I am very pleased to be able to bring you up to date on Michigan Neurology. Since the last edition of this newsletter that was published in winter 2012, our department has continued to grow. We now have 61 physician faculty, 18 residents and more than 20 post-residency trainees in subspecialties ranging from stroke and sleep to sports neurology.

The growth in faculty is reflected in clinical activity. Last year our faculty saw nearly 40,000 outpatient visits—almost twice the number of patient visits recorded in 2007—and activity in all of the related laboratories including EMG, EEG and the 28-bed sleep lab increased commensurately. In the research arena, our faculty has continued to be very successful, even in the face of a challenging funding environment. In the 2013-2014 academic year, Neurology faculty published 291 articles in peer-reviewed journals and secured more than $17 million in external grant

Message from the Chair

2015

funding ($10 million NIH)—a figure that doesn’t include the recently awarded Udall (Parkinson’s) Center grant and the Sudden Unexpected Death in Epilepsy (SUDEP) Center Without Walls grant highlighted in this issue.

Having completed 10 years as chair, I am more aware than ever that a department is not a static entity, but a continuously evolving functional unit. With the formal installation of Hiroko Dodge, Ph.D. as the first Kevreson Research Professor this spring, we will have 14 endowed professorships that recognize the accomplishments of our more senior faculty, and 10 assistant professors with NIH-funded K (mentored career development) awards that recognize promise for the future leaders of the field. These 24 faculty are only part of our group of clinicians, educators and researchers. In an uncertain and rapidly changing environment, Michigan Neurology is ready to face the future with optimism!

Bottom row (left to right): Hank Paulson, Groff Professor; Eva Feldman, DeJong Professor; David Fink, Brear Professor; Ann Little, Albers Collegiate Professor. Top row (left to right): Ben Segal, Holtom-Garrett Professor; Roger Albin, Young Collegiate Professor; Bill Dauer, Levine Professor; Brian Callaghan, Dush Professor; Peter Todd, Harris Professor; Judy Heidebrink, O’Connor Professor; Kelvin Chou, Brown Professor; Ron Chervin, Aldrich Collegiate Professor

Endowed Professors

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This spring we will celebrate the establishment of the Kevreson Research Professorship with the installation of Hiroko Dodge, Ph.D. as the first Kevreson Research Professor. Dr. Dodge is an internationally known expert in Alzheimer’s disease. She has active research programs in dementia prevention, in distinguishing normal cognitive aging from pathological cognitive decline, and in applying demographic methods to clinical studies including cross-national comparative studies of healthy cognitive aging in collaboration with researchers of the Okinawa Centenarian Study.

Since joining the Michigan Alzheimer Disease Center (MADC) team Dr. Dodge has taken an active role in the data management, improving data collection and distribution, and fostering collaboration among the MADC investigators. Dr. Dodge has more than 75 publications and is regularly invited to give seminars and presentations in Japanese universities, as well as international conferences. She is also involved with an extensive network of dementia researchers worldwide.

On the national level, Dr. Dodge served on the Scientific Review Committee for the National Alzheimer’s Coordinating Center (NACC), and currently serves as a member on the NACC Neuropsychological Tests Working Group. She is the chair of the Data Core Steering Committee at NACC, and also chairs the statistical subcommittee. Dr. Dodge is an exceptional addition to our faculty, and an important contributor to our Alzheimer Disease Center.

Hiroko Dodge to be Installed as the First Kevreson Research Professor

NIH Awards $11.5 Million to Fund a Udall Parkinson’s Disease Center at Michigan

Neurology Multidisciplinary Clinics: The Future is Now!

At the end of September, Department of Neurology clinician-researchers, led by William Dauer, director of the UMHS Movement Disorders program and the Elinor Levine Professor, were awarded a five-year, $11.5 million grant from the National Institute of Neurological Diseases and Stroke to establish a Morris K. Udall Center of Excellence in Parkinson’s Disease Research. The Udall Center grant will fund three interrelated projects designed to better understand the role of the cholinergic system in falls, focusing on the effect of lost cholinergic neurons in the basal forebrain and the pedunculopontine nucleus (PPN).

