cognitive disorder clinic provider without routine ACP
• No active areas for resident involvement currently, but anticipate data analysis and write up in 2020-2021 academic year.
Dr. Heilman : Behavioral Neurology:
Possible Resident Research Projects
1. Stroke and Dementia: Development of standardized apraxia test. Patients with stroke and dementia often reveal ideomotor apraxia: However, currently there is no good tests for evaluating patients. The goal of this study would be test development.
2. Stroke and Inattention: Line Bisection: Immediate versus 20 second delay. Many patients with parietal lesions do not reveal neglect on line bisection and with a delay and habituation, they more be more likely to reveal a bias.
3. Limb-Kinetic Praxis : Coin rotation and aging. With aging there is a reduction of callosalconnectivity and thus with aging there may be a reduction in left hand performance.
4. Alzheimer’s Disease: Vertical neglect. The parietal lobes are important for the allocation of attention to lower space and with AD there is degeneration of the parietal lobes.
5. Stroke: Standardization of Florida Cognitive Assessment (FLACA)
6. Aging andAging and Hand (R vs L) Asymmetries Motor Working Memory (fist, edge, palm and more) Hand (R vs L) Asymmetries Motor Working Memory (fist, edge, palm and more)
• TRACS Database Utilization to Develop Standardized Objective Measures to Identify Main Symptom Trajectory and Target Concussion Management
Vision: Build on TRACS Biomarker Papers to Better Understand Genome to Syndrome
This Could Be You!Trainee Research Award from AHS on Objective Exam Measurement of Posttraumatic Migraine
Interface of Sleep and Recovery and Prognosis-Actigraphy
Bhavana Patel, DO
• Racial disparities in LBD in Florida• Project using OneFlorida data trust
• Evaluate prescriptions and referrals for individuals from different backgrounds
• Prevalence of suicide in neurodegenerative dementias • Plan to use Medicare database
• Compare suicide deaths in LBD, AD, FTD, vascular dementia, CJD, and HD
• Laterality of motor symptoms in DLB and hallucinations• Study TBD, could be prospective or retrospective
Melissa J. Armstrong, MD, MSc
• Background in quantitative & qualitative research
• Research foci: Lewy body dementia, values affecting medical decisions (especially in older adults), shared decision making, patient-family-clinician communication, patient engagement, evidence-based guideline methodology
• Project opportunities for residents:• Analysis of patient & caregiver interviews about their clinical and research priorities in dementia
with Lewy bodies (interviews complete; transcripts need qualitative analysis)
• Frequency of DLB diagnosis after surgery (retrospective chart review, protocol in development)
• Documented response to response to AChEI use in LBD (retrospective chart review, protocol in development)
• Evaluating current practices for AVS use and patient instructions in the neurology clinic (protocol in development)
• Open to resident QI project ideas, especially those relating to improving communication
Case reports
Case series myotonic dystrophy type 1 and 2
Pain in channelopathies/periodic paralysis and muscular dystrophies
Axonal GBS UF experience
Prevalence of PMP22 gene deletions (indicative of HNPP) in patients less than 30 yowith multiple mononeuropathies discovered on NCS/EMG.
Prevalence of incidentally discovered polyneuropathy on NCS/EMG in patients with Inclusion Body Myositis.
An assessment of the utility and impact on management (or lack thereof) of electrodiagnostic studies in patients with various clinical presentations. When do they really make a difference?
Studies on Mary Jane?
CAN YOU BREAK PATIENT CARE BARRIER IN THE FIELD OF HEADACHE MEDICINE?
Are neurology residents interested in headache? Are they ready for management
of headache disorders after graduation?
Aim: to assess if residents receive sufficient training in field of headache management, level of involvement and perceived quality
Methods: Self administered questionnaire distributed among neurology residents from different programs
Potential impact:
Identify shortcomings in headache education
Reduce stigma of headache medicine field
Publication and presentation at the professional meeting within reasonable time frame
Risk of stroke associated with estrogen containing oral contraceptives in women with migraine
Use of estrogen containing oral contraceptives is discouraged because of increased risk of stroke in women who have migraine with aura.
Absolute risk of stroke in women without migraine on oral contraceptives is 6.6/100.000, and it is increased to 14.5/100.000 in women with migraine with aura. This calculations are based on low quality of evidence.
Unknown:
The exact impact of combined oral contraceptives in stroke
Is there an dose effect of estrogens:
How estrogen containing contraceptives compare to non-estrogen contraceptives
Methods: retrospective observational cohort analysis of data from Florida One, i2b2 data warehouses
WILLIAM J. TRIGGS, MD
Clinical Correlation of EMG in CIDP
Evaluation of serial neurophysiological studies in CIDP
Do electrophysiological measures of demyelination parallel clinical course?