In patients, Nicolaas Bohnen, M.D., Ph.D., professor of radiology and neurology, will use a new method of PET scanning developed at Michigan to link specific problems of gait and cognition to degeneration of these cholinergic pathways. In a related project, Roger Albin, Anne Young Collegiate Professor, will determine if it may be possible to increase cholinergic traffic and improve gait using the already-approved cholinergic modulating drug varenicline.

Lakritz Gift Jump Starts Program to Study Chorea AcanthocytosisThis October, a generous $1.1 million dollar gift from Bill and Liz Lakritz established a multidisciplinary research effort focused on chorea acanthocytosis and related neurodegenerative disorders.

Because varenicline (known commercially as Chantix) is already available by prescription to help people stop smoking, advancing the treatment to patients would be relatively straightforward if the investigators were to find that it is effective in PD. The education and outreach component of the Udall Center will be led by Kelvin Chou, William Brown Professor and co-director of the Surgical Therapies Improving Movement (STIM) deep brain stimulation program for Parkinson’s disease.

The Center is an interdisciplinary collaborative effort that includes neuroscientist Martin Sarter, Ph.D., the Charles M. Butter Collegiate Professor of psychology in LS&A, who will further develop a rodent model of falling in PD, and a team of biostatisticians and data management specialists led by Ivo Dinov, Ph.D., professor in the School of Nursing and Cathie Spino, Sc.D., research associate professor of biostatistics in the School of Public Health. The biostatistical and data management team will help design and analyze the results of the center’s experiments, using advanced digital tools to parse the massive amounts of data the work will produce.

Chorea acanthocytosis is a rare inherited neurodegenerative disease that disrupts many aspects of movement and thinking, in addition to causing epilepsy. The cause of the disease is a mutation in the gene coding for VPS13a, a protein essential for normal trafficking of proteins in neurons. Bill Dauer, Elinor Levine Professor, will direct the effort. Robert Fuller, Ph.D., professor of biological chemistry in LS&A, whose lab first identified VPS13a in 1997, will pursue fundamental studies of VPS13a function in yeast. Dr. Dauer’s lab will create and study a mouse model of the chorea acanthocytosis. In complementary studies, Jack Parent, professor of neurology and co-director of the epilepsy program, will use skin cells from patients with the disease to create stem cell-derived neurons in order to study their functional properties.

This is the first such multidisciplinary research team ever assembled to study chorea acanthocytosis, and the team’s efforts will synergize with those supported by the Protein Folding Diseases Initiative. Abnormalities of the protein trafficking network involving VPS13a are found in Parkinson’s and Alzheimer’s disease. Studies that compare and contrast these different disorders may therefore provide clues of broad importance for understanding and treating neurodegenerative disease.

Neurology has a long history of multidisciplinary clinics for patients whose condition requires additional expertise outside the purview of neurology. Among the established clinics, perhaps the best known are the multidisciplinary sleep clinics under the direction of Ron Chervin that involves physicians from Pediatrics, Pulmonary Medicine, ENT and Psychiatry in addition to Neurology, with close collaboration with the Department of Oral and Maxillofacial Surgery, and the multidisciplinary ALS clinic, under the direction of Brian Callaghan, Dush Professor, and Stephen Goutman, assistant professor, that includes respiratory therapy, physical therapy, occupational therapy, speech therapy, nutrition services, a social worker, and a wheelchair specialist.

In the last two years, two new multidisciplinary clinics have been added to the roster. Vikram Shakkottai, assistant professor, and Peter Todd, Patti and Bucky Harris Professor partnered with physical therapy, social work, and language and speech pathology to establish a Multidisciplinary Ataxia Clinic. Services offered include providing the best current protocol for balance therapy to promote independence, facilitated planning for care as symptoms progress,

and working with the patients and caregivers to identify community resources as the need for support increases. Language and speech pathologist Karen Kluin, assistant professor, sees patients on the day of the visit to provide a comprehensive evaluation and recommendations regarding speech and swallowing difficulties. The availability of these services further enhances the quality of care that can be provided for patients with ataxia and balance disorders.

And Sindhu Ramchandren, assistent professor, recruited to Neurology from Wayne State, has taken over direction of the transitional/adult Muscular Dystrophy Clinic and the Charcot-Marie-Tooth (CMT) clinic for children and for adults. The CMT Association recognized the Michigan CMT Clinic as one of 10 Centers of Excellence in clinical and research care in the United States, and Dr. Ramchanden expects to receive a similar designation from the Parent Project Muscular Dystrophy for the Duchenne clinic. The pediatric and adult Muscular Dystrophy Clinic has been supported over the years by gifts from the Erwin family, long-time advocates of the University of Michigan Muscular Dystrophy program, and from friends of the Erwin family.

Hiroko Dodge (left) and Hank Paulson Bill and Liz Lakritz with Bill Dauer

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Hank Paulson Co-Directs $9.3 Million ‘Protein Folding Disease’ Fast-forward Initiative

Jack Parent to Direct $3.5 Million NIH-Funded SUDEP ‘Center Without Walls’ Project

Multiple Sclerosis Clinical Programs and Clinical Research Continue to ExpandThe Multiple Sclerosis (MS) program in the department has grown substantially since the recruitment of Ben Segal, Hotom Garrett Professor six years ago. In the last year, the MS Center provided multidisciplinary care for more than 3,000 patients with MS.

The Michigan MS Center, supported for more than a decade by generous gifts from Marge and Dick Garrett and from David Garrett, has been designated a Center of Excellence for Comprehensive MS Care by the National Multiple Sclerosis Society, is staffed by five neurologists with subspecialty expertise in MS, a clinical fellow, a nurse practitioner and dedicated clinical trial coordinators. An MS clinical fellowship program was established in 2007 to train neurologists in the specialized care and diagnosis of patients with MS and related disorders. Three fellows have successfully completed the program, with two (assistant professors Tiffany Braley and Rob Pace) now on our faculty and a third in practice in Minneapolis. The fourth fellow in the program is currently in training.

This year, Yang Mao-Draayer, associate professor (with Ben Segal, Holton Garrett Professor as co-investigator) was funded by the NIH to direct a clinical project as part of the newly awarded U-M Autoimmunity Center of Excellence, and based on a clinical

Sudden unexpected death is up to 24 times higher in patients with epilepsy than it is in the general population, responsible for an estimated 2,750 deaths in the U.S. annually. The problem was given a name 20 years ago: sudden unexpected death in epilepsy (SUDEP) and studies of SUDEP mechanisms point to a complex pathology involving peri-ictal abnormalities in brainstem and autonomic function, heart rate and rhythm, or respiration.

To address the problem, the NIH has begun funding Centers Without Walls for Collaborative Research in the Epilepsies to bring together scientists and physicians with expertise in molecular biology, genetics, histopathology, electrophysiology, brain imaging and data analysis to investigate SUDEP. This year, a University of Michigan team led by Jack Parent, professor of neurology and Lori Isom, Ph.D., interim chair of pharmacology, was awarded a $3.5 million NIH grant as part

In the last year Hank Paulson, Lucile Groff Professor and director of the Alzheimer disease program in the department, along with co-director Andrew Lieberman, Gerald B. Abrams Professor of Pathology, was awarded a Fast Forward grant from the medical school to establish a multidisciplinary Protein Folding Disease Initiative (PFDI). PFDs are disorders of abnormal protein accumulation and aggregation, often associated with perturbations in “protein quality control”, that represent one of the largest (more than 100 PFDs are recognized) and most vexing categories of human disease. In the nervous system Alzheimer’s and Parkinson’s disease are common PFDs, and the PFDI that includes 65 faculty from several departments across the institution has already played an important role in five recently awarded RO1 grants, was an important institutional resource

in support of the successful application to establish a Udall Parkinson Disease Center of Excellence here, and is integrally related to the Michigan Alzheimer Disease Center that Hank also directs.