Ataxia
Myotonic dystrophy
Case reports
Mill’s syndrome
Environmental toxins in ALS
Association of MS and CMT
Clembuterol in CMT
Natural History database
UF experience in SMA
ALS at the VA
Neurocritical Care Research
Team Joint venture – entire division involved in all projects: Babi, Busl, Maciel, Pizzi, Robinson
2 Research Coordinators III – Rebecca Wichman & Jessica Spana
35+ undergrad students
6 medical students
5 neurocritical care fellows
Expectations for resident role: learning about practicing study design, data collection, regulatory aspects of human research, analyses and interpretation of data, leadership role on data collection. You get to practice to be a PI if you are up for the challenge!
Neurocritical Care Saving the Survivors of Cardiac Arrest – Maciel
Improving neuroprognostication:
MOCHA and SPARE trials: prospective international multicenter observational trial (clinicaltrials.gov NCT03261089) aiming at developing a multimodal prognostic algorithm. SPARE is a substudy in Brazil where there is minimal WLST
Cost-effectiveness of delayed final neuroprognostic assessments: collaboration with the Economics department.
Enhancing knowledge re cardiac arrest survivors: retrospective database UF, BU, Yale & CCERMC – lots of clinically impactful scientific questions to be answered.
Novel therapies in post-anoxic status epilepticus: VIGAB-STAT, pilot trial of single load of Vigabatrin in the management of post-anoxic status as adjunct therapy. John Malta
Improving Neuroprognostication in Acute Brain Injury – Busl, Maciel
SPIN: Self-fulfilling Prophecy In Neuroprognostic studies. Several subprojects: cardiac arrest, ICH, SAH, status, TBI. Systematic review of neuroprognostic studies specifically investigating the quality of reporting of WLST, modes of death, timing of death and WLST, blinding of treatment team on tool being investigated. Amreen Farooqi
Neurocritical Care Central Retina Artery Occlusion – Maciel
Multicenter collaboration (Brown, Vanderbuilt, Penn, BU) gathering data on patients with CRAO that underwent systemic thrombolysis and/or endovascular treatment. Keith Kincaid
Pregabalin in acute symptomatic seizures – Maciel, Busl
Multicenter collaboration (Yale, UF) to demonstrate the performance of PGB as adjunct therapy in refractory acute symptomatic seizures. Zach Newcomer, Mitesh Patel. Epi division partnering
Acute pain management in SAH – Busl, Maciel
Database of SAH describing status quo: rates of narcotic use during index hospitalization and prescription of narcotics upon discharge, and effect of cortical spreading depolarization modulators in overall outcome of SAH. Vyas Viswanathan, Brandon Lucke-Wold
BLOCK-SAH: pilot project of anesthetic block to PPF evaluating safety and efficacy of local treatment in HA control and opioid requirements. Partnership with Anesthesia and Neurosurgery
ICH and outcomes – Robinson
Retrospective observational study investigating prognostic factors in ICH and the performance of ICH score in a modern cohort in the stroke belt
Moya-moya – Maciel
Interdisciplinary international survey of perioperative practices on moyamoya syndrome undergoing bypass sgy
Retrospective database at UF –50+ cases
Prospective database and possible QI project
Neuro-Urology – Busl
Urinary retention: who develops retention, and why? Brandon Lucke-Wold
Neurocritical Care Driven Organ Resuscitation in DBD to Improve Donation Yield – Busl, Maciel
Neurocritical care consultation leading the management of the potential brain dead donor. Great opportunity to learn critical care 1:1 with attending (DI management, hemodynamics, procedures) and compassionate bedside skills. Will assess time from BD to OR forharvesting, organ retrieval yield, allograph function
Nursing satisfaction: pre-/post- survey following launch
Evaluation of the Applicability of Alert Scores in the Neurocritical Care Unit – Busl
MEWS Score: How predictive of sepsis in the neurocritically ill population? Mike Morris
Alternatives: Rothman index. Can they perform better?
Neurocritical Care
Predictors of Positive Intracranial Flow on Nuclear Scan During Brain Death Determination –Robinson
Multicenter study of all nuclear brain studies characterizing predictors of non-confirmatory brain death testing to identify flaws in the brain death determination process.
Emergency Neurologic Life Support Education – Robinson
Instrument tool: What is the educational impact in knowledge during training?
NEW: train the trainer in Viet Nam 2020 (Da Nang 9/29-10/2)
Simulation: Can the learning experience be enhanced by educational tools?
ICU EEG Teaching – Maciel, Babi
ICU EEG library : spearhead development of international library for the CCERMC
UF-Emory ICU EEG online course: recording of lectures, and development of an online educational module
Neurologic Emergencies Simulation – Babi
In-vivo simulation in ICU with transdisciplinary team: roles, call outs for safety, and other QI metrics
Neurocritical Care
Biochemical characterization of blood brain barrier degradation of ischemic stroke patients –Pizzi
JAX ASCENT grant. Jacksonville campus.
Prospective study measuring MMPs, inflammatory cytokines, BBB degradation products (hyaluronic acid, syndecan). Opportunities for bench research!
Association of adropin with blood brain barrier degradation and permeability after traumatic brain injury – Pizzi
Prospective study measuring serum adropin, MMPs, BBB degradation products in human severe TBI patients and association with radiographic cerebral edema and elevated ICP. Opportunities for participating in study design, protocol development, IRB submission!