In its first year the PFDI supported four small molecule screens through the Center for Chemical Genomics; proteomics studies by seven laboratories; and, in silico protein folding analyses by seven investigators. PFDI is in the process of developing a collaborative effort with the Department of Computational Medicine & Bioinformatics to expand bioinformatics support necessary to better investigate these diseases.

of the second Center for SUDEP Research to study SUDEP mechanisms in Dravet Syndrome, a childhood epileptic encephalopathy caused by mutations in voltage-gated sodium channels, with an increased risk of sudden death.

The Michigan group will test whether the mutant sodium channels, which are expressed in heart as well as brain, predispose to arrhythmia. Patient-derived cardiac myocytes and autonomic neurons will be generated from skin biopsies using the induced pluripotent stem cell method. Findings from patient-derived cells will be analyzed along with clinical data, including continuous peri-ictal ECG monitoring during seizure recordings, and data from transgenic mouse and rabbit Dravet Syndrome models.

Lesli Skolarus Directs NIH Funded Community-based Stroke Program in Flint

observation, the group has initiated the first-ever novel trial of extracorporeal photopheresis in secondary progressive MS. In 2014, we were pleased to receive a gift from the Sarnes family to David Irani, associate professor that will help accelerate clinical research in progressive MS.

Significant accomplishments from the Michigan Neuroimmunology research team:• Thedemonstration,inanimalmodelsofMS,thatclinically

similar forms of demyelinating disease can be driven by distinct cellular and molecular pathways that translate into different responsiveness to disease modifying modications

• Thediscoverythatimmunedysregulationisevidentinindividuals in the secondary progressive, as well as in relapsing remitting, stages of MS

• Thefindingthatobstructivesleepapneaishighlyprevalent in people with MS and is a significant contributor to fatigue

Lesli Skolarus, assistant professor, has partnered with Elder Sarah Bailey and Bridges into the Future, an African American faith-based organization in Flint, Michigan to create and test a faith-based, peer-led intervention to increase awareness of stroke warning signs and the importance of calling 911 among African American youth and adults. The project, entitled PRAISE (Preparing to ReACT Immediately to Stroke through Education), is funded by an NINDS K23 Mentored Patient-Oriented Research Career Development Award to Dr. Skolarus. In addition to PRAISE, and in response to the community’s request for primary stroke prevention, Dr. Skolarus, her community partners and Devin Brown, professor, designed and are testing a text messaging intervention to reduce blood pressure among African Americans.

In this study, participants are enrolled after church services by Michigan physicians, nurses, residents and medical students with the help of the church health teams. The prevention study is funded by the University of Michigan Cardiovascular Center Inaugural Fund.

Andy Lieberman (left) and Hank Paulson

Jack Parent and Lori Isom

Back row: Doris Allen, Lesli Skolarus, Sister Brenda, Mackenzie Dome, Linda Turner. Front row: Sarah Bailey, Gloria Moses-Colon, Marsha Hill

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NIH K AwardeesWe are again proud to report that this year, of our 11 assistant professors on the instructional (tenure-seeking) track, 10 are recipients of K08 or K23 mentored career development awards from the NIH. This puts us among the top neurology departments nationwide in number of K awardees, and almost certainly highest in ratio of K awardees to assistant professors.

Zach London Creates ‘Boot Camp’ for PGY1 Neurology Trainees

Sami Barmada, M.D., Ph.D. Elucidating the mechanisms underlying mutant TDP43-induced neurodegeneration (Paulson)

Jim Burke, M.D. Using outcomes analyses to inform implementation of NINDS clinical trials (Morgenstern)

Brian Callaghan, M.D. The impact of the metabolic syndrome on neuropathy (Feldman)

Dan Leventhal, M.D., Ph.D. Neuronal oscillations and dysregulated motor learning in parkinsonian rats (Albin)

Sindhu Ramchandren, M.D. Validation of a disease-specific instrument for pediatric inherited neuropathy (Feldman)

This year the core neurology residency became a categorical program so that all residents in the program complete their PGY1 year (the training year formerly known as internship) in the internal medicine program at Michigan. Taking advantage of this opportunity and to facilitate the transition of our trainees from medicine to neurology, Zach London, associate professor and director of the residency training program created “Neurology Boot Camp”.

Working with the department of medicine, he coordinated the schedule so that all of the PGY1 trainees are free of clinical responsibilities during the final month of their internship, and then brought them into neurology for one month of focused training. The boot camp curriculum is primarily non-clinical, with an emphasis on case-based and self-directed learning, communication workshops, and skill workshops. Through these interactive sessions, residents develop a fundamental approach to localizing lesions within the central and peripheral nervous system, and practice using this information to generate a differential diagnosis. They also develop

basic familiarity with the recognition and management of the most common neurologic disorders and those that require emergent intervention. A teaching workshop trains residents to be engaging educators and gives them practice giving and receiving feedback. The boot camp curriculum also includes neurology-based games, exercise classes, and other team-building activities to enhance rapport and trust among residents. The feedback from the 2014 participants was uniformly positive, and Dr. London is excited to refine the curriculum for the 2015 class, with our senior residents and last year’s campers helping to lead many of the educational sessions.

In the 2014 Doximity/USNWR rating, the Michigan Neurology residency was ranked

#10 nationally, #2 among public hospital programs.

2014 Major National Awards & Honors

Vikram Shakkottai, M.D., Ph.D. Targeting physiologic changes as a route towards therapy for degenerative ataxias (Paulson)

Lesli Skolarus, M.D. A community partnership to treat stroke (Morgenstern)

William Stacey, M.D., Ph.D. Modeling seizure precursors and antiepileptic brain stimulation (Parent)

Peter Todd, M.D., Ph.D. Pathogenic mechanisms in fragile X tremor ataxia syndrome (Paulson)

Darin Zahuranec, M.D. Prognosis and end-of-life decision making in intracerebral hemorrhage (Morgenstern)

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Eva Feldman, M.D., Ph.D. DeJong Professor, was one of 6 UM faculty elected to the lnstitute of Medicine of the National AcademiesThe Institute of Medicine is unique in its structure as both an honorific membership organization and an advisory organization. Election to the IOM is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service. New members are elected by current active members through a selective process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care, and public health.– National Academies of Science

David Fink, M.D.Robert Brear Professor and chair, received the 2014 Department of Veterans Affairs Paul B Magnuson Award for Excellence in Rehabilitation ResearchIn recognition of his (Dr. Fink’s) pioneering investigations to develop and test viral gene therapy for intractdable pain, peripheral neuropathy, and spinal cord injury. Dr. Fink has made bold advances based on meticulous laboratory studies to deliver novel treatments to patients with diseases of the nervous system. – Department of Veterans Affairs

Top row (left to right): Peter Todd, Harris Early Career Professor; Bill Stacey; Brian Callaghan, Dush Professor; Sami Barmada; Dan Leventhal; Darin Zahuranec; Jim Burke

Bottom row (left to right): Lesli Skolarus; Vikram Shakkottai; Sindhu Ramchandren

Lewis Morgenstern, M.D.Professor of Neurology, received the 2014 William E Feinberg Award for Excellence in Clinical Stroke (Lifetime Achievement Award) from the American Heart AssociationDr. Morgenstern spent seven years on the faculty at UT Houston where he began the Brain Attack Surveillance in Corpus Christi (BASIC) project. BASIC is currently in its fourth, 5-year NINDS cycle and has resulted in over 65 publications, 5 R-level spin-off grants, several career development awards and has served as the foundation for training graduate students, medical students, residents and fellows about health disparities research. The project has made fundamental contributions to our understanding of disparities, cultural contexts of medicine and clinical observations of stroke in a “real world” non-academic community. – American Heart Association

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2014 Michigan Medical School AwardsRon Chervin, M.D. 2014 MICHR Distinguished Clinical and Translational Research Mentor Award

Lewis Morgenstern, M.D. 2014 Medical School Clinical & Health Services Research Award

Linda Selwa, M.D. 2014 Medical School Local Community Service Award

National, Regional Service RolesMany of our senior faculty members serve in leadership positions in regional and national specialty and subspecialty organizations.