In vivo measurement of BBB degradation and permeability in rat model of TBI treated with adropin. Opportunities for bench research!
Neurocritical Care
Epilepsy Division
Kalamangalam/Epilepsy
Short term projects (3-6 months, resident driven)
• Medication withdrawal in EMU – questionnaire survey of US centers
• Seizures in the EMU – questionnaire/telephone survey + chart review
• Medication responsiveness in the epilepsies – retrospective chart review
• Handedness, language dominance and recovery from neurological deficit (joint project with neuropsychology)
• Creativity and relation to epilepsy (joint with Dr Cibula and Dr Ken Heilman)
• Miscellaneous case reports
Eisenschenk/Epilepsy - Sleep Medicine - Driving
1. Driving in Transient Ischemic Attacks (NIH R21)
2. Epilepsy Surgery Database
1. Database includes seizure type, localization, imaging, neuropsychological data, pathology and outcome
3. VA Epilepsy Centers of Excellence
1. Epidemiology of Epilepsy in Veteran Population
2. Recurrent TBI in Stroke and Epilepsy
3. Brain Sentinel
4. Motor Control Deficits during Driving Following Transient Ischemic Attack- NIH R21
5. Assessment of Driving and Performance Following Sleep Deprivation Associated with Consecutive Night Float
6. Role of Acute EEG and Imaging following stroke as predictors for post-stroke seizures (Smith/Hella/Eisenschenk)
7. Hippocampal Cell Density
1. Comparison of cell densities within CA1, CA2, CA3, CA4, and subiculum to seizure type, frequency, duration, imaging, neuropsychological testing, outcome
Cibula/Epilepsy
• “Risk Factors for Status Epilepticus in the setting of Sepsis” : Christine Smith study: we need assistance for chart review and data entry- would be great opportunity for PGY2
• EEG education : participation as subjects
Bruzzone/Epilepsy
• Short term projects:• Evolution of EEG patterns over time in patients with focal epilepsy
• Efficacy of drug combinations in status epilepticus
• Long term seizure outcomes in patients with ictal interictal continuum patterns on the ICU
• Long term projects• Epilepsy and metabolomics
• Lipid metabolomics in catamenial epilepsy
• Global metabolomics after first non provoked seizure
• Metabolomics and the brain-gut axis in patients with VNS
Hella/Epilepsy
• Seizures post-stroke: EEG and radiologic findings• Ongoing project with Dr.Eisenschenk/Khanna
• Pregabalin in the treatment of refractory status epilepticus• Ongoing project with Dr.Maciel
• Quality project : EEG services at UF Health with aim to improve seizure and status diagnosis and prompt treatment
Stroke
Strategic Planning, Timelines, & Goals
Informational Interviews to Explore Career Opportunities
Stroke Hot Topics Discussions
Mentorship teams
Curriculum Vitae Preparation
Creating an NIH Biosketch
Presentation Skills
Monthly team meetings
Team Science Course
Developing Scientific Questions
Guidance with manuscript and abstract preparation
Tips on scientific communication
Centralizing resources and IRB protocol for chart review studies
Bonus Opportunities: Blogging; Peer Review; Presentations; R25
CAREER DEVELOPMENT RESEARCH
Primary Prevention
•White matter disease•Sepsis EKG Afib and stroke project
Acute Ischemic Stroke Treatment
• Combined Blood and Imaging Biomarkers Project
• Stroke Systems of Care
Secondary Stroke Prevention
• CYP2C19 alleles Plavix and Stroke Prevention
• Pharmacogenomics
Transitions of Care
• Quality Improvement Survey
Alexis Simpkins, MD.PhD., MSCR
Assistant Professor of Neurology
Neurovascular Division
Nandakumar Nagaraja - Stroke
1. UF Stroke Retrospective review projects a) Role of microbleeds on hemorrhagic transformation with
and without t-PA. b) Outcomes of lacunar stroke in patients with and with
perfusion deficits on CTP.
2. Review articlea) FLAIR changes in acute stroke.
3. National Inpatient Sample Database projects
Christina Wilson, MD PhD
• Stroke projects• Factors influencing patient delay in presentation
• Low NIHSS on presentation – database of 300 patients
• QI projects• MRI utilization in the ED
• Improving ED stroke alert accuracy
• Medical education projects• Self-guided neuro-ophthalmology curriculum
-Resident QI project
Looking at delays in tPA administration after 7 pm vs morning and daytime hours
Investigator Initiated Preliminary Project
-Reviewing the CREST 2 Registry database of over 4000 patients to determine which patients enrolled have had a prior ipsilateral carotid occlusion and were later enrolled into the trial after spontaneous recanalization. Aim is to determine which patients recanalize and at what time frame and whether CAS is beneficial.
Hypothesis: Carotid Occlusion is not always benign and can be associated with future stroke recurrence. Patients with a known occlusion should have repeat imaging. The benefit of CAS in those with prior occlusion and subsequent recanalization is unknown.
Anna Khanna MD