Roger Albin, M.D. Chair, NIH NINDS NSD-B Study Section

Larry Charleston IV, M.D. Chair, American Headache Society Underserved Populations in Headache Medicine Special Interest Section

Ron Chervin, M.D. Board of Directors, American Academy of Sleep Medicine Board of Directors, American Sleep Medicine Foundation Board of Directors, Associated Professional Sleep Societies Vice President, International Pediatric Sleep Association Deputy Editor, SLEEP

Bill Dauer, M.D. Chair, NIH NINDS CDIN Study Section

Eva Feldman, M.D., Ph.D. Immediate Past President, American Neurological Association Member (newly inducted), Institute of Medicine of the National Academies of Sciences

David Fink, M.D. President, Association of University Professors of Neurology Board of Directors, American Neurological Association Board of Directors, United Council of Neurologic Subspecialties

Larry Junck, M.D. President, Washtenaw County Medical Society

Jeff Kutcher, M.D. Chair, American Academy of Neurology Sports Neurology Section Associate Editor, Frontiers in Sports Neurology Co-Director, AAN Sports Concussion Conference

Jack Parent, M.D. Secretary, American Neurological Association Board of Directors, American Epilepsy Society Associate Editor, Epilepsy Currents Co-Chair, 2014 Gordon Conference on Epilepsy

Ben Segal, M.D. Chair, Scientific Advisory Board, MS Centers of Excellence – East Co-Chair, Program Committee, Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS)

Sayyed Sohrab, M.D. Fellow, European Board of Neurology (the first and currently only American neurologist who has earned this designation)

Roger Albin and Richard Keep to Direct ‘Clinical Neuroscientist Training Program’ (NINDS R25)This year, Roger Albin, Anne Young Collegiate Professor and Richard Keep, Ph.D, Crosby-Kahn Collegiate Professor of neurosurgery competed successfully for an R25 grant from the NINDS to establish the University of Michigan Clinical Neuroscientist Training Program. The UMCNTP will offer two years of mentored research experience for trainees in neurology, neurosurgery or neuropathology beginning during residency and continuing during the immediate post-residency year. Neurosurgery resident Kevn Chen, is the first R25 trainee, and he will be joined by neurology resident Andrew Sas in the 2015-2016 academic year. The R25 program nicely complements the Neurology Research Training Grant (NINDS T32) directed by Eva Feldman, DeJong Professor and Devin Brown, professor that has supported additional post-doctoral research training in clinically-relevant neuroscience in the department since 1982.

LEADERSHIP OF THE UNIVERSITY OF MICHIGAN HEALTH SYSTEMMichael M.E. Johns, M.D., Interim Executive Vice President for Medical AffairsThomas Campbell, Associate Vice President of Strategic Planning and Business DevelopmentPaul Castillo, C.P.A., Chief Financial Officer, University of Michigan Health SystemT. Anthony Denton, J.D., M.H.A., Acting Chief Executive Officer, and COO, University of Michigan Hospitals and Health CentersDenise A. Gray-Felder, A.P.R., Chief Communication Officer, University of Michigan Health SystemKara Morgenstern, J.D., M.P.H., Interim Associate Vice President and Deputy General Counsel, Office of the U-M Vice President and General CounselDavid A. Spahlinger, M.D., Senior Associate Dean for Clinical Affairs, Executive Director, Faculty Group Practice University of Michigan Medical SchoolQuinta Vreede, Chief Administrative Officer, UMHS Chief of Staff, Office of the EVPMAJames O. Woolliscroft, M.D., Dean, University of Michigan Medical School

THE REGENTS OF THE UNIVERSITY OF MICHIGANMark J. Bernstein, Julia Donovan Darlow, Laurence B. Deitch, Shauna Ryder Diggs, Denise Ilitch, Andrea Fischer Newman, Andrew C. Richner, Katherine E. White, Mark S. Schlissel, ex officio ©2015 Regents of the University of Michigan, Ann Arbor, Michigan 48109

NEWSLETTER DEVELOPMENTMichelle Davis, Associate Director of Development, Neurosciences

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